1.1 MAGNITUDE OF INFECTIOUS AND VACCINE-PREVENTABLE DISEASES IN CHILDREN AND ADOLESCENTS IN INDIA
A Parthasarathy, Hitt Sharma
The WHO 2016 country specific report for India on prevalence of six vaccine-preventable diseases (VPDs), which were targeted for elimination in 1985 through the Universal Immunization Program, is alarming. Although majority of the states have achieved good control of these diseases through sustained and high immunization coverage, there are still many states in the North-Eastern region of the country which could achieve only 30–40% routine immunization coverage. These states with low immunization coverage levels contribute to the maximum number of reported VPDs cases, thus responsible for their heavy burden in the Indian country profile. Thanks to creativity, professionalism and perseverance in the National Polio Surveillance Program today, WHO has removed India from the list of polio-endemic countries in the world with the last case of polio reported from India as of January 13, 2010. However, regarding other pediatric infectious diseases, only little data is available due to lack of countrywide effective surveillance system.
Table 1.1.1 depicts the demography and vital statistics figures pertaining to the years 1980–2016 with comparative figures for the years 1980, 1990, 2000 and 2012–2016.
Table 1.1.2 depicts the number of reported cases of VPDs since the years 2012–2016 with comparative figures for the years 1980, 1990 and 2000.
Although there is a significant reduction in the total number of cases when compared to those in 1980s, it remains a matter of concern that still there are many preventable cases affecting children under 5 years, but this is just the “tip of the iceberg”.
Many cases of measles, pertussis, diphtheria, etc. may still be missing in these reports due to under-reporting.
Around 3380 cases of diphtheria are reported in 2016 from various parts of the country despite the existence of National Immunization Mission since 1985. It is a matter of concern for the planners as well as the implementers. In the absence of subclinical infection in most parts of the country, any new case of diphtheria is bound to cause dreaded complications like diphtheritic myocarditis/neuroparalytic complications, etc.
In India, the state of Andhra Pradesh accounted for 40–70% of diphtheria cases reported from the country during 2003–2006, most of them being reported from Hyderabad, the state capital. In Hyderabad, diphtheria rate increased from 11 per 100,000 in 2003 to 23 per 100,000 in 2006. Integrated Disease Surveillance Programme (IDSP), National Centre for Disease Control (NCDC), Delhi, reported 7 outbreaks of diphtheria in India during the year 2014.
The 2016 surveillance data, which comes from the states of Bihar, Haryana, Kerala, and Uttar Pradesh (UP), shows the importance of examining subnational surveillance data and coverage (Table 1.1.3).
The age distribution of cases for these states is very different, with Bihar having the highest proportion of cases under 5, Kerala having the highest proportion of cases over 10, and Haryana and UP showing the highest proportion of cases between 5 and 10 years of age. Survey data demonstrate that the coverage for both DTP3 and the fifth dose at 5 years of age is also highly variable among regions.
Pertussis continues to be a major public health problem in both developing and developed countries. There is passive reporting of whooping cough cases from the public sector, the data is maintained by the Government of India and also shared with WHO. In India, the incidence of pertussis declined sharply after launch of Universal of Immunization Program (UIP). The shifting age group for new pertussis cases and complications in adolescents is a matter of concern. Pertussis in adolescents and adults is responsible for considerable morbidity in these age groups and also serves as a reservoir for disease transmission to unvaccinated/partially vaccinated young infants. It has become necessary to administer adolescent pertussis vaccine in areas endemic for pertussis.
A total of 3,781 cases of tetanus (inclusive of 227cases of neonatal tetanus) stresses the need for a high diphtheria-tetanus-pertussis (DTP) coverage of under 1 and under 5 children as well as a high coverage of two doses of Td (toxoid dose) to pregnant mothers. Since neonatal tetanus invariably has a high case fatality rate, which adds to the total infant mortality, urgent steps are needed to step up the Td two-dose coverage to nearly 100% of all pregnant mothers. This schedule appears to provide protective levels of antibody for well above 80% of newborns. Both WHO and Indian Academy of Pediatrics Committee on Immunization recommend replacement of tetanus toxoid by Td vaccine in the National Immunization Program (NIP).
Estimates of measles-related deaths have been considered a crucial indicator to evaluate the progress of any nation towards measles elimination. The global estimates for the year 2013 suggest that close to 0.14 million deaths were attributed to measles, accounting for nearly 16 deaths each hour. Study findings have indicated that more than 50% of the global measles associated deaths were reported in India alone. India has made important efforts and gains against measles in recent years. Measles deaths have declined by 51% from an estimated 100,000 in the year 2000 to 49,000 in 2015. This has been possible by significantly increasing the reach of the first dose of measles vaccine, given at the age of nine months under routine immunization programme, from 56% in 2000 to 87% in 2015. The National Family Health Survey-4 (2015–2016) has assessed it to be 81.1%. This is low compared to the 95% coverage level required for elimination. Indian Association of Pediatrics (IAP) has revised its recommendations on Measles and MMR vaccination schedule. The new schedule will have a dose of MMR at 9 months instead of measles, and another dose (2nd) at 15 months of age. The earlier recommendation of 2nd dose of MMR at 4–6 years of age has been removed.
India has made remarkable progress in the control and elimination of poliomyelitis. From an alarming number of nearly 2,000 cases in 1998, the case count as on September 17, 2010 was just 39 cases. Since January 13, 2011 nil case of polio due to wild poliovirus has been reported.
In 2009, India had more polio cases than any other country in the world (756). In just two short years, India has taken a giant step toward eradicating polio globally forever. On January 13, 2012, India reached a major milestone in the history of polio eradication—a 12-month period without any case of polio. The WHO reported that in 2011 India had its first polio-free year and is therefore no longer considered polio-endemic. This date marks the unprecedented progress in India and an endorsement of the effectiveness of the polio eradication strategies and their implementation in India. India is now off the WHO list of polio-endemic countries, but has to remain free of polio for the next 2 years to achieve the status of polio-free country.
The Strategic Plan was developed in response to the May 2012 World Health Assembly which declared the completion of poliovirus eradication to be a programmatic emergency for global public health. Under this plan to achieve and sustain a polio-free world, the use of OPV must eventually be stopped worldwide, starting with OPV containing type 2 poliovirus (OPV type 2). At least one dose of Poliomyelitis vaccine (Inactivated) must be introduced as a risk mitigation measure and to boost population immunity.
Since 25th April 2016 the Ministry of Health and Family Welfare, Government of India (GoI) switched from tOPV to bOPV. Now in India only bOPV will be used both in routine immunization (RI) as well as polio campaigns. To provide protection against type-2 poliovirus to naive children born post-switch. IPV would be the only source of providing type-2 immunity to children after April 2016.
Although we do not have the accurate figures of reported cases, it is evident from the cases seen by pediatricians and family physicians in their office practice that the number of mumps cases is also of a significant proportion in India. With the availability of a safe, effective, indigenous and cost-effective vaccine, mumps should be immediately included in the UIP as MMR vaccine in place of MR vaccine. Further, there is an urgent need of initiating surveillance of clinical cases of mumps all over the country and it should be declared as a ‘notifiable’ disease in India. IAP has recently revised its recommendations on MMR vaccination with first dose at 9 months in place of standalone measles vaccine, and second at 15 months of age.
Although the total number of cases of rubella is not known, rubella is the most common and single cause of blindness in the newborns as reported by ophthalmologists in India with cases of congenital rubella syndrome (CRS). A recent study conducted in both rural and urban areas of 12 districts in Maharashtra shows that rubella virus infection is prevalent in these areas and almost 25% girls reach childbearing age without acquiring natural immunity against the disease. Studies conducted across India suggest similar baseline information on the susceptibility profile of women of childbearing age.
In order to raise the immunity against rubella and prevention of CRS, the following strategy is recommended:
Administration of first dose of rubella containing vaccine, viz. MMR, at 9 months and the second dose at the age 15–18 months and conducting mass immunization campaigns targeting girls up to the age of 15 years. The Ministry of Health and Family Welfare launched Measles Rubella (MR) vaccination campaign in the country in February 2017. The campaign against these two diseases will start from five States/UTs (Karnataka, Tamil Nadu, Puducherry, Goa and Lakshadweep) covering nearly 3.6 crore target children. Following the campaign, Measles-Rubella vaccine will be introduced in routine immunization, replacing the currently given two doses of measles vaccine, at 9–12 months and 16–24 months of age.
Hepatitis B Virus Infection
India is rated to be in the intermediate zone for hepatitis-B prevalence with hepatitis B surface antigen (HBsAg) prevalence between 2% and 10% among populations studied. The fact remains that hepatitis B infection occurs during childhood and causes fatal complications like hepatocellular carcinoma, chronic active hepatitis or cirrhosis of liver and thus accounting for high morbidity and mortality. In India the prevalence of Hepatitis B surface antigen (HBsAg) is 3–4.2% with over 40 million HBV carriers. Every year over 100,000 Indians die due to Hepatitis B complications.
Hepatitis B vaccine is safe and is highly effective in preventing hepatitis B virus (HBV) infection and its serious consequences. Protection afforded by this vaccine is long lasting. Numerous studies have shown that adding hepatitis B vaccine into the expanded program of immunization is highly cost-effective, even in areas with low HBV endemicity. In 1991, the Global Advisory Group of the Expanded Program on Immunization of WHO recommended that hepatitis B vaccine should be introduced into NIPs in all countries by the year 1997. The World Health Assembly approved this in 1992. More than 100 countries have already included this vaccine in their NIPs. In countries that have implemented universal childhood hepatitis B immunization, HBV carrier rate has declined markedly and incidence rate of long-term consequences, like liver cancer, have shown a decrease.
It is a matter of satisfaction that the Government of India has since introduced hepatitis B vaccine in the National Schedule in select pilot project areas from the year 2002 onward, which is now extended to the entire country in a phased manner. As per 2015 national estimates, the hepatitis B vaccination coverage of children is 45% for the birth dose (within 24 hours after birth) and 86% Hepatitis B third dose. Figure 1.1.1 depicts the magnitude of the disease at the global level and in India.
Hepatitis A Virus Infection
A disease of children has now shifted to adolescents. Although complications are less compared to hepatitis B infection, effective vaccines are now available to be given in prime-boost schedule. The actual incidence is not known since many cases of hepatitis A are not reported. May be with the introduction of Integrated Disease Surveillance Project (IDSP) in India, we will have more number of hepatitis A cases reported. IDSP identified a substantial number of hepatitis cases and outbreaks during 2011–2013. The large number of hepatitis A and E outbreaks might be explained in part by the lack of adequate sewage and sanitation systems; defecation in open fields, which can contaminate surface drinking-water sources, remains a common practice.
The large numbers of hepatitis A cases might also reflect an epidemiologic shift in the affected population in India. Hepatitis A infection during childhood often is asymptomatic and unrecognized, and typically confers lifelong immunity. With increasing age at time of infection, symptomatic cases become more common. With improved hygiene and sanitation reflecting India's improving economy, more children might escape childhood infection and remain susceptible to infection during adolescence and adulthood. The global geographic distribution is given in the Figure 1.1.2. The current recommendation is to administer hepatitis A vaccine at 12 months of age due to absence of maternal antibodies in the newborn. Killed Hep A vaccine: Start the 2-dose Hep A vaccine series for children aged 12 through 23 months; separate the 2 doses by 6–18 months. Live attenuated H2-strain Hepatitis A vaccine: Single dose starting at 12 months and through 23 months of age.
Varicella is widely prevalent mostly in children 5–10 years of age with increasing incidence in children under 5. A vaccine with good protective efficacy is available and is being used by many pediatricians all over the country. The disease usually manifests in early summer and it is estimated that many thousands of cases are not reported to the medical facility due to traditional beliefs and customs, and because of the lesser complications attributed to the disease, per se. However, the available statistics reveal the magnitude to some extent.
Varicella prevalence in India
- Twenty-five million cases annually in India
- Complications: Secondary infection—scars, encephalitis, cerebellitis, H. zoster, pneumonia, congenital varicella syndrome
- Morbidity: School and office absenteeism
- Mortality: 2–25 per 100,000, immunocompromised (IC): 10–30%
- High risk groups include adults, IC host, pregnancy and neonate.
- Following breakthrough infection in 30% of children who had received a single dose of varicella vaccine, the current recommendation is to administer two doses of varicella vaccine at 15 months and 5 years simultaneously with two doses of MMR vaccine.
Human Papillomavirus (HPV) Infection
Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and there is growing evidence of HPV being a relevant factor in other anogenital cancers (anus, vulva, vagina and penis) and head and neck cancers. HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent against HPV 16 and 18 infection are now available and have the potential to reduce the incidence of cervical and other anogenital cancers.
Cancer of the cervix uteri is the 4th most common cancer among women worldwide, with an estimated 5,27,624 new cases and 2,65,672 deaths in 2012. Worldwide, mortality rates of cervical cancer are substantially lower than incidence with a ratio of mortality to incidence to 50.3%.
Current estimates indicate that every year 1,22,844 women are diagnosed with cervical cancer and 67,477 die from the disease. Cervical cancer ranks as the 2nd most frequent cancer among women in India and the 2nd most frequent cancer among women between 15 and 44 years of age. About 5.0% of women in the general population are estimated to harbour cervical HPV-16/18 infection at a given time, and 83.2% of invasive cervical cancers are attributed to HPVs 16 or 18. Prophylactic HPV vaccination has provided a powerful tool for primary prevention of cervical cancer and other HPV-related diseases. Three HPV vaccines are now available: bivalent (against HPVs 16/18), quadrivalent (against HPVs 6/11/16/18) and the recently approved 9-valent vaccine (against HPVs 6/11/16/18/31/33/45/52/58). Two doses of HPV vaccine are advised for adolescent/preadolescent girls aged 9–14 years; for girls 15 years and older, current 3 dose schedule will continue. For two-dose schedule, the minimum interval between doses should be 6 months. Human Papillomavirus (HPV) vaccination program is directed towards the prevention of cervical cancer. Delhi is now the first state to launch the Human Papillomavirus (HPV) vaccine as a public health program for school children (9–13 years).
The disease is prevalent throughout the year and pediatricians and pediatric hospitals get typhoid cases almost throughout the year. Although conjugated vaccine is available, the protective efficacy is around 60% and paratyphoid infection is not protected by the conjugate polysaccharide vaccine. The best ways are to adopt universal precautions and personal hygiene for the protection of typhoid fever.
Prevention of typhoid
- Five million cases annually in India
- Severe morbidity, 1–2% mortality
- Carrier state: Spread through food handlers
- About 50–90% of Salmonella typhi are multidrug-resistant of late quinolone resistance—90%.
Tuberculous Meningitis or Encephalitis
The true incidence is not known. But the fact remains that private and public institutions admit very few cases of TB meningitis or encephalitis when compared to yesteryears due to good control of hematogenous spread of the disease in children with high coverage of bacille Calmette–Guérin (BCG) vaccine. Recent meta-analysis confirms the significant decline in the incidence of TB meningitis or encephalitis, miliary TB and disseminated TB.
Meningococcal Meningitis and Disease
Meningococcal meningitis or cerebrospinal fever occurs sporadically and in small outbreaks in most parts of the world. The zone lying between 5° and 15° N of the equator in tropical Africa is called the “meningitis belt” because of the frequent epidemic waves that have been occurring in that region. During recent years, several serious outbreaks affecting numerous countries occurred, not only in the so-called meningitis belt in Africa but also in both tropical and temperate zones of other continents, viz. Americas, Asia and Europe. WHO estimates that about 500,000 cases of meningococcal disease occur every year worldwide causing 50,000 deaths. The fatality of typical untreated cases is about 80%. With early diagnosis and treatment, case fatality rates have declined.
Before 2010 and the mass preventive immunization campaigns, Group A meningococcus accounted for an estimated 80–85% of all cases in the meningitis belt, with epidemics occurring at intervals of 7–14 years. Since then, the proportion of the A serogroup has declined dramatically. During the 2014 epidemic season, 19 African countries implementing enhanced surveillance reported 11,908 suspected cases including 1146 deaths, the lowest numbers since the implementation of enhanced surveillance through a functional network.
Meningococcal disease is endemic in India. N. meningitidis is the third most common cause of bacterial meningitis in India in children aged <5 years, and is responsible for an estimated 1.9% of all cases regardless of age. The majority of reported cases are due to serogroup A, with rare reports of serogroups B and C. Cases of meningococcal meningitis are reported sporadically or in small clusters. During 2007, about 4,472 cases of meningococcal meningitis were reported in India with about 252 deaths. The decision to undertake mass vaccination following an outbreak is based upon the attack rate within an area. During inter epidemic and epidemic periods, immunoprophylaxis of high-risk populations is implemented and chemoprophylaxis with antimicrobials is used for close contacts.
Invasive Hemophilus Influenzae Disease
Although the exact incidence of the magnitude of invasive H. influenzae and pneumococcal diseases is not known, hospital admissions clearly indicate that these two organisms significantly contribute to invasive diseases like pneumonia and meningitis.
Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years. The incidence in this age group is estimated to be 0.29 episode per child-year in developing and 0.05 episodes per child-year in developed countries. This translates into about 156 million new episodes each year worldwide, of which 151 million episodes are in the developing world. Most cases occur in India (43 million), China (21 million) and Pakistan (10 million), with additional high numbers in Bangladesh, Indonesia and Nigeria (6 million each). Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and South-East Asia.
Effective vaccines are now available for their control and IAP recommends Hib vaccine for routine use preferably in combination formulation of diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB-Hib) at 6, 10 and 14 weeks.
Figure 1.1.3 depicts the global disease burden including India.
Estimated invasive Hib disease in India: Based on community-based report:
- Meningitis 17 per 100,000 children per annum
- Pneumonia 1.5 times meningitis: 25 per 100,000 children per annum
- Total invasive disease: 42 per 100,000 per annum
- Hib disease per 100,000: 266–1,750
- Children below 5 years (15% of total population) 15, 40, 52, 287
- Total estimates in India: 409,640–2,695,000
Case fatality due to invasive Hib diseases
- If CFR 2%: 8,192–53,900 per annum
- If CFR 10%: 40,964–269,500 per annum
Studies reporting invasive Hib disease are limited.
Reported from all parts of India:
- Hib pneumonia: 2–33%
- Hib meningitis: 2–35%
- Almost half of the children are colonized with Hib
- Agent is present in abundance
- Risk factors for increased invasive Hib disease exist in India.
(Source: IAP Immunization update; 2006.)
The proposal to include pentavalent DTPw-HB-Hib vaccine formulation in NIP was recommended by National Technical Advisory Group on Immunization (NTAGI) and approved by the central cabinet to bring down the Hib disease burden in India. Government of India has successfully implemented mass immunization program with pentavalent vaccine, which is now introduced in all the states of India. The use of pentavalent vaccine automatically raises the coverage level of hepatitis B and hib vaccines. If the vaccines are given individually, the coverage of hepatitis B and hib vaccines usually lags behind DPT coverage. This gap can be filled by using pentavalent vaccine in routine immunization program.
Pneumonia is the single largest infectious cause of death among under-five children worldwide, accounting for about 0.92 million deaths in 2015. It is estimated that 1 in 6 deaths in under-five children was due to pneumonia in 2015. Pneumococcal pneumonia in particular is a major public health concern for children globally. This infection accounts for 18% of all severe pneumonia cases and 33% of all pneumonia deaths worldwide. More than 80% of deaths associated with pneumonia occur in children during the first two years of life. Pneumococcal disease is also the number one vaccine-preventable cause of death in children under five, globally and in India (Fig. 1.1.4).
Fig. 1.1.3: Global Hib incidence rate.Source: WHO decision-making and implementation of conjugate Hib vaccines (NUVI); 2009
Fig. 1.1.4: Percentage of deaths among children under age 5 attributable to pneumonia, 2015.Source: WHO and Maternal and Child Epidemiology Estimation Group (MCEE) provisional estimates 2015 http://data.unicef.org/child-health/pneumonia.html#sthash.D7850ssq.dpuf
Incidence of invasive pneumococcal diseases:
- Around 12–35% of all admissions are due to LRT in India. In 2010, 3.6 million episodes of severe pneumonia and 0.35 million all-cause pneumonia deaths occurred in children under the age of 5 years in India. Among those, 0.56 million episodes of severe pneumonia (16%) and 0.10 million deaths (30%), respectively, were caused by pneumococcal pneumonia. India has a pneumonia mortality rate of 7 per 1000 live births.
- Streptococcus pneumococcus is the cause for 50% of community acquired pneumonia, 20–40% of all pyogenic meningitis.
- The rate of invasive pneumococcal disease: 167/100,000 less than 2 years in USA (before vaccination), 224–349/100,000 less than 5 years in developing countries.
The ten countries with the highest numbers and proportions of pneumococcal cases were all in Asia and Africa; they account for 66% (44–88%) of pneumococcal cases worldwide (India 27%, China 12%, Nigeria 5%, Pakistan 5%, Bangladesh 4%, Indonesia 3%, Ethiopia 3%, Congo 3%, Kenya 2% and the Philippines 2%). Of the 14.5 million pneumococcal cases, 95.6% were cases of pneumonia, 3.7% nonpneumonia, nonmeningitis invasive pneumococcal syndromes and 0–7% meningitis.
Pneumococcal deaths in children aged 1–59 months per 100,000 children younger than 5 years (HIV-negative pneumococcal deaths only). The boundaries shown and the designations used on this map do not imply the expression of any opinion by WHO concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines in Figure 1.1.5 represent approximate border lines for which there may not yet be full agreement.
The new 13 valent pneumococcal vaccine, offers about 70–75% protection against the prevalent strains in India. In May 2017, Government of India decided to include pneumococcal conjugate vaccine (PCV) in UIP in a phased approach. With this phased introduction, nearly 2.1 million children in 3 states will be vaccinated with PCV in the first year. The coverage will be expanded across the entire country in the coming years.
Acute Diarrheal Diseases
Diarrhea is a leading killer of children, accounting for 9% of all deaths among children under age 5 worldwide in 2015. This translates to over 1,400 young children dying each day, or about 526,000 children a year, despite the availability of simple effective treatment.
Figure 1.1.6 depicts the global disease burden including India.
In India, diarrheal disease is a major health problem. More than 300 million episodes of acute diarrhea occur every year in children under 5 years of age. During 2005, about 1.07 million cases of acute diarrhea were reported in India with 2,040 deaths. The actual incidence must be many fold. The National Diarrhoeal Disease Control Programme has made a significant contribution in averting deaths among children under 5 years of age. Much attention has been given to acute diarrhea and its management over the last decade, which is dominated by advances in oral rehydration techniques.
Fig. 1.1.5: Ten countries with the greatest number of pneumococcal deaths in children aged 1–59 months.Source: Lancet. Vol 374 September 12, 2009.
Fig. 1.1.6: Percentage of deaths among children under age 5 attributable to diarrhea, 2015.Source: WHO and Maternal and Child Epidemiology Estimation Group (MCEE) provisional estimates 2015
The rotavirus, first discovered in 1973, has emerged as the leading cause of severe, dehydrating diarrhea in children aged under 5 years globally, with an estimated more than 25 million outpatient visits and more than 2 million hospitalizations attributable to rotavirus infections each year. In developing countries, three-quarters of children acquire their first episode of rotavirus diarrhea before the age of 12 months, whereas in developed countries the first episode is frequently delayed until the age of 2.5 years. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. The NTAGI have recommended the introduction of Rotavirus vaccine with GAVI subsidy in the NIP in a phased manner.
India has made steady progress in reducing deaths in children younger than 5 years, with total deaths declining from 2.5 million in 2001 to 1.5 million in 2012. This remarkable reduction was possible due to the inception and success of many universal programs like expanded program on immunization, program for the control of diarrheal diseases and acute respiratory infection. Even though the deaths among children under-5 years have declined, the proportional mortality accounted by diarrheal diseases still remains high. Diarrhea is the third most common cause of death in under-five children, responsible for 13% deaths in this age-group, killing an estimated 3,00,000 children in India each year.
Cholera is an acute diarrheal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development. Globally, the actual number of cholera cases is known to be much higher; the discrepancy is the result of under reporting and inconsistency in case definition and lack of standard vocabulary. Some countries report laboratory confirmed cases only, and so many cases are labeled as acute watery diarrhea. Researchers have estimated that every year, there are roughly 1.3 to 4.0 million cases, and 21,000 to 1,43,000 deaths worldwide due to cholera. Epidemics of cholera are frequent, striking adults as well as children.
India accounts for 675,188 cases and 20,256 deaths. In addition, an issue of concern is that 65–86% of the isolates have been found to be resistant to the commonly used antimicrobials and their prevalence is concentrated in the lowest quintile of wealth. In India, during 2005, the larger endemic foci of cholera were found in Delhi (945 cases), Tamil Nadu (724 cases and one death), West Bengal (235 cases), Andhra Pradesh (165 cases), Karnataka (214 cases and one death), Kerala (27 cases and one death) and Gujarat (82 cases and two deaths). The total number of cases reported was 3,156 with six deaths. In the year 2008, WHO has recorded 2,680 cases of cholera in India.
The most effective prophylactic measure is health education directed mainly to: (a) effectiveness and simplicity of oral rehydration therapy; (b) benefits of early reporting for prompt treatment; (c) food hygiene practices; (d) hand washing after defecation and before eating; and (e) benefits of cooked, hot foods and safe drinking water. Since cholera is a disease of the poor and ignorant, these groups should be tackled first.
Although, a parenteral cholera vaccine of Ogawa and Inaba serotypes of V. cholerae is available, there are still doubts about its usefulness as a preventive measure. The oral cholera vaccine now available in India is recommended for routine use in cholera endemic regions.
Diarrheal Diseases Control Program
The incidence of cholera cases and deaths has decreased in recent years. Oral rehydration therapy program was started in 1986–87 in a phased manner. The main objective of the program is to prevent diarrhea-associated deaths in children due to dehydration. The program highlights the rational management of diarrhea in children, including increased intake of home available fluids, zinc supplementation and breastfeeding. Oral rehydration solution (ORS) is being supplied as a part of subcenter kits and is promoted as a first line of treatment.
India has made steady progress in reducing deaths in children younger than 5 years, with total deaths declining from 2.5 million in 2001 to 1.5 million in 2012. This remarkable reduction was possible due to the inception and success of many universal programs like expanded program on immunization, program for the control of diarrheal diseases and acute respiratory infection. Even though the deaths among children under-5 years have declined, the proportional mortality accounted by diarrheal diseases still remains high. Diarrhea is the third most common cause of death in under-five children, responsible for 13% deaths in this age-group, killing an estimated 300,000 children in India each year.
At present, about 109 countries in the world are considered endemic for malaria, 45 countries within WHO African region. There were an estimated 216 million episodes of malaria in 2010, with a wide uncertainty interval (5th–95th centiles) from 149 million to 274 million cases. Approximately 81%, or 174 million (113–239 million) cases, were in the African region, with the South-East Asian Region (SEAR) accounting for another 13%.
There were an estimated 655,000 (5,37,000–9,07,000) malaria deaths in 2010, of which 91% (596,000, range 4,68,000–8,37,000) were in the African Region. Approximately 86% of malaria deaths globally were of children under 5 years of age.
In the SEAR, during 2009, a total of 2.7 million confirmed malaria cases and 3,188 malaria deaths were reported whereas estimated malaria cases were around 26–36 million and malaria deaths between 42,300 and 77,300. The highest number of laboratory confirmed cases were reported from India (15,63,344) followed by Indonesia (5,44,470) and Myanmar (4,14,008) whereas the lowest number of cases was reported from Sri Lanka (558) followed by Bhutan (972) and Nepal (3,335). In case of malaria deaths, the highest number of deaths were reported from India (1,133) followed by Myanmar (972) and Indonesia (900).
In India, malaria continues to pose a major public health threat, particularly due to plasmodium falciparum which is prone to complications. Experts estimate that more than 1.5 million persons are infected with malaria every year. The most affected states are North-Eastern states, Chhattisgarh, Jharkhand, Madhya Pradesh, Orissa, Andhra Pradesh, Maharashtra, Gujarat, Rajasthan, West Bengal and Karnataka. However, the other states are also vulnerable with local and focal outbreaks of malaria. Much of these areas are remote and inaccessible, fore or forest fringed with operation difficulties and predominantly inhabited by tribal population.
Despite these challenges, India is working – and making progress towards the elimination of malaria. Since 2000, the country has more than halved the number of malaria cases, down from 2 million to 8,82,000 in 2013 and, the trend is continuing. To reach pre-elimination, all states in India will need to have annual parasite incidence (API) of less than 1 per 1000 and all districts within the state will also need to be less than 1. Currently, 74% of India's more than 650 districts have achieved an API of less than 1. Strong financial support, increased surveillance, more health workers, and further program integration in all levels of the health system will be needed for the country to reach elimination.
Currently, there is no vaccine available, but research is going on for a vaccine to prevent infection and/or ameliorate disease. Unlike other vaccines, a malaria vaccine even with only 50% efficacy would still be very useful in controlling the disease. The time-bound objectives set out for the Eleventh (XIth) Five-Year Plan by Ministry of Health (MoH) and Family Welfare, Government of India (GoI) is reduction of malaria mortality rate by 50% up to 2010 and an additional 10% by 2012.
Japanese Encephalitis (JE) is mosquito-borne encephalitis infecting mainly animals and incidentally man. Twenty-five years ago, JE was known as an endemic disease in East Asia, especially in Japan, China and Korea but in recent years, it has spread widely in South-East Asia, and outbreaks of considerable magnitude have occurred in Thailand, Indonesia, Vietnam, India, Myanmar and Sri Lanka.
An estimated 50,000 cases of JE occur globally each year, with 10,000 deaths and nearly 15,000 disabled. About three-quarters of the cases occur in the Western Pacific countries, primarily China and adjacent countries, with the remainder occurring in South-East Asia, especially India.
In India, the states reporting repeated outbreaks are Andhra Pradesh, Assam, Bihar, Haryana, Karnataka, Kerala, Maharashtra, Manipur, Tamil Nadu, Uttar Pradesh and West Bengal. The population at risk is about 300 million. The incidence of JE in India is still increasing, and the case-fatality rate of reported cases is high, i.e. 10–30%. India currently has no national vaccination program, but the MoH has recently drawn up a plan in which children 1–12 years of age will be immunized. In Tamil Nadu and Uttar Pradesh, immunization programs are already running; thus, JE incidence might stabilize in those regions. However, overall trends for India are difficult to predict because JE endemicity is heterogeneous and because socioeconomic conditions for control differ substantially from one state to another. As per the recent figures from WHO (2008), there have been 294 cases of JE reported in India.
According to the Directorate of National Vector Borne Disease Control Programme (NVBDCP), Delhi, 1661 cases of JE were reported in the year 2014 from 15 states and union territories, out of which 293 (17.6%) died. Assam, West Bengal, Uttar Pradesh (UP) and Jharkhand reported maximum number of cases.
Following mass vaccination campaigns with live attenuated SA-14-14-2 JE vaccine among pediatric age group, adult JE cases have outnumbered pediatric cases in some JE endemic states, including Assam. This led the state government of Assam to conduct special campaigns of JE vaccines in adults (>15 years) in some most affected districts. The exact reason behind this shift in age group is not well understood. On 3rd July, 2014 the Government of India (GOI) announced the introduction of four new vaccines, including JE vaccine, in the National immunization program. Recently, NVBDCP has identified 20 high burden districts in three states—Assam, Uttar Pradesh, and West Bengal, for adult JE vaccination (>15–65 years).
It remains a worldwide public health problem. It is estimated that about one-third of the current global population is infected asymptomatically with tuberculosis (TB). Most new cases and deaths occur in developing countries where infection is often acquired in childhood. The annual risk of TB infection in high-burden countries is estimated to be 0.5–2%.
India is the highest TB burden country in the world and accounts for nearly one-fifth (20%) of global burden of TB, two-thirds of cases in SEAR. Of the 9.2 million cases of TB that occur in the world every year, nearly 1.9 million are in India. Two out of every five Indians are infected with TB bacillus. In India, almost 0.37 million people die every year.
India accounts for one fourth of the global TB burden. In 2015, an estimated 28 lakh cases occurred and 4.8 lakh people died due to TB. The table below shows the estimated figures for TB burden globally and for India reported in WHO Global TB Report for the year 2015 (Table 1.1.4).
An estimated 1.3 lakh incident multi-drug resistant TB patients emerge annually in India which includes 79000 MDR-TB patients estimates among notified pulmonary cases. India bears second highest number of estimated HIV associated TB in the world. An estimated 1.1 lakh HIV associated TB occurred in 2015 and 37,000 estimated number of patients died among them.
DOTS-Plus for the management of drug resistant TB in India had been launched in 2007. There was then very limited progress between 2007 and 2009.
But by 2009, it was planned that by the end of 2011 the drug resistant TB services would be available across India. The DOTS-Plus services (now referred to as the “Programmatic Management of Drug Resistant TB”) had been expanded across the whole country by 2012 and the service was available in all districts by 2013. By 2013 it had though been decided to decentralise the DOTS Plus services. The services were to be totally integrated into the main Revised National TB Control Programme (RNTCP) services at local level. In 2015, a total of 9,132,306 cases of suspected TB were examined by sputum smear microscopy and 1,423,181 people were diagnosed and registered for TB treatment by government's RNTCP.
The current vaccine strains are all descendants of the original Mycobacterium bovis isolate that Calmette and Guérin passaged through numerous cycles during the 13-year period, 1909–1921. Although, a number of BCG vaccine strains are available, in terms of efficacy, no BCG strain is demonstrably better than another, and there is no global consensus as to which strain of BCG is optimal for general use. Following closure of BCG vaccine laboratories in India, the GoI is using the BCG vaccine manufactured by Serum Institute of India Ltd., Pune, and Green Signal Bio Pharma Ltd. in its NIP.
The objective set out for TB control by MoH and Family Welfare, GoI, is to maintain 85% cure rate through entire mission period and also sustain planned case detection rate.
The acquired immunodeficiency syndrome (AIDS) is a fatal illness caused by human immunodeficiency virus (HIV) which breaks down the body's immune system, leaving the victim vulnerable to a host of life-threatening opportunistic infections, neurological disorders or unusual malignancies. Acquired immunodeficiency syndrome refers to the last stage of the HIV infection and can be called a modern pandemic affecting both industrialized and developing countries (Table 1.1.5).
Since the beginning of the epidemic, more than 70 million people have been infected with the HIV virus and about 35 million people have died of HIV. Globally, 36.7 million [34.0–39.8 million] people were living with HIV at the end of 2015. An estimated 0.8% [0.7–0.9%] of adults aged 15–49 years worldwide are living with HIV, although the burden of the epidemic continues to vary considerably between countries and regions. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 25 adults (4.4%) living with HIV and accounting for nearly 70% of the people living with HIV worldwide (Fig. 1.1.7).
In Asia, an estimated 4.9 million (4.5–5.5 million) people were living with HIV in 2009. In 2009, an estimated 300,000 (260,000–340,000) people died of AIDS-related illnesses. Asia, home to 60% of the world's population, is second only to sub-Saharan Africa in terms of people living with HIV.
As per the recently released, India HIV Estimation 2015 report, National adult (15–49 years) HIV prevalence in India is estimated at 0.26% (0.22–0.32%) in 2015. In 2015, adult HIV prevalence is estimated at 0.30% among males and at 0.22% among females. Among the States/UTs, in 2015, Manipur has shown the highest estimated adult HIV prevalence of 1.15%, followed by Mizoram (0.80%), Nagaland (0.78%), Andhra Pradesh and Telangana (0.66%), Karnataka (0.45%), Gujarat (0.42%) and Goa (0.40%). Besides these States, Maharashtra, Chandigarh, Tripura and Tamil Nadu have shown estimated adult HIV prevalence greater than the national prevalence (0.26%).
Until a vaccine or cure for AIDS is found, the only means at present available is health education to enable people to make life-saving choices. All mass media channels should be involved in educating the people on AIDS, its nature, transmission and prevention. The development of drugs (antiretrovirals) that suppress the infection rather than its complications has been an important achievement. These antiretroviral chemotherapy, while not a cure, have proved to be useful in prolonging the life of severely ill patients.
This disease is essentially a tropical one and is endemic in large parts of Latin and South America. Of late, its incidence has been on the increase in Asian countries such as India. A large number of infections may be subclinical, that is, the patients may not even be aware that they have had the disease. Treatment is usually supportive and symptomatic. Most patients will recover without any sequel. The overall mortality rate with effective treatment is close to 1% but this may be higher in children. A vaccine is in the late stages of development, but is still not available for commercial use on a large scale. Control of the mosquito population reduces the incidence of dengue, yellow fever and certain other rare fevers that are also transmitted by the same species of mosquito.
Fig. 1.1.7: A global view of human immunodeficiency virus infection. Globally, 36.7 million [34.0–39.8 million] people were living with HIV at the end of 2015.Source : http://www.who.int/gho/hiv/en/
As per the information from the Director, India's National Vector-borne Disease Control Programme, a total of 12,000 cases and 50 deaths have been reported in the country until October, 2010. These figures are as per the reported cases from the states/UTs and the number of actual infections is likely to be far higher.
The time-bound objectives set out for the Eleventh (XIth) Five-Year Plan by MoH and Family Welfare, GoI, is reduction of dengue mortality rate by 50% up to 2010 and sustaining at that level until 2012.
Also in 2015, Delhi, India, recorded its worst outbreak since 2006 with over 15 000 cases. In 2016, till month of September, 39,771 cases and 78 deaths were reported in India.
WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.
A dengue-like disease and manifested by high fever and severe excruciating articular pains in the limbs and spinal column. There was an outbreak of this disease in Kolkata in 1963–1964 and another in Chennai in 1965, which gave rise to 300,000 cases in Chennai city alone.
The disease has reappeared after 41 years. During 2006, there was a large outbreak of chikungunya in India, with 1.39 million officially reported cases spread over 16 states; attack rates were estimated at 45% in some areas. The outbreak was first noticed in Andhra Pradesh and it subsequently spread to Tamil Nadu, Kerala and Karnataka, and then northward as far as Delhi. The other states involved were Maharashtra, Madhya Pradesh, Gujarat, Rajasthan, Puducherry, Goa, Orissa, West Bengal, Uttar Pradesh, Andaman and Nicobar Islands. During 2007, until 12th October, a further 37,683 cases had been reported by the Government of India. In the year 2010, again thousands of people have been reported to be diagnosed with the virus.
Currently in 2016, big upsurge/epidemic due to Chikungunya is going on in Delhi and cases being reported from other States/UTs too. Till, 11th September, 2016 a total of 14,656 clinically suspected cases (including 1724 in Delhi) from 18 states and 2 UT's have been reported.
It is a respiratory infection and transmission is through contact with respiratory secretions from an infected person who is coughing or sneezing. The symptoms are similar to seasonal flu but with a higher intensity. The patient may present with high grade fever (≥38°C), cough, sore throat, runny or stuffy nose, body aches, lack of appetite, lethargy, headache, chills and fatigue. In addition, nausea, vomiting and diarrhea have been reported (higher rate than for seasonal flu). It was first noted in Mexico in March-April, 2009, and then rapidly spread to the US, Canada and throughout the world. More than 214 countries reported laboratory confirmed cases, including more than 18,366 deaths. In India, since 2009 until September 26, 2010, out of the total 44,350 laboratories-confirmed cases of swine flu there have been more than 2,500 deaths reported (Source: www.mohfw-h1n1.nic.in).
A resurgence of swine flu in several states of India has caused a considerable concern in 2012. Fresh outbreaks of the dreaded virus surfaced in Maharashtra, Rajasthan and some other states claiming at least 21 lives from January till March, 2012.
Fig. 1.1.8: Percentage of respiratory specimens that tested positive for influenza.Source: http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/
At least 309 cases were reported in five states including Andhra Pradesh, Karnataka and Gujarat, according to the latest health ministry figures.
Of the total 21 deaths in 2012 so far, Maharashtra has reported nine deaths, followed by seven in Rajasthan and five in Andhra Pradesh. No death has taken place in Karnataka and Gujarat, which have also reported cases of H1N1 virus (Fig. 1.1.8).
In 2014, a total of 218 people died from the H1N1 flu, India recorded 837 laboratory confirmed cases in the year.
Every year, there was a rise in number of cases and deaths during winter as temperature affects virus. During 2014–15 winter, there was a spurt in cases at the end 2014. In 2015, the outbreak became widespread through India. On 12 February 2015, Rajasthan declared an epidemic.
The WHO now considers swine flu also as a seasonal epidemic and has recommended to the global and indigenous flu vaccine manufacturers to manufacture combined seasonal and swine flu vaccine. Accordingly, all WHO prequalified laboratories manufacturing flu vaccines have come out with their combined pH1N1 and the seasonal H3N2 A and B strains of the flu vaccines. For the prevention of swine flu, there are two types of vaccines which are available in the market: (1) live attenuated influenza vaccine—a nasal spray and (2) an inactivated vaccine—injection.
Statistics from sentinel centers may reveal the incidence of other infectious diseases, which are not reliable as they represent only the “tip of the iceberg”. The need for establishing a Center for Disease Control, like the CDC, Atlanta and the effective monitoring of the IDSP, may help in knowing the exact disease burden in India.
FUTURE OF VACCINE PREVENTABLE DISEASES SURVEILLANCE IN INDIA
- The incidence of diphtheria, pertussis, tetanus (including neonatal tetanus), measles is still a matter of concern despite the implementation of NIP since 1985.
- A nationwide high coverage to near 100% in routine immunization is the need of the hour in India.
- The IDSP is a welcome project, but alternately the establishment of a CDC and subsequent guidelines from time-to-time for disease control are the ideal measures for activity control and elimination of infectious diseases in India.
- The updation of immunization practices by the Government and Professional agencies periodically with introduction of new vaccines like pneumococcal, HPV, etc. should also be expedited.
The authors are indebted to Dr Sameer Parekh and Dr Pramod Pujari, Serum Institute of India Pvt. Ltd., Pune, India, for help rendered in the preparation of this section.
- Annual TB Report (TB India 2017). Revised National TB Control Programme (RNTCP). Available on http://tbcindia.gov.in/WriteReadData/TB%20India%202017.pdf
- Bavdekar S, Karande S. Elimination of measles from India: Challenges ahead and the way forward. J Postgrad Med. 2017;63(2):75–8.
- Borrow R, Lee JS, Vázquez JA, et al. Global Meningococcal Initiative. Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative. Vaccine. 2016;34(48):5855–62.
- Bruni L, Barrionuevo-Rosas L, Albero G, et al. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 19 April 2017. [Accessed on 19th July 2017]
- Bull WHO. 1978;56(6):819–32.
- Bull World Health Organ. 2008;86(5):408-16.
- Dengue Cases and Deaths in the Country since 2010. National Vector Borne Disease Control Programme. Ministry of Health and family welfare, Govt of India 2016.
- Drug resistant TB in India—Transmission, diagnosis, treatment. www.tbfacts.org
- Garg R, Singh K. Epidemiological study of rubella outbreaks in Rajasthan, India. Int J Community Med Public Health. 2017;4(7):2417–22.
- Government of India (2006). Health Information of India; 2005, Ministry of Health and Family Welfare, New Delhi, India.
- Government of India (2007), NRHM Newsletter Vol. 3., No. 2, July-Aug. 2007, National Rural Health Mission, Department of Health and Family Welfare, New Delhi, India.
- Government of India (2008), TB India 2008, RNTCP Status report, I am stopping TB, Ministry of Health and Family Welfare, New Delhi, India.
- Government of India (2008). Annual report 2007-08, Ministry of Health and Family Welfare, New Delhi, India.
- Gupta E, Dar L, Broor S. Seroprevalence of rubella in pregnant women in Delhi, India. Indian J Med Res. 2006;123:833–5.
- Gupta SS, Bharati K, Sur D, et al. Why is the oral cholera vaccine not considered an option for prevention of cholera in India? Analysis of possible reasons. Indian J Med Res. 2016;143(5):545–51.
- Hepatitis B Fact sheet 2016 India. http://www.searo.who.int/india/topics/hepatitis/factsheet_b__hepatitisday2016.pdf?ua=1.
- Human Papillomavirus and Related Diseases Report. India HPV information Centre. Feb 2016.
- India drives down malaria rates, sets sights on elimination April 2015. World Health Organization. http://www.who.int/features/2015/india-programme-end-malaria/en/
- India HIV estimations 2015. Technical Report. NACO & National Institute of Medical Statistics, ICMR. Ministry of Health & Family Welfare, Government of India, New Delhi. Available from: http://www.naco.gov.in [Accessed on 19th July 2017.]
- Influenza update – 272 19 September 2016. World Health Organization. http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en
- Jacobson J, Sivalenka S. Japanese encephalitis globally and in India. Indian J Public Health. 2004;48(2):49–56.
- Khare S, Banerjee K, Padubidri V, et al. Lower immunity status of rubella virus infection in pregnant women. J Commun Dis. 1987;19(4):391–5.
- Kristie EN Clarke. US Centers For Disease Control And Prevention. Review Of The Epidemiology Of Diphtheria – 2000-2016. Available on http://www.who.int/immunization/sage/meetings/2017/april/1_Final_report_Clarke_april3.pdf?ua=1
- Malaria. Disease burden in SEA region. WHO regional office report for South-East Asia, 2010.
- Meningococcal vaccines: ploysaccharide and polysaccharide conjugate vaccines, weekly epidemiological Ruord. 2002;77(40): 331–9.
- National Guide for clinical management of Chikungunya 2016. Ministry of Health and family welfare, Gov of India.
- O'Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374(9693):893–902.
- Parida M, Dash PK, Tripathi NK, et al. Japanese Encephalitis Outbreak, India, 2005. Emerg Infect Dis. 2006;12(9):1427–30.
- Sachdeva A. Pneumococcal Conjugate Vaccine Introduction in India's Universal Immunization Program. Indian Pediatr. 2017;54(6):445–6.
- Safety and immunogenicity of tetanus toxoid in pregnant women. J Obstet Gynecol India. 2009;59(3):224–7.
- Sharma HJ, Padbidri VS, Kapre SV, et al. Seroprevalence of rubella and immunogenicity following rubella vaccination in adolescent girls in India. J Infect Dev Ctries. 2011;5(12):874–81.
- Shrivastava S et al. Measles in India: Challenges & recent developments. Infection Ecology and Epidemiology 2015, 5:27784
- UNICEF's global report. One is too many: Ending child deaths from pneumonia and diarrhoea. Key Findings 2016.
- Vashishtha VM, Bansal CP, Gupta SG. Pertussis vaccines: position paper of Indian Academy of Pediatrics (IAP). Indian Pediatr. 2013;50(11):1001–9.
- Vipin M, Vashishtha et al. IAP Position Paper on Burden of Mumps in India and Vaccination Strategies. Indian Pediatrics Volume 52 June 15, 2015.
- Vipin M, Vashishtha et al. Vaccination Policy for Japanese Encephalitis in India: Tread with Caution! Indian Pediatrics Volume 52 October 15, 20.
- WHO (2008), Global Tuberculosis Control, Surveillance, Planning, Financing, WHO Report, 2008.
- WHO. Wkly Epi Rec. 2006; No. 43.
- WHO Epi Rec. No. 13. 2010;85:117-28.
- WHO vaccine-preventable diseases: monitoring system. 2017 global summary. Available on http://apps.who.int/immunization_monitoring/globalsummary/countries?countrycriteria%5Bcountry%5D%5B%5D=IND [Accessed on 18th Jul 2017]
- World Health Report 1996, Report of the Director-General, WHO.
- World Malaria Report, 2001.
1.2 INFECTIOUS DISEASES SURVEILLANCE IN INDIA
T Jacob John
The dictionary meaning of the word surveillance is “close observation of a suspected spy or criminal”. Close observation of diseases in the community—occurrence, numbers and outbreaks—provides clues about the culprits, the causative pathogens. There is thus a parallel between police intelligence in surveillance for protecting citizens against crimes and epidemiological intelligence through disease surveillance for protecting people from infectious diseases, particularly outbreaks. Epidemiological investigation after getting information about diseases through surveillance is, in fact, a form of detective work. Although diseases are kept under surveillance, their causative agents are the target of surveillance.
The World Health Organization (WHO) defines disease surveillance as: “the ongoing systematic collection, collation, analysis and interpretation of data [on diseases], followed by the dissemination of information to those who need to know in order that action may be taken”. In other words, disease surveillance is required for public health action for disease prevention or control. If appropriate action does not follow, the mere collection of information is insufficient to qualify as surveillance as it may serve only the purpose of statistics for administrative understanding, but not that of public health. So, in short, surveillance is “systematic collection of information on diseases for public health action to prevent or control them.” Therefore, it is often referred to as “public health surveillance”. The data collected through public health surveillance will identify diseases to be prioritized for control if not already identified for control. The data will also form the basis of systematic monitoring of the degree of control being achieved year to year.
True public health surveillance has two characteristics—continuity in time and coverage in space. If there are gaps, infectious agents may cause sporadic cases or even outbreaks undetected by the designated staff. Collection of data on the incidence or prevalence of non-infectious diseases is through other methods—such as case registries, surveys of population samples, cumulating hospital statistics, etc. However, many use the term surveillance, inexactly, for other forms of data collection on health conditions, risk factors, etc. or for discontinuous collection of data on infectious diseases. In other words, the term surveillance is often loosely used for various methods of collection of data, diluting its definitional meaning. Therefore, it will be difficult now to restrict its usage strictly according to definition. In each context, it is necessary to redefine surveillance or at least understand that the term is not used according to the precise definition.
The several common usages of the term surveillance have been presented in this chapter. In most such situations the main deficiency is the lack of the requirement of public health action following data collection. As India does not have a public health infrastructure that can respond adequately to surveillance information, true surveillance as practiced in countries with public health infrastructure is not easy. Therefore, collection of data remains in many situations only for statistical purposes, as has been illustrated. Only very few diseases or their infectious agents are kept under surveillance for monitoring progress of control and for responding with public health action. They have been described in detail.
PASSIVE AND ACTIVE SURVEILLANCE
Disease surveillance is classified as passive and active. In countries with public health infrastructure, there would be a set-up for surveillance in all population units (such as districts). It is usually manned by a district officer of public health and supporting staff—epidemiologist, data management expert, laboratory personnel and field staff. The surveillance system has the afferent limb (incoming) for data receiving, a central processing unit (under the public health officer) and efferent limb (outgoing) for investigations and containment actions. This set-up is clearly separated from that which provides medical care to those who become ill. The latter is called healthcare and the former is called public health. Healthcare may be organized in the public sector or in the private sector. Many countries, such as India, have a mix of public and private sector hospitals and clinics and private practitioners, all providing healthcare services on demand. Public health infrastructure, on the other hand, is possible only in the public sector as it requires designated staff free of any responsibility for healthcare, and with legal authority for the officer and staff for enforcing disease surveillance and entering premises for disease investigations or control activities. Government funds staff salaries and all overhead expenses.
Sick people come to the attention of healthcare personnel who diagnose the diseases and treat. There would be a list of specific diseases that have been ‘notified’ (by the health ministry of the government) for surveillance. When a healthcare provider working in public or private sector sees a person with any notified disease, he/she is required (by law) to report that fact to the designated public health official. When all hospitals, clinics and medical practitioners report cases of notified diseases, the public health agency receives, passively so to say, continuous information on the occurrence and distribution of such cases. This method of disease reporting is called “passive surveillance”. In India, every state has a list of notified diseases and the requirement for reporting on their statute books, but in the absence of public health infrastructure surveillance is not enforced. Instead, several ad hoc procedures are practiced for specific disease problems and they remain fragmented but not integrated. In many countries, passive disease surveillance is supplemented by passive reporting of laboratory evidence of specific pathogens infecting any patient.
Imagine that the local public health officer receives a few reports on cholera in a short interval of time, scattered within the community. The officer takes immediate action for searching for unreported cases in the community in order to understand the full extent of the outbreak. Public health staff may now visit all hospitals to check if unreported cases of cholera are admitted and, if any, with cholera-like illness had been seen in the outpatient service, etc. This is an active process, so to say. This is “active surveillance” in which the personnel of the public health agency go out in active search of cases. Information on all cases is required to define the geographic perimeter of the outbreak and to identify risk factors—perhaps the municipal water supply going to a few wards or another common source from which many families had drawn water was the channel of transmission of the pathogen. Further investigations on the quality of water would be done immediately and the contaminated supply would be stopped and disinfected in order to intercept the outbreak. Active surveillance is usually short-lived; once the problem is under control, the system reverts to passive surveillance, which is continuous without break. Often active surveillance is a part of the epidemiological investigations triggered by the detection of a signal from passive surveillance. When a disease is under elimination, active surveillance may become necessary to ensure no case was missed by failure of passive surveillance.
Another way to look at passive and active surveillance is to determine who generates data and how. The nodal agency for disease surveillance is local level (district or city) public health, with its personnel—the public health officer and trained staff. When they search for disease cases, the process is active—for active surveillance. When they receive reports from healthcare personnel, the nodal agency is the passive recipient—in passive surveillance. Passive surveillance per se costs little since healthcare workers earn their income from serving individual patients; their detecting and reporting notified diseases are incidental to their professional work and the only cost involved is postage for mailing the report or for electronic reporting. Those expenses are borne by the public health system—usually by supplying disease reporting forms and post-paid envelopes for enclosing the reports.
THE ROLE OF LABORATORY IN SURVEILLANCE
Although diseases are kept under surveillance, their causative agents are the target of surveillance. Every infectious disease has a specific etiology. In India, the demand for identifying etiology by laboratory testing in healthcare is low for two reasons: (1) patients do not usually demand information and (2) laboratory testing involves additional expenditure. Treating without arriving at etiological diagnosis is not evidence-based and may be unfair to the individual, who alone suffers the risk of diagnostic errors. It is also unfair to the community, since such errors and consequent wrong choice of drug(s) may contribute to the perpetuation of the pathogen in the community and to the development of drug-resistance in pathogens. Unnecessary antibiotics may also lead to drug resistance of normal flora that may be later transferred to pathogens through plasmids. Therefore, scientific medicine demands quality-assured diagnostic laboratory service. This cardinal requirement is not given due importance in many of India's public sector and private sector hospitals. Thus, laboratory surveillance is not practiced in India.
In public health, disease surveillance is to keep pathogens under scrutiny—hence pathogens must be identified in any clustering of cases. No error should be tolerated, as it may jeopardize the health of many in the community. For this reason, in most countries, the public health system maintains laboratories for use by its personnel. They are called public health laboratories, as distinct from clinical laboratories in hospitals. The district officer of public health must have access to public health laboratory. In India, there are public health laboratories, usually a few per state, mostly the continuation what the British had established during colonial era. Microbiology has advanced hugely since then but we have not kept our public health laboratories abreast with the times. In some countries, the central public health laboratory is very advanced and may act as referral laboratory for clinical laboratories in healthcare. In India, the National Centre for Disease Control (previously National Institute of Communicable Diseases) in Delhi is the foremost public health laboratory; it has all the advanced instrumentation and modern techniques for etiological determination of nearly all known pathogens.
THE PURPOSES OF DISEASE SURVEILLANCE
The main reason for establishing passive surveillance was (and continues to be) the early detection of any outbreak. While any one physician may see only one or two cases, collective reporting at the local or regional level will give the overall picture of an outbreak even in the beginning stage. The recognition of an outbreak is the trigger for rapid investigation and application of preventive or control measures. Surveillance of infectious diseases is thus the important link between healthcare and public health. Public health infrastructure was briefly described earlier. Public health is functionally defined as “societal actions for prevention of diseases and promotion of health”. Its effective functioning requires a public health infrastructure. In other countries, it may be called ministry of public health (distinct from ministry of healthcare services), Public Health Department (under ministry of health), health protection agency or public health service. The main purpose of disease surveillance is the early detection of outbreaks in order to intercept them for the present and to pre-empt them from occurring in future. The disease surveillance system of the nation can be assessed by the successes of outbreak detection and control. The reason why many outbreaks in various parts of the country are not effectively and quickly controlled is due to the lack of public health infrastructure.
Another purpose of surveillance is to monitor, quantitatively and in real-time, the degree of decline in incidence of diseases that public health system had targeted for and funds expended for prevention and control. When a government targets a disease for control, it undertakes several activities including the application of preventive interventions and their auditing requires actual measurement of disease reduction over time. The best example in India is the surveillance for polio eradication, which has been described later. Disease control is the term applied for reducing the incidence to a predetermined acceptable level through interventions. Elimination is the extreme degree of control to zero incidence in a defined population, usually a whole country. Global level elimination is eradication. For elimination the disease, surveillance has to be efficient enough to detect even one case anywhere in the country. While control may apply to disease but not necessarily the causative pathogen (as in control of neonatal tetanus) eradication must result in removal of the pathogen from human transmission in order to maintain zero incidence (as in smallpox eradication).
A third purpose of surveillance is to discover new (emerging) diseases. In passive surveillance, physicians are instructed to report not only notified diseases, but also any undiagnosed illness that may be infectious in nature and is serious enough for public health attention. A cluster of undiagnosed illness has to be reported. In 1981, physicians in California reported a few instances of death of young men with an unusual disease. They had pneumonia due to an opportunistic pathogen, Pneumocystis carinii (now renamed jerovicii) that is always associated with severe immune suppression, usually due to malignancies and their treatments. The undiagnosed condition was provisionally named “acquired immune deficiency syndrome” (AIDS)—acquired as these adults had been without any major health problems all their lives. The United States Public Health Service swung into action and by epidemiological studies identified that the common factor among them was practicing male homosexual acts. Wearing of condoms markedly reduced risk of acquiring the putative agent—unknown then and suspected to be some chemical or an infectious agent. Eventually in 1984−85, the causative virus of AIDS was discovered. Imagine, if there was no disease surveillance, or if surveillance did not attract prompt epidemiological investigations, how much time the world would have lost in detecting this emerging infectious disease and its causative agent(s). We now know that AIDS—causing severe unexplained loss of body weight and high case fatality, had been recognized by several physicians in African countries since the early 1970s and the disease even named locally (slim disease). If AIDS had first emerged in India, the situation would not have been much different. This incident illustrates the value of passive surveillance, the sincerity of physicians to diagnose pneumonia by its etiology, their alertness to conclude that the condition was new, their cooperation to report these cases and the efficiency of the public health system in investigating and unraveling the mystery. It also illustrates the importance of identifying risk factors for controlling further spread even before the agent is identified.
SURVEILLANCE FOR ELIMINATION OR ERADICATION
Elimination (in specified countries or cluster of neighboring countries) or eradication (globally) of diseases are examples of extreme disease control. Smallpox was eliminated in India by 1975 and so declared in 1977. Smallpox was eliminated by primary prevention with the smallpox vaccine—and by active surveillance (case-search) and vaccination of all persons who were in contact with every person with smallpox. Fortunately, smallpox did not spread widely, vaccination provided excellent protection and a fair proportion of persons in contact had been already vaccinated under the then existing practice. Immune individuals did not get infected with smallpox virus, or even if infected did not shed virus in sufficient quantity to transmit infection. Without “fever and rash” surveillance, as well as active surveillance following any rumor of fever with rash, smallpox would not have been documented to have been eradicated and eventually certified. After certification of eradication the surveillance was discontinued as the smallpox eradication staffs were reverted to their original work.
Another disease India has eliminated in the 20th century is Dracunculiasis (Guniea worm disease). In addition to human behavior modification resulting in break of the worm's transmission cycle, active surveillance was practiced in endemic geographic regions for two reasons. One was to ensure no contact between the ulcerated skin and surface water collections (to interrupt life cycle) and the second was to document its elimination.
The third major success is elimination of polio caused by natural (wild) polioviruses, as described below. Even though we speak of disease elimination or eradication, in reality what we eliminate is (in most cases) the transmission of the pathogen between humans. Therefore, in addition to clinical surveillance, every suspected case has to be investigated for the pathogen under elimination. These three examples illustrate how ad hoc and single-disease surveillance had to be established in the absence of public health surveillance. They also illustrate the non-sustainability of such efforts.
PASSIVE, ACTIVE, VIROLOGICAL AND ENVIRONMENTAL SURVEILLANCE FOR POLIO ELIMINATION
In 1988, India decided to eliminate polio to join the global polio eradication initiative of the WHO. Because India used live trivalent oral polio vaccine (tOPV) under the Universal Immunization Programme (UIP), the government expected that polio would be controlled first and then eliminated by supplementary pulse immunizations. There was need to document progress toward polio elimination; hence a polio-specific passive disease surveillance system was designed and launched under a special project—the National Polio Surveillance Project (NPSP). It established reporting of acute flaccid paralysis (AFP) by all healthcare institutions where children with AFP would be taken, both in the public and private sectors—for nationwide and continuous AFP surveillance. How does NPSP assess the completeness of AFP reporting? It was known in South America that the incidence of AFP in children under 15 years of age was about 1 per 100,000 per year. The same frequency was applied in India, but soon it was found that our AFP incidence was much greater than in South America. Therefore, surveillance quality is accepted as satisfactory if every district reported annually at least two AFP cases per 100,000 children under-15 per year. In 2011, over 35,000 healthcare institutions are on the AFP reporting network: they report only AFP, no other disease.
Since polio had to be diagnosed by etiology, a network of laboratories was established, by upgrading several existing virus laboratories. They are in Kasauli, Ahmedabad, Kolkata, Lucknow, Delhi, Mumbai, Bengaluru and Chennai. The Mumbai laboratory (Enterovirus Research Centre of Indian Council of Medical Research) has been recognized by the WHO as National Reference Laboratory and as Global Specialized Laboratory, one of seven such units in the world. Stool samples were collected from every child with AFP: the aim was to get two samples from every child to increase diagnostic sensitivity. They were tested in the polio laboratories to detect polioviruses and when detected, to differentiate between vaccine viruses from natural or wild polioviruses (WPVs). This is referred to as “virological surveillance” or “active laboratory surveillance”. If laboratories passively reported the detection of agents under public health surveillance, it would supplement clinical surveillance and would qualify for “passive laboratory surveillance”. Since NPSP staff collected stool samples from all children with AFP and got them tested, the process illustrates “active laboratory surveillance”. In 2011, over 60,740 stool samples were collected and tested but only 1 WPV (type 1) was detected.
Wild polioviruses can circulate silently for short periods of time. For decades, sewage samples had been collected and tested for WPVs, by the Enterovirus Research Centre in Mumbai and WPVs were regularly detected. Since the year 2000, Mumbai sewage showed up imported WPVs with origins in Uttar Pradesh or Bihar. Sewage is equivalent to stools from hundreds of thousands of individuals. Yet, the testing sample comes from the environment. Therefore, in the context of polio, regular (usually weekly) sewage sample testing is referred to as “environmental poliovirus surveillance”. Since 2011, environmental surveillance is conducted in Mumbai, Delhi, Patna and Kolkata. In 2012, so far, all samples have proved negative, adding supportive evidence that India has eliminated WPV transmission.
SURVEILLANCE IN AIDS CONTROL
Acquired immune deficiency syndrome control is another success story in India. While AIDS received wide global media publicity, during the early 1980s, the government lacked a mechanism to monitor its arrival in India. Had we practiced public health surveillance, we could have expected some physicians reporting suspected cases of AIDS or at least diseases or death due to undiagnosed causes. Recognizing this deficiency, the virology department of the Christian Medical College in Vellore conducted systematic search for infection, resulting in detection of infected women in sex work in Chennai, Madurai and Vellore in February 1986. The Indian Council of Medical Research established an AIDS Task Force in mid-1986 and adopted the Vellore model of testing within hospital settings both a high-risk group (male patients in STD clinics) and a low-risk group (antenatal women) for human immunodeficiency virus (HIV) infection as the parameter for monitoring time trends of epidemiology. Thus, annual repetitive sentinel hospital-based anonymous unlinked sample surveys were established—and it got a popular name as “sentinel surveillance”. In 1986 itself, 62 “sentinel surveillance” sites were operative. Since then a number of sites have increased to over 1,000 in 2010, covering all cities and most districts in every State and Union Territory.
Today “sentinel surveillance” for HIV provides annually large samples of denominator-population and their HIV prevalence. This is the method of monitoring infection trends to date, a unique method designed in India. There is no other disease for which denominator-based infection prevalence data are available in India. Other countries did not resort to serological surveys to monitor time trends, as they had passive surveillance of cases of AIDS. However, the term sentinel surveillance is a misnomer as it is not based on principles of public health surveillance. It lacks continuity and has incomplete coverage. However, the objective is to monitor time trend, which it serves well.
THE STATE OF PUBLIC HEALTH SURVEILLANCE IN INDIA
During British Raj, public health surveillance was practiced in all provinces, under the Epidemics Act of 1890 and the Madras Public Health Act of 1939. Each province had established its own list of diseases for reporting. After independence the posts of Director General of Indian Medical Service, Public Health Commissioner of India and India Health Epidemiologist were abolished; thus public health surveillance was orphaned. The newly created post of Director General of Health Services was not assigned the responsibility of public health surveillance. As all emphasis was given to healthcare, the need for surveillance was not appreciated. However, when a disease was brought under control mode, special surveillance for that disease was established. Smallpox, Guinea Worm and polio surveillance activities were described above.
The National Malaria Control Programme was established in 1953. Two modes of surveillance were established: (1) active surveillance where malaria was hyperendemic and (2) passive surveillance everywhere else. Since passive surveillance was not enforced for any disease, malaria surveillance also fell by the wayside. For active surveillance, a worker visits every household once in 2 weeks, and blood smear is collected from anyone who had fever during the interval—smears are examined for malarial parasites. Using the data, the following indices are derived: slide positivity rate; slide falciparum rate; annual parasite incidence; annual blood examination rate; annual falciparum incidence.
The National Leprosy Control Programme was established in 1955. Leprosy-specific diagnosis and treatment centers were established at key locations. The leprosy workers conducted periodic population surveys (active surveillance) for clinical evidence of leprosy—thus annual prevalence rate was calculated. After the goal of leprosy elimination was declared occasional mass surveys were conducted—and continues even now. The aim is to keep the new case detection at less than 1 per 10,000 population, which is used to define “elimination”. However, epidemiologically this is not true elimination—which is zero incidence in the defined geographic community.
Other Diseases under Control Mode
The Union Ministry of Health has targeted a few other diseases for control, namely tuberculosis (TB), lymphatic filariasis, kala azar, dengue, chikungunya fever and Japanese encephalitis (the last five under National Vector-borne Diseases Control). Neither passive nor active surveillance is practiced for them and the status of control remains not properly monitored. In May 2012, the ministry of health has notified pulmonary TB as reportable. However, the modalities of reporting, data receiving agency, follow-up and actions following case reporting have not yet been clearly described. The present requirement is for reporting sputum smear-positive pulmonary TB; other forms including pediatric TB are not yet demanded for reporting.
Expanded Program on Immunization
The National Childhood and Antenatal Immunization Programme, launched in India in 1978–79, has been renamed the Universal Immunization Programme (UIP). Although the objective is to prevent vaccine-preventable diseases in individuals and control their incidence in the community, systematic surveillance of targeted diseases was not established. The numbers of cases reported through the hierarchy of government healthcare units are received and compiled by the union ministry of health; however, neither the sensitivity (what proportion of total cases was captured) nor specificity of case diagnosis (what proportion of cases had accurate diagnosis) is checked for validation. Countries practicing public health surveillance did not have to establish a polio-specific surveillance method, but India had to establish NPSP. Now measles is getting targeted for mortality elimination, followed by disease elimination itself. The responsibility for measles surveillance, including laboratory verification of outbreaks, has been entrusted with the NPSP. The network of polio laboratories have been equipped for measles diagnosis and supplied with the necessary reagents. The NPSP measles outbreak monitoring and laboratory confirmation project was begun in 2006 in Andhra Pradesh, Tamil Nadu and Karnataka; in 2007 Kerala, West Bengal and Gujarat were added; during 2009−2011 Rajasthan, Madhya Pradesh, Assam, Bihar and Chhattisgarh were added. When investigated, many outbreaks clinically named measles turned out to be rubella. Consequently, the UIP is getting ready to include rubella vaccination in India.
INTEGRATED DISEASE SURVEILLANCE PROJECT
The concept of integrated disease surveillance is to link together all existing ad hoc or single disease surveillance activities under one umbrella. Two models of integrated surveillance have been developed in India. In 1994, there was an outbreak of suspected pneumonic plague in Surat city. An expert committee examined the reasons why such an outbreak occurred and how the nation should prepare itself for any future outbreaks of emerging or re-emerging infectious diseases. It recommended the replication of a model established in one district in Tamil Nadu and all districts in Kerala for “district level disease surveillance” (DLDS) in which private sector and public sector physicians or pediatricians reported 15 notified diseases using a preformatted and postpaid post-card. Its advantages included low cost, immediate local action to prevent or control the spread of any outbreak. Feedback to reporting physicians was through a monthly bulletin which provided information on frequency of diseases, outbreaks and actions taken against them. This decentralized district-based system (with the afferent and efferent limbs and central processing unit within the district) was not aligned with the national policy that disease control and outbreak investigations belonged to the Union Government, while only healthcare and training or education of healthcare personnel belonged to State Governments. This tension led to the establishment of centrally sponsored and funded data collection mode named Integrated Disease Surveillance Project (IDSP).
Integrated Disease Surveillance Project was launched in November 2004 to detect disease outbreaks quickly. The Central Surveillance Unit is at National Center for Disease Control (NCDC), Delhi. Until 2012, it was in project mode, but currently it is nested within the National Rural Health Mission. Weekly reports are generated from primary care units (subcenters, primary health centers, community health centers) which were earlier reporting disease statistics using a format different from that supplied by IDSP. Hospitals in public and private sectors are also in the network, but their involvement is incomplete. Instead of case-reporting as in public health surveillance, disease reporting in IDSP is cumbersome—lengthy forms are to be filled in for “syndromic” diagnosis, probable cases and laboratory data. Electronic reporting is encouraged. Here “integration” is not linking all ongoing surveillance activities, but a new concept—combining reporting of non-communicable diseases along with infectious diseases. Thus, IDSP in India is yet another vertical project as the afferent and efferent limbs touch one central agency—the NCDC. It does not encompass the definitional requirements of public health surveillance. Private sector could not be linked as in the case of DLDS.
The weakness of IDSP is that it has not filled the gaps in disease surveillance for those diseases that are already targeted for control, namely vaccine-preventable disease, TB, malaria and several others discussed above. As the need arose for surveillance of outbreaks of acute neurological diseases (meningococcal meningitis, Japanese encephalitis and those of unknown etiology) and of pneumonias, rotavirus gastroenteritis, etc. more surveillance projects had to be launched as described below.
SENTINEL-BASED SURVEILLANCE OF SELECTED DISEASES
Influenza Sentinel Surveillance
The National Institute of Virology has been investigating influenza—epidemiology and viral strain identification—for a few decades. However, nationally influenza had not received much attention. In 2004, a multicenter influenza monitoring laboratory network was established: the sites are at Pune, Delhi, Kolkata and Chennai. After the 2009, pandemic influenza reached India; the network was expanded to more centers including Vellore, Mumbai and Lucknow. The information collected in these laboratories is submitted to the WHO.
Rotavirus Sentinel Surveillance
A network of four laboratories have been assigned the task of identifying and typing rotavirus isolates from ten sentinel hospitals in six States, namely Tamil Nadu, Maharashtra, Madhya Pradesh, West Bengal, Assam and Delhi. Under-5 children with acute gastroenteritis requiring rehydration will be monitored and their stool samples submitted to the designated laboratories (Vellore, Pune, Mumbai, Kolkata).
Invasive Pneumococcal, Haemophilus influenzae and Meningococcal Disease Surveillance
The Indian Council of Medical Research in collaboration with NCDC is in the process of developing 30 sentinel sites to develop data base to monitor the burden of invasive bacterial diseases due to pneumococci, meningococci and Haemophilus influenzae type b. Since vaccines are available against these diseases baseline data are important to help policy decisions on the use of these vaccines. Once vaccines are introduced, the assessment of vaccine effectiveness requires surveillance data. When pneumococcal vaccine is introduced, serotype prevalence needs to be monitored in case new serotypes replace vaccine serotypes.
Encephalitis Sentinel Surveillance
The Indian Council of Medical Research (ICMR), with the help of NPSP is in the process of developing sentinel surveillance in several districts where Japanese Encephalitis is prevalent. These sites will help in monitoring vaccine effectiveness.
If a government wants to control infectious diseases, the first step is to establish surveillance. All diseases targeted for control must be covered in surveillance. Since disease-control activities require a functional Public Health Department, the process of disease surveillance is best conducted by the local (district and city) public health officer and staff. Routine passive surveillance is, therefore, called “public health surveillance”. In India, there is no unified public health surveillance, but instead there are several vertical, but nationwide disease monitoring programs including case-based surveillance for AFP, outbreak monitoring of measles and rubella, IDSP and several sentinel surveillance projects. Ideally integrated surveillance should replace all fragmentary disease monitoring projects, but unfortunately it is not possible under the present circumstances in which healthcare is under State Governments but disease prevention and outbreak control are under the Union Government. A practical redesign of Union–State relationship will help the creation of a truly integrated public health surveillance for all diseases of public health importance.
- Government of India, Ministry of Health and Family Welfare. Integrtaed Disease Surveillance. [online] Avaialble from http://www.idsp.nic.in/ and http://www.mohfw.nic.in/NRHM/PIP_09_10/Delhi/IDSP_text.pdf.
1.3 ROLE OF GAVI IN THE CONTROL OF VACCINE-PREVENTABLE DISEASES IN INDIA
Naveen Thacker, Ashish Pathak
Global Alliance for Vaccines and Immunization (GAVI, the Vaccine Alliance) is an international organization, which was created as a public–private partnership and is committed towards increasing access to immunization in poor countries. GAVI brings together United Nations Children's Fund (UNICEF), the World Bank, the vaccine manufactuers from resource-rich and resource-poor countries, donors from the resource-rich countries, and representatives from governments of the low-income countries across the world and Civil Society Organizations (CSOs).1
Since its inception in 2000, GAVI's support has contributed to the immunization of an additional 500 million children in low-income countries and has averted 7 million deaths due to vaccine-preventable diseases. GAVI has supported more than 200 vaccine introductions and campaigns in low-income countries during the 2011–2015 period between 2016 and 2020, GAVI will help countries to immunize another 300 million children against potentially fatal diseases, saving between 5 and 6 million lives in the long term.2
The mission of GAVI is “saving children's lives and protecting people's health by increasing equitable use of vaccines in lower-income countries”.3
HOW DOES GAVI WORK?
GAVI invites applications for support from governments of those countries whose gross national income per capita is below GAVI's eligibility threshold, this threshold was US dollar 1580 in the year 2015. Based on the eligibility threshold, 73 countries are eligible for GAVI support. GAVI purchases vaccines through UNICEF, and provides them to governments whose applications are approved.1
GAVI's strategy is a roadmap designed to help it respond to changes in the vaccine landscape and set five-year milestones en route to fulfilling its mission.4 The 2016-2020 strategy is the latest in four distinct phases since GAVI's inception:
Phase IV (2016–2020)
Phase III (2011–2015)
Phase II (2007–2010)
Phase I (2000–2006)
Phase IV (2016–2020)
This section details the strategic objectives and operating principles for the current phase (2016–2020) as well as providing an overview of previous strategies.
The 2016–2020 strategy has four goals, each supporting GAVI's overall mission:5
- The vaccine goal: Accelerate equitable uptake and coverage of vaccines.
- The systems goal: Increase effectiveness and efficiency of immunization delivery as an integrated part of strengthened health systems.
- The sustainability goal: Improve sustainability of national immunization programmes.
- The market-shaping goal: Shape markets for vaccines and other immunization products.
The GAVI's strategic framework includes eight principles, intended to define the Vaccine Alliance's characteristics, its business model and its aspirations, these are: country-led, community-owned, globally engaged, catalytic and sustainable, integrated, innovative, collaborative and accountable.4
GAVI'S HEALTH SYSTEM STRENGTHENING GRANTS
GAVI is dependent on the effectiveness of the countries health system to deliver life-saving vaccines, thus GAVI supports countries to strengthen country health system by proving health system strengthening (HSS) grants.1 The strategic objectives under the health systems goal are to:
- Contribute to resolving the major constraints to delivering immunization.
- Increase equity in access to services
- Strengthen civil society engagement in the health sector.
GAVI'S ESTIMATED IMPACT IN 2016–2020 PERIOD
The estimated impact of GAVI in its next phase can be measured by number of children that would be saved from vaccine-preventable diseases per country and thus, globally. In the 2016–2020 period, India will contribute to largest number of deaths averted globally (Fig. 1.3.1).
GAVI'S SUPPORT TO INDIA
India has always been special for GAVI. India is the largest and most populous GAVI-eligible country with a birth-cohort of almost 27 million.
Fig. 1.3.1: Countries that will contribute to highest percentage of deaths averted through vaccine-preventable diseases through GAVI support in the period 2016–20206.
Also, India still accounts for one-fifth of child deaths worldwide and more than a quarter of all under-immunized children in GAVI-eligible countries (please look at Figure 1.3.2 for details). India remains eligible for GAVI support based on its GNI level. But because of the large birth cohort of India, GAVI has limited its support to catalytic funding to India. Until 2011, there was a limit placed on GAVI support to India, which was removed with the condition that the GAVI Board continues to review any new support case-by-case.7
IPV Introduction Support
The National Technical Advisory Group on Immunization (NTAGI), the apex body for decision making on immunization related issues in India, recommended a comprehensive IPV introduction plan to the Government of India (GoI).8 India applied for funding to GAVI in September 2014, for the period of September 2015 to 2018 at an estimated cost of US dollar 160 million. In November 2015, India launched IPV in six states and has expanded it to all states and Union Territories.6
HEALTH SYSTEM STRENGTHENING SUPPORT TO INDIA
As part of HSS initiative, GAVI has disbursed US dollar 30.6 million for the IPV introduction and US dollar 107 million in the year 2014–2015 to India.1 The grant has been focused by GoI for use in 12 states and 127 underperforming districts and is synergistic to Mission Indradhanush.10 Specifically, the grant has been used to strengthen the cold chain management. To enhance human resource capacity, national cold chain vaccine management resource center has been established in New Delhi. National cold chain training center has been strengthened in Pune. In 20 districts across UP, MP and Rajasthan, electronic vaccine intelligence network (eVIN) has been implemented to enable real time information on cold chain temperatures, vaccine stocks and flows. To increase demand for routine vaccination, National Behavioral Change and Communication (BCC) strategy has been developed and immunization messages have been developed and broadcast through mass media. The national monitoring and evaluation plan for immunization has been drafted and monitoring and evaluation of routine immunization is currently functional in 24 of the 36 states and UTs across India. Two rounds of survey for National Immunization Coverage Evaluation have been done in 2015. This evaluation will further identify low-performing districts for routine immunization coverage. Guidelines for tagging high-risk low-coverage areas have been developed along with WHO India National Polio Surveillance Program (NPSP).1
Targeted Country Assistance for India for 2017
GAVI works through its incountry partners in India. They are WHO, UNICEF and the CDC. In 2017, UNICEF through GAVI support will support a) the implementation and national monitoring of Mission Indradhanush, with a focus on 12 low-performing states. The expected outcome is that improvements in immunization coverage are inclusive of the children in the most marginalized, remote and poorest communities and overall inequities within the immunization program are reduced. UNICEF will also support planning, preparedness assessment and roll out of pneumococcal and rotavirus vaccine in identified states, will support the implementation of a high-quality MR state campaigns, with a focus on social mobilization, cold-chain performance and real time monitoring and will support national electronic vial monitoring assessments. The WHO through GAVI support will address immunization equity in states with low-immunization coverage with focus on North-Eastern states. CDC, Atlanta through GAVI support will provide technical assistance to the National Institute of Cholera and Enteric Diseases (NICED), the state of West Bengal, and the Central Ministry of Health to understand the disease and economic burden of cholera in the State of West Bengal.
Impact of GAVI Initiatives in India
GAVI has been providing assistance to the Government of India since 2002. Over the past decade, India has received support in three areas:
a. Hepatitis B Monovalent Vaccine
GAVI, through its New Vaccine Support (NVS) grant, helped India to introduce the hepatitis B monovalent vaccine. Support began in 2002 with a vaccine introduction grant for $100,000. For 6 years, from 2003 to 2009 and excluding 2004, a total of $26,486,033 was disbursed for Hep B mono vaccine; funding was used to purchase the vaccine and injection supplies with the Government of India funding other immunization support.11
In 2002, hepatitis B was introduced in 33 districts and 10 cities in India with GAVI Phase I support. In 2007–2008, coverage was expanded to 10 states with GAVI Phase II support. In 2010, the Government of India took over funding for Hep B immunization in the 10 states, and in 2011 introduced the vaccine nationwide with its own funding.11
Final impact: Universal introduction of hepatitis B vaccine with Government of India supporting 100% immunization.
b. Injection Safety Support
Injection Safety Support (INS) grant helped India to introduce autodisable syringes in its immunization program. Two grants were given in 2005 and 2007 and a total of US$ 18,427,489 was disbursed.
Final impact: Autodisable syringes have become the standard for all routine Expanded Programme on Immunization (EPI), and a national policy for safe disposal of injection waste has been developed. The Government of India is now funding the purchase of auto-disable syringes 100%.11
c. Pentavalent (DTP-HepB-Hib) Vaccine Support
New vaccine support (NVS) to introduce pentavalent DTP-HepB-Hib (Penta) vaccine.
India's NTAGI recommended the introduction of Penta in 2008. GAVI support began in 2008 with a vaccine introduction grant for US$ 1,100,000, although 70% of this was returned when India decided on a phased introduction in 2011 instead of a nationwide introduction as was originally planned. US$ 443,500 of the grant was used to support the phased introduction. In December 2011, India introduced Penta in two states (Keral and Tamil Nadu) with GAVI support. Six additional states introducted in 2012.12
Final impact: Currently, all states have introduced Penta in routine immunization in India. India received a total of US $266,711,053 as of 23rd August, 2017, to support the introduction of Penta.12
IMMUNIZATION IN INDIA AND GAVI'S CRITICAL ROLE IN ACCELERATING GREATER ACHIEVEMENTS OF HEALTH IMPACT
With a birth cohort of 27 million children born each year, India accounts for one third of children born in GAVI-eligible countries. While India has made substantial progress in reducing the number of under-five deaths, it is still the highest in the world (1.3 million in 2013, 20% of the global total). The gravity of the problem varies significantly among states and areas of residence. Vaccine-preventable diseases are a key cause of mortality and morbidity. India has ~20% of pneumococcal, rotavirus and measles deaths worldwide, 25% of cervical cancer deaths, and 38% of the global congenital rubella syndrome (CRS) burden in terms of cases. Under India's Universal Immunisation Programme, vaccination is currently provided to prevent DTP (diphtheria, pertussis, tetanus), polio, measles, severe forms of childhood tuberculosis, hepatitis B (Hep B), Haemophilus influenzae type B (Hib) infections, and Japanese Encephalitis (in selected districts). GAVI provided catalytic support to accelerate the introduction of Hep B, pentavalent and inactivated polio (IPV) vaccines, as well as safe injection devices (INS) and on health systems strengthening. Under an exemption to the Alliance's co-financing policy, GAVI provides time-bound support and the government pays for introduction costs and related immunization commodities, taking on full self-financing for vaccines or devices after GAVI support ends (Fig. 1.3.3).6
The recent years have marked a turning point for the UIP. India's polio-free certification in 2014 and its elimination of maternal and neonatal tetanus in 2015 are landmark achievements. The political environment for immunization is also particularly strong now. In December 2014, the government launched the world's largest immunization drive, “Mission Indradhanush”, aimed at increasing immunization coverage to more than 90% by 2020 by targeting districts that have the most unvaccinated or partially vaccinated children. Initial results are encouraging: 2 million children were fully immunized in the first four rounds of the mission. Mission Indradhanush builds on new approaches that are implemented through GAVI's catalytic HSS grant. The US$ 107 million grant focuses on 12 underperforming states. An innovative pilot electronic information system to manage vaccine logistics is being scaled up in three states. Regular supportive supervision of cold chain points has been initiated at primary care level, and state-level communication plans have been created. The experience and expertise gained in the vast polio infrastructure is being applied to routine immunization, contributing to India's goal of universal coverage.6
Fig. 1.3.3: GAVI support to India to date, with programs sustained/to be sustained by the Government of India (US$ millions).6
A strengthened partnership in the coming years offers considerable benefits for both India and GAVI. GAVI's vision is that between 2016 and 2021, GAVI's targeted support will accelerate India's efforts to introduce new vaccines and achieve universal immunization coverage. Millions more children will be immunized by several vaccines in GAVI's portfolio, increasing the number of future deaths averted with GAVI support by at least half a million. India will reach a position where it can sustain a self-financed, multi-faceted and equitable immunization program. GAVI and India will both benefit by capitalizing on procurement savings and enhancing vaccine supply security, while forging a collaborative, learning-based relationship. To realize this vision, GAVI proposed a comprehensive, multi-pronged strategic alliance partnership with India. The strategy builds on the principles endorsed by the programme and policy committee (PPC), it takes India's priorities and GAVI's added value into consideration, and envisages timebound, catalytic support:
- Increase immunization coverage and equity in India through targeted support to strengthen the routine immunization system.
- Maximize health impact by accelerating adoption of new vaccines in India.
- Maximize procurement savings and vaccine supply security by sharing information, coordinating tactics and building a long-term strategy that strengthens local, public and private sector manufacturers.
- Ensure that vaccine programs in India will be sustainable beyond 2021 by supporting the government to plan for the transition and advocating for increased domestic spending on immunization.
The Coverage and Equity Opportunity
Though the UIP has been operating for more than 30 years, only 65% of children receive all vaccines during their first year. While WHO/UNICEF coverage estimates for India were revised upward this year (from 72% to 83% DTP3 coverage), India is still the country with the largest number of un- or under-vaccinated children in the world, at 4.1 million in 2014 (Fig. 1.3.1). Vaccination coverage varies significantly among geographies (Fig. 1.3.4). Some of India's states are among the largest and poorest in GAVI's portfolio. Uttar Pradesh, for example, is larger than every GAVI-eligible country except Nigeria, has gross national income per capita of only US $422, and has a DTP3 coverage of only ~60%. Coverage also varies depending on gender, area of residence, wealth and caste. Operational challenges in demand generation, cold chain and logistics management, and other areas hinder progress.
Alliance partners have work with the Government of India to develop a detailed proposal with targets and indicators and ensure that future GAVI support further addresses coverage inequity issues in the country. Cold chain and logistics management, demand generation and vaccine-preventable diseases (VPD) surveillance are some potential new areas within which GAVI is looking forward to invest.6
THE NEW VACCINES OPPORTUNITY
With the positive political environment, India has an ambition to eliminate measles, introduce rubella (as part of MR vaccine), rotavirus, and pneumococcal vaccines in 2016–2017, and potentially HPV vaccine at a later time during the transition period.
Fig. 1.3.4: Percent of fully immunized children (FIC) in large Indian states.6
Rollouts of these vaccines are at different stages of planning given the status of recommendations from the National Technical Advisory Group on Immunisation (NTAGI) and political approvals for each vaccine. GAVI support will play an important role in accelerating roll-out of new vaccines, which would be critical to argue for allocation of more domestic resources in the next national Five-Year Plan and cMYP (2018–2022).
THE MARKET-SHAPING OPPORTUNITY
The strategic partnership between GAVI and the Government of India offers opportunities to optimize both short- and long-term vaccine supply security, to capture procurement cost-savings based on the increased demand, and to share information and best practices on managing vaccine markets effectively. Each vaccine market will require a specific approach. The markets with the greatest opportunities today for procurement savings are pentavalent and pneumococcal. While other markets, such as IPV, MR and rotavirus, have limited scope for procurement cost-savings, these markets will require close coordination with regard to supply. Building a strong local base of private and public vaccines and cold chain equipment that complements the global availability will be beneficial across the whole portfolio. Benefits of a well- executed partnership will extend beyond GAVI and India to include low income countries that are dependent on a reliable supply of low-cost and high-quality vaccines and cold-chain equipment.3
ENSURING SUSTAINABLE PROGRAMMING
GAVI engagement in the form of senior leadership advocacy and support via communication and advocacy agencies have resulted in evidence-based policy discussions at both the national and state levels and have achieved a higher prioritization for health issues. Alliance advocacy for political commitment to increase health spending, including immunization, is paramount. A Political Forum on Child Health and Survival which includes selected Members of Parliament was recently formed in 2012. This new structure serves as a forum for political and public discourse around the need for high-quality, cost-effective public health interventions, including vaccines.
India has a successful track record in continuing the Hep B and INS programs with its domestic resources after GAVI support ended. The government has also indicated in writing to the GAVI Secretariat its commitment to sustain and further scale up rotavirus, pneumococcal and HPV programs and self-finance MR routine immunization after future catalytic support ends. However, given the magnitude of increase in resources expected with the launch of new vaccines (two to ten-fold increase by 2021 from the current ~US$ 40 million per year on vaccine costs only 25), GAVI engagement with India to ensure successful transitioning is critical.6
THE IMPORTANCE OF INDIA AS A MANUFACTURING BASE FOR VACCINE AND COLD CHAIN EQUIPMENT
Vaccine manufacturers in India are a key source of supply for GAVI. In 2014, they provided nearly 60% of vaccine volume, representing just over 30% of the total value of procurement. A single Indian manufacturer supplied 100% of measles-rubella (MR) and meningococcal A (MenA) conjugate vaccines and 80% of measles vaccine, while four manufacturers supplied over 80% of pentavalent vaccine.6 Vaccine demand in India could reach nearly 30% of total demand in the 73 GAVI countries. The resulting significant increase in market volumes presents both risk and opportunity. It could disrupt supply of important vaccines if coordination is insufficient. If the increase is managed well, however, it will allow optimization of production costs and procurement savings.6
- Thacker N, Thacker D, Pathak A. Role of Global Alliance for Vaccines and Immunization (GAVI) in Accelerating Inactivated Polio Vaccine Introduction. Indian Pediatr. 2016;53(Suppl 1):S57–S60. PubMed PMID: 27771641.
- GAVI 2016. Every Child Counts: The Vaccine Alliance Progress Report 2014. Available from http://www.gavi.org/progress-report/. Accessed September 11, 2017 http://www.gavi.org/results/gavi-progress-reports/
- GAVI's strategy, Mission 2016–2020 http://www.gavi.org/about/strategy/ Accessed September 11, 2017.
- GAVI, the Vaccine Alliance 2016-2020 Strategy http://www.gavi.org/library/publications/gavi/gavi-the-vaccine-alliance-2016-2020-strategy/ Accessed September 11, 2017.
- GAVI's strategy, phase IV (2016-20) - GAVI, the Vaccine Alliance http://www.gavi.org/about/strategy/phase-iv-2016-20/ Accessed September 11, 2017.
- Szeto C, Malhame M, Gehl D, et al. Report to the Board 2-3 December 2015 Alliance Partnership Strategy with India, 2016-2021.
- GAVI 2015. Alliance Partnership Strategy with India, 2016-2021 Report to the Board 3rd December 2015. Available from http://www.gavi.org/Library/News/Press-releases/2016/Historic-partnership-between-GAVI-and-India-to-save-millions-of-lives/. Accessed September 11, 2017.
- India's National Technical Advisory Group on Immunisation T. Jacob John. National Technical Advisory Group on Immunisation, New Delhi, India www.nitag-resource.org/…/01/6706ca25a105266e834edb78f7f81cec124420ec.pdf
- Joint Appraisal Report India, 2015, Available from http://www.gavi.org/country/india/documents/#approvedproposal. Accessed September 11, 2017.
- Mission Indradhanush http://www.missionindradhanush.in/about.html Accessed September 11, 2017.
- Parthasarathy A. Textbook of Pediatric Infectious Diseases. 2013; New Delhi: Jaypee Brothers Medical Publishers.
- Pentavalent vaccine support http://www.gavi.org/support/nvs/pentavalent/ Accessed September 11, 2017.
1.4 RATIONAL DRUG THERAPY IN PEDIATRIC INFECTIOUS DISEASES
Rational drug therapy means “prescribing right drug for right indication, in adequate dose for optimum duration that delivers safe and appropriate benefit to the clinical needs of the patient at lowest cost”. The concept of rational drug therapy is age-old, as evident by the statement made by the Alexandrian physician Herophilus, 300 BC that states “Medicines are nothing in themselves but are the very hands of God if employed with reason and prudence”. The physician should always bear in mind that drugs do not cure. They may be made valuable adjuncts in our endeavor to restore normal function in an abnormal functioning organ. Improving precision and economy in prescribing drugs is a goal whose importance has much more increased with proliferation of new and potent agents and with growing economic pressures to contain health- care cost.
GENERAL PRINCIPLES OF RATIONAL DRUG SELECTION
Selected drug must be relevant to treatment of concerned disease. Such a drug could be either specific curative drug such as antibiotic or merely a symptomatic reliever. Specific drug therapy is possible only when there exists at least a provisional diagnosis as in case of use of antibiotic for infection. Symptomatic reliever must be used only when symptoms cause a reasonable discomfort to a child. For example, antipyretic should not be used just because of presence of fever. It should be used only if fever is high enough to make a child uncomfortable or pose danger to life as in case of hyperpyrexia. Thus, symptomatic reliever should be used as per the need (on SOS basis) and not on predetermined fixed schedule. It is also true about symptomatic therapy for cough or diarrhea. In fact, there is no cough remedy that “cures” cough. At best, it may relieve discomfort of coughing. Hence, bronchodilator or cough suppressant may be used with caution. It is now well accepted that there is no need for symptomatic control of diarrhea. Besides, stool-binding agents are harmful probiotics are not routinely indicated in diarrhea. Zinc supplement in diarrhea is rational, especially in malnourished children.
Efficacy and Safety
These are most important parameters of rationality. Safety is as much to be ensured as efficacy, more so in case of long-term therapy. It is true that every drug is likely to cause side effects and so, every attempt must be made to use non-pharmacological therapy whenever available, before prescribing a drug. For example, good ventilation, optimum room temperature and light clothing help to control fever. Similarly, hydration and propped up position help to relieve cough. Maintaining good nutrition and hydration is key to treatment of diarrhea. Control of trigger factors in treatment of asthma is vital to therapeutic success. Such measures often obviate need for a drug or can do with minimum drugs.
It is rational to evaluate probable outcome of using or not using a drug. One must compare risk and benefit of administering the drug as well as withholding the drug. Similarly, one must choose the best drug with favorable risk–benefit ratio.
Cost is the concern to less privileged society but even to the affordable population. If alternate drug is cheap, one must not hesitate to use it. It is not true that generic drugs are inferior to branded drugs.
Unfortunately, there is no way for a doctor to assess quality of the drug. It is personal experience that dictates using a drug manufactured by a particular company. Quality of a drug is to be taken for granted although one must keep in mind the possibility of spurious drugs. Past record of the manufacturer and personal experience of a drug helps to decide the quality.
Rationality cannot be considered to be fixed or rigid endpoint of drug therapy in all situations. Cotrimoxazole is a rational choice for the treatment of acute respiratory infection (ARI) in ARI control program in the community because it is cheap, safe, oral, fairly effective and available in simple dosage formulations. But, it is not necessarily the best choice for individual child as specific antibiotic can be considered better, depending upon probable bacteriological diagnosis. Appropriateness should also be decided by capability and competence of local physician to make correct diagnosis and monitor proper therapy. For example, intravenous therapy may be ideal for acute bacterial infection in an infant but may not be feasible due to physician's inability to administer intravenous drug and so intramuscular route may be an alternative, although inferior. Single dose of intramuscular injection of benzathine penicillin or aminoglycoside has been used in specific conditions.
Single Ingredient Drug
Fixed dose combination drugs are best avoided in routine practice, except in specific situations such as cotrimoxazole, anti-tuberculosis drugs or antibiotic with enzyme inhibitor. If two drugs are necessary for treatment, as in case of neonatal sepsis, they are best administered separately so that individual dosage and duration can be suitably adjusted. There are many irrational combinations in the market such as combination of quinolone and metronidazole for mixed gastrointestinal (GI) infection. Such mixed infection is rare in children.
RATIONAL ANTIBIOTIC THERAPY
Infections are common in children and fever is a common presentation. Fever does not equate with infection and not necessarily bacterial infection that may justify an antibiotic. After all, viral infections are common in the community and should not be treated with an antibiotic. Further, not all bacterial infections deserve an antibiotic prescription. However, antibiotics are prescribed for majority of children presenting with fever. In fact, they may also be prescribed for children who have no infection as in case of cough due to hyper-reactive airway disease. Thus, antibiotics are often prescribed without proper diagnosis for fear of probable bacterial infection and antibiotics are often changed or multiple antibiotics used due to fear of worsening condition. Misuse of antibiotics in this way leads to increasing drug resistance which has become a major concern today. Besides, irrational use of antibiotic may suppress but not control infection that would pose difficulty in diagnosis with increased morbidity and risk of mortality. Thus, improper antibiotic use is a threat to the community and also to an individual patient. If this trend continues, it may not be long before even a simple infection may not be amenable to drug therapy.
WHEN SHOULD AN ANTIBIOTIC BE PRESCRIBED?
Attempt a Bacteriological Diagnosis
Antibiotic is indicated only in case of bacterial infection. It is ideal to attempt bacteriological diagnosis in every child with suspected bacterial infection, although it is not practical in routine office practice. However, few conditions demand proof of bacterial infection as in case of urinary tract infection (UTI) and typhoid fever. Urinary tract infection in children is potentially a serious disease with a risk of permanent renal damage if not properly diagnosed and treated. Typhoid fever being a bacteremic infection, blood culture is often positive and technically, it is easy to culture Salmonella typhi. It is, therefore, expected that UTI and typhoid fever are bacteriologically diagnosed as often as possible and empirical treatment is not justified. Gastric lavage for acid-fast bacilli should be tried in the diagnosis of childhood tuberculosis. Throat swab for streptococcal infection is a routine in western countries. In case culture facilities are not available, at least, circumstantial evidence should be collected before embarking on specific antibiotic therapy.
CIRCUMSTANTIAL EVIDENCE OF BACTERIAL INFECTION
Typical clinical syndrome in an acutely febrile child may strongly suggest bacterial infection that may not need further proof for rational antibiotic prescription. Acute tonsillitis is clinically diagnosed by finding beads of pus on inflamed tonsils and tender submandibular lymph nodes. Loose stools with blood and mucus and abdominal cramps suggest acute bacillary dysentery. Localized chest findings in an acutely febrile child who develops tachypnea denotes bacterial pneumonia that may be confirmed by chest X-ray but even without chest X-ray would justify antibiotic therapy.
Laboratory evidence of bacterial infection should not be considered in isolation without clinical correlation. Neutrophilic leukocytosis and high C-reactive protein may favor bacterial infection but not adequate enough by themselves to consider antibiotic therapy. Bacteremic bacterial infections start with moderate degree of fever that becomes more severe by day 3−4 as happens typically in typhoid fever. However, bacterial infections localizing at the site of entry such as tonsillitis or UTI may start with high degree of fever.
WHEN THERE IS NO CLUE TO DIAGNOSIS
This is the most common situation in routine office practice during first few days of onset of fever. Generally, one can arrive at a reasonably correct diagnosis only after disease evolves over few days after onset of symptoms. It means that correct diagnosis is often not possible in a febrile child in first few days with exception sited above such as tonsillitis and bacillary dysentery. At such stage, it is important to assess risk of waiting without specific antibiotic in an acutely febrile child.
Following situations in acutely febrile child are considered to be at risk of serious bacterial infection that demands urgent specific action:
- Age less than 3 months
- Immunosuppressed state
- Behavior abnormality—lethargy or extreme irritability
- Tachycardia and tachypnea disproportionate to degree of fever.
In such situations, laboratory tests should be ordered before starting empirical antibiotic and decision taken for need for hospitalization. Laboratory tests may be prioritized on individual merits and they include complete blood cell, urinalysis, chest X-ray, blood and urine culture and cerebrospinal fluid examination.
WHEN THERE IS NO CLUE TO DIAGNOSIS BUT IS SAFE TO WAIT
In absence of risk factors in a febrile child, it is rational to wait and observe progress without antibiotic therapy. Fever should be controlled with paracetamol. Parents must be counseled about danger symptoms such as behavioral abnormality and reduced urine output that demand reporting to medical facility. Periodic clinical examination is necessary over next few days to pick up clinical clues to diagnosis. Attempt must be made to differentiate acute bacterial infection from acute viral infection. It is possible to a reasonable extent by detailed analysis of history of fever (Table 1.4.1).
PRINCIPLE OF CHOOSING AN ANTIBIOTIC
Once need for an antibiotic is rationally decided, next step is to choose right antibiotic. Choice of antibiotic should depend upon several factors.
Site of Disease
Disease above the diaphragm is generally caused by Gram-positive cocci and is treated with penicillin, macrolide, first-generation cephalosporin. Disease below diaphragm is mostly caused by Gram-negative bacilli and is treated with aminoglycoside, third-generation cephalosporin or quinolone.
Antibiotic should be selected on the basis of local epidemiological data regarding drug sensitivity pattern. It may be variable in different regions and even in the same region in different institutes. It is ideal to monitor periodical changes that may occur in drug sensitivity pattern. This is important especially in critical care units wherein resistant strains may develop easily.
Source of Infection
Community-acquired infection is likely to be sensitive to first line of antibiotics, while nosocomial infection is often antibiotic resistant.
Type of Disease
Choice of antibiotic differs depending upon factors such as localized or generalized, superficial or deep, acute or chronic, mild or severe, extracellular or intracellular disease.
It is always ideal to enquire about history of allergy to drugs. Drug interactions are best avoided by using as minimum number of drugs as possible. One must also keep in mind adverse effects of drugs and communicate effectively with parents so that timely action is taken.
Previous Exposure to Antibiotics
It is likely that organisms may have become resistant to previously used antibiotics in recent past. Hence, it may be rational to use an alternate drug with similar profile. Community-acquired antibiotic-resistant infections are likely to be met with and one must consider such a possibility based on local epidemiology.
DOSAGE, DURATION AND FREQUENCY OF ADMINISTRATION OF ANTIBIOTIC
Intracranial infection must be treated with higher dose for longer time due to variable concentration of drug achieved depending upon blood–brain barrier permeability. Thick wall, acid pH and presence of hydrolyzing enzymes necessitate higher dose of antibiotics. Higher dose for longer duration is required in endocarditis due to poor penetration at the site of infection. So the deep-seated infections, such as osteomyelitis, also demand long-term therapy.
Dosage and/or frequency of administration may vary as per age, nutrition, immune status, renal and hepatic function. Frequency of antibiotic administration depends upon plasma half-life of a drug and generally, 4–5 times plasma half-life maintains adequate serum concentration throughout treatment period.
Route of Administration
Oral route is always preferred except in neonates and young infants and, of course, in serious infections. Intramuscular route is not ideal as it is painful and also has erratic absorption. Single dose of penicillin or ceftriaxone has been tried with success. Intravenous route is most ideal as it ensures achieving adequate concentration although, at times, not practical. Antibiotics that are used systemically should not be used topically.
ANTICIPATING INITIAL RESPONSE TO ANTIBIOTIC
Generally, it depends upon doubling time of organism—greater the doubling time, longer the response time. Partial control of fever may be the first response to antibiotic often accompanied with improvement in other symptoms and general wellbeing. For many common bacterial infections, initiation of response is observed within 2–3 days. It may take 4–5 days for initial response to antibiotic in typhoid fever, while in tuberculosis, initial response may be obtained within 2–4 weeks.
WHEN ANTIBIOTIC FAILS IN SUSPECTED BACTERIAL INFECTION?
Antibiotic rarely fails in routine office practice in treatment of community-acquired infection in a normal host. One should expect response to antibiotic within 3–4 days. If there is no response, it calls for reassessment.
Firstly, confirm whether it is an infection and, if so, a bacterial infection. This may be done by repeated physical examination supported by repeat laboratory tests. Choice of antibiotic and its route of administration may be a factor responsible for poor response. If bacterial infection and choice of antibiotic are reasonably confirmed, look for complications such as empyema in case of bacterial pneumonia or subdural collection in case of meningitis. At times, poor response may be due to iatrogenic factor such as catheter-related infection or nosocomial infection in a hospitalized setting. Only when all such factors are ruled out that one may consider drug resistance. It is ideal even at this stage to send blood culture and then change to best considered empirical antibiotic. However, if this change also fails, bacterial infection is ruled out and one must search for alternate diagnosis. It is not wise to persist with empirical antibiotic trial beyond one change.
WHEN NOT TO PRESCRIBE AN ANTIBIOTIC?
Non-bacterial infections obviously do not call for an antibiotic, and so also non-infective fevers. In routine office practice, it is possible to arrive at a provisional diagnosis by analyzing detailed history and focused physical examination. Typical viral infection starts with high fever at onset of illness that declines by day 3 or 4. Fever is rhythmic, rising every 4–6 hourly. As fever is partly controlled in 20–30 minutes after administration of paracetamol, child becomes active and does not look sick during inter-febrile period. Viral infection results in generalized affection of involved system. Thus, it may be accompanied with symptoms and physical signs of upper and lower respiratory tract involvement. There is often history of similar infection in other family members. Gastrointestinal symptoms in the form of vomiting and watery diarrhea denote involvement of upper (stomach) and lower GI tract (intestine) as a result of viral infection. Thus, viral infection is often disseminated, while bacterial infection is often localized.
Malaria presents with erratic pattern of fever that is essentially nonrhythmic. Child does not appear to be sick during interfebrile period.
Tuberculosis rarely presents as acute infection although acute onset of allergic pleural effusion may be a manifestation of tuberculosis in a healthy child. Non-infective conditions may present with fever wherein there is no localization during initial period. Disease evolves over time and at times may take even few months before being correctly labeled. Differentiation between acute bacterial infection and non-infective inflammatory disorder is, at times, difficult and in such a case, trial of antibiotic would fail to reveal correct diagnosis.
PRESENT SCENARIO OF IRRATIONAL ANTIBIOTIC USE
Antibiotics are considered to be the greatest discovery of twentieth century. In pre-antibiotic era, infectious diseases accounted for significant morbidity and mortality, and invasive procedures were fraught with risk of infection. All this changed with the use of antibiotics. But this miracle seems to be short-lived. Irresponsible and erratic use of these life-saving drugs has resulted in development of drug resistance in many organisms and death due to hospital-acquired infections is on the rise. It appears that our complacency is leading us into bigger problems in the present millennium.
Various studies conducted in developed as well as developing countries during the last few years show that irrational drug use is a global phenomenon.
WHY DO DOCTORS OVERPRESCRIBE ANTIBIOTICS?
Uncertainty of diagnosis and lack of confidence are two major reasons for irrational use of antibiotics. Faulty training of medical students, lack of effective continued medical education and poor communication between doctors and patients have compounded the problem of irrational therapy. Many doctors succumb to peer pressure and parental pressure. Ineffective drug regulation and aggressive pharmaceutical marketing practices have contributed to increasing irrationality of drug prescriptions. “Mixed” infections with bacteria and ameba are not known to occur and this “mixing” is done by drug industry to sell two drugs where none may be indicated. Fear of legal suit makes doctors overreact to patient's need of drugs because of firm belief that error of commission is acceptable but not error of omission. Even, irrational drug prescription can be a bone of contention in courts, more so, if it results in side effects. It is the negligence that is punished and not mistakes, especially if they are within realm of expected competence and scientific limitations.
RATIONAL DRUG THERAPY: RATIONAL PRESCRIBER A PRIORITY!
Although rational drug therapy is a joint responsibility of policy makers, drug manufacturers, healthcare professionals as well as patients, doctors provide final decision of use of drugs. Hence, rational prescriber is a priority to success of rational drug therapy. Rationality should ensure safety at all costs and should try to confine to the limits of acceptable standards. Rationality may have a changing concept. Paracetamol is considered to be an antipyretic of choice but even ibuprofen or mefenamic acid is an acceptable alternative. Oral rehydration solutions have undergone modifications and have been the mainstay of treatment of diarrhea. However, it is well known that not all children suffering from diarrhea accept oral rehydration solution (ORS). It is now proved that those children who do not accept ORS lose much less electrolytes in stool. So rationality demands to hydrate a child suffering from diarrhea with suitable modification but within limits. Knowing that asthma is a chronic inflammatory disease, inhaled steroids have emerged frontline drug for its treatment. Thus, rational prescriber has to learn, unlearn and relearn to keep pace with changing concept.
HOW TO PREVENT MISUSE OF ANTIBIOTICS?
It is vital to arrive at provisional working diagnosis based on clinical analysis of detailed history and focused physical examination. If doctors learn to document provisional diagnosis, drug prescription is likely to be rational. Every doctor is expected to follow standard, national or organizational guidelines and document actions taken with justifications including instructions to parents or patients. Such documentation is a proof of honesty, transparency and responsibility on the part of the doctor. This alone increases confidence in rational therapy. Restricted hospital drug formulary would inculcate ideal therapeutic practice among doctors. Education has a role but may not ensure rational behavior of doctors. There is a need for group audit but best would be self-audit. Drug regulatory authority must ban irrational drugs. Drug controller in USA banned commonly used cold and cough remedies few years ago.
In view of misuse and overuse of antibiotics, council for appropriate and rational antibiotic therapy (CARAT) was formed in USA to guide rational antibiotic therapy.
In summary, rational drug therapy and, in particular rational antibiotic therapy is the need of the hour. Empirical antibiotic therapy has a place in routine practice, but only with rational approach. It includes assessing risk of waiting, clinically evaluating probable etiology of disease, supported by relevant laboratory tests, repeated observation to monitor progress, selecting appropriate empirical drug and reassessment in case of poor response. With indiscriminate antibiotic use, there has been increasing drug resistance and time has come to change this trend lest we are defeated by simple infections.
- Amdekar YK. Rational drug therapy—rational prescriber a priority! Indian Pediatr. 1991;28(10):1107–9.
- Ghai OP, Paul VK. Rational drug therapy in pediatric practice. Indian Pediatr. 1988;25(11):1095–109.
- Mathur GP, Kushwaha KP, Mathur S. Rational drug therapy: reasons for failure and suggestions for its implementation. Indian Pediatr. 1993;30(6):815–8.
- Piparva KG, Parmar DM, Singh AP, et al. Drug utilization study of psychotropic drugs in outdoor patients in a teaching hospital. Indian J Psychol Med. 2011;33(1):54–8.
- Shankar PR, Jha N, Bajracharya O, et al. Feedback on and knowledge, attitude, and skills at the end of pharmacology practical sessions. J Educ Eval Health Prof. 2011;8:12. Epub 2011 Nov 30.
- Slama TG, Amin A, Brunton SA, et al. A clinician's guide to the appropriate and accurate use of antibiotics: the council for appropriate and rational antibiotic therapy (CARAT) criteria. Am J Med. 2005;118:1S–6S.