Donovanosis, is a fascinating, one of the chronic genito ulcerative diseases (GUDs) affecting primarily the genitalia. Its clinical, bacteriological, and histopathological features are characteristic enough to pinpoint the diagnosis. Even then this disease is largely missed or overlooked because it is neither suspected nor entertained in the differential diagnosis of ulcerative lesions on the genitalia.¹ Furthermore, the utilization of syndromic diagnosis and treatment of sexually transmitted infections (STIs) in various parts of the world, and previous use of antibiotics make it difficult to find Donovan bodies in the cytodiagnostic and hystopathological examination, requiring the utilization of technology that is neither routine nor often accessible to confirm the hypothesized diagnosis. Therefore, it is necessary to bring medical professionals up to date about this infectious disease.² It appears to be a universal impression because very little information on the disease is available from different parts of the globe. Its exclusive reporting from tropics and subtropics too seems misleading and evasive. Should the diagnosis of the disease be considered in all earnest in the differential diagnosis of genital ulcerations, more and more cases of the disease may be identified and superfluous connotation can be highlighted. An endeavor has, therefore, been made in the present text to consolidate its current status along with those of the previous works in a solemn bid to focus attention on this relatively neglected disease. Accordingly, the text has been profusely illustrated with black and white and colored photographs. The significance of the condition has relevantly been magnified, because this is one of the major genito ulcerative diseases (GUDs) responsible for propagating and perpetuating Human immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). It is hoped that the present treatise achieves its objective, and serves as “ready reckoner” for practicing venereologists, general practitioners 2and above all under- and postgraduate students across the globe.

Donovanosis, one of the pre-eminent genital ulcerative diseases, is chronic mildly contagious, sexually transmitted disease, characterized by exquisite granulomatous ulceration of the genitalia and neighboring sites, Calymmatobacterium granulomatis being its causative organism.³

The initial precise clinical description of the disease was outlined by Mcleod,⁴ when he named it as serpiginous ulceration of the groin. Ever since, its initial descriptions, the disease has been recognized by names, pointing accurately to its morphological features. An accurate clinical description of the disease was given by Conyers and Daniels⁵ while working in British Guiana. They used the term “lupoid form” of the so-called ‘groin ulceration’. While Galloway⁶ used the term ‘ulcerating granuloma of the pudenda’ in a single case report from London. Maitland⁷ described the condition under the title of ‘chronic venereal sores’. The condition was named ‘granuloma inguinale tropicum’ by Crocker⁸ in his textbook. However, Brooke⁹ coined it as ‘granuloma venereum’, a term which is still in vogue in some places. Donovanosis/Granuloma Inguinale (GI) is the current nomenclature used in practice and research across the globe. The same is adopted for the present text for all intends and purposes.

The major breakthrough came in the wake of recognizing intracellular bodies from an oral lesion of the disease by Donovan.¹ They were later incriminated by the subsequent workers as the causative organisms of the disease. These are now called Donovan bodies as a gesture to their discoverer. Aragao and Vianna² cultured a pleomorphic bacterium from the lesions and named it Calymmatobacterium granulomatis. However, in the following years there was a fierce controversy regarding the etiology of the disease and many conflicting views were expressed. In a review of the literature by McIntosh³ several interesting revelations were brought out. Randall et al were reported to have cultivated a bacillus from only three cases. They were identified as belonging to the Friedlander group. Wise et al were quoted as having found spirochetes on a direct smear from the lesion. Cornwell and Peck had reported isolation of a pleomorphic organism of a beaded morphology, which, when injected subcutaneously into rabbits, produced granulomatous lesions simulating donovanosis at the site of injection.

Studies on the immunologic status of patients with granuloma inguinale really started alongwith the first attempts at culture of the organism. McIntosh¹ had postulated antibody production against the Donovan microorganisms on the basis of agglutinins, precipitin changes in globulins and skin sensitivity in spontaneous and experimental cases studied by him. The definite immunological relationship of D. granulomatis to granuloma inguinale was demonstrated by Anderson et al.² They used an antigen produced from their culture, and demonstrated positive skin tests in six cases of granuloma inguinale. Capsular material used by them was found to elicit distinct precipitation reactions in 18 out of the 19 cases; further, in the same study, complement fixation tests were positive in 12 out of the 15 cases of granuloma inguinale. Dunham and Rake³ reported 86 percent positivity in complement fixation tests, in 58 cases of granuloma inguinale. However, using the same antigen, they also demonstrated 12 percent positivity in patients with history of sexual exposure, but without the disease. Similarly, the test gave affirmative results in 21 percent of cases with nonspecific ulcers. Similar results of complement fixation tests occurred if antigen prepared from Klebsiella pneumoniae replaced that prepared from D. granulomatis. He, therefore, postulated that the organism causing the disease was, perhaps, derived from feces, and had a high degree of mutability, some strains growing only on yolk sac of chick embryo, while others grew on artificial media also. Using a similar antigen, Chen et al⁴ described skin reactions amongst patients with donovanosis and reported 100 percent positive skin reactions in these cases. They also obtained false positive reactions in 7 of the 28 controls. Skin reactions were observed to begin as early as two weeks following the onset of granuloma inguinale and persisted indefinitely thereafter. Packer and Dulaney⁵ demonstrated 83 percent positivity in complement 9fixation tests in patients with donovanosis. Skin tests were reported to be 70 percent positive, but clearcut interpretation was not possible, comprehensive studies on the immunology of D. granulomatis were, however, done by Goldberg et al.^6,7 They used three antigens and showed positive complement-fixation tests in 136 of the 151 donovanosis cases. The duration of the lesion appeared to strongly influence the positivity of the test and directly proportional to it further, they established the antigenic heterogenicity of D. granulomatis for different results were obtained with the use of five different strains as antigens. In a subsequent study by Goldberg et al.⁸ It was reported that 9 out of 62 cases of squamous cell carcinoma of the penis tested with D. granulomatis antigens showed positive results, tending to strengthen the ‘association of donovanosis with squamous cell carcinoma of the penis.

The disease is enemic in New Guinea, Central Australia and the Caribbean¹ in some parts of West New Guinea; the incidence may be as high as 12.35 percent of the population. The disease is relatively uncommon among the Western races and is believed to be common in dark skinned races.² Although earlier, there was a high incidence of the disease in parts of the USA,³ this is no longer true. However, sporadic reporting of the disease has been observed.⁴

Donovanosis is usually considered to be one of the minor venereal diseases, as it constitutes a low percentage of the total venereal diseases—its range being 0.3 to 6.3 percent of the total venereal diseases reported amongst the hospital population in India (See Table 4.1). An isolated paper, however, reported a percentage as high as 23.6.¹⁰

The incidence of donovanosis is greatest from 20 to 40 years, a period of sexual maturiy.^5,20 The author, however, found a large number of cases (82.04%) of donovanosis in the age group ranging between 11 and 30 years (Table 4.2).

The difficulty of accurately determining the marital status of women affected by the disease has been emphasized.⁵ Although a slight preponderance of married over unmarried women was found, yet a close investigation revealed many deserted wives, frequently exchanged mistresses and widows. Amongst males, the unmarried are likely to be affected more often by the disease.⁸ In our study of the 49, (62.82%) unmarried patients, 46 were males and 3 females.

The remaining 27 married patients comprised 20 males and 7 females. Two males were widowers.

As shown by the recent Lok Nayak Jai Parkash Narayan Hospital's data analysis, of the 78 patients, 74 (94.87%) cases were residents of Delhi, the majority coming from its urban parts.

Most patients in the author's study belonged to a low socioeconomic status. They comprised petty businessman, unskilled or semiskilled workers and laborers (Table 4.3), 34 (43.59%) cases having an income of less than Rs. 400 per month.

The recent analysis indicates that 35 (44.87%) were illiterate, 9 (11.54%) had attended primary school, 13 (11.54%) had attended middle school and 17 (21.78%) had been educated up to high school. Only 4 cases were graduates.

The present analysis of the LNJP Hospital data revealed 49 (62.82%) patients had contracted the disease from prostitutes. Casual sexual contact was responsible in 13 (16.67%) while in 9 (11.53%) their spouse had transmitted the infection. History of sodomy was elicited in 7 (8.97%) males with perianal lesions, and promiscuity in 25. Extramarital contact was recorded in a single female and premarital in 2 females.

Only a few sexually transmitted diseases show such wide variation in their incubation period as donovanosis (See Table 4.4). However, Sehgal and Prasad⁸ found the average incubation period in their study to be 17.39 days. Experimental infection of man with D. granulomatis has been attempted to accurately determine the incubation period.²⁷ Such cases developed a full blown picture of the disease in 50 days. Cultured organisms when transplanted in a volunteer yielded Donovan bodies on smear examination from the site in 60 days.²⁸ In the study conducted by the author its range was 3–90 days, with a mean period of 12.79 days (Table 4.5).

Chronicity of the lesions was a marked feature in the earlier series but such a situation is infrequent now because of a greater emphasis on early diagnosis and a prompt, specific and adequate drug therapy. The duration of the disease varied from 6 days to 6 years in the recent data analysis. Only 9 patients applied for treatment 8–15 days after the formation of the lesion whereas 23 took three months to report. The average duration, however, was 152.1 days (Table 4.6). In the past the average duration was around 2.5 years.^{5, 20} 16

The pattern of epidemics of donovanosis in the so-called nonendemic capital city of Delhi was studded.²⁹ Of the 432 genital ulcer cases seen in 1985, 36 had donovanosis, thus forming an incidence of 8.33 percent. In contrast, 42 (6.38%) cases of donovanosis were diagnosed among a total of 658 cases of genital ulcers in 1983. The majority of patients in both epidemics were young unmarried men who contacted 17the disease through extramarital sexual intercourse.

Perianal lesions were seen primarily in those who had a history of sodomy. The disease chiefly affected illiterate persons of low socioeconomic strata. The incubation period varied from 1 to 90 days. Twenty (62.50%) patients in the 1985 epidemic had an incubation period of less than 7 days, in contrast to only 9 (34.61%) in the 1983 epidemic. The epidemics occurred from autumn to the start of winter. Duration of the disease varied from 1 day to 6 years. The clinical features and sites of affliction were usual; however, pseudobubo and pseudoelephantiasis were conspicuous in a significant minority.

Earlier workers^1,2 detailed the clinical features of the disease from the Indian subcontinent. Subsequently, there have been further studies^3–12 on this aspect but Sehgal and Prasad¹³ in a recent study have clearly delineated the morphological variants, the details of which are being recounted.

Most cases present as a single, well-defined, friable, beefy red, nontender, nonindurated ulcer with profuse granulation tissue, bleeding on touch, and showing no necrosis on the surface (Figs 5.1 to 5.8). However, atypical variants were encountered (Figs 5.9 and 5.10).

An irregular, friable raised growth bleeding on touch, or an ulcer with a well-defined raised edge and an elevated granulomatous base was the usual presentation (Figs 5.11 to 5.13 and 5.16). Two cases with unusual presentations were also seen in our study.

However, in the same section, donovan bodies were demonstrable in mononuclear cells.

A single case of this type of donovanosis was seen. A large foul smelling, tender, nonindurated, irregular ulcer was present on the frenum. This was associated with a similar ulcer at the left inguinal region. These had developed rapidly within a few days and had caused some destruction of the genitalia donovan bodies were demonstrable on tissue smears and histopathological section.

One case of sclerotic type was seen. A single deep, undermined, nonbleeding edges, was present on preputial skin for 2 months. Sometimes it would become active and sometimes it showed 29partial healing, leaving behind a zone of depigmentation.

Donovan bodies were seen in Giemsa stained tissue sections of this lesion.

A true bubo is generally not formed in donovanosis. However, sometimes subcutaneous tissue of the groins is affected, probably through lymphatics, leading to a fluctuant swelling which has been named by Greenblatt et al,¹⁴ as pseudobubo. This swelling mostly ruptures forming a clean raised granulomatous ulcer.

They are predominantly involved in donovanosis^1,2 the details of which are shown in Table 5.1. The prepuce, coronal sulcus, shaft, glans and frenum are the common sites of affliction in males, while in females, the labia minora, fourchette and labia majora are affected.¹³ Recounting the findings of the present analysis in males, the prepuce was affected in 31 (39.74%), coronal sulcus in 17 (21.79%), shaft of the penis in 7 (8.97%), glans and frenum in 4 (5.13%) each, while the inguinal region was affected in 3 and the upper thigh in 2 cases, labia minora in 4 cases, while the lesions were located on labia majora in 4 and in the perianal region in 1 case. In addition, affliction of the inguinal lymph nodes was seen in 41 cases. They were bilateral in 53.66% and unilateral in 46.34%. 32

Large, fungating labial ulcers, labial swelling, vaginal discharge, rectovaginal fistulae and hematuria are a few of the clinical presentation of donovanosis in women. The diagnosis of the condition may be missed in favor of common presumptive diagnoses of carcinoma, herpes, syphilis and granuloma inguinale, should the diagnosis of donovanosis not suspected and investigated accordingly.¹⁶ Occasionally, extensive mutilating granuloma inguinale in women may be encountered, especially following rape.¹⁷ Perianal abscess and sinuses are known to occur in granuloma inguinale.¹⁸

The perianal region can also be affected this usually follows homosexual contact. Bedi²⁹ has reported an unusual case of perianal granuloma inguinale in a child, of nonvenereal transmission. At attention has been drawn to primary perianal perineo-crural postpederasty donovanosis recently as a site of affliction.³⁰

The dissemination of the disease to other parts of the body, such as the oral cavity, cheeks, eyelid, sternum, thorax, abdomen, lip, gums, pharynx, ribs and clavicles and colon may also occur.¹

Concomitant infection with other sexually transmitted diseases is frequently seen. Primary syphilis (Fig. 7.1), lymphogranuloma venereum (Fig. 7.2) and gonorrhea are the most frequent associations.^1–3 A reactive serology for syphilis in the absence of any clinical signs is occasionally demonstrated.⁴

The most important sequela of donovanosis which has been studied quite extensively is its relationship to squamous cell carcinoma of the penis. Pund and Greenbl et al,⁵ in a histopathological study of the disease, found pronounced epithelial proliferation, simulating early epitheliomatous changes. Beerman and Sonck⁶ graded pseudoepitheliomatous hyperplasia seen in the disease into grades I, II and III, and concluded that when this extended deeply enough, a diagnosis of carcinoma penis could be made.

Undoubtedly, smears from tissue (Appendices I and II) obtained from lesions of donovanosis are of considerable diagnostic importance. A full description of the organisms as seen in tissue smears, stained with Wright's stain was given by Cannefax.¹ Besides, Giemsa's stain and a special stain composed of 1 percent pinacyanole in methyl alcohol² have been used. The latter stains the nucleus blue and the capsule pink.

The causative organism, Calymmatobacterium granulomatis, was cultured for the first time by Kharsany et al in the year 1996.⁸ It was a break through achievement, which subsequently encourage and provided impetus to another worker⁹ for its replications. Culture of the organism has also been done in HEp2 cells.¹⁰ This aforementioned observation led to the development of use of polymerase chain reaction (PCR) diagnostic using a colorimetric detection system.^11,12 Phylogenetic analysis confirms close similarities with the genus Klebsiella and a proposal made that C. granulomatis be reclassified as Klebsiella granulomatis comb nov.¹³

Earlier it was generally believe, that histopathological changes are nonspecific and not sufficiently characteristic to permit a diagnosis of donovanosis on tissue section. However, Pund and Greenblatt,¹⁴ focused pointed attention to its unique histopathology charatrized by (A) a massiveness of cellular reaction surcharged with plasma cells, (B) a paucity of lymphocytes, (C) a diffuse sprinkling as well as focal collections of polymorphs in papillae, (D) pseudoepitheliomatous changes, and (E) pathognomonic mononuclear cells, filled with intracytoplasmic cysts with darkly staining bodies. These features are to be taken cognizance for confirming the diagnosis, accordingly, Sehgal et al³ had, emphasized the 50distinctive histopathological features which were rather striking and affected the dermis as well as the epidermis.

The aforementioned study was extended to include 65 patients of donovanosis for characterization of circulating lymphocytes by monoclonal antibodies. 53 of them belong to ulcerogranulomatous, while 10 of hypertrophic, and 2 of sclerotic, the hematological profile and quantitation of circulating blood lymphocyte was studied with monoclonal antibodies and an indirect immunofluorescence technique to assess the immunological under-currents of the disease. The ulcerogranulomatous variant had increases in both total and absolute lymphocyte counts. Total T-lymphocytes, CD4, CD8, CD22 and CD4/CD8 ratio was all significantly elevated. The hypertrophic variant, in contrast, showed a significant elevation only in the CD4/CD8 ratio.²⁰

Genito-ulcerative diseases (GUD) including donovanosis are vulnerable to contract Human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS). It is therefore pertinent to subject such candidates to exclude the diagnosis. The later revolves around (I) serology, (II) virus isolation, (III) demonstration of viral NA, (IV) prognostic tests and (V) antiviral susceptibility assays.

The diagnosis of HIV infection by and large is made on the bases of serological tests:

Screening of blood samples for HIV antibody are commonly done by Enzyme-linked immunosorbent assays (ELISAs) the sensitivity and specificity of which is cent percent. However, false positive and negative do occur. Accordingly, passive particle agglutination, immunofluorescence, Western blots and radioimmunopercipitation assay (RIPA) bioassays are acceptable alternative currently in vogue. Western blots, gold standard, are the most accurate for they are capable of detecting the 55antibodies against both the env and egg proteins. Moreover, it is pertinent to point out that HIV antigen can be detected early in the course of HIV infection before the appearance of antibody, the latent period, when antigen-antibody complexes are present. The sensitivity of the test systems are currently being improved by the use of recombinant antigens.

It is primarily used for the characterization of the virus. The virus isolation is achieved either by the cocultivation of the patients’ lymphocytes with fresh peripheral blood cells of healthy donors or with suitable culture lines such as T-lymphomas. The presence of the virus can be confirmed by reverse transcriptase assays, serological tests, or by changes in growth pattern of the indicator cells. The process is tedious and time consuming, and is successful in only 70 to 90 percent.

This may either be accomplished by probes or by polymerase chain reaction (PCR) techniques. The latter may be useful because of its extremely high sensitivity. The latter is preferred because of its high sensitivity.

Human immunodeficiency virus (HIV) antigen detection, serial CD₄ counts, neopterin, B₂-microglobulin and viral load are a few being used for evaluating the prognosis.

Currently, it is considered useful, because of the advent of increasing range of anti-HIV agents available for use. Phenotypic and genotypic are well-recognized for the purpose. The former assist in identifying whether a particular strain of virus is sensitive or resistant to an antiviral agent by determining the concentration of the drug needed to inhibit the growth of virus in vitro. However, phenotypic assays can only be used for viruses that can be cultivated. Whereas, genotypic assays, mutations that are associated with resistance strains of virus 56are done by PCR and LCR. However, they are tedious and are not suitable for a routine diagnostic laboratory.

A couple of other diagnostic tools such as computerized tomography (CT)^24–26 scan and magnetic resonance imaging (MRI)²⁷ to establish the diagnosis of a mass resulting from Calymmatobacterium granulomatus in the genital or extragenital regions have been made use of recently, the briefs of which have been indicated at a relevant place in the text.

Recent studies have been done by means of the electron microscope on the structure of Calymmatobacterium granulomatis. It has been found to have a capsular structure surrounding the bacterium. The other layer of the bacterial cell wall was corrugated, and internal to this was a narrow cytoplasmic membrane. Dense, homogeneous, peripherally located cytoplasmic inclusions 40 millimicrons in diameter, suggestive of a bacteriophage were a regular feature.^28,29 These studies suggest a relation to Klebsiella group of organisms. These findings have been confirmed.^30,31 Both the latter workers disputed the fact that there were bacteriophages present on the cell wall.

The diagnosis of donovanosis may appear simple should the ‘suspicion’ about the condition be adopted as the mainstay for ulcers over the genitalia all the same, at times, other conditions may also have to be considered. Such conditions, may, for the purpose of comprehension, may either be sexually transmitted diseases (STDs)/Sexually transmitted infections (STIs), or Non- Sexually transmitted diseases.

Chancroid is characterized by multiple, small, superficial, painful, dirty, necrotic ulcers of varying sizes (Fig. 9.1). The edges of the ulcers are undermined and surrounded by a narrow zone of erythema and edema. They are tender and bleed on touch. Inguinal bubo may be its accompaniment (Fig. 9.2). Usually it is unilateral, unilocular, fluctuant tender swelling with overlying taut and erythematous skin.

They have recently been defined.¹ They are single ulcers with the morphology of chancroid. They have a longer incubation period of 8 to 11 days and show an absence of lymphadenopathy. Modern culture techniques² which can be used to isolate H. ducreyi in a majority of chancroid cases fail to demonstrate the organism from chancroidal ulcers. Instead, a polymicrobial flora may be lsolated.³

Only rarely can this viral infection (Fig. 9.6) be mistaken for donovanosis. It presents classically as grouped vesicular lesions 65on an underlying erythematous base.

The vesicles quickly rupture in a day or two to form superficial tender, polycyclic erosions on the genitalia. There may be a long history of recurrences and remissions. In early cases, scraping the floor of a vesicle gently with a scalpel, taking the material on a clean glass slide, and staining with Giemsa's stain, reveals characteristic 66multinucleated giant cells in the smear. Cell culture techniques are used to isolate the causative virus. The condition heals spontaneously.

Primary chancre characterizes the primary stage (Fig. 9.7). Incubation period varies from 9 to 90 days. It is a painless, erythematous, indurated papule which gets eroded to form an ulcer. The ulcer is painless, clean, well-defined, indurated and has a raw exuding surface. It resembles a button glued to the skin or the mucous membrane (Fig. 9.8). It affects the coronal sulcus, undersurface of the prepuce, the glans, the prepucial orifice, shaft of the penis and the scrotum in males while in females labia majora, labia minora, the clitoris, the fourchette, the cervix, the vagina and the mons veneris are involved.

Extragenital lesions are seen on the lips, the breast, abdomen, thighs and the anus. Lymphadenopathy characterized by multiple, nontender, discrete, firm and mobile glands is vital component and affects the inguinal glands on both sides. Demonstration of Treponema pallidum the causative organism, under the dark ground microscope is confirmatory (Table 9.2).

This stage is rarely seen now-a-days. The ulcerative variety has a punched out appearance, with sharp vertical edges and a dull-gray “wash-leather slough” base. The nodular and psoriasiform type are unlikely to be mistaken for donovanosis.

Donovanosis and LGV are morphologically distinct from each other. However, the earlier nomenclature (granuloma venereum vs lymphogranuloma venereum), may be a cause of some confusion. LGV presents initially as transient, herpetiform vesicular lesions on the genitalia which heal within a week. Around 2–8 weeks later, the patient has inguinal lymphadenitis and constitutional manifestations. The adenitis is multilocular, tender and non-fluctuant. The overlying skin is usually normal 69unless suppuration occurs, when multiple discharging sinuses are formed. Lymph nodes above and below the inguinal ligament are involved in giving rise to the typical “groove sign” with the inguinal ligament appearing as a groove in between the two lymph node masses (Fig. 9.9). A positive intradermal Frei-test and the modern serological techniques of complement fixation and microimmunoassay further differentiate LGV from donovanosis. Chlamydia trachomatis, the causative organism, may also be cultured from material taken from a bubo, or from the genital.

This common condition is due to an opportunistic yeast candida albicans. It presents in males as balanoposthitis with fissuring of the prepuce.

A moist, sodden whitish plaque is seen, on removal of which an erythematous, erosive area is revealed. There may be isolated, peripheral vesiculopustules.

These are seen in males in the form of sharply demarcated, usually linear cuts on the genitalia. There is a history that the condition developed or is noticed immediately after sexual intercourse. There is a tendency to spontaneous healing if further intercourse is avoided. However, these traumatic ulcers may show superimposition of a sexually transmitted condition whereupon the lesion changes its morphological characteristics. 71

A squamous cell carcinoma of the penis may frequently pose a diagnostic problem. The resemblance to donovanosis can be close, with both conditions exhibiting a granulomatous, ulcerated growth with hypertrophic edges (Fig. 9.11). In later stages, of course, involvement of the inguinal lymph nodes occurs in carcinoma. These are firm to hard and subsequently become fixed to deeper structures. However, in the earlier stages, both a tissue smear and a biopsy are prerequisites. Histopathologically, although epidermal changes can be similar, the presence of numerous mitoses, irregularity and bizarre pattern of nuclei and the presence of horn pearls, in carcinoma, help in differentiating the two conditions.

Scrofuloderma may present in the inguinal region as discharging sinuses and ulcers (Fig. 9.12). However, usually the underlying nodes can be felt as a matted mass, to which the sinuses are fixed. Tuberculous ulcers are necrotic, friable, have undermined edges, and have a bluish margin. Tuberculosis verrucosa cutis may, very rarely, present on the genito-inguinal region. In such cases, confusion with the hypertrophic variant of donovanosis may arise. Histopathology provides the answer; the former will show areas of caseation necrosis with a surrounding granuloma of epithelioid cells and lymphocytes. An admixture of polymorphonuclear cells may be present special staining with Ziehl-Neelsen stain will reveal acid fast bacilli.^5,6

The late stage of filaria presents as elephantiasis of the genitalia However, the absence of genital ulcerations in the past, an 74initial acute episode of fever with (usually) scrotal swelling, and microfilaria seen on a peripheral blood smear taken at night, all distinguish it from donovanosis.

This can be diagnosed by its morphological features namely single well-defined superficial erosive lesions with no regional lymphadenopathy. The lesion is preceded or accompanied by itching and/or burning. Patients often do not relate their complaints to the use of drugs or their nature. This is especially important in developing countries. A drug history should, therefore, be pursued thoroughly and systematically. In cases, where the nature of the drug is not known to the patient, eliciting the complaint for which the drug was taken may be helpful. Provocating the lesion(s) with the suspecting drug confirms the diagnosis and may help in preventing recurrences in future. It also allays the patients’ anxiety regarding the venereal origin of the disease (Fig. 9.13).⁷

Genito ulcerative disease (GUD) is well-recognized in the developing world as a cofactor for heterosexual HIV transmission. Men with GUD are an important high frequency HIV transmitter core group in the general population but few interventions have targeted such individuals so far. Donovanosis is an uncommon GUD with low infectivity characterized by large ulcers that bleed readily and has been identified as a risk factor for HIV in men in Durban, South Africa. Donovanosis is also endemic in Papua New Guinea, India, Brazil and amongst the aboriginal community in Australia. This curious geographical distribution is unique to any of the sexually transmitted diseases (STD) and might lend itself to control measures not tried previously. In the 1950–60s a global eradication program was successfully introduced against yaws but this strategy has not been implemented against any of the STD. Donovanosis is a symptomatic disease usually diagnosed on clinical grounds and could be targeted for eradication. Any program would need to be community-based and require cooperation with both hospital doctors, private general practitioners, nurses, primary health care workers, pharmacists and traditional healers. Donovanosis is usually treated by readily available antibiotics but treatment failure may occur in advanced HIV disease. Drug compliance is often a problem but may be improved by counseling.¹

Donovanosis has, for long, presented difficulties in treatment. Until the early part of this century, surgery was employed to excise the lesion along with the margin of normal tissue. Besides the technical problems, the resulting scar often broke down to cause a recurrence. Aragao and Vianna¹ were the pioneers in the use of potassium antimony tartrate. They used a 1–2 percent solution in normal saline or 5 percent dextrose intravenously, repeated on alternate days. Although successful in the early stages, chronic cases were very resistant to this form of therapy. Fouadin, a trivalent antimony preparation, was also used² as were other antimonials. The toxicity and antimony fastness-recurrent lesions developing resistance—were the main drawbacks of antimonial therapy.

Barton et al³ used this drug in the treatment of donovanosis initially. Greenblatt et al⁴ organized the first large scale trial of streptomycin and attempted to rationalize the dosage schedule. A dosage of 4 g per day in divided doses for 5 days, was found to be optimal. Donovan bodies disappeared from lesions on an average of 6 days after initiation of therapy, while healing occurred 1–2 weeks after its cessation. There were few relapses. Other workers^5–7 confirmed the efficacy of streptomycin but used different dosage schedules. Kupperman et al⁸ in another well-documented study found that streptomycin administered in total dosage of more than 20 g resulted in therapeutic cure in all cases, while recurrences were experienced with smaller dosage Rajam and Rangiah,⁹ however, had commendable results in smaller (10–20 g) daily doses over a period of 10 days. Lal et al¹⁰ too reported similar findings.

Terramycin (oxytetracycline) and Aureomycin l chlortetracycline) were tested in the treatment of donovanosis. Terramycin was found to be effective in its treatment in optimal dosage of 2 g per day over a period of 10–14 days, by the oral route.^15–17

Although sulfonamides are ineffective in the treatment of donovanosis, a combination of sulfamethoxazole and trimethoprim (co-trimoxazole) was found to be useful in treatment of this disease.²² In a subsequent follow-up only 2 out of 116 patients showed a recurrence after administration of two tablets twice a day for 10–15 days. As confirmed by Rosen et al²³ co-trimoxazole has become viable alternative to tetracycline. Treatment schedule is given in the Table 11.1.

This drug is also highly effective in the treatment of donovanosis, both orally and parenterally.^8,19,25–27

As with tetracyclines, the optimal oral dosage is 2 g per day in divided doses for 10–14 days. However, the serious, although rare, side effect of bone marrow depression caused by this drug requires that it should only be used sparingly.

Ampicillin, in the dosage of 1 to 2 g daily for 14 days, was effective in two studies^28,29 but ineffective in another.³⁰ Triacetyloleandomycin was extremely efficacious in a single study.³¹ Erythromycin, both parenterally and orally, are useful in the treatment of donovanosis.^{32, 33} Gentamicin in the dosage of 1 mg/kg body weight thrice a day was found effective in all 9 cases treated with this drug.¹³ Penicillin³⁴ has been found to be ineffective against donovanosis.

This is a semisynthetic macrolide antibiotic chemically related to erythromycin and clarithromycin. It is effective against a wide variety of bacteria, including Calymmatobacterium granulomatis causing donovanosis/granuloma inguinale. It is an unusual antibiotic in that it stays in the body for quite a while (has a long half-life), allowing for once a day dosing and for shorter treatment courses for most infections. It is FDA approved antibiotic. It should be administered empty stomach. Its possible side effects like stomach upset, vomiting and diarrhea should be focused attention at the time of prescribing the drug. This is the most frequently used antibiotic ever since its advent. Its dose variant from 500 to 2000 mg/day till the complete recovery of the lesions of GI is achieved. These aspects have been a subject of several reports.^35–39

Ciprofloxacin hydrochloride, USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. It is a synthetic broad-spectrum 83antimicrobial agent for oral administration. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8. It is available as tablets /suspention for oral use. It has successfully been used in treatment in GI in a single patient.⁴⁰ It is also available for intravenous (IV) infusion. Norfloxacin has also been advocated for use in the treatment of donovanosis.⁴¹

Ceftriaxone (Cefotaxime): It is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous (IV) / intramuscular administration. Ceftriaxone sodium is (6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72-(Z)-(O-methyloxime), disodium salt, sesquihydrate. It is a white to yellowish-orange crystalline powder, which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1 percent aqueous solution is approximately 6.7. The color of Rocephin solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. It contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.

Sterile powder contains spectinomycin hydrochloride which is an aminocyclitol antibiotic produced by a species of soil microorganism designated as Streptomyces spectabilis. Sterile spectinomycin hydrochloride is the pentahydrated dihydrochloride salt of spectinomycin. Spectinomycin hydrochloride is isolated as a white to pale buff crystalline dihydrochloride pentahydrate powder, molecular weight 495, and is stable in the dry state for 36 months.

It is a broad-spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It belongs to the class of drugs called fluoroquinolones. This medication is used to treat serious infections including life-or-limb-threatening infections, pneumonia, complicated abdominal infections, gynecologic and pelvic infections, and skin infections. Its recommended dose is 200 mg/day, either by oral or intravenus for a period 10 to 14 days in adults of diabetic foot infection or skin and skin structure infections. Accordingly, trovafloxacin was used for the treatment of chronic granuloma inguinale with acceptable results.⁴⁵ This a new addition to the existining drugs, and should be made use of feature. Precurability may ba a problem at present.

It is is a broad-spectrum antibiotic, active against both gram-positive and gram-negative bacteria and especially effective against anaerobes. It is the methyl - sulfonyl analog of chloramphenicol and has a similar spectrum of activity, but is 2.5 to 5 times as potent. Like chloramphenicol, it is insoluble in water, but highly soluble in lipids. It is used in many countries as a veterinary antibiotic, but is available in China and Italy for use in humans. Thiamphenicol is also widely used in Brazil, particularly for the treatment of sexually transmitted infections (STIs) and pelvic inflammatory disease (PID).⁴⁶ Its main advantage over chloramphenicol is that it has never been associated with aplastic anemia.

Donovanosis is primarily a disease occurring in the tropics. Inspite of this, emphasis has usually been laid on its occurrence in some parts of India, viz South and South-East, thus making the problem less concentrated in other parts. It is, therefore, imperative to ‘suspect and consider donovanosis’ as an important etiologic cause of genital ulcers which has been well demonstrated¹ where its frequency amongst the STD was found to be 3.99 percent in the capital city. Its frequency has been reported to vary from 0.3 percent² to 6.3 percent³ in the Indian subcontinent, though higher percentages have been reported elsewhere.

Undoubtedly, donovanosis/granuloma inguinale is one of the extraordinary genito ulcerative diseases (GUDs) with exclusive clinical expression, the diagnosis of which is largely made on the basis of the demonstration of intra- and/or extracytoplasmic Donovan bodies. The causative organism Calymmatobacterium granulomatis was initially grouped with enterobacteriaceae, because Donovan bodies isolated from the ulcers cross reacted antigenically with Klebsiella rhinoscleromatis, K. pneumonae, and Escherichia coli. The etiological significance of the Donovan bodies per se is largely uncertain since they fail to produce skin lesions following the inoculation. However, an inoculum obtained from the fresh lesions, on the other hand, may do so easily.

Donovanosis/granuloma inguinale is one of the outstanding genito ulcerative diseases (GUDs). Its recognition through precise clinical description is considered paramount in the current context, for ulcerative/ulcero-granulomatius lesions are deemed favorite for HIV transmission. Although, the monograph recounts its salient clinical overtone, illustrated by exquisite black and white photographs, now a material for archives, yet its documentation by colored visuals is imperative to include, fostering the interest in the entity. An endeavor to rejuvenate/rekindle awareness in the entity is attempted through beautiful colored photographs. The chronological organization, corresponding to the respective text, of the photographs has been done in order to facilitate the learning process, thus enhancing its value as an impeccable document serving has a ‘ready reckon’.

A single, well-defined, friable, beefy red, nontender, nonindurated ulcer depicting profuse granulation tissue, bleeding on touch, and showing no necrosis on the surface (Figs 14.1.1 to 14.1.8). However, atypical variants were encountered (Figs 14.1.9 and 14.1.17).

An irregular, friable, raised growth bleeding on touch, or an ulcer with a well-defined raised edge, and an elevated granulomatous base (Figs 14.2.1 to 14.2.7).

A large, foul smelling, tender, nonindurated, irregular ulcer (Fig. 14.3.1).

A single, deep, undermined, with non-bleeding edges (Fig. 14.4.1).

A fluctuant swelling following affection of subcutaneous tissue of the groins (Fig. 14.5.1).

Giemsa's stained (GS) tissue smears, depict Donovan bodies identified as mature and/or immature organisms, which are largely present inside the cytoplasm of mononuclear cells, and also outside these cells (Figs 14.7.1 to 14.7.3).

Microscopic pathology is fairly specific and may supplement the clinical diagnosis, in addition to Giemsa stained tissue smears (Figs 14.8.1 to 14.8.17).