Dynamics of the antibodies in cohorts of cured cases of visceral leishmaniasis: its implication on the validity of serological test, value in prognosis and in post therapeutic assessment.

The major disadvantage of a Serological test like Direct Agglutination Test (DAT) for Visceral Leishmaniasis (also called Kala-azar) is its inability to distinguish between recent and past infection. The objective of our study was to look at rate of decline of antibodies in fully cured cases of Kala-azar and length of time it takes for DAT to become negative. Cohort Study involving completely treated Kala-azar cases from Government Hospital during one calendar year of study. Cases were selected on the basis of treatment cohorts 0, 3, 6, 9 & 12 mo after completion of treatment.. Phase I--The cases were traced and after obtaining the informed consent they were subjected to Direct Agglutination Test (DAT). Phase II--The five treatment cohorts, constituting 82 cured cases (average of 15 cured cases per each treatment cohort) were tested again with DAT three months after the first test. The titers of Phase-I and phase-II tests were analyzed for the dynamics of the antibodies for the period. Cutoff-Values of DAT below 1:800 are considered negative. Values of 1:800, 1:1200, 1:1600 and so on are considered positive. The mean titer [Geometric Mean Titer (GMT)] at the start of treatment was 1:1120, which showed steady decline up to six months, plummeting below the cutoff titer for the DAT (1:800) at the ninth month. Antibodies continue to linger for about one year in cured Kala-azar cases even after correct and complete treatment. Single DAT results may be misleading due to high false positivity up to one year after the cure. Paired test defined as two tests 3 mo apart on the same subject. Paired test is highly recommended for diagnosis and prognosis. DAT is still a very useful tool for diagnosis if used along with clinical correlation.

Monitoring the chloroquine sensitivity of Plasmodium vivax from Calcutta and Orissa, India.

Chloroquine-resistant Plasmodium vivax malaria was first reported in India in 1995. This report led to the round-the-year monitoring, in Calcutta (West Bengal) and Mayurbhanj district (northern Orissa), of the in-vivo sensitivity of local P. vivax to chloroquine (CQ). Between January 1998 and December 2001, 800 cases with microscopically confirmed P. vivax malaria were enrolled in the study. Each was given CQ in the regimen recommended both by the Government of India and the World Health Organization (i.e. a total of 25 mg/kg, over 3 days). Only six cases, of the 480 who completed the scheduled 28 days of follow-up, failed to clear their parasitaemias by day 5. Even these six cases had only low-level parasitaemias on day 5, and all were aparasitaemic by day 7. In the study area, despite the wide-spread abuse of CQ and the increasingly frequent reports of CQ-resistant P. falciparum, CQ appears to remain an effective drug in the treatment of P. vivax.

Recurrence of kala-azar after PKDL: role of co-factors.

Recurrence of kala-azar after post kala-azar dermal leishmaniasis (PKDL) has remained uncommon. We report here two patients with recurrence of kala-azar (KA) after development of PKDL. In one case the second attack of KA was preceded by repeated attacks of malaria and tuberculosis, and in the other the recurrence of KA followed an attack of measles. While measles has earlier been suggested as co-factor in inducing transformation from sub-clinical to clinical kala-azar, malaria was demonstrated to enhance the virulence and invasiveness of Leishmania in an experimental model as well as under natural condition. We propose that in our cases, measles and repeated attacks of malaria or tuberculosis led to immunosuppression and recurrence of visceral leishmaniasis (VL).

Efficacy of sodium antimony gluconate and ketoconazole in the treatment of kala-azar--a comparative study.

The present study was undertaken to determine the efficacy of ketoconazole in comparison to sodium antimony gluconate (SAG) in the treatment of kala-azar. The study was conducted at two centres: All India Institute of Medical Science, New Delhi and Calcutta School of Tropical Medicine, Calcutta. A total of 180 patients with proven kala-azar were recruited. After preliminary investigations, the patients were randomly divided into 2 groups: One group received ketoconazole in a dose of 600 mg/ day in 3 divided doses for 4 weeks while the other group was treated with SAG at a dose of 20 mg/kg/day up to a maximum of 850 mg/day for 4 weeks. The patients were followed up by clinical examination, liver functions, haemogram and the bone marrow/splenic aspiration. Responders were followed up at 3 and 9 months of intervals. Of 90 cases in SAG, 78 (81.7%) got cured initially while under ketoconazole group, only 26 (33.3%) of 78 patients responded initially (p < 0.001). After 3 months of follow up, 75 of 78 SAG-responders (96.2%) and 24 of 26 ketoconazole-responders (92.3%) continued to be in remission. Despite the fact that 2 patients in each group were lost to follow up at 9 months, similar observations were noted with only one relapse in SAG group. The response to SAG was comparable at the two centres. However, the response to ketoconazole was better at Delhi centre as compared to that at Calcutta. There were no significant side effects or hormonal changes in any of the patients in ketoconazole group at Delhi centre. Significantly higher side effects were reported at Calcutta centre in ketoconazole group (P < 0.05). No satisfactory explanation can be given for this difference in response to ketoconazole at two centres. However, it is known that leishmanial parasites of different geographical origin differ in their response to different drugs and this could be one of the reasons for difference observed in response rate to ketoconazole as the study involved different populations of people.

Laryngeal involvement during post kala-azar dermal leishmaniasis in India.

Post kala-azar dermal leishmaniasis (PKDL) involving the mucus membranes is relatively rare on the Indian sub-continent. We describe 3 cases of PKDL presenting with hoarseness of voice. In one case the skin, nasal, oral, oropharyngeal and laryngeal mucosa had nodular and nodulo-ulcerative lesions; in the 2 other cases, genitalia and anorectal mucosa were also affected. Laryngoscopic examination revealed nodular lesions on the vocal cords. Biopsy smear and culture confirmed their leishmanial origin.

Studies on the life cycle of Artyfechinostomum oraoni Bandyopadhyay, Manna & Nandy 1989: embryogenesis & development in the intermediate host.

A study was undertaken to elucidate the life cycle of the parasite A.oraoni, isolated from man. For the purpose, operculated eggs were isolated from faeces of oraon tribals belonging to the village Bandipore, district North 24-Parganas of West Bengal province of India. The purified eggs were incubated at different temperatures, salinity and pH. Larvae (miracidia) could be observed to develop between the 7th and 8th day of incubation at a temperature range between 22 degrees-30 degrees C. While the optimum pH was observed to be neutral, larval development did not take place at salinity beyond 0.8 per cent. To identify the correct intermediate host, all available species of snails from the study village were colonised and infected with the laboratory hatched miracidia from human derived operculated eggs. It was observed that of all the snails infected, only Lymnaea supported the development of rediae from miracidia, which could be observed on the 32nd post infection day. Considering the results of the experimental study, it was hypothesised that Lymnaea spp. of snails under natural condition also, might act as the first intermediate host for A. oraoni.

Pathogenicity of Artyfechinostomum oraoni in naturally infected pigs.

In an attempt to establish the diarrhoeogenic potential of the newly identified Artyfechinostomum oraoni, which was associated with human diarrhoea in a tribal community near Calcutta, India, two naturally infected domestic pigs of the locality were followed in captivity. Both pigs developed fatal diarrhoea after 5 months. The autopsy revealed a massive infection with the echinostome on a haemorrhagic and oedematous mucosa of the jejunum and duodenum extending up to pyloric end of the stomach. It is suggested that similar pathology might also be operating in the infected man.