Risk factors for Indian kala-azar

A case-control study was conducted to understand the risk factors associated with kala-azar in disease-endemic areas of Bihar, India. A total of 134 kala-azar cases treated at the Rajendra Memorial Research Institute of Medical Sciences in Patna and 406 healthy controls selected randomly from the neighborhoods of cases in their native villages were included in the study. Univariate analysis showed that education, a history of other diseases in the previous year, a history of kala-azar in the family, type of walls in houses, presence of a granary inside houses, presence of vegetation around houses, bamboo trees near houses, and irregular spraying around houses with DDT were risk factors. Multivariate analysis showed that a history of other diseases in the previous year (odds ratio [OR] = 3.6, P = 0.002), a history of kala-azar in the family (OR = 1.8, P = 0.03), mud-plastered walls in houses, (OR = 2.4, P = 0.0001], a granary inside houses (OR = 4.3, P = 0.0001), presence of bamboo trees around houses (OR = 2.3, P = 0.001), and houses not sprayed with DDT in the past six months (OR = 3.4, P = 0.0001) were significant risk factors for kala-azar. These results will be useful in developing kala-azar control programs for identifying intervention strategies such as better housing, regular and proper insecticide spraying, and promoting health awareness to the community residing in disease-endemic areas for reducing transmission and incidence of this disease.     

Susceptibility of Phlebotomus argentipes against DDT in endemic Districts of North Bihar, India

Susceptibility status of Indian kala-azar vector Phlebotomus argentipes after DDT spray from endemic areas of Muzaffarpur and Vaishali district and unsprayed non-endemic area of Patna district, Bihar, India were compared. Higher Lc50 viz. 2.6% and 3.2% and LT50, values 51.0 and 69.0 minutes to 4% DDT were observed for P. argentipes of Muzaffarpur and Vaishali district, whereas P. argentipes of Patna district was 100% susceptible to same concentration, indicating increased tolerance in P. argentipes. It is concluded DDT resistant P. argentipes, particularly in endemic zone growing. The possible explanation could be long-term insecticidal pressure.     

Visceral leishmaniasis (kala-azar)--the Bihar (India) perspective

From a hospital-based surveillance carried out in Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar, India, the socio-economic, demographic and treatment response information of 737 patients admitted with visceral leishmaniasis (VL) during January 2001-December 2003, were analysed. The disease was two times higher in males than in females because of several factors including clothing pattern, sleeping habits and occupation. In Bihar, the second poorest state in India, poverty plays a major role in perpetuation of the disease, contributing to malnutrition, illiteracy (60%), and poor housing (82%). Further, presences of peri-domestic animal shelters around houses (63%) and vegetations (77%) facilitate breeding of sand fly vector. Clinical and laboratory characteristics were similar in the age groups <12 years and >12 years. The increasing unresponsiveness of VL patients to conventional anti-leishmanial drugs, e.g. sodium antimony gluconate (SAG) and pentamidine, has definitely posed a major therapeutic challenge in combating the disease. Amphotericin B, though costly, is highly effective. Miltefosine is a highly promising new oral drug for VL.     

Sandfly survey in Nainital and Almora districts of Uttaranchal with particular reference to Phlebotomus argentipes, vector of kala-azar

Kala-azar continues to pose a major public health problem in Bihar, West Bengal and parts of eastern Uttar Pradesh in India causing great deal of morbidity and mortality. During 1998, several kala-azar cases from Sub-Himalayan region were treated in Delhi hospitals. And a suspected focus of kala-azar was subsequently reported from this area. Therefore a preliminary sandfly survey was carried out during October, 1999 in 18 randomly selected villages at different altitudes in Nainital & Almora districts of Kumaon region Uttaranchal. The surveys revealed relative preponderance of vector sandfly Ph. argentipes as 77%; mainly confined to cattlesheds and mixed dwellings in the villages at an altitude ranging from 350-960 metres main sea level. The other sandfly species encountered were: Ph. papatasi 6.9%, Ph. major 2.9% and 13.2% Sergentomyia spp. 17.4% Ph. argentipes reacted positive with human antisera and 82.6% with bovine but none reacted with goat, pig dog and bird antisera indicating that Ph. argentipes in the area is mainly zoophilic. Ph. argentipes was found to be highly susceptible to DDT; mortality ranging from 98-100%.     

High levels of C-reactive protein in the peripheral blood during visceral leishmaniasis predict subsequent development of post kala-azar dermal leishmaniasis

Post kala-azar dermal leishmaniasis (PKDL) is a known sequel to visceral leishmaniasis in India and East Africa, and in Sudan about 50% of the kala-azar patients develop PKDL. In this study we followed kala-azar patients from diagnosis and up to 2 years after initiation of treatment. During the first 6 months some developed PKDL (group 1), while some did not develop PKDL (group 2). We measured the plasma levels of C-reactive protein (CRP) at diagnosis of kala-azar (day 0), during treatment (day 15), after treatment (day 30) and later during the follow up period. At day 0, plasma CRP levels were higher in patients who later developed PKDL (group 1) than in patients who did not develop PKDL subsequently (group 2) (P = 0.008). At days 15 and 30, the CRP levels were comparable in the two groups, and lower than at day 0. We have previously shown that high plasma levels of IL 10 and in keratinocytes during visceral leishmaniasis predict subsequent development of PKDL. The method however requires expensive equipment and reagents. The results of the present study indicate that kala-azar patients, who have a high risk of developing PKDL after treatment can be identified by measuring plasma CRP.     

Hepatitis B and C viral infections in Indian kala-azar patients receiving injectable anti-leishmanial drugs: a community-based study.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B and hepatitis C viruses have emerged as major blood-borne infections. Several cases of infections through the use of unsterile injection needles also are on record. Kala-azar, or visceral leishmaniasis, is a hemoparasitic disease caused by Leishmania donovani. All the anti-kala-azar medications require multiple intramuscular injections of the anti-leishmanial drugs. To find whether these patients were at higher risk of contracting blood-borne infection, than those who were not on medication, a community-based study was conducted in the kala-azar-endemic state of Bihar, India. METHODS: Five villages (4050 families) of three highly endemic districts of Bihar were included in this study. The sociodemographic data of the affected families and their annual income were determined as per Government of India guidelines. The diagnosis of kala-azar and its sequelae, post-kala-azar dermal leishmaniasis (PKDL), was made, and their therapeutic details were noted. All the leishmania-infected patients, their spouses, family members, and villagemates were tested for hepatitis B surface antigen, hepatitis C virus antibodies, and anti-HIV (1 + 2) antibodies, using commercially available kits. RESULTS: Of the 4050 families, 61 (1.5%) were found affected with kala-azar or PKDL. These 61 families had 77 cases of leishmaniasis, of which 64 (83%) had kala-azar and 13 (17%) PKDL. The most affected (4.5%) age group was 11 to 40 years. Of the 61 families, 57 (93.4%) families belonged to so-called untouchable castes, and 9 of them could not afford to have any anti-kala-azar treatment. Only 64 patients received treatment in the form of injectables. The number of injections received by these patients ranged from 3 to 120. Hepatitis B and C viral infections were found to be significantly more prevalent in those who received multiple injections. Compared to their male counterparts infected with L. donovani, females who received injectable medicines were at higher risk of contracting hepatitis B infections (20% vs. 11.3%) and hepatitis C virus infection (26.7% vs. 18.9%). Overall, hepatitis C virus infections were more common (20.6%) than hepatitis B virus infection (13.2%) in this group of patients. Villagemates with a history of injections for other ailments also were found to have a high rate of infection with hepatitis viruses. One patient with kala-azar was found to be co-infected with HIV, although probably not related to injections. CONCLUSIONS: The treatment of Indian kala-azar and post-kala-azar dermal leishmaniasis consists of multiple intramuscular injections of sodium stibogluconate, pentamidine, or amphotericin B. Though the original disease gets cured, all these therapeutic regimens were found to carry a significantly high risk of transmitting yet more dangerous blood-borne infections, such as HIV and hepatitis B and C viruses, through the shared use of unsterile injection needles. All needles should be appropriately sterilized, if they are to be re-used.     

Hepatitis B, C and human immunodeficiency virus infections in multiply-injected kala-azar patients in Delhi

Sera from 164 patients with parasitologically confirmed kala-azar and 100 patients with non-kala-azar Delhite in 2 Delhi hospitals were tested for anti-human immunodeficiency (anti-HIV) and anti-hepatitis C virus (anti-HCV) antibodies and hepatitis B surface antigens to determine which group is more likely to contract these infections. The mean age of the patients was 32.5 y (+/-6.5 y), (120 M, 44 F). Two patients were from Nepal and the others from the kala-azar endemic state of Bihar, India. As geographical controls, 50 serum samples from sex- and age-matched healthy Bihar residents were also tested for the blood-borne viral infections. All patients had been treated with injectable medicines by 1 or more local physicians before they were referred to the Delhi hospitals. The prevalence of hepatitis B virus (HBV) and HCV infection was significantly different between the 2 patient groups. While 2 kala-azar patients (1.21%) were found to be HIV-1 positive, 54 (32.9%) patients had anti-HCV antibodies detected by ELISA and 51 (31.1%) by RIBA test. The seroprevalence of HCV was only 2% in hospitalized non-kala-azar cases and 4% in the geographical controls (p < 0.001). The seroprevalence of HBV was 13.2% in hospitalized kala-azar cases, but only 1.75% in disease control cases and 1.6% in geographical control cases. The difference in infection rates between cases and controls was significant (p < 0.001). The results indicate that kala-azar patients treated locally in Bihar have a greater chance of contracting blood-borne infections. Interestingly, we found that HCV was more prevalent than HBV. These infections were most likely acquired through the re-use of needles by local medical and paramedical practitioners for administering anti-leishmanial drugs. This trend, if not checked immediately, may have drastic consequences in the horizontal transmission of HIV in Bihar.     

Use of rK39 for diagnosis of post kala-azar dermal leishmaniasis in Nepal

A recently developed nitrocellulose-based dipstick test, rK39, has been widely used for the diagnosis of kala-azar. In this study, we evaluated its use for the diagnosis of post kala-azar dermal leishmaniasis (PKDL). We also investigated the time taken by patients to develop PKDL after apparent cure of kala-azar (visceral leishmaniasis, VL) and the time taken by patients to come to the hospital after the appearance of symptoms of PKDL. A majority of patients developed the disease within three years after the apparent cure of kala-azar (KA). A majority of patients sought treatment within five years after the onset of PKDL. The amastigotes of Leishmania donovani bodies (LDBs) were demonstrated in 70, 20, and 20% of slit-skin smears (SSS) prepared, respectively, from nodular, papular, and macular forms. The presence of highest density (6+) LDBs in the SSS of 20% of nodular PKDL patients indicated that they may have acted as reservoir in the community. Other reservoirs are not known in Nepal. Only 8% cases were detected by aldehyde test. Although this test is obsolete it is still used in rural parts of Nepal. The dipstick (rK39) was 96% sensitive and 100% specific to diagnose PKDL. Its positive predictive value, negative predictive value, and diagnostic efficacy were 100, 91, and 97% respectively. Due to the advantage of cost compared with the direct agglutination test (DAT), and being easy to use and store in field conditions, rK39 is a good tool to diagnose PKDL in rural situations. All the PKDL patients were cured of the disease after treatment by SAG.     

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).     

Clinical and Immunological Aspects of Post–Kala-Azar Dermal Leishmaniasis in Bangladesh

We conducted active surveillance for kala-azar and post–kala-azar dermal leishmaniasis (PKDL) in a population of 24,814 individuals. Between 2002 and 2010, 1,002 kala-azar and 185 PKDL cases occurred. Median PKDL patient age was 12 years; 9% had no antecedent kala-azar. Cases per 10,000 person-years peaked at 90 for kala-azar (2005) and 28 for PKDL (2007). Cumulative PKDL incidence among kala-azar patients was 17% by 5 years. Kala-azar patients younger than 15 years were more likely than older patients to develop PKDL; no other risk factors were identified. The most common lesions were hypopigmented macules. Of 98 untreated PKDL patients, 48 (49%) patients had resolution, with median time of 19 months. Kala-azar patients showed elevated interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and interleukin 10 (IL-10). Matrix metalloproteinase 9 (MMP9) and MMP9/tissue inhibitor of matrix metalloproteinase-1 (TIMP1) ratio were significantly higher in PKDL patients than in other groups. PKDL is frequent in Bangladesh and poses a challenge to the current visceral leishmaniasis elimination initiative in the Indian subcontinent.     

Laryngeal involvement during post kala-azar dermal leishmaniasis in India

Summary 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.     

Knowledge about sandflies in relation to public and domestic control activities of kala-azar in rural endemic areas of Bihar

Visceral Leishmaniasis (VL) control is a global cause of concern. To identify the gaps in People's knowledge/awareness about sand flies and control activities of kala-azar in rural endemic areas of Bihar, this study consisting of 450 respondents with 288 male and 162 female was carried out. The result showed that 95% respondents had heard about the disease up to some extent, but majority respondents were neither aware about the vector of kala-azar, nor they had any idea about transmission of the disease. About 61% had wrong impression that mosquitoes were causing kala-azar. Regarding knowledge about breeding and resting sites of vectors, 20% reported cattle shed, 16% crevices in the household followed by 15% damp dark places. The attitude of respondents towards vector control programme was poor, as 99% lost faith in the DDT spraying because of ineffectiveness, like no reduction in mosquito nuisance. Bed net was considered the best protection method against sand fly or mosquito nuisance but the cost was considered the major constraint in its use. Proper health education programme in Simple and local language along with visual demonstration should be promoted to enhance the awareness and co-operation at community level.     

Post‐kala‐azar dermal leishmaniasis in visceral leishmaniasis‐endemic communities in Bihar,India

We assessed the prevalence of post‐kala‐azar dermal leishmaniasis (PKDL), a late cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL‐endemic communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the post‐kala‐azar dermal leishmaniasis cases are discussed.     

PCR-based detection of Leishmania DNA in skin samples of post kala-azar dermal leishmaniasis patients from an endemic area of Bangladesh

Post kala-azar dermal leishmaniasis (PKDL) is a sequel of visceral leishmaniasis (VL) and PKDL patients are an important reservoir for anthroponotic transmission of VL. Therefore, diagnosis and treatment of PKDL is important for the kala-azar elimination program in South Asia, including Bangladesh. While definitive diagnosis of PKDL is still based on microscopy, despite the low sensitivity of this method of diagnosis, PCR for identification of kinetoplast DNA (kDNA) from Leishmania parasites is expected to be a rapid and sensitive diagnostic method. We attempted PCR-based diagnosis from skin biopsy specimens and compared PCR to other available detection methods in order to determine the acceptability and feasibility of the PCR diagnostic method in an endemic area of VL in Bangladesh. Both skin biopsy specimens and blood samples were collected from 110 patients suspected to have PKDL from 6 subdistrict health complexes in Mymensingh, Bangladesh. Using microscopy, we identified 32 samples (29.1%) that were positive for Leishmania. Immunochromatography tests indicated that 85 samples (77.3%) were positive for Leishmania. In contrast, a total of 104 (94.5%) samples tested positive using nested PCR, while unaffected portions of skin from PKDL patients tested negative. Sequencing analysis of the PCR products indicated that the amplified portion had more than 98% nucleotide sequence identity to the Leishmania donovani reference strain, D10. These findings indicate that the PCR method using a skin biopsy is highly sensitive and useful for confirmatory diagnosis of PKDL.     

Prohibition and Alcohol Intoxication

The effect of total prohibition imposed in Bihar State with effect from April, 1979, was assessed on the basis of the hospital records of Patna Medical College Hospital. During the first seven months of prohibition, there was a significant decrease in the number of alcohol intoxication cases as compared to the numbers of such cases during the corresponding periods of 1976, 1977 and 1978 (P < 0.001). During the subsequent Jive months of prohibition the number of cases increased and the figure was not significantly different from those of previous years (P. > 0.07). Age, sex and urban or rural distributions of cases remained unaltered during prohibition and pre-prohibition periods. A similar trend was observed in Pilgrim Hospital, Goya which is situated 92 km south of Patna. There was however a significant decrease in alcohol related crimes during prohibition compared to previous years (P. < 0.01), and possible reasons for discrepancy between the hospital and arrest indicator are discussed. During the prohibition period there was a 20 per cent increase in illicit trade in liquor. While people from the lower income group favoured prohibition, those from the higher income group did not approve of it. People from both groups got alcohol in the black market. Except for the initial drop in the number of hospital cases, the medical problem of alcohol intoxication was not solved by the ineffective enforcement of prohibition.     

Cold weather and myocardial infarction

We studied 1217 cases of myocardial infarction, admitted to Patna Medical College Hospital, Patna, during the period 1979 to 1983, and correlated the incidence of the disease with air-temperature, seasons and months. There was no monthly variation in the incidence of the disease. The seasons similarly had no influence on incidence. The frequency of myocardial infarction, however, was significantly higher when the minimum air-temperature was 16 degrees C or less (P less than 0.001). This study indicates that drop in atmospheric temperature below a certain level directly increases the incidence of myocardial infarction and suggests simple prevention measures against the adverse effect of cold.     

Sero-epidemiological study of kala-azar in a village of Varanasi district, India

OBJECTIVE: To evaluate five kala-azar serological tests for field use. METHOD: Serological survey in Pandit Ka Purva village in Varanasi district, India, using Sia water test, aldehyde test, direct agglutination test (DAT), micro-enzyme-linked immunosorbent assay (ELISA) and dot-ELISA. RESULTS: The total population of the village was 518, 67 of whom showed typical clinical and parasitological features of kala-azar, including seven who died. The age distribution of kala-azar cases showed significant differences, being highest among the 45-54-year age group. The disease was more prevalent among males. Serum samples were collected from 498 persons (96% of total population) including 67 kala-azar cases and 40 disease controls (malaria, TB, leprosy, typhoid). Ten 10 serum samples from healthy controls living in endemic area were also collected. The test sensitivities were: Sia water test, 85.0%; aldehyde test, 62.7%; DAT, 94.0%; micro-ELISA, 91.0% and dot-ELISA, 97.0%. The test specificities were: Sia water test 92.5%, aldehyde test, 93.2%, DAT, 96.7; micro-ELISA, 97.6% and dot-ELISA, 98.4%. CONCLUSION: The dot-ELISA is highly sensitive and specific, cheap, and easy to interpret with the naked eye, making it a powerful screening test for the surveillance and diagnosis of Indian kala-azar at field level.     

rK39免疫层析试条在新疆黑热病诊断和流行病学调查中的应用

目的观察rK39免疫层析试条对新疆不同类型黑热病的诊断及流行病学调查中的应用价值。方法用rK39试条检查不同地区确诊的黑热病患者;用rK39-ELISA和rK39免疫层析试条检查不同流行地区居民血清标本与利什曼素皮内反应结果进行比较分析。结果对来自新疆不同地区的黑热病患者共1204例,用rK39试条检测抗体阳性者1169例,阳性率97.09%。其中人源型黑热病患者1052例中1031例阳性,阳性率98.0%;荒漠型黑热病患者158例中阳性143例,阳性率90.5%。二者之间差异显著(P<0.001),荒漠型患者阳性率较低。人源型黑热病流行区居民中rK39抗体阳性率在既往有黑热病史者中为42.7%～59.3%,在无既往史的居民中仅为2.2%～5.8%。在随访的rK39阳性,皮内反应阴性的18人中有4人在4和6个月后出现症状,确诊为黑热病。在黑热病治愈后2年内94.6%的患者rK39抗体仍为阳性。9年后仍有82.5%保持阳性。结论rK39层析试条对新疆黑热病患者有很高的诊断价值。其保存、携带方便,操作简单适于在基层现场使用。由于其可在潜伏期中发现黑热病患者。故可用于在流行地区皮内反应阴性的居民中进行免疫学检测,早期发现病人。由于黑热病患者治愈后血清中rK39抗体长期存在,故不适用于预后判定和疗效评价。     

Congenital kala-azar

An 11-month-old male infant was admitted to hospital with fever, pallor and hepatosplenomegaly, and was diagnosed as having kala-azar. The mother also suffered from kala-azar while carrying this baby. As the baby and the mother did not leave Delhi either during or after delivery, and the vector found in Delhi is not competent to transmit leishmaniasis, the infant could not have been infected by the bite of a sandfly. It therefore seems most likely that he was infected in utero--a rare route.     

陕西省韩城市黑热病流行特征及高危因素分析

目的 了解韩城市黑热病流行病学特征及高危因素,为进一步开展流行病学调查奠定基础。方法 对韩城市历史数据进行描述,回访调查2012-2016年报告病例发病诊治经过,按照1∶4匹配的病例对照研究方法,对生活行为习惯和居住环境等因素进行问卷调查,数据用Excel 2007、R软件描述分析。结果 韩城市1953-2016年共报告病例599例,死亡9例,年平均发病率为14.61/10万,病死率为1.50%;2012年至2016年报告病例18例,死亡2例,发病高峰期是5-9月, 占报告病例数的72.22%;病例大部分分布在北部山区;农民发病较多,男性发病高于女性,成人多于儿童;病例主要症状体征为发热、脾大;利用COX回归分析患病因素,养犬OR值为4.618,95%CI为1.519~14.039,P<0.05,病例组与对照组间存在统计学差异,其余因素病例组与对照组不存在统计学差异。结论 韩城市为黑热病历史疫区, 2012年至2016年报告病例呈点状分布,家中养犬是患病的危险因素,综合分析韩城市可能为山丘型或人犬共患型黑热病流行区。