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Background Unhealthy dietary scores have been associated with increased risk of Type 2 Diabetes mellitus, which have a significant impact on affected individuals and healthcare services. However, there is lack of published evidence on quality of diet in type 2 diabetic subjects. Therefore, we aimed to assess dietary pattern scores and their relationship with adiposity, glycemic profile, lipid parameters and nutritional biomarkers in T2DM patients. Methods We included T2DM patients (n = 203) with age group ranging from 30-70 years. All patients were interviewed for their dietary patterns through a derivative questionnaire of UK Diabetes and Diet Questionnaire (UKDDQ). Patient information including socio-demographic and anthropometric details were obtained. All biochemical parameters were estimated and recorded. The SPSS ver. 21 was used to perform statistical analysis. Results The study included 48.8% males and 51.2% females with mean age of 53.92 ± 10.56 years. The mean values of diet scores ranged from healthiest [1.02 ± 0.17(CI = 1.00 to 1.04)] to least healthy [2.65 ± 0.71(CI = 2.55 to 2.74)] respectively. Majority of patients (n = 153) were reported to have a habit of skipping breakfast routinely within 2 h after waking. However, 162 patients were consuming the unnecessary food items between the regular meals. While increasing in diet mean scores i.e. moving from lower quintile Q1(21.86 ± 1.23) to higher quintile Q5(28.94 ± 2.24), a variable relationship was found. The post prandial (PP2)(r = 0.233), fasting blood glucose (FBG) (r = 0.183), HbA1c(r = 0.253) and body mass index (BMI)(r = 0.139) shown a direct association whereas zinc(r = −0.116), vitamin D(r = −0.185) and Albumin(r = −0.043) were inversely correlated between the quintiles. Conclusions Increasing dietary scores are supposed to have a provoking effect on disease condition resulting into worse outcomes at higher scores. The findings from nutritional biomarkers suggested that deficiently found nutrients must be supplemented as a part of therapy to enhance the treatment benefits.

Background Visceral leishmaniasis (VL), also known as kala-azar (KA), is a neglected vector-borne disease, targeted for elimination, but several affected blocks of Bihar are posing challenges with the high incidence of cases, and moreover, the disease is spreading in newer areas. High-quality kala-azar surveillance in India, always pose great concern. The complete and accurate patient level data is critical for the current kala-azar management information system (KMIS). On the other side, no accurate data on the burden of post kala-azar dermal leishmaniasis (PKDL) and co-infections are available under the current surveillance system, which might emerge as a serious concern. Additionally, in low case scenario, sentinel surveillance may be useful in addressing post-elimination activities and sustaining kala-azar (KA) elimination. Health facility-based sentinel site surveillance system has been proposed, first time to do a proper accounting of KA, PKDL and co-infection morbidity, mortality, diagnosis, case management, hotspot identification and monitoring the impact of elimination interventions. Methodology/principal findings Kala-azar sentinel site surveillance was established and activated in thirteen health facilities of Bihar, India, using stratified sampling technique during 2011 to 2014. Data were collected through specially designed performa from all patients attending the outpatient departments of sentinel sites. Among 20968 symptomatic cases attended sentinel sites, 2996 cases of KA and 53 cases of PKDL were registered from 889 endemic villages. Symptomatic cases meant a person with fever of more than 15 days, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen (enlargement of spleen and liver).The proportion of new and old cases was 86.1% and 13.9% respectively. A statistically significant difference was observed for reduction in KA incidence from 4.13/10000 in 2011 to 1.75/10000 in 2014 (p, Author summary Visceral leishmaniasis is a neglected vector-borne disease, and one of the major public health problems of Bihar. The disease has been targeted for elimination by 2020. Bihar still posing challenge i.e. incidence is much high in a number of affected blocks, and even the disease is spreading in newer areas. None availability of an accurate data on the burden of post kala-azar dermal leishmaniasis (PKDL) and co-infections under the current surveillance system may emerge as a serious concern. Therefore, health facility-based sentinel site surveillance system has been attempted for the first time in Bihar for proper accounting of KA, PKDL and co-infection morbidity, mortality, diagnosis, case management, hotspot identification and monitoring the impact of elimination interventions. A system for capturing regional transmission is essential that can target focal areas of infection to monitor progress towards kala-azar elimination. Kala-azar sentinel site surveillance was established and activated in thirteen health facilities of Bihar during 2011 to 2014. The results showed a significant increase in PKDL and co-infection in 2014 when compared to 2011. Findings further revealed that utilization of laboratory services and case management were greatly improved, as majority of patients with KA, PKDL & co-infections were managed by the sentinel sites itself. The final cure rate of AmBisome was found excellent (100%). These observations may be useful to provide the basis for the design, refinement and resource allocation of the kala-azar control program. This system may also be useful in measuring impact of elimination interventions, their effectiveness and finally help in improving program management. It may further be used as an example for changing the practices of health care workers in Bihar and a lesson how to achieve high quality surveillance data in a resource limited setting. Standardization of sentinel site surveillance in terms of improved procedure, training, logistics, etc may further increase the effectiveness of this system. It may possibly be used as a cost-effective approach for capturing real-time kala-azar data under national kala-azar elimination programme.

Background: From Gaya and adjoining regions, the trend in patients admitted with acute neurological illness was investigated. Illnesses were identified as sudden outbreaks of Japanese virus encephalitis (JE), Herpes simplex virus encephalitis (HSV-1&2), and other acute encephalitis syndrome (AES). Objective: In the current study, an investigation was carried out to assess potential infectious pathogens in patients aged 16 years or younger who were admitted to Anugrah Narayan Magadh Memorial Medical College Hospital, Gaya, with encephalitis-like symptoms. Methods: Cross-epidemiological, serological, and molecular biological studies were performed on samples collected from 71 patients below 16 years of age. Patients’ clinical histories, i.e. fever, socio-demographic characteristics, and other clinical data, were extracted from patient files. Results: The results showed confirmed AES cases, including 49.30% JE and 7.04% HSV positive patients. A higher case-fatality rate of 40% in JE and 40% HSV cases below 7 years of age were observed during treatment would become an unavoidable concern. The epidemical sex ratio was observed to be higher in girls than in boys (1.26:1). Conclusion: The results suggested that JE virus was found to be a main causative risk factor responsible for disease transmission in the outbreak area.

BACKGROUND Surveillance of post-kala-azar dermal leishmaniasis (PKDL) is critical to the elimination of visceral leishmaniasis (VL). In this study we assessed the feasibility of using trained field workers for detecting suspected PKDL cases. METHODS A cross-sectional study using a multistage sampling technique was conducted in the Araria district of Bihar. Trained field workers were utilized for identification of suspected PKDL case. RESULTS We investigated 57 099 individuals from 11 300 households. The trained field workers were useful in identifying 107 (18%) probable PKDL cases. The calculated PKDL prevalences were 18.7/10 000 and 9.7/10 000 for probable and confirmed PKDL cases, respectively. The median duration of onset of PKDL was 23 months (interquartile range 16.5-56.5). The younger age group developed PKDL significantly more often compared with the older age group (p=0.007). Of the 107 patients, 25 (55.5%) were positive by microscopy of slit skin smear and 42 (93.3%) by polymerase chain reaction. Of 45 patients, 33 (73%) PKDL cases were cured after full treatment. The risk of not being cured with incomplete treatment was three times higher than with complete treatment (relative risk 3.12 [95% confidence interval 1.23 to 8.67], p=0.004). CONCLUSIONS We conclude that the prevalence of PKDL is high and the use of trained field workers may be feasible to actively detect PKDL cases in VL-endemic areas of Bihar, India.

Background & objectives: In India, kala-azar surveillance is weak and no public-private partnership exists for disease containment. Estimate of disease burden is not reliably available and still cases are going to private providers for the treatment. The present study aimed to assess the magnitude of kala-azar cases actually detected and managed at private set-up and unreported to existing health management information system. Methods: Institution based cross-sectional prospective pilot study was conducted. List of facilities was created with the help of key informants. The information about incidence of kala-azar cases were captured on monthly basis from July 2010 to June 2011. Rapid diagnostic strip test (rk-39) or bone marrow/splenic puncture were applied as laboratory methods for the diagnosis of kala-azar. Descriptive statistics as well as chi-square test for comparison between proportions was conducted. Results: Overall availability of private practitioners (PPs) was 4.59/1,00,000 population and maximum PPs (46; 93.9%) were from qualified category. The median years of medical practice was 25 yr (inter quartile-range [18, 28]). Interestingly, only a small proportion (240; 19%) of cases was managed by PPs. Amongst the PPs, only low proportion (32; 18.2%) managed >2 cases per month. The mean number of kala-azar suspects and cases identified varied significantly between different PPs’ professions with p

A rapid and noninvasive rK39 rapid diagnostic test (RDT) is the best and most reliable tool for visceral leishmaniasis (VL) screening in the field. However, splenic and bone marrow aspiration remain two gold standard methods for microscopic identification of Leishmania donovani (LD) bodies and confirmatory diagnosis of VL. Five patients with signs and symptoms of fever, loss of appetite, loss of weight, hepatomegaly, and massive splenomegaly were found to be false positive with the rK39 RDT. These patients were suspected to have chronic myeloid leukemia (CML) because their blood pictures showed a total white blood cell count of > 100,000/mm(3) and abnormal cells such as stab, segmented promyelocytes, myelocytes, metamyelocytes, and blast cells. Splenic aspirate and bone marrow were negative for Leishmania donovani bodies. The bone marrow showed myeloid series of cells, that is, myelocytes, metamyelocytes, stab and segmented cells, blast cells, and markedly increased myeloid:erythroid ratio. Later, the CML diagnosis was confirmed in all cases by breakpoint cluster region-tyrosine protein kinase (BCR-ABL) gene positive test results. In this study, the rK39 RDT’s false positivity was observed in CML cases. It could have important implications for the differential diagnosis of VL with CML. The rK39 positive test result in CML cases was a serendipitous occurrence; this should be validated further to determine the utility of the rK39 test in the differential diagnosis of VL with CML.

Liposomal amphotericin B is being used increasingly to reduce the burden of kala-azar from the Indian subcontinent. There are studies which have evaluated efficacy and safety of liposomal amphotericin B for visceral leishmaniasis in all age groups. However, the only study that specifically addressed treatment of childhood visceral leishmaniasis did not include all ages or document renal and liver function. We, therefore, felt it was important to reassess the efficacy and safety of single dose liposomal amphotericin B in children and adolescents. A total of 100 parasitologically confirmed visceral leishmaniasis patients aged < 15 years were included in this study. Participants consisted of 65 males and 35 females. All of them had come from the endemic region of Bihar. They were administered one dose intravenous infusion of liposomal amphptericin B at 10 mg/kg body weight. Efficacy was assessed as initial and final cure at 1 and 6 months, respectively, and safety of all participants who were recruited in the study. The initial and final cure rate by per protocol analysis was 100% and 97.9%, respectively. Chills and rigors were the most commonly occurring adverse events (AEs). All the AEs were mild in intensity, and none of the patients experienced any serious AEs. No patients developed nephrotoxicity. Our finding indicates that liposomal amphotericin B at 10 mg/kg body weight is safe and effective in children. Results of our study support the use of single dose liposomal amphotericin B in all age group populations for elimination of kala-azar from the Indian subcontinent.

Background Post kala-azar dermal leishmaniasis (PKDL) is a dermatological disorder caused by protozoal parasite Leishmania donovani. PKDL cases are thought to be a reservoir of parasites and may increase cases of visceral leishmaniasis. The disease is not life threatening but cosmetic disfigurement associated with it may impair the patients’ quality of life. This study aimed to assess the health related quality of life in patients with post kalaazar dermal leishmanasis for the first time. Methods A total of 92 PKDL cases and 96 healthy participants filled out the questionnaires. The Dermatology Life Quality Index (DLQI) and SF 36 questionnaire were used to assess the quality of life. Data on socio-demographic and clinical features were also collected. The collected data were analyzed by using SPSS software (version 16), Student’s t-test, analysis of variance (ANOVA) was applied for comparison of means. Results PKDL patients experienced very large impact on their quality of life. The mean score of DLQI was 11.41. Highest impact was found in symptoms and feelings and lowest impact was observed for personal relationship domain. Patients below 20 years age group found to have lower quality of life. There was a significant difference in mean DLQI scores with regard to age and severity of lesions (P 0.05). Conclusion PKDL significantly impaired the patient’s quality of life. Further studies to assess the impact of treatment on quality of life in these patients are recommended.

Background: Indoor Residual Spraying (IRS) and Insecticide Treated Nets (ITNs) are important tools in the fight against insect vectors of important diseases. In spite of having operational and logistic limitation(s), IRS and ITN are still in practice as conventional tools with mixed results for controlling Phlebotomus argentipes, the vector of Visceral Leishmaniasis (VL) in the Indian subcontinent. A combination of both tools might results better for reducing VL vector densities during the attack phase of the VL elimination initiative. Methods: A comparison-based study was designed for analyzing the field efficacy of a combination strategy of IRS+ITN (PermaNet 3.0®) versus single interventions with IRS and ITNs alone comparing with control respectively. The study was conducted at the villages of Samastipur district of Bihar (India) using aspiration and light traps techniques (i.e., AT and LTT respectively) for collecting sand fly. The numbers of all types of sand flies (male, unfed, fed and gravid female) were recorded during a period of 12 months after the intervention in the three study arms. The bioavailability of insecticide for IRS as well as ITN was also observed at the interval of 3 months with the help of cone bioassay technique established by World Health Organization (WHO). Results: The observed highest percent-reduction of sand flies (93.59% - 100%) at the sites with combined intervention of IRS+ITN, as compared to the sites without any intervention at control (with 0% reduction) or with single control intervention either with IRS (4.29% - 86.77%) or with ITN (60.18% - 97.07%) followed by the reduction in bioavailability of insecticide in IRS (i.e., 52.38%, 58.33%, 45.45% & 50.00%) and ITN (84.44%, 82.50%, 77.78% & 83.33%) over the period of 12 months since intervention, establishes the success of IRS plus ITN as a combined approach for contaminating vector population. Also, through the house-to-house survey at the end of study period, the acceptance of combined approach for IRS plus ITN by the community was accessed to be highest i.e., 100% as compared to the single-intervention approaches for IRS (87%) and ITN (100%). Conclusions: Study results advocate the use of the combined strategy during the attack phase of the VL elimination initiative in order to reduce or interrupt disease transmission. It may also be a valid approach during the maintenance phase in hot-spots of VL transmission.

The diagnosis of visceral leishmaniasis (VL) is one of the foremost barriers in the control of this disease, as demonstration of the parasite by splenic/bone marrow aspiration is relatively difficult and requires expertise and laboratory support. The aim of the present study was to find a noninvasive diagnostic approach using the existing recombinant kinesine-39 (rK-39) immunochromatographic nitrocellulose strips test (ICT) with a human sweat specimen for the diagnosis of VL. The investigation was carried out on specimens (blood, sweat, and urine) collected from 58 confirmed VL, 50 confirmed post kala-azar dermal leishmaniasis (PKDL), 36 healthy control, and 35 patients from other diseases. The data obtained from this study reveal that 96.6% clinically confirmed active VL participants were found to be positive when tested against a sweat specimen. Interestingly, the scenario was similar when tested against a blood specimen (96.6% positive by rK-39). Moreover, a test of both sweats and blood specimens from 50 PKDL participants resulted in 100% positivity, whereas no healthy control participants were found to be rK-39 positive. The sensitivity of the rK-39 ICT in sweat specimen was 94.7%, whereas the specificity was 100% in healthy controls from endemic, nonendemic, and other infectious diseases, respectively. No difference was observed in sweat specimen of VL and PKDL cases which signifies its reliability. However, further evaluation of this method on a larger scale could enhance the reliability of the proposed model so that it could be used efficiently in VL management and eradication.

Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. Methods Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA–MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA. Results 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease. Discussion We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL., Author summary The most threatening form of leishmaniasis is human visceral leishmaniasis, which is caused by L. donovani in Indian subcontinent. The disease accounts for huge annual burden of infectious disease in India. Efforts towards disease elimination programme are far beyond satisfaction and there is need to re-strengthen health monitoring, surveillance programme in endemic areas. There is a greater need to identify asymptomatic individuals amongst endemic healthy control by active surveillance programme. Further, except a few, many asymptomatic subjects become sero-negative without developing VL due to strong inherent cellular immunity possessed by them. This study enumerates use of rK39, DAT and quantitative PCR(qPCR) in asymptomatic detection and then evaluate immunological biomarkers(Adenosine deaminase, IFN-γ, TNF-α and IL-10) which help in disease conversion to symptomatic VL, at 6 month follow- up. Follow–up analysis revealed that antibody testing with rK39 (3.24%), DAT (8.33%) had poor agreement with disease conversion. By qPCR, we could identify the level of parasitemia, and collectively with serology, the test detected 23.80% of asymptomatic cases converted into disease. The level of ADA and IL-10 remained consistently high during conversion. IFN-γ became high in asymptomatic infection but became low on conversion, whereas, no significant change in level of TNF-α was observed at both stages of disease. Thus by use of qPCR, concomitantly with DAT over rK39+ sorted endemic healthy control may be employed for early case detection. Adenosine is produced by ecto-nucleotide during L.donovaniinfection, has been previously reported and in parallel to this study we conclude that determination of adenosine deaminase level (ADA) might help identify early cases with more tendency to convert into disease. This will help to boost health monitoring programme to eradicate Kala-azar in Bihar, India.

Background: Treatment of post-kala-azar dermal leishmaniasis cases is of paramount importance for kala-azar elimination; however, limited treatment regimens are available as of now. Aim: To compare the effectiveness of liposomal amphotericin B vs miltefosine in post-kala-azar dermal leishmaniasis patients. Methodology: This was a randomized, open-label, parallel-group study. A total of 100 patients of post kala azar dermal leishmaniasis, aged between 5 and 65 years were recruited, 50 patients in each group A (liposomal amphotericin B) and B (miltefosine). Patients were randomized to receive either liposomal amphotericin B (30 mg/kg), six doses each 5 mg/kg, biweekly for 3 weeks or miltefosine 2.5 mg/kg or 100 mg/day for 12 weeks. All the patients were followed at 3rd, 6th and 12th months after the end of the treatment. Results: In the liposomal amphotericin B group, two patients were lost to follow-up, whereas four patients were lost to follow-up in the miltefosine group. The initial cure rate by “intention to treat analysis” was 98% and 100% in liposomal amphotericin B and miltefosine group, respectively. The final cure rate by “per protocol analysis” was 74.5% and 86.9% in liposomal amphotericin B and miltefosine, respectively. Twelve patients (25.5%) in the liposomal amphotericin B group and six patients (13%) in the miltefosine group relapsed. None of the patients in either group developed any serious adverse events. Limitations: Quantitative polymerase chain reaction was not performed at all the follow-up visits and sample sizes. Conclusion: Efficacy of miltefosine was found to be better than liposomal amphotericin B, hence, the use of miltefosine as first-line therapy for post-kala-azar dermal leishmaniasis needs to be continued. However, liposomal amphotericin B could be considered as one of the treatment options for the elimination of kala-azar from the Indian subcontinent.

Background This study was aimed to assess the impact of quality of life using WHOQOL-BREF in patients with Visceral leishmaniasis (VL). Methods A total of 95 VL cases and 95 healthy participants filled out the questionnaires. Data on socio-demographic aspects along with disease duration were collected. Data were compared using a t-test, analysis of variance and chi-square test. Results VL patients experienced very high impact on their quality of life. Study cohort had male preponderance (72.63%). Majority (64.21%) were aged 40 years of age group married patients (p

Background: Underreporting of Visceral Leishmaniasis (VL) in India remains a problem to public health controls. Effective and reliable surveillance systems are critical for monitoring disease outbreaks and public health control programs. However, in India, government surveillance systems are affected by levels of scarcity in resources and therefore, uncertainty surrounds the true incidence of asymptomatic and clinical cases, affecting morbidity and mortality rates. The State of Bihar alone contributes up to the 40\% of the worldwide VL cases. The inefficiency of surveillance systems occurs because of multiple reasons including delay in seeking health care, accessing non-authentic health care clinics, and existence of significant asymptomatic self healing infectious cases. This results in a failure of the system to adequately report true transmission rates and number of symptomatic cases that have sought medical advice (thus, high underreporting of cases). Objectives and Methods: There are several methods to estimate the extent of underreporting in the surveillance system. In this research, we use a mathematical dynamic model and two different types of data sets, namely, monthly incidence for 2003-2005 and yearly incidence from 2006-2012 from the Bihar's 21 most VL affected districts out of its 38 districts. The goals of the study are to estimate critical metrics to measure level of transmission and to evaluate the estimation process between the two data sets and 21 districts. In particularly, our focus is on (i) estimating infection transmission potential, underreporting level in incidence and proportion of self-healing cases, (ii) quantifying reproduction number of the$R_0$, and (iii) comparing underreporting incidence levels and proportion of self-healing cases between the two periods 2003-2005 and 2006-2012 and between 21 districts. Results: Our research suggests that the number of asymptomatic individuals in the population who eventually self-heal may have a significant effect on the dynamics of VL spread. The estimated mean self-healing proportion (out of all infected) is found to be $\sim 0.6$ with only 7 out of 21 affected districts having self-healing proportion less than $0.5$ for both data sets. The estimated mean underreporting level is at least $64$\% for the state of Bihar. The estimates of the basic reproduction numbers obtained are similar in magnitude for most of the districts, being in the range of (0.88, 2.79) and (0.98, 1.01) for 2003-2005 and 2006-2012, respectively. Conclusions: The estimates for the two types (monthly and yearly) of temporal data suggest that monthly data are better for estimation if less number of data points are available, however, in general, using such data set results in larger variances in parameters as compared to estimates obtained through aggregated yearly data. Estimated values of transmission related metrics are lower than those obtained from earlier analyses in the literature, and the implications of this for VL control are discussed. The spatial heterogeneity in these control metrics increases the risk of epidemics and makes the control strategies more complex.

Miltefosine, the only oral drug for visceral leishmaniasis (VL), is being used as the first-line drug under the VL elimination program in the Indian subcontinent. Miltefosine is an oral drug which was used as a topical application for skin metastasis of breast cancer. It was found to be effective against Leishmania donovani. The main adverse events (AE) reported previously with miltefosine use includes diarrhea, vomiting, and dehydration. Other AEs include, raised serum alanine transaminase/aspartate aminotransferase and renal parameters such as creatinine. In this study, we report AEs in a large patient cohort of VL treated with miltefosine. The purpose of this pharmacovigilance study was to assess adverse drug reactions (ADRs)/AE of miltefosine treatment under unrestricted condition in the field setup. Patients were followed up to 6 months for therapeutic effectiveness. Outcomes of a larger data set of patients treated with this regimen from April 2012 to March 2015 were recorded. In the present study, 646 patients of VL were given miltefosine. Majority of the study subjects (58%) were male. Relapse occurred in 7% during follow-up period. Main causes of death were VL–pulmonary tuberculosis coinfection, extreme diarrhea, and acute pancreatitis which were reported in 1.7% subjects. Of 553 (85.6%) patients completing full course of treatment, 463 (83.7%) showed ADR with miltefosine during the study period. About 2.3% were suffering severe ADR, 51% from moderate, and the rest had mild ADR. The initial and final cure rate was 97.4% and 85.6%, respectively.

Malaria is the leading cause of morbidity and mortality in Bihar (India), and concomitant with the spatial and temporal discrepancy throughout the region. Present study aims to determine the changes in spatial distribution of Plasmodium falciparum in Bihar from year 2007–2015. We used Moran’s I indices and Getis-Ord G i * statistics to determine the spatial clustering pattern of malaria. The highest variability of disease distribution was observed in 2009. The maximum spatial autocorrelation value was calculated in 2011 (Moran’s I = 0.62, p

Post-kala-azar dermal leishmaniasis (PKDL) is clinical outcome of visceral leishmaniasis (VL) and is thought to be the potential reservoir of parasite. Miltefosine (MF) is the only oral drug existing for treatment of post-kala-azar dermal leishmaniasis (PKDL). Increased miltefosine tolerance in clinical isolates of Leishmania donovani has been reported and is one of the major concerns in the treatment of PKDL. Here, we report a highly ulcerated PKDL case that was successfully cured after miltefosine treatment., Author summary Post-kala-azar dermal leishmaniasis (PKDL) is a dermatological complication which usually occurs among treated VL cases. Despite active surveillance, some exclusive cases have been reported in the areas where VL is endemic. To eliminate VL, all source of reservoir to be managed properly. The appropriate diagnosis and treatment of PKDL cases are key. Here we report the identification and treatment of a highly ulcerated PKDL case. A detailed investigation inferred the possible role of CD8 + T cell in the skin ulcer. This report also describes how to identify the suspected case, to confirm the diagnosis, and to provide a successful treatment option.

Visceral leishmaniasis (VL), a protozoan disease, is 100% fatal if left untreated. Anemia is common in VL which plays a role in expression of clinically overt VL disease. Laboratory clues are scarce for strengthening clinical suspicion for severity in VL. Hypertriglyceridemia has emerged as a new concept for the diagnosis and prognosis in VL. The present study is aimed at correlating the magnitude of hypertriglyceridemia with the severity in VL.A retrospective case-control study was conducted between January 2012 to December 2013 among 124 patients coming for treatment from VL endemic areas, who had fever of more than 15 days and did not respond to antimalarials and antibiotics. The parasitologically confirmed VL cases (n = 87) were categorized as mild/moderate (n = 60) and severe (n = 27) groups according to WHO classification for anemia and parasite burden. Serum triglycerides were assayed in VL groups along with controls (n = 37).Serum triglyceride level was significantly higher in VL than controls [mean values were 173.50 ± 47.67 versus 127.1 ± 53.79 mg/dl, respectively (p0.0001)]. Triglyceride level was significantly higher in severe than in mild/moderate group of VL [211.3 ± 50.2 mg/dl versus 134 ± 45.09 mg/dl, respectively (p0.0001)]. Hypertriglyceridemia (161.7 mg/dl) was noted in all severe VL patients, compared to 31.66% of mild or moderate group (p0.0001). There was no significant difference between mild/moderate VL and controls.It is hypothesized that hypertriglyceridemia could be of additional diagnostic benefit to assess the probability and severity of VL in endemic areas.

Accredited Social Health Activists (ASHAs) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (VL). One of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and disease transmission in the community. To address this problem, we have begun a training program for ASHAs to enhance early detection of potential VL cases and referring them to their local Primary Health Centers (PHCs) for diagnosis and treatment. The result of this training showed increased referral rate to PHCs for diagnosis and treatment. Encouraged with the results from a single training session, we determined in the present study whether repeated training of ASHAs resulted in an a further increase in VL case referral to the local PHCs. After two training sessions, VL referrals by ASHAs increased to 46% as compared to 28% after a single training session in this cohort and a baseline of 7% before training. ASHA training is an effective way to conduct active case detection of VL cases and should be repeated once a year.

Background Visceral Leishmaniasis (VL) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India. Due to efforts from local governments, NGOs and international organizations, the number of VL cases has declined in recent years. Despite this progress, the reservoir for transmission remains to be clearly defined since it is unknown what role post kala-azar dermal leishmaniasis (PKDL) and asymptomatic infections play in transmission. This information is vital to establish effective surveillance and monitoring to sustainably eliminate VL. Methodology/Principal Findings We performed a longitudinal study over a 24-month period to examine VL transmission and seroconversion in households with VL, PKDL and asymptomatic infections in the Saran and Muzaffarpur districts of Bihar. During the initial screening of 5,144 people in 16 highly endemic villages, 195 cases of recently treated VL, 116 healthy rK39 positive cases and 31 PKDL cases were identified. Approximately half of the rK39-positive healthy cases identified during the initial 6-month screening period were from households (HHs) where a VL case had been identified. During the 18-month follow-up period, seroconversion of family members in the HHs with VL cases, PKDL cases, and rK39-positive individuals was similar to control HHs. Therefore, seroconversion was highest in HHs closest to the time of VL disease of a household member and there was no evidence of higher transmission in households with PKDL or healthy rK39-positive HHs. Moreover, within the PKDL HHs, (the initial 31 PKDL cases plus an additional 66 PKDL cases), there were no cases of VL identified during the initial screen or the 18-month follow-up. Notably, 23% of the PKDL cases had no prior history of VL suggesting that infection resulting directly in PKDL is more common than previously estimated. Conclusions/Significance These observations argue that acute VL cases represent the major reservoir for transmission in these villages and early identification and treatment of VL cases should remain a priority for VL elimination. We were unable to obtain evidence that transmission occurs in HHs with a PKDL case., Author Summary Visceral leishmaniasis (also known as kala-azar) caused by infection with L. donovani is a deadly parasitic disease that afflicts some of world’s poorest populations, including the people of the northern Bihar State of India. Once transmitted to a human by an infected sandfly, the L. donovani parasite migrates from the site of the sandfly bite throughout the reticuloendothelial system, resulting in high levels of infection in the spleen, liver and bone marrow that eventually lead to organ failure and death if not treated effectively. India, Nepal and Bangladesh are currently engaged in a program to eliminate visceral leishmaniasis, principally through early case detection, treatment and vector control. As humans are the only reservoir for L. donovani, it is necessary to understand how the disease is transmitted and specifically what role acute visceral leishmaniasis (VL) cases, asymptomatic infections and post kala-azar dermal leishmaniasis (PKDL) cases play in transmission. We therefore performed a study to determine seroconversion for antibodies against the L. donovani rK39 antigen as a surrogate for transmission in households with VL cases, asymptomatic infections and PKDL cases in 16 highly endemic villages over a 2-year period in Bihar, India. We observed that most transmission occurred in the VL households and further that it occurred closest to the time of acute disease. We were unable to confirm that transmission occurred in the households with either asymptomatic infections or PKDL cases. These observations argue that active surveillance to diagnose and treat VL cases as soon as possible to reduce transmission should remain a priority for VL elimination.

The study was carried out on 1104 people of visceral leishmaniasis (VL) endemic region to detect the suitable marker in asymptomatic individuals that illustrate as a marker for conversion in symptomatic VL subject. In this study, 46 individuals (asymptomatic) with rK39 strip test positive without any previous VL sign and symptoms were later found symptomatic. Hematological and immunological investigations illustrated the lower hemoglobin (g/dl) and increase in interleukin-10 (IL-10) respectively from normal range which would be the primary markers in the asymptomatic individuals that might convert to symptomatic VL. [J Med Allied Sci 2019; 9(2.000): 96-99]

There have been relatively few large-scale studies of spread of Post Kala-azar Dermal Leishmaniasis (PKDL) and factors that affects its prevalence. Consequently, little is known about the dynamics of PKDL, or the confounding factors that may give rise to its spread. A large-scale survey-based study of PKDL prevalence was conducted in the endemic region of Araria in Bihar, India. The results of the study indicate a sample prevalence of as high as 7.9 cases per 10,000 individuals. Socio-economic and demographical factors were recorded for each study participant, and the influence of these factors on PKDL and non-PKDL incidence in the sample populations was analysed. Our results suggest that factors of caste, cattle shed proximity, and gender all contribute to the characterization of the PKDL-afflicted population. The mean household size for PKDL households was found to be 4.9, almost doubled the number observed for non-PKDL households. Individuals in the age-group 10-19 years old, Hindus, or those belonging to Schedule Caste are more likely to get PKDL than others in the population. Consideration of these factors can provide a clear starting point for further in-depth examination of their contribution to PKDL patterns.

A cohort of 91 asymptomatic individuals with visceral leishmaniasis (VL) were identified during base line screening using recombinant 39-aminoacid antigen (rk-39) and polymerase chain reaction (PCR) conducted from December 2005 to June 2006 involving 997 individuals of two highly endemic villages of Vaishali district, Bihar. The point prevalence of asymptomatic infection was 98 per 1000 persons at baseline. There was no statistically significant difference between rk-39 and PCR positivity rate (P>0.05), even though PCR positivity alone was found significantly higher (4.2%) than rk-39 positivity alone (2.6%). The monthly follow-up of the asymptomatic cohort revealed a disease conversion rate of 23.1 per 100 persons within a year. There was a statistically significant difference in conversion of disease when individuals were positive by both tests as compared to single tests by rk-39 and PCR (P

Background Lesishmaniasis is a neglected tropical disease endemic in Bihar, India. Inappropriate health seeking behaviour of post kala-azar dermal leishmaniasis (PKDL) patients may increase the disease duration, severity and transmissibility. Simultaneously, lack of knowledge and perceived stigma may also increase the length of delay in receiving treatment. This ultimately effects the kala-azar elimination program. Methods A cross sectional study was conducted in 120 confirmed PKDL patients, aged 18 years and older. Data related to knowledge and health seeking behaviour was collected by a pre-tested questionnaire. EMIC stigma scale was used for assessing the perceived stigma. Patients were personally interviewed after taking informed consent. Data analysis was done by using SPSS 16 software. Results The time between appearance of symptoms and first medical consultation (patient delay) ranged from 15 days to 5475 days (15 years) with a median of 285 days. The time between first medical consultations to onset of specific treatment (system delay) ranged from 2 to 5475 days with a median of 365 days. Many patients approached first to quacks (8.4%), homeopathic and ayurvedic practitioners (25.8%) upon recognition of symptoms. Majority of the patients (68.3%) had poor knowledge about PKDL and its vector. Type of skin lesions and gender had significant association with patient delay and system delay respectively (p

A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75–15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.

The study presents the findings of a population-based survey of the annual incidence of visceral leishmaniasis (VL) in the rural areas of one VL-endemic district in Bihar, India. Stratified multi-stage sampling was applied in the selection of blocks, villages, hamlets, and households. We screened 15 178 households (91 000 individuals) in 80 villages in 7 of 27 administrative blocks of the district, East Champaran. We identified 227 VL cases that occurred in the past 12 months: 149 treated individuals who survived, 14 who died from VL, and 64 active cases. The high-incidence stratum had an estimated incidence of 35.6 cases per 10 000 persons per year (90% CI: 27.7-45.7). The annual incidence rate in the medium stratum areas was 16.8 cases per 10 000 (90% CI: 9.3-30.6). The combined annual incidence rate for the high and medium areas combined was 21.9 cases per 10 000 per year, (90% CI: 14.0-34.2). The Government of India's VL elimination goal is to reduce the VL incidence to one case per 10 000 at the sub-district level; thus, a 35-fold reduction will be required in those areas with the highest VL incidence.

Summary Objective To estimate the economic burden of visceral leishmaniasis (VL) on the rural population of one VL endemic district of Bihar, the state with 85% of India’s cases. Methods Using a survey of a stratified multistage sampling of 15 178 households with 214 individuals with VL in the previous 12 months, the study provides data on VL treatment expenditures, financing and days of work lost in the context of overall household expenditures, income sources and assets. Results Median household expenditures on VL treatment represent, on average, 11% of annual household expenditures and an estimated 7 months of an individual’s income at the daily wage in rural Bihar. With 87% of households forced to take out loans to finance disease costs, VL can contribute to a spiral of increasing poverty. The current pattern of VL treatment, with multiple visits and treatments for a single episode of illness, significantly increases the economic burden on the household. Conclusion India’s National Elimination Program to make effective treatments accessible to the rural poor, if combined with expanded efforts to improve timely access to diagnosis by conducting rapid diagnostic tests closer to the community (and mobilizing the rural population to seek effective treatment earlier), can reduce VL’s economic burden on India’s rural households.

Background Post kala-azar dermal leishmaniasis (PKDL) is a skin disorder that usually occurs among patients with a past history of visceral leishmaniasis (VL). Cases are also reported without a history of VL. There is no satisfactory treatment regimen available at present. We aimed to compare the efficacy and safety of amphotericin B in two different doses (0.5mg/kg vs 1mg/kg) in a prospective randomized trial in 50 PKDL patients. Methods In this open label study 50 patients with PKDL, aged between 5–60 years were randomized in two groups. Group A received amphotericin B in the dose of 0.5 mg/kg in 5% dextrose, daily for 20 infusions for 3 courses at an interval of 15 days between each course and Group B received amphotericin B in the dose of 1mg/kg in 5% dextrose on alternate days, 20 infusions for 3 courses an interval of 15 days between each course and followed up for one year. Results A total of 50 patients were enrolled, 25 in each of group A and group B. Two patients lost to follow up and three patients withdrew consent due to adverse events. The initial cure rate was 92% in group A and 88% in group B by intention to treat analysis and final cure rate by per protocol analysis was 95.65% and 95.45% in group A and group B respectively. Two patients each from either group relapsed. Nephrotoxicity was the most common adverse event occurring in both the groups. Conclusion The lower dose appears to have fewer adverse events however, nephrotoxicity remains a problem in both regimens. The 0.5mg/kg regimen may be considered instead of the higher dosage however safer treatments remain critical for PKDL treatment.

We report two cases of post-kala-azar dermal leishmaniasis (PKDL), which had subsequently developed after successful treatment of visceral leishmaniasis with miltefosine. Both patients had maculo-nodular lesions all over the body, and they were diagnosed as PKDL by parasitologic examination for Leishmania donovani bodies in a skin snip of lesions. Patients were put on amphotericin B and responded very well for nodular lesions with one course of treatment. However, longer duration of the treatment is needed for total clearance of macular lesions from body surface in PKDL cases. This is the first case report of PKDL in India, which developed after successful treatment of visceral leishmaniasis with miltefosine.

Objectives To determine whether medical staff at PHC level would have the time to take up additional activities such as 1-day fever camps for active VL case detection. Methods This article assessed the workload of health staff of different professional categories working at health facilities in Bangladesh, India and Nepal. Data were collected from different sites in high endemic VL areas. The study population was the health staff of government health facilities at all levels. Workload indicators of staffing need (WISN) software were adopted to carry out the analysis of staff workload and their availability in the selected health facility. The WISN difference and WISN ratio for a particular health facility were calculated from actual staffing available and calculated staffing requirement. Results The results showed a mixed picture of the availability of health workers. In most settings of Bangladesh and India, physicians with or without laboratory technicians would have time for active case detection. In Nepal, this would be performed by trained nurses and paramedical personnel. Conclusion If all vacant posts were filled, active case detection could be performed more easily. The elimination programme can be scaled up with the current staffing levels in the endemic areas with some short training if and when necessary. Objectifs Determiner si le personnel medical au niveau des SSP aurait le temps d'entreprendre des activites supplementaires telles que des camps d'une journee de mesure de la fievre pour le depistage actif des cas de LV. Methodes Cette etude a evalue la charge de travail du personnel de sante de differentes categories professionnelles travaillant dans les etablissements de sante au Bangladesh, en Inde et au Nepal. Les donnees ont ete recueillies aupres de differents sites dans les zones d'endemie elevee pour la LV. La population de l’etude etait le personnel de sante des centres de sante publics a tous les niveaux. Un logiciel pour les indicateurs de charge de travail en besoins de personnel (CTBP) a ete adopte pour mener a bien l'analyse de la charge de travail du personnel et leur disponibilite dans l’etablissement de sante choisi. La difference de CTBP et le rapport de CTBP pour un etablissement de sante particulier ont ete calcules a partir de l'effectif de personnel disponible et le besoin en personnel calcule. Resultats Les resultats ont montre une image contrastee de la disponibilite des agents de sante. Dans la plupart des sites au Bangladesh et en Inde, les medecins avec ou sans techniciens de laboratoire auraient le temps pour effectuer la detection active des cas. Au Nepal, cela serait realise par des infirmier(e)s qualifie(e)s et par du personnel paramedical. Conclusion Si tous les postes vacants etaient pourvus, le depistage actif pourrait etre realise plus facilement. Le programme d’elimination peut etre deploye avec les taux actuels de personnel dans les zones endemiques moyennant une certaine courte formation lorsque et si cela est necessaire. Objetivos Determinar si el equipo medico de atencion primaria tendria el tiempo de asumir actividades adicionales tales como campanas de deteccion de fiebre de un dia como parte de la deteccion activa de casos de LV. Metodos En este articulo se evalua la carga de trabajo de los trabajadores sanitarios con diferentes categorias trabajando en los centros sanitarios en Bangladesh, India y Nepal. Se recolectaron datos de diferentes lugares en areas con una altamente endemicas para LV. La poblacion de estudio era el personal sanitarios de centros gubernamentales de todos los niveles. Se adaptaron los indicadores de carga de trabajo del software WISN (Workload Indicators of Staffing Needs) para llevar a cabo el analisis de la carga de trabajo y la disponibilidad del personal sanitario en el centro elegido. Se calculo la diferencia en WISN y el ratio de WISN para un centro sanitario en particular segun el personal sanitario realmente disponible y el personal requerido segun calculos. Resultados Los resultados mostraban un panorama mixto de la disponibilidad de los trabajadores sanitarios. En la mayoria de los emplazamientos de Bangladesh y los medicos hindues con y sin tecnicos de laboratorio tenian tiempo para la deteccion activa de casos. En Nepal lo llevarian a cabo enfermeras entrenadas y personal paramedico. Conclusion Si se ocupasen todos los puestos vacantes, seria mas facil llevar a cabo la deteccion activa de casos. El programa de eliminacion puede llevarse a escala con los niveles actuales de recursos humanos en areas endemicas con poco entrenamiento si fuese necesario.

Background Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. Methodology/Principal findings A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar’s χ² statistics (64; p1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission. Conclusion/Significance Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden., Author Summary Visceral Leishmaniasis, commonly known as kala-azar, is one of the major health concerns for Bihar state in India. Time to time estimation of kala-azar incidence plays a pivotal role in defining and evaluating control strategies under National Kala-azar Elimination programme. The house-to-house survey approach, adopted several times for estimation of kala-azar incidence, requires huge logistics and operational cost as occurrence of kala-azar is clustered in nature. Snowball sampling approach is used to locate potential subjects with help of key informants where subjects are hard to locate. This is the first ever comparative study to assess efficacy, cost and feasibility of snowball sampling approach to house-to-house survey in capturing kala-azar cases. Snowball sampling was found cost-effective, but not sensitive enough as it captured about 50% of kala-azar cases. It captured deaths possibly due to kala-azar more efficiently (77%). However, standardization of snowball approach with improved procedure, training, logistics, etc. may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden.

Background Active case detection (ACD) significantly contributes to early detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India and Nepal. Methods The camp search and index case search strategies were piloted in 2010-11 by national programs in high and moderate endemic districts / sub-districts respectively. Researchers independently assessed the performance and feasibility of these strategies through direct observation of activities and review of records. Program costs were estimated using an ingredients costing method. Results Altogether 48 camps (Bangladesh-27, India-19, Nepal-2) and 81 index case searches (India-36, Nepal-45) were conducted by the health services across 50 health center areas (Bangladesh-4 Upazillas, India-9 PHCs, Nepal-37 VDCs). The mean number of new case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in Bangladesh. The cost (excluding training costs) of detecting one new VL case per camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The camp search strategy detected a substantive number of new PKDL cases. The major challenges faced by the programs were inadequate preparation, time and resources spent on promoting camp awareness through IEC activities in the community. Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical examination skills resulted in a high proportion of patients being subjected to rK39 testing. Conclusion National programs can adapt ACD strategies for detection of new VL/PKDL cases. However adequate time and resources are required for training, planning and strengthening referral services to overcome challenges faced by the programs in conducting ACD.