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Background: Co-endemicity of neglected tropical diseases (NTDs) necessitates that these diseases should be considered concomitantly to understand the relationship between pathology and to support disease management and control programs. The aims of the study were to assess the prevalence of filarial infection in asymptomatic Leishmania donovani infected individuals and the correlation of Wuchereria bancrofti infection with progression to clinical visceral leishmaniasis (VL) in Bihar, India. Methodology/Principal findings: Within the Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) area, a cohort of Leishmania seropositive (n = 476) or seronegative individuals (n = 1130) were sampled annually for three years for filarial infection and followed for progression to clinical VL. To corroborate the results from the cohort study, we also used a retrospective case-control study of 36 VL cases and 71 controls selected from a subset of the HDSS population to investigate the relationship between progression to clinical VL and the prevalence of filarial infection at baseline. Our findings suggest a higher probability of progression to clinical VL in individuals with a history of filarial infection: in both the cohort and case-control studies, progression to clinical VL was higher among filaria infected individuals (RR = 2.57, p = 0.056, and OR = 2.52, p = 0.046 respectively). Conclusion: This study describes that progression to clinical VL disease is associated with serological evidence of prior infection with W. bancrofti. The integration of disease programs for Leishmania and lymphatic filariasis extend beyond the relationship of sequential or co-infection with disease burden. To ensure elimination targets can be reached and sustained, we suggest areas of co-endemicity would benefit from overlapping vector control activities, health system networks and surveillance infrastructure. Author summary: India has committed to eliminate two neglected tropical diseases (NTDs) as a public health problem: visceral leishmaniasis (VL) and lymphatic filariasis (LF), both of which are transmitted by vectors and are caused by the parasites Leishmania donovani and Wuchereria bancrofti, respectively. Notably, the majority of L. donovani infections do not lead to a clinical event of VL and asymptomatic infections significantly outnumber the clinical cases. While mixed infections with Leishmania parasites and those causing lymphatic filariasis have been reported, the influence of the immune response triggered by filarial infection on the clinical manifestations and progression of both disorders is not well understood. The Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) in Bihar is a well-established demographic platform in an area with the highest incidence of L. donovani infections in India which is also co-endemic for lymphatic filariasis. We used both cohort and case-control study designs within the HDSS population to assess the prevalence of filarial infection in blood samples and examine the association between filarial infection and the progression to clinical VL. Our findings strongly suggest there is an increased risk of progression to clinical VL in individuals with a history of infection with W. bancrofti: in both the study designs, progression to clinical VL was higher among filaria-infected individuals. These results highlight that the co-endemicity of these NTDs necessitates an integrated approach in diagnosis and disease management to ensure elimination targets can be achieved and sustained. [ABSTRACT FROM AUTHOR]

Leishmaniasis on the Indian subcontinent is thought to have an anthroponotic transmission cycle. There is no direct evidence that a mammalian host other than humans can be infected with Leishmania donovani and transmit infection to the sand fly vector. The aim of the present study was to evaluate the impact of sand fly feeding on other domestic species and provide clinical evidence regarding possible non-human reservoirs through experimental sand fly feeding on cows, water buffalo goats and rodents. We performed xenodiagnosis using colonized Phlebotomus argentipes sand flies to feed on animals residing in villages with active Leishmania transmission based on current human cases. Xenodiagnoses on mammals within the endemic area were performed and blood-fed flies were analyzed for the presence of Leishmania via qPCR 48hrs after feeding. Blood samples were also collected from these mammals for qPCR and serology. Although we found evidence of Leishmania infection within some domestic mammals, they were not infectious to vector sand flies. Monitoring infection in sand flies and non-human blood meal sources in endemic villages leads to scientific proof of exposure and parasitemia in resident mammals. Lack of infectiousness of these domestic mammals to vector sand flies indicates that they likely play no role, or a very limited role in Leishmania donovani transmission to people in Bihar. Therefore, a surveillance system in the peri-/post-elimination phase of visceral leishmaniasis (VL) must monitor absence of transmission. Continued surveillance of domestic mammals in outbreak villages is necessary to ensure that a non-human reservoir is not established, including domestic mammals not present in this study, specifically dogs. Author summary: Leishmania donovani, the causative agent of visceral leishmaniasis (VL), has unique enzootic, zoonotic and anthroponotic life cycles dependent on geographic region. Most Leishmania spp. are zoonotic, transmitted between humans and non-human mammals. Leishmaniasis is endemic in over 98 countries and the estimated population at risk on the Indian sub-continent (ISC) is around 0.2–0.4 million people. Herein, we assess knowledge gaps in disease transmission that challenge dogma regarding the reservoir(s) of visceral leishmaniasis and control efforts on the Indian sub-continent. Better understanding of L. donovani infection in domestic animals and its transmission to sand flies will provide answers to fundamental questions in VL epidemiology and ecology. Blood samples were collected from livestock and rodents in endemic villages and colonized sand flies were fed on these animals and analyzed post feeding to see if they could pick up parasites via bloodmeal. We found that livestock and to a smaller extent rodents could be infected with or exposed to Leishmania infection. However, these mammals were not infectious to Phlebotomus argentipes, the predominant vector species incriminated as transmitting L. donovani in India. The inability of these domestic mammals to transmit L. donovani to sand flies in Bihar suggests that they play a limited role in the spread of infection. A key component in reducing and preventing the re-emergence of VL in the context of the elimination program is to understand the role of vector feeding on non-human animals in the transmission cycle. Better estimation of the proportion of the livestock and rodent population exposed to sand flies during different seasons and ensuring that there are not reservoir species that contribute to transmission will help implement appropriate control strategies for sustainable elimination. [ABSTRACT FROM AUTHOR]

Background: In the endgame of the elimination initiative of visceral leishmaniasis (VL) on the Indian subcontinent, one of the main questions remaining is whether asymptomatically infected individuals also contribute to transmission. We piloted a minimally invasive microbiopsy device that could help answer this question. While the potential of this device has been previously illustrated in Ethiopia, no such information is available for the setting of the Indian subcontinent. In this proof of concept study we aimed to assess 1) to what extent skin parasite load obtained with the new microbiopsy device correlates with disease status, 2) to what extent skin parasite load correlates with blood parasite load in the same subject, and 3) to what extent the skin parasite load obtained from different sampling sites on the body correlates with one another. Methods: We performed a pilot study in Bihar, India, including 29 VL patients, 28 PKDL patients, 94 asymptomatically infected individuals, 22 endemic controls (EC), and 28 non-endemic controls (NEC). Presence of infection with L. donovani in the blood was assessed using Direct Agglutination Test, rK39 ELISA, Whole Blood Analysis measuring IFN-γ and qPCR. A skin sample was collected with the microbiopsy device on two different locations on the body. PKDL patients provided a third skin sample from the edge of a PKDL lesion. Parasite load in the skin was measured by qPCR. Findings: We found a clear correlation between the skin parasite load obtained with the microbiopsy device and disease status, with both higher skin parasite loads and higher proportions of positive skin samples in VL and PKDL patients compared to asymptomatics, EC, and NEC. No clear correlation between skin parasite load and blood parasite load was found, but a moderate correlation was present between the skin parasite load in arm and neck samples. In addition, we found four positive skin samples among asymptomatic individuals, and 85% of PKDL lesions tested positive using this microbiopsy device. Conclusions: In line with previous pilot studies, our results from an Indian setting suggest that the microbiopsy device provides a promising tool to measure skin parasite load, and – if validated by xenodiagnosis studies – could facilitate much needed larger scale studies on infectiousness of human subgroups. In addition, we advocate further evaluation of this device as a diagnostic tool for PKDL. [ABSTRACT FROM AUTHOR]

Post-kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that is a late clinical outcome of visceral leishmaniasis (VL). Its presentation is similar to leprosy, and the differential diagnosis is not always easy. In VL endemic rural areas of Bihar, India, both infectious diseases co-exist. This observational study aimed to determine the prevalence and distribution of both conditions in an area that had until recently been highly endemic for VL. We conducted a door-to-door survey in an area that belongs to the Health and Demographic Surveillance Site (HDSS) of Muzaffarpur, Bihar, India. Within the HDSS we selected the villages that had reported the highest numbers of VL cases in preceding years. All consenting household members were screened for skin conditions, and minor conditions were treated on the spot. Upon completion of screening activities at the level of a few villages, a dermatology clinic ("skin camp") was conducted to which suspect leprosy and PKDL patients and other patients with skin conditions requiring expert advice were referred. We studied the association between distance from an index case of leprosy and the probability of disease in the neighborhood by fitting a Poisson model. We recorded a population of 33,319, out of which 25,686 (77.1%) were clinically screened. Participation in skin camps was excellent. Most common conditions were fungal infections, eczema, and scabies. There were three PKDL patients and 44 active leprosy patients, equivalent to a prevalence rate of leprosy of 17.1 per 10,000. Two out of three PKDL patients had a history of VL. Leprosy patients were widely spread across villages, but within villages, we found strong spatial clustering, with incidence rate ratios of 6.3 (95% C.I. 1.9–21.0) for household members and 3.6 (95% C.I. 1.3–10.2) for neighbors within 25 meters, with those living at more than 100 meters as the reference category. Even in this previously highly VL endemic area, PKDL is a rare condition. Nevertheless, even a single case can trigger a new VL outbreak. Leprosy is also a rare disease, but current prevalence is over 17 times the elimination threshold proclaimed by WHO. Both diseases require continued surveillance. Active case finding for leprosy can be recommended among household members and close neighbors of leprosy patients but would not be feasible for entire populations. Periodic skin camps may be a feasible and affordable alternative. We describe a survey for post kala azar dermal leishmaniasis (PKDL) and leprosy carried out in a surveillance site in Bihar, India, that has until recently been highly endemic for visceral leishmaniasis (VL). Both leprosy and VL are subject to elimination initiatives, for both diseases the target prevalence is set at less than 1 case per 10,000 population. PKDL, a dermatological sequel of VL, is important because it can act as a reservoir for VL in inter-epidemic periods. So far very little is known about prevalence of PKDL in India and the frequency of PKDL among former VL patients. Our survey was population based, allowing us to assess PKDL prevalence not only among former VL patients but also among those not known to have suffered from VL in the past. We conducted door-to-door screening and suspect cases of leprosy and PKDL were referred to a 'skin camp', an outreach consultation for skin conditions at village level. We recorded geographic coordinates of each household screened, thus we were able to explore spatial associations. Participation in the survey and in the skin camps was very good. On a population of over 25,000 screened we found only three PKDL cases but 44 active leprosy patients. For leprosy this equates to a prevalence of 17.1 per 10,000, way above the elimination threshold. Of our three PKDL cases, two had occurred in known former VL cases, one was in a person who reported never to have suffered from VL. For leprosy we found strong spatial associations with a six-fold increase in risk for household members but also a three to four-fold increase for neighbors at less than 25 meters. The three PKDL cases were from three different villages, their numbers were too low for any meaningful spatial analysis. We conclude that leprosy is still a major problem in the area that requires more efforts. Active screening of household contacts is rational but should be extended to nearby neighbors. Though relatively efficient, this approach would miss out on the bulk of leprosy patients. PKDL is a rare condition but needs to be kept under surveillance. Skin camps can provide a feasible alternative to door-to-door screening, allowing to target both conditions simultaneously. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). Methods: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6–12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Results: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1–8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. Conclusion: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated. [ABSTRACT FROM AUTHOR]

• Feasibility study of solar Solar/Wind/Bio-generator/Diesel/Battery based microgrids for rural areas. • Implementation of Hybrid PSO-GWO for solving optimal sizing problem. • Comparison of well-established optimization tools with the implemented method. • Study implementation on selected rural locations in Indian state of Bihar. • A framework for minimal cost of energy and loss of power supply probability added with appreciable renewable factor. The suitability of microgrids depends upon the balance between the size, cost-efficiency and reliability of the system. The work involves optimal planning of microgrid taking a case of three locations in the Indian state of Bihar. A combination of Solar/Wind/Bio-generator energy generation units along with diesel generation and the battery is implemented for this purpose. The tradeoff between Cost Of Electricity (COE) and Deficiency of Power Supply Probability (DPSP) has been analysed and an objective function is defined as a combination of the two with a bound of Renewable Factor (RF). A hybrid Particle Swarm Optimisation-Grey Wolf Optimiser (PSO-GWO) is implemented for optimisation. The performance of the algorithm is compared with numerous others using 13 classical benchmark test functions and 10 CEC-06 2019 benchmark functions. The obtained microgrids are analysed to supply at an average Cost of Electricity of 0.17 ($ / kWh) meeting at least 93 % of the demand. Besides, an average renewable factor of 0.93 makes the system environmental friendly. The work also includes a sensitivity analysis of Cost of Electricity. The results are compared with those using other previously used algorithms in the literature and the effectiveness of the implemented algorithm is established. [ABSTRACT FROM AUTHOR]