Age trends in asymptomatic and symptomatic Leishmania donovani infection in the Indian subcontinent: A review and analysis of data from diagnostic and epidemiological studies
"As the elimination target for visceral leishmaniasis (VL) in the Indian subcontinent (<1 case/10,000 people/year) is approached, there is a growing need for surveillance tools with which to monitor transmission to ensure the target is sustained, especially given the large proportion of infections which are asymptomatic (~75–95%). One potential approach to estimate underlying transmission patterns may be to track age patterns in infection or cumulative exposure using diagnostic tests. However, current understanding of age patterns in asymptomatic infection and clinical VL is poor, in particular regarding possible age-dependence of infection rates. Our systematic review and pooled-analysis of age-stratified data on infection prevalence and disease incidence suggests that available diagnostics, as currently implemented, fail to meet the requirements for a reliable tool for assessing transmission, due to inconsistent standardisation and highly variable age-prevalence patterns across different settings. It also finds weak evidence for infection rates increasing with age, though further longitudinal studies are needed to test this hypothesis and to assess whether properly standardised diagnostic tests could be used to monitor ongoing transmission."
Intervention Packages for Early Visceral Leishmaniasis Case Detection and Sandfly Control in Bangladesh: A Comparative Analysis
A xenodiagnosis study on PKDL and VL patients using laboratory-reared Phlebotomus argentipes was conducted to determine whether PKDL patients can act as an infection reservoir. The study concludes that nodular and macular PKDL, and VL, can be infectious to sand flies. The authors therefore advise that "active PKDL case detection and prompt treatment should be instituted and maintained as an integral part of VL control and elimination programs".
The role of case proximity in transmission of visceral leishmaniasis in a highly endemic village in Bangladesh
"Visceral leishmaniasis (VL), a fatal parasitic disease transmitted by sandflies, has been targeted for elimination as a public health problem in the Indian subcontinent by 2020. The goal has been reached in the majority of endemic regions in Bangladesh, India and Nepal, but the disease persists in several hotspots. Better understanding of spatial clustering of VL cases and the role of asymptomatically infected individuals in transmission is required to improve control interventions and sustain the elimination target. To address this issue, we have fitted an individual-level spatiotemporal model of VL transmission to geo-located incidence data from Bangladesh to estimate the rate at which VL risk decreases with distance from a case and the potential contribution of asymptomatic individuals to transmission. Our results suggest that VL risk decreases quickly with distance and that symptomatic individuals are the main drivers of transmission, highlighting the potential for spatially-targeted control interventions to reduce transmission".
"In the Indian subcontinent, visceral leishmaniasis (VL) has a strongly clustered distribution. The “index case approach” is promoted both for active case finding and indoor residual spraying (IRS). Uncertainty exists about the optimal radius. Buffer zones of 50–75 m around incident cases have been suggested for active case finding, for IRS the recommendation is to cover a radius of 500 m. Our aim was to establish optimal target areas both for IRS and for (re)active case finding. We plotted incident VL cases on a map per 6-month period (January–June or July–December) and drew buffers of 0 (same household), 50, 75, 100, 200, 300, 400, and 500 m around these cases. We then recorded total population and numbers of VL cases diagnosed over the next 6-month period in each of these buffers and beyond. We calculated incidence rate ratios (IRRs) using the population at more than 500 m from any case as reference category. There was a very strong degree of spatial clustering of VL with IRRs ranging from 45.2 (23.8–85.6) for those living in the same households to 14.6 (10.1–21.2) for those living within 75 m of a case diagnosed, during the previous period. Up to 500 m the IRR was still five times higher than that of the reference category. Our findings corroborate the rationale of screening not just household contacts but also those living within a perimeter of 50–75 m from an index case. For IRS, covering a perimeter of 500 m, appears to be a rational choice."
"The visceral leishmaniasis (VL) elimination programme was launched in the Indian subcontinent (Bangladesh, India and Nepal) in 2005. Although the integrated vector management (IVM) system is one of the important elements highlighted in the Regional VL elimination strategy, indoor residual spraying (IRS) is the sole intervention practice that has been implemented. In fact, in Bangladesh from 1999 to early 2012, no VL vector control was used at all and pre-monsoon IRS was only re-introduced by the national programme in eight high endemic upazilas (sub-districts) in 2012. The present study monitored IRS operation in five upazilas (Fulbaria, Trishal, Mukthagacha, Gaforgaon and Bhaluka). Monitoring took place with the help of using observation check lists and questionnaires included in the WHO/TDR monitoring and evaluation tool kit. The study identified that training of spraymen was insufficient and a supervisor was not always present during spraying. The spraying techniques by all the sprayers were sub-standard. It was also found that all the required personal protective equipment was not provided by the national programme. It is recommended that the national programme should conduct monitoring and evaluation activities to ensure high quality of IRS operations in order to achieve maximum benefit.
"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 96.55% 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 (96.55% 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 94.74%, 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."
Safety and Effectiveness of Short-Course AmBisome in the Treatment of Post-Kala-Azar Dermal Leishmaniasis: A Prospective Cohort Study in Bangladesh.
A prospective cohort observational study focusing on evauating the effectiveness and safety of AmBisome for PKDL patients residing in a highly VL-endemic area in Bangladesh. Clinical response was monitored regularly up to 12 months after treatment, while safety during treatment and up to 1 month after treatment.
The authors conclude that "short-course 15-mg/kg AmBisome regimen proved safe and effective in the treatment of clinically diagnosed PKDL in Bangladesh, and should be considered a treatment option for routine programmatic use in the VL elimination effort in the Indian subcontinent.
This study demonstrates the potential value of using Leishmania strains isolated from VL patients for monitoring drug sensitivty and resistance emergence, as well as for systematic use in high-throughput screening (HTS) during novel anti-leishmanial drug discovery.