Project description:BACKGROUND:Visceral leishmaniasis (VL) or Kala-azar has been a major public health problem in Bihar, India, for several decades. A few VL infected districts including Vaishali have reported >600 cases annually. Hence, in 2015, the Government of India entrusted ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, to implement an integrated control strategy for achieving the VL elimination target (<1 case per 10,000 people at the block level) in the Vaishali District of Bihar. METHODOLOGY:This study was conducted between January 2015 and December 2016. An integrated control strategy including the spatio-temporal mapping of VL-case distribution, active case detection, chemical-based vector control using indoor residual spraying (IRS), community awareness campaigns, the training of IRS members, the training of medical doctors for effective treatment, daily monitoring and the supervision of IRS activities, logistic management, post-IRS quality assurance, epidemiological surveillance, and entomological monitoring was performed. An insecticide quantification test was performed for evaluating the IRS quality on sprayed walls. A modern compression pump was used to maintain spray quality on different wall surfaces. The impact of IRS was assessed through sand fly collection in human dwellings and cattle sheds in pre- and post-IRS. The insecticide susceptibility of local P. argentipes was performed before each IRS round (in February and June) during 2015-2016. Statistical analysis such as the mean, percentage, and 95% CI were used to summarize the results. FINDINGS:All 16 blocks of the Vaishali District achieved the VL elimination target in 2016. The integrated VL control strategy helped reduce the number of VL cases from 664 in 2014 to 163 in 2016 and the number of endemic villages from 282 in 2014 to 142 in 2016. The case reduction rate was increased from 22.6% in 2014 to 58.8% in 2016. On average, 74 VL infected villages became Kala-azar free each year from 2015 to 2016. CONCLUSIONS:The results of this study suggest that the elimination of VL is possible from all endemic blocks of Bihar if the integrated Vaishali VL control strategy is applied under strong monitoring and supervision.
Project description:Sera of kala-azar patients from Bihar, India, were used to identify Leishmania donovani antigens encoded by a phage expression library. Ten antigens were identified, five of which have not been described as leishmania antigens before. The antigens specifically react with sera of leishmania-infected patients but not of toxoplasma- or plasmodium-infected patients.
Project description:BackgroundEffective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India's most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence.MethodsExpenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider's perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD.ResultsDuring 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81, $4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from $1.6-4 million, depending on the extent to which blanket and camp ACD was relied upon.ConclusionCost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India.
Project description:BackgroundFew prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens.Methodology/principal findingsA Phase IV trial included 1761 VL patients treated between 2012-2014 with single dose AmBisome (SDA; N = 891), miltefosine-paromomycin (Milt-PM; n = 512), or AmBisome-miltefosine (AmB-Milt; n = 358). Follow-up for PKDL and VL relapse was scheduled for 6, 12 and 24 months after treatment, lasting until 2017. Patients with lesions consistent with PKDL were tested by rK39 rapid test, and if positive, underwent skin-snip sampling, smear microscopy and PCR. Probable PKDL was defined by consistent lesions and positive rK39; confirmed PKDL required additional positive microscopy or PCR. PKDL and relapse incidence density were calculated by VL treatment and risk factors evaluated in Cox proportional hazards models. Among 1,750 patients who completed treatment, 79 had relapse and 104 PKDL. Relapse incidence density was 1.58, 2.08 and 0.40 per 1000 person-months for SDA, AmB-Milt and Milt-PM, respectively. PKDL incidence density was 1.29, 1.45 and 2.65 per 1000 person-months for SDA, AmB-Milt and Milt-PM. In multivariable models, patients treated with Milt-PM had lower relapse but higher PKDL incidence than those treated with SDA; AmB-Milt rates were not significantly different from those for SDA. Children <12 years were at higher risk for both outcomes; females had a higher risk of PKDL but not relapse.Conclusions/significanceActive surveillance for PKDL and relapse, followed by timely treatment, is essential to sustain the achievements of VL elimination programs in the Indian sub-continent.
Project description:BackgroundThe skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) supported a VL treatment programme in Bihar, India-an area highly endemic for Leishmania donovani-in which 8749 patients received 20 mg/kg intravenous Ambisome as first-line treatment. This study describes the characteristics of patients who returned to the MSF supported treatment programme with PKDL.Methods and principal findingsOver a 5-year period, Ambisome was administered to 8749 patients with laboratory-confirmed VL (clinical signs, rK39 positive, with/without parasite confirmation) in four intravenous doses of 5 mg/kg to a total of 20 mg/kg, with a high initial-cure rate (99.3%) and low default rate (0.3%). All patients received health education highlighting the possibility and symptoms of developing PKDL, and advice to return to the MSF programme if these symptoms developed. This is an observational retrospective cohort study of the programme outcomes. Of the 8311 patients completing treatment for their first episode of VL, 24 (0.3%) returned passively to the programme complaining of symptoms subsequently confirmed as PKDL, diagnosed from clinical history, appearance consistent with PKDL, and slit-skin smear examination. Of the 24 patients, 89% had macular lesions, with a median time (interquartile range) to development of 1.2 (0.8-2.2) years following treatment. Comparison of the demographic and clinical characteristics of the VL patients treated with Ambisome who later developed PKDL, with those of the remaining cohort did not identify any significant risk factors for PKDL. However, the time to developing PKDL was significantly shorter with Ambisome than in a subset of patients presenting to the programme with PKDL following previous sodium stibogluconate treatment for VL.ConclusionsIn this large cohort of patients with VL in Bihar who were treated with 20 mg/kg Ambisome, PKDL following treatment appears to be infrequent with no predictive risk factors. The shorter median time to developing symptoms of PKDL compared with that after conventional VL treatments should be taken into account when counseling patients treated with regimens including Ambisome.
Project description:BackgroundHeath facility-based sentinel site surveillance has been proposed as a means of monitoring trends in malaria morbidity but may also provide an opportunity to improve malaria case management. Here we described the impact of a sentinel site malaria surveillance system on promoting laboratory testing and rational antimalarial drug use.Methodology/principal findingsSentinel site malaria surveillance was established at six health facilities in Uganda between September 2006 and January 2007. Data were collected from all patients presenting to the outpatient departments including demographics, laboratory results, diagnoses, and treatments prescribed. Between the start of surveillance and March 2010, a total 424,701 patients were seen of which 229,375 (54%) were suspected of having malaria. Comparing the first three months with the last three months of surveillance, the proportion of patients with suspected malaria who underwent diagnostic testing increased from 39% to 97% (p<0.001). The proportion of patients with an appropriate decision to prescribe antimalarial therapy (positive test result prescribed, negative test result not prescribed) increased from 64% to 95% (p<0.001). The proportion of patients appropriately prescribed antimalarial therapy who were prescribed the recommended first-line regimen artemether-lumefantrine increased from 48% to 69% (p<0.001).Conclusions/significanceThe establishment of a sentinel site malaria surveillance system in Uganda achieved almost universal utilization of diagnostic testing in patients with suspected malaria and appropriate decisions to prescribed antimalarial based on test results. Less success was achieved in promoting prescribing practice for the recommended first-line therapy. This system could provide a model for improving malaria case management in other health facilities in Africa.
Project description:BackgroundVisceral 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 findingsA 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; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission.Conclusion/significanceSnowball 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.
Project description:IntroductionElimination of kala-azar is planned for South Asia requiring good surveillance along with other strategies. We assessed surveillance in Gaffargaon upazila (a subdistrict of 13 unions) of Mymensingh district, Bangladesh highly endemic for kala-azar.MethodsIn 4703 randomly sampled households, within nine randomly sampled villages, drawn from three randomly sampled unions, we actively searched for kala-azar cases that had occurred between January 2010 and December 2011. We then searched for medical records of these cases in the patient registers of Gaffargaon upazila health complex (UHC). We investigated factors associated with the medical recording by interviewing the cases and their families. We also did a general observation of UHC recording systems and interviewed health staff responsible for the monthly reports of kala-azar cases.ResultsOur active case finding detected 58 cases, but 29 were not recorded in the Gaffargaon UHC. Thus, only 50% (95% CI: 37%-63%) of kala-azar cases were reported via the government passive surveillance system. Interviews with health staff based in the study UHC revealed the heavy reporting burden for multiple diseases, variation in staff experience, high demands on the staff time and considerable complexity in the recording system. After adjusting for kala-azar treatment drug, recording was found more likely for those aged 18 years or more, males, receiving supply and administration of drug at the UHC, and more recent treatment.DiscussionFifty percent of kala-azar cases occurring in one highly endemic area of Bangladesh were recorded in registers that were the source for monthly reports to the national surveillance system. Recording was influenced by patient, treatment, staff and system factors. Our findings have policy implications for the national surveillance system. Future studies involving larger samples and including interviews with health authorities at more central level and surveillance experts at the national level will generate more precise and representative evidence on the performance of kala-azar surveillance in Bangladesh.