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Enhanced case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh.

ABSTRACT: OBJECTIVES:To support the Bangladesh National Kala-azar Elimination Programme (NKEP), we investigated the feasibility of using trained village volunteers for detecting post-kala-azar dermal leishmaniasis (PKDL) cases, using polymerase chain reaction (PCR) for confirmation of diagnosis and treatment compliance by PKDL patients in Kanthal union of Trishal sub-district, Mymensingh, Bangladesh. METHODS:In this cross-sectional study, Field Research Assistants (FRAs) conducted census in the study area, and the research team trained village volunteers on how to look for PKDL suspects. The trained village volunteers (TVVs) visited each household in the study area for PKDL suspects and referred the suspected PKDL cases to the study clinic. The suspected cases underwent physical examinations by a qualified doctor and rK39 strip testing by the FRAs and, if positive, slit skin examination (SSE), culture, and PCR of skin specimens and peripheral buffy coat were done. Those with evidence of Leishmania donovani (LD) were referred for treatment. All the cases were followed for one year. RESULTS:The total population of the study area was 29,226 from 6,566 households. The TVVs referred 52 PKDL suspects. Probable PKDL was diagnosed in 18 of the 52 PKDL suspect cases, and PKDL was confirmed in 9 of the 18 probable PKDL cases. The prevalence of probable PKDL was 6.2 per 10,000 people in the study area. Thirteen PKDL suspects self-reported from outside the study area, and probable and confirmed PKDL was diagnosed in 10 of the 13 suspects and in 5 of 10 probable PKDL cases respectively. All probable PKDL cases had hypopigmented macules. The median time for PKDL development was 36 months (IQR, 24-48). Evidence of the LD parasite was documented by SSE and PCR in 3.6% and 64.3% of the cases, respectively. PCR positivity was associated with gender and severity of disease. Those who were untreated had an increased risk (odds ratio?=?3.33, 95%CI 1.29-8.59) of having persistent skin lesions compared to those who were treated. Patients' treatment-seeking behavior and treatment compliance were poor. CONCLUSION:Improved detection of PKDL cases by TVVs is feasible and useful. The NKEP should promote PCR for the diagnosis of PKDL and should find ways for improving treatment compliance by patients.

SUBMITTER: Mondal D

PROVIDER: S-EPMC2950134 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Enhanced case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh.

Mondal Dinesh D Nasrin Kamrul Nahar KN Huda M Mamun MM Kabir Mamun M Hossain Mohammad Shakhawat MS Kroeger Axel A Thomas Tania T Haque Rashidul R

PLoS neglected tropical diseases 20101005 10

<h4>Objectives</h4>To support the Bangladesh National Kala-azar Elimination Programme (NKEP), we investigated the feasibility of using trained village volunteers for detecting post-kala-azar dermal leishmaniasis (PKDL) cases, using polymerase chain reaction (PCR) for confirmation of diagnosis and treatment compliance by PKDL patients in Kanthal union of Trishal sub-district, Mymensingh, Bangladesh.<h4>Methods</h4>In this cross-sectional study, Field Research Assistants (FRAs) conducted census in ...[more]

PMID: 20957193

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Project description:BackgroundPost kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis, caused by Leishmania donovani, constitutes an important reservoir for the parasite. Parallel functioning of counter acting immune responses (Th1/Th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis.Methodology/principal findingsIn the present study, human cytokine/chemokine/receptor specific cDNA array technique was employed to identify modulations in gene expression of host immuno-determinants during PKDL, followed by evaluation of Th17 type responses by analyzing mRNA and protein expression of Th17 markers (IL-23, IL-17, RORγt) and performing functional assays using Leishmania antigen (TSLA) or recombinant (rec)IL-17. Array analysis identified key immuno-regulatory molecules including cytokines (TNF-α, IFN-γ, IL-10, IL-17), chemokines (MCP-1, MIP-1α), apoptotic molecules (FasL, TRAIL, IRF-1) and receptors (CD40, Fas). Up regulation in lesional expression of Th17 markers was observed during PKDL compared to control (IL-17 and IL-23, P = 0.0008; RORγt, P = 0.02). In follow-up samples, chemotherapy significantly down regulated expression of all markers. In addition, lesional expression of IL-17 was confirmed at protein level by Immuno-histochemistry. Further, systemic presence of Th17 responses (IL-17 and IL-23) was observed in plasma samples from PKDL patients. In functional assays, TSLA stimulated the secretion of IL-17 and IL-23 from PBMCs of PKDL patients, while recIL-17 enhanced the production of TNF-α as well as nitric oxide (NO) in PKDL compared to control (TNF-α, P = 0.0002; NO, P = 0.0013). Further, a positive correlation was evident between lesional mRNA expression of IL-17 and TNF-α during PKDL.Conclusion/significanceThe results highlight key immune modulators in PKDL and provide evidence for the involvement of Th17 type responses in the disease pathogenesis.

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.

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.

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Enhanced case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh.

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Enhanced case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh.

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