Kala-azar control, Uganda.
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ABSTRACT:
SUBMITTER: Kolaczinski JH
PROVIDER: S-EPMC2725906 | biostudies-literature | 2007 Mar
REPOSITORIES: biostudies-literature
Publications
Kala-azar control, Uganda.
Kolaczinski Jan H JH Worku Dagemlidet Tesfaye DT Chappuis François F Reithinger Richard R Kabatereine Narcis N Onapa Ambrose A Brooker Simon S
Emerging infectious diseases 20070301 3
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| S-EPMC11448539 | biostudies-literature
Project description:Kala azar continues to be a medical problem in India and with the increase in incidence of HIV Infection it is likely that kala azar will be encountered more frequently and in its atypical forms. To aid diagnosis, several immunological tests are now available and they are more sensitive and specific than the aldehyde test. Like many other diseases today, the treatment of kala azar is hampered by drug resistance. Newer drugs are available and so are new delivery systems. Kala azar develops frequently in the HIV infected person before development of AIDS. The presentation is atypical and leishmanial species other than L. donovani may also be the infecting agents. A combination of sandfly control, detection and treatment of patients and prevention of drug resistance continues to the ideal approach for the control of the disease.
| S-EPMC5530401 | biostudies-other
Project description:BackgroundThe potential reservoirs of visceral leishmaniasis (VL) in South Asia include asymptomatic and relapsed cases of VL, along with patients with post kala-azar dermal leishmaniasis (PKDL). Accordingly, accurate estimation of their parasite load is pivotal for ensuring disease elimination, presently targeted for 2023. Serological tests cannot accurately detect relapses and/or monitor treatment effectiveness, and therefore, parasite antigen/nucleic acid based detection assays remain the only viable option. An excellent option is the quantitative polymerase chain reaction (qPCR) but the high cost, technical expertise and time involved precludes its wider acceptability. Accordingly, the recombinase polymerase amplification (RPA) assay operated in a mobile suitcase laboratory has emerged not simply as a diagnostic tool for leishmaniasis but also to monitor the disease burden.Methodology/principal findingsUsing total genomic DNA isolated from peripheral blood of confirmed VL cases (n = 40) and lesional biopsies of PKDL cases (n = 64), the kinetoplast-DNA based qPCR and RPA assay was performed and parasite load expressed as Cycle threshold (Ct) and Time threshold (Tt) respectively. Using qPCR as the gold standard, the diagnostic specificity and sensitivity of RPA in naïve cases of VL and PKDL was reiterated. To assess the prognostic potential of the RPA, samples were analyzed immediately at the end of treatment or ≥6 months following completion of treatment. In cases of VL, the RPA assay in terms of cure and detection of a relapse case showed 100% concordance with qPCR. In PKDL following completion of treatment, the overall detection concordance between RPA and qPCR was 92.7% (38/41). At the end of treatment for PKDL, 7 cases remained qPCR positive, whereas RPA was positive in only 4/7 cases, perhaps attributable to their low parasite load.Conclusions/significanceThis study endorsed the potential of RPA to evolve as a field applicable, molecular tool for monitoring parasite load, possibly at a point of care level and is worthy of consideration in resource limited settings.
| S-EPMC10115299 | biostudies-literature
Project description:BackgroundLittle is known about the parasite/host factors that lead to Post Kala-azar Dermal Leishmaniasis (PKDL) in some visceral leishmaniasis (VL) patients after drug-cure. Studies in Sudan provide evidence for association between polymorphisms in the gene (IFNGR1) encoding the alpha chain of interferon-γ receptor type I and risk of PKDL. This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan.MethodsSanger sequencing was used to re-sequence 841 bp of upstream, exon1 and intron1 of the IFNGR1 gene in DNA from 30 PKDL patients. LAGAN and SYNPLOT bioinformatics tools were used to compare human, chimpanzee and dog sequences to identify conserved noncoding sequences carrying putative regulatory elements. The relative expression of IFNG and IFNGR1 in paired pre- and post-treatment RNA samples from the lymph nodes of 24 VL patients, and in RNA samples from skin biopsies of 19 PKDL patients, was measured using real time PCR. Pre- versus post-treatment expression was evaluated statistically using the nonparametric Wilcoxon matched pairs signed-rank test.ResultsTen variants were identified in the 841 bp of sequence, four of which are novel polymorphisms at -77A/G, +10 C/T, +18C/T and +91G/T relative to the IFNGR1 initiation site. A cluster of conserved non-coding sequences with putative regulatory variants was identified in the distal promoter of IFNGR1. Variable expression of IFNG was detected in lymph node aspirates of VL patients before treatment, with a marked reduction (P = 0.006) in expression following treatment. IFNGR1 expression was also variable in lymph node aspirates from VL patients, with no significant reduction in expression with treatment. IFNG expression was undetectable in the skin biopsies of PKDL cases, while IFNGR1 expression was also uniformly low.ConclusionsUniformly low expression of IFN and IFNGR1 in PKDL skin biopsies could explain parasite persistence and is consistent with prior demonstration of genetic association with IFNGR1 polymorphisms. Identification of novel potentially functional rare variants at IFNGR1 makes an important general contribution to knowledge of rare variants of potential relevance in this Sudanese population.
| S-EPMC4265480 | biostudies-literature
Project description:BackgroundThe South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP.Methodology and principal findingWe reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention.Conclusion and significancePKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation.
| S-EPMC5689828 | biostudies-literature
Project description:Leishmania donovani in India causes visceral infection (kala-azar) and dermal infection (post-kala-azar dermal leishmaniasis). We report here the identification of polymorphism in a well-defined genetic locus among the Leishmania parasites causing the visceral and dermal manifestations, in a comparison of 15 post-kala-azar dermal leishmaniasis and 12 kala-azar patient isolates.
| S-EPMC387559 | biostudies-literature
Project description:Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: "shopping around" for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be "hiding," requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.
| S-EPMC5928836 | biostudies-literature
Project description:Kala-azar (KA) is a life-threatening protozoal disease caused by Leishmania parasites (L. donovani, L. chagasi, and L. infantum). The disease, which is also called "visceral leishmaniasis," is prevalent in Africa, South America, Asia, and the Mediterranean basin. Epidemics occur periodically, killing a large number of infected individuals. Factors determining whether a patient remains asymptomatic or develops KA are still largely unknown. In a previous study that was performed during an outbreak of KA in a village on the Ethiopian-Sudanese border, we showed that KA was more frequent in certain families and ethnic groups, thereby suggesting that host genetic factors play an important role in the development of the disease. Here, we report the results of a genomewide linkage study performed on 63 Sudanese families selected from the most affected ethnic group and including 169 children with KA. Significant linkage (LOD score 3.50 [P=3x10-5] in all patients; LOD score 3.90 [P=10-5] in patients who were affected early in the outbreak) was obtained with markers on chromosome 22q12. These results are the first evidence of a major genetic effect on the development of human KA. They may lead to identification of genes critical in the pathogenesis of this disease and to new therapeutic interventions against this parasite, which is developing resistance to available drugs.
| S-EPMC1180485 | biostudies-literature
Project description:We have developed a PCR assay that is capable of amplifying kinetoplast DNA (kDNA) of Leishmania donovani in a species-specific manner among Old World leishmanias. With Indian strains and isolates of L. donovani the assay was sensitive enough to detect kDNA in an amount equivalent to a single parasite or less. The extreme sensitivity of the assay was reflected in its ability to detect parasite DNA from small volumes of peripheral blood of patients with kala-azar (KA) and from skin lesions from patients with post-KA dermal leishmaniasis (PKDL). A total of 107 clinical leishmaniasis samples were analyzed. Of these 102 (95.3%) were positive by PCR. The test provided a diagnosis of KA with 96% sensitivity using patient whole-blood samples instead of bone marrow or spleen aspirates that are obtained by invasive procedures. The assay was also successful in the diagnosis of 45 of 48 PKDL cases (93.8%). Cross-reactions with pathogens prevalent in the area of endemicity, viz., Mycobacterium tuberculosis, Mycobacterium leprae, and Plasmodium spp., could be ruled out. Eighty-one control samples, including dermal scrapings from healthy portions of skin from patients with PKDL were all negative. Two of twenty controls from the area of endemicity were found positive by PCR assay; however, there was a good possibility that these two were asymptomatic carriers since they were serologically positive for KA. Thus, this PCR assay represents a tool for the diagnosis of KA and PKDL in Indian patients in a noninvasive manner, with simultaneous species identification of parasites in clinical samples.
| S-EPMC87840 | biostudies-literature