The epidemiology of Leishmania donovani infection in high transmission foci in India.

OBJECTIVE: Visceral Leishmaniasis (VL) is highly prevalent in Bihar, India. India and its neighbours aim at eliminating VL, but several knowledge gaps in the epidemiology of VL may hamper that effort. The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar. METHODS: Demographic and immunological surveys were carried out in July and November 2006, respectively in 16 highly VL endemic foci in Muzaffarpur district in Bihar. Household and individual information was gathered and capillary blood samples were collected on filter papers. Direct agglutination test (DAT) was used to determine infected individuals (cut-off titre 1:1600). DAT results were tabulated against individual and household variables. A multivariate generalized estimating equation (GEE) model was used to study the prevalence of serologically positive individuals taking into account the clustering at household and cluster levels. RESULTS: Of study subjects 18% were DAT positive, and this proportion increased with age. Women had a significantly lower prevalence than men >14 years old. Owning domestic animals (cows, buffaloes or goats) was associated with a higher risk of being DAT positive [OR 1.16 (95% CI 1.01-1.32)], but socio-economic status was not. CONCLUSIONS: Prevalence of leishmanial antibodies was high in these communities, but variable. Demographic factors (i.e. marriage) may explain the lower DAT positivity in women >14 years of age. Within these homogeneously poor communities, socio-economic status was not linked to L. donovani infection risk at the individual level, but ownership of domestic animals was

Sponsorship in non-commercial clinical trials: definitions, challenges and the role of Good Clinical Practices guidelines.

BACKGROUND: Non-commercial clinical research plays an increasingly essential role for global health. Multiple partners join in international consortia that operate under the limited timeframe of a specific funding period. One organisation (the sponsor) designs and carries out the trial in collaboration with research partners, and is ultimately responsible for the trial's scientific, ethical, regulatory and legal aspects, while another organization, generally in the North (the funder), provides the external funding and sets funding conditions. Even if external funding mechanisms are key for most non-commercial research, the dependence on an external funder's policies may heavily influence the choices of a sponsor. In addition, the competition for accessing the available external funds is great, and non-commercial sponsors may not be in a position to discuss or refuse standard conditions set by a funder. To see whether the current definitions adequately address the intricacies of sponsorship in externally-funded trials, we looked at how a "sponsor" of clinical trials is defined in selected international guidelines, with particular focus on international Good Clinical Practices codes, and in selected European and African regulations/legislations. DISCUSSION: Our limited analysis suggests that the sponsors definition from the 1995 WHO Good Clinical Practices code has been integrated as such into many legislations, guidelines and regulations, and that it is not adequate to cover today's reality of funding arrangements in global health, where the legal responsibility and the funding source are de facto split. In agreement with other groups, we suggest that the international Good Clinical Practices codes should be updated to reflect the reality of non-commercial clinical research. In particular, they should explicitly include the distinction between commercial and non-commercial sponsors, and provide guidance to non-commercial sponsors for negotiating with external funding agencies and other research counterparts. Non-commercial sponsors of clinical trials should surely invest in the development of adequate legal, administrative and management skills. By acknowledging their role and specificities, and by providing them with adapted guidance, the international Good Clinical Practices codes would provide valuable guidance and support to non-commercial clinical research, whose relevance for global health is increasingly evident

Evidence-based vector control? Improving the quality of vector control trials.

Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis cause a high level of morbidity and mortality. Although vector control tools can play a major role in controlling and eliminating these diseases, in many cases the evidence base for assessing the efficacy of vector control interventions is limited or not available. Studies assessing the efficacy of vector control interventions are often poorly conducted, which limits the return on investment of research funding. Here we outline the principal design features of Phase III vector control field studies, highlight major failings and strengths of published studies, and provide guidance on improving the design and conduct of vector control studies. We hope that this critical assessment will increase the impetus for more carefully considered and rigorous design of vector control studies

Sensitivity and specifi city of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study

Background Human African trypanosomiasis (HAT) is a life-threatening infection aff ecting rural populations in sub- Saharan Africa. Large-scale population screening by antibody detection with the Card Agglutination Test for Trypanosomiasis (CATT)/Trypanosoma brucei (T b) gambiense helped reduce the number of reported cases of gambiense HAT to fewer than 10 000 in 2011. Because low case numbers lead to decreased cost-eff ectiveness of such active screening, we aimed to assess diagnostic accuracy of a rapid serodiagnostic test (HAT Sero-K-SeT) applicable in primary health-care centres. Methods In our case-control study, we assessed participants older than 11 years who presented for HAT Sero-K-SeT and CATT/T b gambiense at primary care centres or to mobile teams (and existing patients with confi rmed disease status at these centres) in Bandundu Province, DR Congo. We defi ned cases as patients with trypanosomes that had been identifi ed in lymph node aspirate, blood, or cerebrospinal fl uid. During screening, we recruited controls without previous history of HAT or detectable trypanosomes in blood or lymph who resided in the same area as the cases. We assessed diagnostic accuracy of three antibody detection tests for gambiense HAT: HAT Sero-K-SeT and CATT/T b gambiense (done with venous blood at the primary care centres) and immune trypanolysis (done with plasma at the Institute of Tropical Medicine, Antwerp, Belgium). Findings Between June 6, 2012, and Feb 25, 2013, we included 134 cases and 356 controls. HAT Sero-K-SeT had a sensitivity of 0·985 (132 true positives, 95% CI 0·947–0·996) and a specifi city of 0·986 (351 true negatives, 0·968–0·994), which did not diff er signifi cantly from CATT/T b gambiense (sensitivity 95% CI 0·955, 95% CI 0·906–0·979 [128 true positives] and specifi city 0·972, 0·949–0·985 [346 true negatives]) or immune trypanolysis (sensitivity 0·985, 0·947–0·996 [132 true positives] and specifi city 0·980, 0·960–0·990 [349 true negatives]). Interpretation The diagnostic accuracy of HAT Sero-K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/T b gambiense cannot be done

High Failure Rates of Melarsoprol for Sleeping Sickness, Democratic Republic of Congo

A retrospective chart review of 4,925 human African trypanosomiasis patients treated with melarsoprol in 2001–2003 in Equateur Nord Province of the Democratic Republic of Congo showed a treatment failure rate of 19.5%. This rate increased over the 3 years. Relapse rates were highest in the central part of the province

Community perception and knowledge of cystic echinococcosis in the High Atlas Mountains, Morocco

Cystic echinococcosis (CE), a neglected zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus, remains a public health issue in many developing countries that practice extensive sheep breeding. Control of CE is difficult and requires a community-based integrated approach. We assessed the communities' knowledge and perception of CE, its animal hosts, and its control in a CE endemic area of the High Atlas Mountains, Morocco. We conducted twenty focus group discussions (FGDs) stratified by gender with villagers, butchers and students in ten Berber villages that were purposefully selected for their CE prevalence. This community considers CE to be a severe and relatively common disease in humans and animals but has a poor understanding of the parasite's life cycle. Risk behaviour and disabling factors for disease control are mainly related to cultural practices in sheep breeding and home slaughtering, dog keeping, and offal disposal at home, as well as in slaughterhouses. Participants in our focus group discussions were supportive of control measures as management of canine populations, waste disposal, and monitoring of slaughterhouses. The uncontrolled stray dog population and dogs having access to offal (both at village dumps and slaughterhouses) suggest that authorities should be more closely involved in CE control. This study also highlights the need for improved knowledge about the transmission cycle of the parasite among communities and health professionals. Inter-sectoral collaboration between health staff, veterinarians, and social scientists appears to be crucial for sustainable control of this parasitic zoonosis

Visceral Leishmaniasis-HIV Coinfection as a Predictor of Increased Leishmania Transmission at the Village Level in Bihar, India.

BACKGROUND: Visceral leishmaniasis (VL) is on the verge of being eliminated as a public health problem in the Indian subcontinent. Although Post-kala-azar dermal leishmaniasis (PKDL) is recognized as an important reservoir of transmission, we hypothesized that VL patients co-infected with Human Immunodeficiency Virus (HIV) may also be important reservoirs of sustained leishmania transmission. We therefore investigated to what extent cases of PKDL or VL-HIV are associated with VL incidence at the village level in Bihar, India. METHODS: VL, VL-HIV, and PKDL case data from six districts within the highly VL-endemic state of Bihar, India were collected through the Kala-Azar Management Information System for the years 2014-2019. Multivariate analysis was done using negative binomial regression controlling for year as a fixed effect and block (subdistrict) as a random effect. FINDINGS: Presence of VL-HIV+ and PKDL cases were both associated with a more than twofold increase in VL incidence at village level, with Incidence Rate Ratios (IRR) of 2.16 (95% CI 1.81-2.58) and 2.37 (95% CI 2.01-2.81) for VL-HIV+ and PKDL cases respectively. A sensitivity analysis showed the strength of the association to be similar in each of the six included subdistricts. CONCLUSIONS: These findings indicate the importance of VL-HIV+ patients as infectious reservoirs for Leishmania, and suggest that they represent a threat equivalent to PKDL patients towards the VL elimination initiative on the Indian subcontinent, therefore warranting a similar focus

Perbadanan Kemajuan iktisad negeri Kelantan (PKINK) dalam pembangunan perumahan di negeri Kelantan / Che Azhar Che Abdullah

Perumahan sering di perkatakan oleh setiap masyarakat kerana pembekalannya ke dalam pasaran tidak dapat memenuhi kehendak masyarakat yang memerlukannya. Lapuran Kajian Separuh Penggal RME menyatakan pencapaian pembinaan perumahan di peringkat nasionaL adalah kurang marauaskan atas sebab faktur permintaan dan penawaran. Adalah menjadi mat lamat perumahan nasional untuk menyediakan kemudahan perumahan yang mencukupi bagi semua rakyat di negara ini , terutama golongan berpendapatan rendah dengan kemudahan perumahan yang baik dan selesa. Kadar permintaan rendah di sebabkan oleh kemelesetan ekonomi, harga rumah dan kadar faedah yang tinggi. Penawarannya berkurangan oleh sebab kekurangan tapak bersesuaian dan kelewatan memperolehi kelulusan disamping sebab-sebab lain. Matlamat perumahan nasional ini juga dijalankan di- Negeri Kelantan di raana sebahagian besar projek perumahannya di laksanakan oleh Jabatan Perumahan Negara (JPN) dan Perbadanan Kemajuan Iktisad Negeri Kelantan (PKINK) d i samping sektor awam dan swasta yang lain . Didalam dissertasi ini , penyentuhan akan di buat tentang peranan PKINK dalam pembangunan perumahan di dalam menolong mencapai matlamat di atas. Di dalam mendapatkan maklumat serta penyelidikan untuk penyediaan dissertasi ini , kerjasama yang baik dan memuaskan hati telah diperolehi dari PKINK sendiri, JPN, Bahagian Perumahan Negeri* Jabatan Perangkaan, UPEN, Pejabat Tanah dan Galian, Majlis Perbandaran Kota Bharu serta Pejabat Perancang Bandar dan Desa Negeri Kelantan. Di samping itu , maklumat juga telah diperolehi daripada keratan-kerata n akhbar dan majalah majallah. Maklumat-maklumat yang terakhir tidak dapat diperolehi sepenuhnya kerana kebanyakan kertas-kertas kerja , lapuran serta rekod-rekod adalah di sediakan semasa untuk membuat lapuran bagi penyediaan Lapuran Kajian Separuh Penggal RME yang telah di bentangkan pada penghujung Mac, 1984. Hasil daripada kerjasama yang diberikan, dapatlah saya menyiapkan dissertasi ini dan saya rakamkan kalungan penghargaan keatas setiap pihak berkenaan dengan ucapan "terima kasih daun keladi "

Significantly lower anti-Leishmania IgG responses in Sudanese versus Indian visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. METHODOLOGY/PRINCIPAL FINDINGS: We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001). Mean reciprocal log10 50% end-point titres (1/log10t50) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001). Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old) and adults of either sex from India (mean 1/log10t50: 3.60-4.15) versus Sudan (mean 1/log10t50: 1.88-2.54). The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn(2+) deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential anti-Leishmania IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa