• Field effectiveness of new visceral leishmaniasis regimens after 1 year following treatment within public health facilities in Bihar, India

      Goyal, V; Burza, S; Pandey, K; Singh, SN; Singh, RS; Strub-Wourgaft, N; Das, VNR; Bern, C; Hightower, A; Rijal, S; et al. (The Public Library of Science, 2019-09-26)
      BACKGROUND: An earlier open label, prospective, non-randomized, non-comparative, multi-centric study conducted within public health facilities in Bihar, India (CTRI/2012/08/002891) measured the field effectiveness of three new treatment regimens for visceral leishmaniasis (VL): single dose AmBisome (SDA), and combination therapies of AmBisome and miltefosine (AmB+Milt) and miltefosine and paromomycin (Milt+PM) up to 6 months follow-up. The National Vector Borne Disease Control Program (NVBDCP) recommended an extended follow up at 12 months post-treatment of the original study cohort to quantify late relapses. METHODS: The 1,761 patients enrolled in the original study with the three new regimens were contacted and traced between 10 and 36 months following completion of treatment to determine their health status and any occurrence of VL relapse. RESULTS: Of 1,761 patients enrolled in the original study, 1,368 were traced at the extended follow-up visit: 711 (80.5%), 295 (83.2%) and 362 (71.5%) patients treated with SDA, AmB+Milt and Milt+PM respectively. Of those traced, a total of 75 patients were reported to have relapsed by the extended follow-up; 45 (6.3%) in the SDA, 25 (8.5%) in the AmB+Milt and 5 (1.4%) in the Milt+PM arms. Of the 75 relapse cases, 55 had already been identified in the 6-months follow-up and 20 were identified as new cases of relapse at extended follow-up; 7 in the SDA, 10 in the AmB+Milt and 3 in the Milt+PM arms. CONCLUSION: Extending follow-up beyond the standard 6 months identified additional relapses, suggesting that 12-month sentinel follow-up may be useful as a programmatic tool to better identify and quantify relapses. With limited drug options, there remains an urgent need to develop effective new chemical entities (NCEs) for VL.
    • Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India

      Goyal, Vi; Mahajan, R; Pandey, K; Singh, SN; Singh, RS; Strub-Wourgaft, N; Alves, F; Rabi Das, VN; Topno, RK; Sharma, B; et al. (Public Library of Science, 2018-10-22)
      In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.
    • Kala-azar outbreak in Libo Kemkem, Ethiopia: epidemiologic and parasitologic assessment.

      Alvar, J; Bashaye, S; Argaw, D; Cruz, I; Aparicio, P; Kassa, A; Orfanos, G; Parreño, F; Babaniyi, O; Gudeta, N; et al. (2007-08)
      In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemkem, Ethiopia. In October 2005, a rapid assessment was conducted using data from 492 patients with VL treated in the district health center and a household survey of 584 residents of four villages. One subdistrict accounted for 71% of early cases, but the incidence and number of affected subdistricts increased progressively throughout 2004-2005. In household-based data, we identified 9 treated VL cases, 12 current untreated cases, and 19 deaths attributable to VL (cumulative incidence, 7%). Thirty percent of participants were leishmanin skin test positive (men, 34%; women, 26%; P = 0.06). VL was more common in men than women (9.7% versus 4.5%, P < 0.05), possibly reflecting male outdoor sleeping habits. Molecular typing in splenic aspirates showed L. infantum (six) and L. donovani (one). Local transmission resulted from multiple introductions, is now well established, and will be difficult to eradicate.
    • Natural history of a visceral leishmaniasis outbreak in highland Ethiopia

      Herrero, M; Orfanos, G; Argaw, D; Mulugeta, A; Aparicio, P; Parreño, F; Bernal, O; Rubens, D; Pedraza, J; Lima, M A; et al. (American Society of Tropical Medicine and Hygiene, 2009-09-01)
      In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemken, Ethiopia, a highland region where only few cases had been reported before. We analyzed records of VL patients treated from May 25, 2005 to December 13, 2007 by the only VL treatment center in the area, maintained by Médecins Sans Frontières-Ethiopia, Operational Center Barcelona-Athens. The median age was 18 years; 77.6% were male. The overall case fatality rate was 4%, but adults 45 years or older were five times as likely to die as 5-29 year olds. Other factors associated with increased mortality included HIV infection, edema, severe malnutrition, pneumonia, tuberculosis, and vomiting. The VL epidemic expanded rapidly over a several-year period, culminating in an epidemic peak in the last third of 2005, spread over two districts, and transformed into a sustained endemic situation by 2007.
    • Outdoor Residual Insecticide Spraying (ODRS), a New Approach for the Control of the Exophilic Vectors of Human Visceral Leishmaniasis: Phlebotomus orientalis in East Africa

      Elnaiem, DA; Dakein, O; Alawad, AM; Alsharif, B; Khogali, A; Jibreel, T; Osman, OF; Has'san, H; Atia, AM; Elhag, M; et al. (Public Library of Sciences, 2020-10-20)
      Visceral Leishmaniasis (VL) due to Leishmania donovani is a neglected protozoan parasitic disease in humans, which is usually fatal if untreated. Phlebotomus orientalis, the predominant VL vector in East Africa, is a highly exophilic/exophagic species that poses a major challenge to current Integrated Vector Management (IVM). Here we report results of pilot studies conducted in rural villages in Gedarif state, Sudan, to evaluate outdoor residual spraying of 20mg active ingredient (a.i.) /m2 deltamethrin insecticide applied to the characteristic household compound boundary reed fence and to the outside of household buildings (Outdoor Residual Insecticide Spraying, ODRS), and as an alternative, spraying restricted to the boundary fence only (Restricted Outdoor Residual Insecticide Spraying, RODRS). Four to six clusters of 20 households were assigned to insecticide treatments or control in three experiments. Changes in sand fly numbers were monitored over 2,033 trap-nights over 43–76 days follow-up in four sentinel houses per cluster relative to unsprayed control clusters. Sand fly numbers were monitored by sticky traps placed on the ground on the inside (“outdoor”) and the outside (“peridomestic”) of the boundary fence, and by CDC light traps suspended outdoors in the household compound. The effects of ODRS on sand fly numbers inside sleeping huts were monitored by insecticide knockdown. After a single application, ODRS reduced P. orientalis abundance by 83%-99% in outdoor and peridomestic trap locations. ODRS also reduced numbers of P. orientalis found resting inside sleeping huts. RODRS reduced outdoor and peridomestic P. orientalis by 60%-88%. By direct comparison, RODRS was 58%-100% as effective as ODRS depending on the trapping method. These impacts were immediate on intervention and persisted during follow-up, representing a large fraction of the P. orientalis activity season. Relative costs of ODRS and RODRS delivery were $5.76 and $3.48 per household, respectively. The study demonstrates the feasibility and high entomological efficacy of ODRS and RODRS, and the expected low costs relative to current IVM practises. These methods represent novel sand fly vector control tools against predominantly exophilic/exophagic sand fly vectors, aimed to lower VL burdens in Sudan, with potential application in other endemic regions in East Africa.