The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan

Parasitic diseases, including human visceral leishmaniasis, are multifactorial. Factors that are expected to play an important role in the parasite-human interaction are exposure, parasite "virulence" and host resistance factors. In populations exposed to Leishmania donovani most subjects do not allow the parasites to establish themselves or remain asymptomatic. Some individuals, however, fail to control parasite expansion and dissemination and develop a visceral disease. We report here the results of a longitudinal survey whose aims were to identify risk factors underlying visceral leishmaniasis (VL) susceptibility during an outbreak that occurred in a Sudanese village between 1995 and 1999. Most of the 660 subjects (90%) living in the central district were exposed to Leishmania and 20.9% (n = 138), mostly teenagers, developed VL. VL cases increased markedly in adults late in the outbreak, suggesting some changes in adult resistance status or in Leishmania "virulence" during the epidemic. Age and ethnic origin of the patients were the most important critical risk factors to account for the distribution of the VL cases that were recorded during the whole epidemic. This and the high frequency of VL in certain families suggest that host genetic factors played an important role in shaping the outbreak in this village. However, environmental factors (the presence of cows and neems in the households) that increase/decrease exposure to the parasite had significant effects on the distribution of VL cases in the village in the first phase of the outbreak.     

Sandflies (Diptera: Psychodidae) in a focus of visceral leishmaniasis in White Nile, Sudan

Visceral leishmaniasis (VL) has been known to occur since the 1980s on the western bank of the White Nile River (Central Sudan), 150 km south of Khartoum, and has resulted in high mortality. The most recent outbreak of the disease in this area began in 2006. Entomological surveys were carried out during May 2008, June 2010 and May and July 2011 in the White Nile area. Sandflies were collected using Centers for Disease Control light traps and sticky oil traps in the village of Kadaba and the nearby woodland. Phlebotomus females were dissected for the presence of Leishmania promastigotes. A total of 17,387 sandflies, including six species of Phlebotomus and 10 species of Sergentomyia, were identified. The Phlebotomus species recorded were Phlebotomus orientalis, Phlebotomus papatasi, Phlebotomus bergeroti, Phlebotomus duboscqi, Phlebotomus rodhaini and Phlebotomus saevus. P. orientalis was collected in both habitats. The relative abundance of P. orientalis in the woodland habitat was higher than that recorded in the village habitat. In the woodland habitat, there was a notable increase in the relative abundance of P. orientalis during the surveys conducted in 2008 and 2010 compared to 2011. None of the 311 P. orientalis females dissected were infected with Leishmania promastigotes, although relatively high parous rates were recorded in both habitats. Based on the distribution of P. orientalis recorded in this study, this species is the most likely vector of VL in the endemic focus in the White Nile area. Further investigation is required to elucidate the seasonal abundance and distribution of the vector, as well as the transmission season of VL in both habitats so that appropriate control strategies for the vector can be designed.     

Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study

Background

A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.

Methods

This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg.

Findings

42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively).

Conclusion

Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00255567","term_id":"NCT00255567"}}NCT00255567     

Protective efficacy of lambdacyhalothrin-impregnated bednets against Phlebotomus orientalis, the vector of visceral leishmaniasis in Sudan

Field investigations on the sandfly Phlebotomus orientalis (Diptera: Psychodidae), the vector of Leishmania donovani causing visceral leishmaniasis (VL) in Sudan, were undertaken in two villages (Bellow and Elgamel) and Dinder National Park, to determine the protective value of bednets (polyester, 100 denier) impregnated with lambda-cyhalothrin 10 mg a.i./m2 pyrethroid insecticide. After exposure to treated netting for 30 s, P. orientalis females all died within 1 h. When field-tested in Acacia woodland, treated bednets provided complete protection from bites of the vector. Numbers of P. orientalis females landing on human collectors without bednets or using untreated bednets averaged 32.0 +/- 8.3 or 6.9 +/- 2.7 per man-night, respectively, whereas collectors using treated bednets experienced no sandfly bites during the same period (18.00-06.00 hours, 12 nights in June 1995). Socio-behavioural observations on the bed-time of people living in both study villages indicated that the use of impregnated bednets against P. orientalis would give more potential protection for women and children than for male adults. Overall the proportions of people and their durations of exposure to the risk of sandfly bites (i.e. after sunset until they went to bed) were 40% unprotected for< 1h, 50% for 1-2h and >10% for > or = 2h. Because visceral leishmaniasis in Sudan occurs mainly in children, the use of impregnated bednets (outdoors as well as indoors), and going to bed early could provide a high degree of personal protection against this zoonotic infection.     

A recent chikungunya outbreak associated with the occurrence of Aedes vectors (Diptera: Culicidae) in Kassala state,eastern Sudan in 2018

Aedes aegypti and Ae. albopictus (Diptera: Culicidae) are primary vectors of human arboviral diseases such as dengue, chikungunya, yellow fever, and Zika viruses. Aedes aegypti is well distributed in Sudan, except in Northern and Khartoum states, while Ae. albopictus has not been previously reported. Recently, Eastern Sudan witnessed an unprecedented large outbreak of chikungunya fever between 31 May 2018 and 30 March 2019. The outbreak was composed of four waves; one of them was in Kassala state. Aedes survey in localities of Kassala state (rather than Kassala city) is carried out to assess the possible expansion of the disease in the state. The results showed the presence of immature stages of Aedes spp. in four localities from ten localities. From the four localities that recorded Aedes spp., two localities (Rural Kassala and West Kassala) were reported with chikungunya cases. From this investigation, Ae. albopictus was reported for the first time in Sudan. Also, this investigation showed the importance of conducting entomological surveys with epidemiological surveys during outbreaks of arboviral diseases.     

Epidemiology of visceral leishmaniasis through spatial analysis, in Belo Horizonte municipality, state of Minas Gerais, Brazil

The geographic information system approach has permitted integration between demographic, socio-economic and environmental data, providing correlation between information from several data banks. In the current work, occurrence of human and canine visceral leishmaniases and insect vectors (Lutzomyia longipalpis) as well as biogeographic information related to 9 areas that comprise the city of Belo Horizonte, Brazil, between April 2001 and March 2002 were correlated and georeferenced. By using this technique it was possible to define concentration loci of canine leishmaniasis in the following regions: East; Northeast; Northwest; West; and Venda Nova. However, as for human leishmaniasis, it was not possible to perform the same analysis. Data analysis has also shown that 84.2% of the human leishmaniasis cases were related with canine leishmaniasis cases. Concerning biogeographic (altitude, area of vegetation influence, hydrographic, and areas of poverty) analysis, only altitude showed to influence emergence of leishmaniasis cases. A number of 4673 canine leishmaniasis cases and 64 human leishmaniasis cases were georeferenced, of which 67.5 and 71.9%, respectively, were living between 780 and 880 m above the sea level. At these same altitudes, a large number of phlebotomine sand flies were collected. Therefore, we suggest control measures for leishmaniasis in the city of Belo Horizonte, giving priority to canine leishmaniasis foci and regions at altitudes between 780 and 880 m.     

Lutzomyia longipalpis in Clorinda, Formosa province, an area of potential visceral leishmaniasis transmission in Argentina

Phlebotomine captures were performed during 2004 in Clorinda, Argentina. Clorinda is located across the branches of the Paraguay river in front of Asunción city, Paraguay. Reports of canine and human visceral leishmaniasis in Asunción have been increasing since 1997, however neither leishmaniasis cases nor sand flies were ever recorded from Clorinda. Light traps were located in migration paths (bridges, port), and peridomestic environments of Clorinda and surrounding localities. Lutzomyia longipalpis was found in Clorinda and Puerto Pilcomayo, first report in a potential visceral leishmaniasis transmission area for Argentina. Active surveillance is required immediately in the localities involved and the surrounding area.     

Canine visceral leishmaniasis in Rio de Janeiro, Brazil. Clinical, parasitological, therapeutical and epidemiological findings (1977-1983)

Forty dogs from the periphery of the city of Rio de Janeiro were studied. All dogs where diagnosed as positive for leishmaniasis either parasitologically and/or serologically. Among them, 19 came from areas where only Visceral Leishmaniasis (VL) occurs (Realengo, Bangu, Senador Camará). Clinical signs of the disease were seen in 36.8% of the cases, including emaciation - 100%, lymphadenopathy and depilation - 85.7%. The other 21 dogs came from an area (Campo Grande) where both diseases (VL, and American Cutaneous Leishmaniasis - ACL) occur. Clinical signs of the disease, mainly cutaneous or mucocutaneous ulcers were seen in 76.2% of the cases. Leishmania parasites were found in 39 cases: 22% in viscera, 42.5% in viscera and normal skin and 35% in cutaneous or mucocutaneous ulcers. All the Leishmania stocks isolated from dogs which came from Realengo, Bangu, Senador Camará (VL area), and from Campo Grande (VL + ACL area) were characterized as L. donovani (except in one case) according to their schizodeme, zymodeme and serodeme. The only stock characterized as L. b. braziliensis, was isolated from the lymph node of a dog from Campo Grande with visceral disease and without skin lesions. Antimony therapy attempted in eight Leishmania donovani positive dogs was unsuccessful.     

Distribution of phlebotomine fauna (Diptera: Psychodidae) across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil

The number of visceral leishmaniasis (VL) cases has increased over the past 10 years in Brazil, especially in the North and Northeast regions of the country. The aim of this study was to evaluate the urbanisation of VL vectors in Barcarena, Pará, an area in northern Brazil where VL is endemic. Sandflies were captured using Centers for Disease Control (CDC) light traps along an urban-rural gradient. The CDC traps were installed inside hen houses at a height of 150 cm. A total of 5,089 sandflies were collected and 11 species were identified. The predominant species was Lutzomyia longipalpis (rate of 95.15%), which suggests its participation in the transmission of VL. A total of 1,451 Lu. longipalpis females were dissected and no Leishmania infections were detected. Most of the sandflies were captured at the border of a forest (88.25%) and no flies were captured in the urban area, which suggests that transmission is still restricted to rural sites. However, the fact that a specimen was collected in an intermediate area indicates that urbanisation is a real possibility and that vector monitoring is important.     

An outbreak of cholera (El Tor) in Samarkand Province, Uzbekistan in 1990]

A group outbreak of cholera caused by Vibrio eltor in the Samarkand Province++ in 1990 is analyzed. The retrospective analysis of the isolation of V. cholerae from water of surface reservoirs has been made. The study points out that since the cholera epidemic of 1985 V. cholerae avirulent strains, serogroup O1, have been periodically isolated in the Samarkand Province. The conclusion has been made that the isolation of even avirulent strains only from environmental objects is indicative of the unfavorable epidemiological situation in this area and of the necessity to take measures for improving epidemiological surveillance.     

An outbreak of the desert sub-type of zoonotic visceral leishmaniasis in Jiashi,Xinjiang Uygur Autonomous Region,People's Republic of China

Few outbreaks of the desert sub-type of zoonotic visceral leishmaniasis (VL) have been described worldwide. In 2008, the incidence rate of VL in Jiashi County, Xinjiang Uygur Autonomous Region in the western part of the People's Republic of China, increased more than twenty-folds compared to the average annual incidence rate. The majority of the cases (96.6%) occurred among < 2 year-old infants. For the first time in the desert area of Xinjiang, the parasites were isolated from bone marrow aspirates, using the NNN medium culture approach. The genetic analysis of the ITS-1 nucleotide sequence indicated that three isolates from eastern Jiashi County were genetically closely related and belonged to the Leishmania infantum group. However, they differed from an isolate from Kashi city which was classified as a member of the Leishmania donovani group.     

Epidemiology of nodding syndrome in the Greater Mundri area,South Sudan: Prevalence,spatial pattern and environmental risk factors

BackgroundNodding syndrome (NS) is a progressive neurological disease that has been described in several sub-Saharan African counties, but South Sudan is considered the most affected. However, knowledge about the exact burden and the epidemiological risk factors of NS in South Sudan is lacking.ObjectiveTo determine the prevalence, distribution and epidemiological risk factors of NS in the Greater Mundri area, the epicenter of NS in South Sudan.MethodsA NS prevalence house-to-house survey was conducted in multiple villages between February 2018 and November 2019. Geographical distribution and clustering of NS cases was identified using spatial and binomial regression analysis. Epidemiological risk factors of NS were identified using univariate and multivariate models.ResultsOf the 22,411 persons surveyed in 92 villages, 607 (2.7%) persons with NS were identified, of which 114 (19%) were new-onset cases. The highest prevalence was found in Diko village with a prevalence of 13.7%. NS showed a significant spatial pattern with clustering of cases between adjacent households and along rivers. Risks factors for NS include all behaviors around rivers (drinking, cooking, handwashing and bathing) and exposure to poultry. On the other hand, ownership of mobile phone decreased the risk of NS. Many other factors, including prior ivermectin treatment and internal displacement were not associated with NS.ConclusionOur study demonstrates a very high burden of the NS disease in the Greater Mundri area, strengthens the association with rivers, and identified possible new clues for an underlying cause.     

Application of Direct Agglutination Test (DAT) and Fast Agglutination Screening Test (FAST) for sero-diagnosis of visceral leishmaniasis in endemic area of Minas Gerais,Brazil

Background  

The direct agglutination test (DAT) has proved to be a very important sero-diagnostic tool combining high levels of intrinsic validity and ease of performance. Otherwise, fast agglutination screening test (FAST) utilises only one serum dilution making the test very suitable for the screening of large populations.     

Phlebotomine sand flies in Porteirinha, an area of American visceral leishmaniasis transmission in the State of Minas Gerais, Brazil

A study of the phlebotomine sand fly fauna was carried out in an endemic area of American visceral leishmaniasis (AVL) in the municipality of Porteirinha, in the Brazilian state of Minas Gerais. Captures were performed with CDC light traps in 7 districts, 5 days per month, during 2 consecutive years (January 2000 to December 2001). A total of 3240 sand flies were captured and identified. Sixteen species were found, among which 15 belonged to the genus Lutzomyia and one to the genus Brumptomyia. Lutzomyia longipalpis, a proven vector of AVL, was the predominant species (71.85%) throughout the time period. The interference of climatic factors (temperature, humidity, and rainfall) over the populational dynamics of the sand flies was determined. Statistical analysis of the data showed a significant correlation among the number of phlebotomine sand flies collected, rainfall, and humidity, whereas the effect of temperature was negligible, in that particular region. The amount of collected phlebotomine, the number of human cases, and the prevalence of canine AVL in the districts of Porteirinha are discussed.