Risk Factors for Foot-and-Mouth Disease in Tanzania, 2001-2006

We developed a model to quantify the effect of factors influencing the spatio-temporal distribution of foot-and-mouth disease (FMD) in Tanzania. The land area of Tanzania was divided into a regular grid of 20 km x 20 km cells and separate grids constructed for each of the 12-month periods between 2001 and 2006. For each year, a cell was classified as either FMD positive or negative dependent on an outbreak being recorded in any settlement within the cell boundaries. A Bayesian mixed-effects spatial model was developed to assess the association between the risk of FMD occurrence and distance to main roads, railway lines, wildlife parks, international borders and cattle density. Increases in the distance to main roads decreased the risk of FMD every year from 2001 to 2006 (ORs ranged from 0.43 to 0.97). Increases in the distance to railway lines and international borders were, in general, associated with a decreased risk of FMD (ORs ranged from 0.85 to 0.99). Increases in the distance from a national park decreased the risk of FMD in 2001 (OR 0.80; 95% CI 0.68-0.93) but had the opposite effect in 2004 (OR 1.06; 95% CI 1.01-1.12). Cattle population density was, in general, positively associated with the risk of FMD (ORs ranged from 1.01 to 1.30). The spatial distribution of high-risk areas was variable and corresponded to endemic (2001, 2002 and 2005) and epidemic (2003, 2004 and 2006) phases. Roads played a dominant role in both epidemiological situations; we hypothesize that roads are the main driver of FMD expansion in Tanzania. Our results suggest that FMD occurrence in Tanzania is more related to animal movement and human activity via communication networks than transboundary movements or contact with wildlife

A randomized, blinded, controlled trial to assess sand fly mortality of fluralaner administered orally in dogs

Background: Leishmania infantum is the parasite responsible for the disease in humans known as zoonotic visceral leishmaniasis (ZVL). Dogs are considered the main domestic reservoir of ZVL and sand flies are the proven vectors. The use of systemic insecticides in dogs has been studied as an alternative strategy to control ZVL in endemic areas. One systemic insecticide in dogs, fluralaner, has a proven anti-sand fly effect in membrane-fed studies. However, the efficacy and duration on sand flies directly feeding from dogs treated with fluralaner remains unknown. Methods: Direct feeding bioassays were performed on 10 beagle dogs that had been randomly assigned to two groups: one with five dogs orally treated with Bravecto® (fluralaner) and other five as a control. About 30 females of Phlebotomus papatasi were allowed to directly feed from dogs at seven days before the administration of the treatment and Days 3, 17, 31, 45 and 73 post-treatment. Sand fly mortality after feeding was observed every 24 h for 5 days. The Kaplan-Meyer method, Henderson-Tilton formula and a negative binomial mixed model were used to respectively calculate: (i) mortality and its 95% confidence interval (CI); (ii) efficacy of the insecticide at killing sand flies in 24 h; and (iii) differences in the risk of sand fly death at 24 h after feeding. Results: Control sand fly mortality 24 h after feeding was always ≤ 20% and mortality in the fluralaner group ranged from 2% (95% CI: 0–4%) 7 days before treatment to 100% at 3 days post-treatment. Fluralaner efficacy was 100, 93, 94 and 75% at Days 3, 17, 31 and 45, respectively (P < 0.0001). The increase in the risk of sand fly death was 32.9 (95% CI: 4–263), 76 (95% CI: 8–705), 95.8 (95% CI: 9–1029) and 10.6 times (95% CI: 1.43–79) on Days 3, 17, 31 and 45, respectively Conclusions: The efficacy of fluralaner, orally administered to dogs, against sand-flies was above 90% for 31 days. Fluralaner administered to dogs should be further evaluated as a control strategy in ZVL endemic areas

Visceral leishmaniasis: Spatiotemporal heterogeneity and drivers underlying the hotspots in Muzaffarpur, Bihar, India

Background: Despite the overall decrease in visceral leishmaniasis (VL) incidence on the Indian subcontinent, there remain spatiotemporal clusters or ‘hotspots’ of new cases. The characteristics of these hotspots, underlying transmission dynamics, and their importance for shaping control strategies are not yet fully understood and are investigated in this study for a VL endemic area of ~100,000 inhabitants in Bihar, India between 2007–2015. Methodology/Principal findings VL incidence (cases/10,000/year) dropped from 12.3 in 2007 to 0.9 in 2015, which is just below the World Health Organizations’ threshold for elimination as a public health problem. Clustering of VL was assessed between subvillages (hamlets), using multiple geospatial and (spatio)temporal autocorrelation and hotspot analyses. One to three hotspots were identified each year, often persisting for 1–5 successive years with a modal radius of ~500m. The relative risk of having VL was 5–86 times higher for inhabitants of hotspots, compared to those living outside hotspots. Hotspots harbour significantly more households from the two lowest asset quintiles (as proxy for socio-economic status). Overall, children and young adelescents (5–14 years) have the highest risk for VL, but within hotspots and at the start of outbreaks, older age groups (35+ years) show a comparable high risk. Conclusions/Significance: This study demonstrates significant spatiotemporal heterogeneity in VL incidence at subdistrict level. The association between poverty and hotspots confirms that VL is a disease of ‘the poorest of the poor’ and age patterns suggest a potential role of waning immunity as underlying driver of hotspots. The recommended insecticide spraying radius of 500m around detected VL cases corresponds to the modal hotspot radius found in this study. Additional data on immunity and asymptomatic infection, and the development of spatiotemporally explicit transmission models that simulate hotspot dynamics and predict the impact of interventions at the smaller geographical scale will be crucial tools in sustaining elimination

Clinical and immunological characteristics of tegumentary leishmaniasis cases in Bolivia

Background Tegumentary leishmaniasis (TL) is a parasitic disease that can present a cutaneous or mucocutaneous clinical form (CL and MCL, respectively). The disease is caused by different Leishmania species and transmitted by phlebotomine sand flies. Bolivia has one of the highest incidences of the disease in South America and the diagnosis is done by parasitological techniques. Our aim was to describe the clinical and immunological characteristics of CL and MCL patients attending the leishmaniasis reference center in Cochabamba, Bolivia, in order to gain updated clinical and epidemiological information, to evaluate the diagnostic methods used and to identify biomarkers related to clinical disease and its evolution. Methodology/Principal findings The study was conducted from September 2014 to November 2015 and 135 patients with lesions compatible with CL or MCL were included. Epidemiological and clinical data were collected using a semi-structured questionnaire. Two parasitological diagnostic methods were used: Giemsa-stained smears and culture of lesion aspirates. Blood samples obtained from participants were used to measure the concentrations of different cytokines. 59.2% (80/135) were leishmaniasis confirmed cases (CL: 71.3%; MCL: 28.7%). Sixty percent of the confirmed cases were positive by smears and 90.6% were positive by culture. 53.8% were primo-infections. Eotaxin and monokine induced by IFN-γ presented higher serum concentrations in the MCL clinical presentation compared to CL cases and no-cases. None of the cytokines presented different concentrations between primo-infections and secondary infections due to treatment failure. Conclusions/Significance In Bolivia, parasitological diagnosis remains the reference standard in diagnosis of leishmaniasis because of its high specificity, whereas the sensitivity varies over a wide range leading to loss of cases. Until more accurate tools are implemented, all patients should be tested by both smears and culture of lesion aspirates to minimize the risk of false negatives. Our results showed higher concentrations of several cytokines in MCL compared to CL, but no differences were observed between CL and no-cases. In addition, none of the cytokines differed between primary and secondary infections. These results highlight the need of further research to identify biomarkers of susceptibility and disease progression, in addition to looking at the local cellular immune responses in the lesions

Systemic insecticide treatment of the canine reservoir of Trypanosoma cruzi induces high levels of lethality in Triatoma infestans, a principal vector of Chagas disease

BACKGROUND: Despite large-scale reductions in Chagas disease prevalence across Central and South America, Trypanosoma cruzi infection remains a considerable public health problem in the Gran Chaco region where vector-borne transmission persists. In these communities, peridomestic animals are major blood-meal sources for triatomines, and household presence of infected dogs increases T. cruzi transmission risk for humans. To address the pressing need for field-friendly, complementary methods to reduce triatomine infestation and interrupt T. cruzi transmission, this study evaluated the systemic activity of three commercial, oral, single dose insecticides Fluralaner (Bravecto(R)), Afoxolaner (NexGard(R)) and Spinosad (Comfortis(R)) in canine feed-through assays against Triatoma infestans, the principal domestic vector species in the Southern Cone of South America. METHODS: Twelve healthy, outbred dogs were recruited from the Zoonosis Surveillance and Control Program in Santa Cruz, Bolivia, and randomized to three treatment groups, each containing one control and three treated dogs. Following oral drug administration, colony-reared second and third stage T. infestans instars were offered to feed on dogs for 30 min at 2, 7, 21, 34 and 51 days post-treatment. RESULTS: Eighty-five per cent (768/907) of T. infestans successfully blood-fed during bioassays, with significantly higher proportions of bugs becoming fully-engorged when exposed to Bravecto(R) treated dogs (P < 0.001) for reasons unknown. Exposure to Bravecto(R) or NexGard(R) induced 100% triatomine mortality in fully- or semi-engorged bugs within 5 days of feeding for the entire follow-up period. The lethality effect for Comfortis(R) was much lower (50-70%) and declined almost entirely after 51 days. Instead Comfortis(R) treatment resulted in substantial morbidity; of these, 30% fully recovered whereas 53% remained morbid after 120 h, the latter subsequently unable to feed 30 days later. CONCLUSIONS: A single oral dose of Fluralaner or Afoxolaner was safe and well tolerated, producing complete triatomine mortality on treated dogs over 7.3 weeks. While both drugs were highly efficacious, more bugs exposed to Fluralaner took complete blood-meals, and experienced rapid knock-down. Coupled with its longer residual activity, Fluralaner represents an ideal insecticide for development into a complementary, operationally-feasible, community-level method of reducing triatomine infestation and potentially controlling T. cruzi transmission, in the Gran Chaco region

Intradomiciliary and peridomiciliary captures of sand flies (Diptera: Psychodidae) in the leishmaniasis endemic area of Chapare province, Tropic of Cochabamba, Bolivia

In South America, cutaneous leishmaniasis is the most frequent clinical form of leishmaniasis. Bolivia is one of the countries with higher incidence, with 33 cases per 100,000 individuals, and the disease is endemic in 70% of the territory. In the last decade, the number of cases has increased, the age range has expanded, affecting children under 5 years old, and a similar frequency between men and women is found. An entomological study with CDC light traps was conducted in three localities (Chipiriri, Santa Elena and Pedro Domingo Murillo) of the municipality of Villa Tunari, one of the main towns in the Chapare province (Department of Cochabamba, Bolivia). A total of 16 specimens belonging to 6 species of the genus Lutzomyia were captured: Lu. aragaoi, Lu. andersoni, Lu. antunesi, Lu. shawi, Lu. yuilli yuilli and Lu. auraensis. Our results showed the presence of two incriminated vectors of leishmaniasis in an urbanized area and in the intradomicile. More entomological studies are required in the Chapare province to confirm the role of vector sand flies, the intradomiciliary transmission of the disease and the presence of autochthonous cases of cutaneous leishmaniasis

"Kala-Azar is a Dishonest Disease": Community Perspectives on Access Barriers to Visceral Leishmaniasis (Kala-Azar) Diagnosis and Care in Southern Gadarif, Sudan

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

Target product profile for a test for the early assessment of treatment efficacy in Chagas disease patients: An expert consensus.

Six to 7 million people are estimated to be infected by Trypanosoma cruzi, the parasite causing Chagas disease. Thirty to 40% of them, i.e., 1.8 to 2.4 million people, will suffer cardiac disorders and/or digestive clinical manifestations if they are not treated early during the course of the infection [1, 2]. However, only a small fraction of patients are properly diagnosed and treated [3]. Current clinical guidelines recommend treating T. cruzi–infected people if they are asymptomatic or present early symptoms of the disease (Table 1) [4, 5]. Benznidazole (BNZ) and nifurtimox (NFX) are the first-line antiparasitic treatments currently available, both with long administration regimens (60 days) that can produce adverse side effects [6–8]. Despite the fact they are not 100% effective in patients with chronic disease [9–12], they are the only drugs currently registered, and the benefits of their administration have been confirmed in several clinical studies. Currently, clinical trials with new compounds, using alternative regimens that aim to maintain efficacy whilst reducing toxicity, are ongoing and could lead to new therapeutic opportunities and/or policy change

Risk assessment of BTV-3 incursion from Sardinia by wind dispersal of Culicoides midges

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