Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but also are poised to help solve two of the most important future NTD challenges-how to maintain control of STH infections after the community-based LF "treatment platform" ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease.

Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis: longitudinal study and meta-analysis.

BACKGROUND: There is a need for sensitive and specific rapid diagnostic tests (RDT) for canine visceral leishmaniasis. The aims of this study were to evaluate the diagnostic performance of immunochromatographic dipstick RDTs using rK39 antigen for canine visceral leishmaniasis by (i) investigating the sensitivity of RDTs to detect infection, disease and infectiousness in a longitudinal cohort study of natural infection in Brazil, and (ii) using meta-analysis to estimate the sensitivity and specificity of RDTs from published studies. METHODOLOGY: We used a rK39 RDT (Kalazar Detect Canine Rapid Test; Inbios) to test sera collected from 54 sentinel dogs exposed to natural infection in an endemic area of Brazil. Dogs were sampled bimonthly for up to 27 months, and rK39 results compared to those of crude antigen ELISA, PCR, clinical status and infectiousness to sandflies. We then searched MEDLINE and Web of Knowledge (1993-2011) for original studies evaluating the performance of rK39 RDTs in dogs. Meta-analysis of sensitivity and specificity was performed using bivariate mixed effects models. PRINCIPAL FINDINGS: The sensitivity of the rK39 RDT in Brazil to detect infection, disease and infectiousness was 46%, 77% and 78% respectively. Sensitivity increased with time since infection, antibody titre, parasite load, clinical score and infectiousness. Sixteen studies met the inclusion criteria for meta-analysis. The combined sensitivity of rK39 RDTs was 86.7% (95% CI: 76.9-92.8%) to detect clinical disease and 59.3% (37.9-77.6%) to detect infection. Combined specificity was 98.7% (89.5-99.9%). Both sensitivity and specificity varied considerably between studies. CONCLUSION: The diagnostic performance of rK39 RDTs is reasonable for confirmation of infection in suspected clinical cases, but the sensitivity to detect infected dogs is too low for large-scale epidemiological studies and operational control programmes.

Sand fly fauna in Chapare, Bolivia: an endemic focus of Leishmania (Viannia) braziliensis.

Data on the distribution and abundance of Lutzomyia spp. (Diptera: Psychodidae) in Bolivia is scarce. Sand flies from an area of Leishmania (Viannia) braziliensis endemicity in the Isiboro-Secure National Park in the Department of Cochabamba were captured and identified to species. In total, 945 sand flies (789 females and 156 males) belonging to 15 species were collected from the four collection points in two study villages in 2007. With 549 (58.1%) specimens, Lutzomyia shawi was the most abundant species, followed by Lutzomyia (Trichophoromyia) sp. (22.2%), Lutzomyia llanosmartinsi (8.3%), Lutzomyia antunesi (4.3%), and Lutzomyia olmeca (2.1%). Abundance and species composition varied between rainy and dry seasons, with 99.3% of all sand flies being collected outdoors. Because of species abundance and confirmed Leishmania infection in previous entomological collections, we believe Lu. shawi is the vector of L. (Viannia) braziliensis in Isiboro-Secure National Park.

Prevalence of Leishmania spp. infection in domestic dogs in Chapare, Bolivia.

Data on Leishmania spp. infection in dogs in Bolivia is scarce. Dogs from an area where 90% of human cutaneous leishmaniasis (CL) cases are due to Leishmania (Viannia) braziliensis were screened for Leishmania infection using established enzyme-linked immunosorbent antibody test (ELISA) protocols. Although none of the 51 dogs surveyed had clinical lesions indicative of CL, 6 out of 51 (11.8%) sampled dogs tested positive by ELISA.

Rapid detection of Trypanosoma cruzi in human serum by use of an immunochromatographic dipstick test.

We evaluated a commercially available immunochromatographic dipstick test to detect Trypanosoma cruzi infection in 366 human serum samples with known serological results from Argentina, Ecuador, Mexico, and Venezuela. One hundred forty-nine of 366 (40.7%) and 171/366 (46.7%) samples tested positive by dipstick and serology, respectively. Dipstick sensitivity was calculated to be 84.8% (range between countries, 77.5 to 95%), and specificity was 97.9% (95.9 to 100%).

Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia.

We describe the first case of Leishmania/HIV co-infection reported in Bolivia. Initially hospitalized with a diagnosis of pneumonia and bronchitis, the patient had numerous cutaneous and mucosal lesions caused by Leishmania (Viannia) braziliensis. The patient was also diagnosed as severely immunocompromised because of HIV infection.

Leishmaniases in Bolivia: comprehensive review and current status.

The leishmaniases are protozoan, zoonotic diseases transmitted to human and other mammal hosts by the bite of phlebotomine sandflies. Bolivia has the highest incidence of cutaneous leishmaniasis (CL) in Latin America (LA), with 33 cases per 100,000 population reported in 2006. CL is endemic in seven of the country's nine administrative departments. Visceral leishmaniasis (VL) is comparatively rare and is restricted to one single focus. Most CL cases are caused by Leishmania (Viannia) braziliensis (85% cases); VL is caused by L. (L.) infantum. Seven sandfly species are incriminated as vectors and Leishmania infections have been detected in several non-human mammal hosts. Transmission is associated with forest-related activities, but recently, cases of autochthonous, urban transmission were reported. Because most cases are caused by L. (V.) braziliensis, Bolivia reports the greatest ratio (i.e., up to 20% of all cases) of mucosal leishmaniasis to localized CL cases in LA. Per national guidelines, both CL and VL cases are microscopically diagnosed and treated with pentavalent antimony.

Effects of topical application of fipronil spot-on on dogs against the Chagas disease vector Triatoma infestans.

We assessed the insecticidal effects of fipronil spot-on applied to experimental dogs on the blood-feeding success and other vital parameters of the Trypanosoma cruzi vector Triatoma infestans. In the first trial, the cumulative mortality of 30 third or fourth instar nymphs exposed to eight fipronil-treated dogs differed significantly from those exposed to untreated dogs at 1 week post-treatment, but not at baseline or at 2-6 weeks post-treatment. In the second trial, the effects of multiple exposures to fipronil-treated dogs on bug population dynamics were assessed. A population of 80-84 bugs of various life stages were allowed to colonize eight closed experimental huts, and then exposed twice weekly to control or treated dogs over a period of 110 days and censused at monthly intervals. Throughout the trial, multiple exposure to fipronil did not significantly affect bug population size, fecundity, hatching, molting, survival, blood-feeding success and degree of engorgement. Only when engorgement was taken to include only fully fed bugs, did fipronil significantly reduce their degree of engorgement relative to bugs exposed to control dogs. We conclude that at tested dosages fipronil spot-on would have little effect in controlling (peri)domestic Tri. infestans or protecting dogs from contact with the bugs.

The efficacy of thermotherapy to treat cutaneous leishmaniasis in Colombia: a comparative observational study in an operational setting.

An open label, comparative study to compare the efficacy of thermotherapy to meglumine antimoniate in treating cutaneous leishmaniasis patients in an operational context was carried out in Chaparral, Colombia. After enrollment patients were followed-up for up to 100 days. Per protocol and intention-to-treat cure rates for 47 patients treated using thermotherapy (one-time 50 degrees C applications for 30s) were 100 and 19%, respectively. Per protocol and intention-to-treat cure rates for meglumine antimoniate (20 mg/kg body weight administered intramuscularly for 21 d) were 78 and 23%, respectively.

Short communication: The cost-effectiveness of cutaneous leishmaniasis patient management during an epidemic in Chaparral, Colombia in 2004.

We calculated ranges for the cost per disability adjusted life year (DALY) averted for cutaneous leishmaniasis (CL) treatment during an ongoing epidemic of CL in Chaparral, Colombia. Using operational clinical and cost data, we calculated that the cost of treating leishmaniasis patients with standard pentavalent antimony was US$345 (95% CI 277-488) per patient treated and cured. The cost per DALY averted per patient cured with antimony was estimated to be approximately US$15 000 (95% CI 12 226-21 532).

Use of an immunochromatographic dipstick test for rapid detection of Trypanosoma cruzi in sera from animal reservoir hosts.

We evaluated an immunochromatographic dipstick test to detect Trypanosoma cruzi in canine serum samples from areas of endemicity (n = 141) and nonendemicity (n = 28) for Chagas' disease with known serological and xenodiagnostic test results. The dipstick test had a specificity of at least 94% and a sensitivity of at least 96%. The dipstick tested could become the first choice for screening purposes in disease surveillance or intervention programs.

Extinction of experimental Triatoma infestans populations following continuous exposure to dogs wearing deltamethrin-treated collars.

Dogs are domestic reservoir hosts of Trypanosoma cruzi, the etiological agent of Chagas disease. We evaluated the effect of deltamethrin-treated dog collars (DTDCs) over time on the population dynamics of Triatoma infestans, a main T. cruzi vector. Forty founder bugs of mixed life stages were allowed to colonize mud-thatched experimental huts and exposed continuously to either uncollared control dogs (N = 3) or dogs wearing DTDCs (N = 7) for a period of up to 196 days. When compared with bugs exposed to control dogs, bugs exposed to collared dogs were shown to have reduced feeding success (odds ratio [OR] = 0.40; 95% confidence interval [CI], 0.26-0.63; P < 0.001) and lower survival (OR = 0.15; 95% CI, 0.08-0.29; P < 0.001); in fact, all of the bug populations exposed to collared dogs became extinct 77-196 days after study initiation. Bugs exposed to DTDC-wearing dogs were also shown to have a lower fecundity (i.e., number of eggs produced per live female bug: OR = 0.64; 95% CI, 0.51-0.81; P < 0.001) and molting rate to first-instar nymphs (OR = 0.32; 95% CI, 0.13-0.75; P < 0.01) than those bugs exposed to control dogs. DTDCs could represent a novel tool to prevent and control canine and (hence) human Chagas disease.

Are insecticide-impregnated dog collars a feasible alternative to dog culling as a strategy for controlling canine visceral leishmaniasis in Brazil?

In a zoonotic visceral leishmaniasis (ZVL)-endemic area in Brazil, deltamethrin-impregnated collars (DMC) were fitted to 136 dogs for 5 months and significantly reduced the odds of increasing their anti-Leishmania antibody titer during this period by 50% (95% confidence interval 29-87%, P=0.01), as compared with a population of 97 uncollared dogs with pre-intervention prevalence within the same town. Mathematical modeling suggests that under typical Brazilian ZVL-endemic conditions, the epidemiological impact of community-wide DMC application should be greater than the currently practiced dog culling strategy, but that its impact will be dependent on collar coverage and loss rate. Both interventions should have a higher proportional impact in regions of lower endemicity, but the relative advantage of DMC over culling increases with transmission rate. Sensitivity analyses indicate that the impact of either intervention is not significantly affected by variation in the biology of the sandfly vector, but is greatly influenced by variation in dog mortality and serorecovery rates.

The transmission dynamics of canine American cutaneous leishmaniasis in Huánuco, Peru.

The epidemiology of canine American cutaneous leishmaniasis (ACL) due to Leishmania (Viannia) spp. was investigated in Huánuco, Peru to 1) describe the natural course of canine L. (Viannia) infections and 2) assess the role of domestic dogs as ACL reservoir hosts. Over a three-year period 1,022 dogs were surveyed, with cumulative village L. (Viannia) prevalence being 26% (range = 0-100%). The incidence of L. (Viannia) was estimated to be 0.285 dogs/year (95% confidence interval [CI] = 0.160-0.410) using cross-sectional data and 0.291 dogs/year (95% CI = 0.195-0.387) using data from 108 dogs that were surveyed prospectively. The recovery rate was estimated to be 0.456 dogs/year (95% CI = 0.050-0.862) and 0.520 dogs/year (95% CI = 0.302-0.738), respectively. Using those findings, the basic reproduction number was estimated to be R0 approximately to 1.9; if dogs were the principal ACL reservoirs, the mean yearly effort (i.e., coverage or elimination) of a dog control intervention (e.g., collaring, culling, or vaccination) to ensure the elimination of L. (Viannia) spp. transmission would be as low as 47%.

Domestic dog ownership: a risk factor for human infection with Leishmania (Viannia) species.

An epidemiological study has shown that cumulative, village prevalence of Leishmania (Viannia) infection in dogs ranges from 8% to 45% in Huánuco, Peru. Using data from a prospective survey of human American cutaneous leishmaniasis (ACL) collected during 1994-98, it was shown that the village-level risk of human ACL did not significantly increase with dog abundance, neither in absolute terms (P = 0.659) nor in relation to dog:human ratios (P = 0.213). A significant positive association was observed between risk of human ACL and village dog ACL prevalence (P = 0.022). When controlled for village dog ACL prevalence, there also was an association between the average number of dogs per household and risk of human ACL (P = 0.033). The results suggest that dogs play a role in the (peri)domestic transmission of Le. (Viannia) to humans in Huánuco and indicate that a control intervention targeting dogs to control human ACL is warranted.

The epidemiology and control of leishmaniasis in Andean countries

Revisa o conhecimento atual sobre a epidemiologia da leishmaniose na Venezuela, Colômbia, Equador, Peru e Bolívia, países nos quais a doença é endêmica, tanto nos Andes quanto na Amazônia. Os vetores flebótomos pertencem a vários subgêneros e ao grupo Verrucarum. A maioria dos casos de infecçäo humana é causada pelos parasitas Leishmania do subgênero Viannia. As infecçöes humanas por Leishmania provocam lesöes cutâneas, com uma minoria de infecçöes por L. (Viannia) levando à leishmaniose mucocutânea. Tanto a leishmaniose visceral quanto a leishmaniose cutânea difusa säo raras. Em cada país, parte significativa da transmissäo de Leishmania ocorre no intra ou peridomicílio, muitas vezes próximo à lavoura de café ou cacau. Näo se sabe ao certo quais säo os hospedeiros reservatórios para os ciclos de transmissäo doméstica. Discute-se a carga da doença provocada pela leishmaniose na regiäo, chamando atençäo para os coeficientes de incidência e para a variabilidade dos sintomas. Tal informaçäo fornecerá uma base racional, visando priorizar os recursos voltados para o controle da doença e selecionar esquemas terapêuticos. Descreve também a variaçäo na ecologia da transmissäo, delineando as variáveis que poderiam afetar a definiçäo de estratégias preventivas.