Madsen Beau de Rochars

A multicenter evaluation of diagnostic tools to define endpoints for programs to eliminate bancroftian filariasis

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes—qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative.

Endpoints for lymphatic filariasis programs.

In 2000, annual mass administration of diethlycarbamazine and albendazole began in Leogane Commune, Haiti, to interrupt transmission of lymphatic filariasis (LF). After 5 years of treatment, microfilaremia, antigenemia, and mosquito infection rates were significantly reduced, but LF transmission was not interrupted. These finding have implications for other LF elimination programs.

Participation in three consecutive mass drug administrations in Leogane, Haiti.

Objectives  In the global effort to eliminate lymphatic filariasis, mass drug administrations (MDAs) are organised annually. The success of this strategy depends on achieving high levels of drug coverage, which reduce the number of persons with circulating microfilariae and consequently transmission. Persons who consistently fail to participate in MDAs represent a potential threat to the goal of filariasis elimination. We wanted to know the drug coverage, the proportion of persons who were systematically non‐compliant and factors associated with this behaviour.

Performance of the CareStart Glucose-6-Phosphate Dehydrogenase (G6PD) Rapid Diagnostic Test in Gressier, Haiti

Administering primaquine (PQ) to treat malaria patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can pose a serious risk of drug-induced hemolysis (DIH). New easy to use point-of-care rapid diagnostic tests are being developed as an alternative to labor-intensive spectrophotometric methods, but they require field testing before they can be used at scale. This study screened 456 participants in Gressier, Haiti using the Access Bio CareStart qualitative G6PD rapid detection test compared with the laboratory-based Trinity Biotech quantitative spectrophotometric assay. Findings suggest that the CareStart test was 90% sensitive for detecting individuals with severe deficiency and 84.8% sensitive for detecting individuals with moderate and severe deficiency compared with the Trinity Biotech assay. A high negative predictive value of 98.2% indicates excellent performance in determining those patients able to take PQ safely. The CareStart G6PD test holds much value for screening malaria patients to determine eligibility for PQ therapy.

Assessing the Impact of a Missed Mass Drug Administration in Haiti

Lymphatic filariasis (LF) is a disfiguring and debilitating parasitic disease that is endemic in 81 countries, placing a staggering 1.3 billion people at risk for filarial infection [1]. In 1997, the World Health Assembly resolved to eliminate LF as a public health problem, and in 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) was officially launched. Coupled with the development of essential diagnostic tools, the primary strategy devised to achieve LF elimination was to implement annual mass drug administration (MDA) using combinations of albendazole plus either diethylcarbamazine or ivermectin for at-risk populations [2]. These single-dose treatment regimens were chosen for their ability to significantly reduce microfilaremia for periods of up to one year, limiting the transmission potential. Through generous donations of drugs from GlaxoSmithKline and Merck & Co., the global program began its first treatments in 2000. Since then, 48 of the 81 endemic countries have implemented MDA and almost 2 billion treatments have been provided [1]. These treatments have led to dramatic reductions in microfilaremia and have provided significant collateral benefit by reducing soil-transmitted helminthiasis [3],[4]. Furthermore, more than 6 million cases of hydrocele and 4 million cases of lymphedema have been prevented in the last eight years, translating into more than 32 million disability-adjusted life years averted [3]. Through the efforts of a national program, China became the first country to declare the elimination of LF as a public health problem, and in March 2008, the Republic of Korea also made a similar announcement [1].

Water-related infrastructure in a region of post-earthquake Haiti: high levels of fecal contamination and need for ongoing monitoring.

We inventoried non-surface water sources in the Leogane and Gressier region of Haiti (approximately 270 km2) in 2012 and 2013 and screened water from 345 sites for fecal coliforms and Vibrio cholerae. An international organization/non-governmental organization responsible for construction could be identified for only 56% of water points evaluated. Sixteen percent of water points were non-functional at any given time; 37% had evidence of fecal contamination, with spatial clustering of contaminated sites. Among improved water sources (76% of sites), 24.6% had fecal coliforms versus 80.9% in unimproved sources. Fecal contamination levels increased significantly from 36% to 51% immediately after the passage of Tropical Storm Sandy in October of 2012, with a return to 34% contamination in March of 2013. Long-term sustainability of potable water delivery at a regional scale requires ongoing assessment of water quality, functionality, and development of community-based management schemes supported by a national plan for the management of potable water.

Therapeutic Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum in Haiti after Many Decades of its Use

Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20-97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti.

A Tale of Two Flaviviruses: A Seroepidemiological Study of Dengue Virus and West Nile Virus Transmission in the Ouest and Sud-Est Departments of Haiti

Though plans to eliminate malaria from the island of Hispaniola have recently received much attention, arbovirus surveillance continues to be largely neglected in Haiti. To support surveillance efforts and encourage vector-control strategies, a cross-sectional study of dengue virus (DENV) and West Nile virus (WNV) transmission was conducted using standard seroepidemiological methods. Blood samples (N = 673) were collected from 278 males and 395 females from three locations in the Ouest and Sud-Est Departments of Haiti. Serum was separated and tested for the presence of anti-DENV and anti-WNV immunoglobulin G (IgG) antibodies using an indirect enzyme-linked immunosorbent assay (ELISA). Anti-DENV IgG antibodies were detected in 72.1% (95% confidence interval [CI] = 68.7, 75.5) of the sample population; with no significant differences in seroprevalence by study location, participant gender, or age group (P > 0.1, in all tests). Anti-WNV IgG antibodies were detected in only 1% (95% CI = 0.3, 1.8) of the sample population, all which originated from participants located in Gressier. The high prevalence of anti-DENV IgG antibodies among all age groups, including those in the youngest age group (2-5 years of age), suggests hyperendemic transmission of DENV in the Ouest and Sud-Est Departments of Haiti. In contrast, the relative absence of anti-WNV IgG antibodies, even among older population members, further supports the notion that WNV transmission in this population is largely absent. These findings highlight the large burden of disease from DENV and the need for enhanced arbovirus surveillance and implementation of vector control strategies throughout Haiti.

Translating Research into Reality: Elimination of Lymphatic Filariasis from Haiti

Abstract. Research provides the essential foundation of disease elimination programs, including the global program to eliminate lymphatic filariasis (GPELF). The development and validation of new diagnostic tools and intervention strategies, critical steps in the evolution of GPELF, required a global effort. Lymphatic filariasis research in Haiti involved many partners and was directly linked to the development of the national elimination program and to the success achieved to date. Ongoing research efforts involving many partners will continue to be important in resolving the challenges faced by the program today in its final efforts to achieve elimination.

Clinical and Epidemiologic Patterns of Chikungunya Virus Infection and Coincident Arboviral Disease in a School Cohort in Haiti, 2014–2015

Abstract Background Beginning in December 2013, an epidemic of chikungunya virus (CHIKV) infection spread across the Caribbean and into virtually all countries in the Western hemisphere, with >2.4 million cases reported through the end of 2017. Methods We monitored a cohort of school children in rural Haiti from May 2014, through February 2015, for occurrence of acute undifferentiated febrile illness, with clinical and laboratory data available for 252 illness episodes. Results Our findings document passage of the major CHIKV epidemic between May and July 2014, with 82 laboratory-confirmed cases. Subsequent peaks of febrile illness were found to incorporate smaller outbreaks of dengue virus serotypes 1 and 4 and Zika virus, with identification of additional infections with Mayaro virus, enterovirus D68, and coronavirus NL63. CHIKV and dengue virus serotype 1 infections were more common in older children, with a complaint of arthralgia serving as a significant predictor for infection with CHIKV (odds ratio, 16.2; 95% confidence interval, 8.0–34.4; positive predictive value, 66%; negative predictive value, 80%). Conclusions Viral/arboviral infections were characterized by a pattern of recurrent outbreaks and case clusters, with the CHIKV epidemic representing just one of several arboviral agents moving through the population. Although clinical presentations of these agents are similar, arthralgias are highly suggestive of CHIKV infection.