Molecular xenomonitoring for post-validation surveillance of lymphatic filariasis in Togo: no evidence for active transmission.

BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne filarial disease targeted for elimination by the year 2020. The Republic of Togo undertook mass treatment of entire endemic communities from 2000 to 2009 to eliminate the transmission of the disease and is currently the first sub-Saharan African country to be validated by WHO for the elimination of LF as a public health problem. However, post-validation surveillance activities are required to ensure the gains achieved are sustained. This survey assessed the mosquito vectors of the disease and determined the presence of infection in these vectors, testing the hypothesis that transmission has already been interrupted in Togo. METHOD: Mosquitoes were collected from 37 villages located in three districts in one of four evaluation units in the country. In each district, 30 villages were selected based on probability proportionate to size; eight villages (including one of the 30 villages already selected) where microfilaremia-positive cases had been identified during post-treatment surveillance activities were intentionally sampled. Mosquitoes were collected using pyrethrum spray collections (PSC) in households randomly selected in all villages for five months. In the purposefully selected communities, mosquitoes were also collected using human landing collections (HLC) and exit traps (ET). Collected mosquitoes were identified morphologically, and the identification of Wuchereria bancrofti DNA in the mosquitoes was based on the pool screening method, using the LAMP assay. RESULTS: A total of 15,539 mosquitoes were collected during the study. Anopheles gambiae (72.6%) was the predominant LF vector collected using PSC. Pool screen analysis of 9191 An. gambiae in 629 pools revealed no mosquitoes infected with W. bancrofti (0%; CI: 0-0.021). CONCLUSIONS: These results confirm the findings of epidemiological transmission assessment surveys conducted in 2012 and 2015, which demonstrated the absence of LF transmission in Togo. The challenges of implementing molecular xenomonitoring are further discussed.

A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Evaluation of the 2011 long-lasting, insecticide-treated net distribution for universal coverage in Togo.

BACKGROUND: Malaria remains a substantial public health problem in Togo. An integrated child health campaign was conducted in Togo in October 2011. This campaign included a component of free distribution of 2,799,800 long-lasting, insecticide-treated nets (LLINs) to households throughout Togo. This distribution marked the first effort in Togo at universal LLIN coverage and was not targeted specifically to children under five years and pregnant women, but to all household members. This study reports the results of the LLIN distribution campaign in terms of bed net possession and utilization. METHODS: A representative household survey was implemented during the rainy season nine months after the LLIN distribution component of the campaign. Some 6,015 households selected through two stages of probability proportion to size stratified random sampling were interviewed using a brief questionnaire that included a demographic section with questions on the number of household members and sleeping spaces, and a campaign participation section with questions used to evaluate non-LLIN aspects of the campaign. A net roster listed all nets and their characteristics, and a household roster listed all members and visitors with information about bed net use. The questions addressed different aspects of bed net and LLIN possession and utilization. Crude weighted frequencies, percentages, and t- tests of association were calculated using the Stata 12.0 Survey features. RESULTS: Possession of at least one bed net and/or LLIN increased from 41.3% to 96.7% (P <0.001). Household possession of at least one campaign LLIN was 93.3%. Report LLIN among pregnant women was 77.5% and 79.3% for children under five. For the general population LLIN use was 68.3%. CONCLUSIONS: Due to the gap in LLIN possession and use and the significant number of individuals reporting a lack of nets as a reason for non-use, additional national LLIN distribution campaigns with a stronger educational component need to be implemented in order increase the use of available LLINs and to reach and maintain universal coverage of LLINs in Togo. The LLIN distribution campaign focusing on universal coverage of the general population in Togo was more successful at increasing LLIN possession and use of children under five years and pregnant women than other campaigns focusing only on these target groups.

Surveillance of the efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum among children under five in Togo, 2005-2009.

BACKGROUND: Malaria remains a major public health problem in Togo. The national malaria control programme in Togo changed the anti-malarial treatment policy from monotherapy to artemisinin combination therapy in 2004. This study reports the results of therapeutic efficacy studies conducted on artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Togo, between 2005 and 2009. METHODS: Children between 6 and 59 months of age, who were symptomatically infected with P. falciparum, were treated with either artemether-lumefantrine or artesunate-amodiaquine. The primary end-point was the 28-day cure rate, PCR-corrected for reinfection and recrudescence. Studies were conducted according to the standardized WHO protocol for the assessment of the efficacy of anti-malarial treatment. Differences between categorical data were compared using the chi-square test or the Fisher's exact test where cell counts were ≤ 5. Differences in continuous data were compared using a t-test. RESULTS: A total of 16 studies were conducted in five sentinel sites, with 459, 505 and 332 children included in 2005, 2007 and 2009, respectively. The PCR-corrected 28-day cure rates using the per-protocol analysis were between 96%-100% for artemether-lumefantrine and 94%-100% for artesunate-amodiaquine. CONCLUSIONS: Both formulations of artemisinin-based combination therapy were effective over time and no severe adverse events related to the treatment were reported during the studies.