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Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA.
RESUMO
Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. However, in low transmission settings where most mosquitoes become infected with only a single parasite clone, parasites recombine with themselves, and the clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive the persistence and abundance of Plasmodium falciparum clonal lineages in Guyana, a country with relatively low malaria transmission, but the only setting in the Americas in which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. To investigate whether this clonality was potentially associated with the persistence and spatial spread of the mutation, we performed whole genome sequencing on 1,727 Plasmodium falciparum samples collected from infected patients across a five-year period (2016-2021). We characterized the relatedness between each pair of monoclonal infections (n=1,409) through estimation of identity by descent (IBD) and also typed each sample for known or candidate drug resistance mutations. A total of 160 clones (mean IBD ≥ 0.90) were circulating in Guyana during the study period, comprising 13 highly related clusters (mean IBD ≥ 0.40). In the five-year study period, we observed a decrease in frequency of a mutation associated with artemisinin partner drug (piperaquine) resistance (pfcrt C350R) and limited co-occurence of pfcrt C350R with duplications of plasmepsin 2/3, an epistatic interaction associated with piperaquine resistance. We additionally report polymorphisms exhibiting evidence of selection for drug resistance or other phenotypes and reported a novel pfk13 mutation (G718S) as well as 61 nonsynonymous substitutions that increased markedly in frequency. However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation.
RESUMO
Current WHO guidelines set prevalence thresholds below which a neglected tropical disease can be considered to have been eliminated as a public health problem, and specify how surveys to assess whether elimination has been achieved should be designed and analysed, based on classical survey sampling methods. In this paper, we describe an alternative approach based on geospatial statistical modelling. We first show the gains in efficiency that can be obtained by exploiting any spatial correlation in the underlying prevalence. We then suggest that the current guidelines' implicit use of a significance testing argument is not appropriate; instead, we argue for a predictive inferential framework, leading to design criteria based on controlling the rates at which areas whose true prevalence lies above and below the elimination threshold are incorrectly classified. We describe how this approach naturally accommodates context-specific information in the form of georeferenced covariates that have been shown to be predictive of disease prevalence. Finally, we give a progress report of an ongoing collaboration with the Guyana Ministry of Health Neglected Tropical Disease programme on the design of an IDA (ivermectin, diethylcarbamazine and albendazole) Impact Survey of lymphatic filariasis to be conducted in Guyana in early 2023. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
