Dataset Information

High Genetic Diversity of Plasmodium falciparum in the Low-Transmission Setting of the Kingdom of Eswatini.

ABSTRACT:

Background

To better understand transmission dynamics, we characterized Plasmodium falciparum genetic diversity in Eswatini, where transmission is low and sustained by importation.

Methods

Twenty-six P. falciparum microsatellites were genotyped in 66% of confirmed cases (2014-2016; N = 582). Population and within-host diversity were used to characterize differences between imported and locally acquired infections. Logistic regression was used to assess the added value of diversity metrics to classify imported and local infections beyond epidemiology data alone.

Results

Parasite population in Eswatini was highly diverse (expected heterozygosity [HE] = 0.75) and complex: 67% polyclonal infections, mean multiplicity of infection (MOI) 2.2, and mean within-host infection fixation index (FWS) 0.84. Imported cases had comparable diversity to local cases but exhibited higher MOI (2.4 vs 2.0; P = .004) and lower mean FWS (0.82 vs 0.85; P = .03). Addition of MOI and FWS to multivariate analyses did not increase discrimination between imported and local infections.

Conclusions

In contrast to the common perception that P. falciparum diversity declines with decreasing transmission intensity, Eswatini isolates exhibited high parasite diversity consistent with high rates of malaria importation and limited local transmission. Estimates of malaria transmission intensity from genetic data need to consider the effect of importation, especially as countries near elimination.

SUBMITTER: Roh ME

PROVIDER: S-EPMC6743842 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

High Genetic Diversity of Plasmodium falciparum in the Low-Transmission Setting of the Kingdom of Eswatini.

Roh Michelle E ME Tessema Sofonias K SK Murphy Maxwell M Nhlabathi Nomcebo N Mkhonta Nomcebo N Vilakati Sibonakaliso S Ntshalintshali Nyasatu N Saini Manik M Maphalala Gugu G Chen Anna A Wilheim Jordan J Prach Lisa L Gosling Roly R Kunene Simon S S Hsiang Michelle M Greenhouse Bryan B

The Journal of infectious diseases 20190901 8

<h4>Background</h4>To better understand transmission dynamics, we characterized Plasmodium falciparum genetic diversity in Eswatini, where transmission is low and sustained by importation.<h4>Methods</h4>Twenty-six P. falciparum microsatellites were genotyped in 66% of confirmed cases (2014-2016; N = 582). Population and within-host diversity were used to characterize differences between imported and locally acquired infections. Logistic regression was used to assess the added value of diversity ...[more]

PMID: 31190073

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Project description:BACKGROUND: The population structure of the causative agents of human malaria, Plasmodium sp., including the most serious agent Plasmodium falciparum, depends on the local epidemiological and demographic situations, such as the incidence of infected people, the vector transmission intensity and migration of inhabitants (i.e. exchange between sites). Analysing the structure of P. falciparum populations at a large scale, such as continents, or with markers that are subject to non-neutral selection, can lead to a masking and misunderstanding of the effective process of transmission. Thus, knowledge of the genetic structure and organization of P. falciparum populations in a particular area with neutral genetic markers is needed to understand which epidemiological factors should be targeted for disease control. Limited reports are available on the population genetic diversity and structure of P. falciparum in Thailand, and this is of particular concern at the Thai-Myanmar and Thai-Cambodian borders, where there is a reported high resistance to anti-malarial drugs, for example mefloquine, with little understanding of its potential gene flow. METHODS: The diversity and genetic differentiation of P. falciparum populations were analysed using 12 polymorphic apparently neutral microsatellite loci distributed on eight of the 14 different chromosomes. Samples were collected from seven provinces in the western, eastern and southern parts of Thailand. RESULTS: A strong difference in the nuclear genetic structure was observed between most of the assayed populations. The genetic diversity was comparable to the intermediate level observed in low P. falciparum transmission areas (average HS = 0.65 +/- 0.17), where the lowest is observed in South America and the highest in Africa. However, uniquely the Yala province, had only a single multilocus genotype present in all samples, leading to a strong geographic differentiation when compared to the other Thai populations during this study. Comparison of the genetic structure of P. falciparum populations in Thailand with those in the French Guyana, Congo and Cameroon revealed a significant genetic differentiation between all of them, except the two African countries, whilst the genetic variability of P. falciparum amongst countries showed overlapping distributions. CONCLUSION: Plasmodium falciparum shows genetically structured populations across local areas of Thailand. Although Thailand is considered to be a low transmission area, a relatively high level of genetic diversity and no linkage disequilibrium was found in five of the studied areas, the exception being the Yala province (Southern peninsular Thailand), where a clonal population structure was revealed and in Kanchanaburi province (Western Thailand). This finding is particularly relevant in the context of malaria control, because it could help in understanding the special dynamics of parasite populations in areas with different histories of, and exposure to, drug regimens.

Project description:BackgroundMalaria transmission depends on the presence of gametocytes in the peripheral blood of infected human hosts. Understanding malaria infectious reservoirs enables transmission-blocking interventions to target the most important hosts for the disease. This study characterized the distribution of gametocyte carriage as a baseline for the clinical evaluation of a Pfs25-based transmission-blocking vaccine candidate in Bagamoyo, Tanzania.MethodsA malaria survey was conducted in five locations from May to August 2022. A total of 467 participants-192 children (5-12 years), 65 adolescents (13-17 years) and 210 adults (18-45 years)-were enrolled. Malaria was detected using three methods: rapid diagnostic tests, light microscopy and quantitative polymerase chain reaction. The geometric mean of the gametocyte density, and weighted arithmetic mean of the gametocytes sex ratio were estimated.ResultsOverall, 23.5% (110/467) of the participants tested positive for malaria parasites, with the majority of positives (> 92%) being Plasmodium falciparum. The overall gametocytaemia was 5.6%, with a percent positivity of 6.8% (13/192), 6.2% (4/65) and 4.3% (9/210), in children, adolescents, and adults, respectively. The geometric mean gametocyte density (gametocytes/μL) was greater in adults (124.6) than in children (71.7) and adolescents (50.5). Regression analysis revealed that gametocytes were more likely to be present among male participants than among female participants [ORa: 2.79 (95% CI: 1.19 - 6.59) p = 0.019]. The gametocyte sex ratio in children and adult gametocyte carriers was similar but greater than that in adolescents.ConclusionThe observed gametocyte densities and distribution across age groups suggest the need for malaria transmission-blocking interventions to target all populations in heterogeneous transmission settings. The implication of targeting only children may leave residual malaria transmission and reinfection from the left-out groups.

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Dataset Information

High Genetic Diversity of Plasmodium falciparum in the Low-Transmission Setting of the Kingdom of Eswatini.

Background

Methods

Results

Conclusions

Publications

High Genetic Diversity of Plasmodium falciparum in the Low-Transmission Setting of the Kingdom of Eswatini.

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