Yukich, J. O. | Search bioRxiv

bioRxiv2023

Highly multiplexed ddPCR-amplicon sequencing reveals strong Plasmodium falciparum population structure and isolated populations amenable to local elimination efforts in Zanzibar

Over the past 15 years, Zanzibar has made great strides towards malaria elimination; yet progress has stalled. Parasite genetic data of Plasmodium falciparum may inform strategies for malaria elimination by helping to identify contributory factors to parasite persistence. Here we elucidate fine-scale parasite population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. We sequenced 518 P. falciparum samples from 5 districts covering both main islands using a novel, highly multiplexed droplet digital PCR (ddPCR)-based amplicon deep sequencing method targeting 35 microhaplotypes and drug-resistance loci. Despite high genetic diversity, we observe strong fine-scale spatial and temporal structure of local parasite populations, including isolated populations on Pemba Island and genetically admixed populations on Unguja Island, providing evidence of ongoing local transmission. We observe a high proportion of highly related parasites in individuals living closer together, including between clinical index cases and the mostly asymptomatic cases surrounding them, consistent with isolation-by-distance. We identify a substantial fraction (2.9%) of related parasite pairs between Zanzibar, and mainland Tanzania and Kenya, consistent with recent importation. We identify haplotypes known to confer resistance to known antimalarials in all districts, including multidrug-resistant parasites, but most parasites remain sensitive to current first-line treatments. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and reveals actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination.

genomics↗

bioRxiv2019

Quantification of human-mosquito contact rate using surveys and its application in determining dengue viral transmission risk

Aedes-borne viral diseases, including dengue fever, chikungunya, and Zika, have been surging in incidence and spreading to new areas where their mosquito vectors thrive. To estimate viral transmission risks, availability of accurate local transmission parameters is essential. One of the most important parameters to determine infection risk is the human-mosquito contact rate. However, this rate has rarely been characterized due to the lack of a feasible research method. In this study, human-mosquito contact rates were evaluated in two study sites within the Greater New Orleans Region by asking a group of survey participants to estimate mosquito bites they experienced in the past 24 hours. The fraction of the mosquito bites attributed to Ae. aegypti or Ae. albopictus was estimated by human landing sampling. The results showed a significantly higher outdoor mosquito bite exposure than indoor exposure. The number of reported mosquito bites was positively correlated with the time that study participants spent outside during at-risk periods. There was also a significant effect of the study site on outdoor bite exposure, possibly because of the difference in the numbers of host-seeking mosquitoes. We use a mathematical dengue virus transmission model to estimate the transmission risks in the study areas based on local conditions. This compartmental model demonstrated how the observed difference in the human-Aedes contact rates in the two study sites would result in differential dengue transmission risks. This study highlights the practicality of using a survey to estimate human-mosquito contact rates and serves as a basis for future evaluations. Combined with the use of mathematical modeling, this innovative method may lead to more effective mosquito-borne pathogen prevention and control.\n\nAuthor summaryEven though the human-mosquito contact rate is among the most important indicators of mosquito-borne viral transmission risk, it is rarely characterized in the field. Human Landing Capture is a gold standard method to quantify this rate, but it ignores variables such as human behaviors and lifestyles. In this study, we tested the feasibility of using surveys to quantify mosquito bite exposure in the Southern United States. The survey results, combined with mosquito species proportion data, were used to estimate the contact rate. These rates are key parameters used in mathematical models to determine transmission risks. We found that bite exposure occurred more often outside homes and people who spent more time outdoors in the evening and night had a higher exposure. Our model analysis shows that the human-mosquito contact rate is one of the most important parameters determining outbreak potential. Disease control programs should focus their efforts on reducing this rate in addition to the mosquito density. Future studies should test if the entomological contact rates described by surveys correlate with disease incidences or other entomological indices. This study highlights the importance of characterizing how vector-human contact rates may respond to changing human behaviors and environments.

ecology↗