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Pryce, Joseph (2022) Molecular xenomonitoring and xenosurveillance: exploring the potential of entomological screening for the integrated surveillance of neglected tropical diseases, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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J Pryce Final Thesis.pdf - Accepted Version Download (5MB) | Preview |
Abstract
Substantial progress has been made in recent years towards the elimination of neglected tropical diseases (NTDs) including Lymphatic Filariasis (LF) and onchocerciasis, but traditional surveillance methods have limited usefulness for assessments of transmission interruption and post-interruption monitoring. To avoid the risk of recrudescence, there is a need for new methods that are both sensitive and sustainable. Molecular xenomonitoring (MX), the screening of vector insects for the presence of pathogen genetic material, may provide a non-invasive solution. However, its use has been limited by a poor understanding of the sensitivity of MX, the relationship between MX results and human prevalence, and the influence of sampling strategy on the likelihood of detecting exposed vectors. Mosquitoes can be screened for multiple pathogens at once, including those not vectored by mosquitoes, providing optimism that MX could one day provide a mechanism for the integrated surveillance of NTDs. The feasibility of this approach, and a knowledge of which pathogens will be amenable to mosquito-based surveillance, also remains to be fully explored. This research project aimed to investigate these areas of uncertainty, firstly by employing meta-analytical methods to draw novel conclusions from previously-conducted studies, and secondly by using laboratory and field-based methods to collect new data.
The results of this research suggest that, in comparison to traditional methods based on the detection of microfilaria (mf) in human biological samples, MX is highly sensitive to communities with ongoing transmission of LF and onchocerciasis. Furthermore, evidence of a significant linear relationship between MX rates and mf prevalence was found. For both diseases, approximately half of the variation in MX rate was explained by variation in the human mf prevalence. The remaining variation may be explained by differences in study site and sampling methodology. For LF, studies that used consistent mosquito collection methods in the same location over time provided evidence of a strong correlation between MX rates and mf prevalence (R2 = 0.78, p<0.001).
Data from previously-conducted studies suggest that, in given study sites, the rates of parasite detection in collected mosquitoes (MX rates) can differ markedly depending on the mosquito collection method used, though it was not possible to obtain precise and consistent estimates of this impact. In areas of Anopheles-vectored LF, MX rates were approximately seven times higher in Anopheles mosquitoes than Culex mosquitoes (RR 6.91, 95% CI 1.73 to 27.5). MX rates were also found to be significantly higher when DNA was extracted from mosquito carcasses than when extracted from mosquito excreta (Rate Ratio 4.49, 95% CI 2.75 to 7.33).
This finding was corroborated by a subsequent field study which aimed to explore the feasibility of screening mosquito carcasses and excreta for the non-mosquito-borne filarial parasite Loa loa. The study was conducted in a known L. loa transmission area in the Nyong River basin in Cameroon. Although L. loa is diurnally periodic, and the majority of the 770 mosquitoes collected during the study were nocturnally-active Anopheles species, L. loa DNA was detected in both the carcasses and excreta of collected mosquitoes. Further demonstrating the potential of mosquitoes as a sampling target for integrated disease surveillance, DNA from each of the causative agents of LF, mansonellosis and malaria were also detected in the collected samples.
Overall, the findings of this research demonstrate that MX has clear potential as tool for detecting communities with LF and onchocerciasis and as a predictor of human mf prevalence. Current WHO guidelines state a target sample size of mosquitoes to be screened to have certainty in the absence of LF but make no specifications about the preferred target species or sampling method. Programmes looking to implement MX should be aware that the collection method used and genera of mosquito collected can significantly affect the likelihood of detecting parasite DNA.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Subjects: | QX Parasitology > QX 20 Research (General) QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General) |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Depositing User: | Lynn Roberts-Maloney |
| Date Deposited: | 20 Sep 2022 09:37 |
| Last Modified: | 20 Dec 2022 02:02 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/21169 |
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