Filtering by
- All Subjects: Mosquito
- All Subjects: Non-adherence
- Creators: Paaijmans, Krijn
- Creators: Phillips, Keeley Isabella
Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in about 15% of parasites that develop ookinetes in the mosquito abdomen, sporozoites never develop in the salivary glands, indicating that passage across the midgut lumen is a significant barrier in parasite development (Gamage-Mendis et al., 1993). We aim to investigate a possible correlation between passage through the midgut lumen and drug-resistance trends in Plasmodium falciparum parasites. This study contains a total of 1024 Anopheles mosquitoes: 187 Anopheles gambiae and 837 Anopheles funestus samples collected in high malaria transmission areas of Mozambique between March and June of 2016. Sanger sequencing will be used to determine the prevalence of known resistance alleles for anti-malarial drugs: chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1) gene, dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr). We compare prevalence of resistance between abdomen and head/thorax in order to determine whether drug resistant parasites are disproportionately hindered during their passage through the midgut lumen. A statistically significant difference between resistance alleles in the two studied body sections supports the efficacy of new anti-malarial gene surveillance strategies in areas of high malaria transmission.
Treatment non-adherence is a less focused (so far) but crucial factor for the hindrance in WHO’s past VL elimination goals. Moreover, treatment non-adherers, hidden from surveillance, lead to high case-underreporting. Dynamical models are developed capturing the role of treatment-related human behaviors (patients’ infectivity, treatment access and non-adherence) on VL dynamics. The results suggest that the average duration of treatment adherence must be increased from currently 10 days to 17 days for a 28-day Miltefosine treatment to eliminate VL.
For STH, children are considered as a high-risk group due to their hygiene behaviors leading to higher exposure to contamination. Hence, Ghana, a resource-limited country, currently implements a school-based Mass Drug Administration (sMDA) program only among children. School staff (adults), equally exposed to this high environmental contamination of STH, are largely ignored under the current MDA program. Cost-effective MDA policies were modeled and compared using alternative definitions of “high-risk population”. This work optimized and evaluated how MDA along with the treatment for high-risk adults makes a significant improvement in STH control under the same budget. The criticality of risk-structured modeling depends on the infectivity coefficient being substantially different for the two adult risk groups.
This dissertation pioneers in highlighting the cruciality of treatment-related risk groups for NTD-control. It provides novel approaches to quantify relevant metrics and impact of population factors. Compliance with the principles and strategies from this study would require a change in political thinking in the neglected regions in order to achieve persistent NTD-control.