Search

Many models of within-host malaria infection dynamics have been formulated since the pioneering work of Anderson et al. in 1989. Biologically, the goal of these models is to understand what governs the severity of infections, the patterns of infectiousness, and the variation thereof across individual hosts. Mathematically, these models are based on dynamical systems, with standard approaches ranging from K-compartments ordinary differential equations (ODEs) to delay differential equations (DDEs), to capture the relatively constant duration of replication and bursting once a parasite infects a host red blood cell. Using malariatherapy data, which offers fine-scale resolution on the dynamics of infection across a number of individual hosts, we compare the fit and robustness of one of these standard approaches (K-compartments ODE) with a partial differential equations (PDEs) model, which explicitly tracks the "age" of an infected cell. While both models perform quite similarly in terms of goodness-of-fit for suitably chosen K, the K-compartments ODE model particularly overestimates parasite densities early on in infections when the number of repeated compartments is not large enough. Finally, the K-compartments ODE model (for suitably chosen K) and the PDE model highlight a strong qualitative connection between the density of transmissible parasite stages (i.e., gametocytes) and the density of host-damaging (and asexually-replicating) parasite stages. This finding provides a simple tool for predicting which hosts are most infectious to mosquitoes -vectors of Plasmodium parasites- which is a crucial component of global efforts to control and eliminate malaria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background: The measure of new drug- or vaccine-based approaches for malaria control is based on direct membrane feeding assays (DMFAs) where gametocyte-infected blood samples are offered to mosquitoes through an artificial feeder system. Gametocyte donors are identified by the microscopic detection and quantification of malaria blood stages on blood films prepared using either capillary or venous blood. However, parasites are known to sequester in the microvasculature and this phenomenon may alter accurate detection of parasites in blood films. The blood source may then impact the success of mosquito feeding experiments and investigations are needed for the implementation of DMFAs under natural conditions., Methods: Thick blood smears were prepared from blood obtained from asymptomatic children attending primary schools in the vicinity of Mfou (Cameroon) over four transmission seasons. Parasite densities were determined microscopically from capillary and venous blood for 137 naturally-infected gametocyte carriers. The effect of the blood source on gametocyte and asexual stage densities was then assessed by fitting cumulative link mixed models (CLMM). DMFAs were performed to compare the infectiousness of gametocytes from the different blood sources to mosquitoes., Results: Prevalence of Plasmodium falciparum asexual stages among asymptomatic children aged from 4 to 15 years was 51.8% (2116/4087). The overall prevalence of P. falciparum gametocyte carriage was 8.9% and varied from one school to another. No difference in the density of gametocyte and asexual stages was found between capillary and venous blood. Attempts to perform DMFAs with capillary blood failed., Conclusions: Plasmodium falciparum malaria parasite densities do not differ between capillary and venous blood in asymptomatic subjects for both gametocyte and trophozoite stages. This finding suggests that the blood source should not interfere with transmission efficiency in DMFAs.

Highly sensitive and field deployable molecular diagnostic tools are critically needed for detecting submicroscopic, yet transmissible levels of malaria parasites prevalent in malaria endemic countries worldwide. A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and evaluated in comparison with thick blood smear microscopy, an antigen-based rapid diagnostic test (RDT), and an in-house RT-PCR targeting the same RT-LAMP transcript. The optimized assay detected Plasmodium falciparum infections in as little as 0.25ng of total parasite RNA, and exhibited a detection limit of 0.08 parasites/ μL when tested directly on infected whole blood lysates, or ~0.0008 parasites/ μL when using RNA extracts. Assay positivity was observed as early as eight minutes from initiation of the RT-LAMP and in most cases the reaction was complete before twenty minutes. Clinical evaluation of the assay on 132 suspected malaria cases resulted in a positivity rate of 90% for RT-LAMP using extracted RNA, and 85% when using whole blood lysates. The positivity rates were 70% for P. falciparum-specific RDT, 83% for RT-PCR, and 74% for thick blood smear microscopy (Mean parasite density = 36,986 parasites/ μL). Concordance rates between the developed RT-LAMP and comparator tests were greater than 75%, the lowest being with light microscopy (78%, McNemar's test: P = 0.0002), and the highest was with RT-PCR (87%, McNemar's test: P = 0.0523). Compared to reference RT-PCR, assay sensitivity was 90% for RT-LAMP on whole blood, and 96% for RT-LAMP using corresponding RNA extracts. Electricity-free heaters were further developed and evaluated in comparison with a battery-operated isothermal amplification machine for use with the developed test in resource-limited settings. Taken together, the data highlight the benefits of targeting high abundant RNA transcripts in molecular diagnosis, as well as the potential usefulness of the developed RT-LAMP-assay in malaria diagnosis in low to high parasite density settings., Competing Interests: The authors have declared that no competing interests exist.

We obtained health surveillance epidemiologic data on malaria among French military personnel deployed to French Guiana during 1998-2008. Incidence of Plasmodium vivax malaria increased and that of P. falciparum remained stable. This new epidemiologic situation has led to modification of malaria treatment for deployed military personnel.

Background: The effectiveness of malaria chemoprophylaxis is limited by the lack of compliance whose determinants are not well known., Methods: The compliance with malaria chemoprophylaxis has been estimated and analysed by validated questionnaires administered before and after the short-term missions (about four months) in five tropical African countries of 2,093 French soldiers from 19 military companies involved in a prospective cohort study. "Correct compliance" was defined as "no missed doses" of daily drug intake during the entire mission and was analysed using multiple mixed-effect logistic regression model., Results: The averaged prevalence rate of correct compliance was 46.2%, ranging from 9.6%to 76.6% according to the companies. Incorrect compliance was significantly associated with eveningness (p = 0.028), a medical history of clinical malaria (p < 0.001) and a perceived mosquito attractiveness inferior or superior to the others (p < 0.007). Correct compliance was significantly associated with the systematic use of protective measures against mosquito bites (p < 0.001), the type of military operations (combat vs. training activities, p < 0.001) and other individual factors (p < 0.05)., Conclusions: The identification of circumstances and profiles of persons at higher risk of lack of compliance would pave the way to specifically targeted strategies aimed to improve compliance with malaria chemoprophylaxis and, therefore, its effectiveness.