Can field-based mosquito feeding assays be used for evaluating transmission-blocking interventions?

A recent meta-analysis of mosquito feeding assays to determine the Plasmodium falciparum transmission potential of naturally infected gametocyte carriers highlighted considerable variation in transmission efficiency between assay methodologies and between laboratories. This begs the question as to whether mosquito feeding assays should be used for the evaluation of transmission-reducing interventions in the field and whether these field-based mosquito assays are currently standardized sufficiently to enable accurate evaluations. Here, we address biological and methodological reasons for the observed variations, discuss whether these preclude the use of field-based mosquito feeding assays in field evaluations of transmission-blocking interventions, and propose how we can maximize the precision of estimates. Altogether, we underscore the significant advantages of field-based mosquito feeding assays in basic malaria research and field trials

Determinants of Malaria Transmission at the Population Level

Transmission of malaria from man to mosquito defines the human infectious reservoir of malaria. At the population level this is influenced by a variety of human, parasite, and mosquito vector factors some or all of which may vary depending on the epidemiological setting. Here, we review our current state of knowledge related to human infectiousness to mosquitoes and how current malaria control strategies might be adapted to focus on reducing this. While much progress has been made in malaria control, we argue that an improved understanding of human infectivity will allow more effective use of current control tools and make elimination a more feasible goal. C onsiderable progress has been made in our understanding of the production and maturation of Plasmodium falciparum gametocytes and associated factors related to the biology of malaria transmission at the level of the individual malaria-infected patient

Two-Faced Immunity? The Evidence for Antibody Enhancement of Malaria Transmission.

Plasmodium gametocytes can induce an immune response in humans that interferes with the development of sexual-stage parasites in the mosquito gut. Many early studies of the sexual-stage immune response noted that mosquito infection could be enhanced as well as reduced by immune sera. For Plasmodium falciparum, these reports are scarce, and the phenomenon is generally regarded as a methodological artefact. Plasmodium transmission enhancement (TE) remains contentious, but the clinical development of transmission-blocking vaccines based on sexual-stage antigens requires that it is further studied. In this essay, we review the early literature on the sexual-stage immune response and transmission-modulating immunity. We discuss hypotheses for the mechanism of TE, suggest experiments to prove or disprove its existence, and discuss its possible implications

Low-dose primaquine for falciparum malaria

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Malaria Hotspots: Is There Epidemiological Evidence for Fine-Scale Spatial Targeting of Interventions?

As data at progressively granular spatial scales become available, the temptation is to target interventions to areas with higher malaria transmission - so-called hotspots - with the aim of reducing transmission in the wider community. This paper reviews literature to determine if hotspots are an intrinsic feature of malaria epidemiology and whether current evidence supports hotspot-targeted interventions. Hotspots are a consistent feature of malaria transmission at all endemicities. The smallest spatial unit capable of supporting transmission is the household, where peri-domestic transmission occurs. Whilst the value of focusing interventions to high-burden areas is evident, there is currently limited evidence that local-scale hotspots fuel transmission. As boundaries are often uncertain, there is no conclusive evidence that hotspot-targeted interventions accelerate malaria elimination

Quantifying Plasmodium falciparum infections clustering within households to inform household-based intervention strategies for malaria control programs: An observational study and meta-analysis from 41 malaria-endemic countries.

BACKGROUND: Reactive malaria strategies are predicated on the assumption that individuals infected with malaria are clustered within households or neighbourhoods. Despite the widespread programmatic implementation of reactive strategies, little empirical evidence exists as to whether such strategies are appropriate and, if so, how they should be most effectively implemented. METHODS AND FINDINGS: We collated 2 different datasets to assess clustering of malaria infections within households: (i) demographic health survey (DHS) data, integrating household information and patent malaria infection, recent fever, and recent treatment status in children; and (ii) data from cross-sectional and reactive detection studies containing information on the household and malaria infection status (patent and subpatent) of all-aged individuals. Both datasets were used to assess the odds of infections clustering within index households, where index households were defined based on whether they contained infections detectable through one of 3 programmatic strategies: (a) Reactive Case Detection (RACD) classifed by confirmed clinical cases, (b) Mass Screen and Treat (MSAT) classifed by febrile, symptomatic infections, and (c) Mass Test and Treat (MTAT) classifed by infections detectable using routine diagnostics. Data included 59,050 infections in 208,140 children under 7 years old (median age = 2 years, minimum = 2, maximum = 7) by microscopy/rapid diagnostic test (RDT) from 57 DHSs conducted between November 2006 and December 2018 from 23 African countries. Data representing 11,349 infections across all ages (median age = 22 years, minimum = 0.5, maximum = 100) detected by molecular tools in 132,590 individuals in 43 studies published between April 2006 and May 2019 in 20 African, American, Asian, and Middle Eastern countries were obtained from the published literature. Extensive clustering was observed-overall, there was a 20.40 greater (95% credible interval [CrI] 0.35-20.45; P < 0.001) odds of patent infections (according to the DHS data) and 5.13 greater odds (95% CI 3.85-6.84; P < 0.001) of molecularly detected infections (from the published literature) detected within households in which a programmatically detectable infection resides. The strongest degree of clustering identified by polymerase chain reaction (PCR)/ loop mediated isothermal amplification (LAMP) was observed using the MTAT strategy (odds ratio [OR] = 6.79, 95% CI 4.42-10.43) but was not significantly different when compared to MSAT (OR = 5.2, 95% CI 3.22-8.37; P-difference = 0.883) and RACD (OR = 4.08, 95% CI 2.55-6.53; P-difference = 0.29). Across both datasets, clustering became more prominent when transmission was low. However, limitations to our analysis include not accounting for any malaria control interventions in place, malaria seasonality, or the likely heterogeneity of transmission within study sites. Clustering may thus have been underestimated. CONCLUSIONS: In areas where malaria transmission is peri-domestic, there are programmatic options for identifying households where residual infections are likely to be found. Combining these detection strategies with presumptively treating residents of index households over a sustained time period could contribute to malaria elimination efforts

No time to die: An in-depth analysis of James Bond's exposure to infectious agents.

Global travelers, whether tourists or secret agents, are exposed to a smörgåsbord of infectious agents. We hypothesized that agents pre-occupied with espionage and counterterrorism may, at their peril, fail to correctly prioritize travel medicine. To examine our hypothesis, we examined adherence to international travel advice during the 86 international journeys that James Bond was observed to undertake in feature films spanning 1962-2021. Scrutinizing these missions involved ∼3113 min of evening hours per author that could easily have been spent on more pressing societal issues. We uncovered above-average sexual activity, often without sufficient time for an exchange of sexual history, with a remarkably high mortality among Bond's sexual partners (27.1; 95% confidence interval 16.4-40.3). Given how inopportune a bout of diarrhea would be in the midst of world-saving action, it is striking that Bond is seen washing his hands on only two occasions, despite numerous exposures to foodborne pathogens. We hypothesize that his foolhardy courage, sometimes purposefully eliciting life-threatening situations, might even be a consequence of Toxoplasmosis. Bond's approach to vector-borne diseases and neglected tropical diseases is erratic, sometimes following travel advice to the letter, but more often dwelling on the side of complete ignorance. Given the limited time Bond receives to prepare for missions, we urgently ask his employer MI6 to take its responsibility seriously. We only live once

Detecting Gametocytes: How Sensitive Is Sensible?

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Persistent detection of Plasmodium falciparum, P. malariae, P. ovale curtisi and P. ovale wallikeri after ACT treatment of asymptomatic Ghanaian school-children

Two hundred and seventy four asymptomatic Ghanaian school-children aged 5 to 17 years were screened for malaria parasites by examination of blood films. One hundred and fifty five microscopically-positive individuals were treated with dihydroartemisinin-piperaquine and followed for 3 weeks. Retrospective species-specific PCR of all 274 screened samples identified an additional 60 children with sub-patent parasitaemia, and a substantial proportion of co-infections with Plasmodium malariae, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. One hundred individuals harboured at least one non-falciparum parasite species. Using standard double-read microscopy, the 21-day efficacy of treatment against Plasmodium falciparum was 91.4% among the 117 children seen at all 5 visits. Using nested PCR to test 152 visit 5 blood samples, 22 were found to be parasite-positive. Twenty individuals harboured P. falciparum, four harboured P. ovale spp. and two P. malariae, with four of these 22 isolates being mixed species infections. The persistent detection of low density Plasmodium sp. infections following antimalarial treatment suggests these may be a hitherto unrecognised obstacle to malaria elimination. (C) 2013 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved

Persistent detection of Plasmodium falciparum, P. malariae, P. ovale curtisi and P. ovale wallikeri after ACT treatment of asymptomatic Ghanaian school-children.

Two hundred and seventy four asymptomatic Ghanaian school-children aged 5 to 17 years were screened for malaria parasites by examination of blood films. One hundred and fifty five microscopically-positive individuals were treated with dihydroartemisinin-piperaquine and followed for 3 weeks. Retrospective species-specific PCR of all 274 screened samples identified an additional 60 children with sub-patent parasitaemia, and a substantial proportion of co-infections with Plasmodium malariae, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. One hundred individuals harboured at least one non-falciparum parasite species. Using standard double-read microscopy, the 21-day efficacy of treatment against Plasmodium falciparum was 91.4% among the 117 children seen at all 5 visits. Using nested PCR to test 152 visit 5 blood samples, 22 were found to be parasite-positive. Twenty individuals harboured P. falciparum, four harboured P. ovale spp. and two P. malariae, with four of these 22 isolates being mixed species infections. The persistent detection of low density Plasmodium sp. infections following antimalarial treatment suggests these may be a hitherto unrecognised obstacle to malaria elimination