The transmission blocking activity of artemisinin-combination, non-artemisinin, and 8-aminoquinoline antimalarial therapies: A pooled analysis of individual participant data.

Background: Interrupting human-to-mosquito transmission is important for malaria elimination strategies as it can reduce infection burden in communities and slow the spread of drug resistance. Antimalarial medications differ in their efficacy in clearing the transmission stages of Plasmodium falciparum (gametocytes) and in preventing mosquito infection. Here, we present a retrospective combined analysis of six trials conducted at the same study site with highly consistent methodologies that allows for a direct comparison of the gametocytocidal and transmission-blocking activities of 15 different antimalarial regimens or dosing schedules.

Asymptomatic school children and adults are important for the human infectious reservoir for Plasmodium falciparum malaria in an area of low endemicity in The Gambia.

Objectives: In The Gambia, the scale-up of malaria control interventions in the past decades resulted in a substantial decrease of the malaria burden. However, low levels of malaria transmission persist.

Methods: We conducted an observational cohort study in eastern Gambia to better understand the relative contribution of symptomatic and asymptomatic malaria infections to the infectious reservoir.

Anopheles mosquito exposure is associated with age, gender and bed net use in areas in Uganda experiencing varying malaria transmission intensity.

Objectives: The number of Anopheles mosquito bites a person receives determines the risk of acquiring malaria and the likelihood of transmitting infections to mosquitoes. We assessed heterogeneity in Anopheles biting and associated factors in two settings in Uganda with different endemicity.

Methods: Plasmodium falciparum parasites in blood-fed indoor caught Anopheles mosquitoes were quantified using qPCR targeting the Pf18S rRNA gene.

Preferential transmission of minority and drug-resistant clones in polyclonal infections in Mali.

Background: In polyclonal human malaria infections, the roles of individual clones in human-to-mosquito transmission and their relative transmissibility remain poorly understood. In addition, mutations conferring drug resistance can result in a transmission advantage or disadvantage.

Methods: Amplicon sequencing of complexity of infection and drug resistance markers was used to analyse post-treatment stage-specific malaria parasite dynamics in human blood infections and in the midguts of mosquitoes that became infected after direct membrane feeding assays (DMFAs).

mosquito exposure is associated with age, gender and bed net use in areas in Uganda experiencing varying malaria transmission intensity.

Objectives: The number of mosquito bites a person receives determines the risk of acquiring malaria and the likelihood of transmitting infections to mosquitoes. We assessed heterogeneity in biting and associated factors in two settings in Uganda with different endemicity.

Methods: parasites in blood-fed indoor caught mosquitoes were quantified using qPCR targeting the Pf18S rRNA gene.

Effect of weekly fever-screening and treatment and monthly RDT testing and treatment on the infectious reservoir of malaria parasites in Burkina Faso: a cluster-randomised trial.

Background: The majority of Plasmodium spp infections in endemic countries are asymptomatic and a source of onward transmission to mosquitoes. We aimed to examine whether Plasmodium falciparum transmission and malaria burden could be reduced by improving early detection and treatment of infections with active screening approaches.

Methods: In this 18-month cluster randomised study in Sapone, Burkina Faso, households were enrolled and randomly assigned (1:1:1) to one of three groups: group 1 (control) received standard of care only, group 2 received active weekly, at home, fever screening by a community health worker regardless of symptoms, participants with a fever received a rapid diagnostic test (RDT) and treatment if RDT positive, and group 3 received active weekly fever screening (as in group 2) plus a monthly RDT regardless of symptoms, and treatment if RDT positive.

Plasmodium falciparum gametocyte production correlates with genetic markers of parasite replication but is not influenced by experimental exposure to mosquito biting.

Background: Plasmodium blood-stage parasites balance asexual multiplication with gametocyte development. Few studies link these dynamics with parasite genetic markers in vivo; even fewer in longitudinally monitored infections. Environmental influences on gametocyte formation, such as mosquito exposure, may influence the parasite's investment in gametocyte production.

Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali.

Background: Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes.

Methods: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine.

Quantification of sporozoite expelling by mosquitoes infected with laboratory and naturally circulating gametocytes.

It is currently unknown whether all -infected mosquitoes are equally infectious. We assessed sporogonic development using cultured gametocytes in the Netherlands and naturally circulating strains in Burkina Faso. We quantified the number of sporozoites expelled into artificial skin in relation to intact oocysts, ruptured oocysts, and residual salivary gland sporozoites.

Dynamics of asymptomatic Plasmodium falciparum and Plasmodium vivax infections and their infectiousness to mosquitoes in a low transmission setting of Ethiopia: a longitudinal observational study.

Objective: A 15-month longitudinal study was conducted to determine the duration and infectivity of asymptomatic qPCR-detected Plasmodium falciparum and Plasmodium vivax infections in Ethiopia.

Method: Total parasite and gametocyte kinetics were determined by molecular methods; infectivity to Anopheles arabiensis mosquitoes by repeated membrane feeding assays. Infectivity results were contrasted with passively recruited symptomatic malaria cases.

Naturally acquired antibodies to gametocyte antigens are associated with reduced transmission of gametocytes to mosquitoes.

Naturally acquired antibodies may reduce the transmission of gametocytes to mosquitoes. Here, we investigated associations between antibody prevalence and infectivity to mosquitoes. A total of 368 microscopy confirmed symptomatic patients were passively recruited from health centers in Ethiopia and supplemented with 56 observations from asymptomatic parasite carriers.

Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes.

Background: In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detection. However, it is currently unclear how parasite stages that are unaffected by standard drug treatments may contribute to HRP-2 detectability and potentially confound RDT results even after clearance of blood stage infection.

SARS-CoV-2 RNA in exhaled air of hospitalized COVID-19 patients.

Knowledge about contagiousness is key to accurate management of hospitalized COVID-19 patients. Epidemiological studies suggest that in addition to transmission through droplets, aerogenic SARS-CoV-2 transmission contributes to the spread of infection. However, the presence of virus in exhaled air has not yet been sufficiently demonstrated.

Asymptomatic School-Aged Children Are Important Drivers of Malaria Transmission in a High Endemicity Setting in Uganda.

Achieving malaria elimination requires a better understanding of the transmissibility of human infections in different transmission settings. This study aimed to characterize the human infectious reservoir in a high endemicity setting in eastern Uganda, using gametocyte quantification and mosquito feeding assays. In asymptomatic infections, gametocyte densities were positively associated with the proportion of infected mosquitoes (β = 1.

Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial.

Background: Tafenoquine was recently approved as a prophylaxis and radical cure for Plasmodium vivax infection, but its Plasmodium falciparum transmission-blocking efficacy is unclear. We aimed to establish the efficacy and safety of three single low doses of tafenoquine in combination with dihydroartemisinin-piperaquine for reducing gametocyte density and transmission to mosquitoes.

Methods: In this four-arm, single-blind, phase 2, randomised controlled trial, participants were recruited at the Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako in Mali.

A Cohort Study on the Duration of Plasmodium falciparum Infections During the Dry Season in The Gambia.

Background: In areas where Plasmodium falciparum malaria is seasonal, a dry season reservoir of blood-stage infection is essential for initiating transmission during the following wet season.

Methods: In The Gambia, a cohort of 42 individuals with quantitative polymerase chain reaction-positive P falciparum infections at the end of the transmission season (December) were followed monthly until the end of the dry season (May) to evaluate infection persistence. The influence of human host and parasitological factors was investigated.

Pyronaridine-artesunate or dihydroartemisinin-piperaquine combined with single low-dose primaquine to prevent malaria transmission in Ouélessébougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial.

Background: Pyronaridine-artesunate is the most recently licensed artemisinin-based combination therapy. WHO has recommended that a single low dose of primaquine could be added to artemisinin-based combination therapies to reduce transmission in areas aiming for elimination of malaria or areas facing artemisinin resistance. We aimed to determine the efficacy of pyronaridine-artesunate and dihydroartemisinin-piperaquine with and without single low-dose primaquine for reducing gametocyte density and transmission to mosquitoes.

SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms.

Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudinal nasal antibody response in index cases with mild COVID-19 and their household contacts. Nasal and serum antibody responses were analysed for up to nine months.

The effect of anticoagulants in blood collection tubes on Plasmodium falciparum transmission in direct membrane feeding assays.

Background: Direct membrane feeding assays assess the transmission potential of malaria-infected individuals using whole blood collected in anticoagulant vacutainers.

Methods: The potential inhibitory effect of four commonly used anticoagulants on gametocyte infectivity to mosquitoes was assessed in standard membrane feeding assays with cultured Plasmodium falciparum.

Results: Infection burden in mosquitoes was significantly reduced when blood was collected in sodium citrate and EDTA.

Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study.

Background: Symptomatic malaria cases reflect only a small proportion of all Plasmodium spp infections. Many infected individuals are asymptomatic, and persistent asymptomatic Plasmodium falciparum infections are common in endemic settings. We aimed to quantify the contribution of symptomatic and asymptomatic infections to P falciparum transmission in Tororo, Uganda.