Analytical Sensitivity Analysis and Clinical Impact Modeling of Rapigen Rapid Diagnostic Tests for Malaria.

Laboratory benchmarking allows objective analysis of the analytical performance of malaria rapid diagnostic tests (RDTs). We present the analytical detection limits of the Rapigen BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), the Rapigen BIOCREDIT Malaria Ag Pf (pLDH/HRPII), and two best-in-class WHO-prequalified comparator RDTs, generated using standardized panels containing recombinant antigen, in vitro cultured parasites, international standards, and clinical samples. Detection limit antigen concentrations of HRP2, PfLDH, and PvLDH were determined for the Rapigen and comparator RDTs.

Repeat Ivermectin Mass Drug Administrations for Malaria Control II: Protocol for a Double-blind, Cluster-Randomized, Placebo-Controlled Trial for the Integrated Control of Malaria.

Background: The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector.

Performance and utility of more highly sensitive malaria rapid diagnostic tests.

Background: A new more highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum malaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now called NxTek™ Eliminate Malaria Ag Pf) was launched in 2017. The test has already been used in many research studies in a wide range of geographies and use cases.

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.

Evaluating the Performance of Malaria Genetics for Inferring Changes in Transmission Intensity Using Transmission Modeling.

Substantial progress has been made globally to control malaria, however there is a growing need for innovative new tools to ensure continued progress. One approach is to harness genetic sequencing and accompanying methodological approaches as have been used in the control of other infectious diseases. However, to utilize these methodologies for malaria, we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment, which all impact the level of genetic diversity and relatedness of malaria parasites.

Ultra-sensitive RDT performance and antigen dynamics in a high-transmission Plasmodium falciparum setting in Mali.

Background: The recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect-typically histidine rich protein 2 (HRP2) or lactate dehydrogenase (LDH).

Methods: For this analysis, whole blood specimens from a longitudinal study in Bancoumana, Mali were used to evaluate the performance of the ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT).

The potential public health consequences of COVID-19 on malaria in Africa.

The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-2. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed.

Evaluating the Impact of Programmatic Mass Drug Administration for Malaria in Zambia Using Routine Incidence Data.

Background: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, 2 months apart (coverage 70% and 57%, respectively). We evaluated the impact of 1 year of pMDA on malaria incidence using routine data.

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study.

Background: Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use.

False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub-Saharan Africa.

Surveillance and diagnosis of malaria relies predominantly on rapid diagnostic tests (RDT). However, false-negative (FN) RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, gene deletions, poor performance of specific RDT brands and lots, and low-parasite density infections. We used RDT and microscopy results from 85 000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for FN-RDTs in sub-Saharan Africa, where malaria's impact is greatest.

Author Correction: The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impact of seasonal variations in malaria transmission on the surveillance of gene deletions.

Ten countries have reported gene deletions since the first observation of -deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for deletions and mapped the regions in Africa with the greatest selection pressure.

The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density.

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections.

Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial.

Background: Ivermectin is widely used in mass drug administrations for controlling neglected parasitic diseases, and can be lethal to malaria vectors that bite treated humans. Therefore, it could be a new tool to reduce plasmodium transmission. We tested the hypothesis that frequently repeated mass administrations of ivermectin to village residents would reduce clinical malaria episodes in children and would be well tolerated with minimal harms.

Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial.

Background: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150-200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment.

The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia.

Background: The majority of Plasmodium vivax and Plasmodium falciparum infections in low-endemic settings are asymptomatic. The relative contribution to the infectious reservoir of these infections compared to clinical malaria cases is currently unknown.

Methods: We assessed infectivity of passively recruited symptomatic malaria patients (n = 41) and community-recruited asymptomatic individuals with microscopy-detected (n = 41) and polymerase chain reaction (PCR)-detected infections (n = 82) using membrane feeding assays with Anopheles arabiensis mosquitoes in Adama, Ethiopia.

Modelling the drivers of the spread of gene deletions in sub-Saharan Africa.

Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent RDTs detect histidine-rich protein 2 (PfHRP2). However, gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia.

Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

Background: Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission.

Methods: We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models.

A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions.

Background: Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials.