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Malaria remains a threat to public health in Malawi. It is well acknowledged that malaria research and robust evidence can have an impact on malaria policy and practice, resulting in positive population health gains. We report policy-relevant research contributions that the Malawi International Center of Excellence for Malaria Research (ICEMR) in partnership with local and international collaborators has made. Findings from our ICEMR studies have shown that long-lasting insecticide-treated bed nets (LLINs) impregnated with piperonyl butoxide reduced mosquito blood feeding more compared with conventional LLINs. On the other hand, we showed that few LLINs are maintained up to the end of their 3-year life span, and that older nets are less effective. These results support the policy change decisions by the Malawi National Malaria Control Program to switch from conventional LLINs to piperonyl butoxide LLINs, and to conduct mass LLIN distribution campaigns every 2 years. Our studies on epidemiological patterns of malaria infection showed that school-age children have higher malaria infection rates and lower use of control measures compared with younger children and adults. These findings added to the evidence base that influenced the National Malaria Control Program to endorse school-based malaria interventions as part of its national policy. Research supported by the Malawi ICEMR is contributing to in-country policy decisions and to the implementation of evidence-based interventions. Through our long-term studies we intend to continue providing practical and policy-relevant evidence necessary, ultimately, to eliminate malaria infection in Malawi.

BackgroundWhen people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor antimalarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter antimalarial metabolism. We evaluated the therapeutic efficacy of artemether-lumefantrine in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response. MethodsAdults living with HIV ( ≥18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, we conducted therapeutic efficacy monitoring with PCR-correction according to WHO guidelines. We assessed plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between prophylactic treatment arm and malaria treatment failure within 28 days. Pearson’s Chi – squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR). ResultsWe observed 411 malaria episodes among 186 participants over five years. The unadjusted ACPR rate was 81% (95% CI 77 - 86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92 - 97). In our population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48 – 231]) than participants who experienced ACPR (190 ng/ml [95% CI 101 – 378], p-value < 0.008). ConclusionRecurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

Key Points Question What are the characteristics of SARS-CoV-2 G614 viral shedding in incident infections in association with COVID-19 symptom onset and severity? Findings In a cohort study of persons who tested positive for SARS-CoV-2 after recent exposure, viral RNA trajectory was characterized by a rapid peak followed by slower decay. Peak viral load correlated positively with symptom severity and generally occurred within 1 day of symptom onset if the patient was symptomatic. Meaning A detailed description of the SARS-CoV-2 G614 viral shedding trajectory serves as a baseline for comparison with new viral variants of concern and informs models to plan clinical trials to end the pandemic., Importance The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development. Objective To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity. Design, Setting, and Participants This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (, This cohort study characterizes early SARS-CoV-2 viral RNA load in individuals with incident infections in association with COVID-19 symptom onset and severity.

The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gametocytes, sequester in human bone marrow before release into the circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (iRBC) surface. Here, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed Malawians. We identified strong antibody recognition of the earliest immature gametocyte-iRBCs (giRBCs) but not mature stage V giRBCs. Candidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-iRBCs, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. Naturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of giRBCs in vitro. Infected RBC surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. Our data demonstrate that humoral immune responses to immature giRBCs and shared iRBC antigens are naturally acquired after malaria exposure. These humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention.

Background Plasmodium falciparum ( Pf ) resistance to anti-malarial drugs remains a major hindrance to malaria control and elimination. Pf has developed resistance to nearly all antimalarial drugs including chloroquine, the first most frequently used first-line treatment for uncomplicated malaria. In Zambia, chloroquine was used as treatment for uncomplicated malaria for a long time until Pf -developed resistance and rose to as high as 60% in some parts of the country. This prompted the Ministry of Health to effect a drug policy change in 2003. Recent reports have indicated recovery of chloroquine susceptibility in neighbouring like Malawi, Mozambique and Tanzania. To update the information on chloroquine sensitivity in Zambia we conducted a study that assessed the prevalence of mutant Pf in Nchelenge district 10 years post chloroquine withdrawal. Methods Dried blood spots for this study were collected from finger-prick blood of consenting pregnant women. Deoxyribonucleic acid (DNA) was extracted and genotyped for Pf crt-76 resistance marker using specific primers in a nested polymerase chain reaction (PCR). The PCR products obtained were then pyrosequenced and read using PyroMarkTM Q96MD software. The wild-type 3D7 and Dd2 were used as wild-type and mutated controls. Results No chloroquine resistance mutation, Pfcrt 76T was detected in any of the 302 samples that were successfully amplified. This represents a 100% prevalence of Pf that are sensitive to chloroquine in the study population. Conclusions This study demonstrates a total return of chloroquine-sensitive Pf in Nchelenge after over a decade of withdrawal of chloroquine. In combination with another drug, chloroquine could be a good substitute for the currently used artemether lumefantrine, and intermittent preventive treatment in pregnancy (IPTp) and children.

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