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Background By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. Methods We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. Results A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20–49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]). Conclusion The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. METHODS: For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age

ObjectiveAdults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV in the infant pneumococcal conjugate vaccination era, we assessed association between carriage and potential risk factors.MethodsNasopharyngeal swabs were collected from adults aged 18-40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015-2019. We fitted generalised additive models to estimate the risk of sex, social economic status (SES), living with a child ResultsOf 2,067 adults, median age was 33y (range 28-37), 1,427 (69.0%) were females, 1,087 (61.4%) were in low-middle socio-economic-status (SES), 910 (44.0%) were living with a child ConclusionDespite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete VT indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease.

Background: \ud \ud Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants

IntroductionVaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistantStreptococcus pneumoniaeand extended spectrum beta-lactamase-producingEscherichia coliandKlebsiellaspecies. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine.Methods and analysisSix cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence amongS. pneumoniaenasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility).Ethics and disseminationThis study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.

BackgroundPneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibody, effectively reducing vaccine-serotype (VT) carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty around correlate of protection (CoP) estimates and with persistent VT carriage and VT-IPD following PCV13 introduction, we undertook population-level immunogenicity profiling among children MethodsFor 638 children, capsule-specific IgG to PCV13 VTs, two non-VTs, and IgG to three pneumococcal proteins were measured using an enzyme-linked immunosorbent assay and a direct-binding electrochemiluminescence-based multiplex assay. A linear spline regression model estimated population-level, serotype-specific immunogenicity profiles. A linear regression model was used to validate putative CoPs.FindingsImmunogenicity profiles revealed a consistent pattern among VTs except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3 there was no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination-nadir (11·2 [19F, 23F] to 27·3 [7F] months). Titres dropped below IPD CoPs among 9 VTs and below carriage CoPs for 10 VTs. Study data estimated a range of carriage CoPs (0·50μg/mL to 2·5μg/mL). Increasing antibody among older children and seroincident events were consistent with ongoing VT exposure.InterpretationA 3+0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several VTs, potentially contributing to persistent VT carriage and residual VT-IPD in Malawi and other similar settings.FundingBill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health & Care Research.

BackgroundInvasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants aged MethodsWe conducted laboratory-based prospective IPD surveillance in infants aged Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex PCR and latex agglutination testing.ResultsWe identified 130 cases of culture-confirmed IPD in infants ConclusionVaccine serotypes were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. Further strategies need to be considered to protect this vulnerable population, including maternal or neonatal immunization and implementation of an alternative PCV schedule with a booster dose.SummaryThe incidence of invasive pneumococcal disease in infants in Blantyre, Malawi has declined over the past decade and more significantly after introduction of the pneumococcal conjugate vaccine. Vaccine serotypes have remained the main cause of disease in this population.

BackgroundAs at end of July 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been two subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi.MethodsWe measured the seroprevalence of anti-SARS-CoV-2 antibodies among randomly selected blood donor sera in Malawi from January 2020 to February 2021. In a subset, we also assesedin vitroneutralisation against the original variant (D614G WT) and the Beta variant.FindingsA total of 3586 samples were selected from the blood donor database, of which 2685 (74.9%) were male and 3132 (87.3%) were aged 20-49 years. Of the total, 469 (13.1%) were seropositive. Seropositivity was highest in October 2020 (15.7%) and February 2021 (49.7%) reflecting the two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity by February 2021, Balaka (rural, 37.5%), Blantyre (urban, 54.8%), Lilongwe (urban, 54.5%) and Mzuzu (urban, 57.5%). First wave sera showed potentin vitroneutralisation activity against the original variant (78%[7/9]) but not the Beta variant (22% [2/9]). Second wave sera potently neutralised the Beta variant (73% [8/11]).InterpretationThe findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. Since prior exposure augments COVID-19 vaccine immunity, prioritising administration of the first dose in high SARS-CoV-2 exposure settings could maximise the benefit of the limited available vaccines in Malawi and the region.Research in contextEvidence before this studyWe searched PubMed on August 16, 2021, with no language restrictions, for titles and abstracts published between Jan 1, 2020, and August 16, 2021, using the search terms: “SARS-CoV-2 seroprevalence in Africa”[Title/Abstract]) OR “SARS-CoV-2 seroprevalence in blood donors” [Title/Abstract] OR “SARS-CoV-2 seroprevalence in Malawi”, and found 15 records. There are limited SARS-CoV-2 seroprevalence studies in sub Saharan Africa, however the few that are available report high seroprevalence than can be deduced from the respective national reported COVID-19 cases and deaths. Only two published SARS-CoV-2 serosurveys were done on blood donors, from Kenya and Madagascar. Blood donor serosurveys have been recommended by the WHO as an important tool for assessing the spread of SARS-CoV-2 and estimating the burden of COVID-19 pandemic.Added value of this studyUnlike previous SARS-CoV-2 blood donor serosurveys in African populations that were conducted for a maximum period of 9 months, our study covers a full year from January 2020 to February 2021, capturing potential introduction of SARS-CoV-2 into Malawi as well as the two epidemic waves. This study provides evidence against the speculation that SARS-CoV-2 had been circulating more widely in sub-Saharan Africa before the first detected cases. It also provides supporting evidence suggesting that the Beta variant was the likely driver of the second wave that resulted in high SARS-CoV-2 seropositivity in January to February 2021 in Malawi.Implications of all the available evidenceOur results show extensive community transmission of SARS-CoV-2 in Malawi as reflected in the blood donors serosurvey, with almost half the sample population being seropositive for anti-SARS-CoV-2 antibodies by February 2021. This has implications for COVID-19 vaccination policy in sub-Saharan Africa (SSA), where there are limited available vaccine doses. Considering that prior exposure to SARS-CoV-2 augments COVID-19 vaccine immunity, strategies to maximise administration of the first vaccine dose, while waiting for more vaccines to become available, could maximise the benefits of the limited available vaccines in high SARS-CoV-2 exposure settings in SSA such as Malawi.

Streptococcus pneumoniae accounts for at least 300,000 deaths from pneumonia, septicaemia and meningitis among children under 5-years-old worldwide. Protein–polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten to undermine this success. Here, we address the hypothesis that following vaccine introduction in high disease and carriage burden settings, adapted pneumococcal genotypes emerge with the potential to facilitate vaccine escape. We show that beyond serotype replacement, there are marked changes in S. pneumoniae carriage population genetics amongst 2804 isolates sampled 4-8 years after the 2011 introduction of PCV-13 in urban Malawi. These changes are characterised by metabolic genotypes with distinct virulence and antimicrobial resistance (AMR) profiles. This included exclusive genes responsible for metabolism and carbohydrate transport, and toxin-antitoxin systems located in an integrative-conjugative region suggestive of horizontal gene transfer. These emergent genotypes were found to have differential growth, haemolytic, or epithelial adhesion/invasion traits that may confer advantage in the nasopharyngeal niche. Together these data show that in the context of PCV13 introduction in a high burden population, there has been a shift in the pneumococcal population dynamics with the emergence of genotypes that have undergone multiple adaptations extending beyond simple serotype replacement, a process that could further undermine vaccine control and promote the spread of AMR.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies., Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

BACKGROUND\ud The population impact of pneumococcal conjugate vaccines (PCVs) depends on direct and indirect protection. Following Malawi's introduction of the 13-valent PCV (PCV13) in 2011, we examined its impact on vaccine and non-vaccine serotype invasive pneumococcal disease among vaccine-eligible-age and vaccine-ineligible-age children and adults.\ud \ud METHODS\ud We did a prospective observational time-series analysis and a case-control study. We used data from between Jan 1, 2006, and Dec 31, 2018, from laboratory-based surveillance at a government hospital in Malawi. This period included 6 years before and 7 years after introduction of PCV13. By use of negative-binomial regression, we evaluated secular trend-adjusted incidence rate ratio (IRR) in vaccine serotype and non-vaccine serotype invasive pneumococcal disease before and after introduction of PCV. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. The case-control study assessed vaccine effectiveness, comparing PCV uptake among cases of vaccine-eligible-age invasive pneumococcal disease versus matched community controls.\ud \ud FINDINGS\ud Surveillance covered 10 281 476 person-years of observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. A reduction in total (vaccine serotype plus non-vaccine serotype) invasive pneumococcal disease incidence preceded introduction of PCV: 19% (IRR 0·81, 95% CI 0·74 to 0·88, p

Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations., Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.

Background: Population impact of pneumococcal conjugate vaccines (PCV) depend on direct and indirect protection. Following Malawi’s 2011 introduction of the 13-valent PCV (PCV13), we examined impact on vaccine serotype (VT) and non-VT (NVT) invasive pneumococcal disease (IPD) among vaccine-age-eligible and vaccine-age-ineligible children and adults. Methods: Laboratory-based surveillance at a government hospital in Malawi included 6 years before and 7 years after PCV13 introduction. Using negative-binomial regression, we evaluated secular trend-adjusted Incidence Rate Ratio (IRR) in VT- and NVT-IPD prior to and post PCV introduction. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. A case-control study assessed vaccine effectiveness compared PCV uptake among vaccine-age-eligible IPD cases versus matched community controls. Findings: Surveillance covered 10 281 476 person-years observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. IPD decline preceded PCV introduction. Compared to the counterfactually predicted incidence, post-vaccine VT-IPD incidence was 38% (95%CI: 37, 40) lower among infants, 74% (70, 78) among young children, 79% (76, 83) among older children and 47% (44, 51) among adolescents and adults. Though NVT-IPD has increased since 2015 , absolute rates remain low. The case-control study, (19 cases and 76 controls), showed vaccine effectiveness against VT-IPD of 80·7% (-73·7, 97·9). Interpretation: Even with pre-existing declines, infant PCV13 introduction has led to substantial IPD reduction among vaccine-age-eligible children. However, seven years after PCV introduction, indirect effects benefitting unvaccinated infants and adults were more modest. Policy decisions should consider alternative strategies, including targeted vaccination outside infant EP to benefit vulnerable populations. Funding Statement: This work was funded by Bill & Melinda Gates Foundation, USA (OPP117653) to RSH and a Wellcome Trust Programme Grant (WT091909/B/10/Z) to NF, NAC, RSH; National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government (Project number 16/136/46) to RSH. The MLW Clinical Research Programme is supported by a Strategic Award from the Wellcome Trust, UK (206545/Z/17/Z) to SG. Declaration of Interests: NBZ, NAC & NF have received investigator-initiated research grants from GlaxoSmithKline Biologicals. NBZ & NAC received investigator-initiated research grants from Takeda Pharmaceuticals. NAC has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. All other authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by Malawi’s National Health Sciences Research Committee (NHSRC; protocol 867), by the University of Malawi College of Medicine Research and Ethics Committee (COMREC; P.01/08/609 and P.09/09/826) and the University of Liverpool Research Ethics Committee (UoLREC; RETH490). The Centers for Disease Control and Prevention relied on the UoLREC for ethical approval. For the case-control component, the parent/guardian of all child participants provided written informed consent and, in addition, children 8 years or older provided written informed assent. This included consent for publication.

IntroductionStreptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi’s National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy.MethodsA pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15–24 months, randomised at household level, and schoolgoers 5–10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation.AnalysisThe primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15–24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively.Ethics and disseminationThe study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numberNCT04078997.