BACKGROUND:The RTS,S/AS01E malaria vaccine provides partial protection against Plasmodium falciparum, largely mediated by antibodies targeting the circumsporozoite protein. Correlates of protection remain incompletely defined and have focused mainly on peak IgG responses to the immunodominant NANP-repeats, with less known about antibody durability or responses to the C-terminus of circumsporozoite protein. METHODS:In this observational study, we evaluated IgG responses to NANP-repeat, C-terminus, and full-length circumsporozoite protein constructs at five timepoints before and after primary and booster vaccination, in children aged 5-17 months from six African countries enrolled in the RTS,S/AS01E phase 3 trial (NCT00866619, 2009-11). Antibody kinetics were analysed with linear regressions, and associations with clinical malaria risk over 1 year with Cox models. FINDINGS:Between May 25, 2009, to March 5, 2010, 1292 children were recruited and included for analysis in this study. IgG levels declined more slowly for C-terminus than for NANP-repeat over 17 months after primary vaccination (geometric mean fold change 0·099 [95% CI 0·089-0·110] vs 0·055 [0·048-0·062]; p<0·0001). The booster significantly enhanced C-terminal IgG, exceeding post-primary peak levels (geometric mean fold change 1·98 [95% CI 1·77-2·21]), whereas NANP-repeat responses were restored but remained below post-primary levels (geometric mean fold changes 0·57 [95% CI 0·51-0·63]). Higher circumsporozoite protein IgG levels correlated with reduced malaria risk, particularly during maintenance phases, with stronger associations for C-terminus, which remained independently protective after adjustment for NANP-repeat antibodies (hazard ratio 0·60, 95% CI 0·43-0·83; p=0·0021). After boosting, maintenance but not peak IgG levels correlated with reduced malaria risk. INTERPRETATION:IgG to circumsporozoite protein C-terminus are more durable than those to the NANP-repeats. Antibody maintenance emerges as a stronger predictor of RTS,S/AS01E vaccine efficacy than peak responses. FUNDING:USA National Institute of Allergy and Infectious Diseases, National Institutes of Health; PATH and Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad; Instituto de Salud Carlos III; CERCA programme; and Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement, Generalitat de Catalunya.

Background Malaria in urban areas is a growing concern in most sub-Saharan African countries. The growing threats of Anopheles stephensi and insecticide resistance magnify this concern and hamper elimination efforts. It is therefore imperative to identify areas, within urban settings, of high-risk of malaria to help better target interventions. Methods In this study, we combined a set of environmental, climatic, and urban covariates with observed data from a malaria prevalence study and used geospatial methods to predict malaria risk in the Greater Accra Region of Ghana. Georeferenced data from 12,371 surveyed children aged between 6 months and 10 years were included in the analysis. Results Predicted malaria prevalence in this age group ranged from 0 to 52%. Satellite-driven data on tasselled cap brightness, enhanced vegetation index and a combination of urban covariates were predictive of malaria prevalence in the study region. We produced a map that quantified the probability of malaria prevalence exceeding 10%. Conclusions This map revealed areas within the districts earmarked for malaria elimination that have high malaria risk. This work is providing evidence for use by the National Malaria Elimination Program and District Health Managers in planning and deploying appropriate malaria control strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding for the PhD work of the corresponding author is from the Higher Degree Research Scholarship from the Curtin University, Western Australia. This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation INV-009390/OPP1197730. The conclusions and opinions expressed in this work are those of the author(s) alone and shall not be attributed to the Foundation. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Please note works submitted as a preprint have not undergone a peer review process. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The original study was approved by the Ethical review boards of the Ghana health service. Anonymized data for this work was obtained from the Kintampo Health Research Centre through the Ghana National Malaria Elimination Programme. This study is within a PhD projected under the Malaria Atlas Project with ethical approval from the Ethics committee of Curtin University under HRE2021-0734. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available on reasonable request, subject to ethics, governance, and privacy considerations. The code for the analysis is available on the personal GitHub portal of the corresponding author and will be made available when necessary.

BackgroundDengue is endemic in Burkina Faso with sporadic outbreaks during the decade 2011-2021. Dengue control depends on the ability to predict future outbreaks. This study aimed to forecast dengue cases using historical data between 2016 and 2021.MethodsThe study covered the Central Region, Burkina Faso, with dengue monthly data from the National System of Health Information (SNIS) and environmental data from the National Agency of Meteorology (ANAM). The Autoregressive Distributed Lag (ARDL) model was performed to forecast dengue cases between 2022 and 2025.ResultsDengue cases increased gradually between 2016 and 2021, with seasonal spikes during the year. The 95 per cent confidence interval exceeds 5000 cases by 2023 and reaches about 10,000 cases by 2025. From the ARDL results, the lagged variable Dengue cases (-1) showed a strong positive association (coefficient = 0.76; p-value = 0.00) and the variable Dengue cases (-2) a negative association (coefficient = -0.47; p-value = 0.01). The Population statistically impacted dengue incidence (coefficient = 0.00; p-value of 0.01). Relative humidity (-1) and Relative humidity (-4) positively affected dengue cases (coefficient = 114.26; p-value = 0.00 and 90.84; p-value = 0.00 respectively). Furthermore, Rainfall (-4) had a negative influence on dengue incidence (Coefficient = -6.91; p-value = 0.00. D.Minimum temperature (-3) positively influenced dengue cases (Coefficient = 223.20; p-value = 0.01). D.Wind speed showed a negative relationship (Coefficient = -925.31; p-value = 0.02), while D. Wind speed (-3) had a positive relationship (Coefficient = 875.04; p-value = 0.02). In addition, the ARDL long-run results revealed a positive association between dengue cases and population size (p-value = 0.02), Relative humidity (p-value = 0.01), and D.Minimum temperature (p-value = 0.02), and a negative association with Rainfall (p-value = 0.04).ConclusionDengue cases are forecasted to increase in the Central Region between 2022 and 2025. It is then crucial to develop long-term interventions against dengue, integrated with interventions for other neglected tropical diseases.

BACKGROUND:The RTS,S/AS01E malaria vaccine was introduced in selected communities of Ghana, Kenya, and Malawi in 2019 under a WHO-coordinated pilot programme. The scarcity of background disease incidence rates might hamper the assessment of vaccine safety and effectiveness. We aimed to determine the incidence rates of malaria, meningitis, and death, and health outcomes leading to hospital admission in children younger than 5 years enrolled before RTS,S/AS01E implementation. Interim results from EPI-MAL-002 up to Oct 5, 2018, were reported previously. Here, we report results from the final analysis of the pre-vaccine introduction study. METHODS:This disease surveillance study combined two approaches: (1) prospective cohort event monitoring (home visits scheduled to mimic a future four-dose RTS,S/AS01E vaccination schedule [ie, a simulated vaccination schedule], with additional visits after the simulated schedule and continuous disease monitoring of outpatient visits and hospital admission) in children enrolled in two age groups (6-12 weeks [6-12W] and 5-17 months [5-17M]), and (2) hospital-based disease surveillance for children not enrolled in the prospective cohort, in three sites in Ghana and Kenya. Key outcomes were rates of meningitis, malaria, adverse events of special interest, other adverse events leading to hospital admission, all-cause mortality, and malaria-attributable mortality. FINDINGS:The final analysis included 23 427 children: 9032 in the 6-12W age group, 9694 in the 5-17M age group, and 4701 in hospital-based disease surveillance. In the 5-17M age group (corresponding to the WHO-recommended age for RTS,S/AS01E vaccination), the incidence rates of meningitis and cerebral malaria within an at-risk period of 1 year after the simulated vaccination schedule were both equal to 28 (95% CI 9-65) per 100 000 person-years. There were 11 (0·1%) children with an adverse event of special interest during hospital admission. In the 5-17M age group, the all-cause mortality rate was 643 (95% CI 531-771) per 100 000 person-years. INTERPRETATION:Observed incidence of meningitis and cerebral malaria were in the previously published range, whereas childhood mortality was lower, suggesting that the recent efforts to reduce mortality in children younger than 5 years have been impactful. Data from this study have public health use and will form the baseline evidence for ongoing evaluation of the benefit-risk of RTS,S/AS01E. FUNDING:GSK and PATH.

Background The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. Methods In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/ AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E- vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. Findings We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E- vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-002 [95% CI -013 to 010]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-017 [-027 to -006]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-042 [-050 to -033]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-044 [-055 to -033]), and involved antibodies to the central NANP region (r=-039 [-049 to -028]) but not the C-terminal region (r=002 [-010 to 015]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables.

Malaria remains a major public health problem, especially among children in sub-Saharan Africa. Knowledge of malaria parasite prevalence informs targeted interventions and helps to monitor the effectiveness of those interventions. This study aimed to determine prevalence and factors associated with malaria in children aged 6 months to 10 years in the Greater Accra Region of Ghana. A community-based cross-sectional study was conducted among 8,741 children aged 6–59 months and 8,292 children aged 5–10 years in all 29 districts of the Greater Accra Region of Ghana in October 2020. Systematic random sampling was used to select communities, households and study participants. A structured questionnaire was used to collect data from caregivers. Rapid diagnostic test kits were used to determine the presence of malaria parasites in blood samples collected by fingerprick. Factors associated with malaria RDT-positivity were determined using multivariate logistic regression analysis. Of 8727 children aged 6–59 months and 8279 aged 5–10 years from whom blood samples were obtained, positive results were obtained for 289 (3.3

Background:RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group.Methods:To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria to exclude the delayed malaria effect using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and malaria transmission intensity. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.Results:We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by transmission intensity or parasitemia during the primary vaccination series.Conclusions:We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that delayed malaria is likely the main reason for lower efficacy in high transmission settings, not reduced immune responses. This may be reassuring for implementation in high transmission settings, though further studies are needed.

Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of IPTp-SP is, however, threatened by mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to pyrimethamine and sulfadoxine, respectively. This study determined the prevalence of molecular markers of SP resistance among pregnant women in a high malaria transmission area in the forest-savannah area of Ghana. Genomic DNA was extracted from 286 P. falciparum-positive dried blood spots obtained from pregnant women aged ≥18 years (255 at first Antenatal Care (ANC) clinic visit and 31 at delivery from 2017 to 2019) using Chelex 100. Mutations in Pfdhfr and Pfdhps genes were detected using molecular inversion probes and next generation sequencing. In the Pfdhfr gene, single nucleotide polymorphisms (SNPs) were detected in 83.1% (157/189), 92.0% (173/188) and 91.0% (171/188) at codons 51, 59, and 108 respectively in samples collected at first ANC visit, while SNPs were detected in 96.6 (28/29), 96.6% (28/29) and 96.8% (30/31) in isolates collected at delivery. The Pfdhfr triple mutant N51I, C59R and S108N (IRN) was carried by 80.5% (128/159) and 96.5% (28/29) of the typed isolates collected at ANC visit and at delivery respectively. In the Pfdhps gene, SNPs were detected in 0.6% (1/174), 76.2% (138/181), 33.2% (60/181), 1.2% (2/174), 0% (0/183), and 16.6% (27/173) at codons 431, 436, 437, 540, 581 and 613 respectively in samples collected at ANC, and 0% (0/25), 72% (18/25), 40% (10/25), 3.6% (1/25), 0% (0/29) and 7.4% (2/27) in samples collected at delivery. Quadruple mutant Pfdhfr N51I, C59R, and S108N + Pfdhps A437G (IRN-GK) was present in 25.8% (33/128) and 34.8% (8/23) of isolates at ANC and at delivery respectively. Quintuple mutant alleles Pfdhfr N51I, C59R, and S108N + Pfdhps A437G and K540E (IRN-GE) were detected in 0.8% (1/128) and 4.4% (1/23) of samples collected at ANC and at delivery respectively. No mutations were identified at Pfdhfr codons 16 or 164 or Pfdhps 581. There is a high prevalence of Pfdhfr triple mutant P. falciparum infections among pregnant women in the study area. However, prevalence of the combined Pfdhfr/Pfdhps quadruple and quintuple mutants IRN-GK and IRN-GE respectively prior to commencement of IPTp-SP were low, and no Pfdhps A581G mutant was detected, indicating that SP is still likely to be efficacious for IPTp-SP in the forest-savannah area in the middle belt of Ghana.

Background Malaria infection during pregnancy can cause significant morbidity and mortality to a pregnant woman, her fetus and newborn. In areas of high endemic transmission, gravidity is an important risk factor for infection, but there is a complex relationship with other exposure-related factors, and use of protective measures. This study investigated the association between gravidity and placental malaria (PM), among pregnant women aged 14–49 in Kintampo, a high transmission area of Ghana. Methods Between 2008 and 2011, as part of a study investigating the association between PM and malaria in infancy, pregnant women attending antenatal care (ANC) clinics in the study area were enrolled and followed up until delivery. The outcome of PM was assessed at delivery by placental histopathology. Multivariable logistic regression analyses were used to investigate the association between gravidity and PM, identify other key risk factors, and control for potential confounders. Pre-specified effect modifiers including area of residence, socio-economic score (SES), ITN use and IPTp-SP use were explored. Results The prevalence of PM was 65.9% in primigravidae, and 26.5% in multigravidae. After adjusting for age, SES and relationship status, primigravidae were shown to have over three times the odds of PM compared to multigravidae, defined as women with 2 or more previous pregnancies [adjusted OR = 3.36 (95% CI 2.39–4.71), N = 1808, P < 0.001]. The association appeared stronger in rural areas [OR for PG vs. MG was 3.79 (95% CI 3.61–5.51) in rural areas; 2.09 (95% CI 1.17–3.71) in urban areas; P for interaction = 0.07], and among women with lower socio-economic scores [OR for PG vs. MG was 4.73 (95% CI 3.08–7.25) amongst women with lower SES; OR = 2.14 (95% CI 1.38–3.35) among women with higher SES; P for interaction = 0.008]. There was also evidence of lower risk among primigravidae with better use of the current preventive measures IPTp and LLIN. Conclusions The burden of PM is most heavily focused on primigravidae of low SES living in rural areas of high transmission. Programmes should prioritize primigravidae and young women of child-bearing age for interventions such as LLIN distribution, educational initiatives and treatment to reduce the burden of malaria in first pregnancy.

BACKGROUND RTS, S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by WHO. Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies. METHODS Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with three-way interactions between vaccination, time, and transmission intensity. RESULTS Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest transmission intensity group (0.25 CPPY) decreased from 88.02% to 14.55% over 4.5 years, compared to 81.54% to -27.48% in the highest transmission group (3 CPPY). DISCUSSION These findings suggest that interventions, including the fourth RTS, S dose, which protect vaccinated individuals during the potential rebound period should be implemented for high transmission settings.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6–12 weeks) and children (age 5–17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

An amendment to this paper has been published and can be accessed via the original article.

Background: The evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01(E) elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection. Methods: Ninety-five children (age 5-17 months old at first vaccination) from the RTS,S/AS01(E) phase 3 clinical trial who received 3 doses of RTS,S/AS01(E) or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay. Results: RTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses. Conclusions: RTS,S/AS01(E) induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01(E) immunization is necessary for the design of improved second-generation vaccines. (C) 2020 Elsevier Ltd. All rights reserved.

BACKGROUND:Bacterial and fungal microbiotas are increasingly recognized as important in health and disease starting early in life. However, microbiota composition has not yet been investigated in most rural, low-resource settings, and in such settings, bacterial and fungal microbiotas have not been compared. Thus, we applied 16S and ITS2 amplicon sequencing, respectively, to investigate bacterial and fungal fecal microbiotas in rural Ghanaian children cross-sectionally from birth to 5 years of age. Corresponding maternal fecal and breast milk microbiotas were additionally investigated.RESULTS:While bacterial communities differed systematically across the age spectrum in composition and diversity, the same was not observed for the fungal microbiota. We also identified a novel and dramatic change in the maternal postpartum microbiota. This change included much higher abundance of Escherichia coli and much lower abundance of Prevotella in the first vs. fourth week postpartum. While infants shared more bacterial taxa with their mother's stool and breast milk than with those of unrelated mothers, there were far fewer shared fungal taxa.CONCLUSION:Given the known ability of commensal fungi to influence host health, the distinct pattern of their acquisition likely has important health consequences. Similarly, the dynamics of mothers' bacterial microbiotas around the time of birth may have important consequences for their children's health. Both topics require further study.

IntroductionGhana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed the effectiveness and safety of this policy in Ghana.MethodsA total of 1926 pregnant women enrolled at antenatal care (ANC) clinics were assessed for birth outcomes at delivery, and placental histology results for malaria infection were obtained from 1642 participants. Association of reduced placental or peripheral malaria, anaemia and low birth weight (LBW) in women who received ≥4 IPTp-SP doses compared with 3 or ≤2 doses was determined by logistic regression analysis.ResultsAmong the 1926 participants, 5.3% (103), 19.2% (369), 33.2% (640) and 42.3% (817) of women had received ≤1, 2, 3 or ≥4 doses, respectively. There was no difference in risk of active placental malaria (PM) infection in women who received 3 doses compared with ≥4 doses (adjusted OR (aOR) 1.00, 95% CI 0.47 to 2.14). The risk of overall PM infection was 1.63 (95% CI 1.07 to 2.48) in 2 dose group and 1.06 (95% CI 0.72 to 1.57) in 3 dose group compared with ≥4 dose group. The risk of LBW was 1.55 (95% CI 0.97 to 2.47) and 1.06 (95% CI 0.68 to 1.65) for 2 and 3 dose groups, respectively, compared with the ≥4 dose group. Jaundice in babies was present in 0.16%, and 0% for women who received ≥4 doses of SP.ConclusionThere was no difference in the risk of PM, LBW or maternal anaemia among women receiving 3 doses compared with ≥4 doses. Receiving ≥3 IPTp-SP doses during pregnancy was associated with a lower risk of overall PM infection compared with 2 doses. As there are no safety concerns, monthly administration of IPTp-SP offers a more practical opportunity for pregnant women to receive ≥3 doses during pregnancy.

Background: To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. Methods: In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. Results: Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. Conclusions: RTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect. (C) 2020 Elsevier Ltd. All rights reserved.

Although malaria mortality among children under five years of age is high, the characteristics of their infection patterns are not well described. The aim of this study was to examine the longitudinal sequence pattern of Plasmodium falciparum infections in the first year of life within a birth cohort in Kintampo, Ghana (N = 1855). Infants were monitored at home with monthly sampling and also at the clinic for any febrile illness between 2008 and 2011. Light microscopy was performed on monthly scheduled visits and febrile ill visits over twelve months of follow-ups (n = 19231). Microscopy-positive visits accompanied with or without symptoms were rare during the first five months of life but were common from six to twelve months of age. Among 1264 infants with microscopy data over a minimum of eight monthly visits and also throughout in sick visits, some were microscopy negative (36%), and others positive: only-symptomatic (35%), alternating (22%) and only-asymptomatic (7%). The median age of microscopic infection was seven months for the alternating group and eight months for both the only-symptomatic and only-asymptomatic groups. The alternating group had the highest cumulative incidence of microscopic infections, the lowest age at first infection and 87 different infection patterns. Parasite densities detected by microscopy were significantly higher for symptomatic versus asymptomatic infection. We conclude that infants in malaria endemic areas experience diverse infection profiles throughout their first year of life. Further investigations should include submicroscopic reservoir and may shed more light on the factors that determine susceptibility to malaria during infancy.