Background Large-for-gestational-age (LGA) and macrosomic newborns are at increased risk of adverse perinatal outcomes, including death, yet the burden of neonatal mortality associated with these conditions in low- and middle-income countries (LMICs), where ongoing nutritional and epidemiological transitions suggest their prevalence will rise, remains poorly quantified. In this study, we quantify the neonatal mortality risk associated with LGA and macrosomia from 16 subnational birth cohorts in low- and middle-income countries between 2000 and 2017. Methods and findings This is an individual-participant meta-analysis to estimate neonatal mortality rates (NMRs) and relative risks among LGA infants (>90th and >97th percentile birth weight-for-gestational-age using INTERGROWTH-21st) versus appropriate-for-gestational-age (AGA, 10th-90th percentile) infants. Macrosomic (≥4000 g and ≥4500 g) neonates were compared with those weighing 2500 g-3999g. Missing birth weights were imputed using recalibration and multiple imputation methods. We used random effects meta-analysis to pool relative risks. Median prevalences of LGA >90th and >97th percentile were 5.3% (interquartile range 3.6-8.2) and 2.6% (IQR 1.3-4.5), respectively; macrosomia (≥4000 g and ≥4500 g) prevalences were 1.0% (IQR 0.3-3.1) and 0.06% (IQR 0.0, 0.30), respectively. Mortality was highest among preterm plus LGA infants (61.3 per 1000). LGA infants in the >90th percentile had over twofold increased mortality compared with appropriate-for-gestational-age infants (RR: 2.46; 95% CI: 1.86-3.25), while >97th percentile infants had a higher risk (RR: 3.77; 95% CI: 2.50-5.69). Term LGA >97th percentile infants also showed elevated mortality (RR: 3.14; 95% CI: 1.58-6.22). For LGA >97th percentile, the risk was higher in the early neonatal period (RR: 2.71; 95% CI: 1.92-3.82) than late (RR: 1.69; 95% CI: 1.22-2.34). There was no overall association between macrosomia (≥4000 g) and neonatal mortality. Population attributable fractions were 7.2% for LGA >90th percentile and 0.4% for macrosomia (≥4000 g). Conclusions Neonatal mortality risks were elevated among LGA infants in low- and middle-income countries, particularly at extreme values (>97th percentile) and during the early neonatal period. Macrosomia showed weaker, less robust associations. Although LGA prevalence is currently low (∼5%) and contributes less to neonatal mortality than small newborns, ongoing nutritional and epidemiological transitions suggest increasing prevalence. This highlights the need for strengthened surveillance, monitoring, and improved delivery planning to ensure that no population is left behind. ### Competing Interest Statement The authors have declared no competing interest. ### 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 Institutional Review Board of the John Hopkins Bloomberg School of Public Health (IRB No: 28757, approval date: 18 April 2024) waived ethical approval for this work. 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 request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions  Gates Foundation, Investment IDINV-053360

Klebsiella pneumoniae expressing Extended-Spectrum-Beta-Lactamases (ESBLs) are a significant global public health challenge, affecting humans and livestock. However, the molecular epidemiology and relatedness between isolates from human and livestock reservoirs in Tanzania have not been well studied. This study aimed to address this knowledge gap by conducting a cross-sectional analysis in the Korogwe District, Tanzania. Klebsiella pneumoniae complex isolates were collected from children with and without diarrhoea and from chickens in commercial and smallholder farms. ESBL-positive isolates were subsequently tested for phenotypic resistance and analysed by whole-genome sequencing. ESBL-positive K. pneumoniae complex isolates were encountered from children with diarrhoea, 14% (n/N = 37/259), and 7% (n/N = 17/258) without diarrhoea. For chicken isolates, 10% (n/N = 38/371) of the commercial and 5% (n/N = 21/406) of the smallholder farms were ESBL-positive. The sequenced ESBL-positive isolates from humans and chickens comprised 73% (n/N = 69/95) K. pneumoniae, 14% (n/N = 13/95) K. quasipneumoniae subsp. quasipneumoniae, 13% (n/N = 12/95) K. quasipneumoniae subsp. similipneumoniae, and 1% (n/N = 1/95) K. quasivariicola. A broad variety of sequence types was observed, with 15 clusters of clonal identity identified, mostly in chickens from the same farm. Our findings also showed 68 isolates with 44 distinct capsular types. blaCTX-M-15 was the most commonly identified ESBL-expressing gene. In conclusion, the study highlights the possibility of interspecies transmission of ESBL-positive K. pneumoniae complex isolates between humans and chickens in the study area, emphasising the need for integrated One Health strategies to mitigate the spread of antimicrobial resistance in Tanzania.

BACKGROUND:Molecular surveillance is essential to detect emerging artemisinin partial resistance (ART-R) and partner drug resistance in Sub-Saharan Africa. OBJECTIVES:To describe the prevalence of Plasmodium falciparum resistance markers in two high-burden countries using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL): the Democratic Republic of the Congo (DRC) and Tanzania. METHODS:A total of 1254 day-0 P. falciparum-positive samples were analysed: 837 from four sentinel sites of a therapeutic efficacy study (TES) in the DRC (2017) and 417 from an intermittent preventive treatment in schoolchildren (IPTsc) trial in Handeni and Kilindi districts, Tanga Region, Tanzania (2020-2021). Pfkelch13, Pfcrt and Pfmdr1 were analysed by Illumina MiSeq amplicon sequencing. RESULTS:Reliable sequences were obtained for 1193 isolates. The Pfkelch13 wild-type allele predominated (98.4%); none of the four non-synonymous mutations detected (N489Y, K568T, A578S, V589I) are classified as validated, candidate or potential ART-R markers, and the validated markers R561H, P441L and C469Y reported elsewhere in East Africa were absent. Pfcrt K76T was found in 23.3% of Tanzanian and 26.3% of DRC isolates, with substantial between-site variation in the DRC (4.3% to 93.6% at Rutshuru). Pfmdr1 haplotype profiles differed between countries: NFSND predominated in Tanzania (71.5%) while NYSND remained the most frequent in the DRC (60.9%); 86Y was twice as frequent in the DRC (11.1%) as in Tanzania (6.2%). CONCLUSIONS:No validated ART-R marker was detected, but partner-drug haplotype distributions reflected the first-line ACTs used in each country. Continued molecular surveillance is needed to track these signatures alongside the recent emergence of ART-R.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Offspring of GDM mothers have an increased risk of developing type 2 diabetes (T2D), obesity, and other metabolic disorders later in life. We analyzed metabolic, genetic, epigenetic, and transcriptional profiles in umbilical cord blood (UCB) from male and female offspring of GDM mothers versus normoglycemic controls in Tanzania. We constructed polygenic and methylation risk scores for T2D and GDM to assess whether diabetes-related susceptibility is detectable at birth. We identified differentially expressed genes (DEGs) and corresponding epigenome-wide alterations in GDM-exposed UCB. We then integrated genetic (PGS), epigenetic (MRS), and transcriptomic (DEG) data to identify convergent molecular signatures of GDM exposure. We examined their associations with neonatal anthropometry and cord insulin levels to infer potential effects on early growth. We further assessed DEG relevance by examining expression in human fetal and adult islets and by reviewing mouse-knockout data to explore possible roles in β-cell development or function. Offspring of GDM mothers showed sex-specific differences in neonatal anthropometry, particularly among females, who exhibited greater adiposity and growth measures. Female offspring also displayed higher PGS for T2D, especially β-cell dysfunction, and a MRS for GDM/T2D associated with elevated cord insulin. We identified 36 DEGs in GDM-exposed UCB overall, with a striking sex-specific pattern (273 DEGs in females vs. 4 in males). Several DEGs and associated DNA methylation (DNAm) sites correlated with neonatal anthropometry, particularly in females, indicating putative fetal programming signatures. These signals showed convergence across genetic risk, DNA methylation, and gene expression layers. The expression of SESN3, HMBS, NUTM2D, and MAN2A2 associated with insulin levels. MAN2A2 expression also associated with birth weight and length in female offspring. The SLC4A1 gene showed fetal pancreas-specific expression and co-expression with key pancreatic developmental genes, suggesting a role in pancreatic development. We identified integrated multi-omic signatures of GDM exposure in offspring at birth, with markedly stronger effects in females. These genes and pathways may contribute to fetal metabolic programming in this understudied Tanzanian population, offering new insights into biological mechanisms that may influence early development. ClinicalTrials.gov NCT02191683 Registered 2 July 2014.

Several interventional strategies have been implemented in malaria endemic areas where the burden is high, that include among others, intermittent preventive treatment (IPT), a tactic that blocks transmission and can reduce disease morbidity. However, the implementation IPT strategies raises a genuine concern, intervening the development of naturally acquired immunity to malaria which requires continuous contact with parasite antigens. This study investigated whether dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) IPT in schoolchildren (IPTsc) impairs IgG reactivity to six malaria antigens. An IPTsc trial in north-eastern Tanzania administered three doses of DP or ASAQ at four-monthly intervals and the schoolchildren were followed up. This study compared IgG reactivity against GLURP-R2, MSP1, MSP3, and CIDR domains (CIDRa1.1, CIDRa1.4, and CIDRa1.5) of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) in intervention and control groups using enzyme linked immunosorbent assay (ELISA) technique. During the study, 369 schoolchildren were available for analysis, 119, 134 and 116 participants in the control, DP and ASAQ groups, respectively. Breadth of malaria antigen recognition increased significantly during and after the intervention phases and did not differ between the study groups (Trend test: DP, z-score = 5.92, p < 0.001, ASAQ, z-score = 6.64, p < 0.001 and control, z-score = 5.85, p < 0.001). There were no differences between the control and ASAQ group in the recognition of any of the tested antigens at all visits. In the DP group, however, during the intervention period IPTsc did not impair antibody against MSP1, MSP3, CIDRa1.1, CIDRa1.4 and CIDRa1.5, but it did impair against GLURP-R2. The current study has shown that effective IPTsc with DP or ASAQ does not interfere with the development of antibodies against malaria antigens of the blood stages, suggesting that the advancement of naturally acquired immunity to malaria is not impeded by IPTsc interventions.

Background In sub-Saharan Africa, invasive non-typhoidal Salmonella disease, characterized by bloodstream infections with high mortality rates, poses a significant public health burden. In Africa, Salmonella enterica , which are typically livestock- associated pathogens in industrialised countries, have genetically evolved and anthroponotic transmission has been proposed for S . Typhimurium ST313. In this study, we investigated the hypothesis of an exclusively anthroponotic transmission reservoir of Salmonella enterica ST313 and aimed to identify reservoirs for other Salmonella spp . , shedding light on their occurrence in different ecological niches. Methods This study used a One Health approach and Salmonella were isolated from humans, livestock and the environment, in Tanzania and in Ghana. Salmonella spp. were identified by biochemical methods and antibiotic susceptibility was tested. Isolates were subjected to whole genome sequencing. Results Out of 9,086 collected samples, 222 Salmonella enterica were identified comprising 58 serovars. The highest level of antimicrobial resistance was found in humans with emerging fluroquinolone resistance and multidrug resistance being highest in isolates from blood cultures (24%, n/N = 11/46). For the invasive strains, the sequence types S . Typhimurium ST313 and ST19 were most common and ST313 was associated with multidrug resistance, followed by S . Enteritidis ST11 and ST147 and S . Dublin ST10. An overlap of sequence types amongst human-livestock and human-environmental strains was detected for S . Typhimurium ST19 but not found for ST313 and the two serovars Dublin and Enteritidis. Conclusions Our study adds further evidence of S . Typhimurium ST313 being restricted to a human reservoir and linked to multidrug resistance. Additionally, our study provides comprehensive insights into Salmonella genetic diversity and distribution among humans, animals and the environment in Ghana and in Tanzania. This sheds light on other potential reservoirs for infections, all of which show antimicrobial resistance. Further research into stool carriage is warranted, encompassing patients with invasive disease and those with and without diarrhoea, to identify transmission reservoirs in particular for invasive disease-causing strains. These findings underscore the need for integrated One Health approaches to effectively monitor and manage salmonellosis and mitigate public health risks. Continued research into the spread of Salmonella spp. and its evolution is crucial for targeted interventions and disease control.

Geophagia or soil-eating behavior is common among pregnant women in sub-Saharan Africa, however its relationship with nutritional status demands further investigation. Using a prospective pregnancy cohort from north-eastern Tanzania, we examined the characteristics of geophagia and its association with nutritional status parameters (mid-upper arm circumference (MUAC), vitamin B12, folate, ferritin, and hemoglobin) before conception and throughout the gestational period. Pregnant women (n = 530) were interviewed in each trimester regarding their soil-eating habits. Serum concentrations of vitamin B12, folate, ferritin, and hemoglobin, and MUAC were measured before conception and in each trimester. Cross-sectional comparisons between women who ate and did not eat soil were analyzed using Welch’s t-test for continuous variables and χ2-test for categorical variables. The association between changes in nutritional status parameters and the initiation of geophagia was investigated using multivariable logistic regression. The prevalence of geophagia in this cohort was 27

Plasmodium falciparum pathology is driven by the accumulation of parasite-infected erythrocytes in blood capillaries. This sequestration process is mediated by the parasite's P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins, which bind select endothelial cell receptors. A subset of PfEMP1 binding human endothelial protein C receptor (EPCR) through their cysteine-rich interdomain region alpha 1 (CIDRα1) domains drives the pathogenesis to severe malaria. Despite high sequence diversity among CIDRα1 domains, individuals living in malaria-endemic regions become immune to severe disease in part through acquisition of antibodies inhibiting the PfEMP1-EPCR interaction. Here, we demonstrate an approach to identify pathogen-specific human monoclonal antibodies from plasma, combining mass spectrometry analysis of antigen-purified polyclonal plasma IgG and Ig transcript sequencing. We identified a clonal family of broadly reactive and EPCR binding-inhibitory human monoclonal antibodies against CIDRα1. The antibodies, isolated from a 9-y-old child, exhibited potent inhibition of EPCR binding broadly across CIDRα1 domains as well as binding of infected erythrocytes to EPCR. Structural analysis of one antibody variant complexed with CIDRα1 revealed a shared epitope of the clonal antibody family overlapping the EPCR binding site and the epitopes of two previously identified monoclonal antibodies, C7 and C74, with similar functional patterns. However, although C7, C74, and 110-3 antibodies all depend on the same few residues conserved in CIDRα1 to retain EPCR binding, the 110-3 antibodies contact additional variable residues, reducing their breadth of reactivity across the CIDRα1 family. These data bolster the hypothesis that broadly inhibitory antibodies against severe malaria-associated PfEMP1 target similar epitopes and are commonly developed in malaria-exposed individuals.

Objective: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). Design: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. Setting: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. Population: Live birth neonates. Methods: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. Main Outcome Measures: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. Results: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. Conclusions: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

WHO and the Lancet reported that malaria and malnutrition form a double health burden in low and middle-income countries. Despite the massive implementation of malaria control interventions, there is scarce evidence on the impact of intermittent preventive therapy (IPTsc) for malaria on the nutritional status of school-age children. In this study, we aimed to determine malnutrition risk factors and evaluate the impact of IPTsc for malaria on the nutritional status of school-age children in Muheza, Tanga, Tanzania. We analysed secondary data from a cross-sectional baseline survey and a randomized controlled open-label trial conducted in Muheza, Tanga, Tanzania. Participants of our study were children of age 5–15 years. Baseline data collection was carried out between February-April 2019. The study continued through December 2020, during which participants were randomly assigned to one of the three groups: dihydroartemisinin-piperaquine (DP), artesunate-amodiaquine (ASAQ), or a control group, using a 3-arms balanced block design with a 1:1:1 allocation ratio. Intervention treatments were administered at recruitment, 4 months, and 8 months of the trial. Data were analysed using logistic regression and a linear mixed model. At baseline, the prevalence of malaria was 27

Malaria, which affects over half of the world’s population, is controlled through clinical interventions and vector control strategies. However, these efforts are threatened by resistance to anti-malarial drugs and insecticides, as well as affected by environmental, ecological, and climatic changes. This study examined changes in malaria prevalence and related factors based on data from 18 cross-sectional surveys conducted in two villages in northeastern Tanzania. From 2003 to 2021, annual cross-sectional malariometric surveys were conducted in two study villages, Mkokola (lowland) and Kwamasimba (highland), samples collected to determine Plasmodium falciparum infection and human exposure to malaria vector Anopheles. Pearson's chi-squared test was used for comparing proportions, logistic and linear regressions test were used analyse associations. Generalized Estimating Equations (GEE) was used to analyse the relationship between malaria prevalence and climatic variables. Malaria prevalence in Kwamasimba and Mkokola dropped from 25

Aims and MethodsIn low- and middle- income countries (LMICs) consequences of gestational diabetes (GDM) is understudied. Using a prospective cohort of mothers (n = 197)and children (n = 251), from rural north-eastern Tanzania, we assessed prediabetes and type 2 diabetes (T2D) prevalence six years after a pregnancy with/without GDM.ResultsThe prevalence of prediabetes (49.4 % vs. 46.4 %) orT2D (20.0 % vs. 16.1 %), p ≥ 0.36, based on fasting plasma glucose (FPG) or HbA1clevels (prediabetes: 16.9 % vs. 13.8 % and T2D 1.2 % vs. 0 %, p = 0.47), andcardio-metabolic health parameters,weresimilar between women with/without previous GDM. These results were supported by similar perinatal outcomes and child health at follow-up.The overall prevalence ofprediabetes/T2D was high, but no differences in other cardio-metabolic risk markers were observed in women with prediabetes/T2D compared to women with normal glucose tolerance.ConclusionsDespite high prevalence of GDM amongTanzanian women, the diagnosis was not associated with adverse pregnancy outcomes, nor with increased risk of prediabetes or T2D at follow-up. FPG and HbA1c may be poor markers for diabetes in this population, and further follow-up studies with longer time intervals are warranted to evaluate which GDM diagnostic criteria are most optimal for women in rural Tanzania and similar LMIC settings.

Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from A/A to G/G enhanced PPARGC1B expression throughout the adipogenic differentiation, identifying rs10071329 as a cis-eQTL. The higher PPARGC1B expression in G/G cells coincided with greater accumulation of triglycerides, and higher expression of mitochondria-encoded genes, but without significant effects on adipogenic marker expression. Furthermore, G/G cells had improved basal- and norepinephrine-stimulated mitochondrial respiration, possibly relating to enhanced mitochondrial gene expression. The G/G cells also exhibited increased norepinephrine-stimulated glycerol release, indicating improved lipolysis. Altogether, our results showed that rs10071329 is a cis-eQTL, with the G/G genotype conferring enhanced PPARGC1B expression, with consequent improved mitochondrial function and response to norepinephrine in brown adipocytes. This genetic variant, and as yet undetermined eQTLs, at PPARGC1B could prove useful in genotype-based precision medicine for obesity treatment.

OBJECTIVE:To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN:Descriptive multi-country secondary data analysis. SETTING:Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION:Liveborn infants from 15 population-based cohorts. METHODS:Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0, 39+0-41+6 (reference category), 37+0-38+6, 34+0-36+6,34+0-36+6,32+0-33+6, 30+0-31+6, 28+0-29+6 and less than 28 weeks. MAIN OUTCOME MEASURES:Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS:We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370-386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS:In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Objectives Malaria and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are associated with adverse pregnancy outcomes. This study reports the prevalence and risk factors of curable STIs/RTIs, STI/RTI co-infection and STI/RTI and malaria co-infection among HIV-negative pregnant women at their first antenatal care visit in Kenya, Malawi and Tanzania.Methods HIV-negative pregnant women of all gravidae (n=4680) were screened for syphilis with point-of-care tests and treated if positive. Separately, women provided blood samples (n=4569) for rapid plasma reagin (RPR) testing; positive cases were confirmation by Treponema pallidum particle agglutination (TPPA). Women also provided dried blood spots for batch testing of malaria by retrospective polymerase chain reaction (PCR (n=4226) methods. A randomly selected subgroup of women provided vaginal swabs for chlamydia, gonorrhoea and trichomoniasis testing by retrospective PCR batch testing (n=1431), and bacterial vaginosis diagnosis by Nugent scoring (n=1402).Results Malaria prevalence was 14.6% (95% CI 13.6 to 15.7), 45.9% (43.4 to 48.4) of women were positive for at least one curable STI/RTI and 6.7% (5.5 to 8.1) were co-infected with malaria and a curable STI/RTI. Prevalence of individual STIs/RTIs ranged from 28.5% (26.2 to 30.9) for bacterial vaginosis to 14.5% (12.7 to 16.4) for trichomoniasis, 13.8% (12.1 to 15.7) for chlamydia, 2.7% (1.9 to 3.6) for gonorrhoea and 1.7% (1.4 to 2.2) for RPR/TPPA-confirmed syphilis. The prevalence of STI/RTI co-infection was 10.1% (8.7 to 11.8). Paucigravidae, at highest risk of malaria, were also at greater risk of having chlamydia, gonorrhoea and bacterial vaginosis than multigravidae.Conclusions Of women infected with malaria, 49.0% also had a curable STI/RTI and one in five women with at least one STI/RTI were co-infected with more than one STI/RTI. Current antenatal interventions that address malaria and curable STIs/RTIs remain suboptimal. New approaches to preventing and managing these infections in pregnancy are urgently needed.Trial registration number NCT03208179.

ObjectiveTo describe the mortality risks by fine strata of gestational age and birthweight among 230679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DesignDescriptive multi-country secondary data analysis. SettingNine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. PopulationLiveborn infants from 15 population-based cohorts. MethodsSubnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999g (reference category), macrosomia as >= 4000g, moderate low as 1500-2499g and very low birthweight as <1500g. We analysed fine strata classifications of preterm, term and post-term: >= 42(+0), 39(+0)-41(+6) (reference category), 37(+0)-38(+6), 34(+0)-36(+6),34(+0)-36(+6),32(+0)-33(+6), 30(+0)-31(+6), 28(+0)-29(+6) and less than 28weeks. Main outcome measuresMedian and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (<= 25 versus >25 neonatal deaths per 1000 live births). ResultsWe found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 37(0)-38(6)weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. ConclusionsIn addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

OBJECTIVES:Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru.METHODS:The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies.RESULTS:PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC).CONCLUSIONS:R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.

ObjectiveIntermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; To explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania.MethodsSNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13 and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379).ResultsThe prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, p=0.013), but no differences were observed between the treatment arms (χ2=0.05, p=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, p=0.32).ConclusionsThe IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.

Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.