The WHO Global Health Sector Strategy aims to reduce worldwide syphilis incidence by 90% between 2018 and 2030. If this goal is to be achieved, interventions that target high-burden groups, including men who have sex with men (MSM), will be required. However, there are no global prevalence estimates of syphilis among MSM to serve as a baseline for monitoring or modelling disease burden. We aimed to assess the global prevalence of syphilis among MSM using the available literature. In this global systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and AIM databases, and Integrated Bio-Behavioral Surveillance (IBBS) reports between April 23, 2019, and Feb 1, 2020, to identify studies done between Jan 1, 2000, and Feb 1, 2020, with syphilis point prevalence data measured by biological assay among MSM (defined as people who were assigned as male at birth and had oral or anal sex with at least one other man in their lifetime). Studies were excluded if participants were exclusively HIV-infected MSM, injection-drug users, only seeking care for sexually transmitted infections (STIs) or genital symptoms, or routine STI clinic attendees. Data were extracted onto standardised forms and cross-checked for accuracy and validity. We used random-effects models to generate pooled prevalence estimates across the eight regions of the Sustainable Development Goals. We calculated risk of study bias based on the Appraisal tool for Cross-Sectional Studies, and stratified results based on low versus high risk of bias. This systematic review and meta-analysis was registered with PROSPERO, CRD42019144594. We reviewed 4339 records, 228 IBBS reports, and ten articles from other sources. Of these, 1301 duplicate records were excluded, 2467 records were excluded after title and abstract screening, and 534 articles were excluded after full-text analysis. We identified 345 prevalence data points from 275 studies across 77 countries, with a total of 606 232 participants. Global pooled prevalence from 2000-20 was 7·5% (95% CI 7·0-8·0%), ranging from 1·9% (1·0-3·1%) in Australia and New Zealand to 10·6% (8·5-12·9%) in Latin America and the Caribbean. Unacceptably high syphilis prevalence among MSM warrants urgent action. Wellcome Trust.

ContextMalaria and sexually transmitted infections/reproductive tract infections (STIs/RTIs) in pregnancy are direct and indirect causes of stillbirth, prematurity, low birth weight, and maternal and neonatal morbidity and mortality.ObjectiveTo conduct a systematic review and meta-analysis of malaria and STI/RTI prevalence estimates among pregnant women attending antenatal care facilities in sub-Saharan Africa.Data SourcesPubMed, MEDLINE, EMBASE, the World Health Organization International Clinical Trials Registry, and reference lists were searched for studies reporting malaria, syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, or bacterial vaginosis among pregnant women attending antenatal care facilities in sub-Saharan Africa.Study SelectionIncluded studies were conducted in 1990-2011 with open enrollment. Studies from South Africa, where malaria is no longer endemic, were excluded.Data ExtractionPoint prevalence estimates were corrected for diagnostic precision. A random-effects model meta-analysis was applied to produce pooled prevalence estimates.ResultsA total of 171 studies met inclusion criteria, providing 307 point prevalence estimates for malaria or STIs/RTIs and including a total of 340 904 women. The pooled prevalence estimates (with 95% CIs and number of women with positive diagnosis) among studies in 1990-2011 in East and Southern Africa were as follows: syphilis, 4.5% (3.9%-5.1%; n = 8346 positive diagnoses), N gonorrhoeae, 3.7% (2.8%-4.6%; n = 626), C trachomatis, 6.9% (5.1%-8.6%; n = 350), T vaginalis, 29.1% (20.9%-37.2%; n = 5502), bacterial vaginosis, 50.8% (43.3%-58.4%; n = 4280), peripheral malaria, 32.0% (25.9%-38.0%; n = 11 688), and placental malaria, 25.8% (19.7%-31.9%; n = 1388). West and Central Africa prevalence estimates were as follows: syphilis, 3.5% (1.8%-5.2%; n = 851), N gonorrhoeae, 2.7% (1.7%-3.7%; n = 73), C trachomatis, 6.1% (4.0%-8.3%; n = 357), T vaginalis, 17.8% (12.4%-23.1%; n = 822), bacterial vaginosis, 37.6% (18.0%-57.2%; n = 1208), peripheral malaria, 38.2% (32.3%-44.1%; n = 12 242), and placental malaria, 39.9% (34.2%-45.7%; n = 4658).ConclusionThe dual prevalence of malaria and STIs/RTIs in pregnancy among women who attend antenatal care facilities in sub-Saharan Africa is considerable, with the combined prevalence of curable STIs/RTIs being equal to, if not greater than, malaria.

The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages. Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention. US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship.

Objectives: To estimate where intermittent preventive treatment (IPTp) using sulphadoxine–pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G.Methods: We conducted a systematic review and meta‐analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp‐SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta‐regression models to these data and conducted sensitivity analysis of the 581G mutation.Results: Variation in the protective effect of IPTp‐SP against LBW could not be explained by malaria transmission intensity. Among primi‐ and secundigravidae, IPTp‐SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = 10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random‐effects models among multigravidae showed that IPTp‐SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was >10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47).Conclusion: There appears to be a prevalence of 581G above which IPTp‐SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is >10.1% to define the specific prevalence threshold where new strategies should be deployed.

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp.

We conducted a prospective cohort study in Zambia among pregnant women who received intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP). We calculated the odds ratios (ORs) of adverse birth outcomes by IPTp-SP exposure, 0–1 dose (n = 126) vs ≥2 doses (n = 590) and ≥2 doses (n = 310) vs ≥3 doses (n = 280) in 7 categories of malaria infection and sexually transmitted and reproductive tract infections (STIs/RTIs). We found no significant differences in baseline prevalence of infection across IPTp-SP exposure groups. However, among women given 2 doses compared to 0–1 dose, the odds of any adverse birth outcome were reduced 45% (OR, 0.55; 95% confidence interval [CI], 0.36, 0.86) and 13% further with ≥3 doses (OR, 0.43; 95% CI, 0.27, 0.68). Two or more doses compared to 0–1 dose reduced preterm delivery by 58% (OR, 0.42; 95% CI, 0.27, 0.67) and 21% further with ≥3 doses (OR, 0.21; 95% CI, 0.13, 0.35). Women with malaria at enrollment who received ≥2 doses vs 0-1 had 76% lower odds of any adverse birth outcome (OR, 0.24; 95% 0.09, 0.66), and Neisseria gonorrhoeae and/or Chlamydia trachomatis had 92% lower odds of any adverse birth outcome (OR, 0.08; 95% CI, 0.01, 0.64). Women with neither a malaria infection nor STIs/RTIs who received ≥2 doses had 73% fewer adverse birth outcomes (OR, 0.27; 95% CI, 0.11, 0.68). IPTp-SP appears to protect against malaria, STIs/RTIs, and other unspecified causes of adverse birth outcome.