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Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries. We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane's Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger's test (bias if p<0.1). Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7-23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37-1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28-0.64). When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03-1.65). A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59-2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30-3.14). The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.

In The Gambia, national estimates of under-five mortality (U5M) were from censuses and multiple indicator cluster surveys (MICS). The country's first demographic and health survey (DHS) conducted in 2013 provided empirical disaggregated national estimates of neonatal, post-neonatal and child mortality trends. To assess the consistency and accuracy of the estimates of U5M from the existing data sources and its age-specific components in rural Gambia and produce reliable up-to-date estimates. Available national data on under-five mortality from 2000 onwards were extracted. Additionally, data from two DHS regions were compared to those from two health and demographic surveillance systems (HDSS) located within them. Indirect and direct estimates from the data were compared and flexible parametric survival methods used to predict mortality rates for all empirical data points up to 2015. Internal consistency checks on data quality for indirect estimation of U5M suggest that the data were plausible at national level once information from women aged 15-19 years was excluded. The DHS and HDSS data used to make direct U5M estimates were plausible, however HDSS data were of better quality. For 2009-2013, the DHS estimates agreed well with the 2013 census and 2010 MICS reports of U5M but was less accurate about the early births of older women. The most recent estimates from the 2013 DHS, which refer to 2011-12, are an U5M rate of 54/1000 livebirths (95% CI: 43-64) and a neonatal mortality rate of 21/1000 livebirths (95% CI: 15-27), contributing almost 40% of U5M in The Gambia. The DHS showed that for the decade prior to the survey, child mortality dropped by 55% and neonatal mortality by 31%. This indicates the importance of neonatal mortality in The Gambia, and the need to focus on neonatal survival, while maintaining currently successful strategies to further reduce U5M.

Aims/hypothesisTranslocation of bacterial debris from the gut causes metabolic endotoxemia (ME) that results in insulin resistance, and may be on the causal pathway to obesity-related type 2 diabetes. To guide interventions against ME we tested two hypothesised mechanisms for lipopolysaccharide (LPS) ingress: a leaky gut and chylomicron-associated transfer following a high-fat meal.MethodsIn lean women (n = 48; fat mass index (FMI) 9.6 kg/m2), women with obesity (n = 62; FMI 23.6 kg/m2) and women with obesity-diabetes (n = 38; FMI 24.9 kg/m2) we used the lactulose-mannitol dual-sugar permeability test (LM ratio) to assess gut integrity. Markers of ME (LPS, EndoCAb IgG and IgM, IL-6, CD14 and lipoprotein binding protein) were assessed at baseline, 2 h and 5 h after a standardised 49 g fat-containing mixed meal. mRNA expression of markers of inflammation, macrophage activation and lipid metabolism were measured in peri-umbilical adipose tissue (AT) biopsies.ResultsThe LM ratio did not differ between groups. LPS levels were 57% higher in the obesity-diabetes group (P < 0.001), but, contrary to the chylomicron transfer hypothesis, levels significantly declined following the high-fat challenge. EndoCAb IgM was markedly lower in women with obesity and women with obesity-diabetes. mRNA levels of inflammatory markers in adipose tissue were consistent with the prior concept that fat soluble LPS in AT attracts and activates macrophages.Conclusions/interpretationRaised levels of LPS and IL-6 in women with obesity-diabetes and evidence of macrophage activation in adipose tissue support the concept of metabolic endotoxemia-mediated inflammation, but we found no evidence for abnormal gut permeability or chylomicron-associated post-prandial translocation of LPS. Instead, the markedly lower EndoCAb IgM levels indicate a failure in sequestration and detoxification.

Background Maternal mortality has been used as the major indicator of maternal health for more than thirty years, but approximately two decades ago, the exploration of women with maternal near-miss (MNM) became a complement indicator to the investigation of maternal deaths (MD). Our objective was to determine the frequencies and causes of severe maternal outcomes (SMO: MNM + MD) in regional and district hospitals in Benin, Burkina Faso and Niger. Methods Between 1st February 2008 and 31st October 2010, we conducted an SMO incidence study in 36 hospitals in the three countries. Results Overall, the incidence study found 77 women with MNM per 1,000 live births (LB) (54 in Benin, 81 in Burkina Faso and 108 in Niger), a maternal mortality ratio (MMR) of 1,775 per 100,000 LB (1,370 in Benin, 2,360 in Burkina Faso and 1,833 in Niger), an MNM to MD ratio of 4.32:1 (3.94 in Benin, 3.44 in Burkina Faso and 5.89 in Niger), and a mortality index [MI = MD / SMO] of 18.8% (20.3% in Benin, 22.5% in Burkina Faso and 14.5% in Niger). The majority of women with SMO (71.9%) were referred from another health facility. In the aggregate of maternal near miss of 1,788 cases, it was observed that 90.0% of women had a near miss complication on admission to a participating hospital. Conclusions At the time of our study the burden of severe maternal outcomes was high in Benin, Burkina Faso and Niger. We found that most women had a near miss complication on admission to a participating hospital, indicating the need to facilitate access to obstetric care for women with high risk pregnancies and complications.

How do choices in criminal law and rights protections affect disease-fighting efforts? This long-standing question facing governments around the world is acute in the context of pandemics like HIV and COVID-19. The Global AIDS Strategy of the last 5 years sought to prevent mortality and HIV transmission in part through ensuring people living with HIV (PLHIV) knew their HIV status and could suppress the HIV virus through antiretroviral treatment. This article presents a cross-national ecological analysis of the relative success of national AIDS responses under this strategy, where laws were characterised by more or less criminalisation and with varying rights protections. In countries where same-sex sexual acts were criminalised, the portion of PLHIV who knew their HIV status was 11% lower and viral suppression levels 8% lower. Sex work criminalisation was associated with 10% lower knowledge of status and 6% lower viral suppression. Drug use criminalisation was associated with 14% lower levels of both. Criminalising all three of these areas was associated with approximately 18%–24% worse outcomes. Meanwhile, national laws on non-discrimination, independent human rights institutions and gender-based violence were associated with significantly higher knowledge of HIV status and higher viral suppression among PLHIV. Since most countries did not achieve 2020 HIV goals, this ecological evidence suggests that law reform may be an important tool in speeding momentum to halt the pandemic.

•This is the first study to evaluate clinical effectiveness of PPV23 revaccination in older adults.•This observational study did not identify evidence to support PPV23 revaccination in older adults.•There is no evidence of benefit of PPV23 revaccination regardless of dosing interval or age. Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23). A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups. Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74–2·20) and IPD (aHR 1·44; 95 %CI 1·41–1·46). In participants aged 64–74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75–2·33) and HP (aHR 1·46; 95 %CI 1·42–1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08–1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94–1·52). No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required.

MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37°C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs.

DREAMS promotes a comprehensive HIV prevention approach to reduce HIV incidence among adolescent girls and young women (AGYW). One pathway that DREAMS seeks to impact is to support AGYW to stay in school and achieve secondary education. We assessed the impact of DREAMS on educational outcomes among AGYW in Nairobi, Kenya. In two informal settlements in Nairobi, 1081 AGYW aged 15-22 years were randomly selected in 2017 and followed-up to 2019. AGYW reporting invitation to participate in DREAMS during 2017-18 were classified as \"DREAMS beneficiaries\". Our main outcome was being in school and/or completed lower secondary school in 2019. We used multivariable logistic regression to quantify the association between being a DREAMS beneficiary and the outcome; and a causal inference framework to estimate proportions achieving the outcome if all, versus no, AGYW were DREAMS beneficiaries, adjusting for the propensity to be a DREAMS beneficiary. Of AGYW enrolled in 2017, 79% (852/1081) were followed-up to 2019. In unadjusted analysis, DREAMS beneficiaries had higher attainment than non-beneficiaries (85% vs 75% in school or completed lower secondary school, Odds Ratio (OR) = 1.9; 95%CI: 1.3,2.8). The effect weakened with adjustment for age and other confounders, (adjusted OR = 1.4; 95%CI: 0.9,2.4). From the causal analysis, evidence was weak for an impact of DREAMS (estimated 83% vs 79% in school or completed lower secondary school, if all vs no AGYW were beneficiaries, difference = 4%; 95%CI: -2,11%). Among AGYW out of school at baseline, the estimated differences were 21% (95%CI: -3,43%) among 15-17 year olds; and 4% (95%CI: -8,17%) among 18-22 year olds. DREAMS had a modest impact on educational attainment among AGYW in informal settlements in Kenya, by supporting both retention and re-enrolment in school. Larger impact might be achieved if more AGYW were reached with educational subsidies, alongside other DREAMS interventions.

There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1 (n = 33) was the control group and comprised infants who received PCV7 after 6 months and came from unvaccinated communities. Group 2 (n = 30) came from unvaccinated communities and Group 3 (n = 39) came from vaccinated communities. Both group 2 and 3 received PCV7 at 2, 3 and 4 months. Culture and 16 S rRNA gene sequencing were performed on nasopharyngeal specimens collected at regular intervals from infants. Nasopharyngeal carriage of PCV7 serotypes in Group 1 was significantly higher than in Group 2 and 3 (p < 0.01). However, pneumococcal carriage remained comparable due to an expansion of non-vaccine serotypes in Groups 2 and 3. Determination of phylogenetic dis(similarities) showed that the bacterial community structures were comparable across groups. A mixed effects model showed no difference in community richness (p = 0.15) and Shannon α -diversity (p = 0.48) across the groups. Immediate replacement of pneumococcal vaccine serotypes with non-vaccine serotypes may mitigate the impact of PCV7 on nasopharyngeal bacterial community structure and ecology.

Background The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. Methods Female and male children aged 1–14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1–3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1–3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1–3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. Results From 9 to 22 June 2022, 627 children aged 1–14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13–5.00, p = 0.63). Conclusions Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. Trial registration : The study is registered at Clinical Trial.gov NCT05354258.