21367 research outputs found
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Tracking the spatial and longitudinal dynamics of mixed infections of urogenital and intestinal schistosomiasis, inclusive of Schistosoma mattheei, in two sentinel rural communities from southern Malawi
Full text linkThe World Health Organization's 2030 neglected tropical disease roadmap aims to eliminate schistosomiasis as a public health problem with preventive chemotherapy (PC) as a foundational stratergy; however, mixed infections of Schistosoma haematobium with zoonotic species, inclusive of putative hybrids, present a potential challenge. We sought to address the importance of mixed species infections through a 2-year, longitudinal epidemiological investigation at two villages in southern Malawi (Samama and Mthawira). Participants (approx. 2000) were sampled at baseline (BL), a 12-month follow-up (FU1) and a 24-month follow-up (FU2). PC was provided annually (BL-FU1) and biannually (FU1-FU2). Urine samples underwent microscopical examination and circulating cathodic antigen (CCA) rapid-diagnostic testing, with egg-patent urine filters undergoing additional molecular screening for five non-S. haematobium species using real-time polymerase chain reaction (rtPCR). Prevalence of schistosomiasis by microscopy was statistically higher in Samama than Mthawira (±0.0563, p-value = 1.3 × 10 -11), as was mixed infections with Schistosoma mattheei, by rtPCR (± 0.17, p-value = 3.84 × 10 -10). By FU2, PC reduced the prevalence of S. haematobium and Schistosoma mansoni, but that of S. mattheei remained relatively stable, rising by 0.98% at Samama (± 0.19, p-value = 0.41) and decreasing by 0.43% at Mthawira (± 0.39, p-value = 0.33). We conclude that treatment alone will not be sufficient for control of zoonotic S. mattheei, but additional interventions will be required. This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.</p
Adiposity and reproductive characteristics across the lifespan: a multi-ethnic population-based study in Northwest China
Full text linkBackground: Reproductive characteristics significantly shape physiological adaptations, little is known about how they relate to adiposity in women of multi-ethnic regions undergoing a rapid increase in obesity burden. This study aims to address this gap by assessing how reproductive patterns correlate with adiposity and identifying potential moderating factors among Chinese adults. Methods: In 2018–2019, 107,679 participants from the Regional Ethnic Cohort Study in China were included in this cross-sectional analysis. Restricted cubic spline and generalized linear regression models were used to assess the association of reproductive characteristics such as age at menarche and menopause, number of children, menopause status, duration of post-menopause, and reproductive years, as well as reproductive pattern with adiposity using body mass index (BMI). Reproductive pattern was characterized using a Higher-Risk Reproductive Score (HRRS), which incorporates key landmarks such as early menarche (≤ 12 years), having ≥ 3 children, and later age at menopause (≥ 51 years). Results: Females’ mean BMI was 24.4 (standard deviation, SD 3.8) kg/m2, with the median age at menarche and menopause of 15.0 (interquartile range, IQR 2.0) and 49.0 (IQR 5.0), median number of children and reproductive years of 2.0 (IQR 1.0) and 34.0 (IQR 6.0). Age at menarche was non-linearly associated with an average drop of 0.13 kg/m2 in BMI, particularly in Uyghur ethnic and younger adults. Age at menopause and reproductive years was non-linearly related to higher BMI by 0.05 and 0.07 kg/m2 per year delay. Adiposity exhibited an inverted U-shape with number of children. The duration of post-menopause correlated with a BMI reduction of 0.08 kg/m² on average. The HRRS was associated with an increase of 0.56 kg/m2 in BMI. Conclusions: Among Chinese women, earlier age at menarche and later age at menopause were associated with increased adiposity. Adiposity showed an inverted U-shaped relationship with number of children, and a higher-risk reproductive pattern was linked to increased adiposity.</p
Genomic population structure and insecticide resistance mechanisms in the malaria vector An. coluzzii across contrasting bioclimatic zones in West Africa
Full text linkBackground: Environmental barriers influencing the movement of insect vectors can govern adaptive gene flow, including the dispersal of insecticide resistance mechanisms that compromise population control. We sought to understand population connectivity of the major malaria vector, An. coluzzii, across the different bioclimatic zones of West Africa including Ghana, Mali and Côte d’Ivoire using SNPs from whole genomes and inversion karyotypes previously associated with environmental adaptation. Methods: We used Ghana as a case study to investigate how adaptive alleles are shared across geographical space. Paired-end 100–150 bp sequencing reads were aligned to the AgamP4 reference genome using BWA version 0.7.15 and single nucleotide polymorphisms (SNP) called using GATK version 3.7.0. We characterised known target site and metabolic insecticide resistance markers, including amino acid substitutions and copy number variants. We also performed genome-wide scans for novel signals of selection with a potential link to insecticide resistance using the H12 homozygosity statistic across defined windows of the genome. Results: Based on analysis of population connectivity, we identified restricted gene flow between An. coluzzii from the northern savannah and southern forested regions of West Africa. We further found marked differences in insecticide resistance profiles across the different bioclimatic zones in Ghana, suggesting that population connectivity impacts on adaptive allele sharing. Greater evidence for target site pyrethroid resistance substitutions at the Vgsc gene and metabolic resistance markers at carboxylesterases and Gste2 in the North reflected differences in insecticide use across the country. Based on insecticide resistance marker profiles and selection scans, we also observed distinct resistance mechanisms in the coastal region of Greater Accra which may result from intense urban agricultural activity. These included a unique selection signal on the 3R chromosome at a cytochrome P450 gene, Cyp12f and a UDP glucuronosyltransferase. Conclusion: Overall, findings suggest that environmental conditions restrict An. coluzzii gene flow to impact the geographical distribution of molecular insecticide resistance.</p
Deinfibulation for improving obstetric, neonatal, gynecologic, and sexual health outcomes in women and girls with type III female genital mutilation: A systematic review and meta-analysis
No full textBackground: Type III female genital mutilation (FGM) is corrected by the scar tissue removal of the vaginal opening, known as deinfibulation. Objectives: To determine the current evidence on whether deinfibulation leads to improved obstetric, neonatal, gynecologic, and sexual health outcomes. Search Strategy: The following databases were searched from inception to May 18, 2023: CINAHL Plus (EBSCOhost), MEDLINE (Ovid), PsycINFO (EBSCOhost), SCOPUS, and Web of Science. Selection Criteria: Two review authors independently screened the titles and abstracts, extracted data, and performed the risk of bias assessment. Data Collection and Analysis: Meta-analysis was conducted with RevMan, and the quality of evidence was assessed using the GRADE approach. Main Results: Eight studies with serious risk of bias involving 3166 women were included. Very low-certainty evidence indicates that deinfibulation for women with type III FGM reduced the odds of an emergency cesarean birth (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06–0.42) and genital tract lacerations (OR 0.48, 95% CI 0.29–0.79) when compared to women with type III FGM without deinfibulation. Reduced odds of an emergency cesarean birth apply when compared to women without FGM (OR 0.59, 95% CI 0.37–0.93). Antepartum deinfibulation, compared to intrapartum deinfibulation, may lead to a reduction in the duration of labor, with little or no difference in the risk of prolonged labor (low-certainty evidence). Antepartum deinfibulation may increase the likelihood of postpartum hemorrhage and cesarean births in pregnant women with type III FGM (low-certainty evidence). We found no studies for inclusion on gynecologic, urologic, and sexual health outcomes for this update. Conclusions: The evidence of deinfibulation for women with type III FGM is available only for obstetrics outcomes. Larger observational studies in settings where type III FGM is predominantly practiced are required to improve the certainty of the evidence in these findings.</p
Pooled analysis of PCV13 efficacy from controlled human infection trials in Malawi and the UK
No full textWe conducted the first pooled analysis of two randomized controlled vaccine trials on experimental pneumococcal serotype 6B carriage, registered in Malawi(PACTR202008503507113) and the UK (ISRCTN45340436). This post-hoc exploratory study examined the sex-based differences in carriage, vaccine efficacy and vaccine-induced responses. PCV-13 reduced colonisation by 76% (p<0.001) with non-significant interaction by sex (RR=1.549, p=0.413). Females showed a higher carriage rate than males (28% vs. 19%, p=0.066). Baseline anti-6B Capsular Polysaccharide Immunoglobulin G (IgG) titres were higher in females, significantly in Malawi (2.62 μg/ml vs males 2.05 μg/ml, p=0.015). Post-vaccination titres did not differ by sex. The pooled fold change in IgG pre-post vaccination, was higher in vaccinated females (5.47 vs 3.30, p=0.053). This analysis demonstrates the utility and challenges of integrating CHIM data between diverse settings to evaluate vaccine efficacy, describe intersetting differences, investigate biological and immunological factors influencing protection against pneumococcal carriage and ultimately inform future vaccine development strategies
Prevalence of preserved ratio impaired spirometry: A systematic review and meta-analysis
No full textObjective: To summarise the prevalence of preserved ratio impaired spirometry (PRISm), intending to inform prevention strategies and clinical management. Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library databases for cohort studies investigating the prevalence of PRISm. The quality of included studies was assessed with appropriate tools for evaluating risk of bias in prevalence studies. Publication bias was assessed using funnel plots and Egger’s test. Results: After deduplication, 24 of the 33 initially eligible studies were included in the meta-analysis. The pooled prevalence of PRISm was 10% (95% CI: 0.08, 0.12). Smoking was a significant risk factor for PRISm, while no significant association was found with respiratory symptoms. PRISm was significantly associated with comorbidities including hypertension, diabetes, cardiovascular disease, and stroke. Moreover, individuals with PRISm had higher all-cause mortality (OR 1.84, 95% CI: 0.99, 3.41) and cardiovascular mortality (OR 1.82, 95% CI: 1.35, 2.44). Lung function trajectories were heterogeneous, with 10–50% reverting to normal, 20–60% remaining stable, and 6–53% progressing to chronic obstructive pulmonary disease (COPD). Conclusions: PRISm is associated with a high prevalence, smoking, cardiometabolic comorbidities, increased all-cause and cardiovascular mortality, and heterogeneous lung function trajectories, underscoring its clinical importance beyond COPD.</p
Development and evaluation of a novel RT-qPCR assay for detection of Crimean Congo haemorrhagic fever virus using the Genedrive(R) point-of-care platform
Full text linkINTRODUCTION: Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever classed by the World Health Organization as a priority disease due to the lack of countermeasures. A point-of-care (POC) diagnostic test for rapid detection of positive cases to expedite patient management is not currently available but urgently needed. METHODS: We have developed an RT-qPCR assay to be used with the commercially available POC Genedrive(R) PCR platform enabling viral detection in serum with minimal sample preparation. The sensitivity and specificity of the novel assay in the Genedrive(R) was evaluated against the RealStar(R) CCHFV RT-qPCR Kit (Altona Diagnostics, Germany). RESULTS: The sensitivity and specificity in assay V1 (sample n = 150) were 94.4 % (95 % CI, 88.2-97.9) and 97.6 % (95 % CI, 87.1-99.9). For assay (n = 55) V2 sensitivity was 92.3 % (95 % CI, 74.9-99.5) and specificity was 100 % (95 % CI, 87.7-100). CONCLUSIONS: This study supports the feasibility of diagnosing CCHF using POC RT-qPCR platforms, having the potential to reduce turnaround times, leading to improved clinical management
Emerging infectious diseases and pandemic responsiveness
No full textEmerging and re-emerging infectious diseases have been a constant threat throughout human history. An estimated 70% of emerging infectious diseases are thought to be zoonoses. Global urbanization and technological advances continue to change the way we interact with our environment, augmenting the risk of rapid spread, as seen with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally in 2020. Meanwhile multifaceted issues such as climate change, human–wildlife interactions, mis- and disinformation and geopolitical instability can impact the risk of an emerging infectious disease through shifting transmission dynamics and/or undermining of public health and medical countermeasures. Mis/disinformation and reduced public trust after the coronavirus disease (COVID-19) pandemic reduce engagement with medical countermeasures for endemic infections, while poor public and healthcare worker awareness around antimicrobial resistance increases the risk of a worsening ‘silent pandemic’. Greater collaboration is urgently required across ‘One Health’, by academic, private and political stakeholders, to reduce the social inequities of emerging infectious disease and build a resilient and responsive global security.</p
Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia: A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage
Full text linkBackground: Klebsiella pneumoniae causes ∼20% of sepsis in neonates, with ∼40% crude mortality. A vaccine administered to pregnant women, protecting against =70% of K. pneumoniae infections, could avert ∼400,000 cases and ∼80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine-targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. Methods and findings: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and =70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n=14 types). We estimate the top-5 (O1αβ,2α O1αβ,2β, O2α, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ∼99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. Conclusions: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover =70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.</p
13-valent pneumococcal conjugate vaccine-induced B cells produce serotype 6B but not serotype 3 capsule-specific IgG antibodies in young Malawian adults
Full text linkPneumococcal conjugate vaccine (PCV13) introduction has reduced vaccine-type carriage and disease; however pneumococcal carriage persists at high rates particularly in high-transmission settings. Serotype 3 remains a particular problem in Malawi and globally, with high carriage rates, as well as strain resistance to antibiotics and antibody-mediated killing. We studied antibody and B cell responses to PCV13 in 65 healthy Malawian adults (18–40 years) taking part in a randomized controlled trial. Serum, nasal fluid, and PBMC samples were collected before and after vaccination. Anti-capsular IgG for serotypes 3 and 6B were measured by ELISA, and capsule-specific B cells were assessed by spectral flow cytometry. PCV13 increased both serum and mucosal IgG levels, and IgG+ B cells in blood for serotype 6B but not serotype 3. The poor immunogenicity of serotype 3 capsular polysaccharide in Malawian young adults highlights the need for alternative vaccines to address persistent serotype 3 carriage and disease.</p