Baobab Index

The HPV-Automated Visual Evaluation Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost human papillomavirus (HPV) assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positive participants combines HPV genotyping (4 groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment. We analyzed CIN3+ yield for each HPV-Automated Visual Evaluation risk level (HPV genotype crossed by automated cervical visual evaluation classification) from 9 clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and automated cervical visual evaluation classification strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.

Approximately 1.25 million individuals died of tuberculosis in 2023, in part due to ineffective treatment. In patients with paucibacillary tuberculosis, microbiologic confirmation and drug resistance testing via respiratory specimens is challenging; hence, stool samples are increasingly used for microbiologic confirmation. Targeted next-generation sequencing (tNGS) of stool DNA may improve detection of drug-resistant (DR) tuberculosis, helping patients receive appropriate treatments. We assessed the ability of a nanopore tNGS approach using stool to detect drug resistance in a prospective, nested cohort of consecutive participants in Eswatini with pulmonary tuberculosis confirmed via sputum culture or sputum GeneXpert Ultra from 2020 to 2023. We compared stool tNGS with (1) a composite reference standard of diagnostic tools available in the study setting, (2) sputum culture tNGS, and (3) whole-genome sequencing of sputum culture. Participants ranged in age from 2 to 80 years (median age, 28 years; interquartile range, 20-40 years), and 45.6% (26 of 57) had human immunodeficiency virus. Based on stool tNGS, 14% of our cohort (8 of 57) had drug resistance, and 8.8% (5 of 57) would have received a different treatment regimen had stool tNGS informed clinical decision making. Stool tNGS with nanopore technology was 94.4% concordant (in 17 of 18) for identifying DR mutations with whole-genome sequencing and identified 90% of resistant mutations (9 of 10) indicated by composite reference standard. Stool tNGS detected resistance not detected by standard methods, including detection of rifampicin resistance associated with Stool tNGS of

Children have paucibacillary tuberculosis and cannot provide expectorated sputum. Invasive specimen collection, by gastric aspiration or sputum induction, has a low diagnostic yield. In this study, we aimed to evaluate the diagnostic performance and additive yield of a novel stool-based assay in children diagnosed with tuberculosis in sub-Saharan Africa. We conducted a prospective case-control study from October 2020 to June 2023 in Eswatini, Mozambique, and Tanzania. Children under 15 years newly diagnosed with tuberculosis completed clinical examination, chest radiography, culture, sputum Xpert Ultra, stool Xpert Ultra, and stool-based quantitative polymerase chain reaction (stool qPCR) assessment. Stool qPCR sensitivity was calculated against culture, a composite microbiological reference standard, and a clinical reference standard. Specificity was calculated in a control population of healthy, TB disease-free, child household contacts. Among 456 children, 232 were diagnosed with TB and 224 controls. Stool sample collection was achieved in 95.6% of children. The qPCR was positive in 17.2% (40/232) of clinically diagnosed participants. In the same population, test positivity was 8% (13/162) for culture, 13.4% (27/202) sputum Xpert Ultra, and 14.8% (33/223) stool Xpert Ultra. When compared to a microbiological reference standard (any positive test), the sensitivity of stool qPCR was 35.6% (21/59). Specificity in the control population was 96.1% (196/204), and the additive yield of qPCR with all tests performed was of 8.7%. This stool qPCR assay can increase the microbiologic confirmation of tuberculosis in pediatric populations from TB high-burden settings. It may be particularly useful where resource limitations or clinical capacity impedes diagnostic specimen collection via sputum induction or gastric aspiration.

Interferon-gamma release assays (IGRAs) that evaluate an individual's T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater diagnostic sensitivity in individuals with HIV-1 co-infections (93.8% versus 67%), comparable diagnostic sensitivity in HIV-negative individuals (92.8%) and faster detection (4 h versus 24-48 h). We also find that a self-powered ASTRA chip that analysed microsample (~25 μl) whole-blood samples produced comparable results. ASTRA holds the potential to facilitate efforts to control the global TB epidemic and serve as a versatile platform for analysing T-cell responses across various infectious diseases and immunotherapeutic interventions.

Biodiversity is severely threatened globally, with habitat loss and other human pressures accelerating species extinctions. Protected areas (PAs) are a critical conservation tool; however, their effectiveness in safeguarding many taxa, such as bats, remains unclear. Using georeferenced occurrence records and species distribution models (SDMs) for 263 sub-Saharan African bat species, we evaluated the coverage of bats in 7875 terrestrial PAs. Eighty-nine percent of bat species were recorded in at least 1 PA, yet 28 species, including 5 threatened and 15 data deficient species, were absent from all PAs. Species with large extents of occurrence were represented in more PAs, and fruit bats occupied significantly more PAs than clutter, edge, or open-air insectivorous foragers. The SDMs revealed high species richness in some undersurveyed areas, particularly in West and Central Africa and the Albertine Rift, emphasizing the need for targeted surveys. Our findings underscore critical data deficiencies related to bat conservation and stress the urgency of integrating bats into broader conservation planning. More surveys, enhanced data-sharing, and tailored conservation strategies are needed to improve bat representation in PAs and safeguard their ecological roles in Africa's biodiverse landscapes. Subrepresentación de los murciélagos en las áreas protegidas de África Resumen La biodiversidad sufre una amenaza grave en todo el mundo, y la pérdida de hábitats y otras presiones humanas aceleran la extinción de especies. Las áreas protegidas (AP) son una herramienta de conservación fundamental; sin embargo, su eficacia para proteger muchos taxones, como los murciélagos, sigue sin estar clara. Utilizamos registros georreferenciados de presencia y modelos de distribución de especies (MDE) de 263 especies de murciélagos del África subsahariana para evaluar la cobertura de murciélagos en 7,875 AP terrestres. El 89% de las especies de murciélagos se registraron en al menos una AP, sin embargo 28 especies, incluyendo 5 especies amenazadas y 15 especies con datos deficientes, estuvieron ausentes en todas las AP. Las especies con presencia extensa estuvieron representadas en más AP, y los murciélagos frugívoros ocuparon significativamente más AP que los insectívoros forrajeros de densidad vegetal, de borde o al aire libre. Los MDE revelaron una alta riqueza de especies en algunas áreas poco estudiadas, particularmente en África Occidental y Central y en la falla Albertina, lo que resalta la necesidad de estudios específicos. Nuestros hallazgos destacan las graves deficiencias de los datos relacionados con la conservación de los murciélagos y enfatizan la urgencia de integrar a los murciélagos en una planificación de conservación más amplia. Para mejorar la representación de los murciélagos en las áreas protegidas y salvaguardar su papel ecológico en la biodiversidad de los paisajes africanos se necesitan más estudios, un mejor intercambio de datos y estrategias de conservación adaptadas. 全球生物多样性正面临严重威胁, 栖息地丧失和其他人类活动正在加速物种灭绝。保护地是重要保护工具, 然而, 其在许多类群(如蝙蝠)保护方面的有效性仍不清楚。本研究利用263种撒哈拉以南非洲蝙蝠的地理参考出现记录和物种分布模型, 评估了7875个陆地保护地对蝙蝠的覆盖情况。结果表明, 89%的蝙蝠物种在至少1个保护地中有记录, 但有28种蝙蝠(包括5种受威胁物种和15种数据不足物种)在所有保护地中均未被记录。出现范围较广的物种在更多保护地中有分布记录, 而果蝠在保护地中的分布显著多余在杂乱环境、植被边缘或开放空间觅食的食虫性蝙蝠。物种分布模型显示, 一些调查不足的地区物种丰富度较高, 尤其是西非、中非和艾伯丁裂谷地区, 这强调了开展针对性调查的必要性。我们的研究结果突显了蝙蝠保护相关的关键数据空缺, 并强调了将蝙蝠纳入更广泛的保护规划的紧迫性。未来还应开展更多调查、加强数据共享, 以及制定针对性保护策略, 来提升蝙蝠在保护地中的代表性, 并保护其在非洲高生物多样性景观中的生态角色。【翻译:胡怡思;审校:聂永刚】.

In 2023, an estimated 1.3 million children (aged 0-14 years) became ill with tuberculosis, and 166,000 children (aged 0-15 years) died from the disease. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that detects Mycobacterium tuberculosis complex and rifampicin resistance. This is an update of a Cochrane review first published in 2020 and last updated in 2022. Parts of the current update informed the 2024 WHO updated guidance for the diagnosis of tuberculosis. To assess the diagnostic accuracy of Xpert Ultra for detecting pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance in children (aged 0-9 years) with presumed tuberculosis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 6 October 2023. For study design, we included cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children aged birth to nine years. Regarding specimen type, we included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis); cerebrospinal fluid (tuberculous meningitis); and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). Reference standards for detection of tuberculosis were microbiological reference standard (MRS; including culture) or composite reference standard (CRS); for stool, we considered Xpert Ultra in sputum or gastric aspirates in addition to culture. Reference standards for detection of rifampicin resistance in sputum were phenotypic drug susceptibility testing or targeted or whole genome sequencing. Two review authors independently extracted data and assessed methodological quality using the tailored QUADAS-2 tool, judging risk of bias separately for each target condition and sample type. We conducted separate meta-analyses for detection of pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance. We used a bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We assessed certainty of evidence using the GRADE approach. This update included 23 studies (including 9 new studies since the previous review) that evaluated detection of pulmonary tuberculosis (21 studies, 9223 children), tuberculous meningitis (3 studies, 215 children), lymph node tuberculosis (2 studies, 58 children), and rifampicin resistance (3 studies, 130 children). Seventeen studies (74%) took place in countries with a high tuberculosis burden. Overall, risk of bias and applicability concerns were low. Detection of pulmonary tuberculosis (microbiological reference standard) Sputum (11 studies) Xpert Ultra summary sensitivity was 75.3% (95% CI 68.9% to 80.8%; 345 children; moderate-certainty evidence), and specificity was 95.9% (95% CI 92.3% to 97.9%; 2645 children; high-certainty evidence). Gastric aspirate (12 studies) Xpert Ultra summary sensitivity was 69.6% (95% CI 60.3% to 77.6%; 167 children; moderate-certainty evidence), and specificity was 91.0% (95% CI 82.5% to 95.6%; 1792 children; moderate-certainty evidence). Stool (10 studies) Xpert Ultra summary sensitivity was 68.0% (95% CI 50.3% to 81.7%; 255 children; moderate-certainty evidence), and specificity was 98.2% (95% CI 96.3% to 99.1%; 2630 children; high-certainty evidence). Nasopharyngeal aspirate (6 studies) Xpert Ultra summary sensitivity was 46.2% (95% CI 34.9% to 57.9%; 94 children; moderate-certainty evidence), and specificity was 97.5% (95% CI 95.1% to 98.7%; 1259 children; high-certainty evidence). Xpert Ultra sensitivity was lower against CRS than against MRS for all specimen types, while the specificities were similar. Extrapulmonary tuberculosis Meta-analysis was not possible for lymph node tuberculosis and tuberculous meningitis due to low study numbers. Interpretation of results For a population of 1000 children, where 100 have pulmonary tuberculosis: In sputum: • 112 would be Xpert Ultra positive, of whom 75 would have pulmonary tuberculosis (true positives) and 37 would not (false positives). • 888 would be Xpert Ultra negative, of whom 863 would not have pulmonary tuberculosis (true negatives) and 25 would have pulmonary tuberculosis (false negatives). In gastric aspirate: • 151 would be Xpert Ultra positive, of whom 70 would have pulmonary tuberculosis (true positives) and 81 would not (false positives). • 849 would be Xpert Ultra negative, of whom 819 would not have pulmonary tuberculosis (true negatives) and 30 would have pulmonary tuberculosis (false negatives). In stool: • 85 would be Xpert Ultra positive, of whom 68 would have pulmonary tuberculosis (true positives) and 17 would not (false positives). • 915 would be Xpert Ultra negative, of whom 883 would not have pulmonary tuberculosis (true negatives) and 32 would have pulmonary tuberculosis (false negatives). In nasopharyngeal aspirate: • 68 would be Xpert Ultra positive, of whom 46 would have pulmonary tuberculosis (true positives) and 22 would not (false positives). • 932 would be Xpert Ultra negative, of whom 878 would not have pulmonary tuberculosis (true negatives), and 54 would have pulmonary tuberculosis (false negatives). Detection of rifampicin resistance Three studies with 76 children evaluated detection of rifampicin resistance (sputum only); two of these studies reported no cases and one reported rifampicin resistance in two children. Xpert Ultra sensitivity was moderate in sputum, gastric aspirate, and stool specimens. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both MRS and CRS. We were unable to determine the accuracy of Xpert Ultra for detecting tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance due to a paucity of data. This update was funded through WHO. The protocol for this review was originally published through Cochrane in 2019. The protocol for this update was a generic protocol that consolidated previously published Cochrane protocols of Xpert Ultra for tuberculosis detection and can be accessed at https://osf.io/26wg7/. Protocol (2019) DOI: 10.1002/14651858.CD013359 Original review (2020) DOI: 10.1002/14651858.CD013359.pub2 Review update (2022) DOI: 10.1002/14651858.CD013359.pub3.

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in

The sub-Saharan Africa endemic dormouse genus Graphiurus is a morphologically diverse group of rodents that has lacked a genus-wide genetic framework, hindering inference of their evolution and biogeography. Here, we assembled the first comprehensive, range-wide genomic dataset for Graphiurus, including ultraconserved elements and the cytochrome b gene. We used phylogenetic reconstruction, divergence-time estimation, and ancestral area reconstruction to clarify biogeographic histories and evaluate how historical range dynamics may have influenced lineage diversification. Graphiurus is the earliest-diverging lineage within Gliridae sister to all other extant genera. Within Graphiurus, we recovered 24 molecular operational taxonomic units (MOTUs) forming two reciprocally monophyletic, deeply divergent clades: a West African lineage comprising three MOTUs and a pan-sub-Saharan Africa lineage comprising 21 MOTUs. Genetic distances between these clades are equal to or greater than those used to distinguish genera. Diversification within Graphiurus started in the middle Miocene, peaking in a rapid radiation during the Plio-Pleistocene. These diversification events coincided with increased climatic instability that fragmented forests into isolated refugia. Ancestral-area reconstructions suggest a Graphiurus origin in the Upper Guinean rainforest, followed by jump dispersal across the Afrotropics, with most subsequent divergences occurring in East Africa. As the first comprehensive phylogenetic analysis of Graphiurus, our study underscores the urgent need for an integrated taxonomic revision of the genus that couples genomic data with detailed morphology and critical re-examination of type material to resolve species limits and formally describe the recovered MOTUs. Many MOTUs appear range restricted, underscoring vulnerability to ongoing habitat loss within montane refugia.

Drug-resistant tuberculosis is entering a new and dangerous phase. Bedaquiline and other newer drugs have transformed drug-resistant tuberculosis treatment, yet resistance to these agents is now being reported across high-burden settings. In some regions, baseline bedaquiline resistance is substantial, treatment outcomes for extensively drug-resistant tuberculosis remain poor and mortality is unacceptably high. At the same time, the tuberculosis drug pipeline is stronger than it has been in decades, with several promising investigational compounds advancing to late-stage trials. However, regulatory approval remains years away, leaving people with few or no effective treatment options to wait-and often die-while drugs with potential benefit remain inaccessible. Here, we argue that the central barrier to addressing complex drug-resistant tuberculosis is not scientific, but moral and organisational. Drawing on lessons from earlier pre-approval access programmes for bedaquiline and delamanid, we propose the establishment of compassionate-use support platforms (CUSPs): coordinated, global mechanisms to facilitate equitable access to investigational tuberculosis drugs before formal approval. Well designed CUSPs could balance urgency with safety, share responsibility across stakeholders, strengthen diagnostic and pharmacovigilance capacity, and ensure that people with the most difficult-to-treat tuberculosis are not excluded from scientific progress.

HIV-tuberculosis (HIV-TB) coinfection poses a significant public health challenge among children in high-burden African regions. Most previous transcriptomic studies have concentrated on adults and non-African populations, primarily analyzing gene-level differential expression. This approach overlooks multi-isoform complexity and may obscure both inherent and pathogen-induced intragenic heterogeneity. This multi-center case-control study aimed to identify and characterize the transcript-level landscape of HIV-TB coinfection in children from different African regions. We analyzed whole-blood RNA sequencing data from 97 children with and without tuberculosis from Uganda (East Africa) and from Botswana and Eswatini (Southern Africa). Reads were quality-controlled, and low-abundance transcripts filtered out. Differential transcript expression was estimated using models that adjusted for batch, age, and sex, with multiple testing controlled by the Benjamini-Hochberg procedure. Pathway enrichment was performed on the set of differentially expressed transcripts. Our analyses show geographic heterogeneity in immune responses; however, the top three gene pathways - immune system, innate immune system, and neutrophil degranulation are consistently conserved across regions. Although there is limited overlap among upregulated transcripts, four of the six shared differentially expressed transcripts (DETs) are enriched in neutrophil degranulation pathways, indicating a conserved transcriptional signature of HIV-TB coinfection. Additionally, we identify five genes with region-specific, non-overlapping isoforms, a distinction not detectable through gene-level analysis. These findings demonstrate a conserved whole-blood transcriptomic signature in pediatric HIV-TB coinfection, while also highlighting regional variation at the isoform level. This supports the use of transcript-level analyses to identify biomarkers and enhance understanding of host responses in diverse African settings. Tuberculosis (TB) is difficult to diagnose in children with HIV, yet they are at a high risk of contracting it. We analyzed gene expression in the blood of children living with HIV with and without TB in Uganda, Botswana, and Eswatini. We focused on transcripts with at least a fourfold increase in abundance in HIV-TB coinfection. While children from different regions had different gene expression, many were involved in similar cellular processes, such as certain parts of the innate immune system, with four of the six shared transcripts. Our findings highlight the conserved nature of the immune response and underscore the need for studies across different regions to better understand these infections in children.