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Maternal and neonatal outcomes after infection with monkeypox virus clade I during pregnancy in DR Congo: a pooled, prospective cohort study: a pooled, prospective cohort study
No full textBackground Monkeypox virus (MPXV) has been linked to vertical transmission, but systematic data are scarce. We aimed to describe the sociodemographic, clinical, and virological characteristics and assess the frequency and determinants of adverse outcomes in pregnant women with MPXV clade I infection. Methods In this prospective cohort study, we pooled data from three cohort studies (MBOTE-SK, PREGMPOX, and Uvira mpox) and one randomised controlled trial (PALM007) conducted in the South Kivu, Maniema, and Sankuru provinces of DR Congo between Dec 29, 2022, and June 20, 2025. Pregnant women and adolescent girls with a PCR-confirmed diagnosis of mpox were followed up throughout hospitalisation for mpox, delivery, and until discharge during the postpartum period. We extracted data on sociodemographic characteristics, MPXV exposure, clinical and obstetric presentation, and laboratory results. In a univariable analysis, we examined factors associated with the following adverse outcomes: spontaneous or missed abortion (<20 weeks of gestation), stillbirth (≥20 weeks of gestation), preterm birth (<37 weeks of gestation), live birth of a neonate with macroscopic mpox-like lesions, early (first 7 days) neonatal death, congenital anomaly, or maternal death (during pregnancy or discharge postpartum). Findings We collected data from 89 pregnant women in the first (25 [28%]), second (31 [35%]), and third (33 [37%]) trimesters across all four studies: MBOTE-SK (36 [40%]), PREGMPOX (24 [27%]), PALM007 (25 [28%]), and Uvira mpox (four [4%]). All participants recovered from mpox; no maternal deaths were reported. During hospitalisation for mpox, fetal loss was reported in 17 (19%) women. Final pregnancy outcomes were known for 69 (78%) participants; adverse outcomes were reported in 35 (51%) women (95% CI 38–63), including fetal loss in 31 (45%; 95% CI 33–57; 16 [52%] spontaneous abortions, four [13%] missed abortions, and 11 [35%] stillbirths). Of the 38 live births, four neonates had congenital mpox-like lesions; one infant died a few hours after birth. No preterm births or congenital abnormalities were recorded. MPXV infection during the first trimester was associated with a higher risk of adverse pregnancy outcomes than during the second (risk ratio [RR] 0·6 [95% CI 0·4–0·9]) and third (0·2 [0·1–0·4]) trimesters (p=0·0008). Adverse outcomes were also associated with high viral load in skin lesions (PCR cycle threshold ≤30; RR 3·5 [95% CI 1·0–12·3]; p=0·045), direct sexual contact with the index case (1·6 [1·1–2·4]; p=0·026), positive HIV status (2·0 [1·4–2·9]; p=0·0002), and the presence of genital lesions (1·9 [1·1–3·2]; p=0·025). Interpretation MPXV clade I infection in pregnancy is associated with a high risk of fetal loss and congenital infection, particularly during the first trimester. Targeted preventive and clinical strategies are urgently needed to protect pregnant women and their infants in settings that are endemic and epidemic for mpox. Funding The European and Developing Countries Clinical Trials Partnership, the Belgian Directorate-General Development Cooperation and Humanitarian Aid, the Swiss National Science Foundation, the Research Foundation–Flanders, the Gates Foundation, the Intramural Research Program of the National Institutes of Health, and the National Cancer Institute.</p
Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial
No full textBackgroundHerpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis.MethodsIn this multicentre, observer-blind, randomised, phase 3 trial, adults with HSV encephalitis admitted to 53 hospitals in the UK were randomly assigned to receive intravenous dexamethasone (10 mg, four times daily for 4 days) plus intravenous aciclovir (10 mg/kg three times daily for at least 14 days; dexamethasone group), or intravenous aciclovir alone (control group). Eligible patients aged 16 years or older had suspected encephalitis (a febrile illness with new onset seizure, new focal neurological signs or alteration in consciousness, cognition, personality, or behaviour), with positive HSV type 1 or type 2 PCR test in CSF. Participants were randomly assigned by the trial team at the recruiting site, using a secure web-based randomisation programme. The primary outcome was verbal memory score at 26 weeks, measured by the Wechsler Memory Scale (WMS)-IV auditory memory index. Analyses of primary and secondary outcomes were performed according to the modified intention-to-treat principle, and safety analyses were based on whether participants received at least one dose of the study drug. Trial neuropsychologists assessing the primary outcome, and statisticians involved in the study's primary outcome, were masked to treatment group allocation. The trial is registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN11774734, and EudraCT, EudraCT2016-004835-19, and is completed.FindingsBetween Sept 22, 2016, and Feb 2, 2022, 94 patients with HSV encephalitis were recruited, 47 (20 [43%] female and 27 [57%] male) to the dexamethasone group, and 47 (24 [51%] female and 23 [49%] male) to the control group. Dexamethasone was initiated a median 7 (IQR 4–8) days after hospital admission. Seven patients withdrew consent, and six were lost to follow-up. Thus, 81 were included in the modified intention-to-treat analysis (39 in the treatment group and 42 in the control group). The primary outcome, verbal memory score at 26 weeks, did not differ significantly between the groups (71 [SD 26] in the dexamethasone group, and 69 [SD 25] in the control group; adjusted difference 1·77 [95% CI –9·57 to 13·12; p=0·76). There were 27 adverse events involving 18 (38%) participants in the control group, and 25 adverse events involving 18 (40%) participants in the dexamethasone group. The most common serious adverse events were seizures requiring readmission to hospital (affecting one [2%] patient in the dexamethasone group and one [2%] patient in the control group) and thrombotic events, including deep vein thrombosis (affecting one [2%] patient in the dexamethasone group) and pulmonary embolism (affecting one [2%]patient in the dexamethasone group). There were no treatment-related deaths.InterpretationIn adults with HSV encephalitis, dexamethasone plus aciclovir had a satisfactory safety profile but did not improve verbal memory score compared with aciclovir alone. Given the established role of corticosteroids in other inflammatory encephalitides, our findings suggest that their early use in suspected encephalitis is unlikely to be harmful. Future studies should assess more targeted immunomodulatory approaches in HSV encephalitis.FundingNational Institute for Health and Care Research.Research in contex
Early neonatal admissions with feeding difficulties to acute paediatric services at a tertiary paediatric hospital in England: sequential audits pre-COVID-19 and during the COVID-19 pandemic
Full text linkIntroduction Our objective was to describe the population of infants <7days of age admitted to the acute general paediatric services at Alder Hey Children’s Hospital and ascertain the proportion with feeding difficulties amenable to community-based support. Methods Sequential retrospective audits of all infants <7days of age admitted to acute paediatrics at Alder Hey Children’s Hospital, Liverpool, England, from March to September 2019 (pre-COVID-19) and March to September 2020 (during COVID-19). All the infants were born and discharged from maternity units in Merseyside, Northwest England. Anonymised data were extracted from the electronic clinical records by three members of the clinical team. Results Pre-COVID-19, 38.6% (93) of the 241 admissions to acute general paediatric services had feeding difficulties. 31.2% (29) presented solely with feeding difficulties and 31.2% (29) were exclusively breastfed. However, during COVID-19, although there were fewer admissions (104), more than half (51%, 54) had feeding difficulties and for 54% (29), this was the only reason for admission. Over half (53.7%, 29) were exclusively breastfed. Conclusion Our audits showed that at least a third of infants <7days of age admitted with feeding difficulties did not have any other features of severe illness. These admissions unnecessarily expose infants to hospital-acquired infections while disrupting the opportunity for families to build close and loving relationships that enhance the establishment of breastfeeding. Co-designing infant feeding strategies with the mothers and stakeholders will be a crucial next step to enhance infant feeding support, particularly in impoverished communities in the region.</p
Establishing the Kenya National Antivenom Quality Control Laboratory Preclinical Efficacy Results of Four Antivenoms Against Venoms from the “Big Five” Snake Species in Kenya
No full textAntivenom administration is currently the only therapy for snakebite envenoming. However, in sub-Saharan Africa, inadequate quality control systems have led to deficits in the availability, accessibility, efficacy and safety of regionally available antivenoms, which, in turn, hinder snakebite treatment and management in the region. To address this impediment to snakebite treatment in Kenya, this study aimed to assess the preclinical neutralising potencies of four different antivenoms previously or currently available in Kenya (SAIMR polyvalent, AFRIVEN, PANAF-PremiumTM and InoserpTM) against key snakes of medical importance in the region, towards establishing a national antivenom quality control laboratory. Venoms were extracted from the Kenyan “big five” medically important snake species: Naja ashei, Naja pallida, Naja nigricollis, Dendroaspis polylepis and Bitis arietans, and their lethal potencies were determined using a murine median lethal dose (LD50) assay. In vitro immunological assays (ELISAs and immunoblotting) and an established preclinical murine in vivo neutralisation assay (median effective dose [ED50]) were used to assess the immunoglobulin-binding and venom-neutralising efficacies of the test antivenoms. In vitro assays revealed high venom-binding titres of SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM, and reactivity to a wide range of venom proteins across the different snake venoms. Contrastingly, InoserpTM antivenom had low binding titres and poor reactivity to the snake venom proteins. These findings were aligned with the in vivo results, where SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM showed potent venom-neutralising efficacies against all the tested snake venoms, while InoserpTM had low potency and failed to neutralise the lethal effects of N. ashei, N. pallida and D. polylepis venoms at the manufacture-claimed doses. Based on these robust preclinical results, we conclude that SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM antivenoms offer considerable potential for the treatment of envenoming by diverse medically important snakes in Kenya. The observed deficiencies with the InoserpTM product highlight the importance of (i) robust, independent preclinical antivenom efficacy testing and (ii) the value of establishing a quality control laboratory to inform local regulatory and procurement decision making.</p
Machine learning-driven identification of serotype-independent pneumococcal vaccine candidates using samples from human infection challenge studies
Full text linkIdentifying conserved, immunogenic proteins that confer protection against Streptococcus pneumoniae (pneumococcus) colonization could enable development of serotype-independent vaccines. In our controlled human infection model, no individual IgG or cytokine/chemokine response correlated significantly with protection against colonization with pneumococcus, suggesting that effective immunity reflects a coordinated, multi-antigen response. To capture these complex patterns, we trained independent Random Forest models on humoral and cellular datasets. The humoral model identified IgG responses to PdB, SP1069, and SP0899 as predictive of protection. The cellular model revealed that MCP-1 responses to SP1069 and SP0899, and IL-17A production in response to SP0648-3, were associated with protection. Elevated baseline IFN-γ, RANTES, and anti-protein IgG levels were linked to reduced colonization density. We highlight SP1069 and SP0899 as potential serotype-independent vaccine candidates and demonstrate the utility of machine learning to identify immune correlates of protection.</p
Chlorfenapyr bednets effectively overcome pyrethroid resistance escalation in highly resistant Anopheles malaria vectors in Uganda
Full text linkEscalating insecticide resistance threatens the efficacy of LLINs, undermining malaria control in Africa. We conducted the first experimental hut trials in Uganda using highly resistant free-flying wild Anopheles mosquitoes and F2 hybrids of FANG and Uganda An. funestus to evaluate the performance of bednets. The interceptor G2 (chlorfenapyr) bednet demonstrated superior efficacy compared to Interceptor (pyrethroid-only) net [mortality odds ratio (OR): 18.7 (8.05–48.6) P < 0.0001], achieving an overall mortality rate of 70.6% and 63.2% against An. funestus and An. gambiae respectively. In contrast, PermaNet 3.0 and Olyset Plus (piperonyl butoxide (PBO)) and Royal Guard (pyriproxyfen (PPF)-treated) bednets exhibited significantly lower mortality against An. funestus [Olyset Plus: 36.1%, PermaNet 3.0: 31.0% and Royal Guard (37.6%], though performance against An. gambiae was moderate [PermaNet 3.0: 61.4%, Olyset Plus: 50.0%, Royal Guard: 51.6%]. Interceptor net produced the lowest mortality (~ 25%) against both species. Regarding blood-feeding inhibition (BFI), PBO nets, particularly Olyset Plus, outperformed Interceptor G2 and Royal Guard, while Interceptor produced minimal BFI (< 36%). Further evaluation of Royal Guard’s PPF effect on oviposition revealed no significant reduction in oviposition rates compared to controls with An. funestus (63.9% vs. 63.3%, P > 0.05). Genetic analysis using the hybrid crosses revealed that pyrethroid resistance markers (4.3 Kb-SV and G454A-Cyp9K1) were significantly associated with mosquito survival and blood-feeding success against PermaNet 2.0 (pyrethroid-only) and PermaNet 3.0 but showed no significant association with Interceptor G2 net. These findings support Interceptor G2 as a promising intervention for regions dominated by both highly resistant An. funestus s.l. and An. gambiae s.l. Piperonyl butoxide and PPF nets emerge as a good alternative for areas mostly dominated by resistant An. gambiae s.l. populations. Critically, the demonstrated variable impact of insecticide resistance on bednet efficacy underscores the imperative need for a comprehensive vector distribution mapping, continuous field efficacy assessments, and systematic resistance monitoring. This evidence-based triad should guide strategic LLIN distribution and rotations to sustain malaria control efficacy in resistance-prone settings.</p
Multiplex PCR to Differentiate Monkeypox Virus Clades
No full textWe designed a multiplex quantitative PCR to differentiate monkeypox virus clades. For clinical samples collected in the United Kingdom and Nigeria, sensitivity was 78% (95% CI 67.67%-86.14%) and specificity 94% (95% CI 80.84%-99.30%); for samples with cycle thresholds <35, sensitivity was 98% (95% CI 91.72%-99.96%) and specificity 94% (95% CI 80.84%-99.30%).</p
“Should I tell him I have something in my vagina?” Female sex workers’ perceptions and experiences of using a menstrual cup, and client reactions: A qualitative study in Western Kenya
Full text linkIntroduction: The menstrual cup is worn intravaginally, holding blood up to 12 h before emptying and reinserting. It offers protection from sexually transmitted infections and bacterial vaginosis, whilst preserving a Lactobacillus crispatus–dominant vaginal microbiome. The menstrual disc, a type of menstrual cup, is positioned near the cervix and can remain in place during sex, enabling female sex workers (FSWs) to avoid unsafe practices to conceal menstruation during work. In this study, we aim to examine the perceptions and experiences of a convenience sample of FSWs 6 months after they received a menstrual disc, along with client views. Methods: In a qualitative design, our Kenyan study recruited 38 FSWs in 4 focus group discussions (FGDs) and 86 clients in 9 FGDs. Using a semi-structured guide, a Kenyan moderator and note-taker facilitated audio-recorded discussions. Following translation and transcription, the discussions were analysed using deductive thematic analysis. Results: Six themes emerged: Anticipation and reaction to seeing the menstrual cup, Apprehension and determination to use, Benefits, Challenges, Secrecy, and Use during sex. Some FSWs were able to insert the cup on initial attempt, typically others encountered discomfort, pain, or misalignment during insertion or difficulty in removing. By the end of the third month, the majority were using the cup without experiencing any leakage, pain, or concerns. Benefits noted included ease, convenience, reduced leakage, and comfort. Financial advantage over pads and ability to work regularly were also noted. Nearly all FSWs used the cup during sex, despite prior anxiety that a client would detect it and react negatively. In three instances, the FSWs reported that a client “may” have felt the disc, whilst noting just two clients “may” have felt something. None reacted badly. In summing up their experience, the FSWs spoke very positively about the disc, with the intention to keep wearing it in the future. Many clients were supportive of the disc but did not want to know whether an FSW was wearing it. Conclusions: The FSWs quickly adapted to using the disc, finding it a comfortable, reliable menstrual product with financial advantages. With clients remaining mostly unaware of its use, the FSWs enthusiastically embraced the disc with the intention to keep using it. These positive outcomes have implications for future scale-up and roll-out to other vulnerable female populations.</p
Attenuated viral strains of priority pathogens for potential use in controlled human infection model studies: A scoping review
No full textBackgroundThere are several known pathogens and families identified as high risk for pandemic potential. It is essential to study these pathogens and develop medical countermeasures to mitigate disease prior to potential pandemics. Controlled human infection models (CHIMs) using attenuated viral strains may offer an efficient and safe way to do this.ObjectiveOur aim was to systematically examine the literature for attenuated, but replication competent, strains of Coalition for Epidemic Preparedness Innovations (CEPI) identified priority pathogens (Ebola, Lassa virus, Nipah virus, Rift Valley fever virus, chikungunya virus and Middle East respiratory syndrome-related coronavirus) that have been administered to humans.DesignA comprehensive literature search of multiple databases was performed by an information specialist. All search results were screened by two authors against inclusion/exclusion criteria from a pre-specified protocol. The primary outcome was confirmation that the administered viral strain could subsequently be recovered from participants. The secondary outcome was attenuated virus safety.ResultsOur searches yielded 13078 results and 5998 articles remained for screening after removing duplicates and animal studies. Subsequently, 351 articles were selected for full text review and nine were included for data extraction. Four distinct attenuated strains were identified across two priority pathogens – TSI-GSD-218 and VLA1553 for chikungunya virus and MP-12 and hRVFV-4s for Rift Valley Fever virus. Attenuated virus was recovered for each strain except hRVFV-4s. There were no major safety concerns for these identified strains in Phase 1–3 studies.ConclusionsWe have identified three attenuated viral strains that may be amenable to development into novel CHIMs for two priority pathogens. Of these, VLA1553 for chikungunya is a licenced and commercially available vaccine product suitable for use in CHIM. There is a research gap for the creation of new attenuated mutants that could be utilised in CHIM for other priority pathogens
Susceptibility of Anopheles stephensi SDA500 strain to common insecticides and efficacy of glazed tile bioassay for resistance characterization
Full text linkResearch on the urban malaria vector Anopheles stephensi has intensified in recent years following its rapid spread throughout the Horn of Africa and beyond. In addition to behavioural and ecological traits which may limit the efficacy of control efforts, insecticide resistance is a notable problem in invasive An. stephensi populations. The most frequently used laboratory reference strain for An. stephensi is SDA500 originally colonized from Pakistan; though considered insecticide susceptible, quantitative demonstration of this crucial assumption is lacking. We characterized the susceptibility status of SDA500 against multiple insecticide classes used for adult and larval control using the standard WHO techniques for larval bioassays and two alternatives for adults: bottle bioassays and glazed tile bioassays. SDA500 showed full susceptibility against all insecticides tested, and via dose-response assays, we provide the first comprehensive LC50 dataset for a strain of An. stephensi, filling a key knowledge gap and providing an important resource for all future studies of resistance in this important malaria vector. Whilst tile and bottle adult bioassays produced broadly comparable results for both SDA500 and additional laboratory strains, differences were found when testing neonicotinoids and butenolides, which require the addition of the compound MERO® for effectiveness. Nevertheless, the glazed tile bioassay represents a much higher throughput and less resource-intensive technique than bottle bioassays for simultaneous screening of multiple insecticides.</p