Abstract Background Gene drive-modified mosquitoes (GDMMs) have been promoted as one of the innovative technologies that may control and eliminate malaria and other mosquito-borne diseases. Several products are in early stages of development, targeting either population suppression or population modification of the mosquito vector. However, there is no direct experience of conducting risk assessment for environmental releases and subsequent policies regarding conditions for post-release. This study was carried out to gain additional insights on the possible post-release concerns that may arise, as they may inform future risk assessment and planning for deployment. Methods This study involved desktop reviews on post release monitoring experiences with previously released biological control products. Stakeholder consultations involving online surveys, and face to face workshop with experts from selected African countries from Eastern, Western, and Southern African regions was then carried out to establish post-release monitoring concerns for GDMMs. Results Review of genetic biocontrol technologies showed only limited lessons from post-release monitoring regimes with a focus largely limited to efficacy. For genetically modified organisms general surveillance and case-specific monitoring is expected in some of the regions. A number of post-release monitoring concerns in relation to the protection goals of human and animal health, biodiversity, and water quality were identified. Conclusion Based on established- protection goals, several post-release monitoring concerns have been identified. Subject to a rigorous risk assessment process for future GDMMs products, the concerns may then be prioritized for post-release monitoring. …

Abstract Background Insecticide-treated nets (ITNs) are the most commonly deployed tools for controlling malaria transmission in sub-Saharan Africa. However, some reports associate multiple alternative uses of nets with poor disposal practices, prompting this study to assess existing alternative uses and disposal practices of old ITNs in Burkina Faso after four universal distribution campaigns. Methods A quantitative survey combined with qualitative data collection was used to describe existing alternative uses and disposal practices for old ITNs in households from selected study sites in the three climatic zones of Burkina Faso. A survey questionnaire was distributed to 3,780 participants, and 12 focus groups were held to elucidate responses regarding existing disposal practices and alternative uses of ITNs. Results Of the 3780 households surveyed, 87.4% (3,330) reported having disposed of their ITNs when they were no longer usable due to age or wear. The most commonly cited disposal methods included alternative uses (67.4%), disposal with other garbage (61.4%), and burying (9%). In addition, the most common alternative uses included fencing for crops and seedlings (51.8%); ropes for tying items (40.4%); animal protection fencing (17.8%); house fencing (16.8%); bed covers (13.3%) and curtains for doors or windows (12.6%). Furthermore, trends in ITNs disposal mechanisms and alternative uses differed between study sites in each climate zone. All these ITNs disposal mechanisms and the different types of alternative use of old ITNs were confirmed in the focus group discussions. Conclusion The findings underscore the need for comprehensive strategies to manage the disposal and repurposing of old ITNs in Burkina Faso. Addressing gaps in disposal guidelines, promoting safe and beneficial reuse practices, and actively involving communities in the decision-making process can help mitigate health risks associated with the improper disposal and repurposing of old insecticide-treated nets and improve the overall effectiveness of malaria control programmes. Through these efforts, both public health and environmental concerns can be addressed in a sustainable and collaborative manner. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background The JYNNEOS vaccine (two doses given 28 days apart) was recommended in the United States for people at high risk of exposure to monkeypox virus during the 2022 mpox outbreak. Our objective was to assess the safety of JYNNEOS using two complementary epidemiologic methods. Methods This observational cohort included patients of eight large integrated healthcare organizations who received JYNNEOS. Adverse events were identified using ICD-10 coded diagnoses assigned to medical visits. The first analysis used standardized incidence ratios (SIR) to compare the observed incidence of ten prespecified adverse events of special interest (AESI) during the 28 days after receipt of each dose of JYNNEOS to the expected incidence adjusted for several risk factors. The second analysis used tree-based data mining to identify temporal clustering of cases for more than 60,000 diagnoses and diagnosis groups within 70-days after JYNNEOS dose 1 administration. Results The SIR analysis included 53,583 adults who received JYNNEOS dose 1 and 38,206 who received dose 2. Males received 92% of the doses. There were no statistically significant elevated SIRs for any of the ten AESI. The tree-based data mining analysis included 36,912 vaccinees. Analysis of diagnoses in inpatient, emergency department, and outpatient settings identified statistically significant clusters of visits for rash and unspecified adverse effects. Conclusions No new or unexpected safety concerns were identified. AESI did not occur more frequently than expected by chance alone. Non-serious medically attended adverse events, such as rash, have been previously reported and occurred infrequently. …

Journal of Medical Virology, Volume 96, Issue 11, November 2024.

Journal of Medical Virology, Volume 96, Issue 11, November 2024.

Nigeria, Africa\'s most populous country, and 6th largest country by population in the world [1], experienced at least four waves of COVID-19 infection from February 2020 to November 2023 [2]. An estimated 267,146 confirmed cases [3] and a cumulative 3,155 deaths were reported up to November 2, 2023.[4] COVID-19 cases peaked in late December 2021, with a positive COVID-19 test rate greater than 21·8% [4], and over 1,950 daily new confirmed COVID-19 cases. COVID-19 vaccination was introduced in Nigeria in March 2021.

Acute gastroenteritis (AGE) is one of the leading causes of death in children under the age of 5 years. In this pediatric age group, noroviruses are estimated to cause 200 million annual AGE cases worldwide [1]. With widespread vaccination against rotavirus, norovirus has become the predominant cause of childhood AGE in several Latin American countries such as Peru [2]. A recent systematic review and meta-analysis found noroviruses to be associated with 15% of all AGE cases in Latin America [3], complementing the prevalence reported worldwide (18% of AGE cases) and in low- and middle-income countries (15%) [4,5].

Abstract Chlamydia psittaci is a zoonotic pathogen known to cause respiratory diseases in humans. Chlamydia infections are closely associated with apoptosis, in which miRNAs play regulatory roles. Herein, we demonstrated that C. psittaci infection induces apoptosis in human bronchial epithelial (HBE) cells and investigated regulatory mechanism involving miR-124-3p and the PI3K/AKT signaling pathway. Following C. psittaci infection in HBE cells, we observed an elevated of HBE cells apoptosis, accompanied by upregulation of miR-124-3p levels. Mechanistically, we identified EIF3B as a novel target gene of miR-124-3p, supported by the inverse correlation of their mRNA expressions. MiR-124-3p inhibitors reduced apoptosis induced by C. psittaci, increased the replication of C. psittaci and inhibited the PI3K/AKT activated, whereas miR-124-3p mimics produced opposite effects, and transfection with EIF3B siRNA reversed the effects of miR-124-3p inhibitors. Our findings suggest that miR-124-3p targeting EIF3B promotes apoptosis in C. psittaci-infected HBE cells through the activation of PI3K/AKT signaling pathway.

Abstract Background The persistence of latently infected cells prevents a cure of HIV. The intestinal mucosa contains numerous target cells, and high levels of HIV-1 DNA persist in this compartment under ART. While CD4+ T cells are the best characterized reservoir of HIV-1, the role of long-lived intestinal macrophages in HIV-1 persistence on ART remains controversial.Methods We collected duodenal and colonic biopsies from 12 people living with HIV (PLWH) on suppressive ART, enrolled in the ARNS EP61 GALT study. Total, integrated, intact and defective HIV-1 proviruses were quantified from sorted T cells and monocytes/macrophages. HIV-1 env quasispecies were analyzed by single-molecule next-generation sequencing and env-pseudotyped viruses were constructed to assess macrophage versus T-tropism.Results Total HIV-1 DNA levels in intestinal T cells were significantly higher than those in monocytes/macrophages (P

Abstract Tuberculosis (TB) necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of two compounds to reduce triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages. Each inhibitor reduced the cellular triglyceride content in bronchoalveolar lavage samples of Mtb-infected mice. After 6 weeks of treatment, p70S6Ki alone reduced the lung bacterial burden in Mtb-infected mice. However, DGATi alone, and DGATi or p70S6Ki in combination with isoniazid did not reduce lung bacterial burden or alter lung inflammation. These findings provide further insight into the role of foam cells in tuberculosis pathogenesis and the utility of interventions targeting these cell populations as adjunctive host-directed therapies.

Community-onset meticillin-resistant Staphylococcus aureus (MRSA) (CO-MRSA) has been under recognised and under described outside the USA and we welcome this themed issue comprising 4 narrative reviews on the topic which cover a wide range of issues.

ObjectivesThis study aims to evaluate and compare health outcomes and costs between home hospitalisation and traditional hospitalisation for three common diagnoses—cellulitis, urinary tract infection (UTI) and pneumonia. DesignA retrospective cohort study. SettingPrimary care, nationwide. Participants1311 patients in home hospitalisation and 992 in traditional hospitalisation. InterventionsThe primary intervention is home hospitalisation, compared with traditional hospitalisation. The intervention was performed according to medical considerations by a specialised team, and this study was done retrospectively to evaluate it. Primary and secondary outcome measuresPrimary measures included healthcare costs, length of hospitalisation, referrals for further medical services and mortality. ResultsCosts of home hospitalisation were lower compared with traditional hospitalisation (6056 vs 9619 NIS for pneumonia, 6011 vs 9767 NIS for cellulitis, 6466 vs 8552 NIS for UTI and p value

ObjectivesEffective, real-time surveillance of dengue may provide early warning of outbreaks and support targeted disease-control intervention but requires widespread accurate diagnosis and timely case reporting. Research directing innovation in diagnostics for dengue surveillance is lacking. This study aimed to describe experience and requirements of relevant prospective users. DesignA qualitative, focus group study was conducted. ParticipantsData were collected from 19 users of diagnostic technology who work across the Thai dengue surveillance system. Data collection and analysisContextual knowledge, experience and needs were explored in focus groups. Discussions were translated, transcribed, analysed thematically and mapped to Consolidated Framework for Implementation Research domains. ResultsParticipants expressed a need for rapid, accurate, serotype-specific tests which can be operated easily by non-expert users without laboratory equipment. They supported integration of diagnostics with surveillance systems and felt this would increase the quantity and speed of case reporting as well as provide healthcare professionals with up-to-date information about the number of cases locally, thereby aiding interpretation of test results. Concerns included those relating to data security and the cost of tests. ConclusionsEngagement to understand prospective user experience and requirements can improve relevance and uptake of new technology, leading to system efficiencies. The present study highlights specific needs for accurate, serotype-specific, remote-connected diagnostics which are integrated with surveillance systems and support dengue case reporting at the point-of-care. …

ObjectiveTo estimate the herd effects of anti-microbial-based decontamination (ABD) interventions on bloodstream infections (BSIs) among groups of intensive care unit (ICU) patients in relation to group mean length of stay (LOS). To deduce which of three competing hypotheses of ABD effect mediation best accounts for the observed effects. DesignArms-based meta-regression of ICU-acquired BSI incidence against group mean LOS for control and interventions arms of ABD and non-ABD controlled trials each versus that in arms of observational studies. ExposuresWithin controlled trials of ABD, intervention, concurrent control (CC) and non-concurrent (NCC) groups are directly, indirectly and non-exposed, respectively. Main outcomes and measuresBSI incidence, both overall and for BSI subtypes. ResultsIn the arms-based meta-regression, the predicted BSI incidence per 100 patients in the ABD intervention arms increased from 4.6 (95% CI 3.8 to 5.5) at mean LOS 7 days to 13.0 (10.4–16.0) at mean LOS 20 days (n=60 arms) and CC arms 8.5 (6.7–11.0) increasing to 19.3 (14.8–24.8; n=52). These increases were double those in the observational (7.2; 6.1–8.5 increasing to 12.9; 10.4–16.7; n=99) and NCC arms and non-ABD arms. These results triangulate with the notional effect size observed in contrast-based meta-analyses. ConclusionsThe increased tempo of BSI acquisition, both overall and for various BSI subtypes, within intervention and CC groups of ABD randomised concurrent controlled trials versus other groups implicate rebound and spillover, respectively. Mechanisms other than colonisation resistance mediate ABD effects. …

Abstract Background Common non-COVID respiratory viruses, such as influenza virus (IFVA/IFVB), parainfluenza virus (PIV), respiratory syncytial virus (RSV), and adenovirus (ADV), often cause acute respiratory infections (ARIs). This study aimed to explore the epidemiological characteristics of these five viruses in patients with ARIs before, during, and after the COVID-19 pandemic from 2018 to 2023. Methods A total of 37,139 serum specimens and epidemiological data from all-aged patients who presented with ARIs were collected from January 2018 to December 2023. The IgM antibodies of five non-COVID respiratory viruses were tested by an IgM kit with indirect immunofluorescent assay (lFA). Results 12,806 specimens were screened as positive for any one of the targeted viruses, with an overall positivity rate of 34.48%. Among all age groups, the most prevalent respiratory viruses were PIV (21.30%) and influenza virus (17.30% of IFVB and 9.91% of IFVA). Children aged 1–14 years were most vulnerable to lower respiratory viruses, and children aged 4–6 years have the highest prevalence no matter the positivity rate for overall viruses (53.06%) or for each virus. From 2018 to 2023, the annual percentage change (APC) revealed that the prevalence of total viruses have a 13.53% rise (p  60 years) were all the highest in 2023, and the number of samples collected in 2023 sharply increased, increasing by 77.10% compared to the average of the number of detected in 2018–2022. Conclusions The data from this study indicate that the epidemiological characteristics of five non-COVID respiratory viruses are vulnerability to the environment, age, sex, and epidemics status among AIR patients, and that the detected number and positivity rate of these viruses have increased in the “post-pandemic era”, which is critical for the late or retrospective diagnosis and can serve as a useful surveillance tool to inform local public policy in Weifang, China. …

Abstract Background The HIV epidemic in Kenya remains a significant public health concern, particularly among gay, bisexual, and other men who have sex with men (GBMSM), who continue to bear a disproportionate burden of the epidemic. This study’s objective is to describe HIV phylogenetic clusters among different subgroups of Kenyan GBMSM, including those who use physical hotspots, virtual spaces, or a combination of both to find male sexual partners. Methods Dried blood spots (DBS) were collected from GBMSM in Kisumu, Mombasa, and Kiambu counties, Kenya, in 2019 (baseline) and 2020 (endline). HIV pol sequencing was attempted on all seropositive DBS. HIV phylogenetic clusters were inferred using a patristic distance cutoff of ≤ 0.02 nucleotide substitutions per site. We used descriptive statistics to analyze sociodemographic characteristics and risk behaviors stratified by clustering status. Results Of the 2,450 participants (baseline and endline), 453 (18.5%) were living with HIV. Only a small proportion of seropositive DBS specimens were successfully sequenced (n = 36/453; 7.9%), likely due to most study participants being virally suppressed (87.4%). Among these sequences, 13 (36.1%) formed eight distinct clusters comprised of seven dyads and one triad. The clusters mainly consisted of GBMSM seeking partners online (n = 10/13; 76.9%) and who tested less frequently than recommended by Kenyan guidelines (n = 11/13; 84.6%). Conclusions Our study identified HIV phylogenetic clusters among Kenyan GBMSM who predominantly seek sexual partners online and test infrequently. These findings highlight potential unmet HIV prevention, testing, and treatment needs within this population. Furthermore, these results underscore the importance of tailoring HIV programs to address the diverse needs of GBMSM in Kenya across different venues, including both physical hotspots and online platforms, to ensure comprehensive prevention and care strategies. …

Abstract Background Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy. Methods We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016–2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography. Results Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim. Conclusions As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses. …

Abstract Background Brucellosis poses a significant public health challenge in China. Inner Mongolia, characterized by its developed livestock industry, is the most severe endemic area for human brucellosis. This study aims to describe the epidemiology, explore the spatial–temporal distribution patterns, and clustering characteristics of human brucellosis in Inner Mongolia. Methods Data on human brucellosis cases from 2010 to 2021 were obtained from the Centers for Disease Control and Prevention in Inner Mongolia. Spatial autocorrelation analysis was used to identify high-risk areas, while spatial–temporal scan statistics were employed to detect changes in clusters over time. Results A total of 153,792 brucellosis cases were reported in Inner Mongolia from 2010 to 2021, with an average annual incidence rate of 52.59 per 100,000 persons. The incidence showed a decreasing trend from 2010 to 2016, followed by a significant increase from 2016 to 2021. The disease exhibited distinct seasonality, peaking in spring and summer (March to August). Middle-aged individuals, males, and farmers/herdsmen had higher incidence rates. Spatially, incidence rates decreased from north to south and from the central and eastern regions to the west. Clear spatial clusters were observed during 2010–2013 and 2016–2021 in the global Moran’s I test. Local spatial autocorrelation analysis revealed that high-high clusters expanded from the central and eastern regions towards the west over time. Spatio-temporal scan analysis further indicated that high-risk clusters were primarily concentrated in the central and eastern regions, with a continuous expansion towards the west and south, leading to an increasingly broad geographical spread. Conclusion Human brucellosis cases in Inner Mongolia exhibit spatio-temporal clustering, with spatial concentration in the central and eastern regions, but also observed expansion towards the western and southern regions. The most of cases occur between March and August each year. For high-risk areas and populations, more timely and effective prevention and control measures should be implemented to mitigate the spread of brucellosis and protect public health. …

Volume 15, Issue 1, December 2024 .

Proceedings of the National Academy of Sciences, Volume 121, Issue 48, November 2024.