Publications

BACKGROUND AND OBJECTIVE: Human immunodeficiency virus (HIV) is a major public health concern among pregnant women in Nigeria, with seven in every hundred women likely to have an HIV infection. Understanding factors associated with HIV infection among pregnant women is critical to improving prevention strategies, especially in conflict regions. This study investigates demographic, socio-economic, and behavioral determinants of HIV among pregnant women in Nigeria, with conflict exposure included as a key predictor in the analysis.

METHODS: This study is a cross-sectional design using data from the 2018 Nigeria HIV/Acquired Immunodeficiency Syndrome (AIDS) Indicator and Impact Survey, the largest population-based HIV survey globally, implemented between July and December 2018 across all 36 states and the Federal Capital Territory of Nigeria. We analyzed weighted data from 3,879,192 pregnant women (both HIV-positive and negative), conducting bivariate and multivariate analyses to identify predictors of HIV infection among women aged 15-49 years while adjusting for potential confounders. Adjusted Odds Ratios (AORs) with 95% confidence intervals (CIs) were generated using unconditional logistic regression models to determine significant predictors.

RESULTS: Our analysis revealed that women in conflict zones were younger, less educated, and more likely to be in polygynous marriages and the lowest wealth quintile compared to those in non-conflict zones. In a multivariable analysis, residence in a conflict zone was associated with nearly twofold adjusted odds of HIV positivity (AOR = 1.93; CI: 0.98-3.82; p = 0.057). Increasing maternal age (AOR = 1.06; CI: 1.02-1.10; p = 0.002) and middle to fourth wealth quintile status (AOR = 4.10 and 3.80, respectively; p < 0.05) were significantly associated with a higher likelihood of HIV infection. Recent non-marital sexual activity was also significantly associated with HIV positivity (AOR = 2.96; p = 0.037).

CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: The study identifies conflict exposure and socio-economic status as significant predictors of HIV infection among pregnant women in Nigeria. Our analysis reveals important demographic, socio-economic, and behavioral factors associated with HIV prevalence in this population. These findings underscore the need for comprehensive HIV prevention strategies that address the complex interplay of social determinants, particularly in vulnerable populations.

BACKGROUND: The COVID 19 pandemic led to significant disruptions in health services, including immunisation programs, which contributed to a major post-pandemic diphtheria outbreak in Kano State, Nigeria. This region accounted for 85% of the nation's documented diphtheria cases.

METHODS: This study examined the epidemiology, clinical characteristics, and mortality outcomes of cases diagnosed between February 2022 and April 2024. Data were collected through the Surveillance Outbreak Response Management and Analysis System (SORMAS), and case definitions followed WHO guidelines. Case fatality rate (CFR) was calculated, and a logistic regression model was used to assess mortality-related risk factors, reporting adjusted odds ratios (AOR).

FINDINGS: A total of 18,320 cases were analysed, with the outbreak showing a bimodal distribution. The primary peak occurred in August 2023, followed by a smaller secondary peak in early 2024. The case fatality rate (CFR) was 4.5%. Patients who were not vaccinated had more than double the likelihood of death compared to fully vaccinated individuals (AOR 2.45; 95% CI: 2.05, 2.94, p < 0.0001; logistic regression). Similarly, patients without vaccination documentation also had greater odds, with more than 87% increase likelihood of mortality compared to fully vaccinated individuals (AOR 1.87, 95% CI: 1.27, 2.68, p < 0.0001; logistic regression).

INTERPRETATION: Our study reinforces previous reports of the weakening preventive health delivery systems in resource constrained settings, particularly after the disruptions caused by the COVID 19 pandemic leading to the resurgence of vaccine preventable diseases, such as diphtheria. These highlight the need for improved vaccination coverage and surveillance systems.

FUNDINGS: This research did not receive any external funding.

UNLABELLED: We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)-1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection.

IMPORTANCE: The role of "non-classical immune cells," that is, fibroblasts, epithelial cells, adipocytes, etc., except for the "classical immune cells," that is, macrophages and lymphoid cells, is not well known in the infection of Mtb bacilli. We have previously found that live, but not dead, Mtb bacilli induce cell death in human lung fibroblasts, except in human macrophages and monocytes. The present study reveals that fibroblasts ingest Mtb bacilli the same as macrophages and that in vivo Mtb bacilli within fibroblasts attempt to survive in the host cells, and pyroptosis, including the production of inflammatory cytokines, is induced in the Mtb-infected fibroblasts. Our results suggest that pyroptosis of the host fibroblasts activates the immune system against the infection.

BACKGROUND: Nigeria bears a high burden of infectious diseases, with the second-highest human immunodeficiency virus (HIV) prevalence globally and the largest tuberculosis (TB) burden in Africa. The country faces significant challenges from armed conflicts, insurgency, kidnapping and banditry, which severely strain its healthcare system, particularly for people living with HIV (PLHIV). This study hypothesizes that PLHIV in conflict-affected regions of Nigeria experience a higher burden of TB than those in non-conflict areas.

METHODS: This cross-sectional household survey utilised a two-stage cluster sampling design to examine HIV/TB co-infection and associated behaviours in Nigeria, based on data from the 2018 Nigeria HIV/ acquired immune deficiency syndrome (AIDS) Indicator and Impact Survey. The sample included adults aged 15 to 64 in the selected households. We mapped the distribution of HIV/TB co-infection across the country and calculated its prevalence, stratified by conflict and non-conflict zones. Adjusted odds ratios (AOR) and 95% confidence intervals (CIs) from survey-weighted logistic regression models were used to assess the likelihood of being diagnosed with TB disease among PLHIV.

RESULTS: We analysed weighted data from 1,319,719 PLHIV across Nigeria, with 200,201(15.2%) residing in conflict zones and 1,119,518 (84.8%) in non-conflict zones. Overall, the prevalence of HIV/TB co-infection was 40.4% (52,118), with PLHIV residents of conflict zones exhibiting a significantly higher prevalence (59%, 14,976) compared to those from non-conflict zones (36%, 37,413). After adjusting for confounders, PLHIV in conflict zones were more than four times more likely to acquire TB than those from non-conflict zones (AOR: 4.21, 95% CI: 1.72-10.5, p = 0.002).

CONCLUSIONS: Conflicts amplify the risk of TB among PLHIV in Nigeria, highlighting an urgent need for targeted interventions to strengthen healthcare access in these regions. The efforts are essential in achieving the goals of reducing TB prevalence by 50% and TB mortality by 75% by 2025, as well as meeting the 95-95-95 targets to control HIV by 2030.

The Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as well as academic groups on multiple continents. Nine reference labs analyzed antibody features, including in vivo protection in a mouse model of infection, spike protein affinity, high-resolution epitope binning, ACE-2 binding blockage, structures, and neutralization of pseudovirus and authentic virus infection, to build a publicly accessible dataset in the database CoVIC-DB. High-throughput, high-resolution binning of CoVIC antibodies defines a broad and predictive landscape of antibody epitopes on the SARS-CoV-2 spike protein and identifies features associated with durable potency against multiple SARS-CoV-2 variants of concern and high in vivo efficacy. Results of the CoVIC studies provide a guide for selecting effective and durable antibody therapeutics and for immunogen design as well as providing a framework for rapid response to future viral disease outbreaks.

In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb's complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids change in relation to drug resistance. In this study, we examined levels of cell envelope lipids [phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and PIMs associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 22 M.tb strains that ranged in drug resistance profile. We show that the PDIMs:PIMs ratio increases as drug resistance increases, and provide evidence of PDIM isomers only present in the DR-M.tb strains studied. Overall, the LM and ManLAM levels did not differ between drug resistance categories, but ManLAM surface exposure increased with drug resistance. Infection of human macrophages revealed that DR-M.tb strains have decreased association compared to drug susceptible (DS) strains, and that the pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth at early during infection compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that an increase in hydrophobic cell envelope lipids may influence M.tb-host interactions.

The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States (US). Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins didn't affect their antiviral susceptibility to PA and NA inhibitors. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight the potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak in the US.

BACKGROUND: The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era has been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship.

METHODS: A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status.

RESULTS: The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB in people with DM was 2.7-fold higher among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19.

CONCLUSION: DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in past COVID-19 persons with DM. Future studies are warranted with a longitudinal design and larger sample size to confirm our findings.