Biphasic MERS-CoV Incidence in Nomadic Dromedaries with Putative Transmission to Humans, Kenya, 2022-2023.

Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedaries in Africa, but camel-to-human transmission is limited. Sustained 12-month sampling of dromedaries in a Kenya abattoir hub showed biphasic MERS-CoV incidence; peak detections occurred in October 2022 and February 2023. Dromedary-exposed abattoir workers (7/48) had serologic signs of previous MERS-CoV exposure.

Early antiretroviral therapy and its impact on natural killer cell dynamics in HIV-1 infected men who have sex with men: a cross-sectional pilot study evaluating the impact of early ART initiation on NK cell perturbation in HIV infection.

Phenotypic changes and functional impairment of natural killer (NK) cells occur early in HIV-1 infection. Antiretroviral therapy (ART) effectively restores CD4+ T cell counts and suppresses HIV-1 to undetectable levels. The role and efficacy of immediate ART initiation in mitigating NK cell aberrations remain to be elucidated comprehensively. This study hypothesized that HIV-1 infection negatively influences NK cell evolution and that early ART initiation restores these perturbations. Blood samples were collected longitudinally from five acutely HIV-1 infected men who have sex with men in Nairobi, Kenya. Participants were immediately initiated on ART after HIV-1 diagnosis. Blood samples were drawn pre-infection and at sequential bi-weekly post-infection time points. Peripheral blood mononuclear cells were stained with panel NK cells surface markers to assess HIV-induced phenotypic changes by flow cytometry. Some cells were also stimulated overnight with K562 cell line, IL-2, and IL-15 and stained for flow cytometry functionality. HIV-1 infection was associated with significant reductions in the production of IFN-γ (P = 0.0264), expression of CD69 (P = 0.0110), and expression of NK cell inhibitory receptor Siglec7 (P = 0.0418). We observed an increased NK cell degranulation (P = 0.0100) and an upregulated expression of cell exhaustion marker PD-1 (P = 0.0513) at post-infection time points. These changes mainly were restored upon immediate initiation of ART, except for Siglec7 expression, whose reduced expression persisted despite ART. Some HIV-associated changes in NK cells may persist despite the immediate initiation of ART in acute HIV-1 infections. Our findings suggest that understanding NK cell dynamics and their restoration after ART can offer insights into optimizing HIV-1 treatment and potentially slowing disease progression.IMPORTANCENatural killer (NK) cells play a crucial role in controlling of HIV-1 replication and progression to disease. Perturbations of their functionality may therefore result in deleterious disease outcomes. Previous studies have demonstrated reduced NK cell functionality in chronic HIV-1 infection that positively correlated to HIV-1 viral load. This may suggest that control of HIV-1 viremia in acute HIV-1 infection may aid in enhancing NK cell response boosting the inate immunity hence effective control of viral spread and establishment of viral reservoir. Antiretroviral therapy (ART) effectively supresses HIV-1 viremia to undectable levels and restores CD4+ T cell counts. Our study highlights the significant role of early ART initiation in mitigating NK cell disruptions caused by acute HIV-1 infection. Our results suggest that early initiation of ART could have benefits beyond suppressing viral load and restoring CD4+ T cell counts. In addition, it could boost the innate immunity necessary to control disease progression.

Towards pharmacogenomics-guided tuberculosis (TB) therapy: N-acetyltransferase-2 genotypes among TB-infected Kenyans of mixed ethnicity.

BACKGROUND: Though persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD). METHODS: We isolated genomic DNA from cryopreserved Peripheral Blood Mononuclear Cells of 79 volunteers. We amplified the protein-coding region of the NAT2 gene by polymerase chain reaction (PCR) and sequenced PCR products using the Sanger sequencing method. Sequencing reads were mapped and aligned to the NAT2 reference using the Geneious software (Auckland, New Zealand). Statistical analyses were performed using RStudio version 4.3.2 (2023.09.1 + 494). RESULTS: The most frequent haplotype was the wild type NAT2*4 (37%). Five genetic variants: 282C > T (NAT2*13), 341 T > C (NAT2*5), 803A > G (NAT2*12), 590G > A (NAT2*6) and 481C > T (NAT2*11) were observed with allele frequencies of 29%, 18%, 6%, 6%, and 4% respectively. According to the bimodal distribution of acetylation activity, the predicted phenotype was 76% rapid (mainly consisting of the wildtype NAT2*4 and the NAT2*13A variant). A higher proportion of rapid acetylators were female, 72% vs 28% male (p = 0.022, odds ratio [OR] 3.48, 95% confidence interval [CI] 1.21 to 10.48). All variants were in HWE. NAT2 341 T > C was in strong complete LD with the 590G > A variant (D' = 1.0, r2 = - 0.39) but not complete LD with the 282C > T variant (D' = 0.94, r2 = - 0.54). CONCLUSION: The rapid acetylation haplotypes predominated. Despite the LD observed, none of the SNPs could be termed tag SNP. This study adds to the genetic characterisation data of African populations at NAT2, which may be useful for developing relevant pharmacogenomic tools for TB therapy. To support optimised, pharmacogenomics-guided TB therapy, we recommend genotype-phenotype studies, including studies designed to explore gender-associated differences.

Confronting the human papillomavirus-HIV intersection: Cervical cytology implications for Kenyan women living with HIV.

Background: High-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer, leading to over 311 000 global deaths, mainly in low- and middle-income countries. Kenyan women living with HIV (WLHIV) face a disproportionate burden of HR-HPV. Objectives: We determined the prevalence of HR-HPV infections and their association with cervical cytology findings among Kenyan WLHIV. Method: We conducted a cross-sectional study among WLHIV attending the HIV care and treatment clinic at the Kenyatta National Hospital (KNH), Kenya's national referral hospital. Study nurses collected a cervical sample with a cytobrush for HR-HPV genotyping using Gene Xpert® assays and HPV Genotypes 14 Real-TM Quant V67-100FRT. Bivariate analysis explored the associations. Results: We enrolled 647 WLHIV (mean age of 42.8 years), with 97.2% on antiretroviral therapy (ART) and 79% with a suppressed viral load (< 50 copies/mL plasma). The prevalence of any and vaccine-preventable HR-HPV was 34.6% and 29.4%, respectively, with HPV 52 being the most common genotype (13.4%). Among WLHIV with HR-HPV infections, 21.4% had abnormal cervical cytology. Women with multiple HR-HPV infections were more likely to have abnormal cytology compared to those with single HR-HPV infections (34.9 vs 9.3%, adjusted odds ratio [aOR] = 6.2, 95% confidence interval [CI]: 2.7-14.1, P = 0.001). Women with HR-HPV infection (single or multiple) were more likely to be on the second-line ART regimen compared to those without HR-HPV infections (53.1% vs 46.7%, aOR = 2.3, 95% CI: 1.3-4.1, P = 0.005). Conclusion: Among WLHIV at KNH, abnormal cytology was common and more frequent among women with multiple HR-HPV infections.

Metabolic and mitochondrial dysregulation in CD4+ T cells from HIV-positive women on combination anti-retroviral therapy.

BACKGROUND: For optimal functionality, immune cells require a robust and adaptable metabolic program that is fueled by dynamic mitochondrial activity. In this study, we investigate the metabolic alterations occurring in immune cells during HIV infection and antiretroviral therapy by analyzing the uptake of metabolic substrates and mitochondrial phenotypes. By delineating changes in immune cell metabolic programming during HIV, we may identify novel potential therapeutic targets to improve anti-viral immune responses. METHODS: After consent and voluntary participation was confirmed, whole blood was drawn from HIV uninfected women and women with chronic HIV infection on long-term combination antiretroviral therapy (HIV/cART). Peripheral blood mononuclear cells-derived immune cells were directly incubated with different fluorescently tagged metabolites and markers of mitochondrial activity: FITC-2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose), FITC-BODIPY (4,4-Difluoro-5,7-Dimethyl-4-Bora-3a,4a-Diaza-s-Indacene-3-Hexadecanoic Acid), FITC-MitoTracker Green and APC-MitoTracker Deep Red. The uptake of glucose and fats and the mitochondrial mass and potential were measured using flow cytometry. All values are reported quantitatively as geometric means of fluorescence intensity. RESULTS: During chronic HIV infection, cellular uptake of glucose increases in HIV+ dendritic cells in particular. CD4+ T cells had the lowest uptake of glucose and fats compared to all other cells regardless of HIV status, while CD8+ T cells took up more fatty acids. Interestingly, despite the lower utilization of glucose and fats in CD4+ T cells, mitochondrial mass increased in HIV+ CD4+ T cells compared to HIV negative CD4+ T-cells. HIV+ CD4+ T cells also had the highest mitochondrial potential. CONCLUSIONS: Significant disparities in the utilization of substrates by leukocytes during chronic HIV/cART exist. Innate immune cells increased utilization of sugars and fats while adaptive immune cells displayed lower glucose and fat utilization despite having a higher mitochondrial activity. Our findings suggest that cART treated HIV-infected CD4+ T cells be dysfunctional or may prefer alternative fuel sources not included in these studies. This underscores the importance of understanding the metabolic effects of HIV treatment on immune function.

Seroprevalence and related risk factors of Brucella spp. in livestock and humans in Garbatula subcounty, Isiolo county, Kenya.

BACKGROUND: Brucellosis is a neglected zoonotic disease that affects both animals and humans, causing debilitating illness in humans and socio-economic losses in livestock-keeping households globally. The disease is endemic in many developing countries, including Kenya, but measures to prevent and control the disease are often inadequate among high-risk populations. This study aimed to investigate the human and livestock seroprevalence of brucellosis and associated risk factors of Brucella spp. in a pastoralist region of northern Kenya. METHODS: A cross-sectional survey was conducted using a two-stage cluster sampling method to select households, livestock, and humans for sampling. Blood samples were collected from 683 humans and 2157 animals, and Brucella immunoglobulin G (IgG) antibodies were detected using enzyme-linked immunosorbent assays. A structured questionnaire was used to collect data on potential risk factors associated with human and animal exposures. Risk factors associated with Brucella spp. exposures in humans and livestock were identified using Multivariate logistic regression. RESULTS: The results indicated an overall livestock Brucella spp. seroprevalence of 10.4% (95% Confidence Interval (CI): 9.2-11.7). Camels had the highest exposure rates at 19.6% (95% CI: 12.4-27.3), followed by goats at 13.2% (95% CI: 9.3-17.1), cattle at 13.1% (95% CI: 11.1-15.3) and sheep at 5.4% (95% CI: 4.0-6.9). The herd-level seroprevalence was 51.7% (95% CI: 47.9-55.7). Adult animals (Adjusted Odds Ratio (aOR) = 2.3, CI: 1.3-4.0), female animals (aOR = 1.7, CI: 1.1-2.6), and large herd sizes (aOR = 2.3, CI: 1.3-4.0) were significantly associated with anti-brucella antibody detection while sheep had significantly lower odds of Brucella spp. exposure compared to cattle (aOR = 1.3, CI: 0.8-2.1) and camels (aOR = 2.4, CI: 1.2-4.8). Human individual and household seroprevalences were 54.0% (95% CI: 50.2-58.0) and 86.4% (95% CI: 84.0-89.0), respectively. Significant risk factors associated with human seropositivity included being male (aOR = 2.1, CI:1.3-3.2), residing in Sericho ward (aOR = 1.6, CI:1.1-2.5) and having no formal education (aOR = 3.0, CI:1.5-5.9). There was a strong correlation between human seropositivity and herd exposure (aOR = 1.6, CI:1.2-2.3). CONCLUSIONS: The study provides evidence of high human and livestock exposures to Brucella spp. and identifies important risk factors associated with disease spread. These findings emphasize the need for targeted prevention and control measures to curb the spread of brucellosis and implement a One Health surveillance to ensure early detection of the disease in Isiolo County, Northern Kenya.

Assessment of gestational age at antenatal care visits among Kenyan women to inform delivery of a maternal respiratory syncytial virus (RSV) vaccine in low- and middle-income countries.

Background: Maternal respiratory syncytial virus (RSV) vaccines that are likely to be implementable in low- and middle-income countries (LMICs) are in final stages of clinical trials. Data on the number of women presenting for antenatal care (ANC) per day and proportion attending within the proposed gestational window for vaccine delivery, is a prerequisite to guide development of vaccine vial size and inform vaccine uptake in this setting. Methods: We undertook administrative review and abstraction of ANC attendance records from 2019 registers of 24 selected health facilities, stratified by the level of care, from Kilifi, Siaya and Nairobi counties in Kenya. Additional data were obtained from Mother and Child Health (MCH) booklets of women in each of the Health and Demographic Surveillance System (HDSS) areas of Kilifi, Nairobi and Siaya. Data analysis involved descriptive summaries of the number (mean, median) and proportion of women attending ANC within the gestational window period of 28-32 weeks and 24-36 weeks. Results: A total of 62,153 ANC records were abstracted, 33,872 from Kilifi, 19,438 from Siaya and 8,943 from Nairobi Counties. The median (Interquartile range, IQR) number of women attending ANC per day at a gestational age window of 28-32 and 24-36 weeks, respectively, were: 4 (2-6) and 7 (4-12) in dispensaries, 5 (2-9) and 10 (4-19) in health centres and 6 (4-11) and 16 (10-26) in county referral hospitals. In the HDSS areas of Kilifi, Siaya and Nairobi, pregnant women attending at least one ANC visit, within a window of 28-32 weeks, were: 77% (360/470), 75% (590/791) and 67% (547/821), respectively. Conclusions: About 70% of pregnant women across three distinct geographical regions in Kenya, attend ANC within 28-32 weeks of gestation. A multidose vial size with about five doses per vial, approximates daily ANC attendance and would not incur possible wastage in similar settings.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context.

BACKGROUND: Tuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking. We estimated the prevalence and determinants of TB infection among PLHIV within a high TB and HIV burden context. METHODS: This cross-sectional study included data from adult PLHIV age ≥18 years in whom QuantiFERON-TB Gold Plus (QFT-Plus) assay, an IGRA, was performed. TB infection was defined as a positive or indeterminate QFT-Plus test. Participants with TB and those who had previously used TPT were excluded. Regression analysis was performed to identify independent predictors of TB infection. RESULTS: Of 121 PLHIV with QFT-Plus test results, females were 74.4% (90/121), and the mean age was 38.4 (SD 10.8) years. Overall, 47.9% (58/121) were classified as TB infection (QFT-Plus test positive and indeterminate results were 39.7% (48/121) and 8.3% (10/121), respectively). Being obese/overweight (body mass index ≥25 kg/m2; p=0.013, adjusted OR (aOR) 2.90, 95% CI 1.25 to 6.74) and ART usage for >3 years (p=0.013, aOR 3.99, 95% CI 1.55 to 10.28) were independently associated with TB infection. CONCLUSION: There was a high TB infection prevalence among PLHIV. A longer period of ART and obesity were independently associated with TB infection. The relationship between obesity/overweight and TB infection may be related to ART use and immune reconstitution and requires further investigation. Given the known benefit of test-directed TPT among PLHIV never exposed to TPT, its clinical and cost implications for low and middle-income countries should be explored further.

Challenges and Opportunities in the Genetic Analysis of Inherited Retinal Dystrophies in Africa, a Literature Review.

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develops genetic tests and genetic therapies for IRDs, yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 11 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs, respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were included in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

Haematological predictors of poor outcome among COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

BACKGROUND: Studies from Asia, Europe and the USA indicate that widely available haematological parameters could be used to determine the clinical severity of Coronavirus disease 2019 (COVID-19) and predict management outcome. There is limited data from Africa on their usefulness in patients admitted to Intensive Care Units (ICUs). We performed an evaluation of baseline haematological parameters as prognostic biomarkers in ICU COVID-19 patients. METHODS: Demographic, clinical and laboratory data were collected prospectively on patients with confirmed COVID-19, admitted to the adult ICU in a tertiary hospital in Cape Town, South Africa, between March 2020 and February 2021. Robust Poisson regression methods and receiver operating characteristic (ROC) curves were used to explore the association of haematological parameters with COVID-19 severity and mortality. RESULTS: A total of 490 patients (median age 54.1 years) were included, of whom 237 (48%) were female. The median duration of ICU stay was 6 days and 309/490 (63%) patients died. Raised neutrophil count and neutrophil/lymphocyte ratio (NLR) were associated with worse outcome. Independent risk factors associated with mortality were age (ARR 1.01, 95%CI 1.0-1.02; p = 0.002); female sex (ARR 1.23, 95%CI 1.05-1.42; p = 0.008) and D-dimer levels (ARR 1.01, 95%CI 1.002-1.03; p = 0.016). CONCLUSIONS: Our study showed that raised neutrophil count, NLR and D-dimer at the time of ICU admission were associated with higher mortality. Contrary to what has previously been reported, our study revealed females admitted to the ICU had a higher risk of mortality.

An empiric tool to identify Kenyans living with HIV who will have unsuppressed viremia 18 months following treatment initiation to guide differentiated care models.

BACKGROUND: With the global push towards universal access to Antiretroviral Treatment (ART), patient numbers are increasing, further straining already under-resourced healthcare systems in sub-Saharan Africa. A simple scoring tool could be useful in optimizing differentiated service delivery by identifying individuals likely to have unsuppressed viral load. METHODS: Using existing data of patients accessing ART at public health facilities that were extracted from the Kenya Electronic Medical Record (KenyaEMR) and standard methods of developing a clinical prediction tool; we created and validated a risk scoring tool to identify persons likely to be virally unsuppressed at 18 months post-ART initiation. Data from the KenyaEMR were cleaned, merged and reviewed for completeness. We utilized multivariate modelling to determine key predictors of viral load suppression that could be measured in clinical settings. RESULTS: We assessed clinical reports of 3,968 patients on ART who had been on ART for at least 18 months and had at least one viral load result and were ≥ 18 years old. Of these, the majority (81%) were virally suppressed 18 months post-ART initiation. The final risk score included age, sex, body mass index at HIV diagnosis, number of years of formal education, disclosure status, and duration of time between HIV diagnosis and initiating ART. The maximum risk score was 78; a risk score of ≥22 was associated with unsuppressed viral load (>1000copies/mL). The area under the curve (AUC) for the probability of the risk score to correctly predict unsuppressed viral load was 0.55 (95% CI: 0.52 to 0.56). Internal and external validation showed similar predictive ability. CONCLUSIONS: Routinely collected variables in a public HIV clinic medical record predicts, with modest accuracy, individuals likely to have unsuppressed HIV viremia 18 months after they initiate ART. The use and application of this tool could improve and complement efficiency in differentiated care models for patients on ART.

Prognostic value of biochemical parameters among severe COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

Association between human leukocyte antigen class II (HLA-DRB and -DQB) alleles and outcome of exposure to Mycobacterium tuberculosis: a cross-sectional study in Nairobi, Kenya.

Introduction: human leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease. Methods: an analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status. Results: the HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040). Conclusion: the higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.

Imported SARS-COV-2 Variants of Concern Drove Spread of Infections Across Kenya During the Second Year of the Pandemic.

Background: Using classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression. Methods: SARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health facilities. COVID-19-associated fatality data were also obtained from these health facilities and communities. Whole SARS-CoV-2 genome sequencing were carried out on 1241 specimens. Results: Over the pandemic duration (March 2020 - January 2022) Kenya experienced five waves characterized by attack rates (AR) of between 65.4 and 137.6 per 100,000 persons, and intra-wave case fatality ratios (CFR) averaging 3.5%, two-fold higher than the national average COVID-19 associated CFR. The first two waves that occurred before emergence of global variants of concerns (VoC) had lower AR (65.4 and 118.2 per 100,000). Waves 3, 4, and 5 that occurred during the second year were each dominated by multiple introductions each, of Alpha (74.9% genomes), Delta (98.7%), and Omicron (87.8%) VoCs, respectively. During this phase, government-imposed restrictions failed to alleviate pandemic progression, resulting in higher attack rates spread across the country. Conclusions: The emergence of Alpha, Delta, and Omicron variants was a turning point that resulted in widespread and higher SARS-CoV-2 infections across the country.

Near-Complete SARS-CoV-2 Seroprevalence among Rural and Urban Kenyans despite Significant Vaccine Hesitancy and Refusal.

Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city of Nairobi (n = 781) and a rural western county (n = 810) between January and February 2022. The overall SARS-CoV-2 seroprevalence was 90.2% (95% CI, 88.6−91.2%), including 96.7% (95% CI, 95.2−97.9%) among urban and 83.6% (95% CI, 80.6−86.0%) among rural populations. A comparison of immunity profiles showed that >50% of the rural population were strongly immunoreactive compared to <20% of the urban population, suggesting more recent infections or vaccinations in the rural population. More than 45% of the vaccine-eligible (≥18 years old) persons had not taken a single dose of the vaccine (hesitancy), including 47.6% and 46.9% of urban and rural participants, respectively. Vaccine refusal was reported in 19.6% of urban and 15.6% of rural participants, attributed to concern about vaccine safety (>75%), inadequate information (26%), and concern about vaccine effectiveness (9%). Less than 2% of vaccine refusers cited religious or cultural beliefs. These findings indicate that despite vaccine inequity, hesitancy, and refusal, herd immunity had been achieved in Kenya and likely other African countries by early 2022, with natural infections likely contributing to most of this immunity. However, vaccine campaigns should be sustained due to the need for repeat boosters associated with waning of SARS-CoV-2 immunity and emergence of immune-evading virus variants.

Assessment of independent comorbidities and comorbidity measures in predicting healthcare facility-onset Clostridioides difficile infection in Kenya.

INTRODUCTION: Clostridioides difficile is primarily associated with hospital-acquired diarrhoea. The disease burden is aggravated in patients with comorbidities due to increased likelihood of polypharmacy, extended hospital stays and compromised immunity. The study aimed to investigate comorbidity predictors of healthcare facility-onset C. difficile infection (HO-CDI) in hospitalized patients. METHODOLOGY: We performed a cross sectional study of 333 patients who developed diarrhoea during hospitalization. The patients were tested for CDI. Data on demographics, admission information, medication exposure and comorbidities were collected. The comorbidities were also categorised according to Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). Comorbidity predictors of HO-CDI were identified using multiple logistic regression analysis. RESULTS: Overall, 230/333 (69%) patients had comorbidities, with the highest proportion being in patients aged over 60 years. Among the patients diagnosed with HO-CDI, 63/71(88.7%) reported comorbidities. Pairwise comparison between HO-CDI patients and comparison group revealed significant differences in hypertension, anemia, tuberculosis, diabetes, chronic kidney disease and chronic obstructive pulmonary disease. In the multiple logistic regression model significant predictors were chronic obstructive pulmonary disease (odds ratio [OR], 9.51; 95% confidence interval [CI], 1.8-50.1), diabetes (OR, 3.56; 95% CI, 1.11-11.38), chronic kidney disease (OR, 3.88; 95% CI, 1.57-9.62), anemia (OR, 3.67; 95% CI, 1.61-8.34) and hypertension (OR, 2.47; 95% CI, 1.-6.07). Among the comorbidity scores, CCI score of 2 (OR 6.67; 95% CI, 2.07-21.48), and ECI scores of 1 (OR, 4.07; 95% CI, 1.72-9.65), 2 (OR 2.86; 95% CI, 1.03-7.89), and ≥ 3 (OR, 4.87; 95% CI, 1.40-16.92) were significantly associated with higher odds of developing HO-CDI. CONCLUSION: Chronic obstructive pulmonary disease, chronic kidney disease, anemia, diabetes, and hypertension were associated with an increased risk of developing HO-CDI. Besides, ECI proved to be a better predictor for HO-CDI. Therefore, it is imperative that hospitals should capitalize on targeted preventive approaches in patients with these underlying conditions to reduce the risk of developing HO-CDI and limit potential exposure to other patients.

Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya.

BACKGROUND: Non-tuberculous mycobacteria (NTM) treatment constitutes a macrolide-based antibiotic regimen in combination with aminoglycosides for Rapid-Growing Mycobacteria (RGM), and rifampicin for Slow-Growing Mycobacteria (SGM). Mutations in the anti-NTM drug target regions promote NTM evolution to mutant strains that are insusceptible to NTM drugs leading to treatment failure. We, therefore, described the mutation patterns of anti-NTM drug target genes including rrl, rrs, and rpoB in NTM isolates from Kenya.  Methods: We carried out a cross-sectional study that included 122 NTM obtained from the sputum of symptomatic tuberculosis-negative patients in Kenya. All 122 NTM underwent targeted sequencing of the rrl gene. The 54 RGM were also sequenced for rrs, and the 68 SGM were sequenced for rpoB genes using ABI 3730XL analyzer. The obtained sequences were aligned to their wild-type reference sequences for each gene using Geneious then mutations were identified. Pearson chi-square at a 95% confidence interval tested the association of NTM to mutation patterns for each gene. RESULTS: NTM harboring mutations associated with resistance to at least one of the antibiotics used in the macrolide-based therapy were 23% (28/122). Of these NTM, 10.4% (12/122) had mutations in the rrl gene with 58.3% (7/12) comprising RGM and 41.7% (5/12) being SGM. Mutation at position 2058 (A2058G, A2058C, A2058T) of the rrl gene was seen for 83.3% (10/12) of NTM, while 16.6% (2/12) harbored a A2059G mutation. Of the 54 RGM included for rrs characterization, 11.1% (6/54) exhibited mutations  at position 1408(A1408G), while 14.7% (10/68) of the SGM had mutations in the rpoB gene at positions S531W, S531L, S531Y, F506L, E509H with M.gastri having multiple mutations at positions D516V, H526D and, S531F. CONCLUSION: We demonstrated a significant level of mutations associated with drug resistance for macrolides, aminoglycosides, and rifampicin in NTM isolated from symptomatic TB negative patients in Kenya.

Systemic and Mucosal Concentrations of Nine Cytokines Among Individuals with Neisseria gonorrhoeae infection in Nairobi Kenya.

Introduction: The human-restricted sexually transmitted Neisseria gonorrhoeae (NG) has been shown to modulate the immune response against it and consequently the cytokines produced. The levels of cytokines in NG infection in the African population have not been well described. We aimed to quantify the systemic and mucosal cytokines in NG infection. Methods: This was a comparative cross-sectional study. Levels of nine cytokines (IL-1ß, IL-2, IL-4, 1L-6, 1L-10, 1L-12p70, IL-17A, TNF-α and INF-γ) were measured from plasma and genital samples (urethral swabs in men and cervicovaginal lavage in women) from 61 Neisseria gonorrhoeae infected individuals seeking treatment for sexually transmitted infections (STIs) at Casino Health Centre in Nairobi, Kenya. A comparative group of 61 NG-uninfected individuals, seeking treatment at the same facility but with laboratory-confirmed negative Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis(TV) was also included. The Mann-Whitney U test was used to compare the cytokine levels between NG-infected and uninfected individuals. Data was analyzed using STATA ver. 15.1. Results: Overall, systemic IL-6, TNF-α and IL-10 were elevated while genital IL-10 and TNF-α were lower in NG positive participants. On subgroup analysis by sex, the levels of genital IL-1ß and IL-6 and systemic IL-6 were elevated in NG-infected men. None of the genital cytokines were elevated in NG-infected women, while all systemic cytokines, except INF-γ, were elevated in NG-infected women. Conclusions: Neisseria gonorrhoeae induced the production of different cytokines in men and women, with men having a pro-inflammatory genital response. These differences should be taken into consideration during development of various interventions e.g. vaccine development.

Diagnostic accuracy of the syndromic management of four STIs among individuals seeking treatment at a health centre in Nairobi, Kenya: a cross-sectional study.

INTRODUCTION: the syndromic approach to the management of sexually transmitted diseases (STIs) is recommended in areas without adequate laboratory support. We assessed the diagnostic accuracy of this approach in diagnosing Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) among 18 to 49 year-old individuals seeking treatment for STIs in a health centre in Nairobi, Kenya. METHODS: participants were recruited between April and June 2019. After providing written informed consent, an interviewer-administered questionnaire was completed. Endocervical swabs from women and urethral swabs from men were collected for STI testing using polymerase chain reaction (PCR). Diagnostic accuracy of reported symptoms was calculated using PCR as the gold standard. RESULTS: a total of 297 individuals (148 men and 149 women) were recruited. Majority of the participants had at least one reported symptom (130/148; 87.8% men and 145/148; 97.3% women). The most commonly diagnosed STI was NG (85/297; 28.6% 95%CI 23.5%-34.1%). Vaginal discharge syndrome had moderate (44.4%) to high (92.9%) sensitivity, low specificity, low positive predictive value (PPV) (2.4 % to 31.5%) and high negative predictive value (NPV) (68.2% to 95.2%). The lower abdominal pain syndrome had moderate to high sensitivity (40% to 71.4%), low specificity (30.9% to 35.6%), low PPV (9.9% to 15.8%) and high NPV (79.2% to 93.8%). The urethral discharge syndrome had high sensitivity (71.4% to 84.8%); moderate specificity (37.6% to 51.7%); low to moderate PPV (5.4% to 53.8%) and high NPV (83.6% to 96.4%). The kappa scores for the three syndromes were generally poor. CONCLUSION: these findings support the need for the review of the syndromic management of STIs.