Department of Biomedical Sciences

Impact of age, HIV1, sickle-cell genotypes, and interferon-gamma gene upstream variants on malaria disease outcomes in a longitudinal pediatric cohort

2025-09-10T13:05:58Z

Impact of age, HIV1, sickle-cell genotypes, and interferon-gamma gene upstream variants on malaria disease outcomes in a longitudinal pediatric cohort Raballah, Evans; Anyona, B.Samuel; Osata, W.Shamim.et.al This prospective cohort study explored the association between two upstream IFN-γ variants (rs2069709: G>T and rs2069705: A>G) and hazard factors for malaria outcomes in a longitudinal cohort of children (n=941, 3–36 mos.), followed for three years. The impact of age, sex, previous malaria exposure, HIV1 infection, and sickle-cell genotypes (HbAA, HbAS, and HbSS) was also investigated. Reduced malaria episodes were associated with older age at enrollment [HR=0.957 (95% CI=0.953–0.961) per month, P<2.2e-16], HIV1 infection [0.687 (0.545–0.866), P=0.001], being female [0.910 (0.859–0.964), P=0.040], and HbAS [0.823 (0.754–0.898), P=0.005]. The GA/ TA diplotype [0.376 (0.230–0.614), P=0.002] also reduced the hazard of malaria, while TA haplotype increased susceptibility [1.749 (1.159–2.640), P=0.029]. Factors protecting against the development of SMA [Hemoglobin (Hb<6.0 g/dL)] included older age [0.927 (0.913–0.942) per month, P<2.2e-16], previous malaria episodes [0.576 (0.542–0.614, P=9.5e-32)], HbAS [0.553 (0.400-0.766), P=0.015]. The rs2069705AG genotype increased the hazard of SMA [1.697 (1.002–2.875), P=0.042]. Reduced hazard of mortality was observed for older children [0.898 (0.857–0.941), P<2.2e-16], while a higher hazard was present in HIV-infected children [12.475 (6.380-24.392), P<2.2e-16], and in those with HbSS [6.341 (1.944–20.686), P=0.007]. The GG haplotype increased the mortality hazard [1.817 (0.936– 3.527), P=0.078]. The results here highlight critical factors influencing the hazard of malaria, SMA, and mortality

Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance

2025-09-10T12:50:25Z

Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance Wasena, A. Sharley; Onyango, O.Clinton; Osata, W.Shamim.et.al Malaria remains a significant cause of childhood morbidity and mortality, with Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, persistent PfHRP2 antigenemia and gene deletions can cause false-positive and false-negative results, compromising their accuracy for malaria case management and surveillance. This study evaluated the diagnostic performance and antigen persistence of PfHRP2-mRDTs using data from a longitudinal birth cohort of 750 children followed monthly from birth to 36 months in a holoendemic region of Kenya. Malaria diagnosis was performed using both microscopy and mRDTs, with a total of 15,006 clinical events recorded from 573 children between 2017 and 2023. Data from an independent acute febrile cohort of 937 children (<5 years) followed for 14 days was analyzed to validate the findings. The mRDT showed a high sensitivity of 97.27% but a moderate specificity of 65.00% in acute febrile illness, indicating frequent false-positive results. The positive predictive value was low (35.10%), suggesting that confirmatory testing is needed, while the negative predictive value was high (98.89%), reinforcing the reliability of mRDTs in ruling out malaria. Persistent PfHRP2 antigenemia was observed, with a median antigen clearance time of 51.14 days, respectively. Higher initial parasite densities (>50,000/μL) were associated with a slower antigen decay rate (p = 0.001), highlighting the challenge of interpreting positive mRDT results after treatment. Validation using the acute febrile cohort showed that mRDT specificity exceeded 95% at initial diagnosis and follow-up. Overall, PfHRP2-based mRDTs remain valuable for frontline malaria diagnosis but are limited by antigen persistence, leading to false positives in follow-up testing. Where feasible, integration of confirmatory diagnostic methods, such as microscopy or molecular assays, could improve the performance of malaria case management and clinical decision making, particularly in high-transmission settings.

Distribution of nontuberculous Mycobacteria among presumptive drug resistance tuberculosis patients from a ministry of health drug resistance surveillance program, in western Kenya

2025-09-10T09:32:32Z

Distribution of nontuberculous Mycobacteria among presumptive drug resistance tuberculosis patients from a ministry of health drug resistance surveillance program, in western Kenya Okumu, Albert; Odeny, Lazarus; Ochieng, John Benjamin.et.al Nontuberculous Mycobacteria (NTM) species are emerging pathogens causing Pulmonary diseases with no definitive treatment. Molecular techniques enable characterization and drug resistance profiling, this study sought to determine NTM prevalence, circulating species, and distribution factors among presumptive multidrug-resistant tuberculosis (MDR-TB) patients in western Kenya.

Factors associated with tuberculosis drug resistance among presumptive multidrug resistance tuberculosis patients identified in a DRTB surveillance study in western Kenya

2025-02-26T10:53:09Z

Factors associated with tuberculosis drug resistance among presumptive multidrug resistance tuberculosis patients identified in a DRTB surveillance study in western Kenya Albert Okumu, James Orwa, Ruth Sitati, Isaiah Omondi, Ben Odhiambo, Jeremiah Ogoro, George Oballa, Benjamin Ochieng, Steve Wandiga, Collins Ouma Multidrug-resistant tuberculosis (MDR-TB) is caused by M. tuberculosis (Mtb) with resistance to the first-line anti-TB medicines isoniazid (INH) and rifampicin (RIF). In Western Kenya, there is reported low prevalence of drug resistant strains among HIV tuberculosis patients, creating a need to determine factors associated with drug resistance patterns among presumptive MDR-TB patients. To determine factors associated with drug resistance patterns among presumptive MDR-TB patients in western Kenya. Three hundred and ninety (3 9 0) sputum sample isolates from among presumptive multidrug TB patients, were analyzed for TB drug resistance as per Ministry of Health (MoH) TB program diagnostic algorithm. Frequency and percentages were used to summarize categorical data while median and interquartile range (IQR) were used for continuous data. Multivariable logistic regression was carried out to identify factors associated with TB drug resistance. Out of 390 participants enrolled, 302/390 (77.4 %) were males, with a median age of 34 years. The HIV-infected were 118/390 (30.3 %). Samples included 322 (82.6 %) from presumptive patients, while 68/390 (17.4 %) were either lost to follow-up patients, failures to first-line treatment or newly diagnosed cases. A total of 64/390 (16.4 %) of the isolates had at least some form of drug resistance. Out of 390, 14/390 (3.6 %) had MDR, 12 (3.1 %) were RIF mono-resistance, 34 (8.7 %) had INH, while 4 (1 %) had ethambutol resistance. The category of previously treated patients (those who received or are currently on TB treatment) had a 70 % reduced likelihood of resistance (aOR: 0.30; 95 % CI: 0.13–0.70). In contrast, older age was associated with an increased likelihood of resistance to INH and RIF, with an adjusted odds ratio of 1.04 per year (95 % CI: 1.00–1.08). Prompt MDR-TB diagnosis is essential for appropriate patient care, management, and disease prevention and control. We recommend active surveillance on drug resistant TB in these regions to detect drug resistance patterns for rapid disease management. https://www.sciencedirect.com/science/article/pii/S2405579424000536

Uro-pathogens: Prevalence of bacterial agents, and antimicrobial susceptibility profiles of urinary tract infections among pregnant women living with HIV in Kisumu County, Kenya

2025-02-24T09:17:23Z

Uro-pathogens: Prevalence of bacterial agents, and antimicrobial susceptibility profiles of urinary tract infections among pregnant women living with HIV in Kisumu County, Kenya KISUBA, K; GUYAH, B; AWUOR, S.O; OUMA, C During pregnancy, urinary Tract Infections (UTIs) are among the most common infections, particularly in women living with HIV worldwide, and can lead to poor perinatal and maternal outcomes. This study determined the prevalence of UTIs during pregnancy, associated risk factors, and antimicrobial susceptibility profiles of associated bacterial pathogens in pregnant women living with HIV attending a highvolume hospital in Kisumu County, Kenya. http://www.doi.org/10.52768/2766-7820/3421

Measuring the effect of antenatal family planning counseling on the intention for early postpartum family planning among postpartum mothers in Western Kenya

2025-02-24T09:07:08Z

Measuring the effect of antenatal family planning counseling on the intention for early postpartum family planning among postpartum mothers in Western Kenya SHISANYA, Morris; KIPMEREWO, Mary; MOREMA, Everlyne; OUMA, Collins Maternal and Child Health (MCH) care continuum provides a great opportunity for PPFP interventions integration especially antenatal FP counseling. This study measured the effect of antenatal FP counseling on the intention for early PPFP among postpartum mothers in Kisumu County. https://ejrh.org/index.php/ejrh/article/view/834/274

Assessing the application of adapted theory of planned behaviour in predicting postpartum family planning intentions in a pragmatic randomized control trial in Western Kenya

2025-02-24T08:57:18Z

Assessing the application of adapted theory of planned behaviour in predicting postpartum family planning intentions in a pragmatic randomized control trial in Western Kenya SHISANYA, Morris Senghor; KIPMEREWO, Mary; MOREMA, Everlyne; OUMA, Collins In developing countries like Kenya, addressing the high population growth rate necessitates a focus on early Postpartum Family Planning (PPFP) use. Despite the critical need for PPFP, few researchers explore the application of health behaviour change theories to enhance FP use among postpartum women. This study assesses the application of adapted Theory of Planned Behaviour (TPB) in predicting intention for early PPFP in postpartum women in Western Kenya. https://doi.org/10.1371/journal.pone.0315029

Disproportionate impact of COVID-19 severity and mortality on hospitalized American Indian/Alaska Native patients

2024-11-04T08:07:17Z

Disproportionate impact of COVID-19 severity and mortality on hospitalized American Indian/Alaska Native patients Ivy Hurwitz, Alexandra V Yingling, Teah Amirkabirian, Amber Castillo, Jehanzaeb J Khan, Alexandra Do, Dominic K Lundquist, October Barnes, Christophe G Lambert, Annabeth Fieck, Gregory Mertz, Clinton Onyango, Samuel B Anyona, J Pedro Teixeira, Michelle Harkins, Mark Unruh, Qiuying Cheng, Shuguang Leng, Philip Seidenberg, Anthony Worsham, Jens O Langsjoen, Kristan A Schneider, Douglas J Perkins Epidemiological data across the United States of America illustrate health disparities in COVID-19 infection, hospitalization, and mortality by race/ethnicity. However, limited information is available from prospective observational studies in hospitalized patients, particularly for American Indian or Alaska Native (AI/AN) populations. Here, we present risk factors associated with severe COVID-19 and mortality in patients (4/2020–12/2021, n = 475) at the University of New Mexico Hospital. Data were collected on patient demographics, infection duration, laboratory measures, comorbidities, treatment(s), major clinical events, and in-hospital mortality. Severe disease was defined by COVID-related intensive care unit requirements and/or death. The cohort was stratified by self-reported race/ethnicity: AI/AN (30.7%), Hispanic (47.0%), non-Hispanic White (NHW, 18.5%), and Other (4.0%, not included in statistical comparisons). Despite similar timing of infection and comparable comorbidities, admission characteristics for AI/AN patients included younger age (P = 0.02), higher invasive mechanical ventilation requirements (P = 0.0001), and laboratory values indicative of more severe disease. Throughout hospitalization, the AI/AN group also experienced elevated invasive mechanical ventilation (P < 0.0001), shock (P = 0.01), encephalopathy (P = 0.02), and severe COVID-19 (P = 0.0002), consistent with longer hospitalization (P < 0.0001). Self-reported AI/AN race/ethnicity emerged as the highest risk factor for severe COVID-19 (OR = 3.19; 95% CI = 1.70–6.01; P = 0.0003) and was a predictor of in-hospital mortality (OR = 2.35; 95% CI = 1.12–4.92; P = 0.02). Results from this study highlight the disproportionate impact of COVID-19 on hospitalized AI/AN patients, who experienced more severe illness and associated mortality, compared to Hispanic and NHW patients, even when accounting for symptom onset and comorbid conditions. These findings underscore the need for interventions and resources to address health disparities in the COVID-19 pandemic.

Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism

2024-11-04T07:55:30Z

Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism Clinton O Onyango, Samuel B Anyona, Ivy Hurwitz, Evans Raballah, Sharely A Wasena, Shamim W Osata, Philip Seidenberg, Benjamin H McMahon, Christophe G Lambert, Kristan A Schneider, Collins Ouma, Qiuying Cheng, Douglas J Perkins Severe malarial anemia (SMA, Hb < 6.0 g/dL) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission zones. This study explored the entire expressed human transcriptome in whole blood from 66 Kenyan children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25), focusing on host immune response networks. RNA-seq analysis revealed 6862 differentially expressed genes, with equally distributed up-and down-regulated genes, indicating a complex host immune response. Deconvolution analyses uncovered leukocytic immune profiles indicative of a diminished antigenic response, reduced immune priming, and polarization toward cellular repair in SMA. Weighted gene co-expression network analysis revealed that immune-regulated processes are central molecular distinctions between non-SMA and SMA. A top dysregulated immune response signaling network in SMA was the HSP60-HSP70-TLR2/4 signaling pathway, indicating altered pathogen recognition, innate immune activation, stress responses, and antigen recognition. Validation with high-throughput gene expression from a separate cohort of Kenyan children (n = 50) with varying severities of malarial anemia (n = 38 non-SMA and n = 12 SMA) confirmed the RNA-seq findings. Proteomic analyses in 35 children with matched transcript and protein abundance (n = 19 non-SMA and n = 16 SMA) confirmed dysregulation in the HSP60-HSP70-TLR2/4 signaling pathway. Additionally, glutamine transporter and glutamine synthetase genes were differentially expressed, indicating altered glutamine metabolism in SMA. This comprehensive analysis underscores complex immune dysregulation and novel pathogenic features in SMA.

Methodological assessment for efficient collection of Schistosoma mansoni environmental DNA and improved schistosomiasis surveillance in tropical wetlands

2024-10-28T16:04:13Z

Methodological assessment for efficient collection of Schistosoma mansoni environmental DNA and improved schistosomiasis surveillance in tropical wetlands Ryosuke Osawa, Toshiaki S Jo, Risa Nakamura, Kyoko Futami, Tomoaki Itayama, Evans Asena Chadeka, Benard Ngetich, Sachiyo Nagi, Mihoko Kikuchi, Sammy M Njenga, Collins Ouma, George O Sonye, Shinjiro Hamano, Toshifumi Minamoto Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas. https://doi.org/10.1016/j.actatropica.2024.107402