Human coronavirus HKU1 is globally endemic but genomically understudied. We present six near-complete HKU1 genomes from samples collected in coastal Kenya (2024-2025) that fell into genotypes A (n = 3) and B (n = 3). The data expand the global HKU1 genomic database and will support molecular assay development and phylogeography studies.

Background:SARS-CoV-2 is a major cause of outpatient-attended acute respiratory infections (ARIs). Data from Africa are limited on SARS-CoV-2 infection, variants, symptom profile, and longitudinal trends for outpatient presentation. Methods:Starting December 2020, we established ARI surveillance at 5 outpatient clinics in coastal Kenya, recruiting ∼15 participants (any age) per week per clinic for SARS-CoV-2 testing and genome analysis. Participants provided respiratory samples, demographic details, and vaccination and symptom data. We compared SARS-CoV-2 clinical and molecular epidemiology before and during Omicron waves using multivariate logistic regression. Results:By February 2025, we had recruited 14 562 ARI cases, with 1053 (7.2%) testing positive for SARS-CoV-2. The median age of cases was 25 years (IQR, 15-41) and 65.0% were female. Nine infection waves were recorded, with positivity ranging 8.2% to 25.6%. Interwave intervals increased from ≤3 months in 2021 to ≥6 months in 2024. Sixty-eight PANGO lineages were identified from 782 (74.2%) sequenced cases, with 4 predominating local waves (AY.116, BQ.1.8, FY.4.1, LF.7.3.2), which were rare globally (<0.5%) during their detection period. Overall, common symptoms among positive cases were cough (91.5%), nasal discharge (76.7%), and fever (53.1%). Loss of sense of smell was strongly predictive of COVID-19 in the pre-Omicron era, but body malaise, sore throat, joint pain, and nasal discharge were predictive during the Omicron period. Conclusions:SARS-CoV-2 increasingly shows seasonal annual patterns in coastal Kenya, with its clinical features resembling established endemic respiratory viruses. Its case burden is most pronounced in young adults. Locally dominant genetic variants may differ from those globally.

BACKGROUND:Respiratory syncytial virus (RSV) is the leading cause of hospital admission for lower respiratory infection in infants worldwide, with more than 95% of deaths occurring in low-income and middle-income countries. Predictors of adverse outcomes following RSV hospitalisation remain poorly defined. We aimed to identify clinical and anthropometric predictors of mortality among infants admitted with RSV pneumonia and to assess changes in mortality over a 25-year surveillance period. METHODS:In this retrospective cohort study, we analysed 25 years of paediatric surveillance at Kilifi County Hospital, Kilifi, Kenya, spanning 25 successive RSV seasons. Neonates (aged <28 days) and post-neonatal infants (aged 28 days to 12 months) admitted with WHO-defined pneumonia were tested for RSV and demographic, anthropometric, and clinical data were recorded at admission. The primary outcome was in-hospital death among infants admitted with RSV pneumonia. Predictors of mortality were identified using random-forest and multivariable logistic regression, and temporal trends in mortality and anthropometric status were examined. FINDINGS:Of 75 482 admissions of infants to Kilifi County Hospital between Jan 1, 2001, and July 13, 2025, 19 299 (25·6%) met WHO pneumonia criteria and 2745 (22·7%) had RSV. Of these infants, 2390 (87·1%) were post-neonatal, of whom 58 (2·4%) died in hospital with 44 (76%) deaths within 7 days of admission. Mortality was independently associated with congenital heart disease (odds ratio 3·51 [95% CI 1·37-8·97]), severe undernutrition (per 1-unit reduction in weight-for-age Z score: 1·59 [1·28-1·99]), and hypoxaemia (per 1% decrease in peripheral oxygen saturation: 1·05 [1·03-1·08]). 38 (70·4%) of 54 infants with RSV who died in hospital had a mid-upper arm circumference below the severe acute malnutrition threshold of 11·5 cm. There was no evidence of a sustained decline in RSV-associated in-hospital mortality or improvement in anthropometric status over the 25-year study period. INTERPRETATION:RSV mortality in Kenyan infants remains high and has not declined over 25 years. Severe undernutrition and congenital heart disease identify infants with RSV who are at the highest risk of in-hospital death. These findings highlight the role of chronic anthropometric deficits in RSV outcomes and support targeted nutritional interventions to reduce mortality. FUNDING:Bill & Melinda Gates Foundation and Wellcome.

Background Human metapneumovirus (hMPV) is a major contributor of acute respiratory infections (ARI) in childhood and vulnerable adults. It comprises two antigenically distinct lineages (A and B), with multiple sub-lineages. Genomic analyses of hMPV strains enable monitoring of viral evolution and transmission to inform future interventions but remain underutilized in Africa. Methods We generated 52 near-complete hMPV genomes from respiratory samples collected in Kilifi, Coastal Kenya, using a tiled-amplicon approach and Oxford Nanopore Technologies sequencing. These samples had been identified as hMPV positive by quantitative PCR during (a) a multi-facility outpatient ARI surveillance in nine health facilities in Kilifi between 2016 and 2017, and 2021 to 2023 and (b) a community-based respiratory infection cohort surveillance study between 2023-2024 that sampled enrolled participants irrespective of symptom status. Results Of the 192 positive samples analyzed from the two studies, children under 5 years accounted for most hMPV cases (134/186, 72%). 52 samples were sequenced (>70% genome coverage), and hMPV-A (27/52, 53.8%) and hMPV-B (25/52, 46.2%) lineages were identified. The recovered sequences mapped into sub-lineages A2c (27/52, 53.8%), B1 (12/52, 21.2%), and B2b (13/52, 25%). A shift in the predominant sub-lineage was observed from B2b (2016) to B1 (2021), and finally to A2c-wild type (2023). In February 2021, for the first time, we detected a single A2c strain with a 111-nucleotide duplication in the G gene among Kenyan samples. Conclusion Our study expands the global nucleotide sequence database for hMPV by adding new whole-genome sequences from Kenya collected over the last decade. It highlights the ongoing replacement of locally predominant hMPV lineages and the importation and local transmission of globally circulating strains. These findings underscore the importance of sustained hMPV genomic surveillance to detect emerging variants and monitor lineage circulation patterns that may impact viral transmission, molecular detection, and future control measures.

BACKGROUND:Pneumonia remains the leading cause of infectious mortality in children under 5, with the highest burden in sub-Saharan Africa. Dysbiosis in nasopharyngeal (NP) microbiota may influence pneumonia susceptibility and progression, but little is known about its composition or clinical relevance in low- and middle-income countries. We characterized the NP microbiota of children hospitalized with severe pneumonia in East Africa and investigated associations with clinical outcomes. METHODS:We performed 16S rRNA partial gene sequencing of NP swabs collected at hospital admission from 876 children enrolled in the COAST trial across 5 sites in Kenya and Uganda. Clinical, demographic, and virological data were prospectively collected. Microbial profiles were analyzed using hierarchical clustering, nonmetric multidimensional scaling, and multivariable regression to assess associations with respiratory viral infections, sepsis, cyanosis, bacteremia, coma, HIV status, malnutrition, sickle cell disease, malaria, and mortality. RESULTS:The NP microbiome was structured in 6 distinct clusters, each dominated by different genera, including Staphylococcus, Streptococcus, Haemophilus, Dolosigranulum, Corynebacterium, and Moraxella. Multivariable models adjusting for study site and age showed a positive association between Corynebacterium and early mortality. Temporal analysis showed elevated Corynebacterium abundance in children who died within 48 hours of admission, then declined over longer 56 survival intervals, approaching levels observed in survivors. However, time-continuous models did not support this persistent association, suggesting a subgroup effect. CONCLUSIONS:We provide one of the largest high-resolution surveys of the pediatric upper airway microbiome in Africa, identifying microbial patterns associated with viral infection, HIV status, early death, and bacteremia.

Background Acute respiratory illnesses (ARI) are a major cause of morbidity and mortality globally. With (re)emergence of novel viruses and increased access to childhood bacterial vaccines, viruses have assumed greater importance in the aetiology of ARI. There are now promising candidate vaccines against some of the most common endemic respiratory viruses. Optimal delivery strategies for these vaccines, and the need for interventions against other respiratory viruses, requires geographically diverse data capturing temporal variations in virus circulation. Methods We leveraged three health facility-based respiratory illness surveillance platforms operating in 11 sites across Kenya. Nasopharyngeal (NP) and/or oropharyngeal (OP) specimens, patient demographic, and clinical characteristics were collected in 2014 from individuals of various ages presenting with respiratory symptoms at the surveillance facilities. Real time multiplex polymerase chain reaction was used to detect rhinoviruses, respiratory syncytial virus (RSV), influenza virus, human coronaviruses (hCoV), and adenoviruses. Results From 11 sites, 5451 NP/OP specimens were collected and tested from patients. Of these, 40.2% were positive for at least one of the targeted respiratory viruses. The most frequently detected were rhinoviruses (17.0%) and RSV A/B (10.5%), followed by influenza A (6.2%), adenovirus (6.0%) and hCoV (4.2%). RSV was most prevalent among infants aged <12 months old (18.9%), adenovirus among children aged 12–23 months old (11.0%), influenza A among children aged 24–59 months (9.3%), and rhinovirus across all age groups (range, 12.7–19.0%). RSV had a higher virus positivity in the inpatient setting (12.5%) compared to outpatient setting (4.8%). The overall percent virus positivity varied by surveillance site, health facility type and case definition used in surveillance. Conclusions We identify rhinoviruses, RSV, and influenza A as the most prevalent respiratory viruses. Higher RSV positivity in inpatients, and in infants, strengthens the case for RSV vaccination. To inform the design and delivery of public health interventions, long-term surveillance is required to establish regional heterogeneities in respiratory virus circulation and seasonality.

Background: Acute respiratory illnesses (ARI) are a major cause of morbidity and mortality globally. With (re)emergence of novel viruses and increased access to childhood bacterial vaccines, viruses have assumed greater importance in the aetiology of ARI. There are now promising candidate vaccines against some of the most common endemic respiratory viruses. Optimal delivery strategies for these vaccines, and the need for interventions against other respiratory viruses, requires geographically diverse data capturing temporal variations in virus circulation. Methods: We leveraged three health facility-based respiratory illness surveillance platforms operating in 11 sites across Kenya. Nasopharyngeal (NP) and/or oropharyngeal (OP) specimens, patient demographic, and clinical characteristics were collected in 2014 from individuals of various ages presenting with respiratory symptoms at the surveillance facilities. Real time multiplex polymerase chain reaction was used to detect rhinoviruses, respiratory syncytial virus (RSV), influenza virus, human coronaviruses (hCoV), and adenoviruses. Results: From 11 sites, 5451 NP/OP specimens were collected and tested from patients. Of these, 40.2% were positive for at least one of the targeted respiratory viruses. The most frequently detected were rhinoviruses (17.0%) and RSV A/B (10.5%), followed by influenza A (6.2%), adenovirus (6.0%) and hCoV (4.2%). RSV was most prevalent among infants aged <12 months old (18.9%), adenovirus among children aged 12–23 months old (11.0%), influenza A among children aged 24–59 months (9.3%), and rhinovirus across all age groups (range, 12.7–19.0%). The overall percent virus positivity varied by surveillance site, health facility type and case definition used in surveillance. Conclusions: We identify rhinoviruses, RSV, and influenza A as the most prevalent respiratory viruses. Higher RSV positivity in inpatient settings compared to outpatient clinics strengthen the case for RSV vaccination. To inform the design and delivery of public health interventions, long-term surveillance is required to establish regional heterogeneities in respiratory virus circulation and seasonality.

Influenza B virus (IBV) genomic surveillance occurs unevenly across the globe, obscuring its epidemiology. We analysed 83 near complete IBV genomes collected between 2010 and 2022 in Kenya and Uganda. Alternating IBV lineage predominance and clade turnover was observed consistent with global patterns. No B/Yamagata strains were detected at the study sites after 2019. Multiple B/Victoria clade/subclades (V1A, V1A.3, V1A.3a, V1A.3a.2) and B/Yamagata clades (Y2 and Y3) were identified with no inter-lineage reassortants observed. Over time, the clades/subclades appeared to diversify through the accumulation of amino acid changes along the hemagglutinin (HA) segment backbone, especially within the known antigenic sites. Local outbreak strains appeared to be introduced from both within and outside Africa. The congruence of local and global strains in circulating lineages and amino acid changes suggests potentially similar effectiveness of vaccines recommended for the Northern and Southern Hemispheres in East Africa.

Several African countries experienced a surge in acute hemorrhagic conjunctivitis (AHC) cases in 2024. Investigations in Kenya, Mayotte and Tanzania identified coxsackievirus A24 variant (CV-A24v) as the causative agent. To date, limited genomic data exist to elucidate the sources, epidemiology, and evolution of CV-A24v in Africa. We generated 245 CV-A24v genomes from samples collected between January and September 2024 in coastal Kenya. Phylogenetic analysis showed that these viruses belonged to genotype IV, with two major clusters identified that differed by 52 nucleotides and five amino acids, with recombination detected in the 3D pol gene. The sequences clustered closely with contemporaneous Mayotte and Malawi sequences but were distinct from Asian sequences from 2023. Molecular clock dating revealed that the Kenyan sequences had a Most Recent Common Ancestor (MRCA) between June and October 2023. Our study provides the first detailed genomic analysis of CV-A24v from Africa to inform its future control strategies.

The ongoing SARS-CoV-2 evolution has produced over 5,200 genetically distinct PANGO lineages whose epidemiological trajectories differ across regions. In early 2025, a new recombinant SARS-CoV-2 variant named XFG emerged, predominating in most global regions by June 2025. Here we describe XFG introduction and molecular epidemiological patterns in Kenya, May - July 2025. Of 7,564 nasopharyngeal/oropharyngeal swabs sampled across three surveillance platforms (a community cohort and two outpatient ARI) and tested by quantitative PCR, only 23 (0.03%) were positive. From these, we recovered six near-complete genomes that mapped to PANGO lineages XFG.12, XFG.4.1, XFG.7 and XFG.21. The median age of the positive cases was 18 years (IQR 10.0–21.8) and presented mainly with runny nose (47.6%), cough (42.9%), sore throat (33.3%) and fever (33.3%). Phylogenetic analysis including 14 sequences from Nairobi deposited on GISAID suggested at least 13 introduction events of the XFG variant into Kenya. Amino acid differences were observed between the Kenyan XFG.12 and XFG.4.1 in the ORF1a (H45Y) and ORF1b (D1848X/Y) proteins respectively. We confirm introduction but limited transmission of the XFG variant in Kenya during May–July 2025. This observation underlines the importance of regional genomic surveillance for appropriate and optimized intervention design.

We report nine nearly complete Cryptosporidium parvum virus 1 genome sequences (both segments) recovered from stool samples of pediatric diarrhea patients admitted to Kilifi County Hospital, coastal Kenya. This will be an important resource for monitoring C. parvum infections in humans.

BACKGROUND:Influenza B virus (IBV) contributes significantly to morbidity and mortality during Influenza seasons annually. However, IBV genomic surveillance occurs unevenly across the globe, particularly within the African region, obscuring its epidemiology. This study aims to elucidate the epidemiological dynamics of IBV in Kenya and Uganda between 2010 and 2022. METHODS:In this study, 83 near complete IBV genomes circulating in Kenya and Uganda between 2010 and 2022 were generated through Oxford Nanopore Technologies sequencing (ONT). Publicly available IBV datasets were incorporated to evaluate the public context of these genomes. Further evolutionary dynamics analysis investigated the antigenic mutation, reassortment and glycosylation patterns of IBVs circulating in Kenya and Uganda within this period. RESULTS:Alternating IBV lineage predominance and clade turnover was observed consistent with global patterns. No B/Yamagata strains were detected at the study sites after 2019. Multiple B/Victoria clade/subclades (V1A, V1A.3, V1A.3a, V1A.3a.2) and B/Yamagata clades (Y2 and Y3) were identified with no inter-lineage reassortments observed. Over time, the clades/subclades appeared to diversify through the accumulation of amino acid changes along the hemagglutinin (HA) segment backbone, especially within the known antigenic sites. Local outbreak strains appeared to be putatively introduced from both within and outside Africa. CONCLUSIONS:The congruence of local and global strains in circulating lineages and amino acid changes suggests potential effectiveness of vaccines recommended for the Northern and Southern Hemispheres in East Africa.

The recombinant FY.4 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant was first reported in Kenya in March 2023 and was the dominant circulating variant between April and July 2023. The variant was characterized by two important mutations: Y451H in the receptor-binding domain of the spike protein and P42L in open reading frame 3a. Using phylogenetics and phylodynamic approaches, we investigated the emergence and spread of FY.4 in Kenya and the rest of the world. Our findings suggest FY.4 circulated early in Kenya before its export to North America and Europe. Early circulation of FY.4 in Kenya was predominantly observed in the coastal part of the country, and the estimated time to the most recent common ancestor suggests FY.4 circulated as early as December 2022. The collected genomic and epidemiological data show that the FY.4 variant led to a large local outbreak in Kenya and resulted in localized outbreaks in Europe, North America, and Asia-Pacific. These findings underscore the importance of sustained genomic surveillance, especially in under-sampled regions, in deepening our understanding of the evolution and spread of SARS-CoV-2 variants.

Between November 2023 and March 2024, coastal Kenya experienced another wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections detected through our continued genomic surveillance. Herein, we report the clinical and genomic epidemiology of SARS-CoV-2 infections from 179 individuals (a total of 185 positive samples) residing in the Kilifi Health and Demographic Surveillance System (KHDSS) area ( 900 km2). We analyzed genetic, clinical, and epidemiological data from SARS-CoV-2 positive cases across pediatric inpatient, health facility outpatient, and homestead community surveillance platforms. Phylogenetic analyses were performed using maximum-likelihood and Bayesian frameworks. Temporal trends were summarized, comparisons conducted using Kruskal–Wallis and Wilcoxon tests, and associations examined using univariate and multivariable logistic regression models. Sixteen SARS-CoV-2 lineages within 3 subvariants [XBB.2.3-like (58.4

The recombinant FY.4 SARS-CoV-2 variant was first reported in Kenya in March 2023 and was the dominant circulating variant between April and July 2023. The variant was characterised by two important mutations: Y451H in the receptor binding domain of the spike protein and P42L in open reading frame 3a. Using phylogenetics and phylodynamic approaches, we investigated the emergence and spread of the FY.4 in Kenya and the rest of the world. Our findings suggest FY.4 circulated early in Kenya before export to North America and Europe. Early circulation of FY.4 in Kenya was predominantly observed in the coastal part of the country and the estimated time to the most recent common ancestor suggests FY.4 circulated as early as December 2022. The collected genomic and epidemiological data show that the FY.4 variant led to a large local outbreak in Kenya and resulted in localised outbreaks in Europe, North America and Asia-pacific. These findings underscore the importance of sustained genomic surveillance especially in under sampled regions in deepening our understanding of the evolution and spread of SARS-CoV-2 variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was support by multiple funding sources that included the New Variant Assessment Platform (NVAP), Wellcome grants (220985/Z/20/Z and 226002/A/22/Z). The Rockerfeller Foundation subaward (OXFFDG01) and the Department of Health and Social Care grant (project references 17/63/82 and 16/136/33). The views expressed in this publication are those of the author (s) and not necessarily those of the Department of Health and Social Care, Foreign Commonwealth and Development Office, Wellcome Trust or the UK government ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The whole genome sequencing study protocol was reviewed and approved by the Scientific and Ethics Review Committee (SERU) residing at the Kenya Medical Research Institute (KEMRI) headquarters in Nairobi (SERU # 4035). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript

The epidemiology and circulation patterns of various rhinovirus types within populations remains under-explored. We generated 803 VP4/VP2 gene sequences from rhinovirus-positive samples collected from acute respiratory illness (ARI) patients, including both in-patient and outpatient cases, between 1st January and 31st December 2014 from eleven surveillance sites across Kenya and used phylogenetics to characterise virus introductions and spread. RVs were detected throughout the year, with the highest detection rates observed from January to March and June to July. We detected a total of 114 of the 169 currently classified types. Our analysis revealed numerous virus introductions into Kenya characterized by local expansion and extinction, and extensive spatial mixing of types within the country due to the widespread transmission of the virus after an introduction. This work demonstrates that in a single year, the circulation of rhinovirus in Kenya was characterized by substantial genetic diversity, multiple introductions, and extensive geographical spread.

Respiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya. A structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019–2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness. We enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9

Background The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. Methods A total of 870 stool samples from children under 13 years of age admitted to Kilifi County Hospital between January 2019, and December 2022 were screened for rotavirus group A (RVA), norovirus genogroup II (GII), astrovirus, sapovirus, and adenovirus type F40/41 using real-time reverse-transcription polymerase chain reaction. The proportions positive across the four years were compared using the chi-squared test statistic. Results One or more of the five virus targets were detected in 282 (32.4%) cases. A reduction in the positivity rate of RVA cases was observed from 2019 (12.1%, 95% confidence interval (CI) 8.7–16.2%) to 2020 (1.7%, 95% CI 0.2–6.0%; p < 0.001 ). However, in the 2022, RVA positivity rate rebounded to 23.5% (95% CI 18.2%–29.4%). For norovirus GII, the positivity rate fluctuated over the four years with its highest positivity rate observed in 2020 (16.2%; 95% C.I, 10.0–24.1%). No astrovirus cases were detected in 2020 and 2021, but the positivity rate in 2022 was similar to that in 2019 (3.1% (95% CI 1.5%–5.7%) vs. 3.3% (95% CI 1.4–6.5%)). A higher case fatality rate was observed in 2021 (9.0%) compared to the 2019 (3.2%), 2020 (6.8%) and 2022 (2.1%) ( p < 0.001). Conclusion Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.

Background: In many low-resource settings, the clinical management of children with febrile infections is hindered by poor access to diagnostic tools to determine whether the cause of an infection is bacterial, viral or parasitic. As a result, many clinicians resort to the default prescription of antibiotics as a safety precaution, contributing to the alarming spread of antimicrobial resistance. Commonly used biomarkers for the identification of bacterial sepsis such as CRP lack aetiological specificity and are frequently elevated by non-bacterial infections including malaria. We set out to discover and validate new biomarkers for the characterization of the microbial aetiology of febrile acute infections in Kenyan children. Methods: We recruited a discovery cohort comprising of children who had been admitted to hospital with a variety of severe acute infections. Diagnostic identification of viral infections was done using a 15-target virus PCR panel, bacterial infections were identified using blood culture while malaria infections were identified by microscopy. Using mass spectrometry analysis, we identified a set of 76 plasma proteins whose abundance varied significantly by the microbial aetiology of infection and used machine learning to generate a shortlist of candidate biomarkers that had the highest diagnostic performance in distinguishing aetiologies. To validate these candidate biomarkers, we recruited a separate validation cohort where the plasma levels of the shortlisted biomarkers were assayed among children with different infectious aetiologies using a custom protein microarray. Results: In the discovery study, six candidate biomarkers whose plasma abundance was significantly different in children with bacterial and viral infections were shortlisted by random forest for cross-cohort validation (AGT, HRG, LBP, PON1, SERPINA1, SERPINA3). In the validation study, we found that of the six biomarkers, only AGT compared favourably to CRP and identified febrile bacterial infections with a sensitivity of 72.4% (95% CI 48.4% - 83.6%) compared to CRP which distinguished febrile bacterial infections with a sensitivity of 69.5% (30.8% - 88.2%). Plasma AGT was superior to CRP in distinguishing children with febrile bacterial infections from those with febrile malaria episodes, with a sensitivity of 72.5% (40% - 84.6%) for AGT and 26% (15% - 32.8%) for CRP. Conclusions: We report the discovery of AGT, as a sensitive plasma biomarker for the identification of febrile bacterial infections among African children living in a malaria-endemic setting.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by the Wellcome Trust### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Scientific Ethics Review Unit of the Kenya Medical Research Institute gave ethical approval for this work. The parents and legal representatives of all children in this study provided written informed consent before recruitment into the study.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript

Background Although seven human adenovirus (HAdV) species are known to exist,only F (types 40 and 41) and G, are identified as diarrhoeal disease agents. The role of other HAdV species in diarrhoeal disease remains unclear and data of their prevalence is limited. We describe HAdV species and types in hospitalised children with diarrhoea in coastal Kenya. Methods 329 stool samples collected between June 2022 and August 2023 from children aged <13-years were screened for HAdV using quantitative polymerase chain reaction (qPCR). Positive HAdV cases were genotyped by adenovirus primers from the RespiCoV panel by amplification, next generation sequencing followed by phylogenetic analysis. Results 65 samples (20%) tested HadV positive from which five HAdV species were identified. Other than HAdV F, other species included A, B, C and D; these were detected as either mono-detections or coinfections. Six HAdV F identified by NGS had been missed by our q PCR typing method. This appeared to be as a result of a 133-nucleotide deletion in the long fiber protein which abrogated a primer and probe binding site. Based on VESIKARI scores grading of diarrheal disease severity, 93% of the HAdV cases presented with severe disease. One child with an HAdV F infection died. Conclusion Our study shows the enormous diversity and clinical characteristics of HAdV species in children with diarrhoea in coastal Kenya. These data offers an opportunity to improve current diagnostic assays, increase knowledge of HAdV in Africa for control of outbreaks in the future. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded in part by the Cambridge-Africa ALBORADA Research Fund to Drs Agoti and Houldcroft. This research was funded in part by the Wellcome Trust [226002/Z/22/Z]. For the purpose of Open Access, the author has applied a CC-BY public copyright license to any author accepted manuscript version arising from this submission. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research protocol for the study was approved at Kenya Medical Research Institute (KEMRI), by the Scientific and Ethics Review Unit (SSC#2861) in Nairobi, Kenya. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and/or analyzed during the current study are available from the KWTRP Research repository via <https://doi.org/10.7910/DVN/XCHBND>. The HAdV sequences were deposited on GenBank and can be accessed using the accession numbers [PP318651][1]-[PP318703][2]. [1]: /lookup/external-ref?link_type=GEN&access_num=PP318651&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F26%2F2024.03.21.24304701.atom [2]: /lookup/external-ref?link_type=GEN&access_num=PP318703&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F26%2F2024.03.21.24304701.atom