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.

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.

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 COVID-19 pandemic has been characterised by sequential variant-specific waves shaped by viral, individual human and population factors. SARS-CoV-2 variants are defined by their unique combinations of mutations and there has been a clear adaptation to more efficient human infection since the emergence of this new human coronavirus in late 2019. Here, we use machine learning models to identify shared signatures, i.e., common underlying mutational processes and link these to the subset of mutations that define the variants of concern (VOCs). First, we examined the global SARS-CoV-2 genomes and associated metadata to determine how viral properties and public health measures have influenced the magnitude of waves, as measured by the number of infection cases, in different geographic locations using regression models. This analysis showed that, as expected, both public health measures and virus properties were associated with the waves of regional SARS-CoV-2 reported infection numbers and this impact varies geographically. We attribute this to intrinsic differences such as vaccine coverage, testing and sequencing capacity and the effectiveness of government stringency. To assess underlying evolutionary change, we used non-negative matrix factorisation and observed three distinct mutational signatures, unique in their substitution patterns and exposures from the SARS-CoV-2 genomes. Signatures 1, 2 and 3 were biased to C→T, T→C/A→G and G→T point mutations. We hypothesise assignments of these mutational signatures to the host antiviral molecules APOBEC, ADAR and ROS respectively. We observe a shift amidst the pandemic in relative mutational signature activity from predominantly Signature 1 changes to an increasingly high proportion of changes consistent with Signature 2. This could represent changes in how the virus and the host immune response interact and indicates how SARS-CoV-2 may continue to generate variation in the future. Linkage of the detected mutational signatures to the VOC-defining amino acids substitutions indicates the majority of SARS-CoV-2’s evolutionary capacity is likely to be associated with the action of host antiviral molecules rather than virus replication errors.

BACKGROUND:Pandemic preparedness is critical to respond effectively to existing and emerging/new viral pathogens. Important lessons have been learned during the last pandemic at various levels. This revision discusses some of the major challenges and potential ways to address them in the likely event of future pandemics.OBJECTIVES:To identify critical points of readiness that may help us accelerate the response to future pandemics from a clinical microbiology laboratory perspective with a focus on viral diagnostics and genomic sequencing. The potential areas of improvement identified are discussed from the sample collection to information reporting.SOURCES:Microbiologists and researchers from five countries reflect on challenges encountered during the COVID-19 pandemic, review published literature on prior and current pandemics, and suggest potential solutions in preparation for future outbreaks.CONTENT:Major challenges identified in the pre-analytic and post-analytic phases from sample collection to result reporting are discussed. From the perspective of clinical microbiology laboratories, the preparedness for a new pandemic should focus on zoonotic viruses. Laboratory readiness for scalability is critical and should include elements related to material procurement, training personnel, specific funding programmes, and regulatory issues to rapidly implement "in-house" tests. Laboratories across various countries should establish (or re-use) operational networks to communicate to respond effectively, ensuring the presence of agile circuits with full traceability of samples.IMPLICATIONS:Laboratory preparedness is paramount to respond effectively to emerging and re-emerging viral infections and to limit the clinical and societal impact of new potential pandemics. Agile and fully traceable methods for sample collection to report are the cornerstone of a successful response. Expert group communication and early involvement of information technology personnel are critical for preparedness. A specific budget for pandemic preparedness should be ring-fenced and added to the national health budgets.

IntroductionUnderstanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. MethodsHere, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. ResultsDuring acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. DiscussionLower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.

Supplementary Methods and Figure from Cellular Targets of Gefitinib

Supplementary Figure 1 from Proteomic Characterization of the Angiogenesis Inhibitor SU6668 Reveals Multiple Impacts on Cellular Kinase Signaling

ABSTRACTThe introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline of childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes, has increased, which may result from non-vaccine-type replacement. Here we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix® vaccine. We examined the 63 RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, Coastal Kenya, pre- (2012 to June 2014) and post- (July 2014-2018) rotavirus vaccine introduction. All the 63 genome sequences showed a typical DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. G2 sub-lineage IVa-3 strains predominated in the pre-vaccine era co-circulating with low numbers of G2 sub-lineage IVa-1 strains, whereas sub-lineage IVa-3 strains dominated the post-vaccine period. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid changes in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre- and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically, but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and infect individuals. The exterior surface of the SARS-CoV-2 virion is dominated by the spike protein, and the current work examined spike protein biochemical features that have changed during the 3 years in which SARS-CoV-2 has infected humans. Our analysis identified a striking change in spike protein charge, from -8.3 in the original Lineage A and B viruses to -1.26 in most of the current Omicron viruses. We conclude that in addition to immune selection pressure, the evolution of SARS-CoV-2 has also altered viral spike protein biochemical properties, which may influence virion survival and promote transmission. Future vaccine and therapeutic development should also exploit and target these biochemical properties.

Supplementary Methods from Proteomic Characterization of the Angiogenesis Inhibitor SU6668 Reveals Multiple Impacts on Cellular Kinase Signaling

Supplementary Table 1 from Cellular Targets of Gefitinib

Abstract Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib and provide rationales for the development of related drugs.

Supplementary Table 2 from Cellular Targets of Gefitinib

We describe a cluster of COVID-19 breakthrough infections after vaccination in Kyamulibwa, Kalungu District, Uganda. All but 1 infection were from SARS-CoV-2 Omicron strain BA.5.2.1. We identified 6 distinct genotypes by genome sequencing. Infections were mild, suggesting vaccination is not protective against infection but may limit disease severity.

There is an urgent need for better immunoassays to measure antibody responses as part of immune-surveillance activities and to profile immunological responses to emerging SARS-CoV-2 variants. We optimised and validated an in-house conventional ELISA to identify and quantify SARS-CoV-2 spike- (S-), receptor binding domain- (RBD-), and nucleoprotein- (N-) directed IgG, IgM, and IgA binding antibodies in the Ugandan population and similar settings. Pre- and post-pandemic specimens were used to compare the utility of mean ± 2SD, mean ± 3SD, 4-fold above blanks, bootstrapping, and receiver operating characteristic (ROC) analyses in determining optimal cut-off optical densities at 450 nm (OD) for discriminating between antibody positives and negatives. "Limits of detection" (LOD) and "limits of quantitation" (LOQ) were validated alongside the assay's uniformity, accuracy, inter-assay and inter-operator precision, and parallelism. With spike-directed sensitivity and specificity of 95.33 and 94.15%, respectively, and nucleoprotein sensitivity and specificity of 82.69 and 79.71%, ROC was chosen as the best method for determining cutoffs. Accuracy measurements were within the expected CV range of 25%. Serum and plasma OD values were highly correlated (r = 0.93, p=0.0001). ROC-derived cut-offs for S-, RBD-, and N-directed IgG, IgM, and IgA were 0.432, 0.356, 0.201 (S), 0.214, 0.350, 0.303 (RBD), and 0.395, 0.229, 0.188 (N). The sensitivity and specificity of the S-IgG cut-off were equivalent to the WHO 20/B770-02 S-IgG reference standard at 100% level. Spike negative IgG, IgM, and IgA ODs corresponded to median antibody concentrations of 1.49, 3.16, and 0 BAU/mL, respectively, consistent with WHO low titre estimates. Anti-spike IgG, IgM, and IgA cut-offs were equivalent to 18.94, 20.06, and 55.08 BAU/mL. For the first time, we provide validated parameters and cut-off criteria for the in-house detection of subclinical SARS-CoV-2 infection and vaccine-elicited binding antibodies in the context of Sub-Saharan Africa and populations with comparable risk factors.

The rapid global spread of new SARS-CoV-2 variants despite travel restrictions has revealed deficiencies in existing strategies and a need to evaluate them.1Mendelson M Venter F Moshabela M et al.The political theatre of the UK's travel ban on South Africa.Lancet. 2021; 398: 2211-2213Google Scholar Such strategies—eg, vaccine passports, reactive flight bans, isolation of travellers who test positive for SARS-CoV-2 or blanket quarantines, and major changes to travel protocols—have often had weak accompanying justifications. Many governments continue to adapt various combinations of international travel measures and, increasingly, scale them back (figure) without stating clear objectives or the evidence behind them. In an era of SARS-CoV-2 variants and for future pandemic preparedness, there is a need for a transparent and evidence-based approach to travel strategies, supported by the development of clear international standards. In our view, there are several potential objectives that travel testing and restrictions can help address, including: monitoring incoming SARS-CoV-2 variants among travellers; reducing risk of outbreaks resulting from imported cases; delaying introduction and establishment of new variants of concern; and estimating SARS-CoV-2 prevalence in other countries to inform risk assessments. The choice of an objective for travel measures should depend on local and global prevalence of SARS-CoV-2 variants. When there is initially a low domestic prevalence of a particular variant, as occurred early in the COVID-19 pandemic, temporary travel restrictions can delay introductions4Chinazzi M Davies JT Ajelli M et al.The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak.Science. 2020; 38: 395-400Google Scholar and could provide governments time to develop long-term strategies, such as reinforcing surveillance, contact tracing, public health measures, and vaccination campaigns. However, the marginal value of delaying importation of variants such as omicron (B.1.1.529) has declined in many countries because the speed of importations far exceeded the ability of most governments to implement reactive travel policies. Once variants are established locally, ongoing travel restrictions will have extremely limited impact on the local epidemic.5Russell TW Wu JT Clifford S et al.Effect of internationally imported cases on internal spread of COVID-19: a mathematical modelling study.Lancet Public Health. 2021; 6: e12-e20Google Scholar Furthermore, imposing travel restrictions on countries that discover and report new variants could be a disincentive to rapidly reporting findings, damaging a vital early warning system for the rest of the world. If the objective is to monitor importation of SARS-CoV-2 variants, full genome sequencing of incoming infections is typically required, but a lag in reporting data will hinder reactive travel measures. Given the costs and delays involved, targeted national genomic sampling would be more efficient if the objective is to identify variants of concern and provide early situational awareness to support local planning and response.6Wohl S Lee EC DiPrete BL Lessler J Sample size calculations for variant surveillance in the presence of biological and systematic biases.medRxiv. 2021; (published online Dec 30.) (preprint).https://doi.org/10.1101/2021.12.30.21268453Google Scholar Although SARS-CoV-2 testing can help identify infections, quarantine has been used in many countries to reduce risks of onward transmission from incoming travellers with unknown or uncertain infection status. Quarantine is unable to fully prevent local transmission;7Grout L Katar A Ait Ouakrim D et al.Failures of quarantine systems for preventing COVID-19 outbreaks in Australia and New Zealand.Med J Aust. 2021; 215: 320-324Google Scholar stringent domestic restrictions were required to contain subsequent outbreaks in the pre-vaccine era, and containment has become harder with more transmissible variants. Stringent quarantine for all travellers also comes with substantial individual and societal costs. However, such costs may be mitigated through the use of testing after arrival, with test-to-release schemes decreasing the time required for quarantine.8Crozier A Rajan S Buchan I McKee M Put to the test: use of rapid testing technologies for covid-19.BMJ. 2021; 372: n208Google Scholar Given the volume of indirect connections in the global flight network, efforts to merely delay introductions—rather than prevent them entirely—have limited value unless the aim is simply to delay spread by a few days, or if the delay is supplemented by additional domestic measures. In the face of new variants, a less economically disruptive alternative to outright travel bans is to use arrival SARS-CoV-2 testing, as many countries require. Although rapid antigen tests are less sensitive than PCR tests in detecting infection, most have high sensitivity for detecting individuals at the point they are likely to transmit infection.9Mina MJ Parker R Larremore DB Rethinking Covid-19 test sensitivity—a strategy for containment.N Engl J Med. 2020; 383: e120Google Scholar Modelling studies have estimated that repeat rapid antigen tests are more likely to detect active infection than less frequent PCR tests, which are often associated with slower results and higher costs.10Hay JA Hellewell J Qiu X When intuition falters: repeated testing accuracy during an epidemic.Eur J Epidemiol. 2021; 36: 749-752Google Scholar Daily testing of individuals considered a potential transmission risk with rapid antigen tests might also feasibly replace home quarantine with no expected increase in onwards transmission.11Quilty BJ Clifford S Hellewell J et al.Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study.Lancet Public Health. 2021; 6: e175-e183Google Scholar Another potential approach might include trained dogs that distinguish between infected and uninfected individuals using odour samples.12Guest C, Dewhirst SY, Lindsay SW, et al. Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study. J Travel Med (in press).Google Scholar, 13Grandjean D Sarkis R Lecoq-Julien C et al.Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study.PLoS One. 2020; 15e0243122Google Scholar An advantage of this approach would be its speed and the fact that a laboratory specimen or test kit is not required; dogs can potentially screen up to 250 travellers per hour per dog, and trials are underway in the UK.14Jones RT Guest C Lindsay SW et al.Could bio-detection dogs be used to limit the spread of COVID-19 by travellers?.J Travel Med. 2020; 27taaa131Google Scholar However, more evidence is needed before such an approach could be routinely implemented. Alongside testing, COVID-19 vaccination certification has increasingly been used in international travel requirements, and in some cases as a substitute for more disruptive testing and quarantine measures. However, if a strategic objective is to reduce the risk from variants against which vaccines are less effective,15Wu M Wall EC Carr EJ et al.Three-dose vaccination elicits neutralising antibodies against omicron.Lancet. 2022; 19: 715-717Google Scholar then proof of vaccination alone would not be sufficient to prevent the importation of such variants, as shown by the spread of omicron. Certification can therefore only be one component of a wider risk mitigation strategy. Moreover, fake vaccination certificates and test results are being identified in many countries,16Georgoulias D Pedersen JM Falch M Vasilomanolakis E COVID-19 vaccination certificates in the Darkweb.arXiv. 2021; (published online Nov 25.) (preprint).https://doi.org/10.48550/arXiv.2111.12472Google Scholar and as more countries redefine fully vaccinated to include boosters and introduce domestic vaccine passport policies, ensuring alignment of standards internationally will become increasingly important. As governments reassess barriers to international travel, a principle that many have used is equivalent epidemiology—ie, permitting travel between countries with similar levels of SARS-CoV-2 transmission and variants of concern. In 2020, this was successfully used to permit less restrictive travel between countries with low SARS-CoV-2 prevalence, such as in the Western Pacific or Baltic regions.17Webb E Winkelman J Scarpetti G et al.Lessons learned from the Baltic countries' response to the first wave of COVID-19.Health Policy. 2021; (published online Dec 13.)https://doi.org/10.1016/j.healthpol.2021.12.003Google Scholar However, use of reported cases as a measure of equivalency is fraught with difficulty: routine case data do not account for the limited reporting capacity in many countries or variation in actual testing strategy from country to country. Given the extensive SARS-CoV-2 testing for travel that is being used globally, it is a missed opportunity that test data have not been better used to improve understanding of global SARS-CoV-2 dynamics. Testing at arrival not only provides information about incoming infections, it also enables estimation of prevalence in countries of departure. Routine sharing of such data could inform risk assessments for any future measures based on equivalent epidemiology. Governments have a strong evidence base to help them identify and address rational objectives for international travel. As population immunity to SARS-CoV-2 increases in countries both from natural infection and vaccination, earlier objectives will change. However, the rise of omicron has shown that it is crucial to have objectives and travel measures that are transparent and well aligned. The International Health Regulations (2005),18WHOInternational Health Regulations (2005). World Health Organization, Geneva2006Google Scholar negotiated by WHO member states, could serve as a clearing house for evidence obtained from various government strategies, and help coordinate actions by governments to decrease variant risk and disruption to international travel. JGL is an academic at the London School of Hygiene & Tropical Medicine (LSHTM) and the Chief Executive Officer of Arctech Innovation, a spin out company from LSHTM; the company is working on the development of sensors for the detection of diseases including COVID-19. AJK is supported by the Wellcome Trust (206250/Z/17/Z). SC is funded by the Wellcome Trust (208812/Z/17/Z) and UK Medical Research Council (MC_PC_19065). MC is funded by the Wellcome Trust (220977/Z/20/Z). All the other authors declare no competing interests.

Based on its predicted ability to affect transmissibility and pathogenesis, surveillance studies have highlighted the role of a specific mutation (P681R) in the S1/S2 furin cleavage site of the SARS-CoV-2 spike protein. Here we analyzed A.23.1, first identified in Uganda, as a P681R-containing virus several months prior to the emergence of B.1.617.2 (Delta variant). We performed assays using peptides mimicking the S1/S2 from A.23.1 and B.1.617 and observed significantly increased cleavability with furin compared to both an original B lineage (Wuhan-Hu1) and B.1.1.7 (Alpha variant). We also performed cell-cell fusion and functional infectivity assays using pseudotyped particles and observed an increase in activity for A.23.1 compared to an original B lineage spike. However, these changes in activity were not reproduced in the B lineage spike bearing only the P681R substitution. Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R substitution, this substitution needs to occur on the background of other spike protein changes to enable its functional consequences. IMPORTANCE During the course of the SARS-CoV-2 pandemic, viral variants have emerged that often contain notable mutations in the spike gene. Mutations that encode changes in the spike S1/S2 (furin) activation site have been considered especially impactful. The S1/S2 change from proline to arginine at position 681 (P681R) first emerged in the A.23.1 variant in Uganda, and subsequently occurred in the more widely transmitted Delta variant. We show that the A.23.1 spike is more readily activated by the host cell protease furin, but that this is not reproduced in an original SARS-CoV-2 spike containing the P681R mutation. Changes to the S1/S2 (furin) activation site play a role in SARS-CoV-2 infection and spread, but successful viruses combine these mutations with other less well identified changes, occurring as part of natural selection.

The introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline of childhood diarrhoea disease burden. However, it remains unclear whether implementation of the monovalent Rotarix vaccine (G1P[8]) into national immunization programmes of countries drives the temporal shifts of Rotavirus A (RVA) genotypes in the pre- and post-vaccine periods. Here we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix vaccine. We examined the 63 RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, Coastal Kenya, pre- (2012 to June 2014) and post-(July 2014-2018) rotavirus vaccine introduction. All the 63 genome sequences showed a typical DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. G2 sub-lineage IVa-3 strains predominated in the pre-vaccine era co-circulating with low numbers of G2 sub-lineage IVa-1 strains, whereas sub-lineage IVa-3 strains dominated the post-vaccine period. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid chnages in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre-and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically, but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.

Objective The objective of this study was to evaluate the performance of seven antigen rapid diagnostic tests (Ag RDTs) in a clinical setting to identify those that could be recommended for use in the diagnosis of SARS-CoV-2 infection in Uganda. Methods This was a cross-sectional prospective study. Nasopharyngeal swabs were collected consecutively from COVID-19 PCR positive and COVID-19 PCR negative participants at isolation centers and points of entry, and tested with the SARS-CoV-2 Ag RDTs. Test sensitivity and specificity were generated by comparing results against qRT-PCR results (Berlin Protocol) at a cycle threshold (Ct) cut-off of ≤39. Sensitivity was also calculated at Ct cut-offs ≤29 and ≤33. Results None of the Ag RDTs had a sensitivity of ≥80% at Ct cut-off values ≤33 and ≤39. Two kits, Panbio ™ COVID-19 Ag and VivaDiag ™ SARS-CoV-2 Ag had a sensitivity of ≥80% at a Ct cut-off value of ≤29. Four kits: BIOCREDIT COVID -19 Ag, COVID-19 Ag Respi-Strip, MEDsan ® SARS-CoV-2 Antigen Rapid Test and Panbio ™ COVID-19 Ag Rapid Test had a specificity of ≥97%. Conclusions This evaluation identified one Ag RDT, Panbio ™ COVID-19 Ag with a performance at high viral load (Ct value ≤29) reaching that recommended by WHO. This kit was recommended for screening of patients with COVID -19-like symptoms presenting at health facilities.