Infection patterns of endemic human coronaviruses in rural households in coastal Kenya.
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ABSTRACT:
SUBMITTER: Nyaguthii DM
PROVIDER: S-EPMC8669777 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHuman coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime.MethodsNasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing.ResultsHCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching.ConclusionsIn this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.
| S-EPMC6037089 | biostudies-literature
Project description:Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the sensitivity of local molecular diagnostics.
| S-EPMC4966474 | biostudies-literature
Project description:BackgroundHouseholds are high-intensity close-contact environments favorable for transmission of respiratory viruses, yet little is known for low-income settings.MethodsActive surveillance was completed on 47 households in rural coastal Kenya over 6 months during a respiratory syncytial virus (RSV) season. Nasopharyngeal swabs (NPSs) were taken from 483 household members twice weekly irrespective of symptoms. Using molecular diagnostics, NPSs from 6 households were screened for 15 respiratory viruses and the remainder of households only for the most frequent viruses observed: rhinovirus (RV), human coronavirus (HCoV; comprising strains 229E, OC43, and NL63), adenovirus (AdV), and RSV (A and B).ResultsOf 16928 NPSs tested for the common viruses, 4259 (25.2%) were positive for ≥1 target; 596 (13.8%) had coinfections. Detection frequencies were 10.5% RV (1780), 7.5% HCoV (1274), 7.3% AdV (1232), and 3.2% RSV (537). On average, each household and individual had 6 and 3 different viruses detected over the study period, respectively. Rhinovirus and HCoV were detected in all the 47 households while AdV and RSV were detected in 45 (95.7%) and 40 (85.1%) households, respectively. The individual risk of infection over the 6-month period was 93.4%, 80.1%, 71.6%, 61.5%, and 37.1% for any virus, RV, HCoV, AdV, and RSV, respectively. NPSs collected during symptomatic days and from younger age groups had higher prevalence of virus detection relative to respective counterparts. RSV was underrepresented in households relative to hospital admission data.ConclusionsIn this household setting, respiratory virus infections and associated illness are ubiquitous. Future studies should address the health and economic implications of these observations.
| S-EPMC6206121 | biostudies-literature
Project description:BACKGROUND:Human metapneumovirus (HMPV) is an important global cause of severe acute respiratory infections in young children and the elderly. The epidemiology of HMPV in sub-Saharan Africa is poorly described and factors that allow its recurrent epidemics in communities not understood. METHODS:We undertook paediatric inpatient surveillance for HMPV in Kilifi County Hospital (KCH) of Coastal Kenya between 2007 and 2011. Nasopharyngeal samples collected from children aged 1 day-59 months admitted with severe or very severe pneumonia, were tested for HMPV using real-time polymerase chain reaction (RT-PCR). Partial nucleotide sequences of the attachment (G) and fusion (F) surface proteins of positive samples were determined and phylogenetically analyzed. RESULTS:HMPV was detected in 4.8 % (160/3320) of children [73.8 % (118/160) of these less than one year of age], ranging between 2.9 and 8.8 % each year over the 5 years of study. HMPV infections were seasonal in occurrence, with cases predominant in the months of November through April. These months frequently coincided with low rainfall, high temperature and low relative humidity in the location. Phylogenetic analysis of partial F and G sequences revealed three subgroups of HMPV, A2 (74 %, 91/123), B1 (3.2 %, 4/123) and B2 (22.8 %, 28/123) in circulation, with subgroup A2 predominant in majority of the epidemic seasons. Comparison of G sequences (local and global) provided a greater phylogenetic resolution over comparison of F sequences and indicated presence of probable multiple G antigenic variants within the subgroups due to differences in amino acid sequence, encoded protein length and glycosylation patterns. CONCLUSION:The present study reveals HMPV is an important seasonal contributor to respiratory disease hospitalization in coastal Kenya, with an evolutionary pattern closely relating to that of respiratory syncytial virus.
| S-EPMC4912817 | biostudies-literature
Project description:Introduction: Human coronaviruses (HCoVs) circulate endemically in human populations, often with seasonal variation. We describe the long-term patterns of paediatric disease associated with three of these viruses, HCoV-NL63, OC43 and 229E, in coastal Kenya. Methods: Continuous surveillance of pneumonia admissions was conducted at the Kilifi county hospital (KCH) located in the northern coastal region of Kenya. Children aged <5 years admitted to KCH with clinically defined syndromic severe or very severe pneumonia were recruited. Respiratory samples were taken and tested for 15 virus targets, using real-time polymerase chain reaction. Unadjusted odds ratios were used to estimate the association between demographic and clinical characteristics and HCoV positivity. Results: From 2007 to 2019, we observed 11,445 pneumonia admissions, of which 314 (3.9%) tested positive for at least one of the HCoV types surveyed in the study. There were 129 (41.1%) OC43, 99 (31.5%) 229E, 74 (23.6%) NL63 positive cases and 12 (3.8%) cases of HCoV to HCoV coinfection. Among HCoV positive cases, 47% (n=147) were coinfected with other respiratory virus pathogens. The majority of HCoV cases were among children aged <1 year (66%, n=208), though there was was no change in the proportion infected by age. HCoV-OC43 was predominant of the three HCoV types throughout the surveillance period. Evidence for seasonality was not identified. Conclusions: Overall, 4% of paediatric pneumonia admissions were associated with three endemic HCoVs, with a high proportion of cases co-occurring with another respiratory virus, no clear seasonal pattern, and with the age-distribution of cases following that of pneumonia admissions (i.e. highest in infants). These observations suggest, at most, a small severe disease contribution of endemic HCoVs in this tropical setting and offer insight into their potential future burden and epidemiological characteristics.
| S-EPMC7512035 | biostudies-literature
Project description:Background: Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden. The virus circulates as many different types (168), each generating strong homologous, but weak heterotypic, immunity. The influence of these features on transmission patterns of HRV in the community is understudied. Methods: Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016. HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced. Phylogenetic analysis was used to determine the HRV types. Classification models and G-test statistic were used to investigate HRV type spatial distribution. Demographic characteristics and clinical features of ARI were also compared. Results: Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced. HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively. In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively. HRV types presented heterogeneous temporal patterns of persistence. Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks. Conclusion: This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity. Patterns of occurrence suggest frequent and independent community invasion of different types. Temporal differences of persistence between types may reflect variation in type-specific population immunity. Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread.
| S-EPMC6234744 | biostudies-literature
Project description:The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the common cold, their evolutionary histories, and host associations could provide important insights into the natural history of past human pandemics. For two of these viruses, we have strong evidence suggesting an origin in major livestock species while primordial associations for all four viruses may have existed with bats and rodents. HCoV-NL63 and -229E may originate from bat reservoirs as assumed for many other coronaviruses, but HCoV-OC43 and -HKU1 seem more likely to have speciated from rodent-associated viruses. HCoV-OC43 is thought to have emerged from ancestors in domestic animals such as cattle or swine. The bovine coronavirus has been suggested to be a possible ancestor, from which HCoV-OC43 may have emerged in the context of a pandemic recorded historically at the end of the 19th century. New data suggest that HCoV-229E may actually be transferred from dromedary camels similar to Middle East respiratory syndrome (MERS) coronavirus. This scenario provides important ecological parallels to the present prepandemic pattern of host associations of the MERS coronavirus.
| S-EPMC7112090 | biostudies-literature
Project description:Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtained similar tMRCA (time to the most recent common ancestor) estimates for the four coronaviruses, ranging from 72 (HCoV-229E) to 54 (HCoV-NL63) years ago. The split times of HCoV-229E and HCoV-OC43 from camel alphacoronavirus and bovine coronavirus were dated ~268 and ~99 years ago. The split times of HCoV-HKU1 and HCoV-NL63 could not be calculated, as their zoonoticic sources are unknown. To compare the timing of coronavirus emergence to that of another respiratory virus, we recorded the occurrence of influenza pandemics since 1500. Although there is no clear relationship between pandemic occurrence and human population size, the frequency of influenza pandemics seems to intensify starting around 1700, which corresponds with the initial phase of exponential increase of human population and to the emergence of HCoV-229E. The frequency of flu pandemics in the 19th century also suggests that the concurrence of HCoV-OC43 emergence and the Russian flu pandemic may be due to chance.
| S-EPMC9148137 | biostudies-literature
Project description:Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10-4 (95% highest posterior density (HPD), 5.4-7.5 × 10-4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10-4 (95% HPD, 5-6.5 × 10-4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10-3 (95% HPD, 2.3-2.7 × 10-3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.
| S-EPMC7980080 | biostudies-literature
Project description:BackgroundParasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya.Methodology/principal findingsChildren enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years. Anthropometrics were measured at each visit. We used generalized estimating equation (GEE) models to examine the relationship between parasitic infections experienced in the first three years of life and growth outcomes (weight, length and head circumference). Of 545 children, STHs were the most common infection with 106 infections (19%) by age three years. Malaria followed in period prevalence with 68 infections (12%) by three years of age. Filaria and Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively. Seven percent were infected with multiple parasites by three years of age. Each infection type (when all STHs were combined) was documented by six months of age. Decreases in growth of weight, length and head circumference during the first 36 months of life were associated with hookworm, Ascaris, E. histolytica, malaria and Schistosoma infection. In a subset analysis of 180 children who followed up at every visit through 24 months, infection with any parasite was associated with decelerations in weight, length and head circumference growth velocity. Multiple infections were associated with greater impairment of linear growth.Conclusions/significanceOur results demonstrate an under-recognized burden of parasitism in the first three years of childhood in rural Kenya. Parasitic infection and polyparasitism were common, and were associated with a range of significant growth impairment in terms of weight, length and/or head circumference.
| S-EPMC4440755 | biostudies-literature