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1.  Rapid Spread and Diversification of Respiratory Syncytial Virus Genotype ON1, Kenya 
Emerging Infectious Diseases  2014;20(6):950-959.
Surveillance of this new genotype helps clarify the mechanisms of rapid emergence of respiratory viruses.
Respiratory syncytial virus genotype ON1, which is characterized by a 72-nt duplication in the attachment protein gene, has been detected in >10 countries since first identified in Ontario, Canada, in 2010. We describe 2 waves of genotype ON1 infections among children admitted to a rural hospital in Kenya during 2012. Phylogenetic analysis of attachment protein gene sequences showed multiple introductions of genotype ON1; variants distinct from the original Canadian viruses predominated in both infection waves. The genotype ON1 dominated over the other group A genotypes during the second wave, and some first wave ON1 variants reappeared in the second wave. An analysis of global genotype ON1 sequences determined that this genotype has become considerably diversified and has acquired signature coding mutations within immunogenic regions, and its most recent common ancestor dates to ≈2008–2009. Surveillance of genotype ON1 contributes to an understanding of the mechanisms of rapid emergence of respiratory viruses.
PMCID: PMC4036793  PMID: 24856417
attachment protein; G glycoprotein; G protein gene; phylogenetic analysis; ON1; genotype ON1; respiratory syncytial virus; RSV; viruses; respiratory viruses; pneumonia; epidemics; humans; surveillance; Kenya
2.  Examining strain diversity and phylogeography in relation to an unusual epidemic pattern of respiratory syncytial virus (RSV) in a long-term refugee camp in Kenya 
BMC Infectious Diseases  2014;14:178.
A recent longitudinal study in the Dadaab refugee camp near the Kenya-Somalia border identified unusual biannual respiratory syncytial virus (RSV) epidemics. We characterized the genetic variability of the associated RSV strains to determine if viral diversity contributed to this unusual epidemic pattern.
For 336 RSV positive specimens identified from 2007 through 2011 through facility-based surveillance of respiratory illnesses in the camp, 324 (96.4%) were sub-typed by PCR methods, into 201 (62.0%) group A, 118 (36.4%) group B and 5 (1.5%) group A-B co-infections. Partial sequencing of the G gene (coding for the attachment protein) was completed for 290 (89.5%) specimens. These specimens were phylogenetically analyzed together with 1154 contemporaneous strains from 22 countries.
Of the 6 epidemic peaks recorded in the camp over the period, the first and last were predominantly made up of group B strains, while the 4 in between were largely composed of group A strains in a consecutive series of minor followed by major epidemics. The Dadaab group A strains belonged to either genotype GA2 (180, 98.9%) or GA5 (2, < 1%) while all group B strains (108, 100%) belonged to BA genotype. In sequential epidemics, strains within these genotypes appeared to be of two types: those continuing from the preceding epidemics and those newly introduced. Genotype diversity was similar in minor and major epidemics.
RSV strain diversity in Dadaab was similar to contemporaneous diversity worldwide, suggested both between-epidemic persistence and new introductions, and was unrelated to the unusual epidemic pattern.
PMCID: PMC4021307  PMID: 24690157
Attachment (G) protein; Displaced population; Epidemics; Genetic diversity; Genotype; Refugee; RSV
3.  Treatment Failure among Kenyan Children with Severe Pneumonia – a Cohort Study 
Pneumonia is the leading cause of childhood mortality worldwide. The WHO recommends presumptive treatment based on clinical syndromes. Recent studies raise concerns over the frequency of treatment failure in Africa.
We applied a definition of treatment failure to data prospectively collected from children who were 2-59 months with severe, or very severe pneumonia admitted to Kilifi District Hospital, Kenya form May 2007 through May 2008 and treated using WHO guidelines. The primary outcome was treatment failure at 48 hours.
Of 568 children, median age 11 months, 165 (29%) had very severe pneumonia, 30 (5.3%) a positive HIV test and 62 (11%) severe malnutrition. 111 (20%, 95% CI 17-23%) children failed treatment at 48 hours and 34 (6.0%) died, 22 (65%) deaths occurred before 48 hours. Of 353 children with severe pneumonia, without HIV or severe malnutrition, 42 (12%) failed to respond at 48 hours, 15 (4.3%) failed at 5 days and one child (0.3%) died. Among 215 children with either severe pneumonia complicated by HIV or severe malnutrition, or very severe pneumonia, 69 (32%) failed to treatment at 48 hours, 47 (22%) failed at 5 days and 33 (16%) died. Treatment failure at 48 hours was associated with shock, bacteremia, very severe pneumonia, Sa02<95%, severe malnutrition, HIV, and age <1 year in multivariable models.
In this setting, few children with uncomplicated severe pneumonia fail treatment or die under current guidelines. Deaths mainly occurred early and may be reduced by improving prevention, pre-hospital care and treatment of sepsis.
PMCID: PMC3691501  PMID: 22692700
Pneumonia; Treatment Failure; Kenya
4.  Respiratory Syncytial Virus Infection and Disease in Infants and Young Children Studied from Birth in Kilifi District, Kenya 
Within the developing country setting data are few that characterise the disease burden due to RSV and which clearly define the age group to target vaccine intervention.
Children numbering 635, recruited 2002-03, were intensively monitored until each experienced three RSV epidemics. RSV was diagnosed by use of immunofluorescence on nasal washings collected on occurence of acute respiratory infection. Incidence estimates were adjusted for seasonality in RSV exposure.
From 1187 child years of observation (cyo) a total of 409 RSV episodes were identifed; 365 primary and 82 repeat. Adjusted incidence estimates (per 1000cyo) of lower respiratory tract infection (LRTI), severe LRTI and hospital admission were 90, 43, and 10, respectively, and corresponding estimates in infants were 104, 66 and 13. The proportion of all-cause LRTI, severe-LRTI and hospitalizations in the cohort due to RSV was 13%, 19% and 5%, respectively. 55-65% of RSV LRTI and severe-LRTI occured in children over 6 months old. The risk of RSV disease following primary symptomatic infection remained significant beyond the first year of life and a quarter of all re-infections were associated with LRTI.
RSV accounts for a substantial proportion of the total respiratory disease in this rural population: we estimate 85,000 infant cases of severe LRTI annually in Kenya. The majority of this morbidity occurs in late infancy and early childhood; ages at which the risk of disease following infection remains significant. Disease from re-infection is common. Our results inform the debate on vaccine target age group and effectiveness.
PMCID: PMC2358944  PMID: 18171213
respiratory syncytial virus; incidence; burden of disease; vaccination strategy; Kenya
5.  A Preliminary Study of Pneumonia Etiology Among Hospitalized Children in Kenya 
Background. Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden.
Methods. We conducted a case-control study of pneumonia etiology among children aged 1–59 months in rural Kenya. Case patients were hospitalized with World Health Organization–defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls.
Results. Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1–51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered.
Conclusions. A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia.
PMCID: PMC3297554  PMID: 22403235
6.  Estimation of the National Disease Burden of Influenza-Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology 
PLoS ONE  2013;8(2):e56882.
Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden.
Methods and Findings
This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases.
Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.
PMCID: PMC3584100  PMID: 23573177
7.  Severe Lower Respiratory Tract Infection in Early Infancy and Pneumonia Hospitalizations among Children, Kenya 
Emerging Infectious Diseases  2013;19(2):223-229.
Close postdischarge follow-up could help prevent future severe respiratory disease.
Severe lower respiratory tract infection (LRTI) in infants caused by respiratory syncytial virus (RSV) has been associated with later pneumonia hospitalization among children. To determine risk for pneumonia after RSV hospitalization in infancy, we conducted a retrospective cohort analysis of 2,813 infants admitted to a hospital in Kenya and identified readmissions for pneumonia among this group during early childhood (<60 months of age). Incidence of readmission for pneumonia was higher for children whose first admission as infants was for LRTI and who were <3 months of age than for children who were first admitted as infants for non-LRTI, irrespective of RSV status. Incidence of readmission for pneumonia with wheeze was higher for children whose first admission involved RSV compared with those who had non-RSV LRTI. Excess pneumonia risk persisted for 2 years after the initial hospitalization. Close postdischarge follow-up of infants with LRTI, with or without RSV, could help prevent severe pneumonia later in childhood.
PMCID: PMC3559052  PMID: 23347702
respiratory syncytial virus; lower respiratory tract infection; pneumonia; infancy; childhood; wheeze; postdischarge; respiratory infections; hospitalization; viruses; Kenya
8.  The Incidence and Clinical Burden of Respiratory Syncytial Virus Disease Identified through Hospital Outpatient Presentations in Kenyan Children 
PLoS ONE  2012;7(12):e52520.
There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting.
We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence.
Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively.
The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis.
PMCID: PMC3530465  PMID: 23300695
9.  Influenza Surveillance Among Children With Pneumonia Admitted to a District Hospital in Coastal Kenya, 2007–2010 
The Journal of Infectious Diseases  2012;206(Suppl 1):S61-S67.
Background. Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders.
Methods. Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data.
Results. Of 2002 admissions, influenza A virus infection was diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1 of 196 without acute respiratory infection were influenza positive. The annual incidence of severe or very severe pneumonia, of influenza (any type), and of influenza A, was 1321, 60, and 43 cases per 100 000 <5 years of age, respectively. Peak occurrence was in quarters 3–4 each year, and approximately 50% of cases involved infants: temporal association with bacteremia was absent. Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio, 1.78; 95% confidence interval, 1.04–1.96). Influenza A virus subtypes were seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%).
Conclusions. The burden of influenza was small during 2007–2010 in this pediatric hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic influenza A virus subtype H1N1 had little impact.
PMCID: PMC3502370  PMID: 23169974
10.  Group- and Genotype-Specific Neutralizing Antibody Responses Against Respiratory Syncytial Virus in Infants and Young Children With Severe Pneumonia 
The Journal of Infectious Diseases  2012;207(3):489-492.
The effect of genetic variation on the neutralizing antibody response to respiratory syncytial virus (RSV) is poorly understood. In this study, acute- and convalescent-phase sera were evaluated against different RSV strains. The proportion of individuals with homologous seroconversion was greater than that among individuals with heterologous seroconversion among those infected with RSV group A (50% vs 12.5%; P = .0005) or RSV group B (40% vs 8%; P = .008). Seroconversion to BA genotype or non-BA genotype test viruses was similar among individuals infected with non-BA virus (35% vs 50%; P = .4) or BA virus (50% vs 65%; P = .4). The RSV neutralizing response is group specific. The BA-associated genetic change did not confer an ability to escape neutralizing responses to previous non-BA viruses.
PMCID: PMC3541697  PMID: 23175761
respiratory syncytial virus; neutralizing antibody; immunity
12.  A Cost Effectiveness and Capacity Analysis for the Introduction of Universal Rotavirus Vaccination in Kenya: Comparison between Rotarix and RotaTeq Vaccines 
PLoS ONE  2012;7(10):e47511.
Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.
Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.
The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.
Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.
PMCID: PMC3480384  PMID: 23115650
13.  Genetic Relatedness of Infecting and Reinfecting Respiratory Syncytial Virus Strains Identified in a Birth Cohort From Rural Kenya 
The Journal of Infectious Diseases  2012;206(10):1532-1541.
Background. Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear.
Methods. Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori.
Results. Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections.
Conclusions. The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear.
PMCID: PMC3475639  PMID: 22966119
14.  Improved Detection of Respiratory Viruses in Pediatric Outpatients with Acute Respiratory Illness by Real-Time PCR Using Nasopharyngeal Flocked Swabs▿ 
Journal of Clinical Microbiology  2011;49(9):3365-3367.
Detection of respiratory viruses by real-time multiplexed PCR (M-PCR) and of respiratory syncytial virus (RSV) by M-PCR and immunofluorescence (IF) was evaluated using specimens collected by nasopharyngeal flocked swabbing (NFS) and nasal washes (NW). In children with mild respiratory illness, NFS collection was superior to NW collection for detection of viruses by M-PCR (sensitivity, 89.6% versus 79.2%; P = 0.0043). NFS collection was noninferior to NW collection in the detection of RSV by IF.
PMCID: PMC3165583  PMID: 21775539
15.  Added Value of an Oropharyngeal Swab in Detection of Viruses in Children Hospitalized with Lower Respiratory Tract Infection▿ 
Journal of Clinical Microbiology  2011;49(6):2318-2320.
Paired nasopharyngeal and oropharyngeal swabs collected from 533 children hospitalized with lower respiratory tract infection were assessed by multiplex reverse transcription-PCR. Oropharyngeal swabs increased the number of viral infections detected by 15%, compared to collection of a nasopharyngeal swab alone. This advantage was most pronounced for detection of influenza, parainfluenza, and adenovirus.
PMCID: PMC3122752  PMID: 21490188
16.  Intrapatient Variation of the Respiratory Syncytial Virus Attachment Protein Gene▿  
Journal of Virology  2010;84(19):10425-10428.
Intrapatient variability of the attachment (G) protein gene of respiratory syncytial virus (RSV) was examined using both population and single-genome sequencing. Samples from three patients infected with a group B virus variant which has a 60-nucleotide duplication in the G protein gene were examined. These samples were chosen because occasional mixed sequence bases were observed. In a minority of RSV genomes from these patients considerable variability was found, including point mutations, insertions, and deletions. Of particular note, the deletion of the exact portion of the gene which had been duplicated in some isolates was observed in viral RNAs from two patients.
PMCID: PMC2937772  PMID: 20660195
17.  Viral etiology of severe pneumonia among Kenyan young infants and children 
Pneumonia is the leading cause of childhood death in sub-Saharan Africa. Comparative estimates of the contribution of causative pathogens to the burden of disease are essential for targeted vaccine development.
To determine the viral etiology of severe pneumonia among infants and children at a rural Kenyan hospital using comprehensive and sensitive molecular diagnostic techniques.
Design, Setting & Participants
Prospective observational and case control study during 2007 in a rural Kenyan district hospital. We recruited children age 1 day to 12 years who were resident in a systematically enumerated catchment area: i) those admitted to Kilifi District Hospital meeting WHO clinical criteria for ‘severe pneumonia’ or ‘very severe pneumonia’; ii) those presenting with mild upper respiratory tract infection but not admitted and iii) well infants and children attending for immunization.
Main Outcome Measures
The presence of respiratory viruses and the odds ratio for admission with severe disease.
759/922 (83%) eligible admissions were sampled (median age 9 months). One or more respiratory viruses were detected in 425/759 (56%, 95% CI 52 to 60%). Respiratory syncytial virus (RSV) was detected in 260 (34%, 95% CI 31 to 38%) and other respiratory viruses in 219 (29%, 95% CI 26 to 32%), the commonest being human coronavirus 229E (n=51, 6.7%, 95% CI 5.0 to 8.7%), influenza type A (n=44, 5.8%, 95% CI 4.2 to 7.7%), parainfluenza type 3 (n=29, 3.8%, 95% CI 2.6 to 5.4%), adenovirus (n=29, 3.8%, 95% CI 2.6 to 5.4%) and human metapneumovirus (n=23, 3.0%, 95% CI 1.9 to 4.5%). Compared to well controls, detection of RSV was associated with severe disease (4% in controls, adjusted odds Ratio 6.11 [95% CI 1.65 to 22.6]) whilst collectively, other respiratory viruses were not (23% in controls, adjusted odds Ratio 1.27 [95% CI 0.64 to 2.52]).
In a sample of Kenyan infants and children admitted with severe pneumonia to a rural hospital, RSV was the predominant viral pathogen.
PMCID: PMC2968755  PMID: 20501927
18.  Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis 
Lancet  2010;375(9725):1545-1555.
The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005.
We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.
In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting.
Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority.
WHO; Bill & Melinda Gates Foundation.
PMCID: PMC2864404  PMID: 20399493
19.  Duration of shedding of respiratory syncytial virus in a community study of Kenyan children 
Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions.
In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods.
From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age.
We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community.
PMCID: PMC2822777  PMID: 20096106
20.  The Level and Duration of RSV-Specific Maternal IgG in Infants in Kilifi Kenya 
PLoS ONE  2009;4(12):e8088.
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants. The rate of decay of RSV-specific maternal antibodies (RSV-matAb), the factors affecting cord blood levels, and the relationship between these levels and protection from infection are poorly defined.
A birth cohort (n = 635) in rural Kenya, was studied intensively to monitor infections and describe age-related serological characteristics. RSV specific IgG antibody (Ab) in serum was measured by the enzyme linked immunosorbent assay (ELISA) in cord blood, consecutive samples taken 3 monthly, and in paired acute and convalescent samples. A linear regression model was used to calculate the rate of RSV-matAb decline. The effect of risk factors on cord blood titres was investigated.
The half-life of matAb in the Kenyan cohort was calculated to be 79 days (95% confidence limits (CL): 76–81 days). Ninety seven percent of infants were born with RSV-matAb. Infants who subsequently experienced an infection in early life had significantly lower cord titres of anti-RSV Ab in comparison to infants who did not have any incident infection in the first 6 months (P = 0.011). RSV infections were shown to have no effect on the rate of decay of RSV-matAb.
Maternal-specific RSV Ab decline rapidly following birth. However, we provide evidence of protection against severe disease by RSV-matAb during the first 6–7 months. This suggests that boosting maternal-specific Ab by RSV vaccination may be a useful strategy to consider.
PMCID: PMC2779853  PMID: 19956576
21.  Identifying Infections with Respiratory Syncytial Virus by Using Specific Immunoglobulin G (IgG) and IgA Enzyme-Linked Immunosorbent Assays with Oral-Fluid Samples▿  
Journal of Clinical Microbiology  2008;46(5):1659-1662.
Currently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology. Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting. We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test. For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class. Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true. For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses. Our data show significant promise for the use of oral fluid alone in RSV infection surveillance. The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.
PMCID: PMC2395083  PMID: 18305129
22.  Incidence and Clinical Characteristics of Group A Rotavirus Infections among Children Admitted to Hospital in Kilifi, Kenya  
PLoS Medicine  2008;5(7):e153.
Rotavirus, predominantly of group A, is a major cause of severe diarrhoea worldwide, with the greatest burden falling on young children living in less-developed countries. Vaccines directed against this virus have shown promise in recent trials, and are undergoing effectiveness evaluation in sub-Saharan Africa. In this region limited childhood data are available on the incidence and clinical characteristics of severe group A rotavirus disease. Advocacy for vaccine intervention and interpretation of effectiveness following implementation will benefit from accurate base-line estimates of the incidence and severity of rotavirus paediatric admissions in relevant populations. The study objective was to accurately define the incidence and severity of group A rotavirus disease in a resource-poor setting necessary to make informed decisions on the need for vaccine prevention.
Methods and Findings
Between 2002 and 2004 we conducted prospective surveillance for group A rotavirus infection at Kilifi District Hospital in coastal Kenya. Children < 13 y of age were eligible as “cases” if admitted with diarrhoea, and “controls” if admitted without diarrhoea. We calculated the incidence of hospital admission with group A rotavirus using data from a demographic surveillance study of 220,000 people in Kilifi District. Of 15,347 childhood admissions 3,296 (22%) had diarrhoea, 2,039 were tested for group A rotavirus antigen and, of these, 588 (29%) were positive. 372 (63%) rotavirus-positive cases were infants. Of 620 controls 19 (3.1%, 95% confidence interval [CI] 1.9–4.7) were rotavirus positive. The annual incidence (per 100,000 children) of rotavirus-positive admissions was 1,431 (95% CI 1,275–1,600) in infants and 478 (437–521) in under-5-y-olds, and highest proximal to the hospital. Compared to children with rotavirus-negative diarrhoea, rotavirus-positive cases were less likely to have coexisting illnesses and more likely to have acidosis (46% versus 17%) and severe electrolyte imbalance except hyponatraemia. In-hospital case fatality was 2% among rotavirus-positive and 9% among rotavirus-negative children.
In Kilifi > 2% of children are admitted to hospital with group A rotavirus diarrhoea in the first 5 y of life. This translates into over 28,000 vaccine-preventable hospitalisations per year across Kenya, and is likely to be a considerable underestimate. Group A rotavirus diarrhoea is associated with acute life-threatening metabolic derangement in otherwise healthy children. Although mortality is low in this clinical research setting this may not be generally true in African hospitals lacking rapid and appropriate management.
Combining prospective hospital-based surveillance with demographic data in Kilifi, Kenya, James Nokes and colleagues assess the burden of rotavirus diarrhea in young children.
Editors' Summary
Rotavirus is a leading global cause of diarrhea in babies and young children. Indeed, most children become infected at least once with this virus before their fifth birthday. Rotavirus is usually spread by children or their caregivers failing to wash their hands properly after going to the toilet and then contaminating food or drink. The symptoms of rotavirus infection—diarrhea, vomiting, and fever—are usually mild, but if the diarrhea is severe it can quickly lead to dehydration. Mild to moderate dehydration can be treated at home by providing the patient with plenty of fluids or with a special rehydration drink that replaces lost water and salts. However, for infants or toddlers who become severely dehydrated, rehydration with intravenous fluids (fluids injected directly into a vein) in hospital may be essential. Unfortunately, in developing countries in sub-Saharan Africa and elsewhere, this treatment is not widely available and every year more than half a million young children die from rotavirus infections.
Why Was This Study Done?
Two rotavirus vaccines that could reduce this burden of disease are currently undergoing clinical trials to determine their effectiveness in sub-Saharan Africa. However, very little is known about the incidence of severe rotavirus infections among children living in this region (that is, how many children develop severe disease every year) or about the clinical characteristics of the disease here. Public-health officials need this baseline information before they can make informed decisions about the mass introduction of rotavirus vaccination and to help them judge whether the intervention has been successful if it is introduced. In this study, the researchers examine the incidence and clinical characteristics of rotavirus infections (specifically, group A rotavirus [GARV] infections; there are several different rotaviruses but GARV causes most human infections) among children admitted to the district hospital in Kilifi, Kenya.
What Did the Researchers Do and Find?
During the 3-year study, more than 15,000 children under the age of 13 years were admitted to Kilifi District Hospital, a little under a quarter of whom had severe diarrhea. Nearly a third of the patients admitted with diarrhea who were tested had a GARV-specific protein in their stools (faeces); by contrast, only three in 100 children admitted without diarrhea showed any evidence of GARV infection. Two-thirds of the GARV-positive children were infants (under 1 year old). Using these figures and health surveillance data (records of births, deaths, and causes of death) collected in the area around the hospital, the researchers calculated that the annual incidence (per 100,000 children) of GARV-positive hospital admissions in the region was 1,431 for infants and 478 for children under age 5 years. Children with GARV-positive diarrhea were less likely to have other illnesses (for example, malnutrition) than those admitted with GARV-negative diarrhea, the researchers report, but were more likely to have life-threatening complications such as severe dehydration and salt imbalances in their blood. However, despite being more ill on admission, only 1 in 50 children with GARV-positive diarrhea died, compared to nearly 1 in 10 of the children with GARV-negative diarrhea; the GARV-positive children also left hospital quicker than those who were GARV-negative.
What Do These Findings Mean?
These findings indicate that severe GARV-positive diarrhea is a major cause of hospital admission among otherwise healthy young children in the Kilifi region of Kenya. By the time they are 5 years old, the researchers estimate that 1 in 50 of the children living in this region will have been admitted to hospital with severe GARV-positive diarrhea. Because rotavirus vaccines prevent virtually all severe rotavirus-associated disease (at least in developed countries where their effectiveness has been extensively tested), the researchers estimate that vaccination might prevent more than 28,000 hospitalizations annually across Kenya; however, this prediction assumes that it is valid to extrapolate from the data obtained from this one district hospital to the entire country.
Additional Information.
Please access these Web sites via the online version of this summary at
The US Centers for Disease Control and Prevention provides information about rotavirus infections, surveillance, and vaccination (in English and Spanish)
The UK National Health Service Direct health encyclopedia provides information on rotavirus infections
MedlinePlus also provides links to information on rotavirus (in English and Spanish)
The African Rotavirus Surveillance Network is working to improve knowledge about rotavirus infections in Africa
The Rotavirus Vaccine Program aims to reduce child illness and death from diarrhea by increasing the availability of rotavirus vaccines in developing countries (in English and Spanish)
PATH, a nonprofit international organization that aims to create sustainable, culturally relevant solutions to global health problems, also provides detailed information on rotavirus surveillance and disease burden
PMCID: PMC2488191  PMID: 18651787
23.  Molecular analysis of respiratory syncytial virus reinfections in infants from coastal Kenya 
Individuals are reinfected with respiratory syncytial virus (RSV) repeatedly. The nature of reinfections in relation to RSV genetic and antigenic diversity is ill defined and has implications to persistence and vaccine control.
We examined the molecular relatedness of RSV causing primary and repeat infections by phylogenetic analysis of the attachment (G) gene in 12 infants from a birth cohort in rural Kenya, using nasal washings collected over a 16 month period in 2002-03 spanning two successive epidemics.
Six infants were infected in both epidemics, 4 with RSV-A in the first epidemic followed by RSV-B in the second epidemic and 2 infected with RSV-A strains in both epidemics with no significant G gene sequence variability between samples. Two children showed infection and reinfection with different RSV-A strains within the same epidemic. Possible viral persistence was suspected in the remaining 4 infants, although reinfection with same variant cannot be excluded.
These are the first data specifically addressing strain-specific reinfections in infancy in relation to the primary infecting variant. The data strongly suggest that following primary infection some infants lose strain-specific immunity within 7-9 months (between epidemics) and group-specific immunity within 2-4 months (within an epidemic period).
PMCID: PMC2384051  PMID: 16323133
Respiratory syncytial virus; infants; reinfection
24.  On the determinants of population structure in antigenically diverse pathogens. 
Many pathogens exhibit antigenic diversity and elicit strain-specific immune responses. This potential for cross-immunity structure in the host resource motivates the development of mathematical models, stressing competition for susceptible hosts in driving pathogen population dynamics and genetics. Here we establish that certain model formulations exhibit characteristics of prototype pattern-forming systems, with pathogen population structure emerging as three possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with travelling waves in strain-space. Results are robust to strain number, but sensitive to the mechanism of cumulative immunity.
PMCID: PMC1690892  PMID: 11839191
25.  Identification of group B respiratory syncytial viruses that lack the 60-nucleotide duplication after six consecutive epidemics of total BA dominance at coastal Kenya 
Respiratory syncytial virus BA genotype has reportedly replaced other group B genotypes worldwide. We report the observation of three group B viruses, all identical in G sequence but lacking the BA duplication, at a coastal district hospital in Kenya in early 2012. This follows a period of six consecutive respiratory syncytial virus (RSV) epidemics with 100% BA dominance among group B isolates. The new strains appear only distantly related to BA variants and to previously circulating SAB1 viruses last seen in the district in 2005, suggesting that they were circulating elsewhere undetected. These results are of relevance to an understanding of RSV persistence.
Please cite this paper as: Agoti et al. (2013) Identification of group B RSVs that lack the 60-nucleotide duplication after 6 consecutive epidemics of total BA dominance at coastal Kenya. Influenza and Other Respiratory Viruses 7(6), 1008–1012.
PMCID: PMC3963446  PMID: 23782406
Attachment (G gene); BA genotype; genetic diversity; respiratory syncytial virus

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