Mwanajuma Ngama

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Summary Background 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. Methods 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by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies.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mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings 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. Interpretation 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. Funding WHO; Bill & Melinda Gates Foundation.

Viral etiology of severe pneumonia among Kenyan infants and children.

CONTEXT 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. OBJECTIVE 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, AND PARTICIPANTS Prospective observational and case-control study during 2007 in a rural Kenyan district hospital. Participants were children aged 1 day to 12 years, residing in a systematically enumerated catchment area, and who either were admitted to Kilifi District Hospital meeting World Health Organization clinical criteria for severe pneumonia or very severe pneumonia; (2) presented with mild upper respiratory tract infection but were not admitted; or (3) were well infants and children attending for immunization. MAIN OUTCOME MEASURES The presence of respiratory viruses and the odds ratio for admission with severe disease. RESULTS Of 922 eligible admitted patients, 759 were sampled (82% [median age, 9 months]). One or more respiratory viruses were detected in 425 of the 759 sampled (56% [95% confidence interval {CI}, 52%-60%]). Respiratory syncytial virus (RSV) was detected in 260 participants (34% [95% CI, 31%-38%]) and other respiratory viruses were detected in 219 participants (29%; 95% CI, 26%-32%), the most common being Human coronavirus 229E (n = 51 [6.7%]), influenza type A (n = 44 [5.8%]), Parainfluenza type 3 (n = 29 [3.8%]), Human adenovirus (n = 29 [3.8%]), and Human metapneumovirus (n = 23 [3.0%]). Compared with well control participants, detection of RSV was associated with severe disease (5% [corrected] in control participants; adjusted odds ratio, 6.11 [95% CI, 1.65-22.6]) while collectively, other respiratory viruses were not associated with severe disease (23% in control participants; adjusted odds ratio, 1.27 [95% CI, 0.64-2.52]). CONCLUSION In a sample of Kenyan infants and children admitted with severe pneumonia to a rural hospital, RSV was the predominant viral pathogen.

Respiratory Syncytial Virus Infection and Disease in Infants and Young Children Observed from Birth in Kilifi District, Kenya

BACKGROUND In developing countries, there are few data that characterize the disease burden attributable to respiratory syncytial virus (RSV) and clearly define which age group to target for vaccine intervention. METHODS Six hundred thirty-five children, recruited during the period 2002-2003, were intensively monitored until each experienced 3 epidemics of RSV infection. RSV infection was diagnosed using immunofluorescence of nasal washing specimens collected at each episode of acute respiratory infection. Incidence estimates were adjusted for seasonality of RSV exposure. RESULTS For 1187 child-years of observation (CYO), a total of 409 (365 primary and 82 repeat) episodes of RSV infection were identified. Adjusted incidence estimates of lower respiratory tract infection (LRTI), severe LRTI, and hospital admission were 90 cases per 1000 CYO, 43 cases per 1000 CYO, and 10 cases per 1000 CYO, respectively, and corresponding estimates among infants were 104 cases per 1000 CYO, 66 cases per 1000 CYO, and 13 cases per 1000 CYO, respectively. The proportion of cases of all-cause LRTI, and severe LRTI and hospitalizations attributable to RSV in the cohort was 13%, 19%, and 5%, respectively. Fifty-five percent to 65% of RSV-associated LRTI and severe LRTI occurred in children aged >6 months. The risk of RSV disease following primary symptomatic infection remained significant beyond the first year of life, and one-quarter of all reinfections were associated with LRTI. CONCLUSIONS RSV accounts for a substantial proportion of the total respiratory disease in this rural population; we estimate that 85,000 cases of severe LRTI per year occur in infants in Kenya. The majority of this morbidity occurs during late infancy and early childhood--ages at which the risk of disease following infection remains significant. Disease resulting from reinfection is common. Our results inform the debate on the target age group and effectiveness of a vaccine.

Incidence and Severity of Respiratory Syncytial Virus Pneumonia in Rural Kenyan Children Identified through Hospital Surveillance

BACKGROUND Although necessary for developing a rationale for vaccination, the burden of severe respiratory syncytial virus (RSV) disease in children in resource-poor settings remains poorly defined. METHODS We conducted prospective surveillance of severe and very severe pneumonia in children aged <5 years admitted from 2002 through 2007 to Kilifi district hospital in coastal Kenya. Nasal specimens were screened for RSV antigen by immunofluorescence. Incidence rates were estimated for the well-defined population. RESULTS Of 25,149 hospital admissions, 7359 patients (29%) had severe or very severe pneumonia, of whom 6026 (82%) were enrolled. RSV prevalence was 15% (20% among infants) and 27% during epidemics (32% among infants). The proportion of case patients aged 3 months was 65%, and the proportion aged 6 months was 43%. Average annual hospitalization rates were 293 hospitalizations per 100,000 children aged <5 years (95% confidence interval, 271-371 hospitalizations per 100,000 children aged <5 years) and 1107 hospitalizations per 100,000 infants (95% confidence interval, 1012-1211 hospitalizations per 100,000 infants). Hospital admission rates were double in the region close to the hospital. Few patients with RSV infection had life-threatening clinical features or concurrent serious illnesses, and the associated mortality was 2.2%. CONCLUSIONS In this low-income setting, rates of hospital admission with RSV-associated pneumonia are substantial; they are comparable to estimates from the United States but considerably underestimate the burden in the full community. An effective vaccine for children aged >2 months (outside the age group of poor responders) could prevent a large portion of RSV disease. Severity data suggest that the justification for RSV vaccination will be based on the prevention of morbidity, not mortality.

Causes and outcome of young infant admissions to a Kenyan district hospital

Aims: To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya. These data, currently lacking, are important given present efforts to standardise their care through the integrated management of childhood illness (IMCI) and for prioritising both health care provision and disease prevention strategies. Methods: Prospective, 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward. Results: A total of 1080 infants were studied. Mortality was 18% overall, though in those aged 0–7 days it was 34%. Within two months of discharge a further 5% of infants aged <60 days on admission had died. Severe infection and prematurity together accounted for 57% of inpatient deaths in those aged <60 days, while jaundice and tetanus accounted for another 27%. S pneumoniae, group B streptococcus, E coli, and Klebsiella spp. were the most common causes of invasive bacterial disease. Hypoxaemia, hypoglycaemia, and an inability to feed were each present in more than 20% of infants aged 0–7 days. Both hypoxaemia and the inability to feed were associated with inpatient death (OR 3.8 (95% CI 2.5 to 5.8) and 7.4 (95% CI 4.8 to 11.2) respectively). Conclusions: Young infants contribute substantially to paediatric inpatient mortality at the first referral level, highlighting the need both for basic supportive care facilities and improved disease prevention strategies.

Respiratory syncytial virus epidemiology in a birth cohort from Kilifi district, Kenya: Infection during the first year of life

We report estimates of incidence of respiratory syncytial virus (RSV) infection during the first year of life for a birth cohort from rural, coastal Kenya. A total of 338 recruits born between 21 January 2002 and 30 May 2002 were monitored for symptoms of respiratory infection by home visits and hospital referrals. Nasal washings were screened by use of immunofluorescence. From 311 child-years of observation (cyo), 133 RSV infections were found, of which 48 were lower respiratory tract infections (LRTIs) and 31 were severe LRTIs, resulting in 4 hospital admissions. There were 121 primary RSV infections (248 cyo), of which 45 were LRTIs and 30 were severe LRTIs, resulting in 4 hospital admissions; there was no association with age. RSV contributed significantly to total LRTI disease in this vaccine-target group.

Factors associated with increased risk of progression to respiratory syncytial virus-associated pneumonia in young Kenyan children*

Objectives  To identify factors associated with developing severe respiratory syncytial virus (RSV) pneumonia and their commonality with all‐cause lower respiratory tract infection (LRTI), in order to isolate those risk factors specifically associated with RSV‐LRTI and identify targets for control.

Molecular analysis of respiratory syncytial virus reinfections in infants from coastal Kenya

BACKGROUND Individuals are reinfected with respiratory syncytial virus (RSV) repeatedly. The nature of reinfection, in relation to RSV genetic and antigenic diversity, is ill defined and has implications for persistence and vaccine control. METHODS 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 wash samples collected during a 16-month period in 2002-2003, which spanned 2 successive epidemics. RESULTS Six infants were infected during both epidemics, 4 with RSV-A in the first epidemic followed by RSV-B during the second epidemic and 2 with RSV-A during both epidemics, with no significant G gene sequence variability between samples. Two infants were infected and reinfected with different RSV-A strains during the same epidemic. Possible viral persistence was suspected in the remaining 4 infants, although reinfection with the same variant cannot be excluded. CONCLUSIONS These are the first data that specifically address 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 (during an epidemic period).

Molecular epidemiology of human rhinovirus infections in Kilifi, coastal Kenya†

This study reports pediatric surveillance over 3 years for human rhinovirus (HRV) at the District Hospital of Kilifi, coastal Kenya. Nasopharyngeal samples were collected from children presenting at outpatient clinic with no signs of acute respiratory infection, or with signs of upper respiratory tract infection, and from children admitted to the hospital with lower respiratory tract infection. Samples were screened by real‐time reverse transcriptase polymerase chain reaction (real‐time RT‐PCR) and classified further to species by nucleotide sequencing of the VP4/VP2 junction. Of 441 HRV positives by real‐time RT‐PCR, 332 were classified to species, with 47% (155) being HRV‐A, 5% (18) HRV‐B, and 48% (159) HRV‐C. There was no clear seasonal pattern of occurrence for any species. The species were present in similar proportions in the inpatient and outpatient sample sets, and no significant association between species distribution and the severity of lower respiratory tract infection in the inpatients could be determined. HRV sequence analysis revealed multiple but separate clusters in circulation particularly for HRV‐A and HRV‐C. Most HRV‐C clusters were distinct from reference sequences downloaded from GenBank. In contrast, most HRV‐A and HRV‐B sequences clustered with either known serotypes or strains from elsewhere within Africa and other regions of the world. This first molecular epidemiological study of HRV in the region defines species distribution in accord with reports from elsewhere in the world, shows considerable strain diversity and does not identify an association between any species and disease severity. J. Med. Virol. 84:823–831, 2012.

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

BackgroundOur 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.MethodsIn 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.ResultsFrom 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.ConclusionWe 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.