Our surveillance at a district hospital in coastal Kenya spanning 6 years provides a highly detailed description of the burden of RSV severe disease in young children in a typical rural developing country setting. Over the period 2002 to 2007 we identified clinically severe or very severe pneumonia in roughly one third of under 5 year olds and 38% of infants admitted to KDH, of which an estimated 15% and 19%, respectively, were associated with RSV infection. The rate of hospital admissions with RSV-associated pneumonia within the demographically well-defined user population was 293 cases per 1000,000 per annum in children under 5 years and 1,107 cases per 100,000 per annum in infants. These data are similar in magnitude to those reported for an intensively monitored birth cohort within the same population (1,300 infant cases of RSV-associated severe pneumonia admitted to KDH per 100,000 child years of observation) [13
], and for the small number of other denominator-based studies of hospital admissions in resource-poor countries[6
]. Furthermore, our reported rates mirror closely population-based hospitalization rates recently described for various locations in the US[17
Thus our data indicate that an effective pediatric RSV vaccine could prevent a sizeable proportion of hospital pneumonia admissions. A useful reference point is afforded by comparison with severe rotavirus diarrhoea, targeted for vaccination[18
], which exhibited an annual rate of hospitalization at KDH for the period 2002-04 of 478 per100,000 in the under 5 year olds and 1431 per 100,000 in infants[12
]. Furthermore, the ‘distance decay’ in rates of hospitalization (), previously reported in The Gambia [8
], indicates a large (~two fold) additional burden of severe RSV present in the community but not recorded through in-patient surveillance. If we assume the estimates close to the hospital are more realistic of the community burden and representative of Kenya as a whole, the annual number of RSV-associated severe or very severe pneumonia cases in children under 5 and infants throughout the country are estimated at 37,000 and 29,500, respectively (based on population estimates for children <5 years and births in 2008 of 6.5m and 1.4m, respectively[19
We further point out an additional burden of RSV severe pneumonia in the community, missed by hospital surveillance, in the form of cases presenting to out-patient health facilities and not admitted, as was shown in our previous report of a birth cohort in the same setting as the present study[13
]. A potential further source of under-estimation of RSV disease in our study arises from the immunofluorescence assay used to detect the virus, which has been shown to be less sensitive than molecular based detection methods [20
A clear impediment to vaccine intervention is the absence of an effective candidate for use in the key target age group of 0-2m [4
]. Nevertheless, studies consistently show good safety and immunogenicity of live attenuated RSV vaccines in older infants and young children[5
]. Data from the present study show that around 2/3 of hospitalised RSV-associated pneumonia occurs in children 3 months and over, and hence delayed vaccine delivery has the potential to prevent a significant fraction of RSV disease. Reduced transmission from older vaccinated infants to the vulnerable early infants may enhance the benefit of delayed vaccination.
Our data show that the incidence of RSV disease varies considerably year-by-year, particularly in infants, which varied by a factor in excess of two between the lowest and highest years, suggesting that short-term studies may present a biased picture of RSV disease burden. Interestingly the distribution of disease by age was roughly constant over time (in contrast to observations from The Gambia[24
In relation to pneumonia severity our study shows that non-life-threatening clinical features were more strongly associated with being RSV positive than negative, whereas the risks of very severe conditions, risk factors and concurrent illness were significantly higher in RSV negative cases. A similar clinical pattern was reported from an in-patient study in Mozambique[25
]. The low case fatality rate of 2.2% for RSV positives (in line with most other reports[6
]), compared with 4.7% in RSV negative cases, is therefore not surprising. These data support the rationale for a RSV vaccine based on prevention of morbidity rather than mortality. Nevertheless, as in previous studies there is some concern over bias in sampling of less severe cases[6
], since 18% of eligible children were not tested, and the case fatality in the enrolled was less that half that found in all eligible children (4.4% versus 9.9%). In our setting, faced with a child undergoing emergency management, it was not a clear priority of the clinician to collect a nasal sample. Hence, it is possible that the true case fatality rate associated with RSV is significantly higher than observed, and consideration should be given to collecting a specimen post-mortem to address this unknown.
The prospect of widespread use of vaccines against H. influenza
type b and S. pneumoniae
across the developing world is set to alter substantially the landscape of pneumonia aetiology[3
]. Surveillance for a broad aetiology of the remaining significant burden of childhood pneumonia is of increasing importance. Arguably, the most important remaining cause of childhood pneumonia potentially preventable by vaccine intervention is RSV. The present study reports a substantial burden of RSV associated severe pneumonia in a low-income setting that is equivalent to that identified in the high-income setting. This argues a need to investigate the potential use of vaccines for both developed and developing countries. This study also demonstrates the power of long-term surveillance in understanding the role of RSV in morbidity and mortality patterns in children in a low resource setting, and the requirement for population evidence in developing a rational strategy for future RSV vaccine intervention.