Patrick Munywoki

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by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies.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mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.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.

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.

Evolving Friendships and Shifting Ethical Dilemmas: Fieldworkers’ Experiences in a Short Term Community Based Study in Kenya

Fieldworkers (FWs) are community members employed by research teams to support access to participants, address language barriers, and advise on culturally appropriate research conduct. The critical role that FWs play in studies, and the range of practical and ethical dilemmas associated with their involvement, is increasingly recognised. In this paper, we draw on qualitative observation and interview data collected alongside a six month basic science study which involved a team of FWs regularly visiting 47 participating households in their homes. The qualitative study documented how relationships between field workers and research participants were initiated, developed and evolved over the course of the study, the shifting dilemmas FWs faced and how they handled them. Even in this one case study, we see how the complex and evolving relationships between fieldworkers and study participants had important implications for consent processes, access to benefits and mutual understanding and trust. While the precise issues that FWs face are likely to depend on the type of research and the context in which that research is being conducted, we argue that appropriate support for field workers is a key requirement to strengthen ethical research practice and for the long term sustainability of research programmes.

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Summary Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.

Treatment Failure among Kenyan Children with Severe Pneumonia – a Cohort Study

Background: Pneumonia is the leading cause of childhood mortality worldwide. The World Health Organization recommends presumptive treatment based on clinical syndromes. Recent studies raise concerns over the frequency of treatment failure in Africa. Methods: We applied a definition of treatment failure to data prospectively collected from children who were 2–59 months of age with severe, or very severe, pneumonia admitted to Kilifi District Hospital, Kenya, from May 2007 through May 2008 and treated using World Health Organization guidelines. The primary outcome was treatment failure at 48 hours. Results: 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. One hundred eleven (20%; 95% confidence interval: 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 1 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, oxygen saturation in hemoglobin <95%, severe malnutrition, HIV and age <1 year in multivariable models. Conclusions: 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, prehospital care and treatment of sepsis.

Quantifying maternally derived respiratory syncytial virus specific neutralising antibodies in a birth cohort from coastal Kenya.

Highlights • We report on the characteristics of RSV neutralising antibodies in a birth cohort.• The levels of cord RSV antibodies increase during seasonal virus transmission.• The rate of decay of RSV antibodies following birth is independent of cord titre.• There is a high degree of variation between individuals in rate of decay.• Important baseline data to maternal RSV vaccine development are provided.

Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

Background The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. Methods A case control study nested in a birth cohort (2002–07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. Results The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3). Conclusions From this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

Influenza activity in Kenya, 2007-2013: timing, association with climatic factors, and implications for vaccination campaigns.

Information on the timing of influenza circulation remains scarce in Tropical regions of Africa.

Prevalence and correlates of home delivery amongst HIV-infected women attending care at a rural public health facility in Coastal Kenya

Background Home delivery, referring to pregnant women giving birth in the absence of a skilled birth attendant, is a significant contributor to maternal mortality, and is encouragingly reported to be on a decline in the general population in resource limited settings. However, much less is known about home delivery amongst HIV-infected women in sub-Saharan Africa (sSA). We described the prevalence and correlates of home delivery among HIV-infected women attending care at a rural public health facility in Kilifi, Coastal Kenya. Methods A cross-sectional design using mixed methods was used. Quantitative data were collected using interviewer-administered questionnaires from HIV-infected women with a recent pregnancy (within 5 years, n = 425), whilst qualitative data were collected using focused group discussions (FGD, n = 5). Data were analysed using logistic regression and a thematic framework approach respectively. Results Overall, 108 (25.4%, [95% CI: 21.3–29.8]) participants delivered at home. Correlates of home delivery included lack of formal education (aOR 12.4 [95% CI: 3.4–46.0], p<0.001), history of a previous home delivery (2.7 [95% CI:1.2–6.0], p = 0.019) and being on highly active antiretroviral therapy (HAART, 0.4 [95% CI:0.2–0.8], p = 0.006).Despite a strong endorsement against home delivery, major thematic challenges included consumer-associated barriers, health care provider associated barriers and structural barriers. Conclusion A quarter of HIV-infected women delivered at home, which is comparable to estimates reported from the general population in this rural setting, and much lower than estimates from other sSA settings. A tailored package of care targeting women with no formal education and with a history of a previous home delivery, coupled with interventions towards scaling up HAART and improving the quality of maternal care in HIV-infected women may positively contribute to a decline in home delivery and subsequent maternal mortality in this setting.