Understanding the potential drivers for respiratory syncytial virus rebound during the COVID-19 pandemic

Non-pharmaceutical interventions (NPIs) were widely introduced to combat the COVID-19 pandemic. These interventions also likely led to substantially reduced activity of respiratory syncytial virus (RSV). From late 2020, some countries observed out-of-season RSV epidemics. Here, we analyzed the role of NPIs, population mobility, climate, and SARS-CoV-2 circulation in RSV rebound through a time-to-event analysis across 18 countries. Full (re)-opening of schools was associated with an increased risk for RSV rebound (HR = 23.29 [95% CI: 1.09–495.84]); every 5°C increase in temperature was associated with a decreased risk (HR = 0.63 [0.40–0.99]). There was an increasing trend in the risk for RSV rebound over time, highlighting the role of increased population susceptibility. No other factors were found statistically significant. Further analysis suggests increasing population susceptibility and full (re)-opening of schools could both override the counter-effect of high temperatures, which explains the out-of-season RSV epidemics during the COVID-19 pandemic

Respiratory syncytial virus seasonality and prevention strategy planning for passive immunisation of infants in low-income and middle-income countries:a modelling study

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial burden of disease in young infants in low-income and middle-income countries (LMICs). Because RSV passive immunisations, including maternal vaccination and monoclonal antibodies, can only grant a temporary period of protection, their effectiveness and efficiency will be determined by the timing of the immunisation relative to the underlying RSV seasonality. We aimed to assess the potential effect of different approaches for passive RSV immunisation of infants in LMICs. METHODS: We included 52 LMICs in this study on the basis of the availability of RSV seasonality data and developed a mathematical model to compare the effect of different RSV passive immunisation approaches (seasonal approaches vs a year-round approach). For each candidate approach, we calculated the expected annual proportion of RSV incidence among infants younger than 6 months averted (effectiveness) and the ratio of per-dose cases averted between that approach and the year-round approach (relative efficiency). FINDINGS: 39 (75%) of 52 LMICs included in the study had clear RSV seasonality, defined as having more than 75% of annual RSV cases occurring in 5 or fewer months. In these countries with clear RSV seasonality, the seasonal approach in which monoclonal antibody administration began 3 months before RSV season onset was only a median of 16% (IQR 13-18) less effective in averting RSV-associated acute lower respiratory infection (ALRI) hospital admissions than a year-round approach, but was a median of 70% (50-97) more efficient in reducing RSV-associated hospital admissions per dose. The seasonal approach that delivered maternal vaccination 1 month before the season onset was a median of 27% (25-33) less effective in averting hospital admissions associated with RSV-ALRI than a year-round approach, but was a median of 126% (87-177) more efficient at averting these hospital admissions per dose. INTERPRETATION: In LMICs with clear RSV seasonality, seasonal approaches to monoclonal antibody and maternal vaccine administration might optimise disease prevention by dose given compared with year-round administration. More data are needed to clarify if seasonal administration of RSV monoclonal antibodies or maternal immunisation is programmatically suitable and cost effective in LMICs. FUNDING: The Bill & Melinda Gates Foundation, World Health Organization

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations

Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study.

Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of \u3c0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia

Healthcare-use for Major Infectious Disease Syndromes in an Informal Settlement in Nairobi, Kenya

A healthcare-use survey was conducted in the Kibera informal settlement in Nairobi, Kenya, in July 2005 to inform subsequent surveillance in the site for infectious diseases. Sets of standardized questionnaires were administered to 1,542 caretakers and heads of households with one or more child(ren) aged less than five years. The average household-size was 5.1 (range 1-15) persons. Most (90%) resided in a single room with monthly rents of US$ 4.50-7.00. Within the previous two weeks, 49% of children (n=1,378) aged less than five years (under-five children) and 18% of persons (n=1,139) aged ≥5 years experienced febrile, diarrhoeal or respiratory illnesses. The large majority (>75%) of illnesses were associated with healthcare-seeking. While licensed clinics were the most-frequently visited settings, kiosks, unlicensed care providers, and traditional healers were also frequently visited. Expense was cited most often (50%) as the reason for not seeking healthcare. Of those who sought healthcare, 34-44% of the first and/or the only visits were made with non-licensed care providers, potentially delaying opportunities for early optimal intervention. The proportions of patients accessing healthcare facilities were higher with diarrhoeal disease and fever (but not for respiratory diseases in under-five children) than those reported from a contemporaneous study conducted in a rural area in Kenya. The findings support community-based rather than facility-based surveillance in this setting to achieve objectives for comprehensive assessment of the burden of disease

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data.

Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data

Nutritional Status of Under-five Children Living in an Informal Urban Settlement in Nairobi, Kenya

Malnutrition in sub-Saharan Africa contributes to high rates of childhood morbidity and mortality. However, little information on the nutritional status of children is available from informal settlements. During the period of post-election violence in Kenya during December 2007–March 2008, food shortages were widespread within informal settlements in Nairobi. To investigate whether food insecurity due to post-election violence resulted in high prevalence of acute and chronic malnutrition in children, a nutritional survey was undertaken among children aged 6-59 months within two villages in Kibera, where the Kenya Medical Research Institute/Centers for Disease Control and Prevention conducts population-based surveillance for infectious disease syndromes. During 25 March–4 April 2008, a structured questionnaire was administered to caregivers of 1,310 children identified through surveillance system databases to obtain information on household demographics, food availability, and child-feeding practices. Anthropometric measurements were recorded on all participating children. Indices were reported in z-scores and compared with the World Health Organization (WHO) 2005 reference population to determine the nutritional status of children. Data were analyzed using the Anthro software of WHO and the SAS. Stunting was found in 47.0% of the children; 11.8% were underweight, and 2.6% were wasted. Severe stunting was found in 23.4% of the children; severe underweight in 3.1%, and severe wasting in 0.6%. Children aged 36-47 months had the highest prevalence (58.0%) of stunting while the highest prevalence (4.1%) of wasting was in children aged 6-11 months. Boys were more stunted than girls (p<0.01), and older children were significantly (p<0.0001) stunted compared to younger children. In the third year of life, girls were more likely than boys to be wasted (p<0.01). The high prevalence of chronic malnutrition suggests that stunting is a sustained problem within this urban informal settlement, not specifically resulting from the relatively brief political crisis. The predominance of stunting in older children indicates failure in growth and development during the first two years of life. Food programmes in Kenya have traditionally focused on rural areas and refugee camps. The findings of the study suggest that tackling childhood stunting is a high priority, and there should be fostered efforts to ensure that malnutrition-prevention strategies include the urban poor

High prevalence of <i>Rickettsia africae</i> variants in <i>Amblyomma variegatum</i> ticks from domestic mammals in rural western Kenya: implications for human health

Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae–genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya

Healthcare-seeking Behaviour for Common Infectious Disease-related Illnesses in Rural Kenya: A Community-based House-to-house Survey

Community surveys of healthcare-use determine the proportion of illness episodes not captured by health facility-based surveillance, the methodology used most commonly to estimate the burden of disease in Africa. A cross-sectional survey of households with children aged less than five years was conducted in 35 of 686 census enumeration areas in rural Bondo district, western Kenya. Healthcare sought for acute episodes of diarrhoea or fever in the past two weeks or pneumonia in the past year was evaluated. Factors associa-ted with healthcare-seeking were analyzed by logistic regression accounting for sample design. In total, 6,223 residents of 981 households were interviewed. Of 1,679 children aged less than five years, 233 (14%) had diarrhoea, and 736 (44%) had fever during the past two weeks; care at health facilities was sought for one-third of these episodes. Pneumonia in the past year was reported for 64 (4%) children aged less than five years; 88% sought healthcare at any health facility and 48% at hospitals. Seeking healthcare at health facilities was more likely for children from households with higher socioeconomic status and with more symptoms of severe illness. Health facility and hospital-based surveillance would underestimate the burden of disease substantially in rural western Kenya. Seeking healthcare at health facilities and hospitals varied by syndrome, severity of illness, and characteristics of the patient