Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Prevalence and Correlates of Vitamin D Deficiency among Young South African Infants: A Birth Cohort Study.

Early-life vitamin D deficiency is associated with adverse child health outcomes, but the prevalence of vitamin D deficiency and its correlates in infants remains underexplored, particularly in sub-Saharan Africa. We aimed to investigate the prevalence of vitamin D deficiency and its correlates among young infants in South Africa. This study included 744 infants, aged 6-10 weeks from the Drakenstein Child Health Study, a population-based birth cohort. Infants were categorized into distinct categories based on serum 25(OH)D concentration level including deficient (<50 nmol/L), insufficient (50-74 nmol/L), and sufficient (≥75 nmol/L). Using multivariable Tobit and logistic regression models, we examined the correlates of serum 25(OH)D3 levels. The overall prevalence of vitamin D deficiency was 81% (95% confidence intervals (CI]) 78-83). Multivariable regression analysis showed that serum 25(OH)D3 concentration was independently associated with study site, socioeconomic status, and sex. Birth in winter and breastfeeding were the strongest predictors of lower serum 25(OH)D3 concentration levels. Compared to non-breastfed children, children breastfed were at higher risk of vitamin D deficiency (AOR, 1.96; 95% CI, 1.04-3.67) and breastfeeding for more than one month was associated with greater likelihood of vitamin D deficiency (AOR, 5.40; 95% CI, 2.37-12.32) and lower vitamin D concentrations (-16.22 nmol/L; 95% CI, -21.06, -11.39). Vitamin D deficiency in infants is ubiquitous, under-recognised, and strongly associated with season of birth and breastfeeding in this setting. Nutritional interventions with vitamin D supplementation in national health programs in low- and middle-income countries are urgently needed to improve early-life vitamin D status in infants.

Infant feeding practices in a South African birth cohort-A longitudinal study.

Childhood malnutrition is highly prevalent in low- and middle-income countries. The choices of complementary foods, which are important in infant nutrition, are poorly described in this setting. We investigated infant feeding practices in a South African birth cohort, the Drakenstein Child Health Study. Longitudinal feeding data were collected from March 2012 to March 2015. Feeding practices at birth, 6-10 and 14 weeks and 6, 9, and 12 months, were investigated using food frequency questionnaires. Anthropometry was measured at birth and 12 months. The quality of the diet was analyzed using the World Health Organization infant and young child feeding indicators. Regression models were used to explore associations between feeding and growth outcomes at 1 year. Exclusive breastfeeding for 6 months was low (13%), and 19% of infants were introduced to solid foods before 4 months. There was high daily consumption of processed meat (56%) and inappropriate foods such as fruit juice (82%), soft drinks (54%), and refined sugary foods (51%) at 1 year. Dietary diversity and consumption of iron rich foods were low at 6 months (5% and 3%, respectively) but higher by 12 months (75% and 78%). Longer duration of exclusive breastfeeding was associated with a lower height-for-age z-score at 1 year. Several dietary deficits and a rising trend in the consumption of inappropriate nutritionally poor foods were identified. These findings raise concern about poor dietary practices and the impact on child and long-term health.

Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings.

BACKGROUND: Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. METHODS: Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. RESULTS: Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. CONCLUSIONS: Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.

Chronic lung disease in human immunodeficiency virus (HIV) infected children.

The development of chronic lung disease is common in HIV-infected children. The spectrum of chronic HIV-associated lung disease includes lymphocytic interstitial pneumonia (LIP), chronic infections, immune reconstitution inflammatory syndrome (IRIS), bronchiectasis, malignancies, and interstitial pneumonitis. Chronic lung disease may result from recurrent or persistent pneumonia due to bacterial, mycobacterial, viral, fungal or mixed infections. In high tuberculosis (TB) prevalence areas, M. tuberculosis is an important cause of chronic respiratory illness. With increasing availability of highly active antiretroviral therapy (HAART) for children in developing countries, a rise in the incidence of IRIS due to mycobacterial or other infections is being reported. Diagnosis of chronic lung disease is based on chronic symptoms and persistent chest X-ray changes but definitive diagnosis can be difficult as clinical and radiological findings may be non-specific. Distinguishing LIP from miliary TB remains a difficult challenge in HIV-infected children living in high TB prevalence areas. Treatment includes therapy for specific infections, pulmonary clearance techniques, corticosteroids for children with LIP who are hypoxic or who have airway compression from tuberculous nodes and HAART. Children who are taking TB therapy and HAART need adjustments in their drug regimes to minimize drug interactions and ensure efficacy. Preventative strategies include immunization, chemoprophylaxis, and micronutrient supplementation. Early use of HAART may prevent the development of chronic lung disease.

Childhood pneumonia--progress and challenges.

UNLABELLED: Remarkable progress has been made in the development of antimicrobial therapy, effective vaccines and pneumonia management guidelines in the past 50 years. However, pneumonia is currently the leading cause of death in children younger than 5 years in developing countries, accounting for approximately 20% of childhood deaths. This article reviews changes in the epidemiology, management and prevention of childhood pneumonia in developing countries, specifically in Africa and South Africa, and addresses future challenges. MAIN FINDINGS: The HIV epidemic has sharply increased the incidence, severity of, and mortality due to, childhood pneumonia. Bacterial infection remains a major cause of pneumonia mortality. Additional pathogens such as Pneumocystis jirovecii and Gram-negative bacteria are found in HIV-infected children, associated with a high mortality. Mycobacterium tuberculosis is an important cause of acute pneumonia in both HIV-infected and uninfected children. Use of case management guidelines can substantially reduce neonatal, infant and under-5 mortality and pneumonia-specific mortality. General preventive interventions including micronutrient supplementation with zinc and vitamin A, and immunisations can substantially reduce the burden of childhood pneumonia. Despite a lower efficacy in HIV-infected children, vaccination protects against disease in a significant proportion of children. In South Africa, new advances over the past 50 years have included greater access to primary health care for children, the use of Integrated Management of Childhood Illness guidelines in primary care, development of guidelines for diagnosis and management of childhood pneumonia and adoption of an expanded immunisation programme that includes coverage for Haemophilus influenzae type b. The pneumococcal conjugate vaccine recently licensed in South Africa also has the potential to significantly reduce the burden of childhood pneumonia. Recent roll-out of the national antiretroviral programme can reduce the incidence and severity of HIV-associated pneumonia through the prevention of HIV infection, use of cotrimoxazole prophylaxis and treatment with antiretrovirals. CONCLUSION: Available, effective interventions for prevention and treatment of childhood pneumonia exist; the challenge is to achieve widespread implementation and high coverage rates in developing countries. Greater access to newer vaccines and to antiretroviral therapy and co-trimoxazole prophylaxis in HIV-infected children is necessary to further reduce the burden of childhood pneumonia and the discrepancies in global child lung health.

Pneumonia in HIV-infected and HIV-uninfected children in developing countries: epidemiology, clinical features, and management.

PURPOSE OF REVIEW: Pneumonia is a leading cause of illness and death in children younger than 5 years in developing countries, accounting for approximately 20% of childhood deaths. The HIV epidemic has sharply increased the incidence, severity, and mortality of childhood pneumonia in the developing world, particularly in sub-Saharan Africa. This article reviews recent findings on the epidemiology, clinical features, and management of HIV-infected and -uninfected children with pneumonia in developing countries. RECENT FINDINGS: Bacterial infection remains a major cause of pneumonia mortality; in HIV-infected children, a broader spectrum of pathogens including gram-negative infections and Pneumocystis jiroveci occurs. Mycobacterium tuberculosis is an important cause of acute pneumonia among children from high tuberculosis prevalence areas. Use of case management guidelines substantially reduces neonatal, infant, and under-5 mortality and pneumonia-specific mortality in developing countries. New advances in therapy include the use of short-course antibiotics and high-dose amoxicillin twice daily for ambulatory treatment of HIV-negative children with pneumonia. New preventive interventions include the development of conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae, but these are not widely affordable nor available in developing countries. Despite a lower efficacy in HIV-infected children, these vaccines still protect against disease in a significant proportion of children. Available preventive interventions including micronutrient supplementation with zinc and vitamin A, and immunization as contained in the WHO Expanded Program of Immunization can substantially reduce the burden of childhood pneumonia. SUMMARY: Urgent measures to implement existing available, effective interventions for prevention and treatment of childhood pneumonia and achieve high coverage rates in developing countries are needed.