Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis.

OBJECTIVE: To explore excess paediatric mortality after discharge from Kilifi District Hospital, Kenya, and its duration and risk factors. METHODS: Hospital and demographic data were used to describe post-discharge mortality and survival probability in children aged < 15 years, by age group and clinical syndrome. Cox regression models were developed to identify risk factors. FINDINGS: In 2004-2008, approximately 111,000 children were followed for 555,000 person-years. We analysed 14,971 discharges and 535 deaths occurring within 365 days of discharge. Mortality was higher in the post-discharge cohort than in the community cohort (age-adjusted rate ratio, RR: 7.7; 95% confidence interval, CI: 6.6-8.9) and declined little over time. An increased post-discharge mortality hazard was found in children aged < 5 years with the following: weight-for-age Z score < -4 (hazard ratio, HR: 6.5); weight-for-age Z score > -4 but < -3 (HR: 3.4); hypoxia (HR: 2.3); bacteraemia (HR: 1.8); hepatomegaly (HR: 2.3); jaundice (HR: 1.8); hospital stay > 13 days (HR: 1.8). Older age was protective (reference < 1 month): 6-23 months, HR: 0.8; 2-4 years, HR: 0.6. Children with at least one risk factor accounted for 545 (33%) of the 1655 annual discharges and for 39 (47%) of the 83 discharge-associated deaths. CONCLUSION: Hospital admission selects vulnerable children with a sustained increased risk of dying. The risk factors identified provide an empiric basis for effective outpatient follow-up.

Children's Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial.

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the 'Treat' element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome. Methods: COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO 2 <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia, assessment of muscle and fat mass and host genetic studies.   Discussion: This study is the first step in providing an option for nutritional support following severe pneumonia and will help in the design of a large Phase III trial. Registration: ISRCTN10829073 (6 th June 2018) PACTR202106635355751 (2 nd June 2021).

New strategies for control of respiratory syncytial virus infection.

PURPOSE OF REVIEW: To report on recent progress on the development and implementation of a vaccine against respiratory syncytial virus (RSV), on investigations of the mechanism of action of prophylactic antibodies and the potential for increased efficacy of those antibodies, and on candidate antiviral drugs against RSV. RECENT FINDINGS: Follow-up data from RSV live attenuated vaccine trials in naïve infants and young children strengthen the view that live attenuated vaccines will not predispose to exacerbated pneumonia upon natural infection. Data on the age distribution of RSV disease from the developing country setting highlight a need to investigate the effectiveness of live attenuated vaccination outside the 0-2 month age group. It has recently been shown that palivizumab, the only approved monoclonal antibody for prophylaxis of RSV, and which is used mainly in infants at high risk of severe RSV disease, allows abortive replication of the virus in the lungs of cotton rats. It has also been reported that a variant of palivizumab, motavizumab, has greater affinity for RSV and is now being investigated in clinical trials. Progress has been made on the development of antiviral compounds including RSV604, a novel benzodiazepine, and ALN-RSV01, based on a small interfering RNA. SUMMARY: Advances in the treatment of RSV are more evident than in prevention. Obstacles to prevention of paediatric RSV disease may require new approaches to vaccine delivery.

Demographic impact of AIDS in a low-fertility urban African setting: projection for Addis Ababa, Ethiopia.

The study estimated the potential demographic impact of acquired immunodeficiency syndrome (AIDS) in a low-fertility urban setting in sub-Saharan Africa. The prevalence of human immunodeficiency virus (HIV) projected using a deterministic mathematical model was put into the AIDS Impact Model (AIM) of the SPECTRUM Policy Modelling System to estimate the potential demographic impact ofAIDS in Addis Ababa, Ethiopia. Demographic indicators from 1984 (the start of the HIV epidemic in Ethiopia) to 2024, including and excluding the HIV epidemic, were compared. Addis Ababa is experiencing a demographic transition in which the total fertility rate has declined from 3.8 to below replacement level over the last 20 years. The prevalence of HIV is predicted to stabilize at 10% in adults, resulting in a total number of people living with HIV at 200,000 and a cumulative number of deaths due to AIDS at 50,000. About 60% of adult deaths can be attributable to AIDS by 2000. The epidemic is predicted to reduce life expectancy by 10 and 17 years in 2000 and 2024 respectively, and to turn to negative, the rate of natural increase after 2009. Accordingly, the rate of natural increase will be -0.18%, -0.35%, and -0.71% per annum by 2009, 2014, and 2024 respectively. Population growth is expected to continue with or without HIV, as a result of high net in-migration, although data for migration are scanty. In a low-fertility urban society of Africa, this study shows the potential for the HIV/AIDS epidemic to turn the rate of natural increase to negative.

Evaluation of a measles vaccine campaign in Ethiopia using oral-fluid antibody surveys.

We undertook a study to demonstrate the potential contribution of oral-fluid (OF) antibody prevalence surveys in evaluating measles vaccine campaigns. In Asela town, southern Ethiopia, oral fluids were collected from 1928 children aged 9 months to 5 years attending for campaign immunization in December 1999 and 6 months later, from 745 individuals aged 9 months to 19 years, in the same location. Measles antibody status was determined by microimmune measles specific IgG enzyme immunoassay (EIA). Antibody prevalence was estimated at 48% in children attending for vaccination (pre-campaign), and 85% post-campaign in the comparable age group. The estimated reduction in the susceptible proportion was 75%. In older children the proportion antibody negative post-campaign was 28% in 7-9 year olds, and 13% in 10-14 year olds levels of susceptibility which raise concern over continued measles transmission. This is the first evaluation of a measles vaccine campaign based on oral-fluid seroprevalence surveys and it demonstrates the merit of oral-fluid surveys in informing health authorities about vaccination strategy refinement.