Randomised controlled trials in child health in developing countries: trends and lessons over 11 years.

Using a uniform systematic approach annually, we reviewed 1553 publications from randomised controlled trials in child health in developing countries published between July 2002 and June 2013. There were annual increases in such publications, from 38 in the 12 months to July 2003 to over 200 in each of 2012 and 2013. These trials involved children in 76 developing countries. Studies of nutrition (366 publications, 23.6%) and malaria (336 publications, 21%) predominated. 79% of nutrition trials have been of micronutrients (288 publications), with comparatively few publications related to macronutrient interventions or complimentary feeding (48 publications) or measures to improve breast feeding (20 publications). Trials of malaria have involved a comprehensive range of treatment and preventive strategies and have heralded the implementation of new interventions as routine health strategies, and reductions in malaria in each affected country in the world in the last decade. There have been a relatively small number of trials of interventions for treatment or prevention of acute respiratory infection (98 publications, 6.3%), neonatal health (64 publications, 4.1%) and tuberculosis in children (26 publications, 1.7%). In the last 5 years there has been increasing focus on non-communicable diseases such as asthma and allergy, obesity, diabetes and cardiac disease, and behavioural-developmental disorders. Mental health conditions have received little attention (21 publications, 1.4% of publications). There is increasing research activity and capacity in child health in developing countries. Some areas have been the subject of a large amount of research, and have led to the design and implementation of effective public health interventions and reduced disease burdens, while in other areas comprehensive approaches and the systematic application of research findings have been lacking.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation.

Application of the Ceditest® FMDV type O and FMDV-NS enzyme-linked immunosorbent assays for detection of antibodies against foot-and-mouth disease virus in selected livestock and wildlife species in Uganda

Diagnosis and control of Foot-and-mouth disease virus (FMDV) requires rapid and sensitive diagnostic tests. Two antibody enzyme-linked immunosorbent assay (ELISA) kits, Ceditest® FMDV-NS for the detection of antibodies against the nonstructural proteins of all FMDV serotypes and Ceditest® FMDV type O for the detection of antibodies against serotype O, were evaluated under African endemic conditions where the presence of multiple serotypes and the use of nonpurified vaccines complicate serological diagnosis. Serum samples from 218 African buffalo, 758 cattle, 304 goats, and 88 sheep were tested using both kits, and selected samples were tested not only in serotype-specific ELISAs for antibodies against primarily FMDV serotype O, but also against other serotypes. The FMDV-NS assay detected far more positive samples (93%) than the FMDV type O assay (30%) in buffalo (P < 0.05), with predominant antibodies against the South African Territories (SAT) serotypes, while the seroprevalence was generally comparable in cattle with antibodies against serotype O elicited by infection and/or vaccination. However, some districts had higher seroprevalence using the FMDV type O assay indicating vaccination without infection, while 1 cattle herd with antibodies against the SAT serotypes had far more positive samples (85%) using the FMDV-NS versus the FMDV type O (10%), consistent with the latter test's lower sensitivity for antibodies against SAT serotypes. Based on the current investigation, the FMDV type O ELISA may be limited by the presence of SAT serotypes. The FMD NS assay worked well as a screening test for antibodies against all FMDV serotypes present in Uganda; however, as long as nonpurified vaccines are applied in the region, this test cannot be used to differentiate between vaccinated and infected animals.