Requirements for high impact diagnostics in the developing world.

Child survival efforts can be effective only if they are based on accurate information about causes of deaths. Here, we report on a 4-year effort by WHO to improve the accuracy of this information. WHO established the external Child Health Epidemiology Reference Group (CHERG) in 2001 to develop estimates of the proportion of deaths in children younger than age 5 years attributable to pneumonia, diarrhoea, malaria, measles, and the major causes of death in the first 28 days of life. Various methods, including single-cause and multi-cause proportionate mortality models, were used. The role of undernutrition as an underlying cause of death was estimated in collaboration with CHERG. In 2000-03, six causes accounted for 73% of the 10.6 million yearly deaths in children younger than age 5 years: pneumonia (19%), diarrhoea (18%), malaria (8%), neonatal pneumonia or sepsis (10%), preterm delivery (10%), and asphyxia at birth (8%). The four communicable disease categories account for more than half (54%) of all child deaths. The greatest communicable disease killers are similar in all WHO regions with the exception of malaria; 94% of global deaths attributable to this disease occur in the Africa region. Undernutrition is an underlying cause of 53% of all deaths in children younger than age 5 years. Achievement of the millennium development goal of reducing child mortality by two-thirds from the 1990 rate will depend on renewed efforts to prevent and control pneumonia, diarrhoea, and undernutrition in all WHO regions, and malaria in the Africa region. In all regions, deaths in the neonatal period, primarily due to preterm delivery, sepsis or pneumonia, and birth asphyxia should also be addressed. These estimates of the causes of child deaths should be used to guide public-health policies and programmes.

The diagnosis and treatment of bacterial pneumonia in patients who are receiving mechanical ventilation remain a difficult challenge. The triggering receptor expressed on myeloid cells (TREM-1) is a member of the immunoglobulin superfamily, and its expression on phagocytes is specifically up-regulated by microbial products. The presence of soluble TREM-1 (sTREM-1) in bronchoalveolar-lavage fluid from patients receiving mechanical ventilation may be an indicator of pneumonia. We conducted a prospective study of 148 patients receiving mechanical ventilation in whom infectious pneumonia was suspected. A rapid immunoblot technique was used to measure sTREM-1 in bronchoalveolar-lavage fluid. Two independent intensivists who were unaware of the results of the sTREM-1 assay determined whether community-acquired pneumonia and ventilator-associated pneumonia were present or absent. The final diagnosis was community-acquired pneumonia in 38 patients, ventilator-associated pneumonia in 46 patients, and no pneumonia in 64 patients. The presence of sTREM-1 by itself was more accurate than any clinical findings or laboratory values in identifying the presence of bacterial or fungal pneumonia (likelihood ratio, 10.38; sensitivity, 98 percent; specificity, 90 percent). In multiple logistic-regression analysis, the presence of sTREM-1 was the strongest independent predictor of pneumonia (odds ratio, 41.5). In patients receiving mechanical ventilation, rapid detection of sTREM-1 in bronchoalveolar-lavage fluid may be useful in establishing or excluding the diagnosis of bacterial or fungal pneumonia. Copyright 2004 Massachusetts Medical Society

More than one billion diarrhea episodes occur every year among children younger than 5 years of age in socioeconomically developing countries causing 2 to 2.5 million deaths. More than twenty viral, bacterial, and parasitic enteropathogens are currently associated with acute diarrhea. Rotavirus and diarrheagenic Escherichia coli are the most common pathogens responsible for acute diarrhea episodes in children; Shigella spp., Salmonella spp, Campylobacter jejuni/coli, Vibrio cholerae, Aeromonas spp, and Plesiomonas spp. occur more commonly in poorer areas and infections caused by protozoa and helminthes occur mainly in areas where environmental sanitation is significantly deteriorated. Initial clinical assessment of a child with diarrhea should focus on obtaining an accurate evaluation of hydration and nutritional status. Assessment of stool characteristics (e.g., liquid non-bloody stools vs. dysenteric or bloody stools) is a key feature in determining potential pathogens causing an acute diarrhea episode. Diagnostic guidelines are discussed in the article. The major therapeutic intervention for all individuals with diarrhea consists of fluid and electrolyte therapy. When antimicrobial therapy is appropriate, selection of a specific agent should be made based upon susceptibility patterns of the pathogen or information on local susceptibility patterns. Current guidelines for administering appropriate antimicrobial treatment are provided in the article. Preventive measures include careful personal hygiene, especially promotion of hand washing. Immunizations currently or soon to be available for Salmonella serotype Typhi, cholera prevention, and rotavirus are discussed.