Community Acquired Bacteremic Syndromes in Young Nigerian Children

Specific Aim 1. To define and characterize the etiologic agents of community acquired bacteremic syndromes in young Nigerian children Hypothesis 1a: the role of vaccine-preventable infections such as those caused by the Pneumococcus, Hib in the etiology of CABS is currently underestimated due to widespread use of non-prescription antibiotics. Hypothesis 1b: Salmonella species are the leading cause of persistent febrile illness (fever > 2 weeks) in young Nigerian children.

Specific Aim 2. To determine the role of respiratory viruses in promoting the severity of bacteremic and radio-logic pneumonia Hypothesis 2: Influenza viruses promote the severity of bacteremic pneumonia

Specific Aim 3. To determine acute host inflammatory response profiles in CABS associated with respiratory distress Hypothesis 3a: Bacteremia induces a pattern of host inflammatory profile that is distinct from those induced by malaria or respiratory viral infections. Hypothesis 3b: Clinical presentation and outcome (death, survival or prolonged hospitalization) is associated with pro-inflammatory and anti-inflammatory cytokine and chemokine dissonance.

The global burden of childhood deaths is largely borne by developing countries. Of the estimated 10 million deaths that occur in children aged less than 5 years, over 90% of these occur in developing countries and more than half of these in sub Saharan Africa. Causes of these deaths have been largely classified based on syndrome presentation, such as pneumonia, malaria, diarrhea, meningitis and septicemia and only recently have attempts been made to define the etiologic pathogens that are responsible for these deaths, an important step to implementing primary prevention. In sub Saharan Africa, malaria has for a long time been perceived as the leading cause of childhood deaths but recent studies from Kenya suggest that more deaths are in fact caused by bacteremia. However, disease burden varies by region and disease burden perceptions also vary, particularly in malaria endemic regions where clinical presentation of acute malaria, pneumonia and sepsis are often indistinguishable. The situation is compounded further in regions where malaria is present all-year round where children who are bacteremic may also have malaria parasitemia and healthy children may have asymptomatic parasitemia. These complex and overlapping features present a challenge for efficient clinical management and implementation of appropriate preventive measures.

In most developing countries, due to lack of local data, clinical management recommendations are often obtained from the World Health Organization for common conditions based on the integrated management of childhood illness approach 3. In such settings, diagnosis is based on a limited number of clinical syndromes. However, because seriously ill children often meet criteria for several clinical syndromes, each of which could be caused by several viral or bacterial pathogens, treatment is empiric and management approach is non-specific. A key component of clinical management in malaria endemic areas with high incidence of invasive bacterial disease is the initiation of antibiotic treatment and anti-malarials. While this approach provides an easy scheme, because it is not pathogen-specific there is a significant risk of promoting long-term antibiotic resistance due to over prescription of antibiotics and paradoxically, there is also the risk of increased mortality and morbidity due to inappropriate medication. An etiology-based management approach would be more effective and also provide data to explore primary preventive measures such as immunization.