The American Journal of Tropical Medicine and Hygiene - Volume 47, Issue 1_Suppl, July 1992

Along with malnutrition and respiratory tract infections, diarrhea and leishmaniasis constitute the leading causes of hospitalization in the pediatric wards at Hospital Walter Cantidio and Hospital Albert Sabin in Fortaleza, Ceara, Brazil. These leading diagnoses exemplify the major contribution that common infectious diseases and malnutrition make to the high morbidity and mortality rates seen among impoverished populations throughout the tropical, developing world. The data from large regional studies of causes of mortality, such as those of Puffer and Serrano, document the impressive contributions of diarrheal diseases, alone or in combination with malnutrition, as being responsible for 52.4% of the high childhood mortality in regions such as northeastern Brazil (see Table 1 in article by Guerrant and others in this symposium). These data are remarkably similar to those obtained from recent family histories such as those in the rural town of Pacatuba or in the urban favela (shantytown), Goncalves Dias, in Fortaleza, Ceara, in the heart of northeastern Brazil (see Table 2 in article by Guerrant and others in this symposium).

This review presents a history of tumor necrosis factor, considers the biology of this pleiotropic mediator, and summarizes the evidence that implicates it as a mediator of cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

Although long associated with infectious diseases, malnutrition is recognized as a major effect of specific infections, especially those of the gastrointestinal tract. Synergistic exacerbation of infections and nutritional deficiency commonly begin with weaning, where the impact of repeated infections and possible monocyte mediator release may have an even greater effect on malnutrition of young children than that of deficient diets in many areas. Reviewed here are the detailed host alterations seen with specific enteric infections that lead to malnutrition. These include mucosal dysfunction, systemic metabolic responses, impaired intake, digestion and absorption, nutrient losses, altered immune responses, and ultimately, impaired growth, development, and nutrition. The tremendous health impact of diarrhea on both morbidity and mortality in many developing areas must be recognized and controlled along with correction of food shortages in order to improve the nutrition, growth, and survival of impoverished children.

Diarrhea and malnutrition, alone or together, constitute major causes of morbidity and mortality among children throughout the tropical world. Data from northeast Brazil, taken with numerous other studies, clearly show that diarrhea is both a cause and an effect of malnutrition. Diarrheal illnesses impair weight as well as height gains, with the greatest effects being seen with recurrent illnesses, which reduce the critical catch-up growth that otherwise occurs after diarrheal illnesses or severe malnutrition. Malnutrition (whether assessed by impaired weight or height for age) leads to increased frequencies and durations of diarrheal illnesses, with a 37% increase in frequency and a 73% increase in duration accounting for a doubling of the diarrhea burden (days of diarrhea) in malnourished children. A multi-pronged approach focusing on those with prolonged diarrhea and severe malnutrition is suggested.

The papers presented at this session again emphasize the interactions between the nutritional status of the host and the occurrence and severity of infectious diseases. For many infections, malnourished subjects are more likely to develop severe clinical manifestations, are at greater risk of complications, and take much longer to recover than well-nourished persons. However, there are exceptions to the general rule that undernourished subjects are more susceptible to infections; malnourished subjects are more resistant to some viral and protozoan infections or they show less severe manifestations of disease.

The effects of acute and chronic infections on the nutritional status of the host are also well-known. For example, an attack of measles is often the precipitating cause of acute manifestations of severe protein-calorie malnutrition in children who are marginally undernourished.