Epidemiology and etiology

While infectious gastroenteritides are the second most common diseases in childhood worldwide, viruses are the most frequent agents of infectious diarrhea. Viral infections of the gastrointestinal tract cause 2 billion cases of diarrhea in children per year, resulting in 18 million hospitalizations and as many as 3 million deaths.1

Acute diarrhea is thus an enormous problem both in developing and in industrialized countries, but with two distinct consequences. In the former, enteric infections are extremely frequent, as the incidence of diarrhea is estimated at 3.8 episodes/ child per year in infants and 2.1 episodes/child per year in children 1-4 years of age.2 A cumulative incidence of 2.5-3 million deaths each year has been estimated, corresponding to 25% of all deaths in childhood up to 5 years of age. In the developing world, one out of 40 children will die because of diarrhea.3

In industrialized countries, on the other hand, the incidence of diarrhea is approximately 1-2 episodes/child per year in subjects younger than 3 years. The case/fatality ratio is far from the figures in poor countries, but not negligible. In the USA, 150-300 infants or younger children die each year because of acute diarrhea, and substantial resources are needed for hospitalizations and medical visits. Diarrhea was associated with an annual average of 35 hospitalizations per 10 000 children younger than 5 years, corresponding to 4% of all hospitalizations.4 It was estimated that 1 in 57 children would be hospitalized by 5 years of age for diarrhea-associated illness. The rate of outpatient visits was 943/10 000 children, corresponding to 2% of all visits. Rotavirus is the leading agent of infectious diarrhea, being responsible for approximately 40% of all cases of diarrhea in the USA.4 Similar figures have been recorded in Europe,5 with rotavirus consistently playing a leading role in younger subjects.6 The estimated average costs for an episode of diarrhea requiring hospital admission may be as high as US$ 2300. Costs for acute diarrhea are not negligible even in less severe cases, particularly when the so-called societal costs are considered. It has been estimated that the cost of an episode of diarrhea requiring an office visit in the USA averages approximately $300,7 half of which is related to the loss of working days by the parents of sick children.

During the past three decades, there has been a dramatic increase in the number of newly recognized etiological agents of gastroenteritis. Before 1970, a pathogen could be identified in fewer than 10% of patients hospitalized with diarrhea; the remaining 90% of cases represented a 'diagnostic void' consisting of various idiopathic, poorly defined conditions. Since 1970, more than 20 different micro-organisms - bacteria, parasites and viruses - have been recognized as etiological agents, and most cases of gastroenteritis are now presumed to have an infectious etiology. Nevertheless, a pathogen is currently identified in only a small proportion of cases. Although numerous viruses have been identified in fecal samples of patients with diarrhea, causal relationships have been determined for relatively few (Table 9.1). Most children are infected with viruses belonging to four distinct families: rotaviruses, caliciviruses, astroviruses and enteric adenoviruses. Other viruses, such as the toroviruses, picornaviruses (the Aichi virus), and enterovirus 22, play a minor epidemiological role. Finally, selected viruses induce diarrhea only in children at risk. These include cytomegalovirus, Epstein-Barr virus and picobirnaviruses. Recent evidence suggests that

Table 9.1 Etiological role of viruses in childhood diarrhea

Conclusively established

Probable

Possible in selected children

Rotavirus

Torovirus

HIV

Adenovirus

Aichi virus

Cytomegalovirus

Astrovirus

Enterovirus 22

Epstein-Barr virus

Calicivirus

Picobirnavirus

HIV-1 virus may directly induce diarrhea through the production and release of TAT, its transacti-vating transfer factor.8

Enteric infections are usually associated with diarrhea and, less frequently, with vomiting. Diarrhea usually lasts a few days and resolves spontaneously without any major problem. However, in selected cases it may be severe, leading to dehydration, requiring hospital admission and possibly even resulting in fatal outcome.

The impact of viral diarrhea is related to the specific strain, but occasionally also to the epidemiological setting, the host baseline features and the efficacy of early medical intervention (Table 9.2). Viral diarrhea may have a major impact in closed communities such as day-care centers and hospitals. It may be severe in malnourished or immunocompromized children, but also in children not belonging to groups at risk. Finally, diarrhea may become severe if rehydration is not initiated in the initial phases of the disease.

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