Ulysses
Fagundes-Neto
Division
of Pediatric Gastroenterology, Escola Paulista de Medicina, Universidade
Federal de São Paulo, São Paulo, Brazil e-mail: ulyneto@osite.com.br
Abstract:
Diarrhea is still responsible for high
rates of morbidity and mortality in children under 5 years of age. The
prolongation of the acute episode may cause digestive and absorptive
malfunction and, consequently, malnutrition, raising the risk of death.
The objective of this review is to
supply the most recent knowledge in the field of persistent diarrhea and to
contribute to the decrease of its incidence. Some possible etiologic agents may
be involved, including viruses, bacteria, and parasites.
Treatment must be addressed to avoid
malabsorption of the nutrients of the diet, associated with replacement of the
hydroelectrolytic losses, to prevent its prolongation. In the great majority of
the episodes, antibiotics are not indicated. Breastfeeding, introduction of
safe dietary strategies to prevent protein-energy malnutrition, and improvement
of sanitary conditions and hygiene are measures to be promoted with the
objective of decreasing the morbidity/ mortality of the diarrheic disease in
children less than 5 years of age.
Introduction
Collectively, the most important cause of death in
children younger than 5 years has been infectious diseases, especially
pneumonia, diarrhea, and malaria [1]. On the other
hand, the most important single causes of death have been pneumonia, diarrhea,
and preterm birth complications. Diarrhea is still responsible for high rates
of death in children worldwide. Diarrhea is the third most common cause of
death (16%) among children under 5 years of age, after neonatal causes (37%)
and pneumonia (17%), despite the decline in the mortality rates that has been
observed since the 1980s [2]. In 2008, diarrheal disease accounted for 1,336
million of the estimated 8,795 million deaths (15%) in children younger than 5
years of age around the world [3]. It is important to mention that 51% (0.678
million) of the deaths caused by diarrhea occurred in India, Nigeria,
Afghanistan, Pakistan, and Ethiopia. Young children suffer from 3.2–12
diarrheal episodes per year [4]. The majority of the diarrheal illnesses are
acute, lasting no more than 7 days; however, an estimated 3%–19% of the acute
episodes lasting longer (14 days and more) are designated as persistent
diarrhea (PD) [5]. PD cases are difficult to treat, their treatment
cost is higher, and a case fatality rate as high as 60% has been reported [6]. It has been
estimated that PD contributes to a loss of 3 million disability-adjusted
life-years annually [7]. In our experience, studying 200 patients under 1
year of age suffering from acute diarrhea, we detected that when some strains
of enteropathogenic Escherichia coli (EPEC) were isolated in the stools, the
evolution to PD reached 28.4% of the cases, versus 6.9% when the process was
due to another enteropathogenic agent [8]. In
developing countries, over 50% of the deaths due to diarrhea are associated
with the perpetuation of the diarrheic syndrome [9]. The majority
of deaths occur in children of early age living in the rural regions of
developing countries, where there is a lack of adequate sanitary conditions [10]. Repeated
episodes of acute diarrhea in the first year of life usually lead to intestinal
malabsorption of the nutrients of the diet and, consequently, malnutrition.
Considering that the perpetuation of the diarrheic
episode in the majority of the cases occurs during a critical developmental
period, both physical and intellectual, it could lead to severe damage to the
rhythm of growth, cognitive and intellectual functions, and future performance
at school, as well as an increasing morbidity/mortality due to other diseases [11–13].
In the early 1980s in Brazil, several interventions
of universal characteristics introduced by the Brazilian Public Health System,
including important improvements in the sanitary conditions and in the quality
of water, led to a dramatic decrease, of up to 90 %, in the mortality rates in
childhood due to diarrhea [14]. Confirming
these data, Maranhão et al. [15] conducted a case–control study in
Natal, Rio Grande do Norte, in the northeast region of Brazil, including 206
infants under 2 years of age with acute diarrhea (103 patients), to evaluate
the potential risk factors for persistence of diarrhea after 1 month of
follow-up. The most frequent enteropathogens found in the
stools in the infants with acute diarrhea were rotavirus (36%), EPEC (11.6%),
and Shigella (11.6%). Only 5.2% of the patients showed persistence of the
diarrhea. These results clearly demonstrated that implementation of vertical
programs and long-term horizontal approaches can make the fourth Millennium
Development Goal—to reduce by two thirds, between 1990 and 2015, the
under-5-year mortality rate—achievable [16].
Definition
PD was defined by the World Health Organization
(WHO) in 1987 as “a diarrheal episode of presumed infectious etiology that
begins acutely, but has an unusually long duration, lasting more than 14 days,” leading
to a deterioration of the nutritional status and a substantial risk of death.
The term does not include chronic or recurrent diarrheal disorders, such as
tropical sprue, celiac disease, cystic fibrosis, or other hereditary diarrheal
disorders [17]. Although these other clinical entities were not
included in the definition of PD by WHO experts, considering the present
knowledge about the high prevalence of celiac disease around the world, it
should be brought to attention as an important cause of protracted diarrhea
that may lead to malnutrition, even in the developing countries [18].
Etiopathogenic Aspects
The enteric infections occur as a consequence of
high levels of environmental contamination due to the lack of sanitary
conditions and of access to potable water, associated with poor personal hygiene.
Several different enteropathogenic agents can cause acute diarrhea in children.
The agents that are isolated in the stools in children with PD are not always
the same as those found in the acute phase of the episode. This finding
suggests that a potential secondary infection may assume a relevant role in the
persistence of the diarrheic process [19]. Moreover,
isolation of multiple enteropathogenic agents in the stools of children with PD
has also been reported [20]. The most frequent enteropathogenic
microorganisms isolated from the stools of children with PD in several
different centers around the world are listed in Table 1, modified from
Bhutta [21].
PD represents the final consequence of a variety of
injuries suffered by the child, who becomes prone to frequent and severe
episodes of diarrhea due to a combination of several factors depending on the
host and the undesirable effect of a prevalent environmental contamination.
These episodes usually occur in children under 3 years of age [22]. Protein-energy
malnutrition is seen as the major risk factor for the persistence of the
diarrheic process [11]. Furthermore, other determinants must also be
considered, such as a recent episode of acute diarrhea [23], zinc
deficiency [24], lack of breastfeeding [2], male sex [25], infection
due to EPEC and enteroaggregative Escherichia coli (EAEC) strains,
Cryptosporidium [26], and past history of intrauterine growth
retardation [25].
Table 1- Pathogens associated with
persistent diarrhea
Enteroaggregative
Escherichia coli
Entropathogenic
Escherichia coli
Campylobacter
Salmonella
Shigella
spp
Clostridium
difficile
Parasites
Giardia
lamblia
Blastocystis
hominis1
Cryptosporidium
spp.1
Entamoeba
histolytica
Cyclospora
cayetanensis1
Enterocytozoon
bieneusi
(Microsporidium spp)1
1 Especially associated with HIV infections
