Persistent diarrhoea.

Persistent diarrhoea (PD) is defined by the World Health Organization as episodes of diarrhoea that last for 14 or more days. (1) The epidemiology and impact on mortality has been well described. (2) PD poses challenges for investigation and management because of the close association with malnutrition and increased vulnerability to infections. This association often makes it difficult to define the initiating event. It is therefore imperative that the care of infants with PD is directed at nutritional support while further investigations and management follow. This review highlights the basic approach to PD of presumed infectious origin and describes selected noninfectious conditions. The purpose of the latter is to illustrate the principles of investigation that may broadly be guided by knowledge of the epidemiology of common conditions, dietary evaluation, timing of onset, and presence of extra-intestinal manifestations.

The reader is referred to the World Health Organization (WHO) manual (2005) for physicians and other senior health workers on the treatment of diarrhoea that provides guidelines for the basic approach to and management of PD. (1) These include initial resuscitation and correction of fluid and electrolyte impairments, initiation of a nutritious diet that may necessitate temporary reductions in lactose intake, micronutrient/mineral supplementation and, where appropriate, use of antibiotics for intestinal and extra-intestinal infections.

The majority of infants and young children in developing countries will benefit from the above approach without requiring invasive gastrointestinal investigations. An important addition to these guidelines, and a gap that has been addressed in the current WHO guidelines for the integrated management of childhood illness, (3) would be that in regions of high HIV prevalence testing for HIV infection is warranted early in the course of management. HIV testing and staging allows timely initiation of antiretroviral therapy. The high prevalence of symptomatic HIV in children hospitalised with diarrhoea in South Africa supports this approach. (4) The HIV epidemic has changed the epidemiology of PD in childhood. Salmonella spp. (2) and Cryptosporidium Parvum (2,5) have assumed increasing importance, but are difficult to eradicate. The HIV-infected child with prolonged or recurrent dysentery requires referral for evaluation of possible cytomegalovirus disease and rarer conditions such as Kaposi's sarcoma. The long-term goal should be to initiate antiretroviral therapy before the child reaches this advanced stage of HIV disease.

The challenge for health workers in our environment is the child who fails to respond to the guidelines described above and in whom basic investigations fail to reveal an aetiology. In these situations a detailed re-evaluation is warranted. This includes obtaining a history of antibiotics and other medications that cause gastrointestinal upset. This is crucial in an era where maintenance therapy is increasingly used for chronic conditions in paediatric practice. The impact on nutrition and quality of life will often determine the extent to which modifications of such treatment regimens are required.

While infectious and post-infectious causes are responsible for the majority of cases of PD globally and locally, an awareness of non-infectious causes is necessary, especially in communities with wide socioeconomic heterogeneity. The proportion of PD attributable to non-infectious causes assumes greater relevance and deserves attention in the setting where the usual risk factors for infectious diarrhoea and malnutrition are not apparent. Non-infectious causes of PD include among others, cow/soy milk protein intolerance, coeliac disease (gluten-sensitive enteropathy) and cystic fibrosis (secondary to pancreatic impairment). The latter are more likely in children of Caucasian origin.

Cow's milk or formula protein intolerance presents within the first 6 months of life, usually with persistent and/or blood-tinged stools and anaemia. A temporal association should be sought with introduction of formula. This entity may be under-recognised in environments where dietary iron deficiency is common. Infants with anaemia and PD should have stools assessed for occult blood to screen for this condition prior to dietary manipulation or biopsy. It is worth noting that the RAST test may be negative in these infants. (6)

In older children coeliac disease should be considered after a careful search for other associated systemic manifestations such as anaemia and dermatitis herpetiformis. (7) Besides serological tests small-intestinal biopsy is warranted for this condition, with assessment of response to dietary manipulation. Extensive dietary restrictions without any investigations must be avoided. Other conditions that warrant endoscopic biopsies include the congenital causes, autoimmune enteropathy and inflammatory bowel disease.

In conditions such as coeliac disease, cystic fibrosis, inflammatory bowel disease and primary immunodeficiency, other systemic manifestations provide clues to the necessity for referral and diagnostic investigations. (7) Unlike the syndromic management of PD these conditions warrant detailed investigations in tertiary centres before definitive treatment is instituted.

Imaging studies are rarely indicated in the investigation of PD. However, in young infants with recurrent unexplained episodes despite appropriate basic management one should consider rare anatomical causes such as intestinal malrotation or chronic small-intestinal obstruction or pseudo-obstruction. Upper gastrointestinal contrast studies with small-bowel follow-through are best conducted in centres with expertise in interpretation of these investigations.

The entity of toddler's diarrhoea is frequently considered in ambulatory care of infants. It should be stressed that this entity should only be considered in the infant who is not having any complications from diarrhoea, that is, there is no evidence of growth failure or fluid and electrolyte imbalance. The stools are not voluminous and may contain undigested food particles but never any blood.

In summary, the contribution of infectious causes, HIV and socioeconomic risk factors to PD makes most cases amenable to existing management guidelines. The child who fails to respond or has symptoms at an age outside of the peak prevalence period or without any of the usual risk factors should be referred for further evaluation.

References

(1.) WHO. The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers, 4th rev 2005.

(2.) Amadi B, Kelly P, Mwiya M, et al. Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition. J Pediatr Gastroenterol Nutr 2001; 32(5): 550-554.

(3.) World Health Organization. Integrated Management of Childhood Illness Complementary Course on HIV/AIDS. 2006. http://www.who.int/ child-adolescent-health/publications/IMCI/ISBN_92_4_159437_3.htm.

(4.) Chhagan MK, Kauchali S. Comorbidities and mortality among children hospitalized with diarrheal disease in an area of high prevalence of human immunodeficiency virus infection. Pediatr Infect Dis J 2006; 25(4): 333-338.

(5.) Tumwine JK, Kekitiinwa A, Bakeera-Kitaka S, et al. Cryptosporidiosis and microsporidiosis in Ugandan children with persistent diarrhea with and without concurrent infection with the human immunodeficiency virus. Am J Trop Med Hyg 2005; 73(5): 921-925.

(6.) Rasanen L, Lehto M, Reunala T. Diagnostic value of skin and laboratory tests in cow's milk allergy/intolerance. Clin Exp Allergy 1992; 22(3): 385-390.

(7.) Fasano A. Clinical presentation of celiac disease in the pediatric population. Gastroenterology 2005; 128(4 Suppl 1): S68-73.

MEERA K CHHAGAN, DCH, FCPaed, MS

Senior Paediatrician/ Lecturer, Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal and King Edward VIII Hospital, Durban