Persistent diarrhea as a cause of childhood mortality in rural Bangladesh

To determine the importance of persistent diarrhea in childhood mortality a multiple-step verbal autopsy method was used to study 1934 deaths in Matlab, Bangladesh. We found that most of the deaths from acute watery diarrhea occurred in infancy, whereas the peak of non-watery diarrhea deaths was in children over 12 months of age. Children suffering from persistent diarrhea and malnutrition were at highest risk of dying during their third year of life. Children with infectious diseases have a two to four times higher risk of dying if they are malnourished, and for diarrhea the risk is 17 times as high. Forty-nine percent of the diarrheal deaths were in children with malnutrition associated with persistent diarrhea. These results imply that fluid and dietary management are key aspects in the treatment of diarrhea, particularly for those episodes which persist. We conclude that attempts to reduce diarrhoeal deaths with vertical ORT programmes will not have a major impact unless other interventions are directed to the persistent diarrhoea-malnutrition complex.     

Epidemiology of persistent diarrhea among Guatemalan rural children

A prospective, longitudinal two-year study to determine the epidemiology of persistent ( 14 days'duration) diarrhea in rural children of Guatemala was undertaken. Three-hundred and twenty-one children aged 0-35 months were kept under surveillance by twice-a-week home visits. The overall incidence of diarrhea was 0.147 per child-week; the incidence of persistent diarrhea was 0.014 per child-week. The peak of persistent diarrhea was observed in infants below six months of age, with a continuous decline thereafter. This trend in incidence of persistent diarrhea was associated with a higher proportion (16%) of illnesses persisting for more than 13 days in children younger than six months of age as compared to children 30-35 months old (4%). Males had more diarrhea (0.156 per child-week) than females (0.139 per child week). Among children above 18 months of age, the proportion of episodes that lasted for more than 13 days was lower in females than in males.     

Persistent diarrhea associated with AIDS

Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli , and Enterocytozoon bieniusi ) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV⁺ and HIV^- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV⁺ compared to HIV^- babies, and 3.5 times greater in HIV^- babies born of HIV⁺ mothers in comparison to HIV^- babies with HIV^- mothers. HIV⁺ babies were also at greater risk than HIV^- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants.     

Deaths due to dysentery, acute and persistent diarrhoea among Brazilian infants

In a population-based study, all infant deaths occurring in a one-year period in the metropolitan areas of Porto Alegre and Pelotas, in southern Brazil, were studied. There were 227 infants who presented diarrhoea during the fatal illness, and in 75% of these diarrhoea was considered to be the underlying cause of death. Acute diarrhoea (< 14 days'duration) accounted for 28% of the deaths, persistent diarrhoea for 62% and dysentery for a further 10%. Approximately one-half of the children with persistent diarrhoea were admitted to a hospital in the first two weeks of the episode. Hospital-acquired infections were likely to have contributed to one- to two-thirds of deaths due to dysentery and persistent diarrhoea. A comparison with neighbourhood controls showed that breast milk provided substantial protection against deaths due to either acute or persistent diarrhoea.     

Epidemiology of persistent diarrhea and etiologic agents in Mirzapur, Bangladesh

To determine the epidemiology and etiologic agents of persistent diarrhea we carried out an intensive diarrhea surveillance on children less than six years old in rural Bangladesh. From March 1987 to February 1989 we examined 363 children through diarrhea recall interviews and analyzed stool samples of all diarrhea cases for potential pathogens. Results showed that children had an average of two episodes per year and the incidence rate of diarrheal episodes denned as acute (<14 d) and persistent (14 d) varied similarly with age. The peak incidence (episodes/child/year) of acute diarrhea (2.8) and persistent diarrhea (0.8) occurred in the 6-11 months age group. The data showed that an episode tended to be prolonged if the stool was loose/mucoid or bloody at onset. Aggregative adherent Escherichia coli was found significantly more often at onset in persistent than in acute episodes, whereas Shigella, Aeromonas, Giardia and toxigenic E. coli were isolated with less frequency in persistent than acute episodes. This suggests that other factors might be more important in the development of persistent diarrhea than specific pathogens.     

Association of indicators of hygiene behavior with persistent diarrhea of young children

We examined the association between water and hygiene-related behaviors and persistent diarrhea (duration 14 days) among children under age three years in an indigenous rural Guatemalan community. Behavior indicators were specific aspects of the appearance of the mother, study child, other children and household that could be observed using a spot observation technique. Thirty-four percent of children had one or more episodes of persistent diarrhea during the year of study. Bivariate analyses found that a higher proportion of observations in which the anti-hygienic condition was observed was significantly associated with persistent diarrhea for 11 of 26 behavior indicators; these 11 indicators were also strongly correlated with each other. In individual logistic regression models, which included overall rate of diarrhea and other child characteristics associated with persistent diarrhea, six behavior indicators maintained significant association with persistent diarrhea: presence of toy on the ground, presence of baby bottle on the ground, the hands of the mother being dirty, presence of a fecally soiled diaper on the ground in the household compound, presence of feces in the yard, and the study child wearing a fecally soiled diaper. Three additional indicators closely approached significant association with persistent diarrhea. Excluding the three soiled diaper indicators, which might be the result rather than the cause of diarrhea, we found the six other behavior indicators to demonstrate a significant dose-response effect in increasing risk of persistent diarrhea. These findings suggest that behaviors which promote increased exposure of young children to enteric pathogens increase risk of persistent diarrhea.     

Household behaviors in the management of diarrhea and their relevance for persistent diarrhea

There has been a great deal of research in recent years on household behaviors related to diarrhea management. Most of the available data on household diarrhea management, however, pertains to acute diarrheal episodes. There is a dearth of knowledge concerning household and caretaker behaviors when the diarrhea is of longer duration. This paper briefly reviews some of what has been learned about household behaviors in the management of acute diarrhea and discusses its relevance for persistent diarrhea. Based upon what has been learned from anthropological studies of acute diarrhea and the little that is known about caretaker behavior during persistent diarrhea, a hypothetical model of the interactions among household behavior and characteristics of diarrheal episodes is presented. The model argues that maternal (or caretaker) concern increases with diarrheal duration, and that changes in behavior, both adaptive and maladaptive, are more likely to occur during an episode of persistent diarrhea, compared to acute. In some cases, these actions may directly influence the outcome of the episode. There is a need to better understand household case management behaviors through the continuum of diarrheal duration and the effect of these behavioral factors on episode outcome. This information is necessary in order to communicate effective messages to caretakers about what they should know and what they should do when persistent diarrhea occurs.     

小儿迁延性、慢性腹泻病83例临床分析

目的 分析小儿迁延性、慢性腹泻病的病因、临床特点及治疗现状.方法 对2002年10月-2007年10月住院并诊断为迁延性、慢性腹泻病83例患儿的临床资料进行回顾性分析.结果 主要病因包括食物过敏29例(85.3%),乳糖不耐受61例(73.5%),免疫功能低下55例(66.3%),感染35例(42.2%)等.长时间腹泻患儿多伴有营养不良,不同程度的离子紊乱、微量元素缺乏、肠道菌群失调等,部分患儿合并其他脏器受累(如心肌、肝脏等).针对病因治疗,同时辅以支持疗法和对症治疗,取得了良好的效果.结论 迁延性、慢性腹泻的病因并不都是感染;其临床表现多样,并发症多;经不同途径联合治疗,可从各个不同环节阻断病情发展,减少并发症,从而缩短病程,提高治愈率.[临床儿科杂志,2009,27(10):930-934]     

Dietary management of acute diarrhea with local foods in a Guatemalan rural community

A community-based, randomized trial was conducted to evaluate a locally available diet for the management of acute diarrhea ( n = 99 episodes) in 90 Guatemalan children, 4–42 months of age. The Test Diet (TD), a combination of a semi-solid pap (maize flour, black beans, oil) and a liquid gruel, Incaparina (maize flour, cotton seed flour, sugar), in addition to breast-milk and other home foods (group TD, n = 45 episodes) was offered for 14 d and compared to usual home feeding (group HF, n = 54 episodes). Diarrhea episodes after admission were significantly shorter for group TD (median 2. 0 d) than group HF (median 4. 4 d, p = 0. 003) after adjusting for potential confounders. Weight gains did not differ significantly between groups. We conclude that community-based dietary management of acute childhood diarrhea using energy-dense, locally available foods is feasible and may shorten diarrhea duration. This may encourage mothers to follow recommendations for continued feeding during diarrhea in developing country environments.     

Immunological background in children with persistent diarrhea in Ghana

BACKGROUND: Persistent diarrheal diseases have become one of the most serious medical problems in developing countries, but few studies have been conducted to determine the risk factors. In the present study, we investigated the nutritional and immunological background in children with persistent diarrhea in comparison with those with acute diarrhea. METHODS: Children with diarrhea who were brought to the Oral Rehydration Salt Clinic of Princess Marie Louise Children's Hospital in Accra were evaluated from an immunological and nutritional aspect. In the follow-up visit, the cases whose diarrhea stopped within 2 weeks after onset were classified into the acute diarrhea group; those with diarrhea lasting more than 2 weeks were classed in the persistent group. Nutritional and immunological data at the initial visit were compared between these two groups. RESULTS: In general, the diarrhea cases had a tendency to undernutrition and impaired cellular immunity compared with healthy control. Persistent cases had lower values for longer half-life, rapid turn-over proteins. Persistent cases had a higher percentage of CD8+ cells and lower CD4/CD8 ratio. CD25 expression in CD4+ cells stimulated by anti-CD3 antibody was lower in the persistent diarrhea group. CONCLUSION: These results appear to support the hypothesis that more severe nutritional status and impairment of cellular immunity is related to the persistence of diarrhea.     

Is small bowel bacterial overgrowth of pathogenic significance in persistent diarrhea?

Bacterial overgrowth in the upper small intestine is postulated to cause persistent diarrhea. We compared the fecal and upper intestinal flora in 82 patients with persistent diarrhea aged 36 months and weight-for-length 90% of National Center for Health Statistics standards (NCHS) and 39 non-diarrheal children with age 36 months, nutritionally matched with the patients and residing in the same environment. In the age groups 12 months and Ygt;12 months the duodenal fluid bacterial counts 10⁵/ml were found with similar frequency in patients and controls for aerobic ( p =0.33; p =0.1) and anaerobic ( p =1.0; p =1.0) bacteria. However, the duodenal isolation rates of any aerobic bacteria ( p <0.05) without regard to counts and Enterobacteriaceae ( p = 0.06) were higher in patients than in controls. Colonization with Enterobacteriaceae was directly correlated with increased stool weight over a 7-day observation period ( p <0.05; p <0.01). One or more pathogens were isolated in the feces of 58% of the patients and 43.8% of the controls. Enteroadherent E. coli of the localized [EAEC-L] ( p <0.01) and aggregative [EAggEC] ( p =0.22) phenotypes were isolated more commonly from the feces of patients. The duodenal fluid detection rates for Klebsiella were significantly greater ( p <0.01) in patients, while Giardia lamblia was detected more commonly in the duodenal fluid of controls ( p <0.01). The presence of specific pathogens in the feces did not seem to be related to the extent of small bowel colonization. Thus small bowel overgrowth with aerobes or anaerobes is common in malnourished children with or without diarrhea. However, specific pathogens such as EAEC-L, EAggEC and Klebsiella may be associated with persistent diarrhea.     

A randomized controlled clinical trial of zinc, vitamin A or both in undernourished children with persistent diarrhea in Bangladesh

In a double-blind randomized controlled clinical trial, moderately malnourished Bangladeshi children (61-75% of the median weight/age) were studied for the effect of zinc and/or vitamin A supplementation on the clinical outcome of persistent diarrhea. Children 6 mo to 2 y of age with diarrhea for more than 14 d were randomly allocated into 4 groups of 24 receiving a multivitamin syrup and (i) zinc (20 mg elemental), (ii) vitamin A, (iii) both zinc and vitamin A, or (iv) neither, in 2 doses daily for 7 d. Clinical data on recovery and on stool output, consistency and frequency were recorded for 7 d, and weight change from day 1 to day 7 was assessed. The baseline characteristics of the four study groups were comparable. The mean daily stool outputs from days 2 to 7 of therapy were significantly less in the zinc and zinc plus vitamin A groups, but not in the vitamin A group, in comparison with the control group. In children receiving zinc, the cumulative stool weight in the 7 d was 39% less than in the control group (p < 0.001) and 32% less than in the vitamin A group (p = 0.006). The cumulative stool weight in the zinc plus vitamin A group was 24% less than in the control group (p < 0.001), but the 14% lower output than in the vitamin A group was not statistically different. The change in body weight over the 7 d study period was significantly different between the group receiving zinc and the control group (+111 g vs -90 g, p = 0.045). The rate of clinical recovery of children within 7 d was significantly greater in the zinc group (88%) compared with the control group (46%, p = 0.002) or vitamin A group (50%, p = 0.005), but not statistically different from the zinc plus vitamin A group (67%, p = 0.086). Conclusion: The results indicate that zinc, but not vitamin A, supplementation in persistent diarrhea reduces stool output, prevents weight loss and promotes earlier recovery.     

Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.     

High-calorie, rice-derived, short-chain, glucose polymer-based oral rehydration solution in acute watery diarrhea

In this study, we have compared the effects of the World Health Organization oral rehydration solution (WHO ORS) and an ORS containing short polymers of glucose (Amylyte ORS) at a high caloric density (five times) and comparable osmolality, on stool output, duration of diarrhea, weight gain and fluid and electrolyte balance, in randomized, open-labeled, controlled clinical trials in five centers. A total of 198 male children (4 months to 10 years) with acute diarrhea (<72 h after onset) were assigned by random allocation to either WHO ORS or Amylyte ORS at five centers in Asia. Children were stratified according to grade of dehydration (mild, moderate or severe) and the initial purging rates during the first 6h (low (<2ml/kg/h), moderate (2–5ml/kg/h) and high (>5ml/kg/h) purgers). The clinical characteristics of the children in the two treatment groups were comparable. Amylyte ORS reduced stool volumes significantly in children with severe dehydration (285.4 ± 74.2 versus 75.5 ±20.0 ml/kg; p < 0.05) and in children with a high initial purging rate (200.3 ±42.8 versus 130.5 ± 9.1 ml/kg; p < 0.05). This was accompanied by a significant (276.4 ±14.6 versus 227.6 ± 11.8 ml/kg; p < 0.01) reduction in ORS requirements in the Amylyte ORS treated group, the effect being greatest in children with severe dehydration (491.5 ± 108.5 versus 155.7 ± 27.3 ml/kg; p < 0.01) or high initial purging rates (394.2 ± 66.2 versus 316.8 ± 34.8 ml/kg; p < 0.05). In mild or moderate dehydration and low or moderate purgers, duration of diarrhea in children treated with Amylyte ORS was not reduced. A significant (p < 0.05) reduction in duration of diarrhea was found in children with severe dehydration (56.4 ± 1.8 versus 34.0 ± 5.6h) or high purging rates (51.5 ± 7.1 versus 38.2 ± 4.8 h). Significantly (p < 0.0001) greater weight gain (520.3 ± 48.5 g versus 228.5 ± 42.1 g) and percent gain in weight (4.8 ± 0.4% versus 2.3 ± 0.4%) were found in children given Amylyte ORS compared with those given WHO ORS. Amylyte ORS rehydrated children with acute diarrhea, reduced stool volume, duration of diarrhea and ORS requirements in children with severe dehydration or high initial purging rates, and improved weight gain. Amylyte ORS has the advantage of containing short polymers of glucose that provide over five times the calories per liter than the glucose-based WHO ORS.     

Evaluation of a maize-cowpea-palm oil diet for the dietary management of Nigerian children with acute, watery diarrhea

A randomized clinical trial was carried out to compare a locally available maize-cowpea-palm oil diet (group MCP) with a commercially produced lactose-free, soy protein isolate formula (group SF) for the dietary management of 69 Nigerian boys, 6–24 months of age, hospitalized for acute, watery diarrhea. Although the treatment groups were generally similar initially, the children in group SF had slightly lower mean weight-for-age z scores ( p = O.OS), lower serum bicarbonate levels ( p = 0.04) and greater stool outputs during the period of rehydration before the diets were initiated ( p = 0.01). Rates of treatment failure in group MCP (5.7%) and group SF (8.8%) were similar ( p = 0.67). There were no significant differences in the adjusted mean stool outputs by study group on days 1–5, but the children in group SF had slightly lower fecal weights on day 6 ( p = 0.05). Children in group MCP had a substantially reduced duration of liquid stool excretion (estimated median duration 42 h versus 140 h; p < 0.001). On the other hand, children in group SF consumed considerably more of their diet, had greater net absorption of macronutrients and greater rates of weight gain than those in group MCP. We conclude that children can safely consume the MCP diet during acute, watery diarrhea without increasing their risk of treatment failure or augmenting stool output. However, the diet may not be adequate as a sole source of nutrients beyond the period of acute illness.     

Prevalence of cryptosporidium in children with acute diarrhea

Cryptosporidium is an intestinal protozoa known to cause diarrhea in animals and more recently has been recognised as a cause of diarrhea in humans. The present study was designed to determine the prevalence of cryptosporidium as a cause of diarrhea in children. Faecal samples of 180 children admitted to the hospital for acute gastroenteritis and from 100 normal children were analysed. Eight out of 180 (4·4%) stools from children with acute diarrhea and none from normal showed cryptosporidi. We conclude that this parasite does play a role in the etiology of human diarrhea.     

The child's disease (Doença de criança): popular paradigm of persistent diarrhea?

According to popular report, the folk illness, Doença de criança (The Child's Disease) is the leading cause of infant and childhood death in Northeast Brazil; most health professionals, however, are unaware it exists. Doença de criança is described based on ethnographic interviews with 50 traditional healers and 50 bereaved mothers whose children have died from the condition. Doença de criança is a sociocultural label developed by the popular medical system and applied to the end stages of severe childhood infectious diseases and malnutrition against a background of grinding poverty. Doença de criança is discussed as an analog to persistent diarrhea. Practical treatment and management implications of this relationship are presented. Doença de criança , most importantly, offers a new, holistic paradigm for the future study of persistent diarrhea.     

儿童迁延性及慢性腹泻病因研究进展

儿童迁延性、慢性腹泻的病程为2周至2个月或超过2个月,是一组多病因导致的临床综合征。本文对其常见病因进行了综述,常见病因包括感染、非特异性炎症性肠病、食物过敏、乳糖不耐受以及抗生素相关性腹泻、神经调节异常、免疫缺陷病、营养不良、乳糜泻、锌缺乏等。     

Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú

In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Perú, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re-infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries.     

布拉酵母菌治疗儿童急性腹泻的多中心随机对照研究

目的 评价布拉酵母菌治疗儿童急性腹泻的疗效及安全性.方法 采用多中心、随机、对照研究方法.对象为儿科门诊年龄在1个月～8岁之间、病程在48 h内、镜下大便白细胞<10个/HP、未使用任何抗腹泻治疗方法的急性腹泻患儿共137例,随机分组分别给予布拉酵母菌或双八面体蒙托石口服,治疗5 d后判断疗效.结果 共有134例完成本试验,治疗后48 h大便好转率双八面体蒙托石组为69.35%,布拉酵母菌组为84.00%;治疗后72 h愈合率双八面体蒙托石组为53.22%,布拉酵母菌组为60.00%;患儿平均止泻时间双八面体蒙托石组约3.58 d,布拉酵母菌组为3.12 d;病程在7 d以内的患儿比率均超过85%;两组患儿的止泻时间和腹泻病程差异无统计学意义.所有病例未发生明显不良反应或过敏反应.结论 布拉酵母菌治疗急性腹泻的疗效等同于双八面体蒙托石,且无任何不良反应发生,布拉酵母菌作为治疗腹泻病的新型药物,可于临床应用.