Methods of analysis of enteropathogen infection in the MAL-ED Cohort Study.

Studies of diarrheal etiology in low- and middle-income countries have typically focused on children presenting with severe symptoms to health centers and thus are best equipped to describe the pathogens capable of leading to severe diarrheal disease. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study was designed to evaluate, via intensive community surveillance, the hypothesis that repeated exposure to enteropathogens has a detrimental effect on growth, vaccine response, and cognitive development, which are the primary outcome measures for this study. In the setting of multiple outcomes of interest, a longitudinal cohort design was chosen. Because many or even the majority of enteric infections are asymptomatic, the collection of asymptomatic surveillance stools was a critical element. However, capturing diarrheal stools additionally allowed for the determination of the principle causes of diarrhea at the community level as well as for a comparison between those enteropathogens associated with diarrhea and those that are associated with poor growth, diminished vaccine response, and impaired cognitive development. Here, we discuss the analytical methods proposed for the MAL-ED study to determine the principal causes of diarrhea at the community level and describe the complex interplay between recurrent exposure to enteropathogens and these critical long-term outcomes.

Intraperitoneal migration of epicardial pacemakers.

Intraperitoneal migration of epicardial leads and abdominally placed generators is a potentially serious complication. We report the case of an 83-year-old man who experienced intraperitoneal migration of an epicardial pacing system and consequent small-bowel obstruction. Laparotomy was required in order to free constrictive lead adhesions. The patient's postoperative recovery was satisfactory after the placement of a new pacemaker generator in the abdominal wall. Predisposing factors are analyzed and the literature is reviewed in order to clarify the mechanisms of sequelae associated with the migration of epicardial pacemakers from the abdominal wall. To the best of our knowledge, this is the 1st report of pacemaker migration having caused bowel obstruction that required urgent laparotomy in an adult.

Diarrea con sangre.: Etiología y tratamiento antibiótico en niños asistidos en el Centro Hospitalario Pereira Rossell. Enero 2003-abril 2004

Introducción: la diarrea con sangre continúa siendo un motivo frecuente de consulta y de internación. Constituye aproximadamente el 15% de todos los casos de diarrea, siendo su morbi-mortalidad elevada. Shigella spp es el germen más frecuentemente aislado. De acuerdo a lo recomendado por la Organización Panamericana de la Salud, la Organización Mundial de la Salud y otros autores, se recomienda el tratamiento antibiótico, ya que si se trata de Shigella se logra mejoría de los síntomas, prevención de complicaciones y disminución de excreción fecal. La elección del antibiótico constituye un problema dada la creciente resistencia de este agente. Objetivo: describir los hallazgos microbiológicos, y analizar la aplicación de la recomendación en los niños asistidos en el Centro Hospitalario Pereira Rossell. Material y métodos: se realizó una revisión retrospectiva de las historias clínicas que incluyó todos los niños asistidos por diarrea con sangre en el HP-CHPR, entre el 1 de enero de 2003 y el 1 de abril de 2004. Se revisaron: edad, criterios de internación, resultado de coprocultivo, antibióticoterapia y evolución. Resultados: en el año 2003 fueron asistidos 498 pacientes con diagnóstico de diarrea con sangre. De estos ingresaron 102 menores de 1 año que representaron el 30% de los ingresos por diarrea (n = 344). Durante los tres meses del 2004 se asistieron 1180 niños con diagnóstico de diarrea, de los cuales 202 (17,1%) presentaban diarrea con sangre. De estos ingresaron 52 (25,7%) que eran menores de un año, representando el 22,3% de los ingresos por diarrea (n=233). Se obtuvieron 700 coprocultivos, siendo negativo en 638 (91%). Se aislaron 51 S. flexneri, tres S. sonnei y ocho Salmonella sp., en ambos períodos. Todos los pacientes hospitalizados recibieron ceftriazona intravenosa. En los pacientes tratados en forma ambulatoria (n=546), los antibióticos utilizados fueron: azitromicina en 283 pacientes, trimetroprim-sulfametoxasol en 193, cefuroxime-axetil 18, amoxicilina en dos. 50 niños no recibieron tratamiento antibiótico. No falleció ninguno de los 700 pacientes incluidos en esta serie. Conclusiones: Shigella flexneri sigue siendo el germen más frecuentemente aislado en nuestro medio. Ningún paciente falleció. Será necesario continuar la vigilancia clínico-microbiológica para continuar mejorando el tratamiento de estos niños.

Introduction: bloody diarrhea is still a frequent cause of hospitalization. It constitutes 15% approximately of all cases of diarrhea. The morbimortality is high. Shigella spp is the agent most frequently isolated. OMS/OPS and others authorities recommend antimicrobial therapy because symptoms are diminished; it prevents complications and shortens its excretion. The selection of an antibiotic is complicated by the increased resistance found. Objective: to describe microbiologic findings and analyse the application of the recommended treatment in hospitalized children. Material and methods: a retrospective revision of all patients hospitalized with bloody diarrhea from January 1st 2003 til April 1st 2004, was realized. Age, admission criteria, stool culture results, evolution, and antimicrobial therapy were the aspects analyzed. Results: 498 patients with bloody diarrhea were assisted in 2003. Of these, 102 were less than a year old, representing 30% of admissions by diarrhea (n= 344). During the first three months of 2004, 1180 children with diarrhea were assisted; 202(17.1%) had bloody diarrhea. 52 (25.7%) were infants less than a year old, representing 22.3% of hospitalizations due to diarrhea (n=233). 700 stool cultures were obtained; 638(91%) were negative. 51 S. flexneri, 3 S. sonnei, and 8 Salmonella sp were isolated in both periods. All admitted patients were treated with ceftriaxone. Non-hospitalized patients( n=546 ) received: azithromycin( 283 ), trimethoprim ( 193 ), cefuroxime axetil( 18 ), amoxicillin( 2 ). 50 patients didn't receive antibiotics. None of them died. Conclusions: S. flexneri is still the most frequently isolated agent. No patient died. Clinical and laboratory surveillance is necessary in order to improve treatment.

Mothers' management of childhood diseases in Yorubaland: the influence of cultural beliefs.

Several studies have noted that, besides inadequate availability of health care services in many areas, especially the less developed countries, certain disease-specific and non-disease-specific cultural beliefs may influence people's health seeking behaviour. It has even been noted that health services may be underutilized and several health and child care instructions may be ineffective or ignored in traditional and transitional societies where people's ideas and behavioural patterns conflict with the knowledge being passed to them (Feyisetan and Adeokun 1992; Feyisetan 1992). Feyisetan and Adeokun (1992) argued that non-adoption of modern preventive and curative measures cannot be attributed to poverty alone since the costs of some preventive and curative measures are not exorbitant in several of these societies. Rather, they suggested that the gap between awareness of modern health measures and health seeking behaviour must be sought in the social and cultural determinants of behaviour in such matters as child care and disease management. Earlier studies have noted that children in Nigeria die mainly from malaria, diarrhoea, measles, neonatal tetanus, whooping cough, tuberculosis, and bronchopneumonia (Morley and MacWilliam 1961; Ogunlesi 1961; Morley, Woodland and Martin 1963, 1966; Baxter-Grillo and Leshi 1964; Animashaun 1977; Tomkins 1981). Because these diseases are preventable at low cost to the individual, there is a need to investigate why large percentages of children are still subjected to many episodes of these diseases. In this paper, we examine (1) the mothers' perceptions of the aetiology of the three most cited childhood diseases in our study areas, measles, diarrhoea and fever, and the effect of these perceptions on the mothers' suggested curative measures; and (2) the persistence of the belief in abiku and how this cultural belief can influence mothers' management of childhood diseases. Since, for most mothers, perceptions of the aetiology of the childhood diseases are rooted in cultural beliefs, a brief review of disease-specific cultural beliefs is undertaken. In order to determine the effect of socio-economic factors, the mothers' perceptions of the aetiology of the childhood diseases, their recommended curative measures and the belief in abiku are examined according to selected socio-economic variables.

PIP: This study examines data from a two-round survey undertaken in September 1991 and April-May 1992 in Nigeria to reveal the "Impact of Cultural Beliefs and Practices on Child Health among the Yoruba." Data were analyzed to determine 1) mothers' perceptions of the etiology of measles, diarrhea, and fever and the effect of these beliefs on which curative measures they suggested and 2) the persistence of the belief in "abiku" (special children who have come from the spirit world and can die at will unless certain rituals are performed) and how this belief can influence the way mothers manage childhood diseases. The data for this study, collected via formal interviews with 1559 respondents supplemented by in-depth interviews and focus group discussions, were submitted to simple cross tabulation and logistic regression analysis. It was found that 1) many of the mothers lack accurate information about the causes of the selected childhood diseases, especially measles; 2) many of the mothers nevertheless recommended modern curative methods; 3) the belief in abiku remains strong among these mothers; and 4) the curative measures adopted by a mother may depend upon whether the sick child is believed to an abiku. Over half of the mothers believed that an abiku required treatment from traditional healers and religious institutions irrespective of the nature of the illness. Thus, the probability of a child receiving modern curative treatment depends upon whether or not that child is perceived to be abiku. This study underscores the need to consider local beliefs and practices when implementing health policies.

Epidemiological study on infectious diarrheal diseases in children in a coastal rural area of Kenya.

Diarrheal diseases are major causes of morbidity and mortality among children in developing countries. We have analyzed the causative agents of diarrhea in children under five years of age who resided in rural environments but attended a hospital in Malindi, a coastal town in Kenya. Bacterial diarrhea was found in 239 (27.7%) of 862 patients with diarrhea. Diarrheagenic Escherichia coli, including enteropathogenic, enterotoxigenic, and enterohaemorrhagic strains, was isolated from 119 (13.8%) patients, followed by Salmonella spp. (63 cases, 7.3%) and Shigella spp. (56 cases, 6.5%). Intestinal parasites were found in 109 (12.6%) of the patients. Entamoeba histolytica and Giardia lamblia were found in 67 (7.8%) and 42 (4.9%) of the cases, respectively. Rotavirus was found in 69 (16.1%) of 428 cases, a part of the 862 cases. Significant differences in age distribution were seen in diarrheal cases due to Campylobacter spp., G. lamblia, and rotavirus. No significant seasonal incidence of specific pathogens was found, but the number of diarrheal patients was significantly correlated to rainfall. Drinking water was contaminated with bacteria at concentrations ranging from 10(3) to 10(6) CFU/ml in 98% of the households and by coliform bacteria at concentrations of 10(2) to 10(5) CFU/ml in 72% of the households. These results suggest that the main routes of infection may be contaminated drinking water and fecal-oral transmission of enteric pathogens. Consequently, we propose that the enhancement of hygienic practice through health education is a feasible control measure of diarrhea in the study area.

Clinicopathogenic studies of acute diarrhea in children.

AIM: To identify etiologic pathogens of acute diarrhea in children and to determine the diagnostic value of stool pH. METHODS: From May 1988 to April 1992, 368 children with acute diarrhea were studied. Fresh stools were routinely examined, and stool pH was tested with pH paper. Samples were placed in Cary-Blair culture medium and were sent to the lab for bacterial isolation and identification. Rotavirus was identified in the supernatant by ELISA. RESULTS: Thirty-one pathogens and 385 bacterial strains were found in the 368 samples, with a detection rate of 67.7%, including 37.8% of mixed infections. Among the bacteria families, vibrionaceae was the most common (39.7%), and among bacteria genera, aeromonas was the most common (26.8%). In bacterial diarrhea, stool pH tended to be basic, while in viral diarrhea it tended to be acidic. CONCLUSION: There are 31 pathogens for children's acute diarrhea in this area. It is quite difficult to make an etiologic diagnosis only by clinical signs. However, stool pH is of some value for early disease diagnosis.

Microbiology of HIV associated bacteraemia and diarrhoea in adults from Nairobi, Kenya.

We undertook a retrospective descriptive comparison of the spectrum of pathogens responsible for bacteraemia and diarrhoea in HIV antibody positive and negative patients over 4 years (1988-92), in Nairobi, Kenya. The study population was recruited from primary to tertiary centres of clinical care and consisted of 2858 adults (15 years or older). There were 415 significant blood culture isolates, 192 from 1785 HIV negative patients and 223 from 953 HIV positive patients. There were 233 significant faecal isolates, 22 from 115 HIV negative patients and 211 from 531 HIV positive patients. The most common pathogens detected in blood were Streptococcus pneumoniae and Salmonella typhimurium and in faeces Shigella flexneri, S. typhimurium and Cryptosporidium parvum. The agents causing illness in HIV positive patients in Nairobi are similar to those prevalent in the HIV negative community and the investigation of a febrile illness with or without diarrhoea in an HIV positive patient should reflect this.

PIP: Researchers conducted a retrospective analysis of stool specimens from 646 adult patients and of blood cultures from 2738 adult patients to examine the etiology of opportunistic infection in HIV-positive individuals in Nairobi, Kenya, and to compare this etiology with the range of pathogens causing disease in the HIV-negative population. Adults at least 15 years old contributed the stool and blood samples that were received at the Wellcome Trust-Kenya Medical Research Institute during 1988-92. The 415 significant blood culture isolates comprised 192 from 1785 HIV-negative patients and 223 from 953 HIV-positive patients. The most frequently detected pathogens in blood included Streptococcus pneumoniae (58 in HIV-positive cases and 25 in HIV-negative cases) and Salmonella typhimurium (56 in HIV-positive cases; 5 in HIV-negative cases). There were 233 significant stool isolates, 211 from 531 HIV-positive patients and 22 from 115 HIV-negative patients. 20 blood cultures and 21 stool cultures had more than 1 significant pathogen. The most commonly detected organisms in the stools were Shigella flexneri (49 for HIV-positive cases and 9 in HIV-negative cases), S typhimurium (40 in HIV-positive cases and 3 in HIV-negative cases), and Cryptosporidium parvum (45 in HIV-positive cases and 0 in HIV-negative cases). With two exceptions, the spectrum of pathogens associated with infection in HIV-positive patients was the same as that for HIV-negative patients. Physicians should consider this when they investigate and manage febrile illness with or without diarrhea in an HIV-positive patient.

Oral rehydration therapy.

PIP: Oral rehydration solution (ORS), the best treatment of dehydration due to acute diarrhea, is the most important medical advance of this century since it is key to reducing infant and child morbidity and mortality. Pathogens responsible for acute diarrhea include those which produce enterotoxin at the intestinal mucosal surface, inducing secretion but are not invasive (e.g., Vibrio cholerae); those which invade and disrupt the mucosal lining (e.g., shigella species); and rotavirus. The World Health Organization (WHO)/UNICEF ORS is considered a universal ORS. Much research has been done on the ideal composition of an ORS. An ORS must have sufficient sodium to replace losses on a volume to volume basis, a glucose concentration that matches that of sodium to ensure its delivery to the ileum, sufficient amounts of potassium and base (e.g., sodium bicarbonate or trisodium citrate dihydrate) to correct acidosis and to enhance sodium absorption, and sufficient amounts of liquid. The risk of hypernatremia with use of the WHO/UNICEF ORS is a concern since infants and young children have an immature renal concentrating capacity, increased insensible water losses, and an impaired natriuretic response. Neonates and young infants may be prone to relatively slow correction of acidosis. It appears that the potassium content (20 mmol/l) of WHO-ORS should be higher to promote a net positive potassium retention. Too much glucose in the ORS will induce reverse osmosis of water into the gut, effectively making the ORS a dehydrating solution rather than a hydrating solution. Some carbohydrates other than glucose have proven effective glucose substitutes (e.g., sucrose, rice starch and powder, other cereals). Cereals have higher acceptability levels in developing countries. Research is investigating the nutritional benefits of supplementing ORS with micronutrients (e.g., vitamin A, folic acid, and zinc). ORS use with early refeeding has a beneficial effect on nutritional status after an acute diarrhea episode.^ieng

Understanding of hygiene behaviour and diarrhoea in two villages in Botswana.

This paper describes a study which took place in two villages in north-east district of Botswana from July 1990 through July 1991. Qualitative data collection methods were used including: observations, key-informant interviews, focus groups, and in-depth interviews. The data were used for understanding and interpreting the cultural belief systems regarding specific hygiene behaviours and diarrhoea, with emphasis on hand washing. Hand washing was said to occur for three main reasons: to remove contamination, for social reasons, and for comfort reasons. Sources of dirt on the hands included human blood and faeces. Many perceived causes of diarrhoea were identified, including pogwana (dehydration associated with sunken anterior fontanelle). Traditional concepts regarding the treatment and prevention of diarrhoea were also identified. It is suggested that beliefs surrounding hygiene behaviour and diarrhoea should be incorporated into health education programmes.

PIP: During July 1990 to July 1991, in northeastern Botswana, focus groups, observations, and interviews were conducted in two villages largely inhabited by people from the Tswana and Kalanga tribes. Researchers examined hygiene behaviors (especially hand washing) and attitudes towards infantile diarrhea in these villages. Villagers considered hand washing after defecation to be a modern idea. Hand washing was not always done, especially if one went into the bush to defecate. People considered it more important to wash hands before meals. Identified sources of contamination were one's own body (through scratching, touching oneself while urinating, blowing the nose, hands [especially the left hand], blood [especially menstrual blood], and adult feces), soil, weeds, chicken feces, laundry water, and sometimes dish-washing water, but not cow dung and mud. Hand washing after touching each source was not always done. The focus groups identified a list of words for diarrhea in Setswana and Kalanga so health workers could track diarrhea morbidity. Both languages had a word for diarrhea that characterized the condition as having more frequent stools than usual and being affected by general ill health. Pogwana referred to dehydration associated with sunken anterior fontanelle. Many mothers did not know the cause of diarrhea. Some perceived causes of diarrhea were worms in the brain or in the stomach, a bewitched child, malnutrition, teething, watermelons, contaminated water or food, or cold weather. Ways to prevent diarrhea identified by the traditional healer included not feeding the child dirty food, not storing cooked food overnight, not giving too many different foods each day, and keeping yards swept. Diarrhea treatment options were: take the child to the clinic right away; visit a faith or traditional healer; and treat the child at home with oral rehydration salts, a home-made sugar/salt solution, or a traditional herb tea. All mothers mentioned additional fluids. Traditional healers sometimes used enemas. These findings suggest that health education programs should incorporate the beliefs revolving around hygienic behavior and diarrhea.

Cryptosporidiosis in children seen at the children's clinic of Yekatit 12 Hospital, Addis Ababa.

The stools of 214 children under five years of age with diarrhoea were examined for Cryptosporidium oocysts using the Modified Ziehl Nelson Technique. Twelve (5.6%) of the children had Cryptosporidium oocysts in their faeces. All of these were above 6 months of age and were either partially or fully weaned. There were 15 exclusively breast fed children of whom 11 were less than 6 months of age. None of these cases had the evidence of Cryptosporidial infection. The present study indicates the importance of Cryptosporidium as a possible etiologic agent in patients with diarrhoeal diseases. However, a comprehensive investigation is needed in order to rule out other enteropathogens.

PIP: During March 1992 to March 1993, in Addis Ababa, Ethiopia, health workers collected stool samples from 214 children under 5 years old with diarrhea who were attending the children's clinic of Yekatit 12 Hospital. The prepared thin smears were microscopically examined for Cryptosporidium oocysts at 40x and 100X magnifications. 12 (5.6%) children 1-43 months old (7 boys, 5 girls) had Cryptosporidium oocysts. Nine children had watery diarrhea. The other 3 had watery mucoid diarrhea. Nine children had vomiting. All 12 children had a temperature somewhat higher than 38 degrees Celsius. They were either partially or fully weaned. 15 children with no Cryptosporidium oocysts were exclusively breast fed. The last two statements suggest that, in children with diarrhea, there is an association between breast feeding and Cryptosporidium infection. 11 of the 15 patients with no oocysts were less than 6 months old.

Rotavirus diarrhoea in Thai infants and children.

One hundred and three children aged from 1 month to 5 years were assessed for human rotavirus (HRV) infection over a 5-week period at Children's Hospital, Bangkok. HRV was present in 18% and adenovirus in 10.7% of the children with gastro-enteritis. None of the controls excreted HRV. Vomiting and dehydration were significantly associated with HRV diarrhoea. A comparison of the reliability of the detection methods showed the following sensitivities: RNA-polyacrylamide gel electrophoresis (PAGE) 90%, electron microscopy (EM) 84% and Rotascreen latex particle agglutination (LPA) 80%. PAGE and EM were 100% specific while the Rotascreen LPA was 81% specific. Rotascreen LPA gave 15.5% false positive results. Of the HRV positive samples analyzed by PAGE, 5.3% and 94.7% were of subgroups I and II, respectively. The ID enzyme immunoassay and PAGE are reliable and inexpensive methods which can be recommended for HRV detection, particularly in areas with little technical support.

PIP: During July 6-August 2, 1990, at the outpatient clinic at Children's Hospital in Bangkok, Thailand, pediatricians recruited the first 5-7 children aged less than 5 with acute diarrhea to a study to determine the incidence, clinical presentation, and severity of human rotavirus (HRV) diarrhea during the monsoon season. The study also aimed to examine the reliability of the detection methods for HRV and the different HRV electropherotypes. 103 cases of gastroenteritis were compared with 44 controls. 17% of cases had a household diarrheal contact. 18% of cases excreted HRV, while none of the controls did. 69% of HRV cases were infants. Vomiting and moderate dehydration occurred significantly more often in HRV cases than non-HRV cases (84% vs. 57% and 47% vs. 12%, respectively; p 0.05). HRV cases were more likely to receive intravenous fluids than non-HRV cases (47% vs. 19%; p 0.01). The researchers used IDEIATM ELISA as the standard for comparison with other screening methods since it is highly reliable. Electron microscopy (EM) and polyacrylamide gel electrophoresis (PAGE) had the highest sensitivity and specificity levels (84 and 90 vs. 80 for latex particle agglutination [LPA] and 100 vs. 81 for LPA, respectively). PAGE found 94.7% of HRV positive samples were of subgroup II and 5.3% of subgroup I. Nine different HRV electropherotypes were identified. EM identified adenovirus in 11 cases. These findings suggest that IDEIATM ELISA and PAGE can be both diagnostically and epidemiologically useful for HRV infection in areas with limited access to expensive equipment.

Severe illness in African children with diarrhoea: implications for case management strategies.

To identify clinical disorders associated with severe illness in African children with diarrhoea, we studied a group of under-5-year-olds with diarrhoea who had been brought to a large public hospital in central Cote d'Ivoire. The general condition of children with diarrhoea was assessed and classified according to criteria recommended by WHO, and then used as a nonspecific indicator of severity. Of the 264 children with diarrhoea who were enrolled in the study, 196 had nonsevere illness and 68 severe illness. Children with severe illness were significantly more likely than those with nonsevere illness to be dehydrated (45% versus 11%), moderate-to-severely wasted (47% versus 29%), bacteraemic (26% versus 9%), severely anaemic (haemoglobin level <6 g/dl; 15% versus 6%), have Plasmodium falciparum parasitaemia (27% versus 14%), and have two or more of these five conditions (60% versus 14%). Nontyphoidal Salmonella spp. were present in 68% of the blood isolates but were not associated with seropositivity to human immunodeficiency virus (HIV). The study demonstrates the need for a more comprehensive approach to assessment and management of children with diarrhoea that ensures prompt recognition of bacteraemia, anaemia, wasting and malaria, as well as dehydration. Simple nonspecific observational criteria, such as those recommended by WHO for assessing and classifying general condition, are useful for identifying children with diarrhoea who are at high risk of having life-threatening clinical disorders, and can readily be used by health workers whose clinical training and access to diagnostic laboratory facilities are both limited.

PIP: Researchers prospectively studied 264 children aged less than 5 years with diarrhea who were admitted to the Bouake Regional Hospital Center in the Ivory Coast between June 10 and August 11, 1991, to identify clinical disorders associated with severe diarrhea. They compared data on the 196 children with non-severe diarrhea with data on 68 children with severe diarrhea. All but three of the children were breast fed. The severely ill children were more likely than the non-severely ill children to have dehydration (45% vs. 11%; p 0.01), severe wasting (22% vs. 7%; p 0.01), anemia (29% vs. 13%; p = 0.01), bacteremia (26% vs. 9%; p 0.01), and malarial parasitemia (27% vs. 14%; p = 0.02). 68% of the blood isolates had nontyphoidal Salmonella spp. 6% of children had HIV-1 or HIV-2 infection. The most common pathogens in the stool specimens were rotavirus (41 cases), Campylobacter jejuni (22), Shigella spp. (21), and Salmonella spp (10). These findings indicate a need for a more comprehensive approach to assessment and management of children with diarrhea that secures immediate recognition of bacteremia, anemia, wasting, malaria, and dehydration.

Diagnostic strategies in HIV-infected patients with diarrhea.

PIP: Infectious disease specialists have proposed guidelines on diagnostic evaluation of HIV infected patients with diarrhea. They are based on using clues from a careful history, physical examination, and evaluation of known laboratory data. Early on, clinicians must differentiate between small and large bowel diarrhea to properly evaluate any patient with diarrhea. If available, they should use the patient's absolute CD4 count, duration of diarrhea, frequency and characteristics of stools, degree of weight loss, and exposure history (e.g., residence and water supply). When conducting the patient history, clinicians should ask about recent antibiotic or antiretroviral use, previous opportunistic infections, and other illnesses or hospitalizations. The physical exam should include height and weight, orthostatic blood pressure, and degree of wasting. Abnormalities of skin and mucous membrane may indicate nutrient deficiencies (e.g., vitamin B deficiency = stomatitis). The disease specialists provide us with an algorithm to the diagnostic evaluation of HIV infected patients with diarrhea using the CD4 cell count and the type of diarrhea (small or large bowel) as the defining factors. For example, clinicians should request stool cultures for Salmonella, Campylobacter, and Yersinia and examination with saline and iodine for the presence of ova and parasites for patients with CD4 counts greater than 200 cells x 1 million/l and small bowel diarrhea. If the patient also has a fever, blood cultures should be done to test for Salmonella. If all these tests are negative and the patient still has symptoms, modified acid-fast staining should be done to look for cryptosporidium oocysts. If this test is negative and symptoms continue, upper endoscopy with biopsy is warranted. This strategy should result in a less time-consuming and more directed diagnostic strategy that may improve quality of life.^ieng

Asymptomatic Shigella infections in a cohort of Mexican children younger than two years of age.

The proportion of Shigella infections that occur asymptomatically in young children has not been established. A community-based cohort study of 367 infants was followed prospectively by weekly home visits from January, 1990, through December, 1991. Stool samples were collected weekly and when diarrhea occurred and were tested for Shigella and other enteropathogens. There were 2925 child months of observation and 65 episodes of Shigella infection. There were 3.1 episodes/100 child months during the warm season (May through September) and 0.97 episode/100 child months during the cold season. Shigella infections were rare during the first 6 months of life but increased with age (P < 0.0001). Overall 55% of detected infections were asymptomatic. The proportion of infections that were asymptomatic increased as age increased (P < 0.01). Symptom status was not significantly associated with Shigella species or season. All isolates from symptomatic and asymptomatic children had the 120- to 140-megadalton virulence plasmid. We conclude that infections with virulent strains of Shigella are commonly asymptomatic in Mexican children during the first 2 years of life.

PIP: During January 1990-December 1991, each week, field workers visited the home of 367 children aged 0-24 months from a periurban area southwest of Mexico City (San Pedro Martir and San Andres Totoltepec, Tlalpan) and collected stool specimens from them to determine whether Shigella infections are often asymptomatic. The crude incidence rate of diarrhea, regardless of etiology, was 29 episodes/100 child months during the warmer and rainy months (May-September), while it was 21 episodes/100 child months for the rest of the year (October-April) (relative risk [RR] =1.38). 53 of all children (l4%) had 65 Shigella infections. The overall monthly incidence of symptomatic and asymptomatic Shigella infection was higher during May-September than October-April (3.13 vs. 0.97 episodes/100 children; RR = 3.22). 55% of all Shigella infections (36) were asymptomatic. 32% developed secretory-type diarrhea and 13% had blood present in the stool. The incidence of Shigella infections grew as did the age (0.4-8.2 episodes/100 child months for 0-6 month olds to 18-24 month olds; p 0.0001). The proportion of asymptomatic Shigella infections also increased with age (33% for 0-6 month olds, 40% for 7-12 month olds, 46% for 13-18 month olds, and 78% for 18-24 month olds; p 0.01). Shigella sonnei, S. flexneri, and S. boydii were the only species detected. The 120-140 megadalton virulence plasmid was present in all isolates from asymptomatic and symptomatic children. Mixed infections were rather common in both asymptomatic (47%) and symptomatic (45%) children. Among infants aged less than 12 year months, breast feeding infants were less likely to be infected with Shigella than nonbreast feeding infants (RR = 2.41). On the other hand, among children aged 12-24 months, nonbreast feeding was associated with a lower risk of Shigella infection (RR = 0.69). These findings show that Shigella infections in Mexican children aged 0-24 months range from asymptomatic infections to secretory diarrhea to bloody diarrhea.

Enteropathogens associated with acute diarrhoeal diseases.

PIP: Five types of Escherichia coli are responsible for as much as 25% of all diarrheal diseases in developing countries. They tend to be transmitted via contaminated foods, particularly weaning foods, and water. They include enterotoxigenic, enteropathogenic, enteroadherent, enteroinvasive, and enterohemorrhagic E. coli. Shigella species are responsible for 10-15% of acute diarrheas in children less than 5 years old and the most common etiologic agents of childhood dysentery. Shigellosis is common in the warm season. An outbreak of shigella dysentery in West Bengal, India, had a high attack rate in children less than 5 years old and was resistant to many drugs. Nontyphoid Salmonella species cause watery diarrhea with nausea, cramps, and fever. Worldwide, various Salmonella strains exhibit resistance to ampicillin, chloramphenicol, and co-trimoxazole. Campylobacter jejuni produces watery diarrhea which, in 33% of cases and 1-2 days after onset, contains blood and mucus. Many normal healthy children in developing countries are carriers of C. jejuni. Vibrio cholerae O1 is endemic in parts of Africa and Asia (e.g., 5-10% of hospitalized diarrhea patients). The ElTor cholera biotype is responsible for the 7th pandemic. Other bacterial enteropathogens are Aeromonas species, Bacteroides fragilis, and Providencia alcalifaciens. Rotavirus is a major cause of sporadic and epidemic diarrhea among 6-23 month olds. Its incidence peaks in cold or dry seasons. Other viral enteropathogens are Norwalk virus, adenoviruses, astroviruses, and coronaviruses. In India, the prevalence of Entamoeba histolytica varies from 3.6% to 47.4%. It occurs equally in high and low socioeconomic classes. Giardia lamblia usually infects 1-5 year old children. Its transmission routes are food, water, and the fecal-oral route. Cryptosporidia produce acute watery diarrhea, especially in children less than 2 years old. Cryptosporidia diarrhea is common among AIDS patients. Oral rehydration therapy and proper feeding during and after diarrhea reduces deaths from diarrhea.^ieng

Usefulness of ORT in certain special situations of diarrhoeal diseases.

PIP: Diarrhea is one of the most common causes of morbidity and mortality in infants and children less than 5 years old in developing countries. Diarrheal diseases are a major cause of childhood malnutrition. Toxin-producing bacteria are responsible for many acute diarrheas. Oral rehydration solution (ORS) treats dehydration caused by acute diarrheal episodes. WHO promotes the use of a single oral rehydration formula which contains 3.5 g sodium chloride, 2.5 g sodium bicarbonate or 2.9 g trisodium citrate dihydrate, 1.5 g potassium chloride, and 20 g glucose to 1 liter of water. This ORS formula can safely be used for all age groups and all etiologies of diarrhea. ORS replaces the lost fluid and electrolytes and maintains fluid and electrolytes. Pediatricians in most developed countries do not accept this ORS formula in cases of rotavirus-caused diarrhea because rotavirus blunts some absorptive villi and reduces the activity of lactase and other disaccharidase, resulting in reduced absorption. Yet, the unaffected villus cells may absorb enough water and electrolytes to be effective. In cases of vomiting, ORS should be administered in small amounts and slowly. Some health workers are concerned that 90 mmol/l sodium in the WHO formula causes hypernatremia in neonates and young infants who have low sodium levels in their stools. Specialists suggest ORS with 30-60 mmol/l or additional water administered in a 2:1 ratio for these young infants. Hypernatremia is also a concern for malnourished children, but studies show that WHO's ORS is safe and effective in treating malnourished children. Bottle fed children are more vulnerable to hypernatremia than breast fed children. Hypernatremia has neurological effects. Hyponatremia is more common in developing countries than developed countries. It also has neurological effects. In severe dehydration cases, intravenous fluid or ORS delivered via a nasogastric tube should be given immediately.^ieng

An outbreak of diarrhoea associated with rotavirus serotype 1 in a day care nursery in Rio de Janeiro, Brazil.

Faeces from 17 children less than 1.6 years old and 15 adults more than 22 years old were collected during an outbreak of gastroenteritis in a day care nursery and screened for the presence of adenovirus and rotavirus by enzyme immunoassay (EIARA) and other viruses by electron microscopy (EM) and polyacrylamide gel electrophoresis (PAGE). Ten samples (58.8%) from children and one (6.7%) from adults were positive for rotavirus and all samples were negative for bacteria and parasites. No other viruses were observed in EM. An enzyme immunoassay test using monoclonal antibodies (MAb-EIA) to determine the subgroup(s) and the serotype(s) of rotavirus was performed and the results showed that all positive samples belong to serotype 1, subgroup II of group A rotaviruses. In PAGE test all samples had the same profile and the 10 and 11 dsRNA segments corresponded to the "long" profile of group A of rotaviruses. These results corroborated the MAb-EIA results and indicate a sole source of infection. The major symptoms observed were: vomiting (60%), fever (70%) and diarrhoea (100%). In previous years (1989 to 1991) we observed only rotavirus serotype 2 in this same day care nursery, but no outbreak was reported.

PIP: Acute gastroenteritis in children under 5 years of age is caused mainly by rotaviruses. Severe dehydration is commonly associated with this condition, which may lead to death if left untreated. Epidemiologic studies have attempted to describe the etiology of acute gastroenteritis caused by rotaviruses; however, much is still not understood. This paper describes a diarrhea outbreak in a children's day care center in Brazil that was caused by rotavirus serotype 1, subgroup II. 17 infants and 15 adults had their feces virologically analyzed. Rotavirus-positive samples were analyzed by enzyme immunoassay (EIA). Bacteriological analysis was performed after culturing. All samples were negative for both parasites and pathogenic bacteria. Rotavirus was found in 10/17 (58.8%) of the infant and in 1/15 (6.7%) of the adult fecal samples tested. The major clinical symptoms observed in rotavirus-positive children were fever (70%), vomiting (60%), and diarrhea (100%).

[Etiology of acute diarrhea in children]. / Etiologie de la diarrhée aigue de l'enfant.

PIP: 170 children aged a few days to six years underwent outpatient examinations at a maternal-child health center in Tunis for acute diarrhea between July and September 1986. Examination and analysis of stool samples led to positive identification of etiology in 59 cases, or 34.5%. 27 cases were of bacterial origin, including 4 cases of salmonella, 7 of shigella, 8 of campylobacter, and 8 of E. coli. 21 cases of rotavirus were isolated, including 2 in which campylobacter were also observed, and one each in which E. coli and giardia were observed. Giardia were observed in 10 cases and ascaris in 1 case. 78% of the children were under two years old, 16% were two to four, and 6% were four to six. Most of the patients were from socioeconomically disadvantaged social strata. There were 91 boys and 79 girls. Among the 170 children, 3 were treated for moderate dehydration as outpatients and one was hospitalized with severe dehydration. 84 children without diarrhea and aged under six months served as controls. A positive etiology was found in 7.1% of controls, including 1 of campylobacter, 4 of rotavirus, and 1 of Giardia.^ieng

Epidemiologic studies of Escherichia coli diarrheal infections in a low socioeconomic level peri-urban community in Santiago, Chile.

The incidence of diarrhea due to six categories of diarrheogenic Escherichia coli was determined in two pediatric cohorts in a low socioeconomic level community in Santiago, Chile, with access to chlorinated water. An age cross-sectional cohort of 340 children aged birth to 47 months was assembled. A newborn cohort was assembled by enrolling 10-12 newborns monthly for 12 months. Episodes of diarrhea were detected by twice weekly household visits. E. coli from stool cultures of cases and matched controls were hybridized with DNA probes specific for enterotoxigenic, enteroinvasive, enteropathogenic, enterohemorrhagic, enteroaggregative, and diffuse adherence E. coli. Overall, the incidence of diarrhea was low (2.1 episodes/infant/year). Nevertheless, a putative E. coli enteropathogen was found in a large proportion of diarrheal episodes, particularly during the summer. In both cohorts, enterotoxigenic E. coli were important pathogens. Enteropathogenic E. coli were incriminated during the first year of life in the newborn cohort, where they were found significantly more often in cases (p = 0.021) than in controls; beyond this age, isolation rates were similar. In contrast, the relative risk of isolation of diffuse adherence E. coli increased with age in the age cross-sectional cohort, where, overall, the difference in rate of isolation between cases and controls was significant (p = 0.0024). Enteroinvasive and enterohemorrhagic E. coli were isolated infrequently. Enteroaggregative E. coli were encountered equally in cases and controls. Facile transmission of E. coli enteropathogens is occurring in this community despite the availability of potable water.

PIP: Researchers conducted an age cross sectional cohort analysis of 340 0-47 month old children and newborn cohort analysis of 144 newborns to determine the diarrheogenic Escherichia coli incidence in Santa Julia, a low socioeconomic community in Santiago, Chile. Children in the age cross sectional cohort had age, sex, and sector matched controls. The newborns had sex matched controls. A public health nurse or nurse auxiliary visited the household of each subject 2 times a week to detect diarrhea episodes. Between December 1986 and February 1990, the age cross sectional cohort had 1178 episodes of diarrhea and the newborn cohort had 674 episodes. The overall diarrhea incidence was only 2.1 episodes/child/year. An E. coli enteropathogen was isolated in many of these episodes, especially during the summer (e.g. enterotoxigenic E. coli [ETEC], 2.2 cases/month in summer vs. 0.4 cases/month in winter; p = .00001). Diffuse adherence E. coli (DAEC) and enteropathogenic E. coli (EPEC) infections also peaked in the summer. ETEC contributed greatly to diarrheal episodes in both cohorts. Among newborns, EPEC was isolated significantly more often in cases than controls during the 1st 12 months of life (6.7% vs. 2.5%; p = .021). After 1 year, however, E. coli isolation rates were essentially the same. On the other hand, in the age cross sectional cohort, the relative risk of isolation of DAEC rose with age (e.g., 1.1 for 0.11 months, 1.4 for 36-47 months, and 2.1 for = or 48 months). In the same cohort, DAEC infections were much more common in cases than controls (16.6% vs. 11.9%; p = .0024). Enteroinvasive and enterohemorrhagic E. coli were the most rarely isolated E. coli types. No difference in the isolation rate of enteroaggregative E. coli existed between cases and controls. Since most households in Santa Julia have access to potable water (68%) and an indoor toilet (64%), food contamination were likely the vehicles of E. coli transmission because more than 50% of households do not have a refrigerator.

Prevalence of enteric viruses among hospital patients with AIDS in Kinshasa, Zaire.

Diarrhoea is the most common manifestation of acquired immunodeficiency syndrome (AIDS) in Africa. Numerous parasitic or bacterial agents have been implicated, but a pathogen-specific aetiology has not been found. Enteric viruses (i.e., rotavirus, small round structured viruses, coronavirus, and adenovirus) were detected by enzyme-linked immunosorbent assay or electron microscopy in faecal specimens of 17% of 198 consecutive adult admissions to a general medical ward of an urban hospital in Kinshasa, Zaire. Overall, 57% of patients were seropositive for infection with human immunodeficiency virus (HIV) 1; of these, 50% were classified as World Health Organization AIDS stage IV. The prevalence of enteric viruses in stool specimens did not differ significantly between patients with and without HIV infection, and was not associated with acute or chronic diarrhoea, or constitutional symptoms. However, a trend (P = 0.14) towards greater frequency of virus in stools from patients in the lower 3 quintiles of the CD4/CD8 T cell ratio was seen. This trend approached statistical significance (P = 0.07) with stratification by HIV infection. Although we found no evidence in this population to support a major pathogenic role for these viruses alone in the enteropathy of AIDS, increased viral shedding was weakly associated with immunodeficiency.

PIP: During July-October 1989 in Zaire, a physician examined and took blood and stool samples from 198 adult patients at Mama Yemo Hospital in central Kinshasa to learn the prevalence of enteric viruses and their link to diarrhea, immunosuppression, and wasting among HIV infected and uninfected patients. In Kinshasa, diarrhea is prevalent and heterosexual intercourse is the main mode of HIV transmission. 57.6% of the patients were infected with HIV. 50% of the HIV-positive patients had AIDS. 93% of all HIV-positive patients either had AIDS (stage IV) or advanced stage III disease. 49% of them died while in the hospital. 22% of the HIV-negative patients died while in the hospital. 17% of all adult patients studied were infected with at least 1 enteric virus, especially rotavirus. Enteric viruses were isolated from both HIV infected and uninfected patients (17% and 18%, respectively). State of immunocompromise did not significantly affect viral shedding, but fewer patients in the less immunocompromised stages shed viruses than did those in the advanced stages of immunocompromise (3 vs. 72 patients). When examining the ratio of circulating CD4 and CD8 T cells in HIV-infected patients, however, there was a trend toward greater frequency of enteric viruses (p = .07). Chronic diarrhea was significantly associated with HIV seropositivity (p 0.01), HIV stage (p .001), and CD4/CD8 T cell ratio (p .01). Acute diarrhea was not associated with any of the above, however. These findings suggest that enteric viruses were not a significant cause of diarrhea, but they were isolated somewhat more often in patients of advanced immunosuppression.