Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age.

A longitudinal study of diarrhea was carried out from May 1988 to April 1989 by household surveillance of 705 children less than 5 years old in rural Bangladesh. Stool samples were examined for enteric pathogens at the beginning of each diarrheal episode. For persistent episodes, stool examination was repeated on days 15-17 of the illness. For each case of persistent diarrhea, stool samples from age-matched acute diarrheal and healthy controls were examined. Compared with healthy controls, cases of diarrhea were associated with Shigella species (P = .07) and rotavirus (P less than .05). Diffusely adherent Escherichia coli (P less than .05) and cryptosporidia (P = .07) were the only enteropathogens associated with persistent diarrhea in comparison with acute diarrhea. No more than 15% of children had the same class of pathogen identified from stool on both days 1-3 and days 15-17, indicating that persistent infection was uncommon. However, a different enteropathogen was frequently found on days 15-17, suggesting that sequential infection may be a cause of persistent diarrhea.     

Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Etiology and response to therapy

STUDY OBJECTIVE: To determine the frequency of pathogenic gastrointestinal microorganisms in patients with the acquired immunodeficiency syndrome (AIDS) and diarrhea, and to determine if treatment for identifiable microorganisms improves symptoms. DESIGN: Prospective, consecutive sample study. Setting: Referral-based clinic and wards, National Institutes of Health. PATIENTS: Twenty of twenty-two consecutive homosexual males with AIDS and diarrhea, and 10 homosexual males with AIDS without diarrhea. INTERVENTIONS: All patients had a complete physical examination; serial stool examinations for viral, bacterial, fungal, and protozoan pathogens; and esophagogastroduodenoscopy and colonoscopy to obtain duodenal fluid and mucosal tissue to analyze for enteric pathogens or histopathology. Patients with diarrhea had a malabsorption evaluation. Patients with treatable pathogenic microorganisms received standard antimicrobial therapy. MEASUREMENTS and MAIN RESULTS: The 20 patients with AIDS and diarrhea had greater weight loss, lower mean numbers of helper-inducer (OKT4) lymphocytes, and a higher incidence of extraintestinal opportunistic infections than the 10 patients without diarrhea. One or more enteric pathogen was identified in 17 of 20 patients (85%; 95% confidence interval [CI], 65% to 96%) with diarrhea. Only 1 patient without diarrhea was infected with an enteric pathogen. Nineteen of twenty patients with diarrhea and all 10 patients without diarrhea had chronic inflammatory changes in their intestinal biopsy specimens. Sixteen patients with identifiable enteric pathogens and diarrhea were treated; 11 (69%; 95% CI, 43% to 87%) showed microbiologic, histologic, or clinical improvement. CONCLUSIONS: Thorough diagnostic evaluation can lead to the identification of enteric pathogens in a high percentage of patients with AIDS and diarrhea. Specific therapy can lead to symptomatic improvement.     

Evaluation of chronic diarrhea in patients with human immunodeficiency virus infection

Chronic diarrhea is a common problem for patients with human immunodeficiency virus infection, especially those with advanced disease. The extent of evaluation and whether to do flexible sigmoidoscopy, colonoscopy, and/or upper endoscopy have been areas of significant debate. Based upon the marked improvement in long-term survival since the introduction of highly active antiretroviral therapy, a comprehensive evaluation is currently justified. A stepwise approach to the evaluation of chronic diarrhea appears to be the best approach. The first step is a history, with a focus on any association between the onset of diarrhea and the institution of protease inhibitor therapy, which is associated with significant diarrhea in many patients. If there is no temporal association with antiretroviral therapy, the next step is examination of stool for bacterial and protozoal pathogens. If the stool studies are negative, the next step is to proceed to colonoscopy. Flexible sigmoidoscopy alone has been noted to miss up to 39% of cases of cytomegalovirus colitis. The inclusion of ileoscopy and biopsy of the terminal ileum during colonoscopy has a significant yield for microsporidiosis, which may obviate the need for upper endoscopy. The highest yield can be expected in patients with fever, weight loss, and a CD4 count of under 200 cells/mm3, especially those with a CD4 count less than 50 cells/mm3.     

Diarrheal disease in patients infected with human immunodeficiency virus in Bangkok, Thailand.

Diarrheal disease and its associated morbidities occur frequently in patients infected with human immunodeficiency virus (HIV) and may be associated with a decreased quality of life. We studied the spectrum of symptoms, measures of nutritional status, and the enteric pathogens associated with diarrheal disease in a group of 24 patients infected with HIV in Bangkok, Thailand compared with a group of 19 patients infected with HIV without diarrhea cared for at the same clinic. Patients with diarrhea appeared to have more advanced disease by CD4 cell counts and complained more frequently of symptoms such as anorexia, gas, and bloating than patients without diarrhea. Patients with diarrhea had a tendency toward a lower nutritional status, as measured by body mass index and mid arm circumference. Stool culture and examination revealed that enteric pathogens including Salmonella species and Cryptosporidium parvum sporidia were recovered at equal frequencies in patients with and without diarrhea (27% of the patients with diarrhea and 25% of the patients without diarrhea). Microsporidia was identified in one patient with diarrhea. It was not possible to identify a pathogen in 73% of the patients with diarrhea and 75% of the patients without diarrhea, suggesting that additional agents or factors may be responsible for the diarrheal symptoms in the patients with diarrhea. More extensive studies to identify potentially treatable pathogens in HIV-infected patients with diarrhea in Thailand are warranted and further attempts to better define the syndrome of pathogen-negative diarrheal disease in patients infected with HIV might result in the development of more targeted interventions in these patients.     

Work-up for infectious diarrhea after allogeneic hematopoietic stem cell transplantation: single specimen testing results in cost savings without compromising diagnostic yield

BACKGROUND: Diarrhea is a common complication of allogeneic bone marrow transplantation. Microbiologic stool studies are frequently ordered to rule out infectious etiology. The utility of examining multiple stool specimens per diarrheal episode has not been examined. METHODS:. We performed a retrospective review of 169 adult and pediatric patients who underwent hematopoietic stem cell transplantation at Memorial Sloan-Kettering Cancer Center from January 1, 2000 though December 31, 2001, who had at least 1 microbiologic stool study. We report on the incidence of enteric pathogens in our population and diagnostic yield of stool studies. A diarrheal episode was defined as a 14-day period from the date of the first stool study. Cost savings analysis was based on projected savings from implementation of proposed guidelines to the study population. RESULTS: A total of 1649 stool tests were performed (mean 10.6 tests per patient). An infectious cause of diarrhea was found in 45 (28.8%) patients. Diagnostic yield was 6.2% for Clostridum difficile toxin assay, 12.9% for viral cultures, and 1.3% for rotavirus enzyme immunoassay. Bacterial cultures for enteric pathogens, examination for parasites, and rotavirus antigen assay combined had 0.5% positive yield. CONCLUSIONS: Testing of multiple specimens per diarrheal episode did not increase diagnostic yield. The estimated cost savings by implementing single testing for each type of stool study per diarrheal episode was $49,764 annually (in 2001 US dollars). Judicious use of stool tests to evaluate diarrhea results in significant cost savings without compromising diagnostic yield.     

Investigation of diarrhea in AIDS.

Chronic diarrhea is a common problem in patients with acquired immune deficiency syndrome (AIDS), resulting in significant morbidity and potential mortality. In the early stages of immunodeficiency, human immunodeficiency virus (HIV)-infected patients are susceptible to infection with the same enteric pathogens that cause diarrhea in immunocompetent hosts, but with progressive immunodeficiency, these patients become susceptible to numerous opportunistic disorders. The main factor to consider when tailoring the work-up of diarrhea in the HIV-infected patient is the immune status, which is reflected by the total CD4 lymphocyte cell count. A CD4 count of less than 100 cells/microL is significantly correlated with opportunistic disorders. For the HIV-infected patient with diarrhea, repeated stool studies to investigate for bacteria, ova and parasites should be the first step. When either upper or lower gastrointestinal tract symptoms are present and stool studies are negative, endoscopy directed to the probable organ of involvement is appropriate. If localizing symptoms are absent, the most appropriate next test is sigmoidoscopy with biopsies. Not infrequently, despite extensive evaluation, the cause of diarrhea in patients with AIDS remains unexplained. Recently, the widespread use of highly active antiretroviral therapy, including protease inhibitors, has led to a change in the epidemiology of diarrhea in AIDS patients. As their immune status improves, HIV-infected patients treated with combination therapy become less prone to opportunistic disorders. However, diarrhea appears to be frequent because several antiretroviral agents can themselves cause diarrhea.     

AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea

OBJECTIVE: To investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus (HIV) infection and chronic diarrhea of undefined cause. DESIGN: Case-control study. SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS: Twenty-two patients with advanced HIV infection (19 with the acquired immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic diarrhea, selected because of previously negative stool evaluations for bacterial or parasitic pathogens, were compared with 13 patients with advanced HIV infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis of endoscopic biopsies using light and electron microscopy, viral culture, and morphometric studies. Both groups were convenience samples and had at least 7 months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients with HIV infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens (that is, undetected by routine studies) after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium avium-intracellulare and microsporidia were the most common occult agents in study patients with diarrhea (5 each). Patients with diarrhea and occult enteric infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P less than 0.004) than those with diarrhea but no identified pathogens (defined as "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios because of villus atrophy and crypt elongation in HIV-infected patients both with and without diarrhea compared with normal controls (P less than 0.001 for each). All three groups showed comparable frequencies of epithelial mitoses. CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases. However, altered villus and crypt architecture in advanced HIV infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in response to injury could be a factor, but the underlying cause of the architectural changes remains obscure. We suggest that T-cell dysfunction may play a role.     

Epidemiologic and clinical characteristics of acute diarrhea with emphasis on Entamoeba histolytica infections in preschool children in an urban slum of Dhaka, Bangladesh

The epidemiology, clinical features, nutritional status, and causative agents of diarrhea were studied in 289 Bangladeshi children (147 boys and 142 girls) 2-5 years old. The use of improved diagnostic tests for amebiasis enabled for the first time analysis of the contribution of Entamoeba histolytica to total diarrheal illness in this community setting. The average incidence rate of diarrhea was 1.8/child-year, and the average number of diarrheal days was 3.7 days/child-year over an average observation period of 2.8 years/child. Seventy-five percent of the diarrheal episodes were < or = 2 days in duration. Persistent diarrhea was relatively uncommon (0.2% of the children) and chronic diarrhea was observed in only one episode. Compared with malnourished and/or stunted children, better-nourished children experienced significantly fewer diarrheal episodes. The diarrheal incidence rate for children with blood group A was significantly less that that of the children with blood groups O and AB. The most frequent bacterial enteropathogens isolated from diarrheal stool specimens were enterotoxigenic Escherichia coli (9%) and Aeromonas species (9%), followed by Plesimonas shigelloides (4%) and Shigella flexneri (3.8%). Rotavirus was the most common viral agent isolated from diarrheal stool samples (5%). Giardia lamblia, Cryptosporidium parvum, and E. histolytica were identified in 11%, 8.4%, and 8%, respectively, of the diarrheal stool specimens. Dysentery was observed in 7.7% of all diarrheal episodes. The most common pathogens isolated from dysenteric stool were S. flexneri (11.6%), Aeromonas sp. (10%), E. histolytica (8.7%), Campylobacter jejunii (5.8%), P. shigelloides (4.3%), and A. caviae (4.3%). The overall incidence rate of E. histolytica-associated diarrhea was 0.08/child-year. Visible blood and hemoccult test-detected blood loss was found in 7% and 25%, respectively, of cases of E. histolytica-associated diarrhea. Children who had recovered from a diarrheal episode with E. histolytica, but not E. dispar, had half the chance of developing subsequent E. histolytica-associated diarrhea, consistent with the development of species-specific acquired immunity. In conclusion, the use of modern diagnostic tests demonstrated that E. histolytica contributed to overall morbidity from diarrheal illness. Understanding the etiology, frequency, and consequences of acute diarrhea in children from a developing country should aid in the design of interventions to improve child health.     

INFECTIOUS DIARRHEA IN CHILDREN UNDERGOING BONE-MARROW TRANSPLANTATION

Fecal flora of 12 children undergoing bone-marrow transplantation was monitored prospectively using comprehensive microbiological techniques. Diarrhea developed at least once in ten of the 12 children (83%), and a total of 24 episodes were recorded. Recognised gut pathogens were isolated from 11/21 (52%) diarrheal episodes where fecal specimens were obtained. Enteric pathogens identified included viral pathogens in 19% (rotaviruses, 'enteric' adenoviruses), parasites in 19% (cryptosporidium, Giardia lamblia) and cytotoxic C. difficile (14%). Excretion of clostridial species (including cytotoxin negative C. difficile, C. innocuum ) occurred in 90% of diarrheal episodes when no enteric pathogen was identified. These results suggest that infection is often responsible for diarrhea associated with bone-marrow transplantation. Prophylaxis against enteric infection might reduce the morbidity and mortality associated with severe diarrhea in bone-marrow transplanted children. (Aust NZ J Med 1989; 19: 31–36.)     

Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome

Background and aims The role of non-cytomegalovirus (CMV) enteric viral infection in causing diarrhoea in patients with human immunodeficiency virus (HIV) is poorly understood. We aimed to investigate the prevalence of these infections in acute and chronic diarrhoea. Methods Stool specimens from 377 HIV-infected patients presenting with diarrhoea were studied prospectively for evidence of non-CMV enteric viral infection. Patients with diarrhoea underwent investigation for gastrointestinal pathogens, including electron microscopic examination of stool for enteric viruses. We collected data on patients in whom enteric virus was identified and examined the association of enteric virus infection with diarrhoeal symptomatology. Results Eighty-nine (10.3%) stool specimens from 60 (15.9%) HIV⁺ individuals were positive for coronavirus (n = 13, 22%), rotavirus (n = 11, 18%), adenovirus (n = 30, 50%) and small round structured viruses (n = 5, 8%) or dual infection (n = 2, 3%). Thirty-four of 52 (65%) patients available for analysis had acute diarrhoea, and 18/52 (35%) had chronic diarrhoea. Twenty-three of 52 (44%) patients had a concurrent gut pathogen. After exclusion of concurrent pathogens enteric viral infections were found to be significantly associated with acute as opposed to chronic diarrhoea (P = 0.004). The presence of adenovirus colitis was significantly more likely to be associated with chronic diarrhoea (15/21 cases) than adenovirus isolated from stool alone (9/23 cases) (P = 0.03). There was a trend towards an association between adenovirus colitis and colonic cytomegalovirus infection (P = 0.06). Conclusion Enteric viral infection is strongly associated with acute diarrhoea in patients with HIV. Light microscopic examination of large bowel biopsies can identify adenovirus colitis which is significantly associated with chronic diarrhoea, and in addition may facilitate gastrointestinal co-infection with CMV.     

Intestinal infections in patients with acquired immunodeficiency syndrome

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P=0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P<0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.Computerized treatment of data has been allowed by the Commission Nationale Informatique et Liberté (registration NB. 104713).This work was supported in part by Institut National de la Santé et de la Recherche Médicale, (grant UR/010/237) and by Fondation Médicale pour la Recherche, and by Paris VII Faculté.Portions of this study were presented at the American Gastroenterological Association in May 1987.     

Prevalence of acute enteric viral pathogens in acquired immunodeficiency syndrome patients with diarrhea

Diarrhea due to enteric pathogens is an important complication of advanced human immunodeficiency virus infection. Whereas numerous bacterial and parasitic agents have been implicated, the role of pathogenic enteric viruses is less clear. Stools from 153 human immunodeficiency virus seropositive men were tested by electrophoresis, enzyme-linked immunosorbent assay, and immune electron microscopy for the presence of rotaviruses (group A and non-group A), adenoviruses, and Norwalk agent. Virus was detected in 9% of the patients with acquired immunodeficiency syndrome, 3% of the patients with acquired immunodeficiency syndrome-related complex, and none of the seropositive men without these diagnoses. Virus detection was not more likely in stool from patients with diarrhea.     

Etiologies and manifestations of persistent diarrhea in adults with HIV-1 infection: a case-control study in Lima, Peru

OBJECTIVE We sought to determine the etiologies, manifestations, and risk factors for persistent (> or =7 days) diarrhea in human immunodeficiency virus type 1 (HIV-1)-infected persons in Peru. DESIGN: The present study is a case-control study of 147 HIV-1-infected case subjects with persistent diarrhea and 147 HIV-1-infected control subjects without diarrhea. METHODS: We obtained clinical, demographic, and exposure data, CD4 lymphocyte counts, and stool samples for detection of enteric parasitic and bacterial pathogens and rotavirus. RESULTS: One or more enteric pathogen was identified in 55% of case subjects and 21% of control subjects (odds ratio adjusted for CD4 lymphocyte count, 3.8; 95% confidence interval, 2.2-6.5). The median CD4 lymphocyte count was highest with pathogen-free diarrhea and lowest with Cryptosporidium infection. Cryptosporidium species (the most frequent pathogen), Giardia lamblia, Aeromonas species, Campylobacter species, and rotavirus were all significantly associated with diarrhea. Bacterial pathogens were significantly associated with G. lamblia and rotavirus infection. Of the bacterial pathogens (Aeromonas, Campylobacter, Salmonella, and Vibrio species and enterotoxigenic Escherichia coli), only 24% were susceptible to cotrimoxazole, whereas 90% were susceptible to ciprofloxacin. In no case did the sensitivity or positive predictive value of specific clinical and laboratory findings for curable enteric infections exceed 50%. CONCLUSIONS: Several enteric pathogens were associated with diarrhea in HIV-1-infected case subjects in Peru, especially among those who were heterosexual. Clinical findings were poor predictors of detectable microbial etiology. The guidelines for initial management of chronic diarrhea with sulfamethoxazole-trimethoprim in HIV-1-infected persons require revision, at least in settings where prophylaxis with this agent is common.     

A comprehensive survey of pediatric diarrhea at a private hospital in Metro Manila.

The epidemiology of diarrhea among Filipino pediatric patients, representing a cross-section of socioeconomic strata, was investigated over a one year period. Rotavirus was detected in 33.9% of the diarrhea stools examined and was the leading cause of diarrhea in the study population. Although proportionately more rotavirus was found during the cold season, most children became infected with rotavirus during the rainy season, when diarrheal disease was at its peak in Metropolitan Manila. Enteric adenovirus types 40 or 41 were associated with only 5.4% of the diarrhea cases. Overall, one or more etiologic agents of diarrhea were detected in 67.2% of the stools examined. Many of these positive stools (21.6%) contained multiple diarrheogenic agents. Bacterial enteric pathogens were isolated from 32.3% of the cases. Nearly 70% of these patients with bacterial gastroenteritis became ill during the rainy season. Etiology specific and general risk factors associated with diarrheal illness in the study population are discussed.     

Infectious diarrhea in patients with AIDS

A multitude of opportunistic infections has been documented in virtually every organ system of patients with the acquired immunodeficiency syndrome (AIDS). Prominent among these are infections of the gastrointestinal tract. However, studies of large numbers of patients documenting the frequency of such involvement are lacking. We reviewed the records of 100 patients with AIDS and assessed the frequency and organisms causing infectious diarrhea. We found diarrhea to be more common in homosexuals (80%) than heterosexuals with a risk factor of parenteral drug use (58%). In one third of all cases, no infectious etiology was found. Myobacterium avium intracellulare (MAI) was the most commonly identified cause of infectious diarrhea in our series, followed by cytomegalovirus, cryptosporidium, Salmonellaspp., and herpes virus. In addition, bacteremia was documented in 43% of patients with infectious diarrhea and was most commonly due to MAI. Finally, we demonstrated that multiple concurrent infections are not uncommon (22%) in AIDS patients and that the diarrheal syndrome may not respond unless all pathogens are eradicated.     

Diarrheal morbidity and mortality in children in the Central African Republic

Diarrheal morbidity and mortality in children less than 5 years old were studied in Bangui, Central African Republic, by a cluster survey. We found a high prevalence of diarrheal disease with an estimated annual incidence of 7 episodes of diarrhea per child per year. The estimated annual mortality rate for children less than 5 years old was 28.6 per 1,000 and 85.8 per 1,000 for infants; 51.6% of deaths were reported to be associated with diarrhea. During the survey, stool specimens were collected from 133 children with current diarrhea and 117 control children to study the etiologic agents of diarrheal disease in the community. An enteric pathogen was identified in 58% of diarrheal children's stools and 48% of stools of well children. A statistically significant association between diarrhea and rotavirus was found, with it being isolated from 8 of 33 (24%) of stools of infants with diarrhea compared to 0 of 25 (0%) of control infants. Isolation rates for Campylobacter jejuni, Entamoeba histolytica, pathogenic Escherichia coli, and other bacterial enteropathogens did not differ significantly between children with diarrhea and control children.     

Diarrheagenic Escherichia coli in Human Immunodeficiency Virus (HIV) Pediatric Patients in Lima,Perú

We conducted a prospective study in three hospitals in Lima in human immunodeficiency virus (HIV) children to determine the frequency of diarrheagenic Escherichia coli. Five E. coli colonies/patients were studied by a multiplex real-time polymerase chain reaction to identify the six currently recognized groups of diarrhea-associated E. coli. We have analyzed 70 HIV-associated diarrheal and 70 control samples from HIV-infected children without diarrhea. Among the diarrheal episodes 19% were persistent, 3% dysenteric, and 33% were associated with moderate or severe dehydration. The diarrheagenic E. coli were the most commonly isolated pathogens in diarrhea (19%) and control samples (26%) (P = 0.42), including enteroaggregative (6% versus 10%), enteropathogenic (6% versus 10%), and enterotoxigenic E. coli (4% versus 3%), respectively. The HIV-infected children with diarrhea had the worse age-related immunosuppression, higher viral loads, and were on highly active antiretroviral treatment (HAART) less often than HIV-infected children without diarrhea. Diarrheagenic E. coli were highly resistant to ampicillin (74%) and cotrimoxazole (70%).     

Investigation of chronic diarrhoea in acquired immunodeficiency syndrome. A prospective study of 155 patients.

BACKGROUND AND AIMS: The optimum diagnostic investigation for patients with acquired immunodeficiency syndrome (AIDS) and diarrhoea is not known. Often no pathogen is detected and it is unclear whether this is because pathogens are absent in some patients or the investigations used fail to detect them. The hypothesis that AIDS related diarrhoea is usually due to an infection, which can be identified by a simple diagnostic strategy based on the results of intensive investigation of a cohort of such patients, was investigated. METHODS: 155 patients with AIDS and chronic diarrhoea underwent contemporaneous examination of stools, duodenal, jejunal, and rectal biopsy specimens and duodenal aspirate for bacterial, protozoal, and viral pathogens. A decision tree analysis was used to determine the best sequential diagnostic strategy for clinicians. RESULTS: 128 of 155 patients investigated (83%) had at least one potential pathogen. The presenting clinical features could not predict the presence or site of the pathogens. Stool analysis identified the most pathogens (93 of 199, 47%). Rectal biopsy was essential for the diagnosis of cytomegalovirus and adenovirus. Duodenal biopsy was as helpful as jejunal biopsy and detected some treatable pathogens missed by other methods. Electron microscopy, impression smears, and duodenal aspirate yielded little extra information. If gut biopsy was reserved for patients without a stool pathogen, some treatable pathogens would have been missed. CONCLUSION: Most patients with AIDS and chronic diarrhoea have at least one gut pathogen, which can be identified by stool analysis and light microscopic examination of duodenal and rectal biopsies. Some pathogens will be missed unless all these investigations are done on all such patients.     

Diarrheal disease among HIV-infected adults in Karnataka, India: evaluation of risk factors and etiology

The objectives of this study were to evaluate characteristics associated with diarrhea, the effect of trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis on diarrhea, the response to treatment with ciprofloxacin and tinidazole (Cipro-TZ), and presence of enteric pathogens. Adults infected with human immunodeficiency virus with and without diarrhea served as cases and controls, respectively. Participants provided a medical history and underwent a physical examination. Blood was collected for CD4 cell counts and stool for culture. Cases were treated with Cipro-TZ. Factors associated with a risk of diarrhea included crowded living and no toilet (all P < 0.05). Protective variables (P < 0.05) included a CD4 count greater than 200 cells/mm(3) and TMP/SMX prophylaxis. Cases were more likely to have a pathogen identified (P = 0.05). Eighty-six percent of the cases responded to treatment. Important risk factors for diarrhea were identified. Protection by TMP/SMX reinforces the importance of prophylaxis. These data suggest that treatment with an antibiotic and anti-parasitic medication may be effective.     

Detection by immune electron microscopy of 27-nm viral particles associated with community-acquired diarrhea in children

The proportion of diarrheal illnesses of unknown origin that were associated with small round virus (SRV, 23-38 nm) particles among children less than 2 years old attending an outpatient clinic in Baltimore was determined. During a 9-month period, stool specimens from 188 patients with acute diarrhea and 108 healthy age-matched control children were examined for enteric bacterial pathogens, protozoa, enteric adenovirus, and rotavirus. An enteropathogen was identified in 75 patients (40%) and in 21 controls (20%). A random sample of specimens without an identifiable pathogen was then examined for SRV particles by immune electron microscopy (IEM) using commercial human gamma globulin. Viruses of 26-30 nm diameter that were not enteroviruses were detected in specimens from 9 (12.5%) of the 72 patients and 1 (1.8%) of the 53 control subjects (P less than .04). Of 6 patients with available acute and convalescent sera, 4 demonstrated a significant immune response when tested by IEM. All patients experienced a mild, self-limited (1-3 days) illness. These findings suggest that SRV may be endemic in the Baltimore community and may result in clinically significant diarrheal illnesses.