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Biomedical subjects

H L DuPont

Publications and source records attributed to H L DuPont.

At least 19 recordsLinked to original sources

The infectivity of Cryptosporidium parvum in healthy volunteers.

BACKGROUND: Small numbers of Cryptosporidium parvum oocysts can contaminate even treated drinking water, and ingestion of oocysts can cause diarrheal disease in normal as well as immunocompromised hosts. Since the number of organisms necessary to cause infection in humans is unknown, we performed a study to determine the infective dose of the parasite in healthy adults. METHODS: After providing informed consent, 29 healthy volunteers without evidence of previous C. parvum infection, as determined by the absence of anti-cryptosporidium-specific antibodies, were given a single dose of 30 to 1 million C. parvum oocysts obtained from a calf. They were then monitored for oocyst excretion and clinical illness for eight weeks. Household contacts were monitored for secondary spread. RESULTS: Of the 16 subjects who received an intended dose of 300 or more oocysts, 14 (88 percent) became infected. After a dose of 30 oocysts, one of five subjects (20 percent) became infected, whereas at a dose of 1000 or more oocysts, seven of seven became infected. The median infective dose, calculated by linear regression, was 132 oocysts. Of the 18 subjects who excreted oocysts after the challenge dose, 11 had enteric symptoms and 7 (39 percent) had clinical cryptosporidiosis, consisting of diarrhea plus at least one other enteric symptom. All recovered, and there were no secondary cases of diarrhea among household contacts. CONCLUSIONS: In healthy adults with no serologic evidence of past infection with C. parvum, a low dose of C. parvum oocysts is sufficient to cause infection.

Adult

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea.

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.

Acute Disease

Intestinal parasites in HIV-seropositive Zambian children with diarrhoea.

We undertook a study over a period of 9 months to define the frequency of parasitic infections in hospitalized children with diarrhoea between the ages of 15 months and 5 years. Every alternate day, mothers of all children admitted with diarrhoea between 09.00 hours and 12.00 hours to one of the wards of the Department of Pediatrics and Child Health of the University Teaching Hospital (UTH) in Lusaka, Zambia, were interviewed for enrollment of their children into the study. A total of 178 children with diarrhoea were enrolled in the study. Of these 44 (25 per cent) were HIV seropositive and 134 (75 per cent) were seronegative for HIV. Out of 44 HIV-seropositive patients, 20 (45 per cent) had acute diarrhoea and 24 (55 per cent) had chronic diarrhoea. Of the 134 HIV-seronegative patients, 68 had acute diarrhoea (51 per cent) and 66 (49 per cent) had chronic diarrhoea. At least one intestinal parasite was found in 34 out of the 178 children enrolled. The commonest parasites identified were Ascaris and Cryptosporidia. No associations were identified between parasite isolation and the following: age, sex, or socio-economic status. Cryptosporidium spp. was isolated from 6 out of 44 (14 per cent) HIV-seropositive children, while 8 out of 134 (6 per cent) seronegative children had the parasite (P = 0.01). HIV-seropositive children with chronic diarrhoea had significantly higher cryptosporidium identification rates than those HIV-seropositive children with acute diarrhoea [5 out of 24 (21 per cent) patients with chronic diarrhoea compared to 1 out of 20 (5 per cent) patients with acute diarrhoea; (P > or = 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections

Lack of correlation between diarrhea and weight loss in HIV-positive outpatients in Houston, Texas.

To determine the prevalence of diarrhea and weight loss among human immunodeficiency virus (HIV)-positive patients, we reviewed the records of all patients attending the Harris County HIV Clinic during a 4-month time period. Diarrhea was considered persistent if it had been present for > 14 days or on two or more consecutive clinic visits. Weight loss was defined as moderate (5-10% reduction in weight) or severe (> 10% reduction) when the present weight was compared with the weight found at the initial clinic visit. Records were reviewed for 1,370 patients, of whom 12.2% complained of diarrhea (7.7% acute and 4.5% persistent). Diarrhea was more common among patients with a history of male-to-male sexual contact than in patients with other HIV risk factors (p < 0.003 for acute and p < 0.006 for persistent). The mean CD4 cell count was not significantly different in patients with or without persistent diarrhea (176 versus 212) or acute diarrhea (215 versus 212). Weight loss was reported in 25.2% of subjects (12.8% moderate and 12.4% severe). It did not correlate with CD4 count. Persistent diarrhea also was not associated with weight loss. Acute and persistent diarrhea were common among ambulatory HIV-positive patients, particularly in homosexual men. We did not identify a correlation among diarrhea, weight loss, and CD4 count. Thus, factors other than chronic diarrhea and immunosuppression appear to be responsible for weight loss in HIV-infected patients.

Acute Disease

Intestinal immune response of volunteers ingesting a strain of enteroadherent (HEp-2 cell-adherent) Escherichia coli.

Enteroadherent Escherichia coli (EAEC) strains identified by adherence to HEp-2 tissue culture cells have been incriminated epidemiologically as important etiologic agents of diarrheal disease in both adult travelers and children in developing countries. One strain, JM 221, with no recognized E. coli virulence characteristics other than adherence to HEp-2 cells, caused diarrhea in 5 of 16 volunteers ingesting it. We studied the secretory immunoglobulin A (sIgA) responses to EAEC JM 221 of five volunteers with diarrhea and five volunteers who remained healthy after challenge. sIgA was extracted from stools obtained prechallenge and 7 days postchallenge. Total sIgA was standardized for all specimens. Specific sIgA titers were determined by dot blotting with the following JM 221 antigens: water-extractable surface antigens, whole cells, lipopolysaccharides, and outer membrane proteins. All five subjects who became ill had fourfold or greater rises in titers against each of the four antigens. The five subjects who remained healthy following challenge did not exhibit significant rises in titers to any JM 221 antigens, but their mean titers were significantly higher than the mean prechallenge titers of the volunteers with diarrhea, suggesting that high intestinal sIgA titers may be protective. The significant increases in intestinal antibody against JM 221 in the subjects who became ill is further evidence of the enteropathogenicity of EAEC strains.

Administration, Oral

Methods for detection of an intestinal secretory immunoglobulin A response to Candida spp. and their preliminary application in human immunodeficiency virus-infected patients with chronic diarrhea.

Six of 11 human immunodeficiency virus (HIV)-infected patients with chronic diarrhea, shedding only Candida spp. in their stools, elicited a Candida-specific secretory immunoglobulin A response. Similar responses were identified in only 1 of 10 HIV-positive patients with chronic diarrhea but without Candida spp. and in none of 10 HIV-negative subjects without diarrhea. Candida spp. may play a role in the etiology of chronic diarrhea associated with HIV infection.

AIDS-Related Opportunistic Infections

Pathogenesis of traveler's diarrhea.

Diarrhea is the most common medical complication among persons venturing into tropical and semitropical regions of the developing world from industrialized regions. The illness is characteristically caused by one of a variety of bacterial agents, of which enterotoxigenic Escherichia coli is the most important. Intestinal electrolyte fluid movement explains the pathophysiology of most cases while in certain situations osmotic diarrhea or altered intestinal motility may lead to passage of unformed stools. In 1-2% of traveler, diarrhea lasts more than 1 month. Most of the patients will have diarrhea that is eventually self-limiting. The cause and mechanisms of diarrhea in these settings are largely unknown although a focal intestinal inflammation lesion may be found.

Bacterial Infections

Diarrheal diseases in the developing world.

Acute diarrhea is a major killer of children in the developing world. Underlying malnutrition and occurrence of complications of illness explain the high fatality rate. Oral rehydration prevents death associated with dehydration. Persistent and invasive diarrhea remains an important cause of death. Control of diarrhea through cost-effective public health measures is needed.

Child

Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children.

Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community-based, prospective study of the relation between infant feeding patterns and enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal disease. Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC were symptomatic for diarrhea nearly three times as often as strictly breast-fed infants and twice as often as infants receiving a mixed diet. The fitting of parametric hazard models to durations until LT-ETEC colonization revealed that the hazard for the first colonization was time invariant. The hazard of diarrhea increased by 400-500% during the rainy season or among children 3 months of age or older who received avena, a barley drink. The best-fitting hazard models to durations until symptomatic expression of LT-ETEC infection all increased through time. This hazard was inversely impacted by the overall amount of LT-ETEC-specific, immunoglobulin A antibodies the infant received via the mother's breast milk and by the provision of traditional medicinal teas.

Bacterial Toxins

Human immunodeficiency virus type-1 infection in Zambian children with tuberculosis: changing seroprevalence and evaluation of a thioacetazone-free regimen.

SETTING: This study was conducted at the Department of Paediatrics and Child Health, University Teaching Hospital (UTH), in Lusaka, Zambia. OBJECTIVES: To monitor the seroprevalence of HIV type-1 in children with tuberculosis and to evaluate the response to anti-tuberculosis therapy using a thioacetazone-free treatment regimen. DESIGN: A prospective cross-sectional study of all consecutive newly diagnosed cases of TB in children from 1 month-15 years of age seen at the University Teaching Hospital (UTH) in Lusaka, Zambia between 1 October 1991 and 31 May 1992. RESULTS: 120 children with a clinical diagnosis of tuberculosis and 167 controls were enrolled in the study. The overall HIV type-1 seroprevalence rate in children with tuberculosis was 55.8% (67/120) compared to 9.6% (16/167) amongst the control group (P < 0.0001: odds ratio = 11.50; 95% CI = 5.99-22.7). Common clinical presentations among children with TB were bronchopneumonia (45/162), miliary TB (30/162) and tuberculous lymphadenopathy (21/33). There were no significant differences in clinical presentation of TB between the HIV-negative and HIV-positive groups. The follow-up of those patients with tuberculosis was poor, with only 65 patients (55%) returning to the clinic for scheduled appointments after discharge. All the 16 patients who died did so within 60 days of discharge from hospital; all of them were seropositive for HIV. There were no deaths among the HIV-negative group. Despite the exclusion of thioacetazone from the treatment regimen, cutaneous reactions occurring within 8 weeks of commencing treatment were observed in 7 of the 65 (11%) patients, 2 of whom developed fatal Stevens-Johnson syndrome. All 7 patients were seropositive for HIV-1. CONCLUSIONS: The seroprevalence rate of HIV type-1 among children with tuberculosis in Lusaka continues to rise; careful monitoring of anti-TB therapy (even in regimens excluding thioacetazone) for potentially lethal side effects should be carried out.

Adolescent

Intestinal secretory IgA immune response against human immunodeficiency virus among infected patients with acute and chronic diarrhea.

Diarrhea is common in patients infected with the human immunodeficiency virus (HIV) in Africa. There has been speculation that HIV itself may cause some of the enteropathy seen. The intestinal secretory IgA (sIgA) response was used to evaluate HIV intestinal infections in Zambian patients with acute and chronic diarrhea. sIgA was extracted from stool specimens and evaluated by an ELISA. Seven (58%) of 12 HIV-positive patients with acute diarrhea and 25 (69%) of 36 HIV-positive patients with chronic diarrhea showed an sIgA response to HIV p24, compared with 1 of 10 HIV-positive patients without diarrhea (P < .025 for acute and P < .001 for chronic diarrhea). The mean duration of diarrhea was significantly longer in patients showing an anti-p24 response. An sIgA response to HIV antigens occurs commonly in infected patients with diarrhea and may provide further evidence of an etiologic role of HIV in the diarrhea associated with AIDS.

Acute Disease

Association of rotavirus and human immunodeficiency virus infection in children hospitalized with acute diarrhea, Lusaka, Zambia.

In Lusaka, Zambia, rotavirus (RV) and human immunodeficiency virus (HIV) infection commonly coexist; 132 (25%) of 537 consecutively studied infants < 5 years old hospitalized with diarrhea were positive for both viral infections. Infants with RV infection were younger than those who were RV-negative (P > .05), and infants with both viruses more frequently experienced dehydration (P < .05). HIV-infected children more often exhibited respiratory symptoms on admission to the study (P < .0001) and were more frequently underweight (P < .0001) than were HIV-negative children, independent of RV infection. The mortality rate was highest in HIV-positive infants (P < .05), and coinfection with RV did not increase the risk of fatality. This study demonstrates that while RV and HIV infections commonly coexist in one region of Africa, RV infection is no more common nor is the illness more severe in HIV-positive infants.

Acute Disease

Randomized comparison of aztreonam and chloramphenicol in treatment of typhoid fever.

Patients with clinical typhoid fever plus a blood, bone marrow, or bile positive for Salmonella typhi or Salmonella paratyphi were included in an open clinical trial to compare the efficacy of aztreonam (6 g/day [2 g intravenously every 8 h]) given for 10 days with that of chloramphenicol (50 mg/kg of body weight per day [intravenously or orally]) administered for 14 days. A total of 44 patients, 22 in each group, were included in the study, and both groups were comparable in terms of baseline parameters. All patients randomized to receive chloramphenicol completed the 14 days of treatment, while two patients randomized to receive aztreonam developed an intestinal hemorrhage, and a third patient elected to withdraw from the trial. Defervescence occurred more quickly in the subjects receiving chloramphenicol than in those receiving aztreonam (P < 0.05). All patients in the chloramphenicol group were clinically cured during therapy, while four patients (21%) in the group receiving aztreonam were declared clinical treatment failures. None of the 19 patients receiving aztreonam, compared with 7 of 22 (32%) patients receiving chloramphenicol, had a positive blood culture after 24 h of therapy (P < 0.05). Adverse experiences were unusual and mild. In the study, aztreonam was less effective than chloramphenicol with regard to clinical effectiveness and time of defervescence but was more effective in the elimination of the infecting Salmonella organisms from the bloodstream.

Adolescent

Arginine aminopeptidase, an integral membrane protein of the Cryptosporidium parvum sporozoite.

Cryptosporidium parvum oocysts were studied for the expression of aminopeptidase by using amino acids bound to the synthetic fluorescent substrate 7-amino-4-trifluoromethyl coumarin. After 1 h of incubation, intact oocysts showed no activity; however, homogenization and solubilization with Triton X-114 followed by phase separation yielded a 22-fold increase in aminopeptidase activity in the detergent fraction. With arginyl-6-amino-2-styrylquinoline as a substrate, aminopeptidase activity was observed in permeabilized oocysts and freshly excysted sporozoites but not on intact oocysts or empty oocyst membranes after excystation. These results suggest that C. parvum expresses an arginine aminopeptidase that is an integral protein of the sporozoite membrane.

Aminopeptidases

Shigella sonnei strains isolated from U.S. summer students in Guadalajara, Mexico, from 1986 to 1992.

Plasmid DNA analysis and antibiotic susceptibilities were used to study strains of Shigella sonnei isolated from U.S. travelers to Guadalajara, Mexico, over a period of seven years (1986 to 1992). One hundred sixty-one isolates were analyzed. By the use of cluster analysis, eight different plasmid profiles were identified during this interval. At any point in time, three to seven different plasmid profiles were present in this population. The introduction of strains that carried a new plasmid with a molecular mass of 5.1 MDa was coincidental with an increase in isolation of S. sonnei in 1988. This new plasmid was present in 87.5% of the isolates that were resistant to chloramphenicol. Shigellosis in Guadalajara follows a pattern of hyperendemic transmission with transient peaks of high-frequency isolation of S. sonnei. This pattern results from the concurrent presence of a heterogeneous group of strains as opposed to the widespread transmission of one or a few clones.

Diarrhea

Breast-feeding in Egypt.

Planning, implementation and evaluation of programmes to promote appropriate infant feeding practices require detailed, current information about these practices in the target populations. To estimate the prevalences and identify the correlates of overall breast-feeding and of exclusive breast-feeding in different age periods during infancy, a cohort of 152 apparently healthy neonates and their mothers were followed during October 1987 through April 1989 in rural Bilbeis, Sharqiya Governorate, Egypt. Feeding data were collected through twice weekly home visits thus reducing the potential for bias in our findings due to respondent recall errors. The prevalence of overall breastfeeding in the infants declined from 100% in age period 0-11 weeks to 89% in age period 36-47 weeks. Mothers with previous living children were associated with significantly higher (odds ratio [OR]: 6.53, 95% confidence interval [CI]: 1.33-32.09) and ownership of refrigerators was associated with significantly lower (OR: 0.18, 95% CI: 0.05-0.67) overall breast-feeding prevalences in age periods 24-35 and 36-47 weeks, respectively. The prevalence of exclusive breast-feeding in breast-fed infants dropped from 20% in age period 0-11 weeks to 0% in age period 36-47 weeks. After multivariate adjustment, prelacteal feeding was significantly negatively (OR: 0.12, 95% CI: 0.04-0.37) associated with exclusive breast-feeding in age period 0-11 weeks. Nearly 90% of Bilbeis infants were breast-fed at age 47 weeks, but the initiation of supplementation at 0-11 weeks in 80% of breast-fed infants is contrary to current recommendations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult