Raúl León-Barúa

A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease

BACKGROUND Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. METHODS We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. RESULTS Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. CONCLUSIONS Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.

Rapid Recurrence of Helicobacter pylori Infection in Peruvian Patients after Successful Eradication

Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. Since gastric cancer is common in Peru, eradication of H. pylori may help to reduce the occurrence of gastric cancer. This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens. The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients. Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H. pylori infection. Of 105 patients with H. pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period. Thirty-five patients from whom H. pylori was eradicated and who were tested for antibodies to H. pylori remained consistently seropositive. Rapid recurrence of H. pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H. pylori in developing countries.

Comparison of single-dose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults.

Shigellae have been shown to be highly susceptible to new quinolone agents, with average MICs for 90% of isolates of less than 0.1 microgram/ml. Because these agents also reach high concentrations in the stool after a single dose, the effectiveness of a single 800-mg dose of norfloxacin and of 5-day treatment with trimethoprim-sulfamethoxazole (TMP-SMX) were compared in a randomized trial. Patients with clinical dysentery received one of these treatment regimens, and clinical data and follow-up culture results were analyzed for patients whose stool culture on presentation grew shigellae. When 55 patients with shigellosis (26 treated with TMP-SMX, 29 treated with norfloxacin) whose bacterial isolates were susceptible to the antibiotic given were compared by treatment group, no significant differences were seen in days of illness (mean, 2.5 +/- 0.65 days with TMP-SMX and 2.0 +/- 0.47 days with norfloxacin; P = 0.200) or number of unformed stools after starting treatment (mean, 9.7 +/- 2.37 stools with TMP-SMX and 7.6 +/- 3.19 stools with norfloxacin; P = 0.312). Resistance in vitro to TMP-SMX was seen in 15% of Shigella isolates, whereas none was resistant to norfloxacin. Bacteriologic failure was found in 1 patient among 24 receiving TMP-SMX and in none of 25 patients receiving norfloxacin. One single dose of norfloxacin was as effective as 5 days of treatment with TMP-SMX in these adults with shigellosis.

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

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

Helicobacter pylori Populations in Peruvian Patients

Helicobacter pylori is an extremely diverse species. The characterization of strains isolated from individual patients should give insights into colonization and disease mechanisms and bacterial evolution. We studied H. pylori isolates from patients in the Japanese-Peruvian Polyclinic in Lima, Peru, by determining metronidazole susceptibility or resistance and by random amplified polymorphic DNA (RAPD) fingerprinting (a measure of overall genotype). Strains isolated from several biopsy specimens from each of 24 patients were studied. Both metronidazole-susceptible and -resistant strains were isolated from 13 patients, whereas strains of more than one RAPD type were isolated from only seven patients. We propose that the homogeneity in RAPD fingerprints for strains isolated from most persons reflects selection for particular H. pylori genotypes during chronic infection in individual hosts and the human diversity in traits that are important to this pathogen. Carriage of related metronidazole-resistant and -susceptible strains could reflect frequent metronidazole use in Peru and alternating selection for resistant and susceptible phenotypes during and after metronidazole therapy.

Bicarbonate versus citrate in oral rehydration therapy in infants with watery diarrhea: A controlled clinical trial*

In a double-blind, randomized trial, we compared the efficacy of bicarbonate-containing oral rehydration solution vs citrate-containing solution in the treatment of infantile diarrheal dehydration and acidosis. Ninety-seven infants 3 to 24 months of age were entered in the study; 49 received bicarbonate-containing solution and 48 citrate-containing solution. The two groups were similar in all respects at the beginning of the study. Oral rehydration was successful (i.e., no intravenously administered fluids were required) in 85% of study patients; the success rate was similar in both treatment groups. Serum total CO2 concentration increased in a similar fashion in both groups, reaching near normal values at 48 hours after admission. We conclude that sodium citrate can be substituted for sodium bicarbonate in the formulation of the orally administered rehydration solution recommended by the World Health Organization for treatment of diarrheal dehydration in infants.

Differentiation of osmotic and secretory diarrhoea by stool carbohydrate and osmolar gap measurements

Clinical features and laboratory tests that determine carbohydrate in faeces were evaluated to determine which was best able to distinguish between osmotic and secretory diarrhoea in infants and children. For this purpose 80 boys aged 3 to 24 months, with acute watery diarrhoea, were studied prospectively. The faecal osmolar gap (FOG) was calculated as: serum osmolarity − [2 × (faecal sodium + potassium concentration)]. Fifty eight patients were classified as having predominantly osmotic diarrhoea (FOG >100 mosmol/l), and 22 as having predominantly secretory diarrhoea (FOG ⩽100 mosmol/l). The two groups were comparable in their clinical features on admission, in the results of blood and urine tests, and in the evolution of their diarrhoeal illness. Evidence of steatorrhoea (by positive Sudan III test) and of acid faecal pH on admission were significantly more frequent in patients with osmotic diarrhoea. Mean (SD) faecal osmolarity was not significantly different between the two groups (319 (80) mosmol/l in secretory diarrhoea v 361 (123) mosmol/l in osmotic diarrhoea). Tests for reducing substances in faeces such as Benedict’s test—with and without hydrolysis—and glucose strip, all showed a positive and significant association with osmotic diarrhoea (p <0.05, <0.025, <0.05, respectively). The presence of excess reducing substances (Benedict’s test with hydrolysis >++) on admission was the most sensitive and specific test with the best predictive value for differentiating between the two types of watery diarrhoea.

Chronic Atrophic Gastritis: Early Diagnosis in a Population Where Helicobacter pylori Infection Is Frequent

Chronic atrophic gastritis (CAG) is a premalignant condition characterized by loss of gastric antral deep glands. The histologic changes in antral gastric biopsy specimens from 54 Peruvian patients with dyspepsia were studied to detail the development and characteristics of CAG. Ninety-six percent of the biopsies revealed severe superficial mucosal inflammation and 89% showed deep inflammation. Moderate or severe CAG was present in 36 (67%) of the 54 patients. In the early stages of CAG, a glandular lymphoid adherence lesion was noted in 17 (31%) of the 54 biopsy specimens. This lesion consisted of lymphocytes adherent to the antral deep gland cells and was associated with glandular epithelium alterations. The late stage was characterized by small glands, remnants of glands, and gland replacement with a fibrocellular infiltrate or intestinal metaplasia. We propose that the development of CAG probably proceeds via a stereotyped sequence, with an early deep inflammatory component that may trigger local gland destruction and eventual permanent loss.

Geographic Factors Probably Modulating Alternative Pathways in Helicobacter pylori-Associated Gastroduodenal Pathology: A Hypothesis

It is hypothesized that probable geographic factors of nutritional type, nonrelated to development or socioeconomic level, may modulate the conversion of Helicobacter pylori-associated active chronic gastritis from its early stages to chronic atrophic gastritis (CAG). The factors could be diets low in antioxidant vitamins and other micronutrients such as selenium. In regions of the world where these modulating factors are not present, active chronic gastritis tends to stay in its early stages and to predispose individuals to duodenal ulcer. On the contrary, in regions where the modulating factors are present, the frequency of CAG increases markedly. When CAG becomes severe and extensive, hypochlorhydria ensues. Hypochlorhydria decreases the predisposition to duodenal ulcer, while CAG, a precancerous lesion, predisposes individuals to gastric cancer of the intestinal type. The hypothesis could be tested in a multicenter, multiregional study to (1) determine endoscopically and histologically the prevalence rates of duodenal ulcer, gastric ulcer, gastric cancer, and H. pylori-associated CAG in large series of dyspeptic patients and (2) correlate these prevalence rates with blood levels of micronutrients in these patients.

Comparison of noninvasive breath hydrogen test for gastric acid secretion to standard intubation test in adults

We have developed a noninvasive test for gastric acid secretion based on the reaction of ingested magnesium metal with gastric acid to produce hydrogen gas, which is excreted in exhaled air and belches. This test was compared to the standard intubation test by performing both, on different days, in 36 adult Peruvian outpatients referred for gastric analysis; the correlation coefficient for this comparison was 0.71. The new test was repeated in nine subjects, and the resulting test-retest correlation coefficient was 0.83. The new test thus compares favorably with the standard intubation test. Because it is also noninvasive and should therefore be more acceptable to subjects, this new test may be useful for clinical evaluation and research studies on subjects in whom intubation would be difficult or unacceptable.