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Oral administration of rapanone to a group of female mice at doses of 60 and 120 mg/kg, reduced the percentage of pregnancies compared to control group, suggesting an anovulatory effect. Postcoital administration induced uterine alteration in both the first and second gestation periods. These results seem to indicate inhibition of trophoblast implantation in the first period, and an abortive effect and/or reabsorption in the second. Daily administration of rapanone to a group of male mice resulted in fertility alteration, which is attributed to an antispermatogenic effect. Rapanone did not show acute toxic effects at the doses tested in this research.

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The frequency of Campylobacter jejuni infection in children under 4 years of age, with and without diarrhea, attending the Hospital Infantil de Mexico was studied. Campylobacter was cultured from rectal swabs in 23 (8.7%) of 265 children with diarrhea, with the highest isolation rate in the 7- to 12-month age group, and in 2 (4%) of 54 children without diarrhea. From 5 (22%) of the children infected with Campylobacter, Salmonella or Shigella sp. were simultaneously cultured. Major clinical features of the patients with Campylobacter were similar to those observed in children with nontyphoidal salmonellosis. The isolation rate of Campylobacter was particularly high during the warm season. From these data it is difficult to establish a causative relationship between the presence of Campylobacter and diarrheal disease.

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343 children with acute diarrhea were studied from january 1976 to september 1977. Rotavirus was the agent most frequently isolated (18 per cent) followed by Shigella (12 per cent) and Salmonella (10 per cent). Enterotoxigenic E. coli was identified in 8 per cent and invasive E. coli only in two cases. 80 per cent of isolated rotavirus fell in the neonate group and 25 per cent in the infant group. Diarrhea caused by rotavirus had a short duration, fever was negligible and abundant liquid stools were present without leukocytes in the fecal mucus and with a high percentage (48 per cent) of transient lactose intolerance. Polymorphonuclear leukocytes were found in fecal mucus in 75 per cent of cases caused by Shigella and only in 40 per cent of cases where the causal agent was Salmonella.

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During a 22-month period, 595 children with diarrhea and 210 age-matched controls attending clinics in Houston (367 children) and Mexico (438) were prospectively evaluated for enteric pathogens. Enteropathogens associated with disease were Shigella (18%), rotavirus (14%), Salmonella (9%), toxigenic Escherichia coli (6%), and others (12%), including 14 Proteus isolates that caused rounding of adrenal cells. Enteropathogens were isolated from a greater (P less than 0.001) number of children with diarrhea (59%) than from asymptomatic controls (6%). Paired sera tested for antibody to heat-labile toxin of E. coli rarely demonstrated a fourfold rise during episodes of diarrhea. This study demonstrates: (1) more striking illness in children from Mexico; (2) more common occurrence of Shigella in Houston, and of rotavirus and Salmonella in Mexico; (3) lack of seasonal occurrence of rotavirus isolation in either population and a summertime occurrence of Shigella in Houston; (4) lack of toxigenic E. coli isolation in endemic diarrhea of either population; and (5) a significant (P less than 0.001) age-related acquisition of E. coli LT antibodies.

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Daily food histories for one month were obtained in summer, 1975, from students attending a Mexican university to determine the influence of food consumption on the development and etiology of diarrhea. In newly-arrived students from the U.S. who ate half or more of their meals in the school cafeteria and public restaurants there were significant increases in diarrhea (p less than 0.005); shigella infection (p less than 0.05) and toxigenic E. coli infection (p less than 0.025) compared to the students eating a comparable number of meals in private homes. In the summer U.S. students there was also an association of diarrhea and eating from street vendors (p less than 0.05). In full-time U.S. students who had lived in Mexico a year or longer as well as in Latin American students a relationship between location of meals and occurrence of enteric disease was not apparent. High numbers of enteric bacteria were recovered from food from the school's cafeteria, public restaurants, street vendors and small grocery stores. Shigella were isolated from cooked and uncooked hamburger patties from the school cafeteria. Four shigella carriers were found among kitchen personnel at the school. This study demonstrates that food serves as a major vehicle through which travelers' diarrhea occurs.

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Enteropathogens were investigated as possible agents in pediatric diarrhea occurring in Mexico City during the summer of 1975. Pathogens were identified in 47 (76%) of 62 cases. Rotavirus particles were detected in 16 cases. Enterotoxigenic Escherichia coli was detected in 29 cases; 11 were positive for heat-labile enterotoxin and 18 were positive for only the heat-stable form of enterotoxin. Multiple pathogens were found simultaneously in 15 (24%) of the study population. This study indicates that the etiology of pediatric summertime diarrhea in Mexico City is diverse. ETEC and RV were the most frequently encountered pathogens, yet they frequently occurred together and with other pathogens. ST-only strains of toxigenic E. coli were as frequently recovered as LT-E. coli suggesting that both forms of ETEC must be sought in future field studies.

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Acute- and convalescent-phase sera from 132 students attending a university in rural Mexico were assayed for antibody against the heat-labile enterotoxin (LT) of Escherichia coli by neutralization of LT activity in the Y-1 adrenal cell assay and by passive immune hemolysis of LT-sensitized sheep erythrocytes. The two titration methods produced comparable results with respect to antitoxin responses detected. An inverse relationship was found between acute geometric mean antitoxin titer and the occurrence of diarrhea associated with LT-producing E. coli, especially in newly arrived students from the U.S.A. A significant correlation (P less than 0.00 5) was found between a rise in antitoxin titer detectable by the passive immune hemolysis technique and diarrhea with LT-producing E. coli isolated. Thus, humoral antitoxin titers appear to be a useful indicator of immune status with respect to enterotoxigenic (LT) E. coli diarrhea.

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Ampicillin-resistant strains of Shigella dysenteriae type 1 isolated in epidemics in Mexico, Central America, and Bangla Desh were examined for the presence of plasmid deoxyribonucleic acid (DNA) by gel electrophoresis. All strains contained a heterogeneous population of plasmids. Transfer experiments to Escherichia coli K-12 indicated that the ampicillin resistance determinant (Ap(r)) was located on a 5.5-megadalton (Mdal) plasmid identical in all Shiga strains examined, as judged by DNA hybridization and by its molecular properties. This 5.5-Mdal plasmid contained the ampicillin transposon (TnA) sequences. There was not a high degree of homology between the Shiga Ap(r) plasmid DNA and DNA obtained from Ap(r)Salmonella typhi strains isolated from typhoid epidemics in Mexico, previous to the dysentery outbreaks. Although low, the degree of reassociation observed indicated that probably part of the TnA sequence was present in S. typhi DNA. The DNA hybridization experiments showed, in addition, that there was a high degree of homology among Ap(r) plasmids isolated from different enterobacteria, and this identity was confirmed by restriction endonuclease activity. These results together with their similarities in molecular and replicative properties indicate that the Ap(r) plasmids, as was suggested for the Sm(r) Su(r) plasmids, possibly evolved once and then epidemiologically spread in the Enterobacteriaceae.

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Enterotoxigenic strains of Escherichia coli were isolated from eight (16%) of 50 Mexican children admitted to the hospital with diarrhea and from one of 50 children hospitalized for nonenteric disorders. All of the toxigenic strains tested elaborated a heat-labile enterotoxin, and in seven of nine patients no E. coli capable of concomitant production of heat-stable enterotoxin were found. None of the strains of E. coli with classical enteropathogenic serotypes isolated from nine patients with diarrhea produced either heat-labile or heat-stable enterotoxin. Although the results of this study strongly suggest that enterotoxigenic strains of E. coli are probably responsible for a significant number of cases of diarrhea in an indigenous Mexican pediatric population, further proof will require demonstration of in vivo production of enterotoxin and/or antitoxin.

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A clinic was established at Universidad de las Americas, Cholula, Puebla, Mexico for the study of acute diarrhea rates in newly-arrived students and full-time students. Diarrhea occurred in 22 of 55 newlly-arrived U.S. summer students (40%), compared to 28 of 142 U.S. full-time students (20%), 4 of 29 Venezuelan summer and full-time students (14%) and 7 of 66 Mexican full-time students (11%) (the differences were significant, p less than 0.005). Recurrent episodes of diarrhea during the month of study occurred in 15% of U.S. summer students, 4% of U.S. full-time students, and were non-existent in students from Latin America. As well as the 61 students with diarrhea enrolled in the incidence study, all students who developed diarrhea at the univeristy were encouraged to visit the clinic. This gave a total population of 130 cases of diarrhea. The illness that developed in students form the U.S. varied widely, but it typically consisted of seven to 13 unformed stools during the first 48 hours of illness, with illness persiting three to five days. Illness tended to be more severe in the U.S. students. Fifty per cent of the U.S. students with diarrhea had "severe" illness (greater than or equal to 10 unformed stools in first 48 hours) compared to 23% of the Latin Americans. This study indicates that the agents responsible for diarrhea in Latin America are widespread and that resistance to infection develops after prolonged or repeated exposure.

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The role played by different groups of microorganisms, including aerobic and anaerobic bacteria, viruses, etc., on acute and chronic infections of urinary ducts is discussed, together with general aspects of pathogenesis and diagnosis of such infections.

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The author discusses new knowledge concerning E. coli enterotoxins and Duovirus in the production of diarrheal disease.

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In June 1972, an epidemic of dysentery began in a hospital ward lodging 22 children with tuberculosis. Fifteen of them developed the disease and five children died. The age of the children ranged from five months to four years. A rectal swab culture taken from all hospitalized children three weeks after the initiation of the outbreak revealed Shigella dysenteriae type 1 in five of the patients (28%). The strains isolated were susceptible to cephalothin, gentamicin, kanamycin, colistin, trimethoprim, and nalidixic acid, but were resistant to ampicillin (greater than 5,000 mug/ml), chloramphenicol (300 mug/ml), streptomycin (400 mug/ml), tetracycline (100 mug/ml), and sulfadiazine (1,000 mug per disk). Transfer experiments to Escherichia coli K-12 indicated that these strains were infected with two different plasmids; one was responsible for resistance to chloramphenicol, tetracycline, streptomycin, and sulfonamides, and the other caused resistance to ampicillin. The epidemiological and clinical importance of these findings is emphasized.

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