Onofre Muñoz

A Comprehensive Review of the Natural History of Helicobacter pylori Infection in Children

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life.

A Community-Based Seroepidemiologic Study of Helicobacter pylori Infection in Mexico

A nationwide community-based survey for Helicobacter pylori infection had not been done. This study sought to determine the seroprevalence of infection in Mexico, and the socioeconomic and demographic variables that are risk factors for infection. The survey assessed 11,605 sera from a sample population representing persons ages 1-90 years from all socioeconomic and demographic levels and from all regions of Mexico. Antibodies against H. pylori were studied by ELISA using whole cell antigen. Among the findings were that 66% of the population was infected and that age was the strongest risk factor for infection. By age 1 year, 20% were infected and by age 10 years, 50% were infected. Crowding (odds ratio [OR], 1.4), low educational level (OR, 2.42), and low socioeconomic level (OR, 1.43) were risk factors for infection. Prevalence was similar in urban and in rural communities (OR, 0.95). This study is the largest community-based seroepidemiologic study of H. pylori to date.

Increasing Multidrug Resistance in Helicobacter pylori Strains Isolated from Children and Adults in Mexico

ABSTRACT The susceptibilities to three antimicrobials of 195Helicobacter pylori strains isolated from Mexican patients is reported; 80% of the strains were resistant to metronidazole, 24% were resistant to clarithromycin, and 18% presented a transient resistance to amoxicillin. Resistance to two or more antimicrobials increased significantly from 1995 to 1997.

Diagnostic value of tachypnoea in pneumonia defined radiologically

OBJECTIVE To evaluate whether sensitivity and specificity of tachypnoea for the diagnosis of pneumonia change with age, nutritional status, or duration of disease. METHODS Diagnostic testing of 110 children with acute respiratory infection, 51 of whom presented with tachypnoea. The gold standard was a chest roentgenogram. Thirty five children had a radiological image of pneumonia; 75 were diagnosed as not having pneumonia. Sensitivity, specificity, and percentage of correct classification of tachypnoea, by itself or in combination with other clinical signs for all children, by age groups, nutritional status, and disease duration were calculated. RESULTS Tachypnoea as the sole clinical sign showed the highest sensitivity (74%) and a specificity of 67%; 69% of cases were classified correctly. Sensitivity was reduced when other clinical signs were combined with tachypnoea, and there was no significant increase in correct classification, although specificity increased to 84%. In children with a disease duration of less than three days, tachypnoea had a lower sensitivity and specificity (55% and 64%, respectively), and a lower percentage of correct classification (62%). In children with low weight for age (< 1 Z-score), tachypnoea had a sensitivity of 83%, a specificity of 48%, and 60% correct classification. Sensitivity and specificity did not vary with age groups. CONCLUSIONS Tachypnoea used as the only clinical sign is useful for identifying pneumonia in children, with no significant variations for age. In children with low weight for age, tachypnoea had higher sensitivity, but lower specificity. However, during the first three days of disease, the sensitivity, specificity, and percentage of correct classification were significantly lower.

Helicobacter pylori vacA and cagA Genotypes in Mexican Adults and Children

Studies examining associations between Helicobacter pylori virulence markers and disease have concentrated on adults in developed countries. This study assessed adults and children in Mexico. Ninety patients were recruited, 56 adults (37 with active peptic ulceration and 19 with no ulcers) and 34 children (all with recurrent abdominal pain and no ulcers). H. pylori was cultured from gastric biopsy specimens, and vacA alleles and cagA were typed by use of polymerase chain reaction from multiple colony sweeps. Multiple vacA types were common in single-biopsy isolates and were more frequent in adults with ulcers (95%) than in adults without ulcers (37%; P<.001) or in children (52%; P<.01). vacA s1b and cagA+ strains were more frequent in adults than in children. vacA s1 and cagA+ strains had similar frequencies in adults with and without ulcers. In conclusion, infection with multiple H. pylori strains, defined by different vacA genotypes, is common in Mexico. Such mixed infection is associated with ulcer disease. Strain populations infecting Mexican adults and children differ.

Antibiotic noncompliance and waste in upper respiratory infections and acute diarrhea.

A prospective cohort study was conducted to analyze factors associated with antibiotic noncompliance and waste among patients suffering acute respiratory infection (ARI) and acute diarrhea (AD). The study took place in four primary health care clinics in Mexico City, two belonging to the Ministry of Health (MoH) and two to the Mexican Social Security Institute (IMSS). Two hundred twenty-two patients with ARI and 155 with AD were included. Data about study variables and the assessment of compliance were obtained through patient interviews and direct observation. Factors associated with noncompliance were assessed through a multiple logistic regression procedure. Noncompliance was 60% for ARI and 55.5% for AD in both health care systems. Prescription of an antibiotic was justified only in 13.5% of cases. Associated factors were: increased duration of illness (OR 2.95; 95% CI, 1.17-7.41); complexity of the treatment: 3 or more doses per day (OR 2.47; 95% CI, 1.56-3.92), and treatment for more than 7 days (OR 1.94; 95% CI, 1.16-3.26); younger age of patient (OR 1.89; 95% CI, 1.18-3.02); and an inadequate physician-patient relationship (OR 1.87; 95% CI, 1.16-3.02). Antibiotic waste was higher in IMSS (ARI 39.3%, AD 32.6%), than in the MoH (ARI 21.2%, AD 16.4%). Educational strategies to modify physician prescribing practices and strengthen physician-patient relationships might improve compliance and decrease drug waste.

Validation of a Serologic Test for the Diagnosis of Helicobacter pylori Infection and the Immune Response to Urease and CagA in Children

Objective:Little is known about Helicobacter pylori infections and the immune response to urease and CagA in pediatric populations. Our aims were: 1) to validate serological assays for antibodies against whole cell extract, CagA, and urease of H. pylori; 2) to examine their role in diagnosis of infection in children with recurrent abdominal pain (RAP); and 3) to examine the antibody responses to CagA and urease in children.Methods:An enzyme-linked immunosorbent assay (ELISA) for diagnosis of H. pylori infection using whole cell extracts was validated in 50 children with biopsy-confirmed infection. The IgG and IgA antibody responses against recombinant CagA and urease were compared by ELISA in 82 children with RAP and in 246 age- and sex-matched healthy children.Results:The whole-cell extract ELISA had a sensitivity of 85% and specificity of 87%. Children with RAP were more infected with H. pylori than were healthy control subjects; however, IgG and IgA CagA seropositivity was lower among those with RAP than among asymptomatic children (34% and 23%vs 76% and 55%, respectively; p < 0.0001). In both groups of children, the immune response to urease was low.Conclusion:A serodiagnosis of H. pylori infection using native strains was developed. The difference in the immune response between children with RAP and control subjects suggests that RAP occurs during the acute phase of H. pylori infection. Our results also suggest that urease is a poor immunogen.

Infection with CagA+Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico

Helicobacter pylori strains possessing the Cag pathogenicity island have been associated with increased gastric inflammation and with duodenal ulcer. In contrast, studies on the association of cagA+ H. pylori infections and gastric cancer have shown conflicting results. The aim of our study was to determine whether H. pylori and CagA status are associated with gastric cancer in Mexico. We selected serum samples from 3 geographic areas with gastric cancer mortality rates per 100,000 inhabitants of 2.5 (low risk), 4.5 (medium risk) and 6.4 (high risk). H. pylori infection was determined by the detection of antibodies to H. pylori whole cell antigen by an enzyme‐linked immunosorbent assay (ELISA). To study the prevalence of infection with cagA+ strains, serum IgG antibodies to CagA were determined by ELISA using a recombinant CagA antigen. Of the 2,775 individuals studied, 1,931 were H. pylori seropositive and 1,710 had antibodies against CagA. The risk for gastric cancer in the 3 populations studied increased proportionally as infection with cagA+ strains increased (p < 0.001 for trend). H. pylori infection also showed association with gastric cancer (p < 0.05). Individuals seropositive for CagA, but seronegative for H. pylori whole cell antigen, were more frequent in areas with higher gastric cancer rates (p < 0.01). These results support the possible role of CagA(+) status as predictor of risk for gastric adenocarcinoma in Mexico; this is in agreement with results in European and American populations, but contrary to studies in some Asian countries. Int. J. Cancer 78:298–300, 1998.© 1998 Wiley‐Liss, Inc.

Prevalence and Genetic Diversity of Human Astroviruses in Mexican Children with Symptomatic and Asymptomatic Infections

ABSTRACT The prevalence and type diversity of human astroviruses (HAstV) in children with symptomatic and asymptomatic infections were determined in five localities of Mexico. HAstV were detected in 4.6 (24 of 522) and 2.6% (11 of 428) of children with and without diarrhea, respectively. Genotyping of the detected strains showed that at least seven (types 1 to 4 and 6 to 8) of the eight known HAstV types circulated in Mexico between October 1994 and March 1995. HAstV types 1 and 3 were the most prevalent in children with diarrhea, although they were not found in all localities studied. HAstV type 8 was found in Mexico City, Monterrey, and Mérida; in the last it was as prevalent (40%) as type 1 viruses, indicating that this astrovirus type is more common than previously recognized. A correlation between the HAstV infecting type and the presence or absence of diarrheic symptoms was not observed. Enteric adenoviruses were also studied, and they were found to be present in 2.3 (12 of 522) and 1.4% (6 of 428) of symptomatic and asymptomatic children, respectively.

High Rates of Recurrence and of Transient Reinfections of Helicobacter pylori in a Population With High Prevalence of Infection

OBJECTIVES:Little is known concerning the magnitude of reinfection versus recrudescence of Helicobacter pylori (H. pylori) infection after eradication treatment. The aims of this study were to determine the magnitude of H. pylori reinfection versus recrudescence, and to identify possible risk factors for reinfection.METHODS:Children and adults with upper GI symptoms treated at the Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, in Mexico City, Mexico) were studied. H. pylori infection was diagnosed with urea breath test (UBT), histology, and culture. Infected patients received triple therapy, and those who became UBT negative 4–6 wk after treatment were considered as eradicated and were included in the study. A cohort of 141 patients in whom the disease was eradicated was monitored for recurrence with UBT at 3, 6, 9, 12, 18, and 24 months. H. pylori was isolated from gastric biopsy samples before treatment and at recurrence and isolates compared by genotyping.RESULTS:During this period, 32 (22.7%) cases of recurrence were documented the majority occurring during yr 1. In nine of the 32 (28.1%) cases, recurrence was eradicated spontaneously, suggesting these were transient reinfections. Recurrence rates were significantly higher in the subjects 41–60 yr of age than in younger or older subjects. H. pylori isolates from 12 recurrence cases were genotyped; nine (75%) were classified as true reinfection and three as recrudescence.CONCLUSIONS:In our population, recurrence rate is high in adults and transient reinfection is common. In several cases, reinfection occurred by multiple strains, which suggests that soon after eradication, patients are exposed to multiple sources of reinfection.