A 500-year tale of co-evolution, adaptation, and virulence: Helicobacter pylori in the Americas.

Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.

Natural history of Helicobacter pylori infection in Mexican schoolchildren: incidence and spontaneous clearance.

OBJECTIVES: The aim of the present study was to estimate the incidence and spontaneous clearance rate of Helicobacter pylori infection and the effect of some variables on these outcomes in schoolchildren. METHODS: From May 2005 to December 2010, 718 schoolchildren enrolled in 3 public boarding schools in Mexico City participated in the follow-up. At the beginning of the study and every 6 months thereafter, breath samples were taken to detect H pylori infection; blood samples and anthropometric measurements were taken to evaluate nutritional status. Data on sociodemographic characteristics were collected. RESULTS: The prevalence of H pylori infection was 38%. The incidence rate was 6.36%/year. Schoolchildren with anemia or iron deficiency at the beginning of the study (who received iron supplements) showed a higher infection acquisition rate than those with normal iron nutritional status, hazard ratio (HR) 12.52 (95% confidence interval [CI] 4.01%-39.12%), P < 0.001 and HR 2.05 (95% CI 1.09%-3.87%), P = 0.027, respectively. The spontaneous clearance rate of the infection was 4.74%/year. The spontaneous clearance rate was higher in children who had iron deficiency (who received iron supplements), HR 5.02 (95% CI 1.33%-18.99%), P = 0.017, compared with those with normal nutritional iron status. It was lower in schoolchildren with ≥ 2 siblings compared with schoolchildren with 1 or no siblings, HR 0.23 (95% CI 0.08%-0.63%), P = 0.004. CONCLUSIONS: H pylori infection status is dynamic in schoolchildren. Variables related to health status and infection transmission, such as iron status and number of siblings, are important for the incidence and spontaneous clearance of H pylori infection.

Effect of Helicobacter pylori infection on growth velocity of school-age Andean children.

BACKGROUND: Helicobacter pylori infection affects about half of the world's population and is usually acquired in childhood. The infection has been associated with chronic gastritis, peptic ulcer, and stomach cancer in adulthood. Little is known, however, about its consequences on child health. We examined the effect of H. pylori infection on growth among school-age children in the Colombian Andes by comparing growth velocity in the presence and absence of H. pylori infection. METHODS: Children who were 4-8 years old in 2004 were followed up in a community where infected children received anti-H. pylori treatment (n = 165) and a comparison community (n = 161) for a mean of 2.5 years. Anthropometry measurements were made every 3 months and H. pylori status ascertained by urea breath test every 6 months. Growth velocities (cm/month) were compared across person-time with and without infection, using mixed models for repeated measures. RESULTS: In the untreated community, 83% were H. pylori-positive at baseline and 89% were -positive at study end. The corresponding prevalences were 74% and 46%, respectively, in the treated community. Growth velocity in the pretreatment interval was 0.44 (standard deviation [SD] = 0.13) cm/month. Models that adjusted for age, sex, and height estimated that H. pylori-positive children grew on average 0.022 cm/month (95% confidence interval = 0.008 to 0.035) slower than H. pylori-negative children, a result that was not appreciably altered by adjustment for socioenvironmental covariates. CONCLUSIONS: This study suggests that chronic H. pylori infection is accompanied by slowed growth in school-age Andean children.

Exposure to Helicobacter pylori-positive siblings and persistence of Helicobacter pylori infection in early childhood.

OBJECTIVES: Cross-sectional studies suggest that Helicobacter pylori may be transmitted between siblings. The present study aimed to estimate the effect of an H pylori-infected sibling on the establishment of a persistent H pylori infection. MATERIALS AND METHODS: The authors used data collected from a Texas-Mexico border population from 1998 to 2005 (the "Pasitos Cohort Study"). Starting at age 6 months, H pylori and factors thought to be associated with H pylori were ascertained every 6 months for participants and their younger siblings. Hazard ratios were estimated from proportional hazards regression models with household-dependent modeling. RESULTS: Persistent H pylori infection in older siblings always preceded persistent infection in younger siblings. After controlling for mother's H pylori status, breast-feeding, antibiotic use, and socioeconomic factors, a strong effect was estimated for persistent H pylori infection in an older sibling on persistent infection in a younger sibling (hazard ratio 7.6, 95% confidence interval 1.6-37], especially when the difference in the age of the siblings was less than or equal to 3 years (hazard ratio 16, 95% confidence interval 2.5-112). CONCLUSIONS: These results suggest that when siblings are close in age, the older sibling may be an important source of H pylori transmission for younger siblings.

Exposure to antibiotics in a United States-Mexico border birth cohort.

OBJECTIVE: The goal was to compare the frequency of children's antibiotic intake, emphasizing antibiotics with anti-Helicobacter pylori effects, in El Paso, Texas, and Juarez, Mexico. METHODS: Hispanic children were enrolled prenatally at mother-child clinics in El Paso, and Juarez, in 1998-2000, to identify determinants of H pylori infection. During follow-up examinations targeted every 6 months from 6 to 84 months of age, caretakers reported medication use during the preceding interval. Courses of any systemic and H pylori-effective antibiotics were compared for US and Mexican children. RESULTS: Antibiotic data were available for 602 children, from 2938 follow-up visits. Overall antibiotic intake was higher in Juarez, where 84% of children received > or = 1 course during the follow-up period (52% of visits), compared with El Paso, where 76% of children received > or = 1 course (40% of visits). In contrast, the intake of H pylori-effective antibiotics was higher in El Paso, where 65% of children received > or = 1 course during the follow-up period (27% of visits), compared with Juarez, where 44% of children received > or = 1 course (16% of visits). Of H pylori-effective courses, 94% contained amoxicillin and 2% each clarithromycin, metronidazole, and furazolidone; uses were primarily for throat and ear infections, diarrhea, and cold/flu. CONCLUSIONS: Pediatric antibiotic use was higher in Mexico than on the US side of the border. Apparent misuse of H pylori-effective antibiotics was more frequent in Juarez but also occurred in El Paso. Such misuse of antibiotics may lead to drug resistance and may impair the control of H pylori infection in this region.

The association of drinking water quality and sewage disposal with Helicobacter pylori incidence in infants: the potential role of water-borne transmission.

The mode of transmission of Helicobacter pylori, a bacterium causing gastric cancer and peptic ulcer disease, is unknown although waterborne transmission is a likely pathway. This study investigated the hypothesis that access to treated water and a sanitary sewerage system reduces the H. pylori incidence rate, using data from 472 participants in a cohort study that followed children in Juarez, Mexico, and El Paso, Texas, from April 1998, with caretaker interviews and the urea breath test for detecting H. pylori infection at target intervals of six months from birth through 24 months of age. The unadjusted hazard ratio comparing bottled/vending machine water to a municipal water supply was 0.71 (95% confidence interval (CI): 0.50, 1.01) and comparing a municipal sewer connection to a septic tank or cesspool, 0.85 (95% CI: 0.60, 1.20). After adjustment for maternal education and country, the hazard ratios decreased slightly to 0.70 (95% confidence interval: 0.49, 1.00) and 0.77 (95% confidence interval: 0.50, 1.21), respectively. These results provide moderate support for potential waterborne transmission of H. pylori.

Antibiotics taken for other illnesses and spontaneous clearance of Helicobacter pylori infection in children.

PURPOSE: Factors that determine persistence of untreated Helicobacter pylori (H. pylori) infection in childhood are not well understood. We estimated risk differences for the effect of incidental antibiotic exposure on the probability of a detected clearance at the next test after an initial detected H. pylori infection. METHODS: The Pasitos Cohort Study (1998-2005) investigated predictors of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico. Children were screened for infection at 6-month target intervals from 6 to 84 months of age, using the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. Exposure was defined as courses of any systemic antibiotic (systemic) or those with anti-H. pylori action (HP-effective) reported for the interval between initial detected infection and next test. Binomial regression models included country of residence, mother's education, adequacy of prenatal care, age at infection, and interval between tests. RESULTS: Of 205 children with a test result and antibiotic data following a detected infection, the number of children who took > or =1 course in the interval between tests was 74 for systemic and 33 for HP-effective. The proportion testing negative at the next test was 66% for 0 courses, 72% for > or =1 systemic course, and 79% for > or =1 HP-effective course. Adjusted risk differences (95%CI) for apparent clearance, comparing > or =1 to 0 courses were 10% (1-20%) for systemic and 11% (0-21%) for HP-effective. CONCLUSIONS: Incidental antibiotic exposure appears to influence the duration of childhood H. pylori infection but seems to explain only a small portion of spontaneous clearance.

Correspondence between Helicobacter pylori antibodies and urea breath test results in a US-Mexico birth cohort.

The uncertain accuracy of methods for detecting Helicobacter pylori infection in young children complicates research on this infection in early life. The aim of the present report was to describe the correspondence between positive serology and positive urea breath test (UBT) in children followed from age 0 to 24 months in the Pasitos Cohort Study, conducted along the US-Mexico border at El Paso and Juarez. Children were recruited before birth during 1998-2000 and examined at target ages of 6, 12, 18 and 24 months. H. pylori infection was detected using an enzyme immunoassay for serum immunoglobulin G antibodies and the (13)C-urea breath test corrected for age-dependent variation in CO(2) production. Of 472 children, 125 had one or more positive UBT results and 46 had one or more positive serology results. The prevalence of H. pylori infection at target ages of 6, 12, 18 and 24 months was 7%, 14%, 16% and 19%, respectively, by UBT and 8%, 2%, 3% and 3%, respectively, by serology. Few (<1%) of those tested on both tests were positive on both at any age. Among UBT-positive children, 6% were concurrently seropositive and 6% became seropositive later. Because UBT positivity cut points were selected to minimise false positives, these results suggest that H. pylori infection occurred frequently in this cohort, but rarely produced detectable antibodies. For clinical or epidemiological investigations, serology should not be used as the sole method for detecting H. pylori infection in children aged 2 years or less.

Dynamics of Helicobacter pylori infection in a US-Mexico cohort during the first two years of life.

BACKGROUND: The Pasitos Cohort Study has followed children in El Paso, Texas and Ciudad Juarez, Mexico since 1998 to identify determinants of Helicobacter pylori infection. This paper describes patterns of acquisition and elimination of H. pylori infection in 468 children from birth to 24 months. METHODS: Mothers were recruited during pregnancy at maternal-child clinics; children were targeted for follow-up examinations every 6 months after birth. H. pylori infection was detected using the 13C-urea breath test, corrected for age-dependent variation in CO2 production. RESULTS: Test results were available for 359, 341, 269, and 215 children around target ages of 6, 12, 18, and 24 months, respectively. The person-time at risk of a first detectable infection was 7742 person-months; 128 first infections were detected, thus the incidence rate was 1.7% per month (95% confidence interval 1.4-2.0%). Rates were similar in boys and girls and on both sides of the border; evidence suggests, however, that this similarity could be due to selection bias. Among children with follow-up after a positive test, 77% tested negative at a later visit. CONCLUSIONS: The initial acquisition of detectable H. pylori infection occurred at a rate of 20% per year among Pasitos Cohort children from birth to 24 months of age. A key finding, with implications for clinical, community health, and research settings, is that most of these infections did not persist. The transient nature of early H. pylori infection should be considered when designing research or contemplating therapeutic intervention for this age group.

Determinants of geographic variation in Helicobacter pylori infection among children on the US-Mexico border.

Rates of Helicobacter pylori infection are traditionally higher in developing countries than in developed countries, but the specific reasons for these differences are not fully clear. While chronic diseases resulting from H. pylori are generally of adult onset, chronic infection usually begins in childhood. In this cross-sectional study (1998-2000), the authors compared prevalences of H. pylori infection among children under age 6 years on both sides of the Rio Grande. Participants included 264 children of women from low-income families who were receiving services at health clinics in Juarez, Mexico, or El Paso, Texas, from April 1998 through October 2000. Data were collected through personal interviews and serologic testing for H. pylori antibodies. The crude odds ratio for H. pylori prevalence among Mexican children as compared with US children was 3.94 (95% confidence interval: 1.72, 9.06). After adjustment for covariates, the odds ratio decreased to 1.70 (95% confidence interval: 0.64, 4.52). The adjustments that produced the greatest reduction in the odds ratio for location were those for household crowding and maternal education. This study identified specific factors that may explain geographic variation in H. pylori prevalence among children.

Helicobacter pylori infection in pregnant women from a U.S.-Mexico border population.

Helicobacter pylori infection causes chronic digestive diseases that disproportionately affect Hispanics and other immigrant groups in the United States. Information on the epidemiology of H. pylori infection in pregnant women who reside along the U.S.-Mexico border is critical to understanding the dynamics of current H. pylori transmission patterns within families along the border. We describe the epidemiology of H. pylori infection in pregnant women recruited from Women, Infants, and Children (WIC) clinics in El Paso, Texas, and Mexican Social Security Institute maternal-child clinics in Ciudad Juarez, Mexico, from April 1998 to October 2000. We interviewed participants regarding environmental factors and tested their serum for IgG antibodies. We used logistic regression to estimate associations between environmental exposures and the odds of H. pylori prevalence. Definitive serological tests were available from 751 women. Seroprevalence was 74% in Juarez women and 56% in El Paso women. Prevalence increased with age, crowding, poor sanitation, and residence in Mexico, decreased with education, and was not associated with the woman's number of living children. In the U.S.-Mexico border region, women of reproductive age have a high prevalence of H. pylori infection, apparently related to poor socioeconomic conditions.

Establishment of a binational cohort to study Helicobacter pylori infection in children.

Chronic Helicobacter (H.) pylori infection, typically of childhood onset, causes upper digestive tract diseases of major impact among socioeconomically marginalized populations. This infection is common in children from ethnic minorities in the United States, and particularly so in immigrant children from Mexico. Prevention measures for H. pylori infection do not yet exist, given limited understanding of what causes either acute or persistent infection. To address this gap, we initiated the Pasitos Cohort Study to follow children from low-income families in the border region that includes El Paso County, Texas, and Ciudad Juarez, Chihuahua. The children were enrolled prior to birth, and are examined at 6-month intervals to observe the natural history of H. pylori infection, and to identify risk factors for acquisition, recurrence, and persistence. This report details the study methods, describes how the cohort was established, and discusses the challenges of compliance with follow up in the border setting. Between April 1998 and October 2000, 1,288 pregnant women were screened for eligibility; 807 of 994 eligible women consented to participate. Birth documentation was obtained for 615 infants, and 472 entered follow up. Successful follow up of this cohort requires resources, including a well-trained, dedicated staff, and incentives, to facilitate and motivate long-term participation. Future findings from this ongoing study will help to fill critical gaps in knowledge regarding the epidemiology of H. pylori infection, and will contribute to the identification of prevention strategies.

Implications of Helicobacter pylori infection for stomach cancer prevention

Um acúmulo de evidências aponta para Helicobacter pylori, uma causa comprovada de gastrite e úlcera péptica, na etiologia do câncer gástrico. O controle dessa infecçäo poderia reduzir a ocorrência de gastrite crônica e úlcera péptica, além de diminuir o risco de câncer de estômago. O impacto desse agente infeccioso a nível de saúde pública justifica os esforços no sentido de identificar medidas preventivas. Revê as evidências ligando o H. pylori ao câncer de estômago e avalia o potencial para controle em populaçöes de alto risco. Discute os obstáculos atuais ao controle do H. pylori, inclusive sua associaçäo com condiçöes sócio-econômicas precárias, a dificuldade em identificar casos incidentes, a falta de imunidade natural à reinfecçäo, a eficácia limitada da antibioticoterapia em populaçöes com alta prevalência e o conhecimento incompleto sobre o reservatório da infecçäo, modo de transmissäo fatores envolvidos na susceptibilidade do hospedeiro e possibilidade de desenvolver uma vacina eficaz. Linhas de pesquisa prioritárias incluem estudos projetados para identificar fatores de risco modificáveis para a aquisiçäo da infecçäo, fatores modificáveis no hospedeiro que possam aumentar a resistência à infecçäo, antibioticoterapias mais eficazes e vacinas eficazes.