Longitudinal Analysis of Serological Responses of Adults to<i>Helicobacter pylori</i>Antigens

Perez-Perez, Guillermo I.; Maw, Anna; Feingold-Link, Lani; Gunn, Jennifer; Bowers, Andrea L.; Miñano, Cecilia; Rautelin, Hilpi; Kosunen, Timo U.

doi:10.1086/655660

Cited by 10 publications

(11 citation statements)

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“…Studies on switch class variants for both malaria and other infectious pathogens have found that antibody affinity and avidity will differ between antigens of the same pathogen or even between different domains of a single antigen [ 39 , 40 ]. This can be due to factors such as age and gender, antigen density, strain of the organism, and epitope specificity [ 38 , 41 , 42 ]. Ultimately, current evidence on the associations of antigen-specific IgG subclasses with both exposure and immunity to malaria is varied [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

Mwesigwa

Affara

et al. 2020

BMC Med

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Background As malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools. Methods A prospective cohort study was conducted from 2013 to 2015 in 12 villages across five administrative regions in The Gambia. Serological analysis included samples from the West Coast Region at the start and end of the season (July and December 2013) and from the Upper River Region in July and December 2013 and April and December 2014. Antigen-specific antibody responses to eight Plasmodium falciparum (P. falciparum) antigens—Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175 RIII-V, PfMSP119, PfAMA1, and PfGLURP.R2—were quantified using a multiplexed bead-based assay. The association between antibody responses and clinical and parasitological endpoints was estimated at the individual, household, and population level. Results Strong associations were observed between clinical malaria and concurrent sero-positivity to Etramp5.Ag1 (aOR 4.60 95% CI 2.98–7.12), PfMSP119 (aOR 4.09 95% CI 2.60–6.44), PfAMA1 (aOR 2.32 95% CI 1.40–3.85), and PfGLURP.R2 (aOR 3.12, 95% CI 2.92–4.95), while asymptomatic infection was associated with sero-positivity to all antigens. Village-level sero-prevalence amongst children 2–10 years against Etramp5.Ag1, HSP40.Ag1, and PfMSP119 showed the highest correlations with clinical and P. falciparum infection incidence rates. For all antigens, there were increased odds of asymptomatic P. falciparum infection in subjects residing in a compound with greater than 50% sero-prevalence, with a 2- to 3-fold increase in odds of infection associated with Etramp5.Ag1, GEXP18, Rh2.2030, PfMSP119, and PfAMA1. For individuals residing in sero-positive compounds, the odds of clinical malaria were reduced, suggesting a protective effect. Conclusions At low transmission, long-lived antibody responses could indicate foci of malaria transmission that have been ongoing for several seasons or years. In settings where sub-patent infections are prevalent and fluctuate below the detection limit of polymerase chain reaction (PCR), the presence of short-lived antibodies may indicate recent infectivity, particularly in the dry season when clinical cases are rare. Serological responses may reflect a persistent reservoir of infection, warranting community-targeted interventions if individuals are not clinically apparent but have the potential to transmit. Therefore, serological surveillance at the individual and household level may be used to target interventions where there are foci of asymptomatically infected individuals, such as by measuring the magnitude of age-stratified antibody levels or identifying areas with clustering of above-average antibody responses across a diverse range of serological markers.

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Section: Discussionmentioning

confidence: 99%

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

Mwesigwa

Affara

et al. 2020

BMC Med

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“…Lastly, we have no knowledge of whether H pylori may have been lost or gained in the interval between ascertainment and mortality. However, from longitudinal studies of H pylori- positive adults, we know that rates of ‘spontaneous’ annual loss of the organism among those with established colonisation are low 29. Similarly, early childhood is the nearly exclusive time for colonisation,24 25 thus substantial later-in-life acquisitions are unlikely.…”

Section: Discussionmentioning

confidence: 99%

Association betweenHelicobacter pyloriand mortality in the NHANES III study

Chen

Segers

Blaser

2013

Gut

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Objective Persistent colonization by Helicobacter pylori, and especially by cagA-positive strains, has been related to several health outcomes with effects in opposite directions. Thus, it is important to evaluate its influence on both total and category-specific mortality. Design We conducted prospective cohort analyses in a nationally representative sample of 9895 participants enrolled in the National Health and Nutrition Examination Survey III (NHANES III) to assess the association of H. pylori status with all-cause and cause-specific mortality. Analyses for the association of H. pylori cagA positivity with mortality were conducted in 7,384 subjects with data on H. pylori cagA status. Results In older individuals (> 40.6 years of age), H. pylori was not associated with all-cause mortality (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.84–1.18). There was an inverse association of H. pylori status with stroke mortality (HR, 0.67; 95% CI, 0.44–1.08), and the inverse association was stronger for H. pylori cagA positivity, with the HR of 0.45 (95% CI, 0.27–0.75). H. pylori also was strongly positively related to gastric cancer mortality. After we adjusted p-values using the Benjamini–Hochberg false discovery rate (FDR) method to account for multiple comparisons, these associations remained, and H. pylori status was not related to other outcomes.. Conclusion Our findings suggest that H. pylori has a mixed role in human health, but is not a major risk factor for all-cause mortality.

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“…H. pylori gives rise to a systemic and stable IgG antibody response [25], which only decreases after bacterial eradication by antibiotic treatment or by development of atrophic gastritis. In a previous study by our group, the same ELISA test was used to determine the prevalence of H. pylori in 6‐ to 8‐year‐old Dutch children in 1978 and 1993 [10], showing a marked (52%) decrease in H. pylori prevalence between 1978 and 1993.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter Pylori and the Birth Cohort Effect: Evidence for Stabilized Colonization Rates in Childhood

et al. 2011

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Background The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely due to a birth-cohort effect. We previously observed a decline in H. pylori prevalence in 6- to 8-year old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions. Aim The aim of this study was to investigate whether the birth-cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods Anti-H. pylori IgG antibodies and anti-CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7–9 years who participated in the PIAMA birth cohort. The H. pylori and CagA antibodies were determined by ELISAs that have been extensively validated in children, with a 94% sensitivity for Hp colonization and a 92.5% sensitivity for colonization with a cagA-positive strain. Results Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6–11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1–1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA+ H. pylori strains has become very low, consistent with prior observations that cagA+ strains are disappearing in Western countries.

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Longitudinal Analysis of Serological Responses of Adults toHelicobacter pyloriAntigens

Cited by 10 publications

References 50 publications

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

Association betweenHelicobacter pyloriand mortality in the NHANES III study

Helicobacter Pylori and the Birth Cohort Effect: Evidence for Stabilized Colonization Rates in Childhood

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