Protection From Natural Immunity Against Enteric Infections and Etiology-Specific Diarrhea in a Longitudinal Birth Cohort

Abstract Background The degree of protection conferred by natural immunity is unknown for many enteropathogens, but it is important to support the development of enteric vaccines. Methods We used the Andersen-Gill extension of the Cox model to estimate the effects of previous infections on the incidence of subsequent subclinical infections and diarrhea in children under 2 using quantitative molecular diagnostics in the MAL-ED cohort. We used cross-pathogen negative control associations to correct bias due to confounding by unmeasured heterogeneity of exposure and susceptibility. Results Prior rotavirus infection was associated with a 50% lower hazard (calibrated hazard ratio [cHR], 0.50; 95% confidence interval [CI], 0.41–0.62) of subsequent rotavirus diarrhea. Strong protection was evident against Cryptosporidium diarrhea (cHR, 0.32; 95% CI, 0.20–0.51). There was also protection due to prior infections for norovirus GII (cHR against diarrhea, 0.67; 95% CI, 0.49–0.91), astrovirus (cHR, 0.62; 95% CI, 0.48–0.81), and Shigella (cHR, 0.79; 95% CI, 0.65–0.95). Minimal protection was observed for other bacteria, adenovirus 40/41, and sapovirus. Conclusions Natural immunity was generally stronger for the enteric viruses than bacteria, potentially due to less antigenic diversity. Vaccines against major causes of diarrhea may be feasible but likely need to be more immunogenic than natural infection.

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Blood Pressure and Incident Atrial Fibrillation in Older Patients Initiating Hemodialysis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.13511118 ◽

2019 ◽

Vol 14 (7) ◽

pp. 1029-1038 ◽

Cited By ~ 1

Author(s):

Tara I-Hsin Chang ◽

Sai Liu ◽

Medha Airy ◽

Jingbo Niu ◽

Mintu P. Turakhia ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Older Patients ◽

Cox Model ◽

Intradialytic Hypotension ◽

Hazard Ratios ◽

The Us ◽

Fixed Reference ◽

Lower Hazard ◽

Extended Cox Model

Background and objectivesWe examined the association of predialysis systolic and diastolic BP and intradialytic hypotension with incident atrial fibrillation in older patients initiating hemodialysis.Design, setting, participants, & measurementsWe used the US Renal Data System linked to the records of a large dialysis provider to identify patients aged ≥67 years initiating hemodialysis between January 2006 and October 2011. We examined quarterly average predialysis systolic BP, diastolic BP, and proportion of sessions with intradialytic hypotension (i.e., nadir systolic BP <90 mm Hg). We applied an extended Cox model to compute adjusted hazard ratios (HRs) of each exposure with incident atrial fibrillation.ResultsAmong 17,003 patients, 3785 developed atrial fibrillation. When comparing predialysis systolic BP to a fixed reference of 140 mm Hg, lower predialysis systolic BP was associated with a higher hazard of atrial fibrillation, whereas higher systolic BP was associated with a lower hazard of atrial fibrillation. When comparing across a range of systolic BP for two hypothetical patients with similar measured covariates, the association varied by mean systolic BP: at systolic BP 190 mm Hg, each 10 mm Hg lower systolic BP was associated with lower atrial fibrillation hazard (HR, 0.94; 95% confidence interval, 0.90 to 1.00), whereas at systolic BP 140 mm Hg, a 10 mm Hg lower systolic BP was associated with a higher atrial fibrillation hazard (HR, 1.12; 95% confidence interval, 1.10 to 1.14). Lower diastolic BP was associated with higher atrial fibrillation hazards. Intradialytic hypotension was weakly associated with atrial fibrillation.ConclusionsIn this observational study of older patients initiating hemodialysis, lower predialysis systolic BP and diastolic BP were associated with higher incidence of atrial fibrillation.

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Measuring the Effects of an Ever-Changing Environment on Malaria Control

Infection and Immunity ◽

10.1128/iai.72.4.2248-2253.2004 ◽

2004 ◽

Vol 72 (4) ◽

pp. 2248-2253 ◽

Cited By ~ 6

Author(s):

Thomas F. McCutchan ◽

K. Christiana Grim ◽

Jun Li ◽

Walter Weiss ◽

Darmendar Rathore ◽

...

Keyword(s):

Malaria Control ◽

Environmental Variables ◽

Malaria Infection ◽

Natural Infection ◽

Environmental Parameters ◽

Control Measures ◽

First Year ◽

Natural Immunity ◽

Moderate Degree ◽

Degree Of Protection

ABSTRACT The effectiveness of malaria control measures depends not only on the potency of the control measures themselves but also upon the influence of variables associated with the environment. Environmental variables have the capacity either to enhance or to impair the desired outcome. An optimal outcome in the field, which is ultimately the real goal of vaccine research, will result from prior knowledge of both the potency of the control measures and the role of environmental variables. Here we describe both the potential effectiveness of control measures and the problems associated with testing in an area of endemicity. We placed canaries with different immunologic backgrounds (e.g., naïve to malaria infection, vaccinated naïve, and immune) directly into an area where avian malaria, Plasmodium relictum, is endemic. In our study setting, canaries that are naïve to malaria infection routinely suffer approximately 50% mortality during their first period of exposure to the disease. In comparison, birds vaccinated and boosted with a DNA vaccine plasmid encoding the circumsporozoite protein of P. relictum exhibited a moderate degree of protection against natural infection (P < 0.01). In the second year we followed the fate of all surviving birds with no further manipulation. The vaccinated birds from the first year were no longer statistically distinguishable for protection against malaria from cages of naïve birds. During this period, 36% of vaccinated birds died of malaria. We postulate that the vaccine-induced protective immune responses prevented the acquisition of natural immunity similar to that concurrently acquired by birds in a neighboring cage. These results indicate that dominant environmental parameters associated with malaria deaths can be addressed before their application to a less malleable human system.

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Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease

npj Vaccines ◽

10.1038/s41541-021-00326-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Lionel K. K. Tan ◽

Mark Reglinski ◽

Daryl Teo ◽

Nada Reza ◽

Lucy E. M. Lamb ◽

...

Keyword(s):

Ex Vivo ◽

Natural Infection ◽

Invasive Disease ◽

Full Length ◽

Natural Immunity ◽

Rich Region ◽

Antibody Recognition ◽

Naturally Occurring ◽

Protective Antibodies ◽

Proline Rich Region

AbstractHighly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

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First norovirus outbreaks associated with consumption of green seaweed (Enteromorpha spp.) in South Korea

Epidemiology and Infection ◽

10.1017/s0950268814001332 ◽

2014 ◽

Vol 143 (3) ◽

pp. 515-521 ◽

Cited By ~ 14

Author(s):

J. H. PARK ◽

H. S. JEONG ◽

J. S. LEE ◽

S. W. LEE ◽

Y. H. CHOI ◽

...

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Confidence Interval ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Case Control Study ◽

Case Control ◽

Green Seaweed ◽

Norovirus Gii ◽

Control Study

SUMMARYIn February 2012, an outbreak of gastroenteritis was reported in school A; a successive outbreak was reported at school B. A retrospective cohort study conducted in school A showed that seasoned green seaweed with radishes (relative risk 7·9, 95% confidence interval 1·1–56·2) was significantly associated with illness. Similarly, a case-control study of students at school B showed that cases were 5·1 (95% confidence interval 1·1–24·8) times more likely to have eaten seasoned green seaweed with pears. Multiple norovirus genotypes were detected in samples from students in schools A and B. Norovirus GII.6 isolated from schools A and B were phylogenetically indistinguishable. Green seaweed was supplied by company X, and norovirus GII.4 was isolated from samples of green seaweed. Green seaweed was assumed to be linked to these outbreaks. To our knowledge, this is the first reported norovirus outbreak associated with green seaweed.

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Assessment of the Field Utility of a Rapid Point-of-Care Test for SARS-CoV-2 Antibodies in a Household Cohort

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0592 ◽

2021 ◽

Author(s):

Mehal Churiwal ◽

Kelly D. Lin ◽

Salman Khan ◽

Srijana Chhetri ◽

Meredith S. Muller ◽

...

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Point Of Care ◽

Natural Infection ◽

Field Performance ◽

Antibody Test ◽

Asymptomatic Infection ◽

Point Of Care Test ◽

Antibody Tests ◽

Rapid Antibody

Point-of-care (POC) tests to detect SARS-CoV-2 antibodies offer quick assessment of serostatus after natural infection or vaccination. We compared the field performance of the BioMedomics COVID-19 IgM/IgG Rapid Antibody Test against an ELISA in 303 participants enrolled in a SARS-CoV-2 household cohort study. The rapid antibody test was easily implemented with consistent interpretation across 14 users in a variety of field settings. Compared with ELISA, detection of seroconversion lagged by 5 to 10 days. However, it retained a sensitivity of 90% (160/177, 95% confidence interval [CI] 85–94%) and specificity of 100% (43/43, 95% CI 92–100%) for those tested 3 to 5 weeks after symptom onset. Sensitivity was diminished among those with asymptomatic infection (74% [14/19], 95% CI 49–91%) and early in infection (45% [29/64], 95% CI 33–58%). When used appropriately, rapid antibody tests offer a convenient way to detect symptomatic infections during convalescence.

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An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

10.1101/2021.03.09.21253218 ◽

2021 ◽

Author(s):

Sheila F Lumley ◽

Gillian Rodger ◽

Bede Constantinides ◽

Nicholas Sanderson ◽

Kevin K Chau ◽

...

Keyword(s):

Cohort Study ◽

Single Dose ◽

Positive Result ◽

Healthcare Workers ◽

Natural Infection ◽

Natural Immunity ◽

Symptomatic Infection ◽

Gene Target ◽

Adjusted Incidence Rate ◽

Induced Immunity

AbstractBackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.

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Association between serum α1-antitrypsin levels and all-cause mortality in the general population: the Nagahama study

Scientific Reports ◽

10.1038/s41598-021-96833-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yasuharu Tabara ◽

Kazuya Setoh ◽

Takahisa Kawaguchi ◽

Shinji Kosugi ◽

Takeo Nakayama ◽

...

Keyword(s):

Risk Factor ◽

General Population ◽

Confidence Interval ◽

Cox Model ◽

Prognostic Significance ◽

High Sensitivity ◽

Hazard Ratio ◽

Reactive Protein ◽

All Cause Mortality ◽

Study Participants

AbstractCirculating levels of inflammatory proteins have to be prognostic markers of all-cause mortality. α1-Antitrypsin (AAT) is a major inflammatory plasma protein, but its association with all-cause mortality is unclear. We aimed to evaluate the prognostic significance of AAT levels for all-cause mortality. Study participants comprised 9682 community residents (53.5 ± 13.3 years old). During the 9.8-year follow-up period, 313 participants died from any cause. The mortality rate increased linearly with AAT quintiles (Q1, 18.2; Q2, 24.7; Q3, 23.8; Q4, 31.9; Q5, 64.6 per 10,000 person-years). There were significant correlations between AAT and high-sensitivity C-reactive protein (hsCRP) levels (correlation coefficient, 0.331; P < 0.001). However, the Cox model analysis, when adjusted for possible covariates including hsCRP, identified the fifth AAT quintile as a risk factor for all-cause death (hazard ratio, 2.12 [95% confidence interval, 1.41–3.18]; P < 0.001). An analysis of participants older than 50 years (hazard ratio, 1.98, P < 0.001) yielded similar results. The hazard ratio increased proportionately in combination with high AAT and high hsCRP levels, and the highest hazard ratio reached 4.51 (95% confidence interval, 3.14–6.54, P < 0.001). High AAT levels were determined to be an independent risk factor for mortality in the general population.

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Immune responses to cholera following natural infection: a review

10.1101/2020.07.27.20163139 ◽

2020 ◽

Author(s):

Tiffany Leung ◽

Laura Matrajt

Keyword(s):

Diarrheal Disease ◽

Clinical Symptoms ◽

Natural Infection ◽

Small Sample ◽

Natural Immunity ◽

Symptomatic Infection ◽

Correlates Of Protection ◽

Serological Studies ◽

Small Sample Sizes ◽

One Year

Cholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden. While it is accepted that natural immunity against cholera infection exists, no clear correlate of protection has been identified. In this review, we identify the estimated duration of immunity following cholera infection with and without clinical symptoms from available published studies. We searched Pubmed and Web of Science for studies examining the long-term infection-acquired immunity against cholera infection. We identified 22 eligible studies that included individuals residing primarily in Bangladesh and North America. % We observed the duration of immunity is estimated to last the longest in observational studies than in challenge studies, with serologic evidence of various potential correlates of protection becoming undetectable by one year. Although with small sample sizes, three studies found that most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype, suggesting that a subclinical cholera infection may confer lower protection than a clinical one. We identified the longest duration of immunity recorded by observational and challenge studies to be three years, but all the serological studies showed that various potential correlates of protection became undetectable by one year.

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Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas

Scientific Reports ◽

10.1038/s41598-021-94834-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoshiya Sugiura ◽

Rikuo Machinami ◽

Seiichi Matsumoto ◽

Hiroaki Kanda ◽

Keisuke Ae ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Confidence Interval ◽

Prognostic Value ◽

Cox Model ◽

Hazard Ratio ◽

Rank Test ◽

Log Rank Test ◽

Cd34 Expression ◽

Expression Status

AbstractIt is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.

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Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Vaccines ◽

10.3390/vaccines9101124 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1124

Author(s):

Sara Caucci ◽

Benedetta Corvaro ◽

Sofia Maria Luigia Tiano ◽

Anna Valenza ◽

Roberta Longo ◽

...

Keyword(s):

Single Dose ◽

Natural Infection ◽

Neutralizing Antibody ◽

Natural Immunity ◽

Anamnestic Response ◽

Neutralizing Activity ◽

Immunological Markers ◽

The Cross ◽

One Year

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

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