Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factors.

BACKGROUND: Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. METHODS AND FINDINGS: In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. CONCLUSIONS: In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer

"BACKGROUND: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. METHODS: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. RESULTS: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. CONCLUSION: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries."

Association of serum pepsinogen with atrophic body gastritis in Costa Rica.

Individuals with atrophic gastritis (AG), especially atrophic body gastritis (ABG), are at increased risk of developing gastric cancer. Serum concentrations of pepsinogens (PG) have been proposed as markers for ABG. The aim of this study was to determine the risk factors for AG and ABG and the potential of using serum PG concentrations to detect ABG in a dyspeptic population in Costa Rica, which is one of the countries with the highest incidence and mortality rates of gastric cancer in the world. Seven biopsy specimens, a fasting blood sample and a questionnaire concerning sociodemographic factors were obtained from 501 consecutive dyspeptic patients. The serum PGI level and the PGI/PGII ratios were significantly lower in patients with ABG than in other groups (P<0.000). A cut-off point of 3.4 led to a sensitivity of 91.2% in identifying ABG, a negative predictive value of 98.1%, but a positive predictive value of only 11.2%. Helicobacter pylori were present in 93% of the patients and all those with peptic ulcers were positive. AG was associated with increased age, lower body mass index, high alcohol intake and low fruit consumption. ABG was associated with age, alcohol consumption and PGI/PGII<3.4. In dyspeptic patients with a high prevalence of H. pylori infection, serum PG levels provide an assessment of ABG but it is necessary to introduce other serological and genetic markers in order to achieve a better specificity. Those markers could be serum antibodies to H. pylori-CagA, cytokine gene polymorphisms or others.

Should we eradicate Helicobacter pylori before prescribing an NSAID? Result of a placebo-controlled study.

OBJECTIVE: (1) To determine the prevalence of gastrointestinal (GI) symptoms in patients with and without Helicobacter pylori infection and treated with non-steroidal anti-inflammatory drugs (NSAIDs) and (2) to estimate the impact of H. pylori eradication on these symptoms. METHODS: This was a multicentric, community-based, randomized, case-control study. Patients presenting with a rheumatic disorder motivating the prescription of an NSAID for at least 2 wks were stratified in two groups (H. pylori-positive and H. pylori-negative) by a serological doctor test and H. pylori-positive patients divided further into two subgroups, receiving either an eradication treatment (group 1) or a placebo (group 2). The main outcome measure was the prevalence of GI symptoms estimated in groups 1 and 2 and in noninfected patients (group 3) at weeks 2, 6, and 12. RESULTS: Among H. pylori-negative patients (n=145), GI symptoms were present in 42.6%, 21.4%, and 10.0% at weeks 2, 6, and 12, respectively. In groups 1 and 2, GI symptoms were present in 57.7% and 40.7%, respectively, at week 2 (p= 0.03); 24.7% and 23% at week 6 (p= 0.85); and 9.4% and 17.3% at week 12 (p= 0.13). The prevalence of GI symptoms at week 2 was similar in group 2 and in the H. pylori-negative group (p= 0.77). The highest prevalence of symptoms at week 2 in group 1 was essentially due to diarrhea. The prevalence of GI symptoms was the same for groups 1 and 3 at week 12, and higher in group 2, but the difference did not reach statistical significance. CONCLUSIONS: The short-term (6 wks) GI tolerance of conventional NSAIDs does not differ whether or not the patients are infected by H. pylori. The tendency observed for the medium term (12 wks) deserves to be confirmed.

Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics.

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 microg x l(-1); PGC, 13.2 microg x l(-1); PGA/PGC, 6.7; and gastrin, 62.4 ng x l(-1). For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test.

Risk factors for failure of Helicobacter pylori therapy--results of an individual data analysis of 2751 patients.

AIM: To study risk factors for failure of Helicobacter pylori eradication treatment. METHODS: Individual data from 2751 patients included in 11 multicentre clinical trials carried out in France and using a triple therapy, were gathered in a unique database. The 27 treatment regimens were regrouped into four categories. RESULTS: The global failure rate was 25.8% [95% CI: 24-27]. There was a difference in failure rate between duodenal ulcer patients and non-ulcer dyspeptic patients, 21.9% and 33.7%, respectively (P < 10(-6)). In a random-effect model, the risk factors identified for eradication failure in duodenal ulcer patients (n = 1400) were: to be a smoker, and to have received the group 4 treatment, while to receive a 10 day treatment vs. 7 days protected from failure. In non-ulcer dyspeptic patients (n = 913), the group 2 treatment was associated with failure. In both groups, age over 60 was associated with successful H. pylori eradication. There were less strains resistant to clarithromycin in duodenal ulcer patients than in non-ulcer dyspeptic patients. Clarithromycin resistance predicted failure almost perfectly. CONCLUSION: Duodenal ulcer and non-ulcer dyspeptic patients should be managed differently in medical practice and considered independently in eradication trials.

Seroepidemiology of Helicobacter pylori infection in Guadeloupe.

854 sera collected from blood donors in Guadeloupe were screened for Helicobacter pylori immunoglobulin G antibodies by a commercial enzyme-linked immunosorbent assay kit. The overall prevalence was 55.2%; it increased significantly with age from 36.1% at 18-19 years to 63.7% at 50-59 years (P = 0.003).

Comparison of the E test and agar dilution method for antimicrobial suceptibility testing of Helicobacter pylori.

A multicentre study was carried out in order to validate the E test in comparison with the reference agar dilution method for testing the susceptibility of Helicobacter pylori to amoxicillin, clarithromycin, and metronidazole. Ten clinical isolates and one control collection isolate ( Helicobacter pylori ATCC 43504) were tested blindly at four centres according to a uniform methodology. The E test showed excellent intra- and inter-laboratory correlations with the agar dilution method for amoxicillin and clarithromycin (>98% agreement within 2 log(2) dilution steps). For metronidazole, however, the E test revealed significantly higher minimum inhibitory concentration values (>2 log(2)) against 5 of the 10 Helicobacter pylori strains tested. Overall, neither method was found reliable for testing the susceptibility of Helicobacter pylori to metronidazole, since both tended to lack reproducibility.

[How to determine the diagnosis of Helicobacter pylori infection in the elderly?]. / Comment déterminer le diagnostic de l'infection à Helicobacter pylori chez la personne âgée?

PURPOSE: The real prevalence of Helicobacter pylori (H. pylori) infection is difficult to determine in the elderly because of the frequency of drug intake (antibiotics or anti-secretory drugs). The aim of this study was to evaluate the diagnostic performance of five tests in the elderly. METHODS: The study population consisted of consecutive patients undergoing a routine endoscopy between August 1998 and December 1999. We evaluated the diagnostic performance of four tests in all of the included patients: culture and histology of biopsy specimens, serology (ELISA) and urea breath test (13C-UBT). Detection of H. pylori antigens in stool samples (HpSA) was realized in a subgroup. Patients were considered H. pylori + when result for culture was positive or when two tests were positive. RESULTS: One hundred and sixty-seven patients were included in this study (55 men, 112 women; mean age: 85.6 +/- 5.1 years). Only 38 (22.8%) patients were H. pylori+. Test performances showed the following results: serology sensitivity: 90.9% (IC 95%: 75.6-98.1) versus 86.9% (IC 95%: 63.6-96.9) for culture versus 77.8% (IC 95%: 60.8-89.9) for histology and 74.3% (IC 95%: 56.7-87.5) for 13C-UBT. Eighty-nine (53.3%) took antibiotics or anti-secretory drugs, only 13C-UBT performances decreased significantly (sensitivity: 94.4% [72.7-99.8] versus 52.9% [27.8-77]; P < 10(-6)). When gastric or duodenal ulcer were endoscopically diagnosed in older patients, both histology and 13C-UBT could not improve the diagnosis of H. pylori infection. HpSA was realized in 107 patients (sensitivity: 74.1%, specificity: 98.7%). We showed no statistical difference between HpSA performances and drug intake. CONCLUSION: Diagnostic performances decreased in older patients especially because of drug intake.

Helicobacter pylori infection in patients consulting gastroenterologists in France: prevalence is linked to gender and region of residence.

BACKGROUND: Because of limited data on the epidemiology of Helicobacter pylori in France, the prevalence of this infection by region and its associated risk factors were studied between 1995 and 1997 among patients consulting a representative sample of gastroenterologists by region. METHOD: A cross-sectional study was performed. Patients consulting gastroenterologists for whatever reason were screened for H. pylori infection determined by specific salivary IgG. A questionnaire was filled out by the gastroenterologist. A multivariate analysis was performed with all relevant variables. RESULTS: 3,153 patients were included. The mean age was 48.5 years; 51.8% were women. After stratification by patients consulting for upper digestive tract (UDT) and non-UDT symptoms, H. pylori infection was found to be more prevalent, in both groups, for characteristics such as being born in a developing country, overcrowding during childhood, and primary educational level. Interestingly, gender (odds ratio OR(UDT for women) = 0.7 (95% CI 0.5-0.8] and OR(non-UDT) for women = 0.6 [95% CI 0.5-0.8]) and living in a region other than the south-west (OR(UDT) varying from 1.5 to 2.0 and OR(non-UDT) varying from 1.3 to 2.1, depending on the region) was associated with the odds of prevalent infection. CONCLUSION: These findings show (1) that gender deserves more attention in the epidemiology of H. pylori and (2) a regional disparity in France regarding H. pylori infection.

cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia.

The differences in eradication rates reported in clinical trials aiming to cure Helicobacter pylori infection cannot be entirely explained by the type of regimen, bacterial resistance, or lack of compliance. Using data from a clinical trial, a logistic regression model was constructed to determine whether cagA status, assessed by PCR, affects the outcome of eradication. Resistance to clarithromycin (10% of the strains) predicted failure perfectly. In the model (n = 156), a cagA-lacking strain (odds ratio [OR] = 2.2; 95% confidence interval [CI], (1.1 to 4.7), tobacco smoking OR = 3.1; 95% CI, 1.3 to 7.0), and a double dose of proton pump inhibitor in the treatment regimen (OR = 0.3; 95% CI, 0.2 to 0.7) were associated with the treatment outcome. The exact role of cagA in the outcome of H. pylori eradication therapy has not been explored. However, the type of histological lesions which it causes in the gastric mucosa may be implicated. Regardless of the mechanism involved, cagA status is a good predictive marker of eradication outcome.

[Epidemiology, acquisition and transmission of Helicobacter pylori]. / Epidémiologie, acquisition et transmission d'Helicobacter pylori.

Helicobacter pylori infection is a chronic infection essentially acquired during childhood. Its prevalence in developed countries like France has decreased according to the year of birth all along the twentieth century, reflecting the progressive improvement of socio-economic and environmental conditions. The incidence of acquisition in adulthood is lower than 0.5% per year. In developing countries, the prevalence is still very high, even in early childhood. H. pylori is a strictly human bacterium. Its reservoir is essentially the stomach. Transmission most likely occurs between humans by an oro-oral or a gastro-oral transmission. Faeco-oral transmission, either direct or via the environment, is possible but seems to be rare in France.

Review article: have we found the source of Helicobacter pylori?

Besides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal-oral, oral-oral or gastro-oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.

Long-term effects of Helicobacter pylori eradication on gastric antral mucosa in duodenal ulcer patients.

OBJECTIVES: The aim of this study was to assess the consequences of prolonged Helicobacter pylori eradication on gastric antral mucosa in duodenal ulcer patients. PATIENTS AND METHODS: Forty-three duodenal ulcer patients with confirmed H. pylori eradication after one year of follow-up were included in this retrospective study. Before H. pylori eradication and during the follow-up, four antral prepyloric biopsy samples were taken for histopathological examination and culture. Histopathological lesions were graded semi-quantitatively according to the updated Sydney System for activity, chronic inflammation, glandular atrophy and intestinal metaplasia (IM), as well as presence of lymphoid follicles. RESULTS: After a mean follow-up of 43 +/- 23 months, H. pylori eradication statistically improved all gastritis scores, including the atrophy score and the lymphoid follicle score but excluding the IM score. H. pylori eradication resulted in normalization of gastric mucosa in 51.2% of patients and a significantly lower proportion of patients with non-atrophic gastritis and atrophic gastritis without IM. Atrophy totally disappeared in 16/29 patients (55.2%) in whom IM was absent. No predictive factor for regression of atrophy or normalization of gastric mucosa was identified. CONCLUSION: In duodenal ulcer patients, prolonged absence (more than one year) of H. pylori can lead to normalization of the antral mucosa and the disappearance of mucosa-associated lymphoid tissue, as well as the regression of antral atrophy. Long-term studies involving selected patients with atrophy and IM which persist after H. pylori eradication are needed to determine the potential benefits of treating H. pylori gastritis with regard to gastric cancer prevention.

Randomized study comparing omeprazole with ranitidine as anti-secretory agents combined in quadruple second-line Helicobacter pylori eradication regimens.

BACKGROUND: Few data are available on the efficacy of second-line H. pylori eradication regimens. AIM: To compare the efficacy of either omeprazole or ranitidine in a second-line quadruple regimen in patients with duodenal ulcer or erosive duodenitis. PATIENTS AND METHODS: A total of 37 patients with erosive duodenitis and 119 with duodenal ulcer who have failed eradication of H. pylori with double or triple regimens, without metronidazole, were randomly assigned to receive tripotassium dicitrato bismuthate 600 mg t.d.s. + metronidazole 500 mg t.d.s. + tetracycline hydrochloride 500 mg t.d. s. combined with either omeprazole 20 mg b.d. (group O, 78 patients) or ranitidine 300 mg b.d. (group R, 78 patients) for 14 days. H. pylori eradication was verified by histology, rapid urease test and 13C-urea breath test. STATISTICS: t-test, chi2-test. RESULTS: A total of 143 patients had a post-treatment endoscopy. Eradication rates were: intention-to-treat: group O 77% (67-87), group R 76% (66-85), P=0.85; per protocol analysis: group O 86% (77-95), group R 82 (71-93), P=0.58. Side-effects were frequent but mild. CONCLUSIONS: Omeprazole 20 mg b.d. and ranitidine 300 mg b.d. were equally effective as antisecretory agents combined in a second-line quadruple eradication regimen.

Saliva specimens for diagnosis of Helicobacter pylori obtained in remote areas of Nepal.

A surprising low prevalence rate of Helicobacter pylori infection was found in Dolpo, Nepal, leading the authors to demonstrate the importance of IgG conservation. The interest of studying the genetics of the bacteria in these remote infected populations is also emphasised.

Helicobacter pylori: from the stomach to the heart.

A surprising number of extra-gastrointestinal diseases have been reported to be associated with Helicobacter pylori infection, including coronary heart disease and stroke. Since coronary heart disease is the principal cause of death in western countries, and since the known risk factors cannot fully explain the pathogenic mechanisms of the disease, the exploration of the role of possible causal agents has stimulated intense research. Infectious agents have been linked to coronary heart disease on epidemiological and pathogenic grounds. In 1994, H. pylori infection was reported to be one of them. Since then, a number of studies have been published with controversial results. Studies performed thus far show a high degree of heterogeneity in the selection of patients and also in the type of disease studied, i.e. coronary heart disease in general or acute myocardial infarction. Since the pathogenic development is most likely different for each of these two conditions (one chronic and the other acute) they should be studied separately. H. pylori infection can cause platelet aggregation and induces a procoagulant activity. H. pylori can also contribute to atherosclerosis, through increased concentration of homocysteine in the blood, caused by decreased levels of folic acid and cobalamin, or to an autoimmune process. Prospective cohort studies and interventional trials focusing separately on the chronic and acute phases of coronary heart disease and H. pylori infection should be performed in order to provide firm epidemiological data for a causal relationship.

Is there an association between Helicobacter pylori infection and coronary heart disease?

In addition to gastroduodenal diseases, Helicobacter pylori infection has been associated with extradigestive diseases, including coronary heart disease. Different studies have failed to demonstrate a clear association. The aim of this work was to carry out a meta-analysis of these studies' results, with a special emphasis on heterogeneity. A MEDLINE search of all studies published in English from 1994 to 1998 was conducted. Five criteria for eligibility of studies were defined. The quality of each study was assessed on a five-point scale adapted from studies by the Quebec Task Force. The final results are reported based on a fixed-effects model. Pooled odd ratios were calculated for subgroups of studies (defined on quality of adjustment, on confounding factors, and on the type of control population). Sixty-nine articles and abstracts fulfilling the defined criteria were analyzed. They were all case-control or cross-sectional studies. H. pylori diagnosis was carried out by serology, urea breath test or both; coronary heart disease was diagnosed mainly by coronary angiography. The total sample size was 6603. The quality score varied from 4 to 10. The pooled odds ratios of the 24 articles included in the model was 1.55 (95% confidence interval (CI): 1.38-1.74). It ranged from 1.07 to 2.34 when the quality of adjustment for confounding factors was considered and from 1.25 to 1.99 when the type of control group was considered. In any case there was significant heterogeneity (p < 0.001). The present study demonstrated a possible weak association but the high degree of heterogeneity in the studies impedes a clear demonstration.

Is there a link between the variation in gastric cancer mortality and differences in Helicobacter pylori prevalence in different regions of France?

An ecological study was performed to correlate the cumulative gastric cancer mortality rate to the prevalence of Helicobacter pylori infection in France. National data on mortality, standardized for age and gender, and the results of a nationwide prevalence study on Helicobacter pylori infection among 1,586 patients consulting for symptoms other than upper digestive tract symptoms, in seven defined French regions were used. The correlation was described by linear regression with the standardized data and then evaluated in a linear regression model including age and gender as co-variables. The Southwest region was the least affected by the infection (15.2%) while prevalence varied from 20.5 to 25.3% for the other regions. The cumulative gastric cancer mortality rate varied from 34.4 to 51.8/100,000. The prevalence of Helicobacter pylori infection in the model explained 5% of the variability in the gastric cancer mortality. A number of biases which were difficult to control could explain the lack of association between these variables.