Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru prior to the COVID-19 pandemic (preprint)

OBJECTIVE: To estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, prior to the COVID-19 pandemic. MATERIAL AND METHODS: An ecological study was carried out using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, relative risk of each risk factor, and number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the population attributable fraction (PAF) and confidence intervals. The number of new cancer cases and deaths attributable to each risk factor was calculated by multiplying the number of cases and deaths in each sex by the PAF of each risk factor. RESULTS: 38.4% of new cases (34.4% in men and 41.8% in women) and 43.2% of deaths by cancer in Peru (43.1% in men and 43.2% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,591 (10,616 in men and 14,975 in women) and the number of deaths attributable to cancer was 14,922 (6,996 in men and 7,926 in women). The modifiable risk factors that caused a greater number of cases and deaths were HPV infection (4563 cases, 2410 deaths), current tobacco use (3387 cases, 2198 deaths), and Helicobacter pylori infection (2686 cases, 1874 deaths). The oncogenic infections made up the group of risk factors that presented a greater PAF (16.6% for cases, 19.1% for deaths) followed by other unhealthy lifestyle factors (14.1% for cases, 16.5% for deaths), tobacco (7.2% for cases, 7.3% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSION: Prior to the COVID-19 pandemic, a proportion of 38.4% of cancer cases and 43.2% of cancer deaths in Peru during 2018 were attributable to modifiable risk factors. Most preventable cancer cases and deaths are linked to oncogenic infections, primarily caused by HPV and Helicobacter pylori.

Fatal gastritis and enterocolitis due to concurrent Helicobacter pylori and Campylobacter jejuni infection in a captive cheetah (Acinonyxjubatus).

A 3.5-year-old female cheetah (Acinonyx jubatus) died after a 10-day history of anorexia, regurgitation and diarrhoea despite symptomatic therapy. At gross post-mortem examination, the stomach was blood-filled with mucosal thickening and multifocal ulcerations. The intestinal mucosa was thickened and reddened, and the intestinal lumen was filled with dark red to black pasty content. Gastric histological lesions were compatible with gastritis due to Helicobacter infection, which was confirmed by polymerase chain reaction. Histology of the intestines revealed a severe necrotizing neutrophilic enterocolitis with abundant intralesional curved to spiral bacteria, corresponding to Campylobacter jejuni, which were subsequently isolated from both small and large intestinal contents. No other intestinal pathogens were detected despite thorough investigations. These findings suggest that C. jejuni may have played an aetiological role in the enterocolitis. Such an association has not been previously reported in non-domestic felids.

[Digestive infectious pathology: Diagnoses not to be missed]. / Pathologie infectieuse du tube digestif : diagnostics à ne pas manquer.

The recent context of COVID-19 has renewed the interest of pathologists in diseases of infectious origin. This interest is even stronger in the gastrointestinal tract where symptoms are aspecific, often frustrating with a normal endoscopic appearance sometimes leading to diagnostic erraticity. In this context, systematic biopsies performed by the clinician are sometimes the only way to reach a diagnosis. Nevertheless, the precise diagnosis of these pathologies requires a good knowledge of the context in which they occur, the histopathological aspect and a rigorous analysis using special stains and/or immunohistochemical analyses. Some infectious diseases of the gastrointestinal tract are well known to pathologists who are widely called upon to diagnose them (Helicobacter pylori gastritis, Candida albicans oesophagitis or CMV colitis), but others are more difficult to diagnose. In this article, we will present, after having recalled the various useful special stains, rare or difficult to diagnose bacterial or parasitic pathologies "not to be missed" in the digestive tract.

Immunoinformatic prediction of potential immunodominant epitopes from cagW in order to investigate protection against Helicobacter pylori infection based on experimental consequences.

Helicobacter pylori is a leading cause of stomach cancer and peptic ulcers. Thus, identifying epitopes in H. pylori antigens is important for disease etiology, immunological surveillance, enhancing early detection tests, and developing optimal epitope-based vaccines. We used immunoinformatic and computational methods to create a potential CagW epitope candidate for H. pylori protection. The cagW gene of H. pylori was amplified and cloned into pcDNA3.1 (+) for injection into the muscles of healthy BALB/c mice to assess the impact of the DNA vaccine on interleukin levels. The results will be compared to a control group of mice that received PBS or cagW-pcDNA3.1 (+) vaccinations. An analysis of CagW protein antigens revealed 8 CTL and 7 HTL epitopes linked with AYY and GPGPG, which were enhanced by adding B-defensins to the N-terminus. The vaccine's immunogenicity, allergenicity, and physiochemistry were validated, and its strong activation of TLRs (1, 2, 3, 4, and 10) suggests it is antigenic. An in-silico cloning and immune response model confirmed the vaccine's expression efficiency and predicted its impact on the immune system. An immunofluorescence experiment showed stable and bioactive cagW gene expression in HDF cells after cloning the whole genome into pcDNA3.1 (+). In vivo vaccination showed that pcDNA3.1 (+)-cagW-immunized mice had stronger immune responses and a longer plasmid DNA release window than control-plasmid-immunized mice. After that, bioinformatics methods predicted, developed, and validated the three-dimensional structure. Many online services docked it with Toll-like receptors. The vaccine was refined using allergenicity, antigenicity, solubility, physicochemical properties, and molecular docking scores. Virtual-reality immune system simulations showed an impressive reaction. Codon optimization and in-silico cloning produced E. coli-expressed vaccines. This study suggests a CagW epitopes-protected H. pylori infection. These studies show that the proposed immunization may elicit particular immune responses against H. pylori, but laboratory confirmation is needed to verify its safety and immunogenicity.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Helicobacter pylori eradication rates using clarithromycin and levofloxacin-based regimens in patients with previous COVID-19 treatment: a randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. METHODS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. RESULTS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). CONCLUSION: As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. TRIAL REGISTRATION: The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Geographic distribution of antibiotic resistance of Helicobacter pylori: A study in Bulgaria.

Prevalence of antibiotic resistant Helicobacter pylori was compared between 50 patients living outside the capital city and 50 matched pairs of capital city residents (CCRs). H. pylori isolates from 2018 to 2022 were included. Resistance rates in CCRs and those living elsewhere were 4.0 and 6.0% to amoxicillin, 48.0 and 42.0% to metronidazole, 30 and 30% to clarithromycin, and 4.0 and 4.0% to tetracycline, respectively. Levofloxacin resistance was higher (38.0%) in the capital city vs 20.0% (P = 0.047) in the country. Odd ratio for levofloxacin resistance between pair-matched groups was 2.45 (95% CI, OR 1.0-6.02, P value = 0.05) and relative risk for fluoroquinolone resistance was 1.90 (95% CI for RR 0.98-3.67) for CCRs vs residents in other regions. Resistance rates to levofloxacin and clarithromycin were worryingly high in our study, most probably due to the high quinolone consumption (2.86 DDD/day in 2017) in Bulgaria and the increase in macrolide, lincosamide and streptogramin consumption, especially of azithromycin, by >42% with the start of COVID-19 pandemic. Briefly, antibiotic resistance of H. pylori has a dynamic change, and it can display different patterns in certain geographic regions. The results imply that antibiotic consumption should be carefully controlled and unjustified use of levofloxacin should be restricted, especially in some large cities. Antibiotic policy should be further strengthened and regular monitoring of resistance in various geographic regions is needed for treatment optimization.

Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial.

BACKGROUND & AIMS: Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe. METHODS: In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients. RESULTS: A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P < .001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P < .001; difference 37.7%; 95% CI, 20.5-52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P < .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05). CONCLUSION: Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population. CLINICALTRIALS: gov; NCT04167670.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Nucleic acid extraction without electrical equipment via magnetic nanoparticles in Pasteur pipettes for pathogen detection.

The outbreak of COVID-19 makes epidemic prevention and control become a growing global concern. Nucleic acid amplification testing (NAAT) can realize early and rapid detection of targets, thus it is considered as an ideal approach for detecting pathogens of severe acute infectious diseases. Rapid acquisition of high-quality target nucleic acid is the prerequisite to ensure the efficiency and accuracy of NAAT. Herein, we proposed a simple system in which magnetic nanoparticles (MNPs) based nucleic acid extraction was carried out in a plastic Pasteur pipette. Different from traditional approaches, this proposed system could be finished in 15 min without the supports of any electrical instruments. Furthermore, this system was superior to traditional MNPs based extraction methods in the aspects of rapid extraction and enhancing the sensitivity of a NAAT method, accelerated denaturation bubbles mediated strand exchange amplification (ASEA), to the pathogens from various artificial samples. Finally, this Pasteur pipette system was utilized for pathogen detection in actual samples of throat swabs, cervical swabs and gastric mucosa, the diagnosis results of which were identical with that provided by hospital. This rapid, easy-performing and efficiency extraction method ensures the applications of the NAAT in pathogen detection in regions with restricted resources.

Helicobacter pylori infection and positive Rome IV criteria for functional dyspepsia in Romanian medical students.

Recent data suggest that the prevalence of Helicobacter pylori (HP) infection in Romania has been declining in the last 30 years. However, there are no studies regarding HP prevalence among medical students. The objectives of this study were to estimate the prevalence of HP infection and assess the prevalence of dyspepsia in medical students and the relationship between dyspepsia and infection. We included 150 students from the Iuliu Hatieganu University of Medicine and Pharmacy of Cluj-Napoca, Romania (102 females and 48 males, mean age 21 years). Each student completed a lifestyle questionnaire, personal history, family history as well as the Rome IV questionnaire for functional dyspepsia. The status of HP infection was determined using the C13-urea respiratory test. The prevalence of HP infection was 25.33%, and 18% met the Rome IV criteria for functional dyspepsia. 37% of students with functional dyspepsia had a positive HP test. Of all students, 8% had a history of HP infection. Those with a history of HP infection had a 4.45% (95% CI 1.6 - 12.37) higher risk of having positive Rome IV criteria for functional dyspepsia than those with no previous history of infection (p=0.008). Thus, the present study adds to the body of evidence regarding HP prevalence among medical students, 25.33% being positive. We found no statistically significant correlation between HP infection and functional dyspepsia. Those with a history of HP infection had a higher risk of functional dyspepsia.

Helicobacter pylori - 2021. / Helicobacter pylori - 2021.

Összefoglaló. A Helicobacter pylori továbbra is a világ legelterjedtebb fertozése: prevalenciája a fejlodo országokban 70-80%, a fejlett országokban csökkeno tendenciát mutat. A dél-magyarországi véradókban a prevalencia 32%-ra csökkent. A migráció a befogadó ország számára a fertozés fokozott kockázatával jár. A szövettani diagnózisban az immunhisztokémiai vizsgálat pontosabb a hagyományos Giemsa-festésnél. A mesterséges intelligencia érzékenysége a hagyományos endoszkópiáéval összehasonlítva 87%, pontossága 86%. Az újgenerációs szekvenálással lehetséges egy biopsziás mintából több antibiotikumérzékenység meghatározása. A Helicobacter pylori kezelésének európai regisztere kimutatta, hogy 2013 és 2018 között a bizmutalapú négyes vagy a 14 napos egyideju négyes kezelések hatásosabbak, mint a hagyományos hármas kezelés, de elterjedésük igen lassú folyamat, jelentos földrajzi különbségekkel. Az új típusú koronavírus (SARS-CoV-2) felléphet Helicobacter pylori fertozésben is, egymás kóros hatását felerosítve. A diagnosztikai módszerek korlátozottak. Protonpumpagátlók szedése növeli a COVID-19-fertozés kockázatát és annak súlyos kimenetelét. Elozetesen ismert peptikus fekély, vérzés, illetve antikoguláns kezelés elott az eradikáció a vírusos fertozés lezajlása után indokolt. A probiotikumoknak az eradikációra gyakorolt hatásáról 20, közepes minoségu metaanalízis született, így a konszenzusokban foglalt álláspontok sem egyértelmuek: a jövoben ezt tisztázni kell. Orv Hetil. 2021; 162(32): 1275-1282. Summary. Helicobacter pylori is still the most widespread infection in the world: its overall prevalence is 70-80% in developing regions, but fortunately it is decreasing in the Western world. The prevalence in blood donors from South-Eastern Hungary decreased from 63% in the 1990's to 32% in 2019. Migration constitutes an increased risk of infection for the destination countries. Immunohistochemistry has proven to be more accurate in histological diagnosis than the conventional Giemsa stain. The sensitivity and accuracy of artificial intelligence as compared to videoendoscopy were 87% and 86%, respectively. The European Register on the management of Helicobacter pylori infection revealed that concomitant quadruple and 14-day bismuth-based therapies are more efficient than triple combinations, although their incorporation in practice is a long-lasting process, with large geographical variations. The novel type of coronavirus (SARS-CoV-2) can also occur in Helicobacter pylori-infected patients, mutually enhancing their pathogenetic effects. Diagnostic possibilities are limited in this setting. The use of proton pump inhibitors increases the risk of viral infection and the severity of the disease. Eradication treatment seems justified in patients with previously known peptic ulcers or gastrointestinal bleeding, or before starting anticoagulant treatment, but must be postponed after resolution of viral infection. The effect of probiotics on eradication was addressed by 20, medium-to-low quality meta-analyses and so, the recommendations of the guidelines are equivocal, which must be clarified in the future with higher quality studies. Orv Hetil. 2021; 162(32): 1275-1282.

Eosinophils and Bacteria, the Beginning of a Story.

Eosinophils are granulocytes primarily associated with TH2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers TH2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote TH17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.