Intracellular survival of persistent group A streptococci in cultured epithelial cells

Group A streptococcus (GAS) is the principle etiologic agent of bacterial pharyngotonsillitis and a wide range of other diseases. Failure to eradicate GAS from patients has been documented in 5-30% of patients with pharyngotonsillitis, in spite of the continued sensitivity of GAS to penicillin and other beta-lactams. It was recently proposed that eradication failure might be attributed to the ability of GAS to maintain an intracellular reservoir during antibiotic treatment. We have previously shown that strains derived from patients with bacterial eradication failure, despite antibiotic treatment (persistent strains), adhered to and were internalized by cultured epithelial cells more efficiently than strains that were successfully eradicated. Since, penicillin and other beta-lactams do not penetrate well into mammalian cells, intracellular survival of GAS is crucial in order to persist during prolonged antibiotic treatment. In this study, we compared the survival of GAS strains from cases of eradication failure and eradication success, using an epithelial cell culture model. We found that persistent strains show significantly increased intracellular survival, compared to the 'eradication success' strains. This finding supports the idea that an intracellular reservoir of GAS plays a role in the etiology of antibiotic eradication failure.     

Perspectives on rapid elimination and ultimate global eradication of paralytic poliomyelitis caused by polioviruses

Poliomyelitis caused by polioviruses has already been eradicated from industrialized countries of North America, Europe, Asia and Oceania, but the procedures by which this eradication was achieved are not adequate for the poor tropical and subtropical countries. The major challenge now is first to eliminate it rapidly from Asia and Africa where an estimated 250,000 cases and 25,000 deaths currently occur annually. The great progress toward eradication of wild polioviruses from poor tropical and subtropical countries in Latin America was achieved not by the procedures still recommended by the WHO Expanded Program on Immunization (EPI) but by the independently organized annual, national days of antipolio vaccination — all based on the use of large armies of well-trained non-professional, community volunteers — first used in Cuba (1962), Brazil (1980), Nicaragua (1981), Dominican Republic (1983), Paraguay (1985), and Mexico (1986). This novel approach, described in some detail in this communication, is recommended for the rapid elimination of wild polioviruses from Asia and Africa, and for ultimate global eradication with the help of a special cadre within the EPI of WHO. The extensive use by the Pan American Health Organization (PAHO) of highly sophisticated regional virus laboratories has led to the recognition that, in areas from which poliomyelitis caused by polioviruses has been largely eliminated, there are thousands of cases of acute flaccid paralysis, previously clinically diagnosed as probable poliomyelitis, that have no viral etiology, a phenomenon previously reported by Dr. Manuel Ramos Alvarez in Mexico City in 1967.     

Assessment of poliovirus antibody seroprevalence in polio high risk areas of West Africa

We conducted a serological survey of anti-polio antibodies in polio high-risk areas of Mali, Guinea and Cote d’Ivoire to assess risk of future poliovirus outbreaks.Random community sampling of children 6–11 and 36–48 months-old was conducted; neutralizing antibodies against poliovirus were detected using microneutralization assay.We analysed 1059/1064 (99.5%) of enrolled children. Seroprevalence to poliovirus type 1 (PV1) across all age groups and locations ranged between 92 and 100%, for PV2 it was 77–100%, and 89–95% for PV3. PV2 seroprevalence in the younger age group in Guinea and Cote d’Ivoire was <80%. History of <4 polio vaccine doses and acute malnutrition were associated with seronegativity (OR = 2.1 CI95% = 1.5–3.1, OR = 1.8 CI95% = 1.1–3.3 respectively).The risk of poliovirus outbreak following importation is low because of high population immunity to PV1, however, due to large cohort of PV2 seronegative children any future detection of vaccine-derived poliovirus type 2 requires urgent response to arrest rapid spread.     

Rabeprazole,clarithromycin, and amoxicillin Helicobacter pylori eradication therapy: Report of an efficacy study

AIM:To investigate the efficacy of a standard triple therapy(comprising rabeprazole,clarithromycin,and amoxicillin)for Helicobacter pylori(H.pylori)eradication,noting factors that influence the outcome and documenting any adverse events.METHODS:Following institutional ethical approval,fifty consecutive and consenting symptomatic patients with evidence of H.pylori infection by either a positive urea breath test(UBT)and/or a campylobacter-like organism test who presented to the Gastroenterology clinic of Lagos State University Teaching Hospital between 2012 and 2013 were recruited into the study.Patients were openly randomized to either a 7-d or a 10-d regimen of amoxicillin 1 g,clarithromycin 500mg and rabeprazole 20 mg twice daily.The extent of symptom resolution was noted following the treatment,and at the end of one month after the completion oftreatment,a repeat UBT was performed in each patient to document the eradication of the infection.All data(demographics,symptoms,and eradication rates)were collated and analyzed with SPSS version 18.RESULTS:Forty-seven patients completed the study(three were excluded from the analysis for breaching the study protocol).The patients included 18 males and 29 females within the age range of 13-80 years(mean 43.7,SD 16.8).The clinical features of the study subjects were dyspepsia,reflux symptoms and features of gastrointestinal bleeding.The average eradication rate was 87.2%.Eighteen subjects were enrolled in the 7-d arm,while 29 were in the 10-d arm.There was no statistically significant difference in the age or sex distributions of the two arms.There was no significant advantage of the 10-d treatment duration over the 7-d duration(P=0.78),and the eradication outcomes were not influenced by the gender or age of the subjects.No adverse effects were reported in either arm.CONCLUSION:The triple therapy regime,employing a combination of amoxicillin,clarithromycin and rabeprazole,showed great efficacy and safety in the eradication of H.pylori,and this outcome was not influenced by gender or age.No difference was observed between the 7-d and 10-d regimens.     

The efficacy,safety and tolerability of pantoprazole-based one-week triple therapy in H. pylori eradication and duodenal ulcer healing

SUMMARY

Objective: Recently, proton pump inhibitor (PPi)-based triple therapy has been recommended as a first line treatment in the eradication of Helicobacter pylori. The aim of this open, multicentre trial was to investigate the efficacy, safety, tolerability and the ulcer healing rate of a triple regimen consisting of pantoprazole^? 40?mg, clarithromycin 500?mg and amoxicillin 1000?mg twice daily for 7?days, in the eradication of H. pylori in patients with duodenal ulcer in Turkey.

Research design and methods: H. pylori infection was assessed by histological examination and rapid urease test at baseline and 4?weeks after the completion of the therapy. Seventy-seven patients were enrolled, 5 were excluded due to various reasons and 72 completed the entire course of the trial.

Results: H. pylori eradication was confirmed in 49 of these patients; the eradication rate was 68% by per-protocol analysis and 63.6% by intention-to-treat analysis. The ulcers were completely healed in 61 patients (85%) at the second endoscopic examination. Drug compliance was excellent (97.3%) and there were no serious adverse events.

Conclusion: Pantoprazole-based 1-week triple therapy was well tolerated and the ulcer healing rate was high (85%). Relatively low H. pylori eradication rates may be attributed to rising antibiotic resistance over recent years. A large scale, comparative study with other PPi-based regimens is warranted based on the results of this open study with the pantoprazole-based regimen.     

Recent trends in the prevalence of Helicobacter Pylori in symptomatic children: A 12-year retrospective study in a tertiary centre

Objective

Helicobacter pylori infection is common among Asians. However, evidence in the recent years has demonstrated a decrease in the prevalence of H. pylori infection among children and adults worldwide. Our aim was to update its prevalence in symptomatic children in our locality in the recent 12?years and compared to the results of our previous review published in 2005.

The polio vaccination story of Pakistan

BackgroundTo describe in chronological detail Pakistan’s decades long battle against poliovirus and evaluate the multiple factors impacting it.Main bodyPakistan’s fight is documented through various published research articles and reports on Pakistan’s progress in eradication of polio published by international agencies involved in elimination of poliovirus worldwide. The socioeconomic, religious, and political factors, violent religious militancy, conspiracy theories resulting in vaccine refusals are documented in detail emphasizing the ups and downs in the fight at different times since 1994 to present. Pakistan and Afghanistan are the only two countries in the world reporting cases caused by wild polio virus type 1 (WPV1) since 2017 and the only two countries that have never stopped the transmission of WPV1 Pakistan needs to work on a war footing to eliminate the disease. The need to act urgently is now being increasingly recognized by the Pakistani Government.ConclusionMany difficulties still remain. Pakistan has reached a critical stage in the fight against polio. The world will not accept any further delay or complacency as there is apprehension around the world that Pakistan may “export” polio to other countries and undermine the worldwide success in eradicating polio.     

Status of vaccine research and development of vaccines for malaria

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding.     

Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch’s bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.