Antibiotic susceptibility and molecular analysis of invasive Haemophilus influenzae in Canada, 2007 to 2014.

Background: Previously we studied the antibiotic susceptibility of invasive Haemophilus influenzae collected in Canada from 1990 to 2006 and characterized isolates by serotype, MLST and ftsI gene sequencing for significant PBP3 mutations. Objectives: To provide an update based on isolates collected from 2007 to 2014. Methods: A total of 882 case isolates were characterized by serotype using slide agglutination and PCR. MLST was carried out to determine ST. Isolates were tested for ß-lactamase production, presence of significant PBP3 mutations and antibiotic susceptibility by disc diffusion against 14 antibiotics. MIC values of three antibiotics were determined for 316 isolates using microbroth dilution. Results: Non-typeable H. influenzae accounted for 54.6% of the isolates and 45.4% were serotypeable, predominantly type a (23.1%), type b (8.3%) and type f (10.8%). The overall rate of ampicillin resistance due to ß-lactamase production was 16.4% and increased from 13.5% in 2007-10 to 19% in 2011-14. Significant PBP3 mutations were identified in 129 isolates (14.6%) with 23 (2.6%) also producing ß-lactamase. MLST identified related STs (ST-136, ST-14 and ST-367) associated exclusively with genetically ß-lactamase-negative, ampicillin-resistant isolates and confirmed previously reported associations between significant PBP3 mutations and ST. Conclusions: A significant increase in ß-lactamase-producing isolates was observed from 2007 to 2014; the rate of significant PBP3 mutations has increased since previously reported and 52.5% of non-typeable H. influenzae now show resistance markers. Resistance to trimethoprim/sulfamethoxazole was common and no resistance to fluoroquinolones or third-generation cephalosporins was found.

Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA, factor H binding protein, Neisseria heparin-binding antigen and Neisseria adhesin A).

BACKGROUND: Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB. OBJECTIVE: To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine. METHODS: Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated. RESULTS: The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD. CONCLUSION: From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.

HISTORIQUE: Le Neisseria meningitidis du sérogroupe B (MenB) a toujours été une cause importante de méningococcie invasive (MI) au Canada. Depuis l'adoption d'un vaccin conjugué contre le méningocoque du groupe C, la majorité des MI au Canada sont désormais attribuables au MenB. OBJECTIF: Examiner les isolats de cas de MI dans les Maritimes entre 2009 et 2013. Analyser les données pour déterminer la couverture potentielle du vaccin nouvellement homologué contre le MenB. MÉTHODOLOGIE: Les chercheurs ont déterminé le sérogroupe, le sérotype et les antigènes des sous-types sérologiques des isolats de cas de MI. Ils ont effectué l'analyse clonale au moyen du typage génomique multilocus. Ils ont séquencé les gènes des antigènes du vaccin à base de protéines et examiné les peptides prédits. RÉSULTATS: La majorité des isolats de MI étaient des MenB (82,5 %, 33 sur 40). Notamment, le type séquentiel (TS)-154 B:4:P1,4 était responsable de 47,5 % (19 sur 40) de tous les isolats de cas de MI dans les Maritimes. Les isolats de ce clone ont exprimé l'antigène porA P1.4 et étaient dotés des gènes nhba codant pour le peptide 2 de l'antigène de liaison à l'héparine de Neisseria. Ensemble, ces antigènes correspondaient exactement à deux des quatre composants du nouveau vaccin contre le méningocoque du groupe B à quatre composants. Dix-neuf isolats du MenB étaient dotés de deux correspondances antigéniques, tandis que cinq autres MenB et un isolat de la méningite Y étaient dotés d'une correspondance antigénique. Ces résultats assuraient une couverture potentielle du MenB de 72,7 % (24 sur 33) ou une couverture potentielle globale de la MI de 62,5 % (25 sur 40). CONCLUSION: De 2009 à 2013, dans les Maritimes, la MI était surtout causée par le MenB, en particulier le clone B:4:P1.4 ST-154, responsable de 47,5 % de tous les isolats de cas de MI. Le nouveau vaccin contre le méningocoque du groupe B à quatre composants semble offrir une couverture pertinente contre le MenB dans cette région.

Development of a checklist of quality indicators for clinical trials in resource-limited countries: the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) experience.

BACKGROUND: Since 1994, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) has funded research sites in resource-limited countries (RLCs). These sites implement research on human immunodeficiency virus (HIV) infection and Hepatitis C. In parallel, international regulations and recommendations for clinical trials have evolved and proliferated. However, little guidance exists on how these should be interpreted and applied within academic trials and in the context of RLCs. After developing a specific Ethical Charter for research in developing countries in 2002, ANRS developed a set of quality indicators (QIs) as a monitoring tool for assessing compliance to international guidelines. PURPOSE: We describe here the development process, QIs adopted, and areas for improvement. METHODS: In 2008, a group of experts was convened that included a researcher representing each ANRS site (Cote d'Ivoire, Senegal, Cameroun, Burkina Faso, Egypt, and Cambodia). Our structuring interaction development process combined evidence and expert opinion in two nominal group meetings to identify (1) clinical trial processes involved, (2) issues specific to RLCs in terms of Good Clinical Practice (GCP) and the application of ethical recommendations, and (3) checklists of QIs adapted to clinical trials conducted in RLCs. RESULTS: The trial process reviewed and proposed for RLCs was mostly similar to the one produced in wealthier countries. The scheme generated by our work group added two further processes: 'drug management' and 'biological investigations'. Specific issues regarding trial management in RLCs were therefore described for eight trial steps (1) protocol conception and seeking authorizations, (2) participant enrollment and follow-up, (3) site monitoring, (4) drug management, (5) biological investigations, (6) record management, (7) data management, and (8) site closeout. A total of 58 indicators were identified with at least one indicator for each trial process. LIMITATIONS: Some trial activities require further consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed. CONCLUSIONS: This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.

Risk perception and priority setting for intervention among hepatitis C virus and environmental risks: a cross-sectional survey in the Cairo community.

BACKGROUND: Hepatitis C virus (HCV) recently emerged as a major public health hazard in Egypt. However, dramatic healthcare budget constraints limit access to the costly treatment. We assessed risk perception and priority setting for intervention among HCV, unsafe water, and outdoor air pollution in Cairo city. METHODS: A survey was conducted in the homes of a representative sample of household heads in Cairo city. Risk perception was assessed using the "psychometric paradigm" where health hazards are evaluated according to several attributes and then summarized by principal component analysis. Priority setting was assessed by individual ranking of interventions reducing health hazards by 50% over five years. The Condorcet method was used to aggregate individual rankings of the three interventions (main study) or two of three interventions (validation study). Explanatory factors of priority setting were explored in multivariate generalized logistic models. RESULTS: HCV was perceived as having the most severe consequences in terms of illness and out-of-pocket costs, while outdoor air pollution was perceived as the most uncontrollable risk. In the main study (n = 2,603), improved water supply received higher priority than both improved outdoor air quality (60.1%, P < .0001) and screening and treatment of chronic hepatitis C (66.3%, P < .0001), as confirmed in the validation study (n = 1,019). Higher education, report of HCV-related diseases in the household, and perception of HCV as the most severe risk were significantly associated to setting HCV treatment as the first priority. CONCLUSIONS: The Cairo community prefers to further improving water supply as compared to improved outdoor air quality and screening and treatment of chronic hepatitis C.

Nicotine dependance among adult male smokers in rural Egypt.

Nicotine dependence is a significant public health problem. This study describes the nicotine dependence status among male adults in rural communities in Egypt. A survey was carried out in five rural villages in Egypt to study the smoking prevalence. A total of 938 current smokers were identified and their nicotine dependence status was studied. About 9% of all smokers in the studied villages were found to have heavy dependence to nicotine. Heavy dependence was associated with younger age of smoking initiation (p<0.05) and more smoking in the first hours of the day (p<0.001). Heavy dependent smokers are less likely to quit smoking (p<0.001), lack the confidence to quit by themselves (p<0.001) and less likely to have tried to quit earlier (p<0.001). Dependent smokers are more likely to smoke in the presence of their children (p<0.001). Reasons for smoking included the habit of smoking helping them to keep them going when tired, to make them alert and not knowing what to do with their hands without a cigarette. The main reasons they identified for restarting smoking after quitting were the signs of withdrawal namely headaches, irritability and difficulty in concentration. Nicotine dependence status and attributes were comparable to studies reported in other countries around the world. Enhanced behavioral and medical intervention strategies are needed to motivate helping both low and heavy nicotine dependent smokers to increase the number and effectiveness of quit attempts.