Introducing New Vaccines in Developing Countries: Concepts and Approaches to Estimating Burden of Haemophilus influenzae Type b-associated Disease

In the past 30 years, great strides have been made in immunizing infants and children routinely in developing countries under the Expanded Programme on Immunization. Despite this, the introduction of Haemophilus influenzae type b (Hib) vaccines has progressed rather slowly compared to previously-introduced vaccines for infant immunizations. This slower uptake has been attributed partly to the need for data on the burden of invasive Hib disease. To understand this need, conceptual underpinnings and prerequisites were explored for Hib disease-burden studies. Methodological approaches were also reviewed for conducting Hib disease-burden studies that may be considered in developing countries. Potential studies span a range of designs that provide varying levels of clinical, laboratory and epidemiologic evidence of the burden of invasive Hib disease. Carefully-conducted studies can lay the foundation for complementary studies of long-term disability due to invasive Hib disease, national economic analysis, and field evaluations of vaccine. Studies done in collaboration with national agencies and clinical investigators will maximize study value and provide critical data for national decision- makers who make choices regarding the introduction of Hib vaccines

Ebola Virus Infection: Overview and Update on Prevention and Treatment

In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July 2015, a total of 27,741 EVD cases and 11,284 deaths were reported from all affected countries. Several therapeutic agents and novel vaccines for EVD have been developed and are now undergoing evaluation. Concurrent with active case investigation, contact tracing, surveillance and supportive care to patients and communities, there has been rapid progress in the development of new therapies and vaccines against EVD. Continued focus on strengthening clinical and public health infrastructure will have direct benefits in controlling the spread of EVD and will provide a strong foundation for deployment of new drugs and vaccines to affected countries when they become available. The unprecedented West Africa Ebola outbreak, response measures, and ensuing drug and vaccine development suggest that new tools for Ebola control may be available in the near future

Trends in Legionnaires\u27 Disease-Associated Hospitalizations, United States, 2006-2010

Background: Legionella pneumophila is a waterborne cause of both healthcare-associated and community-acquired pneumonia. Legionella pneumophila serogroup 1 is responsible for 80% of infections. There is currently limited published disease burden data on Legionnaires\u27 disease-associated hospitalization in the United States. Methods: In this study, we estimated the annual incidence of Legionnaires\u27 disease-associated hospitalizations in United States and identified demographic, temporal, and regional characteristics of individuals hospitalized for Legionnaires\u27 disease. A retrospective study was conducted using the National Hospital Discharge Survey (NHDS) data from 2006 to 2010. The NHDS is a nationally representative US survey, which includes estimates of inpatient stays in short-stay hospitals in the United States, excluding federal, military, and Veterans Administration hospitals. All discharges assigned with the Legionnaires\u27 disease International Classification of Diseases 9th Clinical Modification discharge diagnostic code (482.84) were included in this study. Results: We observed the annual incidence and number of Legionnaires\u27 disease-associated hospitalizations (per 100 000 population) in the United States by year, age, sex, race, and region. Over a 5-year period, 14 574 individuals experienced Legionnaires\u27 disease-associated hospitalizations in the United States The annual population-adjusted incidence (per 100 000 population) of Legionnaires\u27 disease-associated hospitalizations was 5.37 (95% confidence interval [CI], 5.12-5.64) in 2006, 7.06 (95% CI, 6.80-7.40) in 2007, 8.77 (95% CI, 8.44-9.11) in 2008, 17.07 (95% CI, 16.62-17.54) in 2009, and 9.66 (95% CI, 9.32-10.01) in 2010. A summer peak of Legionnaires\u27 disease-associated hospitalizations occurred from June through September in 2006, 2007, 2008, and 2010. Conclusions: Legionnaires\u27 disease-associated hospitalizations significantly increased over the 5-year study period. The increasing disease burden of Legionnaires\u27 disease suggests that large segments of the US population are at risk for exposure to this waterborne pathogen

Cross-Sectional Survey of Perceived Barriers Among Community Pharmacists Who Do Not Immunize, in Wayne County, Michigan

Introduction: The goal of the study was to identify perceived barriers to implementation of vaccination services encountered by independent and small-chain community pharmacies in an urban setting. Methods: Pharmacists in independent and small-chain pharmacies located in 29 Michigan ZIP codes were visited and asked to complete a 5- to 10-min semi-structured interview. Results: A total of 93 independent and 12 small-chain pharmacies participated (n = 105; 61%). The pharmacies filled an average of 700 prescriptions each week with 1.1 pharmacist full-time equivalents and 57 h of technician time. The most common services that participating pharmacies provided were dispensing outpatient medication (99%), medication therapy management (MTM, 65.7%), disease management or coaching (54.3%), point-of-care testing (34.3%), and dispensing medications to inpatient facilities (16.2%). Only seven pharmacies (6.7%) administered vaccinations. When pharmacists were asked to identify what it would take to start to administer vaccines, the most common responses were increased demand from patients (37.1%), adequate time (19%), appropriate space (17.1%), appropriate amount of staff (14.3%), change in attitudes or beliefs of the owner or pharmacists at that pharmacy (13.3%), increased profit related to vaccines (11.4%), and increased awareness among patients about the importance of vaccines (11.4%). The majority of pharmacies (65.3%) reported that only one factor would need to change to start to administer vaccines. Conclusion: Independent and small-chain community pharmacies in an urban, primarily low-income area identified several barriers that have prevented implementation of vaccination services. However, the majority of pharmacies reported that only one factor would need to change in order to begin to administer vaccines. Interventional efforts necessary to address commonly cited barriers may include providing education to pharmacists about the need for community pharmacy-based immunization programs in addition to services provided by physician offices, as well as the importance of proactively providing immunization-related recommendations to patients

Trends in Pneumonia and Influenza-associated Hospitalizations in South Korea, 2002-2005

Pneumonia and influenza are leading causes of morbidity and mortality across the globe. Korea has established the national health-insurance system to cover the entire Korean population since 1989. The aim of this study was to describe the epidemiologic trends in pneumonia and influenza-associated hospitalizations and deaths using the Korean National Health Insurance databases and national vital statistics. During 2002-2005, 989,472 hospitalizations and 10,543 deaths due to pneumonia and influenza were recorded. Eighty-one percent of the hospitalizations were related to diagnoses with unspecified aetiology. The average annual rate of hospitalizations due to pneumonia and influenza was 5.2 per 1,000 people [95% confidence interval (CI) 5.2-5.3], and the hospitalization rate increased by 28% (from 4.5 to 5.8 per 1,000 people) during the four-year study period. In addition, deaths due to pneumonia and influenza increased by 48% (2,829 during 2003, 3,522 during 2004, and 4,192 during 2005). Overall, the national burden of hospitalizations and deaths due to pneumonia and influenza in Korea was high, and it increased for all age-groups during the study period. A comprehensive review of potential interventions by the government authorities should aim to reduce the burden of pneumonia and influenza

Loop-Mediated Isothermal Amplification Methods for Diagnosis of Bacterial Meningitis

The rapid, accurate, and efficient identification of an infectious disease is critical to ensure timely clinical treatment and prevention in public health settings. In 2015, meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis was responsible for 379,200 (range: 322,700–444,700) deaths. Clinical features alone cannot determine whether bacterial meningitis is present; an analysis of cerebrospinal fluid (CSF) is essential. Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method offering an alternative to polymerase chain reaction (PCR). LAMP-based assays for detection of three leading bacteria in CSF for diagnosis of meningitis have been established. The typing assays using LAMP for detection of meningococcal serogroups A, B, C, W, X, and Y as well as H. influenzae serotypes a, b, c, d, e, and f were launched. In comparative analysis of the meningitis pathogen assays, LAMP assays did not yield false negative results, and the detection rate of LAMP assays was superior compared with PCR or conventional culture methods. LAMP assays provide accurate and rapid test results to detect major bacterial meningitis pathogens. Accumulating evidence suggests that LAMP assays have the potential to provide urgently needed diagnostics for bacterial meningitis in resource-limited settings of both developed and developing countries

Who is exposed to smoke at home? A population-based cross-sectional survey in central Vietnam

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Development of a Novel Loop-Mediated Isothermal Amplification Method to Detect Guiana Extended-Spectrum (GES) β-Lactamase Genes in \u3cem\u3ePseudomonas aeruginosa\u3c/em\u3e

Infections caused by multidrug-resistant Pseudomonas aeruginosa in hospitalized patients are often fatal, and nosocomial infections caused by Guiana extended-spectrum (GES) β-lactamase-producing strains are of growing concern. Several genotypes of the GES β-lactamase gene (blaGES) include a single missense mutation, a change from G to A at nucleotide position 493 (G493A) that changes glycine to serine; the mutant enzyme exhibits carbapenemase activity. Rapid and reliable identification of drug-resistance is important in clinical settings; however, culture methods remain the gold standard. Conventional and real-time PCR cannot identify carbapenemase-producing genotypes, and direct DNA sequencing is essential. We established a novel loop-mediated isothermal amplification (LAMP) method to detect various genotypes of blaGES and another LAMP method to discriminate carbapenemase genotypes of blaGES. We evaluated the two assays using clinical P. aeruginosa strains. Two primer sets targeting blaGES (GES-LAMP) and the point mutation (Carba-GES-LAMP) were designed and evaluated for specificity and sensitivity. The detection limit of the GES-LAMP method was assessed using purified DNA and DNA-spiked clinical samples (urine, sputum, and blood). To determine the clinical usefulness of the methods, we used different (genotypically and phenotypically) P. aeruginosa clinical isolates, collected from diverse geographical locations between 2003 and 2012. The novel LAMP assay targeting blaGES was highly specific. The detection limit was 10 DNA copies per reaction; the assay was 10-fold more sensitive than conventional PCR. The LAMP assay detected blaGES with high sensitivity in all DNA-spiked samples; PCR did not detect blaGES in blood samples. The GES-LAMP method correctly detected the 5 isolates containing blaGES among the 14 isolates tested. Using these isolates, we confirmed that our Carba-GES-LAMP method of detecting point mutations correctly identified the two blaGES positive organisms with carbapenemase activity. To the best of our knowledge, this is the first report of the GES β-lactamase gene detection assay using the LAMP method. Our new assays effectively detect blaGES and critical unique mutations

Diversity of Rotavirus Strains Causing Diarrhea in \u3c5 Years Old Chinese Children: A Systematic Review

Background: We conducted a systematic review of the diversity and fluctuation of group A rotavirus strains circulating in China. Methods and Findings: Studies of rotavirus-based diarrhea among children less than 5 years, published in English or Chinese between 1994 and 2012, were searched in PubMed, SinoMed, and CNKI and reviewed by applying standardized algorithms. The temporal and spatial trends of genotyping and serotyping were analyzed using a random-effects model. Ninety-three studies met the inclusion/exclusion criteria and were included in the meta-analysis. Overall, 22,112 and 10,660 rotavirus samples had been examined for G and P types, respectively. The most common G types were G1 (39.5%), G3 (35.6%), G2 (1.3%), and G9 (0.1%). Among P types, P[8] (54.6%) was the predominant type, followed by P[4] (11.1%) and P6 (0.1%). The most common G-P combinations were G3P[8] (32.1%) and G1P[8] (24.5%), followed by G2P[6] (13.2%) and G2P[4] (10.1%). Before 2000, serotype G1 was the predominant strain and accounted for 74.3% of all rotavirus infections; however, since 2000, G3 (45.2%) has been the predominant strain. Rotavirus P types showed little variation over the study period. Conclusion: Despite the variation of serotypes observed in China, the G1, G2, G3, and G4 serotypes accounted for most rotavirus strains in recent decades. These results suggest that Chinese children will be adequately protected with currently available or forthcoming rotavirus vaccines

Molecular Serotype-Specific Identification of Streptococcus Pneumoniae using Loop-Mediated Isothermal Amplification

Over the past four decades, the incidence of meningitis caused by Haemophilus influenzae in children has decreased due to widespread vaccination against H. influenzae type b (Hib). The incidence of invasive diseases due to H. influenzae types not included in the vaccines, however, has increased. At present, there are a limited number of diagnostics available to detect non-type b H. influenzae. To address this issue, we developed a rapid, simple, and cost-effective method for detecting serotypes of H. influenzae. We designed LAMP primer sets based on published sequences for H. influenzae capsular types a, c, d, e, and f. The assay was evaluated to determine test reactivity, specificity, and sensitivity. To support its use in patients with suspected meningitis, we evaluated the detection limit of the non-Hib serotype specific LAMP assay using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) specimens. The reactivity and specificity of the LAMP assays were confirmed using six serotypes and non-typeable H. influenzae strains, plus eight strains of other Haemophilus species and non-Haemophilus genera. The detection limits of the LAMP assay for capsular types a, c, d, e, and f were 102, 102, 102, 103, and 10 copies per reaction, while those of the PCR assay were 104, 104, 103, 103, and 104 genome copies per reaction, respectively. Using DNA-spiked CSF specimens, the detection limit of the LAMP assay was equivalent to that using purified DNA as the template. However, the detection limit of the PCR was reduced from 103 to 104 genome copies per reaction for serotype d and from 103 to 105 genome copies per reaction for serotype e. To the best of our knowledge, this is the first report of a serotype-specific identification assay for H. influenzae using the LAMP method. Our results suggest the potential of LAMP methods for patients with suspected meningitis in resource-limited laboratories or public health surveillance systems