The GLP-1 analog liraglutide attenuates acute liver injury in mice.

INTRODUCTION AND OBJECTIVES: Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl4)-induced hepatotoxicity. MATERIALS AND METHODS: Male Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118mgkg-1) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl4 (5mgkg-1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (5mgkg-1, i.p.) and subsequent treatment with liraglutide (0.057mgkg-1) or vehicle (distilled water) for 1 day. In both protocols, 24h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver. RESULTS: Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter. CONCLUSIONS: The present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.

Claviceps purpurea e Bipolaris sp. como causa de ergotismo em bovinos no estado de Santa Catarina / Claviceps purpurea e Bipolaris sp. as a cause of ergotism in cattle in Santa Catarina State

Claviceps purpurea é o fungo associado ao ergotismo. Esta é uma enfermidade causada pela ingestão de escleródios chamados de ergot, que contém alcalóides que atuam em receptores adrenérgicos, dopaminérgicos e seratoninérgicos causando efeito direto em vasos sanguíneos, musculatura lisa e sistema nervoso central e autônomo. Descrevem-se dados epidemiológicos, sinais clínicos e lesões de uma enfermidade de bovinos caracterizada por hipertermia, taquicardia, taquipneia e ulcerações na coroa do casco de bovinos. Entre 2000 e 2014 foram diagnosticados 13 surtos, três da forma distérmica, sete da forma gangrenosa e três da forma convulsiva. Porém, em cinco destes sete surtos, nos locais onde esses animais pastoreavam havia alta incidência de inflorescências de Sporobolus indicus conhecido como "capim-mourão", infectadas por um fungo com coloração enegrecida, identificado como Bipolaris sp. A enfermidade foi reproduzida experimentalmente em cinco bovinos com a administração destas inflorescências. Os bovinos em experimentação receberam inflorescências de S. indicus respectivamente nas doses diárias de 0,1g/kg, 0,2g/kg, 0,2g/kg, 0,26g/kg e 0,34g/kg por um período de 4, 7, 9 e 30 dias. Após três a sete dias de ingestão das inflorescências infectadas, quatro dos cinco bovinos apresentaram diarreia e manifestaram taquicardia, taquipneia e hipertermia em algum período durante a ingestão. Estes sinais coincidiram com os dias mais quentes deste período. Um bovino manifestou hiperemia na coroa do casco e perda de pêlos da extremidade da cauda. Baseado na reprodução experimental é possível afirmar que o capim Sporobolus indicus infectado pelo fungo Bipolaris sp é capaz de causar diarreia, hipertermia, taquicardia, taquipneia, hiperemia na coroa do casco e perda de pêlos da extremidade da cauda.(AU)

Claviceps purpurea is the fungus associated with ergotism. Ergotism is a disease caused by the ingestion of esclerodios called ergot, which contains alkaloids that act on dopaminergic and adrenergic receptors, causing seratoninergic effect on blood vessels, smooth muscles and central nervous and autonomic system. The present study describes epidemiological data, clinical signs and lesions of a bovine cattle disease characterized by hyperthermia, tachycardia, tachypnea and injuries in the coronary band of the hooves. Initially the cause was attributed to the fungus Claviceps purpurea. Between 2000 and 2014, 13 outbreaks were described, being three of distermic form, seven of gangrenous and three of the convulsive form. However, in five out of the seven of the gangrenous form outbreaks, it has been observed a high incidence of smut grass (Sporobolus indicus) inflorescences infected by a blackened fungus, classified as Bipolaris sp., in the places where the bovine grazed. The disease was reproduced experimentally by administration of inflorescences of smut grass contaminated by Bipolaris sp. Five bovine received daily doses of 0.1g/kg, 0.2g/kg, 0.2g/kg, 0.26g/kg and 0.34g/kg during 4, 7, 9, 30 and 30 days respectively. After three to seven days of eating contaminated inflorescences four cattle had diarrhea, tachycardia, tachypnea and intermittent hyperthermia. These clinical signs happened on the warmest days and during the warmest temperatures of the day. A bovine showed hyperemia in the coronary band of the hoof and loss of tail tip hair. According to data obtained during the experimental reproduction, smut grass contaminated by Bipolaris sp. can cause hyperthermia, tachycardia, tachypnea, injuries in the coronary band of the hoof and loss of the tail tip hair in bovine cattle.(AU)

Intoxicação espontânea e experimental por tifton 68 (Cynodon nlemfuensis Vanderyst) em bovinos / Spontaneous and experimental poisoning by tifton 68 (Cynodon nlemfuensis Vanderyst) in cattle

Tifton 68 (Cynodon nlemfuensis Vanderyst) é uma gramínea cultivada na região sul do Brasil, responsável por manifestações clínicas superagudas de dispneia, dificuldade de deglutição, tremores musculares, timpanismo e decúbito em bovinos. A morte ocorre rapidamente após o início dos primeiros sinais e não são encontradas alterações macro e microscópicas significativas. O presente estudo descreve os aspectos epidemiológicos, clínicos e lesionais da intoxicação espontânea por tifton 68 que ocorreu nos municípios de Rio do Sul, Pouso Redondo, Taió e Rio do Campo, estado de Santa Catarina, Brasil, nos anos de 1996, 1997, 1998 e 2010, respectivamente. Experimentalmente foram avaliadas a presença de ácido cianídrico nas folhas verdes e secas desta planta, através do teste do papel picrossódico e a reversão da intoxicação pela utilização de uma solução antídoto específica de tiossulfato de sódio e nitrito de sódio. A reprodução experimental consistiu na administração de folhas verdes de tifton 68 para dois bovinos com doses a partir de 10,3g/kg. O quadro de intoxicação cianogênica foi confirmado pela imediata resposta ao tratamento intravenoso com a solução antídoto. As amostras da planta verde forneceram resposta positiva ao teste do papel picrossódico. O feno de tifton 68 não demonstrou qualquer toxicidade, mesmo em altas doses (18 e 27g/kg), sendo seguro para a alimentação de bovinos.(AU)

Tifton 68 (Cynodon nlemfuensis Vanderyst) is a grass cultivated in southern Brazil which causes peracute clinical manifestations including dyspnea, swallowing difficulties, muscular tremors, tympanism and recumbency in cattle. Animal's death occurs rapidly after the onset of clinical signs and neither macroscopic nor microscopic lesions have been found. This paper describes the epidemiology, clinical findings and lesions of spontaneous poisoning by tifton 68 in cattle in the municipalities of Rio do Sul, Pouso Redondo, Taió and Rio do Campo in the state of Santa Catarina, Brazil, in 1996, 1997, 1998 and 2010 respectively. The presence of hydrocyanic acid was experimentally estimated in green and dried leaves through the picric acid paper test and poisoning treatment using a specific antidote solution of sodium thiosulfate and sodium nitrite. The poisoning was experimentally reproduced by the administration of tifton 68 green leaves to two cattle at a starting dose of 10.3 g/kg. The cyanide poisoning was confirmed by the immediate response to treatment with intravenous antidote. The samples of tifton 68 green leaves gave positive response in the picric acid paper test. The hay of tifton 68 showed no toxicity even at high doses (18 and 27 g/kg) and it is safe for cattle consumption.(AU)

Effect of Combination Vaccines on Hepatitis B Vaccine Compliance in Children in the United States.

BACKGROUND: An increasingly crowded immunization schedule threatens the completion and compliance of hepatitis B vaccinations (HepB), the primary method of hepatitis B prevention. Combination vaccines have been proposed to alleviate this problem. METHODS: Data from the 2011 National Immunization Survey Public-Use Data File were utilized (GSK study identifier: HO-11-770) to compare HepB completion and compliance rates between 3 groups of children: those who received HepB combination vaccine, those who received non-HepB combination vaccine and those who received HepB single-antigen vaccine only. Completion was defined as the accumulation of 3 HepB doses by 18 months. Compliance was defined as the receipt of vaccine doses within the Advisory Committee on Immunization Practices' recommended age ranges. RESULTS: Of a sample of 4,040,116 children, 39.4% received a HepB combination vaccine, 43.0% received a non-HepB combination vaccine and 17.5% received a HepB single-antigen vaccine. Overall, 91.2% of children completed all 3 recommended doses, but only 61.8% completed them at age-appropriate times. Those receiving single-antigen only (odds ratio = 0.25, 95% confidence interval: 0.17-0.35) or non-HepB combination vaccines (odds ratio = 0.50, 95% confidence interval: 0.37-0.69) were substantially less likely to complete 3 doses of HepB than those who received the HepB combination vaccine. CONCLUSIONS: Although completion rates were high, a large proportion of children did not receive HepB doses at age-appropriate times. Combination vaccine was associated with both higher completion and compliance outcomes compared with HepB single-antigen vaccine.

The role of monogamy and duration of heterosexual relationships in human papillomavirus transmission.

BACKGROUND: Published data are equivocal about the relative rates of male-to-female and female-to-male human papillomavirus (HPV) transmission. Our objective was to estimate genital HPV incidence among heterosexual partners from a broad age range and to investigate the effects of monogamy and relationship duration on incidence. METHODS: HPV genotyping was conducted for heterosexual partners, aged 18-70 years, from Tampa, Florida, who provided genital exfoliated cell specimens at semiannual visits during a 2-year study. The rate of incident HPV detection was assessed for 99 couples, and transmission incidence was estimated among a subset of 65 discordant couples. We also evaluated the effect of monogamy and relationship duration on transmission incidence. RESULTS: Couples were followed up for a median of 25 months and had a mean age of 33 years for both sexes. The HPV type-specific transmission incidence rate was 12.3 (95% confidence interval, 7.1-19.6) per 1000 person-months for female-to-male transmission and 7.3 (95% confidence interval, 3.5-13.5) per 1000 person-months for male-to-female transmission. Regardless of monogamy status or relationship duration, there was a similar pattern of increased incident HPV detection among men compared with women. CONCLUSIONS: HPV may be transmitted more often from women to men than from men to women, suggesting a need for prevention interventions, such as vaccination, for men.

A study of typhoid fever in five Asian countries: disease burden and implications for controls.

OBJECTIVE: To inform policy-makers about introduction of preventive interventions against typhoid, including vaccination. METHODS: A population-based prospective surveillance design was used. Study sites where typhoid was considered a problem by local authorities were established in China, India, Indonesia, Pakistan and Viet Nam. Standardized clinical, laboratory, and surveillance methods were used to investigate cases of fever of >or= 3 days' duration for a one-year period. A total of 441,435 persons were under surveillance, 159,856 of whom were aged 5-15 years. FINDINGS: A total of 21,874 episodes of fever were detected. Salmonella typhi was isolated from 475 (2%) blood cultures, 57% (273/475) of which were from 5-15 year-olds. The annual typhoid incidence (per 100,000 person years) among this age group varied from 24.2 and 29.3 in sites in Viet Nam and China, respectively, to 180.3 in the site in Indonesia; and to 412.9 and 493.5 in sites in Pakistan and India, respectively. Altogether, 23% (96/413) of isolates were multidrug resistant (chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole). CONCLUSION: The incidence of typhoid varied substantially between sites, being high in India and Pakistan, intermediate in Indonesia, and low in China and Viet Nam. These findings highlight the considerable, but geographically heterogeneous, burden of typhoid fever in endemic areas of Asia, and underscore the importance of evidence on disease burden in making policy decisions about interventions to control this disease.

Revaccination with locally-produced vi typhoid polysaccharide vaccine among chinese school-aged children: safety and immunogenicity findings.

OBJECTIVE: To evaluate the safety and immunogenicity of revaccination with locally-produced Vi polysaccharide vaccine 3 years after the first dose in Chinese children aged 9 to 14 years. METHODS: A randomized, placebo-controlled trial was conducted in Suzhou, Jiangsu, China. Six hundred and sixty-seven eligible children who had previously received a primary dose of Vi vaccine were randomly assigned to receive 1 dose of 30 mug Vi vaccine or placebo. In addition, 331 eligible children received 1 dose of Vi polysaccharide vaccine as a primary vaccination. Adverse events were followed for 28 days after vaccination. Serum samples were collected from a subgroup of participants on day 0 and day 28, and Vi antibodies were analyzed using a passive hemagglutination method. RESULTS: Revaccination was found to be safe and immunogenic. No severe adverse events were observed. A significant increase in antibody titers after vaccination was observed among children who had and had not been previously vaccinated. Twenty-eight days after injection, the seropositive rate was 79% in both revaccination and primary injection groups; the geometric mean antibody titer was 1:40 in the primary injection group and 1:29 in the revaccination group (P = 0.24). Although the difference of attained geometric mean titers in follow-up sera was not significantly different in these 2 groups, the fold-rise of these titers from baseline was significantly higher in the primary injection group than in the revaccination group (7.7 versus 3.1, P < 0.001). CONCLUSION: We found that revaccination using the locally produced Vi polysaccharide vaccine among Chinese school-aged children was safe and increased antibody titers. Revaccination can be used to extend the duration of protection provided by Vi polysaccharide vaccine.

Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83-->Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.

The use of typhoid vaccines in Asia: the DOMI experience.

BACKGROUND: Two currently licensed typhoid vaccines have been evaluated in Asia, yet few Asian countries have considered including typhoid vaccines in their vaccination programs. The Diseases of the Most Impoverished (DOMI) Program was initiated to provide evidence to decide on the introduction of typhoid vaccines in Asian countries. METHODS: The centerpiece of the program is a multidisciplinary demonstration project with Vi vaccine in 5 Asian countries. The project includes epidemiologic, economic, sociobehavioral, and policy studies. RESULTS: Policy makers want evidence on which to base their vaccine-related decisions. The DOMI Program has provided updated information on the typhoid fever burden at several Asian sites. Cost-of-illness studies found high costs to governments and individuals. Sociobehavioral studies indicated a positive attitude toward typhoid vaccines. The results of the demonstration projects indicate that mass-immunization campaigns are feasible and acceptable. CONCLUSIONS: The DOMI Program has begun to provide momentum for the evidence-based, rational introduction of typhoid vaccines into the public health programs of several Asian countries.

Implementation of good clinical practice guidelines in vaccine trials in developing countries.

The practicalities when applying the ICH GCPs (International Conference on Harmonization 1996 Good Clinical Practices [EU, MHLW, FDA. International Conference on Harmonization Guideline for Good Clinical Practice; 1997] in less developed countries (ldcs) are seldom discussed and we found no guidelines as how to "adapt" them. Below we illustrate how ICH GCP principles can be implemented in different settings. We have recently conducted in Asia (Hechi, China; Karachi, Pakistan; Hue, Vietnam; North Jakarta, Indonesia and Kolkata, India) large-scale cluster-randomized effectiveness evaluations of the Vi polysaccharide typhoid fever vaccine (Vi PS project) among approximately 200,000 individuals(1)[Acosta CJ, Galindo CM, Ali M, Abu-Elyazeed R, Ochiai RL Danovaro-Holliday MC et al. A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design. TMIH 2005;10(12):1219-1228]. There is no doubt on the importance of ICH GCP in its contribution to ethical and scientifically sound clinical research. However, when the ICH GCP is implemented in ldcs some considerations must be made in order to adequately tailor them. Vaccine trials in ldcs are a frequent setting for such challenges because of the increased global interest conducting health research in such countries. The ICH GCP principles are discussed below within the framework of this recent typhoid fever vaccine study experience.

The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy.

We report the coverage, safety, and logistics of a school-based typhoid fever immunization campaign that took place in Hue City, central Vietnam; a typhoid fever endemic area. A cluster-randomized evaluation-blinded controlled trial was designed where 68 schools (cluster) were randomly allocated the single dose Vi polysaccharide vaccine (Typherix) or the active control hepatitis A vaccine (Havrix). A safety surveillance system was implemented. A total of 32,267 children were immunized with a coverage of 57.5%. Strong predictors for vaccination were attending primary schools, peri-urban location of the school, and low family income. Human resources were mainly schoolteachers and the campaign was completed in about 1 month. Most adverse events reported were mild. Safe injection and safe sharp-waste disposal practices were followed. A typhoid fever school-based immunization campaign was safe and logistically possible. Coverage was moderate and can be interpreted as the minimum that could have been achievable because individual written informed consent procedures were sought for the first time in Hue City and the trial nature of the campaign. The lessons learned, together with cost-effectiveness results to be obtained by the end of follow-up period, will hopefully accelerate the introduction of Vi typhoid fever vaccine in Vietnam.

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047].

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future.

Enhanced disease surveillance through private health care sector cooperation in Karachi, Pakistan: experience from a vaccine trial.

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings.

A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine during six years of follow-up.

A locally produced Vi polysaccharide vaccine against typhoid fever was licensed in China following two placebo-controlled, efficacy trials conducted in the early 1990s in Baoying, Jiangsu Province, and Quan-zhou, Guangxi Province. The two trials each enrolled over 80,000 participants and followed participants for 12 and 19 months post-vaccination, respectively. To define the long-term efficacy of this vaccine, we retrospectively assessed the occurrence of typhoid fever, diagnosed with clinical and serological criteria, in the two study populations for 6 years following vaccination. During the second year following vaccination, vaccine efficacy was 100% (95% CI: 17%, 100%) in Baoying and 85% (95% CI: 49%, 96%) in Quan-zhou. There was suggestive protection (51%; PE: -95%, 88%) during the third year in Baoying, nearly identical to the level observed in the third year of an earlier trial in South Africa. These results confirm that this vaccine protects for at least 2 years, and are consistent with the assertion that the vaccine protects for at least 3 years.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; expanding the use of Vi polysaccharide vaccine in southeast China: a cluster-randomized trial.

BACKGROUND: One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. METHODS: The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. RESULTS: The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. CONCLUSION: The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

The role of epidemiology in the introduction of vi polysaccharide typhoid fever vaccines in Asia.

Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.