Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.

The potential for vaccination in leprosy elimination: new tools for targeted interventions

Despite the huge effort and massive advances toward the elimination of leprosy over the last two decades, the disease has proven stubborn; new case detection rates have stabilised over the last few years and leprosy remains endemic in a number of localised regions. The American Leprosy Missions and Infectious Disease Research Institute have undertaken a large research effort aimed at developing new tools and a vaccine to continue the push for leprosy elimination. In this paper, we outline our strategy for the integration of rapid diagnostic tests and lab-based assays to facilitate the detection of early or asymptomatic leprosy cases, as well as the efficient and focused implementation of chemoprophylaxis and immunisation to intervene in leprosy development and transmission.

Influence of Bacille Calmette-Guérin vaccination on size of tuberculin skin test reaction : to what size ?

RESUME Le diagnostic d'infection tuberculeuse repose essentiellement sur le test tuberculinique (test de Mantoux). Cependant, le résultat de ce dernier est également influencé par d'autres facteurs, le plus important étant la vaccination par le Bacille Calmette-Guérin (BCG), interaction connue depuis de nombreuses années. Il est généralement admis que l'effet de la vaccination peut entraîner des réactions positives jusqu'à un diamètre d'induration de 15 mm. Au-delà, la positivité du test est en général attribuée à une primo-infection tuberculeuse. Peu d'études se sont réellement penchées sur le sujet. Chez le personnel de soins soumis à des Mantoux répétés, cette notion revêt une importance particulière pour interpréter correctement une réaction fortement positive en l'absence de facteurs de risque tuberculeux, dans un pays à faible endémie tuberculeuse. Notre étude a cherché à déterminer si le diamètre transversal de l'induration du Mantoux était un critère fiable pour distinguer une positivité associée à une infection tuberculeuse de celle associée à une ancienne vaccination. Elle s'est attachée à rechercher un seuil au-delà duquel l'infection tuberculeuse pourrait être considérée comme probable. Entre janvier 1991 et mars 1998, tous les nouveaux employés du CHUV ont été invités à recevoir un test tuberculinique à l'occasion de leur visite d'entrée à la Médecine du personnel. En cas de réponse négative, un deuxième test a été pratiqué une semaine plus tard, pour détecter un éventuel effet booster. Lors de la première visite, l'infirmière a rempli un questionnaire comprenant les données démographiques usuelles, des informations concernant les facteurs pouvant influencer la positivité du test, notamment les antécédents de vaccination par le BCG, les expositions à la tuberculose et l'existence d'antécédents d'infection tuberculeuse. Parmi les 5117 sujets inclus dans l'étude, nous avons trouvé que l'influence de la vaccination variait en fonction de l'âge. Chez les sujets de moins de 40 ans, la vaccination par le BCG était le prédicteur le plus important d'un Mantoux positif inférieur à 18 mm, de loin supérieur aux facteurs de risque habituels pour une infection tuberculeuse, eux aussi significatifs. L'effet du BCG était présent pour des réactions allant jusqu'à 20 mm. Pour les Mantoux supérieurs à 20 mm, l'odds ratio (OR) relatif au BCG demeure clairement élevé (supérieur à 3,4) bien que non significatif. Par contre, pour les employés âgés de plus de 40 ans, le BCG est un facteur prédictif pour les tests supérieurs à 10 mm (OR 2.4) mais n'est plus un facteur significatif pour une taille supérieure à 15 mm. Ces résultats montrent que l'interprétation d'un test tuberculinique même fortement positif, doit être faite avec prudence et discernement. En effet, notre étude démontre que chez les sujets vaccinés de moins de 40 ans, dans les zones de faible endémie tuberculeuse particulièrement en l'absence de facteurs de risque pour une infection tuberculeuse, un Mantoux positif jusqu'à 18 mm est dû, le plus probablement, à une ancienne vaccination par le BCG, plutôt qu'à une infection par M tuberczilosis. L'interprétation des Mantoux de taille inférieure à 18 mm et les Mantoux effectués chez des sujets de moins de 40 ans, doit prendre en compte l'existence d'un BCG antérieur. En conséquence, la mise en évidence d'une réaction de Mantoux fortement positive ne devrait pas conduire systématiquement à un traitement préventif. L'absence de spécificité du test Mantoux, utilisé pour le dépistage de la tuberculose depuis bientôt une centaine d'année, est un problème connu. Nous démontrons que la taille de l'induration ne peut pas être utilisée de façon fiable comme critère pour identifier une infection tuberculeuse chez une personne vaccinée avec le BCG, avec le risque de sui-traiter un nombre important de sujets. Dans notre étude, 21% des sujets avaient un Mantoux supérieur ou égal à 15 mm et auraient dû être traités selon les recommandations en vigueur en Suisse si l'on ne tenait pas compte du BCG antérieur. Des tests plus spécifiques sont actuellement à l'étude et permettront vraisemblablement, à l'avenir, de palier au problème de l'absence de spécificité du test de Mantoux. Abstract : Background. Previous bacillus Calmette-Guerin (BCG) vaccination can confound the results of a tuberculin skin test (TST). We sought to determine a cutoff diameter of TST induration beyond which the influence of BCG vaccination was negligible in evaluating potential Mycobacterium tuberculosis infection in a population of health care workers with a high vaccination rate and low incidence of tuberculosis. Methods. From 1991 through 1998, all new employees at the University Hospital of Lausanne, Switzerland, underwent a 2-step TST at entry visit. We also gathered information on demographic characteristics, along with factors commonly associated with tuberculin positivity, including previous BCG vaccination, history of latent M. tuberculosis infection, and predictors for M. tuberculosis infection. Results. Among the 5117 investigated subjects, we found that influence of BCG vaccination on TST results varied across categories of age (likelihood ratio test, 0.0001). Prior BCG vaccination had a strong influence on skin test results of mm in diameter among persons <40 years old, compared with the influence of factors predictive of M. tuberculosis infection. Prior latent M. tuberculosis infection and travel or employment in a country in which tuberculosis is endemic also had significant influences. Conclusions. Interpretation of TST reactions of mm among BCG-vaccinated persons <40 years of age must be done with caution in areas with a low incidence of tuberculosis. In such a population, except for persons who have never been vaccinated, TST reactions of ---518 mm are more likely to be the result of prior vaccination than infection and should not systematically lead to preventive treatment.

Incidence of liver damage of uncertain origin in HIV patients not co-infected with HCV/HBV.

BACKGROUND AND AIMS Several studies have reported that a significant number of HIV patients not co-infected with HCV/HBV develop liver damage of uncertain origin (LDUO). The objective of our study was to evaluate the incidence of and risk factors for the development of LDUO in HIV infected patients not co-infected with HCV/HBV. METHODS Prospective longitudinal study that included HIV-infected patients free of previous liver damage and viral hepatitis B or C co-infections. Patients were followed up at 6-monthly intervals. Liver stiffness was measured at each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value greater than 7.2 kPa at two consecutive measurements. For patients who developed ALS, a protocol was followed to diagnose the cause of liver damage. Those patients who could not be diagnosed with any specific cause of liver disease were diagnosed as LDUO and liver biopsy was proposed. RESULTS 210 patients matched the inclusion criteria and were included. 198 patients completed the study. After a median (Q1-Q3) follow-up of 18 (IQR 12-26) months, 21 patients (10.6%) developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and body mass index were independently associated with the development of LDUO. CONCLUSION We found a high incidence of LDUO in HIV-infected patients associated with metabolic risk factors. The leading cause of LDUO in our study was non-alcoholic fatty liver disease.

Vaccination against human papillomavirus in Switzerland: simulation of the impact on infection rates.

OBJECTIVES: Human papillomavirus (HPV) is a sexually transmitted infection of particular interest because of its high prevalence rate and strong causal association with cervical cancer. Two prophylactic vaccines have been developed and different countries have made or will soon make recommendations for the vaccination of girls. Even if there is a consensus to recommend a vaccination before the beginning of sexual activity, there are, however, large discrepancies between countries concerning the perceived usefulness of a catch-up procedure and of boosters. The main objective of this article is to simulate the impact on different vaccination policies upon the mid- and long-term HPV 16/18 age-specific infection rates. METHODS: We developed an epidemiological model based on the susceptible-infective-recovered approach using Swiss data. The mid- and long-term impact of different vaccination scenarios was then compared. RESULTS: The generalization of a catch-up procedure is always beneficial, whatever its extent. Moreover, pending on the length of the protection offered by the vaccine, boosters will also be very useful. CONCLUSIONS: To be really effective, a vaccination campaign against HPV infection should at least include a catch-up to early reach a drop in HPV 16/18 prevalence, and maybe boosters. Otherwise, the protection insured for women in their 20s could be lower than expected, resulting in higher risks to later develop cervical cancer.

High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.

A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.

The aim of T cell vaccines is the expansion of antigen-specific T cells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine-induced T cells are often evaluated, their reactivity for the cognate antigen versus their cross-reactive potential is rarely considered. In fact, little information is available regarding the influence of vaccines on T cell fine specificity of antigen recognition despite the impact that this feature may have in protective immunity. To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo. A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones. While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor-reactive.

DNA prime-protein boost based vaccination with a conserved region of leptospiral immunoglobulin-like A and B proteins enhances protection against leptospirosis

Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of theLeptospira genus. Vaccination with bacterins has severe limitations. Here, we evaluated the N-terminal region of the leptospiral immunoglobulin-like B protein (LigBrep) as a vaccine candidate against leptospirosis using immunisation strategies based on DNA prime-protein boost, DNA vaccine, and subunit vaccine. Upon challenge with a virulent strain ofLeptospira interrogans, the prime-boost and DNA vaccine approaches induced significant protection in hamsters, as well as a specific IgG antibody response and sterilising immunity. Although vaccination with recombinant fragment of LigBrep also produced a strong antibody response, it was not immunoprotective. These results highlight the potential of LigBrep as a candidate antigen for an effective vaccine against leptospirosis and emphasise the use of the DNA prime-protein boost as an important strategy for vaccine development.

An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy.

Vaccination of dogs with Trypanosoma rangeli induces antibodies against Trypanosoma cruzi in a rural area of Córdoba, Argentina

Dogs play a major role in the domestic cycle of Trypanosoma cruzi, acting as reservoirs. In a previous work we have developed a model of vaccination of dogs in captivity with nonpathogenic Trypanosoma rangeli epimastigotes, resulting in the production of protective antibodies against T. cruzi, with dramatic decrease of parasitaemia upon challenge with 100,000 virulent forms of this parasite. The aim of this work was to evaluate the immunogenicity of this vaccine in dogs living in a rural area. Domestic dogs, free from T. cruziinfection, received three immunisations with fixed T. rangeliepimastigotes. Dogs were not challenged with T. cruzi, but they were left in their environment. This immunisation induced antibodies againstT. cruzi for more than three years in dogs in their natural habitat, while control dogs remained serologically negative.

Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.

Toll-like receptor ligands are potentially useful adjuvants for the development of clinical T cell vaccination. Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae. Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals. Adverse reactions were mild-to-moderate. Fourteen patients received at least 8 vaccinations and were thus evaluable for clinical tumor and immune responses. Seven patients experienced progressive disease, whereas 2 patients had stable disease throughout the trial period, 1 of them with regression of multiple skin metastases. The remaining 5 patients had no measurable disease. Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients. Increased percentages of T cells were found in three patients, memory/effector T cell differentiation in 4 patients, and a positive interferon-gamma Elispot assay in 1 patient. Antibody responses to P40 were observed in all patients. We conclude that vaccination with peptide and P40 was feasible and induced ex vivo detectable tumor antigen specific T cell responses in 6 of 14 patients with advanced melanoma.

Support for Seasonal Influenza Vaccination Requirements among US Healthcare Personnel.

Objective. To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements. Design. Between June 1 and June 30, 2010, we surveyed a sample of US HCP ([Formula: see text]) recruited using an existing probability-based online research panel of participants representing the US general population as a sampling frame. Setting. General community. Participants. Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings. Methods. We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models. Results. A total of 57.4% (95% confidence interval, 53.3%-61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective. Conclusions. A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements.

Opportunity for catch-up HPV vaccination in young women after first delivery.

Background Early age at first delivery has been identified as a risk factor for high-risk HPV-type infection and cervical cancer development. Methods A cross-sectional study was carried out in a large public maternity hospital in Sao Paulo, Brazil. During June 2006 to February 2007, 301 women aged 15-24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Detection of HPV DNA in cervical specimens was performed using a standardised PCR protocol with PGMY09/11 primers. The association of selected factors with HPV infection was assessed by using a Generalised Linear Model. Results HPV DNA was detected in 58.5% (95% CI 52.7% to 64.0%) of the enrolled young women. The most common types of HPV found were: HPV16, HPV51, HPV52, HPV58 and HPV71. The overall prevalence of HPV types targeted by the HPV prophylactic vaccines was: HPV 16-12.0%, HPV 18-2.3% and HPV 6 and 11 4.3%. In the multivariate analysis, only age (inversely, p for trend=0.02) and smoking habits were independently associated with HPV infection. Conclusions The findings show that these young primiparous women had high cervical HPV prevalence, suggesting that this is a high-risk group for cervical cancer development. Nevertheless, 17.3% were positive for any of the four HPV types included in HPV vaccines (HPV6, 11, 16 or 18), with 13.3% positive for HPV 16 or 18 and only 1.0% having both vaccine related-oncogenic HPV types. Thus, young primiparous women could benefit from catch-up HPV vaccination programmes.