Hepatitis A virus vaccine escape variants and potential new serotype emergence.

Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants

Systemic Expression of Cytokine Production in Patients with Severe Pneumococcal Pneumonia: Effects of Treatment with a β-Lactam versus a Fluoroquinolone▿

Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1β, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-α, for which lower concentrations were obtained at 120 h in the levofloxacin group (P = 0.014). Basal oxygen saturation (P = 0.034) and heart rate (P = 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro- and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a β-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease

Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence

These authors contributed equally to this article. Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants. In areas where hepatitis A has low to moderate endemicity, introduction of the virus occurs through consumption of imported foods, traveling, or through immigration flows (1–3). Men who have sex with men (MSM) comprise a high-risk group for hepatitis A, and several outbreaks affecting this group have been reported across Europe (4). To prevent the spread of infection, since 1999, vaccination programs have been implemented among preadolescents in the Catalonia Autonomous Community of Spain. Despite some degree of nucleotide heterogeneity at the capsid region of hepatitis A virus (HAV) (5,6), there is not an equivalent degree of amino acid variation (7). HAV replicates as complex dynamic mutant distributions or quasispecies (8) and thus the high degree of conservation of the capsid amino acid sequences among independent strains must be the result o

Hepatitis A Virus Genotype Distribution during a Decade of Universal Vaccination of Preadolescents

A universal vaccination program among preadolescents was implemented in Catalonia, Spain, during the period of 1999–2013 and its effectiveness has been clearly demonstrated by an overall significant attack rate reduction. However, reductions were not constant over time, and increases were again observed in 2002–2009 due to the occurrence of huge outbreaks. In the following years, in the absence of large outbreaks, the attack rate decreased again to very low levels. However, an increase of symptomatic cases in the <5 age group has recently been observed. This is an unexpected observation since children younger than 6 are mostly asymptomatic. Such a long vaccination campaign offers the opportunity to analyze not only the effectiveness of vaccination, but also the influence of the circulating genotypes on the incidence of hepatitis A among the different age groups. This study has revealed the emergence of genotype IC during a foodborne outbreak, the short-lived circulation of vaccine-escape variants isolated during an outbreak among the men-having-sex-with-men group, and the association of genotype IIIA with the increase of symptomatic cases among the very young. From a public health perspective, two conclusions may be drawn: vaccination is better at an early age, and the vaccination schedule must be complete and include all recommended vaccine doses

Hepatitis A Virus genotype distribution during a decade of universal vaccination of preadolescents

A universal vaccination program among preadolescents was implemented in Catalonia, Spain, during the period of 1999-2013 and its effectiveness has been clearly demonstrated by an overall significant attack rate reduction. However, reductions were not constant over time, and increases were again observed in 2002-2009 due to the occurrence of huge outbreaks. In the following years, in the absence of large outbreaks, the attack rate decreased again to very low levels. However, an increase of symptomatic cases in the <5 age group has recently been observed. This is an unexpected observation since children younger than 6 are mostly asymptomatic. Such a long vaccination campaign offers the opportunity to analyze not only the effectiveness of vaccination, but also the influence of the circulating genotypes on the incidence of hepatitis A among the different age groups. This study has revealed the emergence of genotype IC during a foodborne outbreak, the short-lived circulation of vaccine-escape variants isolated during an outbreak among the men-having-sex-with-men group, and the association of genotype IIIA with the increase of symptomatic cases among the very young. From a public health perspective, two conclusions may be drawn: vaccination is better at an early age, and the vaccination schedule must be complete and include all recommended vaccine doses