Epidemiology of tuberculosis in France in 2008

A total of 5,758 tuberculosis cases were notified in France in 2008, giving a rate of nine cases per 100,000 inhabitants. The median age was 45 years and 59% of cases were male patients. Île-de-France (Paris and greater Paris area) and French Guiana had the highest notification rate in 2008 (17.9/10⁵ and 22.6/10⁵ respectively). The rate of tuberculosis was higher in individuals born abroad (43.2/10⁵ vs. 5.0/10⁵ for individuals born in France), especially those recently arrived in France. Pulmonary tuberculosis accounted for 72% of notified cases, 76% of which were potentially contagious (positive sputum smear, or culture). Compared to 2007, the number of notified tuberculosis cases increased by 3.3% in 2008. This increase was not accompanied by a rise of severe cases (meningitis and miliary TB); this seemed to be due partly to improvement in identification and notification of cases. However this trend could require specific monitoring in future years. A national tuberculosis control program was launched in France in 2007, aiming at reducing epidemiological disparities. Clinical and public health expertise needs to be maintained on all the territory to ensure that implemented measures can have the expected impact on the epidemiology of the disease.     

Épidémiologie de la tuberculose en Bretagne : les cas déclarés entre 2000 et 2007

The authors studied the reported cases of tuberculosis diseases in Brittany between 2000 and 2007 via the mandatory notification scheme. One thousand nine hundred and seventy-five cases were notified during the study period. The incidence in French Brittany (eight cases per 100,000) was the third highest in France. A statistically significant negative trend was observed later, mainly attributable to a decrease between 2000 and 2001. The mean patient age at notification was 55 in Brittany versus 46 years of age for the rest of France (p < 0.001). Eighty per cent of the patients were born in France versus 46% for the rest of the country. The rate of multiresistance to antibiotics was 1.3% versus 4.6% for the rest of France (p < 0.001). The estimated completeness of notification was 80% compared to 70% for the whole country. Despite a decrease of tuberculosis incidence in Brittany, the withdrawal of mandatory vaccination suggests strengthening tuberculosis monitoring in the future.     

Tuberculosis and migrants

Migrants, and especially those recently arrived in host countries, are a group at very important risk of tuberculosis. Fifty percent of the new cases of tuberculosis are diagnosed within this risk group. The incidence of tuberculosis is directly correlated to the incidence of tuberculosis in the native countries. Thirty-five percent of new cases of tuberculosis in France were observed in 2001 in foreigners, although they only account for 6% of the total population. The incidence was 6.2 cases/100,000 in French patients and 57.2 cases/100,000 in foreign patients. Moreover, the incidence increased by 7% in foreign patients between 1997 and 2001. The country of birth seems to be a better indication for risk of tuberculosis than nationality. Forty-five percent of patients with tuberculosis were born abroad and the incidence of tuberculosis reached 33.4/100,000 among migrants born in North Africa and 128.9/100,000 for people born in Sub-Saharan Africa.     

Encephalitis due to Mycobacterium tuberculosis in France

Purpose

Two hundred and fifty-three patients were included in a study on the etiology of encephalitis, carried out in France in 2007. Tuberculosis was the second most frequently identified cause, after HSV and with the same number of cases as VZV. The authors report the specific features of patients presenting with tuberculosis encephalitis (TE).

Methods

TE patients were defined as patients presenting with encephalitis, with positive culture or PCR for Mycobacterium tuberculosis, or the association of clinical, biological, imaging, and epidemiological evidence (possible cases). Clinical, microbiological, and brain imaging data was analyzed and compared to that of other included patients.

Results

Twenty cases of TE were identified. The M/F sex-ratio was 1.5, the mean age 53 years. Four (20%) patients had a history of tuberculosis before the encephalitis. The median delay between the onset of general and neurological symptoms was significantly longer for tuberculosis cases than for others (10 days vs. 2; P < 10⁻¹⁰⁾. The median CSF protein level was significantly higher for tuberculosis cases (2.1 g/L vs. 0.8 g/L, P = 0.002). CT scan and MRI were normal on admission for eight patients out of 17. Fourteen isolated strains of M. tuberculosis were susceptible to first-line anti-tuberculosis drugs and one was rifampicin-resistant. Six (33%) patients died during hospitalization and two were lost to follow-up. Ten out of 12 (78.6%) had persisting neurological symptoms on discharge.

Discussion

Despite non-multiresistant MT strains, the case fatality rate among TE patients was high in our series. Early brain imaging is poor contributive for the diagnosis of TE.     

Family history of immigration from a tuberculosis endemic country and low family income are associated with a higher BCG vaccination coverage in Ile-de-France region,France

After withdrawal of multipuncture BCG device from the French market in January 2006, vaccination coverage (VC) with the intradermal device has dropped and since remained sub-optimal in Ile-de-France, the only region of mainland France where BCG is recommended to all children. We conducted a cross-sectional study to identify socio-economic factors associated with BCG VC in children of Paris metropolitan area born after January 2006. Two-stage random sampling was used to include 425 children up to 5 years old from Paris and its suburbs. Information was collected through face-to-face interviews and vaccination status confirmed by a vaccination document. Poisson regression analyzed the association between VC and potential determinants. VC of children from families with the lowest incomes (first quartile of family income/consumption unit (CU) (<883 €) was close to 100% regardless of family origin. In families with higher incomes (≥883 €/CU), VC was significantly higher among children born to families from a tuberculosis highly endemic country (98.2%) compared with other children (76.2%) (p = 0.004). Children of low socio-economic background as well as those with a family history of immigration, regardless of family income, are correctly identified as being at high risk of tuberculosis and properly vaccinated with BCG in this area.     

Epidemiology of tuberculosis in France in 2005

This article presents results on cases of tuberculosis disease notified in France in 2005 by mandatory notification. In 2005, a total of 5,374 cases were notified in France, representing a rate of 8.9 cases per 100,000. The notification rate per 100,000 was below 10 in all French regions, except the Ile-de-France and French Guyana (with respective rates of 19.7/10(5) and 44.0/10(5)). Notification rates were higher in some population groups such as people born abroad (41.5/10(5)), especially those born in sub-Saharan Africa (160/10(5)), and those recently (<2 years) arrived in France (251/10(5)), in homeless people (214/10(5)), and in persons aged 80 years and over (21.7/10(5)). Pulmonary tuberculosis accounted for 73% of notified cases, 79% of which were contagious (positive direct examination of sputum, positive culture). Results from the notification of tuberculosis disease in 2005 indicate a continuing decrease of incidence in France. However, the high incidence in some population groups requires adapting public health actions to the needs of population groups more exposed to tuberculosis.     

Epidemiology of pertussis in a country with high vaccination coverage

Introduction

Pertussis has been a preventable disease in Catalonia since 1965, but the annual number of cases remains high. The aim of this study was to analyze the epidemiology of pertussis in Catalonia and its implications for control purposes.

Methods

An epidemiological study was carried out in Catalonia between 2004 and 2008. Pertussis cases reported to the Department of Health were collected and disease reports were filled out with the case information. Incidence rates, rate ratios (RR) and their 95% confidence intervals (CI) were calculated.

Results

963 cases were reported: 555 (57.6%) were confirmed and 408 (42.4%) were suspected cases. The reported incidence rate was 2.01 × 10⁻⁵ person years in 2004 and 4.34 in 2008. The biggest increase in cases between 2004 and 2008 was observed in the ≥35 years age group (RR: 6.98; 95%CI: 2.11-36.36). 303 (31.5%) patients were hospitalized, of whom 93.7% were aged <1 year. Clinical differences were observed in paroxysmal cough (83.8% in suspected and 76.4% in confirmed cases, p = 0.005), posttussive vomiting (47.1% and 36.1%, respectively, p = 0.001), apnoea (13.7% and 21.3%, respectively, p = 0.003) and fever (20.1% and 12.4%, respectively, p = 0.001).

Conclusion

Pertussis incidence rates increased during the study period, with the greatest increase occurring in the ≥35 years age group. A booster dose of vaccine in young people could reduce the circulation of B. pertussis in adolescents and adults and indirectly reduce the incidence in children.     

Reduction of travellers’ diarrhoea by WC/rBS oral cholera vaccine in young,high-risk travellers

Aims

A bidirectional cohort study investigates whether pre-travel vaccination with whole cell/recombinant B subunit inactivated, killed oral cholera vaccine reduces the incidence of diarrhoea in young adult travellers to high-risk areas.

Scope

Risk of travellers’ diarrhoea was assessed according to destination and reason for travel in high-risk travellers of a travel clinic in Barcelona, Spain.Those at high-risk between January and December 2005 were advised on water/food safety and hygiene. High-risk travellers between January and December 2006 were additionally vaccinated with WC/rBS oral cholera vaccine. Data regarding diarrhoea were gathered by structured telephone interview or e-mailed questionnaire following the travellers’ return.The incidence of diarrhoea in the group vaccinated with WC/rBS oral cholera vaccine (n = 321) was 17.4%, compared with 39.7% in the non-vaccinated group (n = 337) (adjusted risk ratio 0.40). The first episode was significantly shorter in the vaccinated group (mean 2.3 days) than in the non-vaccinated group (mean 3.8 days) (p < 0.001).Conclusions: The protective effect of the WC/rBS oral cholera vaccine was 57% in the young, high-risk travellers. Vaccination with the WC/rBS oral cholera vaccine as well as food safety and hygiene advice could offer effective means of reducing the risk of diarrhoea while abroad.     

Effect of oral immunization with pooled antigens derived from adipose tissue on atherosclerosis and obesity indices

Modulation of the inflammatory response through vaccination has shown promise in animal models of atherogenesis and obesity—main risk factors for cardiovascular diseases. Tableted preparation, V-6, containing pooled antigens derived from pig adipose tissue was administered per os daily to 13 volunteers for 3 months. Total cholesterol and LDL levels have not changed from the baseline value; 193.4 vs 191.8 (p = 0.75) and 113.8 vs 117.2 (p = 0.18), respectively. Triglyceride levels declined by 26.1% from 163 to 120.5 mg/dL (p = 0.29). HDL increased by 25.9% from 38.6 to 48.5 mg/dL (p = 0.000002) in 12 out 13 patients. Despite negligible effect of V6 on weight and body mass index, i.e., 67.87 vs 66.58 kg (−1.9%; p = 0.46) and 26.25 vs 25.75 kg/m² (−1.9%; p = 0.35), statistically significant reduction in waist (−7.6%; p = 0.002), mid-arm (−3.3%; p = 0.049), and thigh (−7.6%; p = 0.0003) circumferences were observed. Blood pressure systolic and diastolic values were not affected, i.e., 115.6 vs 121 (p = 0.2) and 77.1 vs 83 (p = 0.55). No changes were observed in liver ALT and AST enzymes. Creatinine decreased; 0.877 vs 0.842 mg/dL (p = 0.02), while BUN has shown slight increase; 14.8 vs 16.1 mg/dL (p = 0.03) but within normal range. Fasting blood sugar levels were also within normal range, i.e., 94.8 vs 98.8 (p = 0.04). Complete blood cell analysis has not revealed any change except slight decrease in hemoglobin 13.25–13.19 g/dL (p = 0.0004), but its amount per red blood cell (MCH) increased from 25.62 up to 26.42 picograms/cell (p = 0.000003). The average red blood cell size (MCV) increased from 78.5 to 80.0 fl (p = 0.00009) but hemoglobin concentration relative to size of the cell (MCHC) has not changed (p = 0.2). Hematocrit and red blood cells count decreased slightly, but within normal range 40.7–40.2% (p = 0.02) and 5.22–5.05 × 10⁶ cells/mm³ (p = 0.002). The number of platelets moved upward, 2.471 vs 2.921 × 10⁵ per mm³ (p = 0.009). The white blood cells count and percent of leukocytes and neutrophils were not affected. Pro-inflammatory eosinophils declined from 4.0% down to 2.4% (p = 0.29). These results show that V6 is safe and holds a promise as an anti-atherogenic and overweight/obesity immune intervention.     

Probiotics reduce symptoms of antibiotic use in a hospital setting: A randomized dose response study

Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU^® Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n = 503) were randomized among three study groups: HOWARU^® Restore probiotic 1.70 × 10¹⁰ CFU (high-dose, n = 168), HOWARU^® Restore probiotic 4.17 × 10⁹ CFU (low-dose, n = 168), or placebo (n = 167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p = 0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p = 0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.     

Comparative performance of public and private sector delivery of BCG vaccination: Evidence from Sub-Saharan Africa

Background

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public–private differences in Bacillus Calmette–Guérin (BCG) vaccine delivery.

Methods and findings

We used demographic and health surveys from 102,629 children aged 0–59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public–private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public–private differences based on wealth and rural–urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3–8.0; p < 0.001). Most of this difference was driven by for-profit private providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0–11.2; p < 0.001) compared to only 2.4 percentage points for NGOs (95% CI 1.0–3. 8; p < 0.01). Moreover, children born at private for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public–private differences were more pronounced for poorer children and children in rural areas.

Conclusions

The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas.     

Waning immunity to measles in young adults and booster effects of revaccination in secondary school students

The increasing proportions of adult cases were observed in the recent measles outbreaks in Zhejiang Province, China. In order to identify the high-risk age groups of measles for targeted intervention, a seroprevalence survey of measles antibody was conducted among 1961 participants aged 0–60 years randomly selected by age-stratified purpose sampling, and the effect of revaccination program in secondary school was evaluated in Zhejiang Province. The adjusted overall seropositivity rate of measles was 88% (95% confidence interval [CI]: 86–89%) with geometric mean titers (GMT), 976 ± 86 mIU/ml. The seropositivity rate of measles was significantly lower in subjects aged 15–19 years than aged 5–9 years (90% vs 96%, χ² = 5.21, p = 0.022). Both seropositivity rate and GMT level of measles were higher in participants aged 10–14 years with ≥2 doses MCV than those with only 1 dose (95% vs 81%, 1276 mIU/ml vs 666 mIU/ml). The seropositivity rate increased from 91% to 100% after revaccination with MCV among 184 secondary school students. The proportions of measles cases aged ≥15 years were reduced gradually (χ² = 55.47, p = 0.000) from 2009 to 2011 after implementing the revaccination campaign on secondary school students since 2008. Our findings strongly suggested that a revaccination opportunity with MCV for adolescents helps to improve the population immunity, and it can be conducted effectively and practically in secondary school students.     

Actualités épidémiologiques de la leishmaniose viscérale en Tunisie

Objective

Visceral leishmaniasis is an important health problem in Tunisia. The aim of this study was to update the epidemiological and clinical features of the disease.

Design

We performed a retrospective systematic sampling of epidemiological and clinical data collected from the medical records of 1,096 cases of visceral leishmaniasis diagnosed between 1996 and 2006 all over the country.

Results

The mean annual incidence of cases was 99.6 cases/year. The mean annual incidence rate was 1.04 cases/100,000 inhabitants, showing an important increase compared to former studies. As expected, children under 5 years (866 cases) were the most affected with a mean annual incidence rate of 9.6 cases/100,000 (p < 0.001). The geographical distribution of cases revealed the spreading of the disease from the Northern parts of the country to the Central and even to Southern ones. Rural cases (65.3%) were significantly more numerous than urban ones (34.7%), p < 0.001. The sex ratio was 1.03. The diagnostic delay (average of 54 days) was considerably shortened during the study period compared to previous reports, and explains the decrease of the lethality rate (2.9%).

Conclusions

Visceral leishmaniasis has been present in central Tunisia since the early 1990s. Its incidence and the distribution area have increased. This evolution is probably linked to the development of irrigation and agriculture favorable to the multiplication of vector sandflies and dogs reservoirs of Leishmania infantum.     

Deletion of the APOBEC3B gene strongly impacts susceptibility to falciparum malaria

APOBEC3B, a gene involved in innate response, exhibits insertion-deletion polymorphism across world populations. We observed the insertion allele to be nearly fixed in malaria endemic regions of sub-Saharan Africa as well as populations with high malaria incidence in the past. This prompted us to investigate the possible association of the polymorphism with falciparum malaria. We studied the distribution of APOBEC3B, in 25 diverse Indian populations comprising of 500 samples and 176 severe or non-severe Plasmodium falciparum patients and 174 ethnically-matched uninfected individuals from a P. falciparum endemic and a non-endemic region of India. The deletion frequencies ranged from 0% to 43% in the Indian populations. The frequency of the insertion allele strikingly correlated with the endemicity map of P. falciparum malaria in India. A strong association of the deletion allele with susceptibility to falciparum malaria in the endemic region (non-severe vs. control, Odds ratio = 4.96, P value = 9.5E⁻⁰⁶; severe vs. control, OR = 4.36, P value = 5.76E⁻⁰⁵) was observed. Although the frequency of deletion allele was higher in the non-endemic region, there was a significant association of the homozygous deletion genotype with malaria (OR = 3.17, 95% CI = 1.10-10.32, P value = 0.0177). Our study also presents a case for malaria as a positive selection force for the APOBEC3B insertion and suggests a major role for this gene in innate immunity against malaria.     

Differences in stature,BMI, and dietary practices between US born and newly immigrated Hmong children

This study investigated how acculturation influences diet, cultural practices related to cooking and food preparation knowledge, and stature and body mass index (BMI) of Hmong children. Focus groups (n = 12) were conducted during the spring of 2008 in St. Paul/Minneapolis, Minnesota with those born in the US and 9–13 years old (n = 22), those born in the US and 14–18 years old (n = 25), and those born in Thailand or Laos, who had lived in the US ≤ 5 years, and 14–18 years old (n = 21). Respondents also completed a survey instrument to assess acculturation level which was evaluated by questions about social connections, language use, and dietary habits. Compared to those born in the US, those born in Thailand or Laos were significantly shorter and leaner. Those born in the US also showed elevated acculturation levels in language use, social connections, and gender-oriented tasks compared to those born in Thailand or Laos. Themes from focus group discussions were mealtime patterns, determinants of food health, future health concerns, and changing cultural traditions. Acculturation, years lived in the US, and birth place may play an important role in stature and BMI, food and physical activity habits, cooking and food preparation knowledge, and perceptions of health.     

Pneumocystis jirovecii colonization and infection among non HIV-infected patients

Objective and method

The epidemiology of pneumocystosis has changed in the last decade with a decreased incidence in HIV infected patients, and the emerging concept of Pneumocystis colonization. The study objective was to describe Pneumocystis infection as well as colonization among non-HIV infected patients in the Rouen teaching hospital and cancer institute. A retrospective study was made of all patients with a positive respiratory sample for Pneumocystis jirovecii between January 1, 2000 and June 6, 2007.

Results

Fifty-four cases were reported (46 cases of pneumocystosis and eight of asymptomatic carriage) and an increasing yearly incidence over the study period was observed. Underlying diseases for pneumocystosis were haematological malignancies (n = 25; 54%), organ transplantation (n = 8; 17.4%), inflammatory disorders (n = 6; 13%), and solid cancer (n = 5; 10.8%). Sixty-five per cent of patients were under long-term steroid therapy. The overall mortality rate was 21.4%. The CD4 count for 26 patients, ranged from 18 to 1449/mm³ (median: 107). Eight cases of asymptomatic carriage were reported with an underlying immunodepression (n = 6) and pulmonary disease (n = 2).

Discussion

The increasing incidence of pneumocystosis in immunosuppressed patients without AIDS is due to more frequent favorable conditions and progress of diagnostic tools. The clinical presentations are severe. Prophylaxis is badly codified because there is no threshold value for CD4 count. Colonization could present a warning value.     

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30–40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7^® routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13^®, a second-generation vaccine with six new serotypes, replaced Prevenar 7^® in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).     

Invasive pneumococcal disease in Catalonian elderly people, 2002-2009: serotype coverage for different anti-pneumococcal vaccine formulations at the beginning of the new conjugate vaccines era

Population-based surveillance study conducted among persons 65 years or older from the region of Tarragona (Southern Catalonia, Spain) during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) and prevalence of infections caused by serotypes included in different pneumococcal conjugate vaccines (PCVs) and the 23-valent pneumococcal polysaccharide vaccine (PPV-23) were calculated. Overall, 176 IPD cases were observed, which means an incidence of 48 episodes per 100,000 person-year throughout the study period. The most dominant serotypes were 7F (10.1%), 14 (9.4%), 19A (9.4%), 3 (8.6%), 6A (7.9%) and 1 (7.2%). IPD cases due to PCV-7 types (from 37.2% to 14.6%; p = 0.003) and PCV-10 types (from 60.5% to 32.3%; p = 0.002) considerably decreased between 2002-2005 and 2006-2009 periods. Percentage of cases due to PCV-13 types (76.7% vs 62.5%; p = 0.099) and PPV-23 types (81.4% vs 68.8%; p = 0.122) did not significantly change between both periods. As main conclusion, in our setting, the PCV-13 has almost similar serotype coverage to the PPV-23 in preventing IPD among the elderly population, which suggests a possible future use of the conjugate vaccine in all age groups.     

Phase II,dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age

Introduction

ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus (WNV) produced by insertion of the genes encoding the pre-membrane (prM) and envelope (E) proteins of WNV (strain NY99) into the yellow fever 7D vaccine virus. This Phase II, randomized, double-blind, placebo-controlled, multi-center study in the US assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine.

Methods

The study included adults in general good health. Subjects aged ≥50 years were randomized to one of four treatment groups: ChimeriVax-WN02 4 × 10³ plaque-forming units (pfu) (n = 122), 4 × 10⁴ pfu (n = 124), 4 × 10⁵ pfu (n = 113), or placebo (n = 120). A subset of subjects was randomized to assess viremia after vaccination at three different dose levels. Subjects were followed for safety up to 6 months after vaccination.

Results

A total of 121subjects for WN024 × 10³, 122 for WN02 4 × 10⁴, 110 for WN02 4 × 10⁵, and 120 for the placebo group completed the study up to the 6-month safety follow-up. Seroconversion, as measured by plaque reduction neutralization test (PRNT), was achieved at Day 28 by 92.1%, 93.2%, and 95.4% of subjects in the WN02 4 × 10³, the WN02 4 × 10⁴, and the WN02 4 × 10⁵ groups, respectively. Viremia was transient, detected between Days 2 and 14 but not at Day 28, and in most cases did not reach the quantification threshold. The percentage of subjects reporting at least one event of reactogenicity was similar in the placebo and active vaccine groups and showed no dose relationship.

Conclusions

The ChimeriVax-WN02 vaccine was highly immunogenic and well tolerated among subjects ≥50 years old at all dose levels.     

Durability of antibody responses after receipt of the monovalent 2009 pandemic influenza A (H1N1) vaccine among HIV-infected and HIV-uninfected adults

Background

Human immunodeficiency virus (HIV)-infected persons are at risk for severe influenza infections. Although vaccination against the H1N1 pandemic influenza strain is recommended, currently there are no data on the durability of post-vaccination antibody responses in this population.

Methods

HIV-infected and HIV-uninfected adults (18-50 years old) received a single dose of monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1). Antibody levels to the 2009 H1N1 pandemic strain were determined at day 0, day 28, and 6 months by hemagglutination-inhibition assay. A seroprotective response was a post-vaccination titer of ≥1:40 among those with a pre-vaccination level of ≤1:10. Geometric mean titers (GMT) and factors associated with higher levels were also evaluated.

Results

We studied 127 participants with a median age of 35 (interquartile range (IQR) 28, 42) years. Among the HIV-infected arm (n = 63), the median CD4 count was 595 (IQR 476, 819) cells/mm³ and 83% were receiving HAART. Thirty-five percent of all participants had a pre-vaccination level of >1:10. HIV-infected compared to HIV-uninfected adults were less likely to generate a seroprotective response at day 28 (54% vs. 75%, adjusted OR 0.23, p = 0.021) or have a durable response at 6 months post-vaccination (28% vs. 56%, adjusted OR 0.19, p = 0.005). Additionally, although pre-vaccination GMT were similar in both arms (median 7 vs. 8, p = 0.11), the GMT at 6 months was significantly lower among HIV-infected versus HIV-uninfected adults (median 20 vs. 113, p = 0.003). Among HIV-infected persons, younger age (p = 0.035) and receipt of HAART (p = 0.028) were associated with higher GMTs at 6 months.

Conclusions

Despite vaccination, most HIV-infected adults do not generate durable seroprotective antibody responses to the 2009 influenza A (H1N1) virus, and hence may remain vulnerable to infection. In addition to HAART use, more immunogenic vaccines are likely needed for improving protection against influenza in this population.