Solen Kernéis

Long-term immune responses to vaccination in HIV-infected patients: a systematic review and meta-analysis

Vaccine-induced antibodies may wane more quickly in persons living with human immunodeficiency virus (HIV) than in healthy individuals. We reviewed the literature on vaccines routinely recommended in HIV-infected patients to estimate how seroprotection decreases over time in those who initially responded to immunization. For each study retrieved from the literature, the decrease of seroprotection was modeled with a log binomial generalized linear model, and data were pooled in a meta-analysis to provide estimates of seroprotection 2 and 5 years after the last vaccine administration. Our analyses confirmed that the duration of seroprotection was shorter in HIV-infected patients and that with current guidelines, a substantial proportion of patients would have lost protective antibodies before a booster was proposed. We therefore discuss the implications for the monitoring of antibody levels and timing of revaccination in these patients.

Prevalence and risk factors of Lassa seropositivity in inhabitants of the forest region of Guinea: a cross-sectional study.

Background Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i) estimate the prevalence of Lassa virus–specific IgG antibodies (LV IgG) in the human population of a rural area of Guinea, and (ii) identify risk factors for positive LV IgG. Methods and Findings A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou) were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents), and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%–15.0%] and 10.0% [8.1%–11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR]u200a=u200a1.8 [1.1–3.1]), or lived with someone displaying a haemorrhage (ORu200a=u200a1.7 [1.1–2.9]). No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis. Conclusions Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure.

A look back at an ongoing problem: Shigella dysenteriae type 1 epidemics in refugee settings in Central Africa (1993-1995).

Background Shigella dysenteriae type 1 (Sd1) is a cause of major dysentery outbreaks, particularly among children and displaced populations in tropical countries. Although outbreaks continue, the characteristics of such outbreaks have rarely been documented. Here, we describe the Sd1 outbreaks occurring between 1993 and 1995 in 11 refugee settlements in Rwanda, Tanzania and Democratic Republic of the Congo (DRC). We also explored the links between the different types of the camps and the magnitude of the outbreaks. Methodology/Principal Findings Number of cases of bloody diarrhea and deaths were collected on a weekly basis in 11 refugee camps, and analyzed retrospectively. Between November 1993 and February 1995, 181,921 cases of bloody diarrhea were reported. Attack rates ranged from 6.3% to 39.1% and case fatality ratios (CFRs) from 1.5% to 9.0% (available for 5 camps). The CFRs were higher in children under age 5. In Tanzania where the response was rapidly deployed, the mean attack rate was lower than in camps in the region of Goma without an immediate response (13.3% versus 32.1% respectively). Conclusions/Significance This description, and the areas where data is missing, highlight both the importance of collecting data in future epidemics, difficulties in documenting outbreaks occurring in complex emergencies and most importantly, the need to assure that minimal requirements are met.

Does the Effectiveness of Control Measures Depend on the Influenza Pandemic Profile

Background Although strategies to contain influenza pandemics are well studied, the characterization and the implications of different geographical and temporal diffusion patterns of the pandemic have been given less attention. Methodology/Main Findings Using a well-documented metapopulation model incorporating air travel between 52 major world cities, we identified potential influenza pandemic diffusion profiles and examined how the impact of interventions might be affected by this heterogeneity. Clustering methods applied to a set of pandemic simulations, characterized by seven parameters related to the conditions of emergence that were varied following Latin hypercube sampling, were used to identify six pandemic profiles exhibiting different characteristics notably in terms of global burden (from 415 to >160 million of cases) and duration (from 26 to 360 days). A multivariate sensitivity analysis showed that the transmission rate and proportion of susceptibles have a strong impact on the pandemic diffusion. The correlation between interventions and pandemic outcomes were analyzed for two specific profiles: a fast, massive pandemic and a slow building, long-lasting one. In both cases, the date of introduction for five control measures (masks, isolation, prophylactic or therapeutic use of antivirals, vaccination) correlated strongly with pandemic outcomes. Conversely, the coverage and efficacy of these interventions only moderately correlated with pandemic outcomes in the case of a massive pandemic. Pre-pandemic vaccination influenced pandemic outcomes in both profiles, while travel restriction was the only measure without any measurable effect in either. Conclusions Our study highlights: (i) the great heterogeneity in possible profiles of a future influenza pandemic; (ii) the value of being well prepared in every country since a pandemic may have heavy consequences wherever and whenever it starts; (iii) the need to quickly implement control measures and even to anticipate pandemic emergence through pre-pandemic vaccination; and (iv) the value of combining all available control measures except perhaps travel restrictions.

Long-term persistence of humoral immunity after hepatitis A vaccination in HIV-infected adults.

s of the XVIII International AIDS Conference, July 18–23, 2010; Vienna, Austria. 7. Cruciani M, Mengoli C, Serpelloni G, et al. Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients. Vaccine. 2009;27:

Attitude, knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency.

BACKGROUNDnImmunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency.nnnMETHODSnAn anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression.nnnRESULTSnAmong the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57-60]) against seasonal influenza and 49% (95%CI [47-50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated.nnnCONCLUSIONnDespite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.

Mortality trends in systemic sclerosis in France and USA, 1980–1998: an age-period-cohort analysis

We compared trends of Systemic Sclerosis (SS) mortality in France and the USA over the period 1980–1998 and used an Age-Period-Cohort (APC) model to adjust on the age at death of SS patients. All deaths coded with SS as an underlying primary or secondary cause in the national French and US mortality databases from 1980 to 1998 were included in the analysis. SS age-standardized mortality rates increased from 7.2 to 10.3/million in US women (+43%), and from 3 to 3.9/million in French women (+22%). Most of the increase occurred in senior women. In contrast, SS age-standardized death rates remained stable among US men (around 3/million) and French men (around 2/million). In US women, the APC analysis shows a growing cohort effect between 1900 and 1940, tending to stabilize for following cohorts. Similar findings were obtained to a lesser extent in French women. In conclusion, SS mortality rates increased by more than 40% between 1980 and 1998 in the USA, mostly in women born between 1900 and 1940. Whether these trends reflect rising incidence of SS need to be documented. The observed dissimilarity between genders and countries underline that environmental exposure and gender-related factors likely play a major etiological role. Stabilization in the following birth cohorts suggests that the increase of mortality observed since 1980 may slow down in the near future.

Orientation des patients par leur médecin généraliste vers les secteurs hospitaliers publics ou privés en France : étude épidémiologique prospective du réseau Sentinelles

PURPOSEnIn-patients characteristics generate cost differences between hospitals. In France, there are few data on the characteristics on the patients referred to hospitals by their general practitioners (GPs) and none on the predictors of referral to the public or for-profit hospitals. The aim of this study was to analyze those characteristics and the predictors of referral to the public or for-profit hospitals.nnnMETHODSnWe collected, prospectively, the request for hospitalizations made by the GPs of the Sentinelles network in France, from 2007 to 2009. Patients characteristics and also the reasons for that request were analyzed. A logistic regression was used to compare the population between local hospitals.nnnRESULTSnTen thousand seven hundred and eighteen statements were collected. The median age was 73 years. Patients were women in 51% of the cases, and only 14% of the hospitalizations had been planned. Hospitalization in the public sector was preferred for young children and the elderly (P<0.001). When compared to the patients referred to the private sector, patients addressed to the public sector were more often seen for emergencies (OR: 2.3 [2.0-2.8]), by a doctor different from their referring GP (OR: 1.7 [1.4-2.1]) and out of the GPs office. The reasons for hospital admission were different depending on the sector of hospitalization (P<0.001), patients addressed to the public sector hospitals presented with greater comorbidity or more complex diagnosis (for example: feeling ill, fainting or syncope and fever) or a greater disability (for example: stroke, neurological and psychiatric diseases).nnnCONCLUSIONnThis study suggests that GPs send their patients to the public or for-profit hospitals according to criteria of severity, comorbidity and disability.

Staphylococcus aureus osteo-articular infection: usefulness of the determination of daptomycin serum concentration to explain a treatment failure.

We report two cases of treatment failure in patients with osteoarticular infection associated with Staphylococcus aureus bacteremia and receiving daptomycin. Using a published population-pharmacokinetic model and daptomycin blood level in these patients, area under the curve (AUC) was calculated and compared to the pharmacological target. For the first patient, treated with 6 mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC was 820 mg×h×L-1, with a minimal concentration of 23.5 mg/L confirming the right dose adjustment and the absence of underdosing. The methicillin-resistant Staphylococcus aureus (MRSA) strain was still susceptible to daptomycin, but it was not sufficient to observe a favorable outcome. For the second patient, treated with 10 mg/kg/d, the steady state residual concentration was 10.4 mg/L, and the calculated AUC value was 550 mg×h×L-1. AUC/MIC values evolved during treatment to be under the cut-off for bactericidal effects (> 800 hours), and the Staphylococcus aureus (SA) strain became daptomycin resistant. This study highlights the inter-individual pharmacokinetic variation leading sometimes to drug underdosing. Drug monitoring should be encouraged in order to avoid treatment failure.

Chronic meningococcemia in a 16-year-old boy: a case report

Herein, we present a case of meningococcal disease in a patient presenting with of a three-week history of fever, cutaneous vasculitis and joint pain, in whom chronic meningococcemia was retained as presumptive diagnosis, after the disease evolved towards meningitis. This unusual case illustrates the great heterogeneity in possible clinical presentations of Neisseria meningitidis infections and underlines that diagnosis should always be evocated when facing the triad of fever, vasculitic skin eruption and big joints arthralgia, in a person in otherwise good general condition.