Leptospirosis as Cause of Febrile Icteric Illness, Burkina Faso.

Patients in Burkina Faso who sought medical attention for febrile jaundice were tested for leptospirosis. We confirmed leptospirosis in 27 (3.46%) of 781 patients: 23 (2.94%) tested positive using serologic assays and 4 (0.51%) using LipL32 PCR. We further presumed leptospirosis in 16 (2.82%) IgM-positive specimens.

The immune response to sub-clinical mastitis is impaired in HIV-infected women.

BACKGROUND: Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed. METHODS: In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study). The level of 33 immune markers related to Th1/Th2 related response, inflammation and bacterial exposure were compared in ART-naive HIV-infected versus HIV-uninfected women. The associations between HIV infection and SCM on the concentration of immune factors were tested separately by Wilcoxon rank-sum test and corrected for false discovery rate. To control for potential confounder effects and take into account the clustering of breast milk samples from a single woman, multivariate mixed linear models adjusted on child age at the time of sampling were performed for each immune factor. RESULTS: Subclinical mastitis was detected in 15 (37.5%) HIV-infected women and 10 (23.3%) HIV-uninfected women. In the absence of SCM, the breast milk levels of IP-10 and MIG were higher and IL1-RA lower in HIV-infected women than in HIV-uninfected women (respectively p < 0.001, p = 0.001, p = 0.045). In HIV-uninfected women, SCM was characterized by a robust immune response with higher concentrations of a broad panel of Th1 and inflammatory related immune markers than in samples without SCM. By contrast, in HIV-infected women a limited number of immune markers were increased and lower increases were observed in samples with SCM than without SCM. CONCLUSION: HIV infection in ART-naïve women was associated with elevated breast milk levels of IP-10 and MIG, which areTh1-related cytokines induced by IFN-γ. During SCM, a lower and narrower immune response was observed in HIV-infected than HIV-uninfected women, suggesting that HIV infection affects the capacity of the mammary gland to respond to SCM.

Hepatitis B and C virus seroprevalence, Burkina Faso: a cross-sectional study.

OBJECTIVE: To estimate population-wide hepatitis B and C seroprevalence using dried blood spot samples acquired for human immunodeficiency virus (HIV) surveillance as part of the 2010-2011 Demographic and Health Survey in Burkina Faso. METHODS: We used the database acquired during the multistage, clustered, population-based survey, in which 15 377 participants completed questionnaires and provided dried blood spot samples for HIV testing. We extracted sociodemographic and geographic data including age, sex, ethnicity, education, wealth, marital status and region for each participant. We performed hepatitis B and C assays on 14 886 HIV-negative samples between March to October 2015, and calculated weighted percentages of hepatitis seroprevalence for each variable. FINDINGS: We estimated seroprevalence as 9.1% (95% confidence interval, CI: 8.5-9.7) for the hepatitis B surface antigen and 3.6% (95% CI: 3.3-3.8) for hepatitis C virus antibodies, classifying Burkina Faso as highly endemic for hepatitis B and low-intermediate for hepatitis C. The seroprevalence of hepatitis was higher in men than in women, and varied significantly for both with age, education, ethnicity and region. Extremely high HCV-Ab seroprevalence (13.2%; 95% CI: 10.6-15.7) was identified in the Sud-Ouest region, in particular within the youngest age group (15-20 years), indicating an ongoing epidemic. CONCLUSION: Our population-representative hepatitis seroprevalence estimates in Burkina Faso advocate for the inclusion of hepatitis serological tests and risk factor questionnaire items in future surveys, the results of which are crucial for the development of appropriate health policies and infection control programmes.

Subclinical mastitis occurs frequently in association with dramatic changes in inflammatory/anti-inflammatory breast milk components.

BACKGROUND: Subclinical mastitis (SCM) is a frequent, but poorly characterized entity that may influence immune development of breastfed infants. Mechanisms driving the emergence of SCM and changes in immunological content of human milk during SCM remain to be explored. In this study, the breast milk environment was to describe during SCM. METHODS: One hundred and ten samples of mature breast milk were collected from 44 healthy, HIV-negative mothers, included in a large infant feeding intervention cohort (ANRS 1271/Vertical Transmission Study). Immune markers related to inflammatory/anti-inflammatory balances and secreted in response to bacterial exposure were explored in SCM breast milk samples (Na/K ratio > 1) and compared to non-SCM controls. RESULTS: SCM was observed in 23% of women (95% confidence interval (CI): 21-24) and associated with higher levels of inflammatory markers (ß2 microgobulin, PS100A9, TNF-α, IL-6, IL-8, IL-17, and RANTES) and Th1-related cytokines (IL-2R, IL-12p40/70, IFN-α, IFN-γ, CXCL-9, andIP-10). High levels of factors secreted in response to bacteria and lipopolysaccharide (LPS) exposure were observed in SCM breast milk samples (MIP-1α, MIP-1ß, LPS binding protein, α-defensins, and antileukoproteinase 1). CONCLUSION: SCM is associated with important changes in breast milk microenvironment, with a proinflammatory/Th1-cytokine predominant profile. During SCM, cytokine imbalances in breast milk may have a notable influence on mucosal immune system of the infant early in life.

Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5-year follow-up study.

OBJECTIVE: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. METHODS: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. RESULTS: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. SIGNIFICANCE: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.

The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance.

BACKGROUND: Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting. DESIGN AND METHODS: A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period. RESULTS: A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined. CONCLUSIONS: A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.

The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country.

PURPOSE: To determine the prevalence of epilepsy in a defined adult population and identify the frequency and principal features of pharmacoresistant epilepsy. METHODS: From a population over 15 years of age residing in a medium-sized French city, all patients with epilepsy on June 30, 1995 were identified from multiple sources. Pharmacoresistance was defined as failure to control epilepsy by at least two first-line antiepileptic drugs, with a seizure frequency of at least one per month for 18 months. Collected data were examined by experts in epileptology, and responding patients were reexamined using a standardized diagnostic questionnaire. ILAE definitions and classifications were used. RESULTS: The age-adjusted prevalence of active epilepsy was 5.4 per 1,000 (95% CI: 4.7-6.0) and was higher for males (7.8) than for females (5.2). For epilepsy in remission under treatment, this rate was 0.7 per 1,000 (95% CI: 0.5-0.95). Age-specific prevalence was highest in age groups 25-49 years and declined in the oldest age groups. Localization-related seizures represented 61.1% of cases and generalized seizures 30.9%. The proportion of noncontrolled epilepsy (seizure-frequency at least one per month for 18 months) was 15.6%, corresponding to a prevalence of 0.94 per 1,000. In this group, the mean age at onset was lower (p = 0.0007) and localization-related epilepsy more frequent (p = 0.01). CONCLUSION: The findings support previous epidemiological estimates of the prevalence of epilepsy in developed countries. For approximately one patient in eight, epilepsy was not adequately controlled.

Cytosolic RNA:DNA Duplexes Generated by Endogenous Reverse Transcriptase Activity as Autonomous Inducers of Skin Inflammation in Psoriasis.

Psoriasis is a chronic skin disease of unknown ætiology. Recent studies suggested that a large amount of cytosolic DNA (cyDNA) in keratinocytes is breaking keratinocytes DNA tolerance and promotes self-sustained inflammation in the psoriatic lesion. We investigated the origin of this cyDNA. We show that, amongst all the possible DNA structures, the cyDNA could be present as RNA:DNA duplexes in keratinocytes. We further show that endogenous reverse transcriptase activities generate such duplexes and consequently activate the production of Th1-inflammatory cytokines. These observations open a new research avenue related to endogenous retroelements for the aetiology of psoriasis and probably of other human chronic inflammatory diseases.

Impact of an infection control program in an intensive care unit in France.

OBJECTIVE: To evaluate the impact of an infection control program in an intensive care unit (ICU). DESIGN: Prospective before-after study. Two 6-month study periods were compared; between these periods, an infection control program based on isolation was implemented. SETTING: Polyvalent ICU of Montpellier Teaching Hospital.Patients. Any patient who was hospitalized in the ICU for >48 hours and was discharged during 1 of the 2 periods. MAIN OUTCOME MEASURES: The main patient-related variables were sex, age at admission, type of patient (surgical, medical, or trauma), Simplified Acute Physiology Score II, length of ICU stay, need for intubation, duration of exposure to invasive devices, onset of nosocomial infection and pathogens responsible, and death. We compared the 2 study periods with respect to the incidence of 4 nosocomial infections (pneumonia, urinary tract infection, bacteremia, and catheter-associated infection), the frequency of infection with the main multidrug-resistant pathogens, and patient survival. RESULTS: Patients in periods 1 and 2 were similar with regard to sex, age, physiology score, and exposure to invasive devices. The rates of infection with multidrug-resistant pathogens were significantly lower during period 2 than during period 1 (infection rate: 28.1% of patients in period 1 and 9.6% of patients in period 2 [P = .01]; pneumonia rate: 32.6% of patients in period 1 and 4.2% of patients in period 2 [P = .008]). The mortality rate among patients with nosocomial pneumonia was 38.2% in period 1 and 4.3% in period 2 (P = .009). CONCLUSIONS: After implementation of an infection control program, the rate of infection with multidrug-resistant pathogens decreased, as did the mortality rate among patients with nosocomial pneumonia.

Performance of two real-time PCR assays for hepatitis B virus DNA detection and quantitation.

In-house developed real-time PCR (qPCR) techniques could be useful conjunctives to the management of hepatitis B virus (HBV) infection in resource-limited settings with high prevalence. Two qPCR assays (qPCR1 and qPCR2), based on primers/probes targeting conserved regions of the X and S genes of HBV respectively, were evaluated using clinical samples of varying HBV genotypes, and compared to the commercial Roche Cobas AmpliPrep/Cobas TaqMan HBV Test v2.0. The lower detection limit (LDL) was established at 104 IU/ml for qPCR1, and 91 IU/ml for qPCR2. Good agreement and correlation were obtained between the Roche assay and both qPCR assays (r = 0.834 for qPCR1; and r = 0.870 for qPCR2). Differences in HBV DNA load of > 0.5 Log10 IU/ml between the Roche and the qPCR assays were found in 49/122 samples of qPCR1, and 35/122 samples of qPCR2. qPCR1 tended to underestimate HBV DNA quantity in samples with a low viral load and overestimate HBV DNA concentration in samples with a high viral load when compared to the Roche test. Both molecular tools that were developed, used on an open real-time PCR system, were reliable for HBV DNA detection and quantitation. The qPCR2 performed better than the qPCR1 and had the additional advantage of various HBV genotype detection and quantitation. This low cost quantitative HBV DNA PCR assay may be an alternative solution when implementing national programmes to diagnose, monitor and treat HBV infection in low- to middle-income countries where testing for HBV DNA is not available in governmental health programmes.

Comparison of pharmacovigilance algorithms in drug hypersensitivity reactions.

BACKGROUND: A firm diagnosis of drug hypersensitivity, because it may re-induce the reaction, is seldom confirmed. Causality assessment algorithms are therefore of interest. AIMS: The objective of this work was to compare three algorithms in the diagnosis of drug hypersensitivity. METHODS: Evaluation of 120 clinical histories of drug hypersensitivity was carried out: 60 involving beta-lactams (50%) and 60 involving non-steroidal anti-inflammatory drugs (50%). Each of these groups of patients underwent a standardised allergy diagnosis, which included a detailed anamnesis, skin tests and, often, provocation tests under strict hospital surveillance. Unaware of the final allergy diagnosis, scores were established for all of the cases and compared using algorithms suggested by Begaud and coworkers [2, 20], Jones [13] and Naranjo et al. [21]. RESULTS: Although the methods of Jones [13] and Naranjo et al. [21] were perfectly concordant (k=1), no concordance was noted using the Begaud and coworkers [2, 20] method. CONCLUSIONS: All three algorithms are dissimilar regarding the diagnosis of drug hypersensitivity.