Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

International audienceObjective: Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. Methods: In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. Results: In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Conclusions: Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence

Mobile laboratory reveals the circulation of Dengue virus serotype I of Asian origin in Medina Gounass (Guediawaye), Senegal

With the growing success of controlling malaria in Sub-Saharan Africa, the incidence of fever due to malaria is in decline, whereas the proportion of patients with non-malaria febrile illness (NMFI) is increasing. Clinical diagnosis of NMFI is hampered by unspecific symptoms but early diagnosis is a key factor for better patient care and for disease control. The aim of this study was to determine the arboviral aetiologies of NMFI in a low resources settings using a mobile laboratory based on Recombinase Polymerase Amplification (RPA) assays. The panel of tests for this study was expanded to five arboviruses including (Dengue virus (DENV), Zika virus (ZIKV), Yellow fever virus (YFV), Chikungunya virus (CHIKV), and Rift valley fever virus (RVFV). One hundred and four children aged between one month and 115 months were enrolled and screened. Three of 104 blood samples of children < 10 years presenting at an outpatient clinic tested positive for DENV. The results were confirmed by real-time RT-PCR, partial sequencing, and non structural protein 1 (NS1) antigen capture ELISA (Biorad, France). Phylogenetic analysis of the derived DENV-1 sequences clustered them with sequences of DENV-1 isolates from Guangzhou in China in 2014. In conclusion, this mobile setup proved reliable for the rapid identification of the causative agent of NMFI, with results consistent with those obtained in the reference laboratory`s settings

Factors Associated with Negative Direct Sputum Examination in Asian and African HIV-Infected Patients with Tuberculosis (ANRS 1260)

OBJECTIVE: To identify factors associated with negative direct sputum examination among African and Cambodian patients co-infected by Mycobacterium tuberculosis and HIV. DESIGN: Prospective multicenter study (ANRS1260) conducted in Cambodia, Senegal and Central African Republic. METHODS: Univariate and multivariate analyses (logistic regression) were used to identify clinical and radiological features associated with negative direct sputum examination in HIV-infected patients with positive M. tuberculosis culture on Lowenstein-Jensen medium. RESULTS: Between September 2002 and December 2005, 175 co-infected patients were hospitalized with at least one respiratory symptom and pulmonary radiographic anomaly. Acid-fast bacillus (AFB) examination was positive in sputum samples from 110 subjects (63%) and negative in 65 patients (37%). Most patients were at an advanced stage of HIV disease (92% at stage III or IV of the WHO classification) with a median CD4 cell count of 36/mm³. In this context, we found that sputum AFB negativity was more frequent in co-infected subjects with associated respiratory tract infections (OR = 2.8 [95%CI:1.1-7.0]), dyspnea (OR = 2.5 [95%CI:1.1-5.6]), and localized interstitial opacities (OR = 3.1 [95%CI:1.3-7.6]), but was less frequent with CD4 ≤ 50/mm³ (OR = 0.4 [95%CI:0.2-0.90), adenopathies (OR = 0.4 [95%CI:0.2-0.93]) and cavitation (OR = 0.1 [95%CI:0.03-0.6]). CONCLUSIONS: One novel finding of this study is the association between concomitant respiratory tract infection and negative sputum AFB, particularly in Cambodia. This finding suggests that repeating AFB testing in AFB-negative patients should be conducted when broad spectrum antibiotic treatment does not lead to complete recovery from respiratory symptoms. In HIV-infected patients with a CD4 cell count below 50/mm3 without an identified cause of pneumonia, systematic AFB direct sputum examination is justified because of atypical clinical features (without cavitation) and high pulmonary mycobacterial burden

Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up antiviral treatment through decentralized services. However, access to the conventional tools to assess treatment eligibility (liver biopsy/Fibroscan®/HBV DNA) is limited and not affordable in resource-limited countries. We developed and validated a simple score to easily identify patients in need of HBV treatment in Africa. METHODS: As a reference, we used treatment eligibility determined by the European Association for the Study of the Liver based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV DNA. We derived a score indicating treatment eligibility by a stepwise logistic regression using a cohort of chronic HBV infection in The Gambia (n = 804). We subsequently validated the score in an external cohort of HBV-infected Africans from Senegal, Burkina Faso, and Europe (n = 327). RESULTS: Out of several parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT level, constituting a simple score (treatment eligibility in Africa for the hepatitis B virus: TREAT-B). The score demonstrated a high area under the receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the validation set. The score of 2 and above (HBeAg-positive and ALT ≥20 U/L or HBeAg-negative and ALT ≥40 U/L) had a sensitivity and specificity for treatment eligibility of 85% and 77%, respectively. The sensitivity and specificity of the World Health Organization criteria based on the aspartate aminotransferase-to-platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS: A simple score based on HBeAg and ALT had a high diagnostic accuracy for the selection of patients for HBV treatment. This score could be useful in African settings. LAY SUMMARY: Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings

Low Immune Response to Hepatitis B Vaccine among Children in Dakar, Senegal

HBV vaccine was introduced into the Expanded Programme on Immunization (EPI) in Senegal and Cameroon in 2005. We conducted a cross-sectional study in both countries to assess the HBV immune protection among children. All consecutive children under 4 years old, hospitalized for any reason between May 2009 and May 2010, with an immunisation card and a complete HBV vaccination, were tested for anti-HBs and anti-HBc. A total of 242 anti-HBc-negative children (128 in Cameroon and 114 in Senegal) were considered in the analysis. The prevalence of children with anti-HBs ≥10 IU/L was higher in Cameroon with 92% (95% CI: 87%–97%) compared to Senegal with 58% (95% CI: 49%–67%), (p<0.001). The response to vaccination in Senegal was lower in 2006–2007 (43%) than in 2008–2009 (65%), (p = 0.028). Our results, although not based on a representative sample of Senegalese or Cameroonian child populations, reveal a significant problem in vaccine response in Senegal. This response problem extends well beyond hepatitis B: the same children who have not developed an immune response to the HBV vaccine are also at risk for diphtheria, tetanus, pertussis (DTwP) and Haemophilus influenzae type b (Hib). Field biological monitoring should be carried out regularly in resource-poor countries to check quality of the vaccine administered

Liver Stiffness Measurement and Biochemical Markers in Senegalese Chronic Hepatitis B Patients with Normal ALT and High Viral Load

Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10) IU/mL and normal alanine aminotransferase (ALT) values.LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring.225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively.In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis

The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa.

BACKGROUND: Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. METHODS: Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). RESULTS: Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. CONCLUSIONS: The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa

Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159)

To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding.We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score). with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9) versus 2 (±0.7) in non-divergent ones (p<0.0001).Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area