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

Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study

International audienceBackground: The Cambodia pertussis immunization schedule includes three doses given at age 6, 10 and 14 weeks using a whole-pertussis vaccine. No booster doses are included. Pertussis biological diagnosis is unavailable in Cambodia and its burden remains unclear. This study aimed to provide accurate data on pertussis serological status of Cambodian children and adolescents, and to evaluate vaccination timeliness. Methods: Fully vaccinated children aged 3-15 years were recruited at the Rabies Prevention Center, Institut Pasteur in Cambodia, Phnom Penh. Capillary blood samples and information on pertussis vaccination history were collected. Anti-pertussis toxin (PT) IgG titers were quantified by ELISA. Results: Compliance with the national immunization schedule was 95.1%. Initiation of vaccination after 8 weeks of age was observed for 29.0% of the children, but was less frequent in the youngest children (13.0%) compared with the oldest ones (46.4%). Rate of children exhibiting anti-PT IgG varied across age groups, and increased from 35.7% to 55.0% in 3-5 and 12-15 years age groups, respectively. Conclusion: Pertussis circulates among vaccinated Cambodian children and adolescents. These data support the need for public health authorities to strengthen pertussis surveillance and use local epidemiological data to make evidence-based decision for the establishment of an optimal vaccination strategy

A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study

Comment in : Improving human rabies post-exposure prophylaxis. / Blumberg L, Rupprecht CE. Lancet Infect Dis. 2019 Dec;19(12):1273-1274. doi: 10.1016/S1473-3099(19)30525-0. Epub 2019 Sep 27. PMID: 31570310International audienceBackground: The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030. This effort will require improving access to adequate and timely rabies post-exposure prophylaxis as compliance is low with WHO-recommended regimens (given in four to five visits over 1 month). Access could be substantially improved by an abridged regimen to reduce doses, direct and indirect costs, and improve vaccine equity by better sharing of available vaccine. We aimed to compare rabies virus neutralising antibody titres before and after the fourth visit to determine whether that session was needed or the current regimen could be abridged.Methods: In this observational cohort study, we measured rabies virus neutralising antibody titres using rapid fluorescent focus inhibition tests in 116 people bitten by dogs with laboratory-confirmed rabies and 20 control individuals. Percentages of circulating plasmablasts were determined by flow cytometry. All individuals had been referred to the rabies prevention clinic at Institut Pasteur in Cambodia and received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28 (Thai Red Cross regimen) with or without equine rabies immunoglobulin, as per 2010 WHO recommendations.Findings: All individuals had rabies virus neutralising antibody titres considered protective (≥0·5 IU/mL) and plasmablast activation on day 28 before the last injection. The median rabies virus neutralising antibody concentration in the group of individuals bitten by rabies virus-positive dogs was 1·08 IU/mL (IQR 0·37-3·09) on day 7, 26·86 (22·68-49·50) on day 28, and 26·74 (11·78-49·06) on day 42. No significant differences were observed in titres between days 28 and 42, after titres reached a plateau. These titres were reached notwithstanding equine rabies immunoglobulin use, age, sex, nutrition status as indicated by upper-arm circumference in children or BMI in adults, or dog infection status. Titres or plasmablast percentages did not increase between the day of the last injection and 2 weeks later. All patients were alive 1 year after post-exposure prophylaxis.Interpretation: The fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients

Co-infection tuberculose et VIH

La tuberculose est une des principales causes de mortalité chez les adultes infectés par le VIH (virus de l’immunodéficience humaine). L’essai clinique randomisé CAMELIA (ANRS 1295/CIPRA KH001) visait à déterminer le moment optimal de l’initiation du traitement antirétroviral après le début du traitement antituberculeux afin de réduire la mortalité. Nous décrivons ici sa mise en œuvre dans cinq hôpitaux cambodgiens sous la coordination de l’Institut Pasteur du Cambodge, sa conduite dans les établissements de santé, les défis liés à cette thérapie, ainsi que les bénéfices en termes de santé publique au Cambodge et au-delà

Factors associated with sputum smear negativity by univariate and multivariate analysis.

<p>*OR: Odds Ratio.</p

Distribution of AFB-positive and AFB-negative patients with definite tuberculosis in Cambodia and Africa.

<p>Distribution of AFB-positive and AFB-negative patients with definite tuberculosis in Cambodia and Africa.</p

Baseline characteristics of the study population.

<p>*Global comparison among the three countries.</p><p>**Median (Q1, Q3).</p