[Primary isoniazid preventive therapy : A strategy still relevant in the era of test and treat ; literature review]. / Chimioprophylaxie antituberculeuse primaire à l'isoniazide : une stratégie d'actualité à l'ère du tester et traiter ; revue de la littérature.

BACKGROUND: Tuberculosis remains a public health threat responsible as recently as 2018 for more than one million deaths. Chemoprophylaxis with isoniazid is one of the strategies implemented to control the disease. Although it is not yet widely prescribed, its utilization raises additional questions in the "test and treat" era of for anti-retroviral therapy. The objective of this study is to review the different randomized controlled trials of antitubercular Isoniazid Preventive Therapy (IPT). We have distinguished (a) "efficacy trials" (ET) comparing IPT to a placebo or the absence of chemoprophylaxis and (b) "IPT regimen trials" (RT) comparing IPT to one or several other regimens. METHODS: Literature search (keywords from published articles found in the Medline and Scopus data bases: "tuberculosis", "prophylaxis", "HIV", "randomized controlled trial") and standardized reading of selected articles reporting results from randomized trials of IPT in HIV-infected people. RESULTS: Eighteen selected trials (11 ET and 7 RT), including 19,725 participants. The regimens studied were 3H, 6H, 9H, 12H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, and 3HP [H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, P: Rifapentine]. LOCATIONS: Ten in Africa, three in Haiti, one in India, one in the USA, one in the Americas and two multi-continental trials. In ET with or without antiretrovirals (ART), IPT significantly reduces the risk of tuberculosis, by 32 to 71%. In ET prior to ART, IPT does not appear to reduce mortality. In ET in patients receiving ART, on the other hand, IPT reduces mortality. As regards RT, there seems to be no reason to prefer other regimens to IPT. Tolerance is good. Importantly, IPT may reduce (rather than worsen) the risk of multidrug-resistant bacilli selection by decreasing the number of TB episodes and, consequently, the number of curative tuberculosis treatments. CONCLUSION: Far from becoming obsolete due to ARV treatment, IPT has remained a timely and relevant intervention.

Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

Characterization of Staphylococcus aureus from Pasteur Institute in Côte d'Ivoire: Methicillin Resistance, Reduced Sensitivity to Vancomycin, Panton-Valentine Leucotoxin and Exfoliatins.

Staphylococcus aureus, which causes various infections, particularly suppurations, expresses many virulence factors. The resistance of S. aureus to methicillin (MRSA) which can spread to vancomycin constitutes a major challenge in infectiology. The search for virulence and resistance factors is therefore of interest to better understand the mechanisms of this pathogenicity. The objectives of this study were to determine the frequency of phenotypic and genotypic (mecA, vanB) resistances, the frequency of virulence genes (eta, etb, and lukS) and to investigate the resistant strains for the presence of virulence genes. On thirty-one strains isolated from infections at the Pasteur Institute of Côte d'Ivoire, the study of susceptibility to methicillin and vancomycin was carried out by phenotypic and molecular methods. We observed phenotypic and genotypic resistance to methicillin of 41.9% and 32.3% respectively. Despite a suspicion of very high vancomycin susceptibility reduced, 25.8% by phenotypic method, the vanB gene was only found in 3.2% of strains. The prevalence of virulence genes was high with the eta gene, 96.8%, and the lukS gene 45.2%. The mecA gene was present with an eta gene in 32.3% of strains and in 9.7% with the lukS gene, however the vanB gene was not present in any strain carrying virulence factors. These results should lead to the screening of other van genes for resistance to vancomycin.

Screening for active tuberculosis before isoniazid preventive therapy among HIV-infected West African adults.

SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance. OBJECTIVE: To report the frequency of undiagnosed TB in patients enrolled for IPT and describe the results of a 1-month buffer period to avoid prescribing IPT for active TB cases. DESIGN: Patients were screened using a clinical algorithm and chest X-ray at Day 0 and started on isoniazid at Month 1 if no sign/symptom suggestive of TB appeared between Day 0 and Month 1. RESULTS: Of 1030 patients randomised into IPT arms. 10% never started IPT at Month 1. Of these, 23 had active TB, including 16 with prevalent TB. Among the 927 patients who started IPT, 6 had active TB, including 1 with prevalent TB. Only 1 patient with active TB received IPT due to the 1-month buffer period between Day 0 and IPT initiation. CONCLUSION: In this study, 1.6% of adults considered free of active TB based on clinical screening at pre-inclusion actually had active TB.

Erratum.

[This corrects the article on p. 166 in vol. 4, PMID: 25215193.].

Assessment of the genotype MTBDRplus assay for rifampin and isoniazid resistance detection on sputum samples in Cote d'Ivoire.

We conducted an evaluation study on the GenoType MTBDRplus assay's ability to detect mutations conferring resistance to rifampin and isoniazid directly from sputum taken from 120 smear positive pulmonary patients from tuberculosis (TB) centers in Cote d'Ivoire. The sputum was decontaminated by N-acetyl-l-cysteine (NALC) and comparatively analyzed with the MTBDRplus assay version 2.0 and the mycobacterial growth indicator tube (MGIT) 960 automated drug susceptibility testing (MGIT-DST). The Gene-Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay was performed for 21 sputa with absence of hybridization for at least one rpoB wild-type probes. Four and seven, respectively, discordant and concordant results were also analyzed. The mutations in the rpoB gene were 21 (17.5%), 20 (16.7%), 7 (5.8%), and 10 (8.3%), respectively, for D516V, H526Y, H526D, and S531L. S315T mutation in katG gene associated or not with mutation in promoter of inhA was detected in 76 (63.3%) of the sputum. Compared to MGIT-DST, the sensitivity and specificity of the MTBDRplus for rifampin resistance detection were 100% (75-100%) and 73.2% (61.3-84%), respectively. For isoniazid resistance detection, the sensitivity and specificity were, respectively, 95% (90-|99) and 95.1% (88.5-100%). Interpretation of 16 sputa without hybridization of rpoB wild-type probe 8 compared to those obtained with MGIT-DST and GeneXpert MTB/RIF was discordant and concordant, respectively, for 11 and 5.

[Relevance of the systematic culture of the intraoperative swab and drain tip of Redon in orthopaedic-traumatology surgery]. / Intérêt de la culture systématique du prélèvement per opératoire et du drain de Redon en chirurgie orthopédique et traumatologique.

BACKGROUND: Post operative infections are more severe complications in bone surgery. The first stage culture on drain tip or intraoperative swab are not well known according to clear, open and aseptic orthopaedic surgery to predict wounds infections. OBJECTIVE: To show the place of the systemic bacteriological culture of an intraoperative swab and the proximal tip of the Redon in bone surgery. METHODS: This was a prospective continuous series of 92 interventions performed in the service of Orthopaedics Traumatology of Treichville University Hospital (Abidjan, Côte d'Ivoire). The lesions included were allocated into three groups based on the National Research Council classification. Group 1 consisted of 50 subjects with clean lesions and hyper clean. Group 2 was made up of 25 subjects with clean lesions contaminated or contamined ab initio while Group 3 consisted of 17 patients with the septic lesions. Fifty six men and 36 women with an average age of 36.9 years had two types of swabs culture. In the first type sample of intra operative haematoma or the pus before using antiseptic products was used; the second type of culture used the proximal tip of Redon at the time of its ablation. These two swabs were put in a sterile vial and sent to the same laboratory for culture. RESULTS: The overall sepsis rate was of 24(26,1%). The microbial population was dominated by the gram negative bacilli, bacilli positive intraoperative cultures were most frequent in the group 3. 15 (88,2%). The positivity of the culture of the Redon was high in the group 2 (32%) and in the group 3 (52.9%). There was a significant difference between these two groups of surgery. The sensitivity, the specificity, and the predictive values were low. For all groups, the reports of likelihood observed didn't permit to establish a relation of cause or effect between a positive culture and the occurrence of post operative infection. CONCLUSION: The gram negative bacilli were mostly observed on the culture of the site of infection. Although there was no significant relationshionship, it appears from the frequency that there may be a clinical link between the positive culture and open fracture.

15 Month follow up of African children following vaginal cleansing with benzalkonium chloride of their HIV infected mothers during late pregnancy and delivery.

OBJECTIVES: To study mother to child HIV-1 transmission (MTCT) and infant mortality following benzalkonium chloride (BC) disinfection. METHODS: A randomised, double blind phase II placebo controlled trial. Women testing positive for HIV-1 infection in prenatal care units in Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso, from November 1996 to April 1997 were eligible, with their informed consent. Women self administered daily a vaginal suppository of 1% BC (53) or matched placebo (54) from 36 weeks of pregnancy, plus a single dose during labour. The neonate was bathed with 1% BC solution or placebo within 30 minutes after birth. MTCT rate was assessed based on repeated polymerase chain reaction (PCR) and serology results. For the present analysis, children were followed up to 15 months. RESULTS: A total of 107 women were enrolled. Of 103 eligible liveborn children, 23 were HIV infected, 75 uninfected, and five of indeterminate status. MTCT transmission rate was 24.2% overall (95% confidence interval (CI): 14.3% to 30.4%). On an intent to treat basis, the transmission rate did not differ between the two groups (23.5%, CI 13.8 to 38.5, in the BC group and 24.8%, CI 15.0 to 39.6, in the placebo group at 15 months). Similarly, there was no difference in mortality at 15 months (22.9%, CI 13.7 to 36.9, in the BC group and 16.5%, CI 9.0 to 29.4, in the placebo group). CONCLUSION: This analysis failed to suggest any benefit of BC disinfection on mother to child HIV transmission or perinatal and infant mortality.

HIV-1-related morbidity in adults, Abidjan, Côte d'Ivoire: a nidus for bacterial diseases.

We studied mortality and morbidity in 270 HIV-1-infected adults (60% women, median age 31 years, mean baseline CD4 count 331/mm(3) ) observed in a follow-up that lasted a median 10 months in Côte d'Ivoire. Survival and probability of remaining free from any episode of morbidity at 12 months were 0.80 and 0.50, respectively. Baseline CD4 count <200/mm(3) was the only variable associated with global morbidity and mortality, with hazard ratios of 2.50 and 7.57, respectively. The most frequent causes of morbidity were severe bacterial infections (incidence rate: 26.1 per 100 person-years [py]), followed by oral candidiasis (22.3% py), unexplained weight loss over 10% of baseline body weight (13.3% py), tuberculosis (10.1% py), unexplained chronic diarrhea (9.7% py), and isosporiasis (5.1% py). Nontyphoid Salmonella accounted for 37% of isolated strains during severe bacterial infections, followed by Streptococcus pneumoniae (34%), Escherichia coli (15%), and Shigella species (7%). A significant part of bacterial morbidity occurred in patients with baseline CD4 count > or = 200/mm(3), in whom the incidence rate of bacterial diseases was 21.3% py and the probability of remaining free from any bacterial infection at 12 months was 0.80 (vs. 36.4% py and 0.71 in patients with baseline CD4 count <200/mm(3); p =.07).

Hepatitis B and C infections, human immunodeficiency virus and other sexually transmitted infections among women of childbearing age in Côte d'Ivoire, West Africa.

Few studies have been conducted in developing countries to estimate the prevalence of hepatitis C virus (HCV) infection and its association with human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). We have screened for hepatitis B virus (HBV) and HCV markers 200 HIV-1-positive, 23 HIV-2-positive and 206 HIV-negative women attending gynaecology clinics in 1995/96 in Abidjan, Côte d'Ivoire, a sample selected among 2198 consecutive consultants. Taking into account the prevalence of 21.7% for HIV in this population, the overall prevalence of anti-HBV core antibody was 81.6%, that for hepatitis B surface antigen was 9.9% and for HCV antibody was 3.3%. HIV infection and other STDs were not associated with HBV or HCV markers. Moreover, HBV and HCV markers were not statistically associated. Our results confirm the high prevalence of HIV in Abidjan and the endemic situation of HBV infection. Furthermore, HCV infection is not infrequent in this developing country setting, not explained by sexual transmission.

Prognostic value of cross-sectional anthropometric indices on short-term risk of mortality in human immunodeficiency virus-infected adults in Abidjan, Côte d'Ivoire.

In sub-Saharan Africa where weight loss is very difficult to estimate, cross-sectional anthropometric indicators could be useful to predict human immunodeficiency virus (HIV)-associated mortality. The study objective was to look for threshold values of baseline body mass index, arm muscle circumference, and fat mass to predict the risk of death in HIV-infected adults included in a 1996-1998 trial of early cotrimoxazole chemoprophylaxis in Abidjan, Côte d'Ivoire (COTRIMO-CI-ANRS 059 trial). The authors graphically determined if consecutive anthropometric categories with the closest hazards ratios of the risk of death could be clustered to obtain a unique threshold that distinctly separated two categories. When the threshold values were determined, the authors estimated the hazards ratio of mortality of this two-category model. A significant increase of mortality was observed for a body mass index of < or =20.3 in men (hazards ratio = 2.6; 95% confidence interval (CI): 1.4, 5.0) and of < or =18.5 in women (hazards ratio = 2.2; 95% CI: 1.05, 4.5) and for a fat mass of < or =6% in men (hazards ratio = 4.6; 95% CI: 2.3, 9.4) and of < or =18% in women (hazards ratio = 2.4; 95% CI: 1.2, 4.9). No simple threshold could be identified for arm muscle circumference. In Côte d'Ivoire where chemoprophylaxis of opportunistic infections has recently been recommended to be widely initiated on clinical criteria, such thresholds may help to screen patients with higher risks of mortality.

[Causes of fever in adults infected by HIV-1. Ambulatory follow-up in the ANRS 059 trial in Abidjan, Ivory Coast]. / Causes de fièvre chez des adultes infectés par le VIH-1. Suivi en ambulatoire dans le cadre de l'essai ANRS 059 à Abidjan, Côte d'Ivoire.

OBJECTIVE: Describe the causes of fever in HIV-1 infected adults in Abidjan, Ivory Coast. METHODS: Exhaustive analysis of all the morbid episodes with raise in temperature to above 37.5 degrees C in patients followed-up prospectively, within the framework of the ANRS 059 study from April 1996 to March 1998. RESULTS: One hundred and four patients presented 269 episodes of fever. At the start of these episodes, the mean CD4 count was of 311/mm3, fever had lasted a mean of 3.4 days and mean body temperature was 38.7 degrees C. The 269 episodes lead to 288 diagnoses: 152 specific etiologic diagnoses and 136 non-specific syndrome diagnoses. Community bacterial infections represented 55% of the specific diagnoses, followed by malaria (16%) and tuberculosis (12%). The mean CD4 count during the bacterial episodes was 208/mm3, in malaria 384/mm3 and in tuberculosis 245/mm3. Non-typhi salmonella, pneumococci and Escherischia coli represented 37%, 32%, and 15% respectively of the bacteria isolated. The mean duration between the first and last day of fever was 8.4 days. This time lapse was superior or equal to 30 days in 22 episodes (8%), 50% of which were mycobacterioses (36% tuberculosis and 14% atypic mycobacterioses). Nineteen episodes (7%) lead to death within a mean delay of 58 days. The first cause of death was atypic mycobacteriosis (26%). Death was significantly associated with a CD4 count < 200/mm3 and to prolongation of fever for more than 30 days. CONCLUSION: Other than the frequently described role of tuberculosis in HIV morbidity in sub-Saharian Africa, the role of bacterial diseases, responsible for early death, potentially severe, but curable should be underlined. The diffusion of antibiotic treatment algorithms adapted to the principle clinical syndromes encountered, might improve the treatment of adults infected by HIV consulting in sub-Saharian Africa.