ABSTRACT
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.
ABSTRACT
Introduction : L'efficacite des traitements antiretroviraux (ARV) peut entrainer des phenomenes inflammatoires de restauration immune (IRIS) ou auto-immuns paradoxaux sous forme de pathologies infectieuses telles que la tuberculose ou la cryptococcose. Observation: Nous rapportons un cas inhabituel de syndrome inflammatoire de restauration immune sous la forme d'une cryptococcose disseminee avec des atteintes meningees et cerebrales chez un patient de 56 ans infecte par le VIH-1 qui a consulte pour un trouble de la vigilance; des crises convulsives et une hemiparesie droite. Le patient avait repondu favorablement a un traitement antifongique par fluconazole institue pour une meningite a cryptocoque un mois avant son admission. Un traitement ARV avait ete initie une dizaine de jours apres le traitement anticryptococcique. Apres deux semaines effective de traitement ARV; le tableau clinique etait marque par la reapparition des symptomes neuro-meninges et leur aggravation. L'examen a l'encre de chine du liquide cephalorachidien (LCR) mettait en evidence des spores de Cryptococcus neoformans. La recherche de l'antigene cryptococcique etait positive et la culture sur milieu de Sabouraud montrait des colonies de Cryptococcus Neoformans. L'IRM cerebrale notait de multiples lesions d'abces. L'evolution a ete fatale apres 11 jours de traitement. Conclusion : Le cryptococcome associe a l'IRIS est peu decrit en Afrique. La generalisation actuelle des ARV sur ce continent pourrait entrainer une recrudescence de cette manifestation
Subject(s)
Immune Reconstitution Inflammatory Syndrome , Meningitis, CryptococcalABSTRACT
OBJECTIVE: To describe the epidemiological and clinical features and the outcome of tetanus with a surgical wound (open fracture, burn, incision, curettage, etc) as the portal of entry. METHODS: Cross-sectional analysis of records of patients hospitalized in the department of infectious and tropical diseases in Abidjan for surgical tetanus from 2003 to 2008. RESULTS: During the 6-year study period, 29 cases were identified. They accounted for 11% of all tetanus cases admitted to the hospital: 8% from 2003 through 2006 and 14% in 2007 and 2008. The patients' average age was 36 years (range: 11-72). Most cases (86%) involved recent surgery, in both public (51%) and private (49%) health facilities. All patients had generalized tetanus at admission, and 24 (86%) paroxysms. Moderate forms predominated (69%). The lethality of tetanus in these surgical wound cases was 45%. The characteristics statistically associated with death were: age >44 years, time of hospitalization >4 days, the presence of paroxysms, and a Dakar prognosis score ≥4. CONCLUSION: The severity of surgical tetanus remains a concern for practitioners. Its high prevalence in recent years demonstrates the need to increase surgeons' awareness of tetanus prevention.
Subject(s)
Surgical Wound Infection , Tetanus , Adolescent , Adult , Aged , Child , Cote d'Ivoire , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology , Tetanus/diagnosis , Tetanus/epidemiology , Young AdultABSTRACT
OBJECTIVE: The authors had for aim to compare the therapeutic efficiency and tolerance of 2 NRTI+efavirenz (EFV) versus 2 NRTI+indinavir (IDV) in HIV infected adults in Abidjan. METHODS: A retrospective and multicentric study was made on 327 HIV-1 naive patients, 142 in the EFV group and 185 in the IDV group followed in Abidjan from November 1998 to December 2003. The analysis concerned clinical advents (opportunistic infections) and immunovirological parameters (CD4, viral load). Patients received 2 NRTI such as AZT+3TC or D4T+3TC combined either with EFV or IDV. The principal judgement criterion was therapeutic failure. We assessed the percentage of patients with undetectable viral load and the frequency of grade 3-4 adverse effects after 24 months of follow-up. RESULTS: Clinical improvement of patients' state and regression of opportunistic infections were identical in the two groups. The average gain of CD4 was superior to 177 in EFV versus +219 in IDV (p=0.004). The percentage of patients with undetectable viral load was 66% for EFV versus 59% for IDV (p=0.04). The frequency of adverse effects was more elevated with EFV than IDV, 39% versus 23% (p=0.002) initially, but seemed to decrease later. CONCLUSION: HAART with EFV is at least as efficient as with IDV in terms of reduction of viral load and increased CD4 count and is an excellent low-cost first line treatment.
