Insights into Recurrent Tuberculosis: Relapse Versus Reinfection and Related Risk Factors

Recurrent tuberculosis (TB) following successful treatment constitutes a significant challenge to TB control strategies. TB recurrence can be due to either reactivation of the same strain, i.e., relapse, or reinfection with a new strain. Recurrence due to reinfection has become an area of intense study due to its perceived significance in TB endemic settings with high rates of human immunodeficiency virus (HIV) coinfection. This review presents a descriptive analysis of recurrent TB disease and explores risk factors, immunopathogenesis, treatment, and preventative strategies. Currently available laboratory methods used to discriminate tuberculosis recurrence due to reinfection and relapse are discussed. We highlight risk factors for recurrence and strategies for early detection of TB recurrence. Enhanced treatment options such as intensified initial treatment, extension of treatment, and secondary preventative therapy for patients presenting with multiple risk factors are explored in this review. The potential value of identifying immunological correlates of risk and protection in recurrent TB is also briefly examined

Aetiology, Clinical Presentation, and Outcome of Meningitis in Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis

We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART

Challenges in the integration of TB and HIV care : evidence for improving patient management and health care policy.

Doctor of Philosophy in Public Health Medicine. University of KwaZulu-Natal, Medical School 2015.TB infection remains a leading cause of morbidity and mortality among patients with HIV infection, while HIV is the strongest risk factor for development of active TB. Integration of HIV and TB treatment is key to reducing mortality in co-infected patients; but many obstacles stand in the way of effective scale-up of this approach to HIV-TB treatment. The challenges associated with HIV-TB integration extend from clinical complexities in individual patient management, to impediments in health service organization and prioritization to address this urgent public health priority, especially in sub-Saharan Africa where TB-HIV co-infection rates reach 80%. The purpose of this study was to assess and identify strategies to overcome the challenges in immune reconstitution and drug safety/tolerability when integrating HIV and TB care in a cost-effective manner to reduce co-infection mortality. Clinical and operational service data from the Starting Antiretroviral therapy at three Points in Tuberculosis Treatment (SAPiT – CAPRISA 003) study, a 3-arm, randomized control trial in 642 newly diagnosed sputum smear-positive TB-HIV co-infected adult patients with screening CD4+ cell count < 500 cells/mm3, were analysed. In addition, the incidence rate of unmasked clinical TB following ART initiation was assessed through a retrospective chart review conducted in HIV infected patients enrolled at the rural CAPRISA AIDS Treatment Programme. Overall, mortality was 56% lower (RR=0.44; 95% CI: 0.25 to 0.79; P = 0.003) in patients initiated on ART during TB treatment compared to ART deferral to after TB treatment completion. However, the risk of immune reconstitution inflammatory syndrome (IRIS) was higher (incidence rate ratio (IRR), 2.6 (95% CI, 1.5 to 4.8); P < 0.001, in patients initiating ART within the first 2 months compared to later ART initiation during TB treatment. In the most severely immuno-compromised patients (CD4 counts <50 cells/mm3) early ART integration was associated with an almost five-fold increased risk of IRIS (IRR 4.7 (95% CI, 1.5 to 19.6); P = 0.004. Patients initiating ART in the first 2 months of TB therapy had higher hospitalization rates (42% vs. 14%; P = 0.007) and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) than patients in the other two groups. When assessing available evidence, these results indicate that ART initiation in patients with CD4 cell counts >50 cells/mm3 would be most appropriate after completion of intensive phase of TB therapy, a strategy that was found to cost $1840 per patient treated. Among HIV infected patients initially screening negative for TB there was a fourfold higher incidence rate of unmasking TB in the first 3 months after ART initiation, compared to the subsequent 21 months post-ART initiation. The new information generated by this study provides important evidence for policy and clinical management of patients with HIV and TB co-infection. Firstly, careful clinical vigilance for ‘unmasked’ TB is required in patients initiating ART. Secondly, the survival benefit of AIDS therapy in TB patients can be maximized by initiating ART as soon as possible after TB therapy has been started in patients with advanced immunosuppression, i.e., those with CD4+ counts <50 cells/mm3. However, patients with higher CD4+ cell counts should delay ART initiation to at least 8 weeks after the start of TB therapy to minimize the incidence and duration of immune reconstitution disease and consequent hospitalization. Thirdly, this approach, which is at variance with current World Health Organization policy and guidelines, is cost-effective and readily implementable within the clinical setting. Finally, addressing the operational challenges to HIV-TB treatment integration can improve patient outcomes with substantial public health by reducing mortality by the most important causes of death in South Africa

HIV-Associated Tuberculosis

The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6

Tuberculosis treatment outcomes among peri-urban children receiving doorstep tuberculosis care.

CAPRISA, 2016.Abstract available in pdf

Adolescent antiretroviral management: Understanding the complexity of non-adherence

This case-based discussion highlights challenges in adolescent antiretroviral management, focusing on non-disclosure of status and thesubsequent impact of suboptimal treatment adherence. Despite the scale-up of antiretroviral therapy (ART) and recommendations made bythe World Health Organization (WHO) for ART for all human immunodeficiency virus (HIV)-infected paediatric patients, ART coveragein adolescents lags behind that in adults. Challenges of sustaining lifelong ART in children and adolescents require consideration of specificbehavioural, physiological and psychosocial complexities associated with this special group. To preserve future drug options and sustainlifelong access to therapy, addressing non-adherence to treatment is critical to minimising acquisition of ART drug resistance and treatmentfailure. We review the psychosocial and developmental components that influence the course of the disease in adolescents and consider thecomplexities arising from perinatal exposure to ART and the growing risk of transmitted ART drug resistance in high-burden resourcelimitedsettings

A retrospective cohort study of body mass index and survival in HIV infected patients with and without TB co-infection.

CAPRISA, 2018.Abstract available in pdf

Survey of ethical dilemmas facing intensivists in South Africa in the admission of patients with HIV infection requiring intensive care.

Background. Maturing of the burgeoning HIV epidemic in South Africa has resulted in an increased demand for intensive care. Objectives. To investigate the influence of ethical dilemmas facing South African intensivists on decisions about access to intensive care for patients with HIV infection in resource-limited settings. Methods. A cross-sectional, descriptive, quantitative, analytical, anonymous attitudes-and-perception questionnaire survey of 90 intensivists. The main outcome measure was the rating of factors influencing decisions on admission to intensive care and responses to 5 hypothetical clinical scenarios. Results. The number of intensivists who considered the prognosis of the acute disease and of the underlying disease to be most important was 87.9% (n=74). Most (71.6%; n=63) intensivists cited availability of an intensive care unit (ICU) bed as influencing the decision to admit. Intensivists comprising 26.8% (n=22) of the total group rated as probably important or least important the ‘resources available’; ‘bed used to the prejudice of another patient’ was stated by 16.4% (n=14); and ‘policy of the intensive care unit’ by 17% (n=14). Nearly two-thirds (65.9%; n=58) would respect an informed refusal of treatment. A similar number would comply with a written ‘Do not resuscitate’ (DNR) order. In patients with no real chance of recovering a meaningful life, 81.6% (n=71) of intensivists would withhold sophisticated therapy (e.g. not start mechanical ventilation or dialysis etc.) and 75.9% (n=63) would withdraw sophisticated therapy (e.g. discontinue mechanical ventilation, dialysis etc.). Conclusions. A combination of factors was identified as influencing the decision to admit patients to intensive care. Prognosis and disease status were identified as the main factors influencing admission. Patients with HIV/AIDS were not discriminated against in admission to intensive care

Understanding the profile of tuberculosis and Human Immunodeficiency Virus Coinfection : insights from expanded HIV surveillance at a tuberculosis facility in Durban, South Africa.

CAPRISA, 2014.Expanded HIV surveillance in TB patients forms part of the World Health Organization framework for strategic collaborative activity. Surveillance helps understand the epidemiology of the local dual epidemic and enables design of a tailored response to these challenges. Methods. We conducted an observational, cross-sectional study of anonymous unlinked HIV testing for 741 consecutive TB suspects attending an urban TB facility during a seven-week period in 2008. Results. A total of 512 patients were found to have TB. The mean age was 35.7 years, and 63% were male. The prevalence of HIV was 72.2% (95% CI: 68.2–75.9) in all TB cases, 69.8% (95% CI: 65.3–74.2) in pulmonary tuberculosis (PTB), 81.6% (95% CI: 72.9–90.3) in extrapulmonary disease, and 66.8% (95% CI: 60.7–72.9) in those without TB disease. HIV prevalence in TB patients was higher in females than males and in younger age groups (18–29 years). The sex ratio of PTB patients correlated with the sex ratio of the prevalence of HIV in the respective age groups (P < 0.05). Conclusion. The use of a rapid HIV test performed on sputum anonymously provides an opportunity for HIV surveillance in this high-burdened setting, which has the potential to lend valuable insight into the coepidemics

Determinants of optimal adherence over time to antiretroviral therapy amongst HIV positive adults in South Africa : a longitudinal study.

Highly active antiretroviral therapy (HAART) requires strict adherence to achieve optimal clinical and survival benefits. A study was done to explore the factors affecting HAART adherence among HIV positive adults by reviewing routinely collected patient information in the Centre for the AIDS Programme of Research in South Africa’s (CAPRISA) AIDS Treatment Programme. Records of 688 patients enrolled between 2004 and 2006 were analysed. Patients were considered adherent if they had taken at least 95% of their prescribed drugs. Generalized estimating equations were used to analyse the data. The results showed that HAART adherence increased over time, however, the rate of increase differed by some of the socio-demographic and behavioural characteristics of the patients. For instance, HAART adherence increased in both urban and rural treatment sites over time, but the rate of increase was higher in the rural site. This helped identify sub-populations, such as the urban population, that required ongoing adherence counseling