Jantjie Taljaard

Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis.

OBJECTIVES Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are endemic in Africa. However, hepatitis co-infection rates among HIV-infected individuals remain controversial. The aim of this review was to determine the prevalence of HBV and HCV in HIV-infected patients in sub-Saharan Africa and to analyze whether HIV is associated with a higher HBV/HCV prevalence in that region. DESIGN AND METHODS We performed a systematic review and meta-analysis. Studies reporting HBV and HCV prevalence data amongst HIV-infected patients in sub-Saharan Africa were included. Weighted means and medians across studies were calculated. Studies including an HIV-negative control group were used for meta-analysis. Risk ratios (RRs) were calculated using a random effects model. RESULTS Sixty studies were included. Among HIV-infected individuals, mean HBsAg and anti-HCV prevalence rates were 15% and 7%, respectively. RRs for a positive HBsAg and a positive anti-HCV were 1.40 (95% confidence interval (CI) 1.16-1.69) and 1.60 (95% CI 1.05-2.45) for HIV-infected, as compared to HIV-uninfected, patients. CONCLUSIONS Many HIV-positive individuals in sub-Saharan Africa are HBV or HCV co-infected. HIV is associated with a higher prevalence of both HBV and HCV in this region. However, this association is less evident than that observed in Western countries and varies between studies.

High mortality from respiratory failure secondary to swine-origin influenza a (h1n1) in south africa

BACKGROUND The novel influenza A (H1N1) pandemic affected South Africa late during the 2009 Southern hemisphere winter and placed an extra burden on a health care system already dealing with a high prevalence of chronic lung diseases and human immunodeficiency virus (HIV) infection. AIM The aim of this study was to describe the epidemiological characteristics, clinical features, management and outcomes of patients with confirmed influenza A (H1N1) infection complicated by respiratory failure. METHODS We included all adult patients with confirmed influenza A (H1N1) infection that were referred to the medical intensive care unit of a large academic hospital in Cape Town for ventilatory support in this prospective observational study. RESULTS A total of 19 patients (39.5 +/- 14.8 years) needed ventilatory support over a 6-week period. Of these, 15 were female and 16 had identifiable risk factors for severe disease, including pregnancy (n = 6), type 2 diabetes mellitus (n = 6), obesity (n = 4), HIV infection (n = 3), immunosuppressive therapy (n = 3) and active pulmonary tuberculosis (n = 2). The most frequent complications were acute renal failure (n = 13), acute respiratory distress syndrome (n = 12) and ventilator associated pneumonia (n = 10). Thirteen patients died (mortality: 68.4%). Fatal cases were significantly associated with an APACHE II score >or=20 (P = 0.034), but not with a P(a)O(2)/F(I)O(2) <200 (P = 0.085) and a chest radiograph score >or=12 (P = 0.134). CONCLUSION The majority of patients with respiratory failure secondary to influenza A (H1N1) infection were young females and had an underlying risk factor for severe disease. The condition had a high mortality, particularly amongst patients with an APACHE II score >or=20.

Clinical Characteristics, Diagnosis, Management, and Outcomes of Disseminated Emmonsiosis: A Retrospective Case Series

BACKGROUND We describe the geographic distribution, clinical characteristics, and management of patients with disease caused by Emmonsia sp., a novel dimorphic fungal pathogen recently described in South Africa. METHODS We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015. RESULTS Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/µL [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed. CONCLUSIONS Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients.

Evaluation of Paradoxical TB-Associated IRIS With the Use of Standardized Case Definitions For Resource-Limited Settings

Objective: Standardized case definitions have recently been proposed by the International Network for the Study of HIV-associated immune reconstitution inflammatory syndrome (INSHI; [IRIS]) for use in resource-limited settings. We evaluated paradoxical tuberculosis (TB)-associated IRIS in a large cohort from a TB endemic setting with the use of these case definitions. Design: A retrospective cohort study. Method: We reviewed records from 1250 South African patients who initiated antiretroviral therapy (ART) over a 5-year period. Results: A total of 333 (27%) of the patients in the cohort had prevalent TB at the initiation of ART. Of 54 possible paradoxical TB-associated IRIS cases, 35 fulfilled the INSHI case definitions (11% of TB cases). Conclusions: INSHI-standardized case definitions were used successfully in identifying paradoxical TB-associated IRIS in this cohort and resulted in a similar proportion of TB IRIS cases (11%) as that reported in previous studies from resource-limited settings (8%-13%). This case definition should be evaluated prospectively.

Prolonged deferral of antiretroviral therapy in the SAPIT trial: did we need a clinical trial to tell us that this would increase mortality?

Tuberculosis is the major cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.

Potential for nosocomial transmission of multidrug-resistant (MDR) tuberculosis in a South African tertiary hospital

BACKGROUND Tuberculosis (TB) is a major health problem in the Western Cape, with an incidence exceeding 900 per 100 000 people. Nosocomial transmission of TB, and particularly drug-resistant TB, is a potential risk that may be undetected. Rapid diagnosis and rapid institution of effective anti-TB treatment, combined with appropriate infection control measures, are essential to prevent nosocomial transmission of TB. To estimate the potential for nosocomial transmission, we aimed to determine the in-hospital delays in diagnosis and treatment of patients with multidrug-resistant (MDR)-TB at a tertiary care hospital. METHODS A descriptive study, based on retrospective review of patient records and laboratory data, including all adult patients (>13 years) where TB culture and susceptibility testing confirmed MDR- TB on specimens submitted to Tygerberg Hospitals National Health Laboratory Service (NHLS) laboratory in 2007. RESULTS Thirty-one patients with MDR-TB were identified. The median laboratory turnaround time (TAT) from collection of specimen to confirmation of MDR-TB was 40 days, while the median time from the time of first presentation at Tygerberg Hospital to institution of MDR treatment was 44 days. Twenty patients were considered infectious during their hospital stay, generating 345 inpatient infectious days. CONCLUSIONS The study suggests that there is an ongoing substantial risk for nosocomial transmission of MDR-TB at Tygerberg Hospital. We propose improvements, including the use of rapid drug susceptibility testing. The consistent application of infection control measures to prevent nosocomial spread of TB, including MDR-TB, remains vital.

AIDS-Related Endemic Mycoses in Western Cape, South Africa, and Clinical Mimics: A Cross-Sectional Study of Adults With Advanced HIV and Recent-Onset, Widespread Skin Lesions

Abstract Background Skin lesions are common in advanced HIV infection and are sometimes caused by serious diseases like systemic mycoses (SM). AIDS-related SM endemic to Western Cape, South Africa, include emergomycosis (formerly disseminated emmonsiosis), histoplasmosis, and sporotrichosis. We previously reported that 95% of patients with AIDS-related emergomycosis had skin lesions, although these were frequently overlooked or misdiagnosed clinically. Prospective studies are needed to characterize skin lesions of SM in South Africa and to help distinguish these from common HIV-related dermatoses. Methods We prospectively enrolled HIV-infected adult patients living in Western Cape, South Africa, with CD4 counts ≤100 cells/μL and widespread skin lesions present ≤6 months that were deemed clinically compatible with SM. We obtained skin biopsies for histopathology and fungal culture and collected epidemiological and clinical data. Results Of 34 patients enrolled and in whom a diagnosis could be made, 25 had proven SM: 14 had emergomycosis, and 3 each had histoplasmosis and sporotrichosis; for 5 additional patients, the fungal species could not be identified. Antiretroviral therapy (ART) had been initiated in the preceding 4 weeks for 11/25 (44%) patients with SM (vs no patients without SM). Plaques and scale crust occurred more frequently in patients with SM (96% vs 25%, P = .0002; and 67% vs 13%, P = .01, respectively). Conclusions Recent ART initiation and presence of plaques or scale crust should make clinicians consider SM in patients with advanced HIV infection in this geographic area. Clinical overlap between SM and other dermatoses makes early skin biopsy critical for timely diagnosis and treatment.

Cutaneous Mycobacterium kansasii infection in a patient with AIDS post initiation of antiretroviral therapy

The HIV pandemic has resulted in unique clinical presentations in patients, and their diagnosis and management pose challenges to physicians in the developing world. Due to limited resources and difficulties in laboratory diagnosis, most physicians treat according to the most likely etiological agent that might be causing the disease. In South Africa, when acid-fast bacilli are detected, anti-tuberculous treatment is commenced. However, it must be realized that not all acid-fast bacilli are Mycobacterium tuberculosis, and that there are nontuberculous mycobacteria that can cause infections. Clinicians should work closely with the medical microbiologist when unique cases arise to ensure optimal microbial detection, identification, and patient management. This paper describes a very rare case of self-resolving cutaneous Mycobacterium kansasii infection following the initiation of antiretroviral therapy and potentially associated with immune reconstitution inflammatory syndrome.

Management of Adult Active Tuberculosis Disease in Era of HIV Pandemic, Current Practices and Future Perspectives

The global impact of the HIV epidemic on the prevention and management of tuberculosis has resulted in added levels of complexity for physicians and other health- care workers caring for these patients. In addition to the usual difficulties associated with drug toxicities and regimen adherence, the concomitant treatment of HIV and tuberculosis is complicated by drug interactions between antiretroviral agents and the antituberculous containing rifampin-based regimens, and the frequent occurrence of the tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). Currently, the best antitubercular regimens include a rifamycin, usually rifampin, because of the high cost of rifabutin. Two nucleosides combined with efavirenz is the best antiretroviral alternative for patients who are receiving rifampin. Issues regarding the duration of anti-tubercular therapy before starting antiretroviral therapy (ART) need further clarification. The standard recommendation of waiting 8 weeks before starting ART is accompanied by significant morbidity and mortality, and has recently been challenged by data suggesting that 2 weeks is adequate. Ongoing studies looking at concomitant anti-inflammatory therapies for prevention of TB-IRIS may allow initiation of therapy for both diseases nearly simultaneously. The increase rates of M(X)DR tuberculosis isolates is not only testimony to the technical inability of the currently available tools for diagnosis and treatment of resistant TB but also the massive structural, social, political and economical constraints that most affected countries face. There is a critical need for novel antituberculous agents, but before they are made freely available, widespread investments in tuberculosis control programs are needed in order to ensure the application of practical and cost-effective community-based directly observed therapy and thus to protect these novel agents from the same fate as the current first line agents.

Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens.

Objective:To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy. Methods:A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3 ml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60 ml/min per 1.73 m2. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD. Results:Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6–98) weeks. For every 10-year increase in age and 10 ml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratio = 1.70, 95% confidence interval (CI) 1.36–2.13] and 57% (adjusted odds ratio = 1.57, 95% CI 1.38–1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratio = 1.90, 95% CI: 1.10–3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratio = 3.96, 95% CI: 1.06–14.74). Conclusion:About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting.