Human Immunodeficiency Virus-Associated Tuberculosis

摘要: The human immunodeficiency virus (HIV), causing the acquired syndrome (AIDS), was first reported thirty years ago. UNAIDS published latest statistics on global HIV and AIDS epidemic in November 2010 estimated that 2009 there were 33.3 million people living with HIV/AIDS worldwide (Worldwide statistics, http://www.avert.org/worldstats.htm). While annual number of new infections has steadily declined, receiving antiretroviral therapy increased, pandemic so far caused death nearly 30 from AIDS-related causes. sub-Saharan African region carries greatest burden this pandemic, 22.5 adults children 2009. In South Africa alone, are an 5.6 HIV-infected people, more than any other country, almost one three women aged 25–29, over a quarter men 30–34, (HIV Africa, http://www.avert.org/aidssouthafrica.htm). Tuberculosis (TB) is important public health problem representing most frequent opportunistic infection infected persons globally. 1993, World Health Organization (WHO) declared TB emergency, when 7-8 cases 1.3–1.6 deaths occurred each year. Today, remains leading cause low- middle-income countries, WHO report control indicates 8.8 incident 1.4 (http://www.who.int/tb/en/). risk factor for acquiring Mycobacterium tuberculosis (M.tb) developing TB. devastating association between means up to 1.2 (12–14%) amongst 2010, 0.35 people. proportion HIV-M.tb-coinfected highest Region accounting overall 82% among HIV. The increased during all stages about 10% lifetime (in HIV-uninfected individuals) as high 30% per annum patients advanced [1, 2]. These circumstances define analysis immune response context pressing research priority. This special issue therefore devoted HIV-associated It comprises review papers six papers. paper general overview focuses intersecting epidemics countries both infections. Among many challenges, authors discuss diagnosis patients, difficulties posed by drug interactions treating WHO-recommended interventions collectively known collaborative TB/HIV activities, such testing integration services, provision isoniazid preventive (IPT), control, minimizing airborne transmission, managing recurrent crucial question initiate combined treatment (cART) relation treatment, balancing reconstitution inflammatory (IRIS) associated early cART mortality delaying discussed second paper. TB-associated IRIS (TB-IRIS) complication cART, reflecting fact responses may contribute protection pathology. Two forms TB-IRIS recognized: (1) paradoxical, occurs who established before manifest or symptoms clinical features after initiation cART; (2) unmasking TB-IRIS, been defined not started, but present active within 3 months starting show heightened intensity manifestations marked component [3, 4]. conclude compelling evidence should be delayed HIV/TB-coinfected individuals. recommends 2 8 weeks subsequent individuals CD4 counts <200/μL. Three publications (published since paper) trials [5–7] describe survival benefits AIDS-free resulting start therapy, particularly far-advanced immunosuppression (CD4 <50/μL), while indicating higher earlier later initiation. benefit despite those started count <50/μL, itself can (case fatality rate 3.2% recent meta-analysis) [8]. Although guidelines have developed resource-limited settings (3), need detect appropriately treat timely fashion outside controlled study environment major challenge requires further exploration. The third discusses concept “latent infection” Immunological tests, tuberculin skin test (TST) interferon-gamma release assays (IGRAs) provide M.tb sensitization one-third population. Thus, two billion latently no live progression overt disease, coinfection traditional paradigm distinguishes latent distinct compartmentalized states appears too simplistic. Recently, it suggested clinically actually represents extreme spectrum (of responses, mycobacterial metabolic activity, bacillary numbers) runs elimination bacilli subclinical symptomatic disease [9, 10]. propose impact might better conceptualized shift towards poor greater organism load, subsequently model well implications epidemic. The studies follow reviews thematic order. fourth describes predictors tertiary care center Brazil; fifth sixth paradoxical consequences dual Northern India Uganda their predictors, followed approaches diagnosing using existing immunodiagnostic (IGRA) proposed methods (antigen 85 reactivity). final genetic factors (HLA-B∗57) gender influencing incidence Bangalore, India. This shows progress being made unravelling protective pathological mechanisms M.tb-coinfected persons, treatment. Indeed, its 2011 presents encouraging trends globally declining rates at time broadening therapeutic options, vaccine candidates phases II III trials, development fast precise PCR-based diagnostic tools. However, obstacles poverty availability access pandemics, same attention also needed diabetes, cigarette smoking, air pollution endemic areas. Bold goals “Zero Deaths” [11], disease-specific funding programs, diagnostics, vaccines, biomedical presented here will sustain accomplishments decrease health. Katalin A. Wilkinson Stephan Schwander M. Estee Torok Graeme Meintjes