title: The prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study.
abstract: BACKGROUND
  Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis.
  
  
  RESULTS
  We studied a representative sample of 240 adult inpatients (aged 20-45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli.
  
  
  CONCLUSIONS
  Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting. Please see later in the article for the Editors' Summary.
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
authors.forename: Megan
authors.initials: M
authors.lastname: Murray
authors.forename: Kristina
authors.initials: K
authors.lastname: Wallengren
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: Alvarez
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Samuel
authors.forename: Douglas
authors.initials: D
authors.lastname: Wilson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001344:Autopsy; D024881:Drug Resistance, Bacterial; D005260:Female; D006678:HIV; D006679:HIV Seropositivity / Q000150:complications / Q000401:mortality* / Q000821:virology; D006761:Hospitals; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D015995:Prevalence; D012293:Rifampin / Q000627:therapeutic use; D013019:South Africa / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin