title: Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa.
abstract: BACKGROUND
  Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital.
  
  
  METHODS
  This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint.
  
  
  RESULTS
  Of 99 patients (median CD4 count 72 cells/mm³), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002).
  
  
  CONCLUSIONS
  Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute.
authors.affiliation: *Madwaleni Hospital, Elliotdale, South Africa; †Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; ‡Department of Medicine, University of Cape Town, Cape Town, South Africa; §MRC National Institute for Medical Research, London, United Kingdom; ‖Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, United Kingdom; ¶Department of Statistics, Texas A&M University, College Station, TX; #National Science Foundation, Arlington, VA; **Infectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX; and ††Department of Medicine, Imperial College, London, United Kingdom.
authors.forename: Sathyavani
authors.initials: S
authors.lastname: Subbarao
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Clare L
authors.initials: CL
authors.lastname: van Halsema
authors.forename: Suhasini Subba
authors.initials: SS
authors.lastname: Rao
authors.forename: Tom
authors.initials: T
authors.lastname: Boyles
authors.forename: Netanya S
authors.initials: NS
authors.lastname: Utay
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
mesh_terms: D000293:Adolescent; D000328:Adult; D018988:Bacterial Translocation; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000401:mortality*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011446:Prospective Studies; D012424:Rural Population; D013019:South Africa / Q000453:epidemiology; D016019:Survival Analysis; D014376:Tuberculosis / Q000150:complications* / Q000401:mortality*; D055815:Young Adult
chemical_list: D019344:Lactic Acid