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High Early Mortality among HIV-infected Patients with Extensively Drug-resistant or Multidrug-resistant TB in Rural South Africa
Neel Gandhi*1, S Shah1, J Andrews2, V Vella3, A Moll4, M Scott5, P Babaria6, C Marra3, U Lalloo7, G Friedland6, and Tugela Ferry Care and Res (TF CaRes) Collaboration
1Albert Einstein Coll of Med and Montefiore Med Ctr, Bronx, NY, US; 2San Francisco Gen Hosp, Univ of California, San Francisco, US; 3KwaZulu-Natal Dept of Hlth, South Africa; 4Philanjalo and Church of Scotland Hosp, Tugela Ferry, South Africa; 5Harvard Med Sch, Boston, MA, US; 6Yale Univ Sch of Med, New Haven, CT, US; and 7Univ of KwaZulu-Natal, Durban, South Africa
Background: South Africa is experiencing an epidemic of multidrug-resistant
(MDR) and extensively drug-resistant tuberculosis (XDR TB) among HIV-infected
patients. Although MDR and XDR TB are treatable, reports of successful
treatment have been from low HIV-prevalence settings. In our initial report of 53
XDR TB cases in South Africa, 98% died, most within 30 days of sputum
collection, before second-line TB or ART could be initiated. We now further
characterize mortality of both MDR and XDR TB in this setting with high HIV
co-infection.
Methods: We performed a retrospective observational study
of MDR and XDR TB from rural Tugela Ferry, South Africa. We identified cases
diagnosed from 2005 to 2007 from the local TB register, examined vital status
as of June 2008 and abstracted demographics and HIV status in a subset of
patients with available medical records. We determined survival from the date
of sputum collection and further analyzed it by calendar year of diagnosis and
drug-susceptibility patterns.
Results: Among 654 cases identified, 272 (41%) were MDR TB
alone, while 382 (59%) met criteria for XDR TB. MDR and XDR TB groups were
similar in gender (48% and 59% women, respectively), median age (34 and 34.5
years), HIV co-infection (90% and 97%) and median CD4 count (144 and 123
cells/mm3). One-year mortality remained extremely high for XDR TB
patients (82%), but was also exceedingly high (69%) for MDR TB patients: 40%
of MDR and 54% of XDR TB cases died within the first 30 days. Among MDR TB
patients, 1-year mortality improved from 87% in 2005 to 45% in 2007 (p =
0.009); 30-day mortality remained high, but decreased as well (57% in 2005, 37%
2006, 32% 2007); 1-year and 30-day mortality among XDR TB patients did not
change significantly from 2005 to 2007 (p = 0.12); 1-year and 30-day
mortality were proportional to the number of resistant drugs (p <0.001);
90% and 56%, respectively, with 6 resistant drugs; 75% and 47% with 4 to 5
resistant drugs, 65% and 40% with 3 resistant drugs, and 61% and 34% with 2 resistant
drugs.
Conclusions: Mortality in both MDR and XDR TB patients in a
high HIV prevalence setting in South Africa is extraordinarily high,
particularly in the first 30 days after sputum collection. Efforts to improve
this mortality must focus on early identification and initiation of second-line
TB therapy and ART. Diagnostic tests that identify MDR and XDR TB in HIV-co-infected
patients within days of sputum collection must be developed.
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