• 1.

    World Health Organization, 2015. World Health Organization Country Fact Sheet, Tuberculosis, Tanzania, 2015. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/tb/country/data/profiles/en/. Accessed March 31, 2015.

    • Search Google Scholar
    • Export Citation
  • 2.

    Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, Iseman MD, Cook JL, Curran-Everett D, 2004. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis 38: 15381544.

    • Search Google Scholar
    • Export Citation
  • 3.

    Bratviet M, Moen BE, Mashalla YJS, Maalim H, 2003. Dust exposure during small-scale mining in Tanzania: a pilot study. Ann Occup Hyg 47: 235240.

    • Search Google Scholar
    • Export Citation
  • 4.

    Rees D, Murrary J, 2007. Silica, silicosis and tuberculosis. Int J Tuberc Lung Dis 11: 474484.

  • 5.

    United Republic of Tanzania: Ministry of Health and Social Welfare (MoH and SW), 2006. National TB and Leprosy Program, Clinical Guideline for TB Management. Dar es Salaam, United Republic of Tanzania: MoH and SW.

    • Search Google Scholar
    • Export Citation
  • 6.

    Mpagama S, Heysell SK, Ndusilo ND, Kumburu HH, Lekule IA, Kisonga RM, Gratz J, Boeree MJ, Houpt ER, Kibiki GS, 2013. Diagnosis and interim treatment outcomes from the first cohort of multidrug-resistant tuberculosis patients in Tanzania. PLoS One 8: e62034.

    • Search Google Scholar
    • Export Citation
  • 7.

    Burton NT, Forson A, Lurie MN, Kudzawa S, Kwarteng E, Kwara A, 2011. Factors associated with mortality and default among patients with tuberculosis attending a teaching hospital clinic in Accra, Ghana. Trans R Soc Trop Med Hyg 105: 675682.

    • Search Google Scholar
    • Export Citation
  • 8.

    Heysell SK, Mtabho C, Mpagama S, Mwaigwisya S, Ndusilo N, Pholwat S, Gratz J, Aarnouste R, Kibiki GS, Houpt ER, 2011. A plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother 55: 58195825.

    • Search Google Scholar
    • Export Citation
  • 9.

    Tostmann A, Mtabho CM, Semvua HH, van den Boogaard J, Kibiki GS, Boeree MJ, Aarnoutse RE, 2013. Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients. Antimicrob Agents Chemother 57: 32083213.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hoa NB, Lauritsen JM, Rieder HL, 2013. Changes in body weight and tuberculosis treatment outcome in Viet Nam. Int J Tuberc Lung Dis 17: 6166.

    • Search Google Scholar
    • Export Citation
  • 11.

    Barroso EC, Pinheiro VGF, Facanha MC, Carvalho MRD, Moura ME, Campelo CL, Peloquin CA, Guerrant RL, Lima AAM, 2009. Serum concentrations of rifampin, isoniazid and intestinal absorption, permeability in patients with multidrug resistant tuberculosis. Am J Trop Med Hyg 81: 322329.

    • Search Google Scholar
    • Export Citation
  • 12.

    van Ingen J, Aarnoutse RE, Donald PR, Diacon AH, Dawson R, van Balen GP, Gillespie SH, Boeree MJ, 2011. Why do we use 600 mg of rifampicin in tuberculosis treatment? Clin Infect Dis 52: e194e199.

    • Search Google Scholar
    • Export Citation
  • 13.

    Reynolds J, Heysell SK, 2014. Understanding pharmacokinetics to improve tuberculosis treatment outcome. Expert Opin Drug Metab Toxicol 10: 813823.

    • Search Google Scholar
    • Export Citation
  • 14.

    Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, Burke R, Horton CL, Iga B, Wald A, Reynolds SJ, Mayanja-Kizza H, Scheld WM, 2012. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study. Crit Care Med 40: 20502058.

    • Search Google Scholar
    • Export Citation
  • 15.

    Heysell SK, Thomas TA, Moll AP, Gandhi NR, Eksteen FJ, Babaria P, Roux L, Coovadia Y, Lallo U, Friedland G, Shah NS, 2010. Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa. BMC Infect Dis 10: 344.

    • Search Google Scholar
    • Export Citation
  • 16.

    TB CARE I, 2014. International Standards for Tuberculosis Care, 3rd edition. The Hague, The Netherlands: TB CARE I.

  • 17.

    Srivastava S, Pasipanodya JG, Meek C, Leff R, Gumbo T, 2011. Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability. J Infect Dis 204: 19511959.

    • Search Google Scholar
    • Export Citation
  • 18.

    Stuckler D, Basu S, McKee M, Lurie M, 2011. Mining and risk of tuberculosis in sub-Saharan Africa. Am J Public Health 101: 524530.

  • 19.

    Hnizdo E, Murray J, 1998. Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners. Occup Environ Med 55: 496502.

    • Search Google Scholar
    • Export Citation
  • 20.

    Churchyard G, Kleinschmidt I, Corbett EL, Murray J, Smit J, De Cock KM, 2000. Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis. Int J Tuberc Lung Dis 4: 705712.

    • Search Google Scholar
    • Export Citation
  • 21.

    Basu S, Stuckler D, McKee M, 2011. Addressing institutional amplifiers in the dynamics and control of tuberculosis epidemics. Am J Trop Med Hyg 84: 3037.

    • Search Google Scholar
    • Export Citation

 

 

 

 

The Influence of Mining and Human Immunodeficiency Virus Infection Among Patients Admitted for Retreatment of Tuberculosis in Northern Tanzania

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  • Kibong'oto Infectious Disease Hospital, Kilimanjaro, United Republic of Tanzania; Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia

In tuberculosis (TB)–prevalent settings, patients admitted for retreatment of TB may account for a high burden of poor treatment outcome. We performed a retrospective cohort study to characterize retreatment patients and outcomes at a TB referral hospital in northern Tanzania. From 2009 to 2013, 185 patients began a retreatment regimen, the majority for relapse after prior treatment completion. Men accounted for an unexpected majority (88%), 36 (20%) were human immunodeficiency virus (HIV) infected and for 45 (24%) mining was their primary occupation. A poor outcome (death, default, or persistent smear positivity after 7 months of treatment) was found in 37 (23%). HIV infection was the only significant predictor of poor outcome (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [CI] = 1.07–5.83, P = 0.034). Interventions to minimize need for retreatment or improve retreatment success may be regionally specific. In our setting, community-based diagnosis and management among at-risk subpopulations such as miners and those HIV infected appear of highest yield.

In Tanzania, like many tuberculosis (TB) endemic countries, patients categorized as undergoing retreatment for TB account for proportionally the highest rates of death, treatment failure, and default among all TB patients excluding those with known drug resistance.1 The national estimate for treatment success rate in human immunodeficiency virus (HIV)–negative patients without prior treatment was 90%, but was 80% in patients with a history of TB treatment.1 Patients undergoing retreatment are often prescribed the World Health Organization (WHO) Category II regimen of extended total duration, which contains the daily intramuscular injection of streptomycin, a medication with considerable cumulative side effects including ototoxicity and vestibular toxicity that may further compromise treatment completion.2

Kibong'oto Infectious Diseases Hospital (KIDH) is a regional referral hospital for retreatment TB cases, and the national referral hospital for multidrug-resistant (MDR) TB. The Mererani region includes numerous small-scale mining operations, principally involved in the mining of the precious gemstone tanzanite. The mines are run with low-level mechanization, use roughly 8,000 transient workers, and are situated in a community of approximately 200,000 people with interdependence on the mining industry.3 The mining occupation in other TB-endemic settings has been associated with high rates of HIV coinfection, comorbid lung disease such as silicosis and risk of TB reinfection.4 Perception suggests that miners account for a considerable number of patients admitted to KIDH for retreatment and may account for a greater proportion of those with poor retreatment outcome.

We therefore sought to perform a retrospective cohort study of all patients admitted to KIDH for a retreatment regimen over the past 5 years to define the local burden of retreatment, clinical characteristics among retreatment patients, and predictors of retreatment outcome.

The hospital initiative was designed and undertaken by the KIDH administration and approval for analysis was additionally granted by the institutional review board of the University of Virginia. All charts from patients admitted to KIDH from January 1, 2009 to December 31, 2013 were screened. KIDH practice was to treat all patients with a prior history of TB with a WHO Category II regimen excluding those with known drug-resistant TB. Thus, a case was defined as “retreatment,” if prescribed a Category II regimen after having failed a prior drug susceptible TB treatment course, relapsed within 18 months after having completed treatment, or defaulted treatment but remained sputum smear positive. Patients that were treated with a WHO Category II regimen for another reason were labeled as “other,” including smear-negative patients with TB signs and symptoms that had failed an empiric course of antibacterial treatment. Specifically, the regimen was daily injectable streptomycin, oral rifampin, isoniazid, ethambutol, and pyrazinamide given for 2 months, then all oral drugs given for 1 month, followed by 5 months of rifampin and isoniazid.5 Chart review included demographics, comorbidities, HIV status, and among the HIV infected, CD4 cells/mm3 and antiretroviral use at admission. Per hospital protocol, an acid-fast bacilli (AFB) sputum smear was performed on admission for all pulmonary TB patients, again at 2 months after treatment, and monthly thereafter until 7 months after treatment. Similarly, a baseline weight (in kilograms) was recorded and repeated monthly after the second month of treatment. Although MDR-TB treatment began in Tanzania at KIDH in 2009, initially drug susceptibility testing was not routinely performed on retreatment patients given logistical constraints and specimen turnaround at the reference laboratory.6 After 2013, molecular testing with either the Xpert MTB/RIF (Cepheid, Sunnyvale, CA) or the MTBDRplus (Hain Lifescience, Nehren, Germany) has been performed onsite.

During the study period and excluding those with known MDR-TB, total 2,140 patients were admitted for TB treatment, of which 185 (8.6%) received a retreatment regimen (by year of admission: in 2009, 46 [10% of total from that year]; in 2010, 38 [9%]; in 2011, 37 [9%]; in 2012, 36 [8%]; in 2013, 28 [6%]). The majority were men (87.6%) and 36 (19.5%) were HIV infected (Table 1). Among HIV infected, the median CD4 count was 136.5 cells/mm3 (interquartile range [IQR] = 29.7–248.0), and 17 (47.2%) were on antiretrovirals at admission. Although 45 (24.3%) had documentation of mining as their primary occupation, only 3 (1.6%) were labeled as having pneumoconiosis. Unexpectedly, among miners only four (8.9%) were HIV infected, which was a smaller proportion than in the non-miners (22.9%).

Table 1

Clinical characteristics among patients admitted for retreatment, N = 185

CharacteristicResult
Age, mean years ± SD42.4 ± 12.8 (minimum 22, maximum 85)
Gender, male (% N)162 (87.6)
Baseline weight, mean kg ± SD50.9 ± 7.9 (minimum 30, maximum 79)
HIV positive (% N)36 (19.5)
CD4 count, mean cells/mm3167.4 ± 142.3 (minimum 2, maximum 658)
ART at admission (% HIV positive)17 (47.2)
Diabetes (% N)3 (1.6)
Pneumoconiosis (% N)3 (1.6)
Mining as primary occupation (% N)45 (24.3)
Known smoking (% N)*6 (3.2)
Known alcohol use (% N)*13 (7)
Current treatment episode
 Second143 (81.7)
 Third or more32 (18.3)
Reason for retreatment
 Relapse121 (65.8)
 Return after default18 (9.8)
 Failure8 (4.3)
Other37 (20.1)

ART = antiretroviral therapy; HIV = human immunodeficiency virus; SD = standard deviation.

Smoking and alcohol use were considered underreported.

Available in 175 patients.

Available in 184 patients.

Baseline sputum AFB smear microscopy found 36 patients (19.5%) were smear negative, 11 (5.9%) were scanty, 18 (9.7%) were 1+, 35 (18.9%) were 2+, 79 (42.7%) were 3+, and 6 patients had a missing result. Among patients with positive baseline sputum smear and excluding those with early death, default or transfer out of care, the median time of sputum smear conversion to negative was 2 months (IQR = 2–3 months). Time to sputum culture conversion did not vary by HIV status (Mann–Whitney U, P = 0.13).

Twenty-four patients transferred out to another facility and 161 had evaluable outcomes: 124 (77.0%) were cured/treatment complete, 21 (13.0%) died, 12 (7.5%) defaulted, and 4 (1.9%) remained smear positive (three of which were ultimately treated for MDR-TB). Hence 37 patients (23.0% of those evaluable) had a poor outcome (Table 2). Controlling for age, reason for retreatment, and baseline smear status in multivariate logistic regression analysis, HIV infection remained the only significant predictor of poor outcome (odds ratio [OR] = 2.44, 95% confidence interval [CI] = 1.04–5.73, P = 0.04). As 24 patients did not have evaluable outcomes, a modified sensitivity analysis was performed imputing all transferred patients had one of either outcome: no other additional predictor was significant but the OR for HIV infection ranged from 1.62 (imputing all transfers had poor outcome) to 2.53 (imputing all had good outcome). Interestingly, among the HIV infected, 7 (46.7%) of those on antiretrovirals at baseline had a poor outcome compared with only 5 (27.8%) that were not on antiretrovirals (P = 0.22). Yet of the patients that died, 12 (57%) were within the first 2 months of treatment, of whom seven were HIV infected with a median CD4 count of 30 cells/mm3 (IQR = 7–130) that was lower than those without early death, median CD4 count of 178 cells/mm3 (IQR = 90–248) (P = 0.09). Alternatively, among those evaluable beyond the second month of treatment, the median weight gain in patients with a favorable outcome was 4.0 kg (IQR = 1.98–5.85) compared with 2.0 kg (IQR = 0.75–3.0) in patients with poor outcome (P = 0.01).

Table 2

Predictors of retreatment outcome (N = 161)

CharacteristicCured/treatment complete (N = 124)Death/default/smear positive (N = 37)P value
Age, mean years ± SD41.9 ± 12.445.2 ± 14.80.18
Gender0.37
 Male (% N)110 (88.7%)35 (94.6%)
 Female (% N)14 (11.3%)2 (5.4%)
HIV0.04
 Negative (% N)103 (83.1%)25 (67.6%)
 Positive (% N)21 (16.9%)12 (32.4%)
Mining0.82
 No (% N)95 (76.6%)29 (78.4%)
 Yes (% N)29 (23.4%)8 (21.6%)
Baseline smear negative0.12
 No/unknown (% N)102 (82.3%)26 (70.3%)
 Yes (% N)22 (17.7%)11 (29.7%)
Reason for retreatment0.19
 Relapse/failure91 (73.4%)23 (62.2%)
 Other33 (26.6%)14 (37.8%)
Year of treatment0.58
 2009–201060 (48.4%)16 (43.2%)
 2011–201364 (51.6%)21 (56.8%)

HIV = human immunodeficiency virus; SD = standard deviation.

In summary, the majority of patients prescribed a retreatment regimen were admitted for relapse after recent TB treatment, and while nearly 25% had a history of mining as their primary occupation, miners were less likely to be HIV infected and appeared not at increased risk of poor outcome from retreatment. Nevertheless, retreatment outcomes were complicated by a considerable number of patients with death, default, or treatment failure as manifested by persistent sputum smear positivity. Similar to other cohorts from sub-Saharan Africa, HIV infection remained the strongest predictor of poor outcome,7 and patients with the lowest CD4 count on admission frequently suffered from early inpatient death.

Relapse of TB can occur for a number of reasons including suboptimal initial treatment that fails to eradicate the bulk of the infecting mycobacterial population, amplified drug resistance of residual bacilli or host factors that compromise the immune response. Previously we have found plasma drug concentrations of isoniazid and rifampin to be below the expected range in patients treated for pulmonary TB at KIDH.8,9 Such findings may explain why the degree of weight gain as a marker of malabsorption appeared an important predictor of cure/treatment completion as similarly found in other cohorts,10 and calls for more specific study of weight trajectory and its association with nutrient and medication malabsorption.11

Furthermore, empiric dose adjustment or therapeutic drug monitoring of anti-TB drugs may prevent early death or further relapse and we believe warrants controlled study in our setting.12 Such an approach may be particularly important for the HIV infected patients presenting with significant immunosuppression (as manifest by low CD4 count) that were frequently observed to suffer early death in this cohort.13 Other HIV-prevalent settings have found early TB death in the form of sepsis and/or mycobacteremia,14,15 and have suggested that more aggressive anti-TB management should be trialed. Although it was common practice to prescribe antiretrovirals between 2 weeks and 2 months after TB treatment initiation in the antiretroviral naive per international consensus recommendations,16 four of the seven patients with early death were on antiretrovirals prior to admission. As the duration of antiretroviral therapy was not obtained, the contribution of an unmasking immune reconstitution inflammatory syndrome (IRIS) could not be assessed.

As routine culture, susceptibility testing, and Mycobacterium tuberculosis genotyping were not performed on patients initially admitted for retreatment, patients may have been misclassified as relapsed when instead they had drug-resistant TB, reinfected with a new M. tuberculosis strain or non-TB mycobacteria. In a similarly treatment experienced population referred to KIDH for MDR-TB treatment, non-TB mycobacteria were found in ∼5% of patients.6 Indeed, the patients that remained persistently smear positive in this current retreatment cohort and whose sputa were ultimately cultured and found to have MDR-TB may have already had amplified drug resistance on admission for retreatment.13 Our findings emphasize the importance of rapid drug susceptibility testing in retreatment patients and caution against the reliance on sputum smear conversion as a proxy for effective treatment.

As patients with mining as their primary occupation accounted for nearly 25% of all those admitted for retreatment, we believe this represents an important subpopulation in our setting for increased community-based interventions.17 Similarly, although gender did not predict poor outcome, nearly 90% of all patients admitted for retreatment were men, a far larger proportion of the typical 60–65% men in the general TB population at KIDH, and raises concern about gender-based behaviors or occupations that may predispose to relapse or reinfection. For example, the small-scale mines of tanzanite in Mererani are worked largely by young men transiently migrating from other parts of Tanzania or neighboring countries in east Africa. Such workers suffer from poor health access, lack of knowledge of the local medical systems, and fear that declaration of illness may risk losing their job. Aside from the environmental conditions inside the mines themselves with silica dust exposure and poorly ventilated areas leading to increased TB transmission,18,19 as has been observed elsewhere, mining sites such as Mererani may serve as a high burden center for increasing TB transmission to other lower burden settings as the infected worker returns home.20,21

There are limitations to this study inherent in the retrospective design. For instance, although HIV status was reported in all TB patients per hospital protocol, chart review undoubtedly limited the reporting of such conditions as pneumoconiosis and tobacco smoking that were dependent on physician documentation and patient recall. Similarly, the occupation reflected the patient's current employment, and thus a prior history of mining may have been underreported, and could account for the lack of difference in retreatment outcome between miners and “non-miners.” Nonetheless, these findings highlight the need for TB control strategies that emphasize community-based interventions at high burden settings, such as mining sites, and enhance treatment methods to minimize relapse in at-risk patients and among those ultimately admitted with relapse, to assure retreatment success.

  • 1.

    World Health Organization, 2015. World Health Organization Country Fact Sheet, Tuberculosis, Tanzania, 2015. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/tb/country/data/profiles/en/. Accessed March 31, 2015.

    • Search Google Scholar
    • Export Citation
  • 2.

    Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, Iseman MD, Cook JL, Curran-Everett D, 2004. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis 38: 15381544.

    • Search Google Scholar
    • Export Citation
  • 3.

    Bratviet M, Moen BE, Mashalla YJS, Maalim H, 2003. Dust exposure during small-scale mining in Tanzania: a pilot study. Ann Occup Hyg 47: 235240.

    • Search Google Scholar
    • Export Citation
  • 4.

    Rees D, Murrary J, 2007. Silica, silicosis and tuberculosis. Int J Tuberc Lung Dis 11: 474484.

  • 5.

    United Republic of Tanzania: Ministry of Health and Social Welfare (MoH and SW), 2006. National TB and Leprosy Program, Clinical Guideline for TB Management. Dar es Salaam, United Republic of Tanzania: MoH and SW.

    • Search Google Scholar
    • Export Citation
  • 6.

    Mpagama S, Heysell SK, Ndusilo ND, Kumburu HH, Lekule IA, Kisonga RM, Gratz J, Boeree MJ, Houpt ER, Kibiki GS, 2013. Diagnosis and interim treatment outcomes from the first cohort of multidrug-resistant tuberculosis patients in Tanzania. PLoS One 8: e62034.

    • Search Google Scholar
    • Export Citation
  • 7.

    Burton NT, Forson A, Lurie MN, Kudzawa S, Kwarteng E, Kwara A, 2011. Factors associated with mortality and default among patients with tuberculosis attending a teaching hospital clinic in Accra, Ghana. Trans R Soc Trop Med Hyg 105: 675682.

    • Search Google Scholar
    • Export Citation
  • 8.

    Heysell SK, Mtabho C, Mpagama S, Mwaigwisya S, Ndusilo N, Pholwat S, Gratz J, Aarnouste R, Kibiki GS, Houpt ER, 2011. A plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother 55: 58195825.

    • Search Google Scholar
    • Export Citation
  • 9.

    Tostmann A, Mtabho CM, Semvua HH, van den Boogaard J, Kibiki GS, Boeree MJ, Aarnoutse RE, 2013. Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients. Antimicrob Agents Chemother 57: 32083213.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hoa NB, Lauritsen JM, Rieder HL, 2013. Changes in body weight and tuberculosis treatment outcome in Viet Nam. Int J Tuberc Lung Dis 17: 6166.

    • Search Google Scholar
    • Export Citation
  • 11.

    Barroso EC, Pinheiro VGF, Facanha MC, Carvalho MRD, Moura ME, Campelo CL, Peloquin CA, Guerrant RL, Lima AAM, 2009. Serum concentrations of rifampin, isoniazid and intestinal absorption, permeability in patients with multidrug resistant tuberculosis. Am J Trop Med Hyg 81: 322329.

    • Search Google Scholar
    • Export Citation
  • 12.

    van Ingen J, Aarnoutse RE, Donald PR, Diacon AH, Dawson R, van Balen GP, Gillespie SH, Boeree MJ, 2011. Why do we use 600 mg of rifampicin in tuberculosis treatment? Clin Infect Dis 52: e194e199.

    • Search Google Scholar
    • Export Citation
  • 13.

    Reynolds J, Heysell SK, 2014. Understanding pharmacokinetics to improve tuberculosis treatment outcome. Expert Opin Drug Metab Toxicol 10: 813823.

    • Search Google Scholar
    • Export Citation
  • 14.

    Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, Burke R, Horton CL, Iga B, Wald A, Reynolds SJ, Mayanja-Kizza H, Scheld WM, 2012. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study. Crit Care Med 40: 20502058.

    • Search Google Scholar
    • Export Citation
  • 15.

    Heysell SK, Thomas TA, Moll AP, Gandhi NR, Eksteen FJ, Babaria P, Roux L, Coovadia Y, Lallo U, Friedland G, Shah NS, 2010. Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa. BMC Infect Dis 10: 344.

    • Search Google Scholar
    • Export Citation
  • 16.

    TB CARE I, 2014. International Standards for Tuberculosis Care, 3rd edition. The Hague, The Netherlands: TB CARE I.

  • 17.

    Srivastava S, Pasipanodya JG, Meek C, Leff R, Gumbo T, 2011. Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability. J Infect Dis 204: 19511959.

    • Search Google Scholar
    • Export Citation
  • 18.

    Stuckler D, Basu S, McKee M, Lurie M, 2011. Mining and risk of tuberculosis in sub-Saharan Africa. Am J Public Health 101: 524530.

  • 19.

    Hnizdo E, Murray J, 1998. Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners. Occup Environ Med 55: 496502.

    • Search Google Scholar
    • Export Citation
  • 20.

    Churchyard G, Kleinschmidt I, Corbett EL, Murray J, Smit J, De Cock KM, 2000. Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis. Int J Tuberc Lung Dis 4: 705712.

    • Search Google Scholar
    • Export Citation
  • 21.

    Basu S, Stuckler D, McKee M, 2011. Addressing institutional amplifiers in the dynamics and control of tuberculosis epidemics. Am J Trop Med Hyg 84: 3037.

    • Search Google Scholar
    • Export Citation

Author Notes

* Address correspondence to Scott K. Heysell, Division of Infectious Diseases and International Health, University of Virginia, P.O. Box 81340, Charlottesville, VA 22908. E-mail: skh8r@virginia.edu

Authors' addresses: Stellah G. Mpagama, Isaack A. Lekule, Alexander W. Mbuya, and Riziki M. Kisonga, Department of Tuberculosis, Kibong'oto Infectious Diseases Hospital, Kilimanjaro, United Republic of Tanzania, E-mails: sempagama@yahoo.com, lekule228@gmail.com, kiletsa@hotmail.com, and kisonga2002@yahoo.com. Scott K. Heysell, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, E-mail: scott.heysell@gmail.com.

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