A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant M. tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6mm], only 12% had histopathologic evidence of active disease. Reversions (≥ 6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6 to 13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease.

Experience in Eastern Cape Province, South Africa, suggests that patients can be treated for both XDR-TB and HIV. We have also shown that such combination therapy can be well tolerated by patients.

HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients.

BackgroundAdherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa.MethodsA convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence.ResultsOf the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76).ConclusionsThe majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment.

Results underscore the need for timely and adequate treatment for tuberculosis and HIV/AIDS.