Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study

Abstract

Background: Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa.

Methods: We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy.

Findings: If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity.

Interpretation: A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes.

Figures

Figures A1-A4

Model calibration.

Figure 1. Model of tuberculosis pathogenesis

Mortality is not depicted, but occurs from all compartments. HIV status and receipt of antiretroviral therapy further modify the pathogenesis of tuberculosis; transitions between tuberculosis strains due to amplified and acquired resistance or exogenous re-infection also occur.

Figure 2. Epidemiological structure of the model

Tuberculosis states are further characterised by the sub-states of infectious tuberculosis, non-infectious tuberculosis, or treatment failure, as shown in figure 1. One inpatient setting is simulated, representing the tuberculosis ward of the Church of Scotland Hospital in Tugela Ferry. However, susceptible, latently-infected, and recovered patients could be admitted to this ward as false positive tuberculosis cases, and health-care workers also constitute part of the susceptible inpatient population. Mortality is not depicted.

Figure 3. Incident cases of drug-resistant tuberculosis

Number of XDR tuberculosis cases increased from 194 in 2007 (range 122–316) to 234 in 2012 (147–380), whereas the total number of MDR tuberculosis cases rises from 352 in 2007 (223–531) to 425 in 2012 (269–640). Incident cases of overall tuberculosis increased from 1780 in 2007 (1287–2313) to 1890 in 2012 (1397–2423). Error bars in all figures indicate maximum and minimum values obtained through uncertainty analysis, in which the values of parameters were varied across the range of possible values (tables 1 and 2 in the webappendix).

Figure 4. Burden of drug-resistant tuberculosis on the hospital

Without new interventions, the proportion of inpatients with any form of MDR tuberculosis is predicted to increase from 51% in 2007 to 78% in 2012, whereas those with XDR tuberculosis increased from 29% to 48%. XDR tuberculosis consisted of 57% of all MDR tuberculosis inpatients in 2007, increasing to 62% in 2012.

Figure 5. XDR tuberculosis cases averted through administrative measures, 2007–2012

LOS=reducing the length of inpatient stay to 5 days (from the current average of 21 days); use of rapid rifampicin resistance tests for the diagnosis of MDR tuberculosis. GTMD=GenoType Mycobacteria Direct, HAIN Diagnostics. MODS=microscopic-observation drug-susceptibility assay. Detention=enforcing involuntary detention of confirmed XDR tuberculosis patients who refuse therapy, without the implementation of new isolation facilities.

Figure 6. XDR tuberculosis cases averted through environmental measures to reduce nosocomial transmission, 2007–2012

Nat vent=improvements in natural ventilation. Mech=using a mechanical ventilation system. HEPA=high-efficiency particulate air filters. UVGI=ultraviolet germicidal irradiation. Individual=providing individual isolation facilities. Cluster=separation of patients into units of five patients or ten patients (from the baseline 40-patient unit).

Figure 7. XDR tuberculosis cases averted through personal protective measures to reduce nosocomial transmission, 2007–2012

Staff mask=provision of N95 masks to staff members. Staff+patient mask=additionally providing patients with basic surgical masks; Enforce=maintaining a dedicated infection control officer to enforce adherence to mask use. VCT+ARV=provision of voluntary counselling and testing, with subsequent antiretroviral therapy to those admitted patients who qualify.

Figure 8. Efficacy of rapidly-available combinations of strategies to reduce nosocomial transmission

Mask=both staff N95 respirators and patient masks with adherence enforcement. LOS=reducing average length of stay to 5 days. Vent=improvements in natural ventilation. MODS=microscopic observed drug susceptibility assay. VCT=voluntary counselling and testing in admitted patients, with subsequent antiretroviral therapy to those who qualify. 5 pt=isolating patients in groups of five patients.