What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is undermining TB control in South Africa. However, there are hardly any data about the cost of treating DR-TB in high burden settings despite such information being quintessential for the rational planning and allocation of resources by policy-makers, and to inform future cost-effectiveness analyses. METHODOLOGY: We analysed the comparative 2011 United States dollar ($) cost of diagnosis and treatment of drug sensitive TB (DS-TB), MDR-TB and XDR-TB, based on National South African TB guidelines, from the perspective of the National TB Program using published clinical outcome data. Principal FINDINGS: Assuming adherence to national DR-TB management guidelines, the per patient cost of XDR-TB was$26,392, four times greater than MDR-TB ($6772), and 103 times greater than drug-sensitive TB ($257). Despite DR-TB comprising only 2.2% of the case burden, it consumed ∼32% of the total estimated 2011 national TB budget of US $218 million. 45$6930 (26%) per case and reduce the total amount spent on DR-TB by ∼7%. Conclusion/Significance Although DR-TB forms a very small proportion of the total case burden it consumes a disproportionate and substantial amount of South Africa's total annual TB budget. These data inform rational resource allocation and selection of management strategies for DR-TB in high burden settings

Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa

BACKGROUND: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. METHODS: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)]. FINDINGS: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). CONCLUSION: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB

Total costs and breakdown per patient for drug sensitive tuberculosis, multi-drug resistant tuberculosis and extensively drug-resistant tuberculosis. Costs are expressed in $US.

*<p>In the current model 100% of XDR-TB patients are hospitalized whereas in the proposed decentralized model 50% are treated as outpatients and the remaining 50% are hospitalized.</p>†<p>For example, the total costs of illness arising from DS TB per patient were calculated as (0.6*191.66)+(0.2*252.54)+(0.2*455.50) = $256.61.</p><p>DS-TB - Drug sensitive tuberculosis, MDR-TB – Multi-drug resistant tuberculosis, XDR-TB – Extensively Drug-resistant tuberculosis, PCC- primary care clinic, ADR- Adverse Drug reaction.</p

The total drugs costs of notified cases of drug sensitive (DS-TB), multi-drug resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) reported in 2010.

<p>Costs are expressed in $US.</p

The total number, national costs and cost breakdown of notified cases of drug sensitive (DS-TB), multi-drug resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) reported in 2010.

<p>Costs are expressed in $US and refer to the cost of diagnosis and treatment of confirmed cases. *Other indicates surgery, ADRs and death related costs.</p

Costs of components associated with diagnosis and treatment of drug sensitive, multi-drug resistant and extensively drug resistant tuberculosis.

<p>DS-TB - Drug sensitive tuberculosis, MDR-TB – Multi-drug resistant tuberculosis, XDR-TB – Extensively Drug-resistant tuberculosis, ADR - Adverse Drug reaction, OT - Occupational Therapist, PT - Physiotherapist, BCH – Brooklyn Chest Hospital, DOTS – Directly Observed Treatment Short Course, MGIT – Mycobacterial Growth In-tube, DST – Drug susceptibility test, AST - aspartate aminotransferase, ALT - alanine aminotransferase, R - Rifampicin, H - Isoniazid, Z - Pyrazinamide, E - Ethambutol, S - Streptomycin, Km – Kanamycin, Mxf - Moxifloxacin, Eto - Ethionamide, Trd – Terizidone, Cm - Capreomycin, PAS – para-amionsalicylic acid, Cfz – Clofazimine, Clm-Clarithromycin, Aug - Augmentin, hdH - high dose Isoniazid.</p

Sensitivity analysis. Costs represent the cost per case and are expressed in $US.

<p>DS-TB - Drug sensitive tuberculosis, MDR-TB – Multi-drug resistant tuberculosis, XDR-TB – Extensively Drug-resistant tuberculosis, ADR – Adverse Drug reaction, ARVs – Anti-Retroviral drugs.</p

The cost breakdown of the total cost per patient for drug sensitive (DS-TB), multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculosis.

<p>*Other indicates surgery, ADRs and death related costs.</p

Effect of TB strain type on AEs stratified by Beijing and non-Beijing strain type.

*<p>p = 0.03 (severe vs. mild to moderate AEs).</p>**<p>p = 0.0001 (total Beijing versus non-Beijing).</p