The Global Fund in China: Multidrug-resistant tuberculosis nationwide programmatic scale-up and challenges to transition to full country ownership

Abstract

China has the world's second largest burden of multidrug-resistant tuberculosis (MDR-TB; resistance to at least isoniazid and rifampicin), with an estimated 57,000 cases (range, 48,000-67,000) among notified pulmonary TB patients in 2015. During October 1, 2006-June 30, 2014, China expanded MDR-TB care through a partnership with the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund). We analyzed data on site expansion, patient enrolment, treatment outcomes, cost per patient, and overall programme expenditure. China expanded MDR-TB diagnostic and treatment services from 2 prefectures in 2006 to 92 prefectures, covering 921 of the country's 3,000 counties by June 2014. A total of 130,910 patients were tested for MDR-TB, resulting in 13,744 laboratory-confirmed cases, and 9,183 patients started on MDR-TB treatment. Treatment success was 48.4% (2011 cohort). The partnership between China and the Global Fund resulted in enormous gains. However, changes to health system TB delivery and financing coincided with the completion of the Global Fund Programme, and could potentially impact TB and MDR-TB control. Transition to full country financial ownership is proving difficult, with a decline in enrollment and insufficient financial coverage. Given needed improvement to the current treatment success rates, these factors jeopardise investments made for MDR-TB control and care. China now has a chance to cement its status in TB control by strengthening future financing and ensuring ongoing commitment to quality service delivery.

Fig 1. Timeline schematic of China Global Fund MDR-TB programme scale-up.

Quarters (Q) reflect the funding streams and not calendar year. * DST for at least R under NCE only available at selected sites using Xpert, where resistance for R was used as a proxy for MDR-TB. Culture-based DST was run in parallel to adjust treatment options in case of resistance. MDR-TB Regime: Intensive Phase: Z, Km (Am, Cm), Lfx (Mfx), Cs* (PAS, E), Pto; Continuation Phase: Z, Lfx (Mfx), Cs* (PAS, E), Pto. XDR-TB Regime: Intensive Phase: Z, Cm, Mfx, PAS, Cs*, Pto, Clr, Amx/Clv; Continuation Phase: Z, Mfx, PAS, Cs*, Pto, Clr, Amx/Clv. Drug Acronyms: Am = Amikacin, Amx/Clv = Amoxicillin plus clavulanate; Cm = Capreomycin, Clr = Clarithromycin, Cs = Cycloserine, E = Ethambutol, Km = Kanamycin, Lfx = Levofloxacin, Mfx = Moxifloxacin, PAS = p-aminosalicylic acid, Pto = Prothionamide, Z = Pyrazinamide. Drug names in parentheses represent acceptible replacements. Acronyms: DST = Drug-sensitivity testing; Hain = MTBDR(plus) assay machines; LED = LED microscopes; NCE = No cost extension; RV = Round V; RVII = Round VII; SSF = Single-stream funding; Xpert = Xpert MTB/RIF (Cepheid).

Fig 2. Diagnostic algorithm and patient enrolment by administrative level—China, 2006–2013.

DST = Drug sensitivity testing; E = Ethambutol; H = Isoniazid; Km = Kanamycin; MDR-TB = Multridrug-resistant tuberculosis; NCE = No cost extension funding, July 1, 2013 to June 30, 2014; Ofx = Ofloxacin; R = rifampicin; RV = Round V funding, October 1, 2006 to June 30, 2010; RVII = Round VII funding, October 1, 2008 to June 30, 2010; S = Streptomycin; SSF = Single-stream funding, July 1, 2010 to June 30, 2013. Open circles represent continuation along the algorithm for new cases, while open boxes represent continuation for other high risk groups. Curved lines represent exclusion from the programme. * Drug sensitivity testing for at least rifampicin (R) under NCE only available at sites using Xpert.

Fig 3. MDR-TB cases detected (pink) compared with TB cases enrolled on MDR-TB treatment (blue), and ratios of MDR-TB cases detected to tested, by province—China, October 2006–June 2014.

Fig 4. Treatment outcomes for patients diagnosed with MDR-TB by province, 2007 to 2012 cohorts.

Total number of cases in each annual cohort shown in bars.

Fig 5. Cost per patient by line item, under four Global Fund funding rounds.

Round V (RV) funding began on October 1, 2007 and ended on June 30, 2010; Round VII (RVII) began on October 1, 2008 and ended on June 30, 2010; Single-stream funding (SSF) began on July 1, 2010 and ended on June 30, 2013; the no cost extension (NCE) period began on July 1, 2013 and ended on June 30, 2014. ADR Fee refers to “adverse drug reaction fee.” Under SSF, vitamin B6 adjuvant therapy was also provided.

Fig 6. Programme expenditure, by year, and disaggregated by medication, equipment, and activities (in US$1,000).

The Global Fund programme operated only for 3 months (October–December) in 2006, and 6 months (January–June) in 2014.