The Philippines case study
Maria Imelda D Quelapioa, Thelma E Tupasia, Nona Rachel C Miraa, Maria Tarcela S Glera
Most TB patients in the Philippines are treated by private practitioners who do not conform to the international standard of TB care.1 We established a private-public mix DOTS (PPMD) centre to engage private physicians in the DOTS strategy.2 The cure rate in new cases was 83.9% and failure was 0.01%, with corresponding rates in previously treated cases of 58.6% and 39.7%, respectively. All isolates from the treatment failures were MDR-TB, indicating failure of previous TB treatment outside DOTS.
As a DOTS-Plus pilot project, the Green Light Committee (GLC) of the working group on multidrug-resistant TB provided this PPMD access to second-line anti-TB drugs (SLDs) and technical assistance. Our experience illustrates the challenges in MDR-TB management.
More effective anti-TB drugs needed
SLDs used in the management of MDR-TB are less effective, requiring prolonged regimens, and are also associated with significant side-effects.3 Although MDR-TB management was found to be highly cost-effective in our setting, drugs alone cost US$ 3500 per patient.4 Additionally, drug supplies are limited in the face of increased demand with resources provided by the Global Fund to Fight AIDS, TB and Malaria; this is another challenge to drug availability.
With the widespread use of SLDs, XDR-TB (MDR-TB with simultaneous resistance to a fluoroquinolone and one of the injectable SLDs) that is virtually incurable with the available drugs has emerged.5 Although there is substantial fluoroquinolone resistance among the MDR-TB isolates,6 XDR-TB was noted in only 4.6% of MDR-TB patients treated. Although there was no known HIV co-infection in these patients, the risk for failure or death from XDR-TB nevertheless was twice as high as that for other MDR-TB patients.7
Mobilization of more resources and engagement of the scientific community and the pharmaceutical industry to accelerate the development of affordable, novel anti-TB agents is essential for an effective response to the threat of MDR-TB, particularly XDR-TB.
Rapid methods for diagnosis needed
The diagnosis of MDR-TB relies on conventional culture and drug sensitivity testing (DST). The lag time to MDR-TB diagnosis in 2003 to 2005 declined from 8.5 ± 3.8 months to 5.0 ± 2.3 months and delay of treatment was 10.6 ± 5.6 months to 6.7 ± 3.3 months from consultation (personal communication, unpublished data). In our experience, 12%–20% of confirmed MDR-TB patients died during the long process of diagnosis, 7% while awaiting treatment, 4% to 7% refused treatment, and 22% to 26% were lost before treatment. The public health consequences of continuing transmission, further amplification of resistance, clinical deterioration and death before management underscore the need for rapid methods of MDR-TB diagnosis for more timely treatment.
Enhancing treatment adherence
Cure rates in our cohorts increased from 50% to 74% from 1999 to 2004, with corresponding declines in death and failure rates.7 However, the default rate during the prolonged treatment regimen, owing largely to adverse drug events, remained substantial. When patients were referred back from the treatment centre to the DOTS facilities, including PPMDs, within the communities where they live during the continuation phase of treatment, the default rate substantially declined compared to patients who continued to report daily to the treatment centre.8
Management of adverse drug events, group therapy sessions on psychosocial issues, and engaging patient volunteers as treatment partners were also implemented to improve treatment adherence.
Mainstreaming MDR-TB management into DOTS
To attain the goal of a TB-free world, addressing MDR-TB and other major challenges is one of the key strategies. As DOTS implementation prevents generation of MDR-TB, programmatic MDR-TB management prevents generation of XDR-TB and halts the transmission of MDR-TB. The major challenge of mainstreaming MDR-TB management into the national tuberculosis programme is the development of human resources to provide appropriate services for MDR-TB management. ■
- TE Tupasi, R Sistla, VM Co, MLA Villa, MID Quelapio, NV Mangubat, et al. Bacillary disease and health seeking behavior among Filipinos with symptoms of tuberculosis: implications for control. Int J Tuberc Lung Dis 2000; 4: 1126-32.
- MID Quelapio, NRC Mira, MR Abeleda, AB Rivera, TE Tupasi. Directly observed therapy – short-course (DOTS) at the Makati Medical Center. Philippine Journal of Microbiology and Infectious Diseases 2000; 29: 80-6.
- E Nathanson, R Gupta, P Huamani, V Leimane, AD Pasechnikov, TE Tupasi, et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. Int J Tuberc Lung Dis 2004; 8: 1382-4.
- Tupasi TE, Gupta R, Quelapio MID, Orillaza RB, Mira NR, Mangubat NV, et al. Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines. 2006 PLoS Medicine Vol. 3, No. 9, e352. doi:10.1371/journal.pmed.0030352.10.1371/journal.pmed.0030352
- ER Grimaldo, AB Rivera, RC Cardaño, JO Derilo, VA Belen, TE Tupasi. Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2001; 5: 1126-32.
- Emergence of. Mycobacterium tuberculosis with extensive resistance to second-line drugs — worldwide, 2000–2004. MMWR Morb Mortal Wkly Rep 2006; 55: 301-5.
- Tupasi T. Philippines. Report of the meeting of the WHO Global Task Force on XDR-TB. Available at: http://www.who.int/tb/xdr/globaltaskforcereport_oct06.pdf
- NR Mira, MI Quelapio, TE Tupasi, RG Vianzon, V Lofranco, et al. Implementing programmatic MDR-TB management by involving various partners: experiences from Manila, Philippines. Int J Tuberc Lung Dis 2006; 10: S4-.
- Tropical Disease Foundation, Makati Medical Center, Makati City, Philippines.