Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

Factors Associated with Loss to Follow-up during Treatment for Multidrug-Resistant Tuberculosis, the Philippines, 2012-2014.

To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case-control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1-December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients' higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB.

Use of the VNTR typing technique to determine the origin of Mycobacterium tuberculosis strains isolated from Filipino patients in Korea.

With increasing international interchange of personnel, international monitoring is necessary to decrease tuberculosis incidence in the world. This study aims to develop a new tool to determine origin of Mycobacterium tuberculosis strains isolated from Filipino patients living in Korea. Thirty-two variable number tandem repeat (VNTR) loci were used for discrimination of 50 Filipino M. tuberculosis strains isolated in the Philippines, 317 Korean strains isolated in Korea, and 8 Filipino strains isolated in Korea. We found that the VNTR loci 0580, 0960, 2531, 2687, 2996, 0802, 2461, 2163a, 4052, 0424, 1955, 2074, 2347, 2401, 3171, 3690, 2372, 3232, and 4156 had different mode among copy numbers or exclusively distinct copy number in VNTR typing between Filipino and Korean M. tuberculosis strains. When these differences of the VNTR loci were applied to 8 Filipino M. tuberculosis strains isolated in Korea, 6 of them revealed Filipino type while 2 of them had Korean type. Using the differences of mode or repeated number of VNTR loci were very useful in distinguishing the Filipino strain from Korean strain.

Genotypic characteristics of Mycobacterium tuberculosis isolated from household contacts of tuberculosis patients in the Philippines.

BACKGROUND: The Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household. METHODS: Mycobacterium tuberculosis isolates from household contacts of tuberculosis patients in the Philippines were characterized using restriction-fragment-length polymorphism analysis, spoligotyping, and mycobacterial interspersed repetitive units - variable number tandem repeats typing (12-loci) to determine their utility in elucidating transmission in an area of high tuberculosis prevalence. Drug susceptibility patterns for these isolates were also determined. RESULTS: Spoligotyping and MIRU-VNTR typing results matched in 10 (62.5%) of 16 index patient-household contact pairs while IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index patient-household contact pairs had identical drug susceptibility results. CONCLUSIONS: Strain typing of M. tuberculosis isolates from household contacts in the Philippines indicates that transmission of strains does not necessarily occur directly from the index patient living in close proximity in the same household but rather that community-based transmission also frequently occurs. Accurate susceptibility testing of all isolates is necessary to insure optimal care of both the index patients and any culture-positive household contacts.

Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion.

RATIONALE: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients. OBJECTIVES: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months. METHODS: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment. MEASUREMENTS AND MAIN RESULTS: Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10). CONCLUSION: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.

Design and implementation of an HIV/AIDS electronic medical record system (HIV/AIDS EMR) in the Philippines.

An electronic medical record system can help scale up the HIV/AIDS treatment program of a country. The authors illustrate how an HIV/AIDS electronic medical record system (HIV/AIDS EMR) was designed and implemented among treatment facilities across the Philippines.

Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global health problem, and a control strategy known as DOTS-Plus has existed since 1999. However, evidence regarding the feasibility, effectiveness, cost, and cost-effectiveness of DOTS-Plus is still limited. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS-Plus pilot project established at Makati Medical Center in Manila, the Philippines, in 1999. Patients with MDR-TB are treated with regimens, including first- and second-line drugs, tailored to their drug susceptibility pattern (i.e., individualised treatment). We considered the cohort enrolled between April 1999 and March 2002. During this three-year period, 118 patients were enrolled in the project; 117 were considered in the analysis. Seventy-one patients (61%) were cured, 12 (10%) failed treatment, 18 (15%) died, and 16 (14%) defaulted. The average cost per patient treated was US3,355 dollars from the perspective of the health system, of which US1,557 dollars was for drugs, and US837 dollars from the perspective of patients. The mean cost per disability-adjusted life year (DALY) gained by the DOTS-Plus project was US242 dollars (range US85 dollars to US426 dollars). CONCLUSIONS: Treatment of patients with MDR-TB using the DOTS-Plus strategy and individualised drug regimens can be feasible, comparatively effective, and cost-effective in low- and middle-income countries.

Randomized, double-blind, placebo-controlled trial of oromucosal low-dose interferon following prednisone withdrawal for chronic hepatitis B infection in Filipino patients.

OBJECTIVE: To evaluate the efficacy and safety of oromucosal low-dose human lymphoblastoid interferon alpha (IFN-alpha-n1 [INS]) following steroid withdrawal in Filipino patients with chronic replicative hepatitis B virus (HBV) infection. STUDY DESIGN: Randomized, double blind, placebo-controlled trial on IFN-alpha-n1 [INS], two tablets of 200 IU each or placebo, given sublingually once daily for eight months following steroid or placebo priming and withdrawal. RESULTS: A statistically significant clearance of hepatitis B e antigen (HBeAg) (50%) and seroconversion to positive antibody to HBeAg (anti-HBe) (42.9%) was noted in those given IFN-alpha-n1 [INS] compared with the placebo group. Clearance of serum HBV-DNA was not significantly different and none cleared HBsAg in both groups. More patients (57%) had normalization of ALT on IFN-alpha-n1 [INS] compared with controls (31.3%). Oromucosal IFN-alpha-n1 [INS] was devoid of any evidence of toxicity. CONCLUSION: This study conducted on a limited number of patients demonstrates the potential efficacy of oromucosal IFN-alpha-n1 [INS] in chronic HBV infection with therapeutic benefit equal to parenterally administered interferon alpha (IFNalpha) but without the side effects of myelosuppresion. Owing to the small population studied, we are unable to extrapolate these findings to the general population of patients with chronic HBV infection. A large-scale study is needed to confirm these findings.

Mycobacterium tuberculosis infection of a tophaceous pseudogout nodule.

Musculoskeletal infections are uncommon complications of monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, and frequently involve gram positive and negative organisms. Tumoral calcinosis (tophaceous pseudogout) is a rare manifestation of CPPD deposition disease. We describe a highly unusual case of an infection by Mycobacterium tuberculosis (TB) of a tophaceous pseudogout nodule in a patient with endstage renal disease. The highly destructive nature of this case of combined CPPD arthropathy and musculoskeletal TB underscores the urgency of diagnosing this infection in susceptible patients from countries with high prevalence rates of TB infection.