Multidrug-resistant tuberculosis patients lost to follow-up: self-reported readiness to restart treatment.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) patients lost to follow-up (LTFU) from Programmatic Management of Drug-resistant Tuberculosis facilities in the Philippines. OBJECTIVES: To gain insight into patients' readiness to return to treatment. METHODS: MDR-TB patients who initiated treatment and were categorized as LTFU were identified using TB registers, contacted, and asked to consent to an interview and medical record review. At the conclusion of the interview, patients' readiness to restart treatment was assessed and examined in relation to demographic, clinical, and interview data. Odds ratios were calculated. RESULTS: When asked if they would consider restarting MDR-TB treatment, 3% of the 89 participating patients reported that they had already restarted, 34% indicated that they wanted to restart, 33% had not considered restarting, 28% were undecided, and 2% had decided against restarting. Patients who wanted to restart treatment were more likely to report having borrowed money for TB-related expenses (OR 5.97, 95%CI 1.27-28.18), and were less likely to report being self-employed (OR 0.08, 95%CI 0.01-0.67), or perceive themselves at low or no risk for TB relapse (OR 0.30, 95%CI 0.08-0.96) than patients who did not indicate an interest in restarting treatment. CONCLUSIONS: Efforts to re-engage LTFU patients in care should consider financial barriers, knowledge gaps, and personal adherence challenges in patients.

Screening outcomes from patients with suspected multidrug-resistant tuberculosis: lessons learned in the Philippines.

SETTING: The high prevalence of multidrug-resistant tuberculosis (MDR-TB) in the Philippines is a challenge for the National TB Programme. OBJECTIVE: To assess patterns of drug resistance and screening outcomes among MDR-TB suspects evaluated from 2003 to 2008 at DOTS-Plus clinics in the Philippines. METHODS: Descriptive study of 4897 consecutive patients with suspected MDR-TB. RESULTS: The median time from the first visit until a diagnosis of drug-resistant TB was 132 days (IQR 110-166 days). Among patients screened for MDR-TB, the most frequent resistance pattern among those previously treated in DOTS facilities was resistance to isoniazid (INH) and rifampicin (RMP). Resistance to INH+RMP plus fluoroquinolones was the most common pattern among those who had failed Category II treatment and patients treated by non-DOTS facilities. Among patients with MDR-TB, 57% ultimately received appropriate treatment with second-line drugs. The remaining 43% were lost to follow-up (25%), died (14%) or refused treatment (4%). CONCLUSION: Resistance to INH+RMP is the most frequent resistance pattern among patients referred from DOTS clinics in the Philippines for suspected MDR-TB. Initial use of standard regimens based on national survey data and quick uptake of new rapid molecular resistance tests may be useful to reduce diagnostic delays and expedite treatment for drug-resistant TB.

Impact of patient and program factors on default during treatment of multidrug-resistant tuberculosis.

SETTING: In the Philippines, programmatic treatment of drug-resistant tuberculosis (TB) was initiated by the Tropical Disease Foundation in 1999 and transitioned to the National TB Program in 2006. OBJECTIVE: To determine patient and socio-demographic characteristics associated with default, and the impact of patient support measures on default. DESIGN: Retrospective cohort analysis of 583 MDR-TB patients treated from 1999 to 2006. RESULTS: A total of 88 (15%) patients defaulted from treatment. The median follow-up time for patients who defaulted was 289 days (range 1-846). In multivariate analysis adjusted for age, sex and previous TB treatment, receiving a greater number of treatment drugs (≥ 5 vs. 2-3 drugs, HR 7.2, 95%CI 3.3-16.0, P < 0.001) was significantly associated with an increased risk of default, while decentralization reduced the risk of default (HR 0.3, 95%CI 0.2-0.7, P < 0.001). CONCLUSION: Improving access to treatment for MDR-TB through decentralization of care to centers near the patient's residence reduced the risk of default. Further research is needed to evaluate the feasibility, impact and cost-effectiveness of decentralized care models for MDR-TB treatment.

Multidrug-resistant tuberculosis among previously treated patients in the Philippines.

SETTING: Prior treatment has been associated with multidrug-resistant tuberculosis (MDR-TB) in many settings. The Philippines ranks fifth among 27 priority countries for MDR-TB. OBJECTIVE: To determine the rate of MDR-TB among previously treated patients referred for MDR screening and management. DESIGN: Descriptive study of the rate of MDR-TB among 4705 previously treated patients screened from 2003 to 2008. RESULTS: MDR-TB was present in 76% of 2438 screened patients who had positive cultures. The proportion of patients with MDR-TB was the same among patients referred from public or DOTS facilities and private or non-DOTS facilities. MDR-TB occurred most frequently among patients who failed treatment with the Category 2 regimen (97%), those who did not demonstrate culture conversion after 3 months of Category 2 treatment (91%), and Category 1 failures (83%). MDR-TB rates were respectively 78% and 57% for Category 2 relapse and return after default (RAD), and respectively 33% and 22% for Category 1 relapse and RAD. CONCLUSION: MDR-TB is frequent among previously treated patients in the Philippines. Screening with culture and drug susceptibility testing should be considered for these patients.

Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects.

BACKGROUND: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries. OBJECTIVES: To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone. DESIGN: Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy. RESULTS: Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose nal conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment. CONCLUSIONS: Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with de ned end points for treatment failure. The interval between rst and nal conversion among patients whose initial con- version is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.

Responding to the multidrug-resistant tuberculosis crisis: mainstreaming programmatic management to the Philippine National Tuberculosis Programme.

SETTING: The Philippines ranks eighth among 27 priority countries for multidrug-resistant TB (MDR-TB). OBJECTIVE: To describe a model of public-private partnership in MDR-TB management. METHODS: An exploratory study of integrating MDR-TB management initiated in private-public mix DOTS into the National TB Programme (NTP). RESULTS: Recognising that MDR-TB was a threat to DOTS, the Tropical Disease Foundation initiated MDR-TB management in 1999. An official mandate for the integration of MDR-TB services into the NTP was issued by the Department of Health in 2008. With an increased government budget augmented by support from the Global Fund to Fight AIDS, Tuberculosis and Malaria, 1294 MDR-TB patients were placed on treatment from 1999 to 2008. The treatment success rate improved from 64% in 1999 to 75% in 2005. There are now five MDR-TB treatment centres with 181 treatment sites in Metro Manila, and three culture centres. People trained include 12 master trainers, 31 trainers, 25 treatment centre and 381 treatment site staff. CONCLUSION: Mainstreaming into the NTP of this unique model of MDR-TB management through a dynamic public-private collaboration can be considered best practice in implementation science of an evidence-based intervention leading to change in health care policy and practice.

Tuberculosis attributed to household contacts in the Philippines.

Data on the burden of disease from tuberculosis (TB) in Filipino households are limited. To determine the magnitude of undiagnosed TB in TB households, and the demographic and socio-economic factors associated with TB in the Philippines, household contacts of adult smear-positive TB patients seen from July 2001 to June 2003 were assessed based on interview, chest X-ray, tuberculin skin test and sputum examination. History of TB and older age were independently associated with TB disease, and age and duration of cohabitation with TB infection. TB and TB infection are highly prevalent in TB households in the Philippines.

Significant decline in the tuberculosis burden in the Philippines ten years after initiating DOTS.

BACKGROUND: The Philippines ranks ninth among the 22 high-burden countries for tuberculosis (TB). OBJECTIVE: To measure the burden of pulmonary tuberculosis (PTB) in the Philippines and determine the impact of the DOTS strategy. MATERIALS AND METHODS: The 2007 nationwide TB prevalence survey covered 50 clusters selected by multi-stage stratified random sampling from Metro Manila and other urban and rural areas. Subjects aged >or=10 years were screened radiographically for PTB to identify subjects for sputum examination and determine the prevalence of bacteriologically confirmed PTB, i.e., smear- and/or culture-positive PTB. RESULTS: In subjects aged >or=10 years, the 2007 prevalence of radiographic PTB was 6.3% (95%CI 5.5-7.1), bacteriologically confirmed PTB was 6.6 per 1000 (95%CI 5.1-8.1) and sputum smear-positive PTB was 2.6/1000 (95%CI 1.7-3.6). For the total population, the corresponding estimates were respectively 4.7%, 4.9/1000 and 2.0/1000. Between 1997 and 2007, there was a 31% reduction in bacteriologically confirmed PTB (P < 0.02) and a 27% reduction in smear-positive PTB (P = 0.18). This decline occurred despite the increasing poverty in the population. CONCLUSION: The survey demonstrated a significant decline in the TB burden 10 years after the implementation of DOTS, facilitated by a strategic public-private partnership.

Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative.

Adverse events associated with second-line drugs have been mentioned as obstacles in the management of multidrug-resistant tuberculosis (MDR-TB). Data on adverse events were collected from five DOTS-Plus sites in Estonia, Latvia, Peru (Lima), the Philippines (Manila) and the Russian Federation (Tomsk Oblast). The results show that among 818 patients enrolled on MDR-TB treatment only 2% of patients stopped treatment, but 30% required removal of the suspected drug(s) from the regimen due to adverse events. The study shows that adverse events are manageable in the treatment of MDR-TB in resource-limited settings provided that standard management strategies are applied.

Tuberculosis infection and disease in children living in households of Filipino patients with tuberculosis: a preliminary report.

SETTING: DOTS Clinic with a DOTS-Plus pilot project for the management of multidrug-resistant tuberculosis (MDR-TB) in a high burden country. OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection and disease among pediatric household contacts of patients with pulmonary TB (PTB). DESIGN: Cross-sectional study. METHODOLOGY: One hundred and fifty-three children aged 0-15 years in the households of 62 bacteriologically confirmed PTB patients, including 44 with MDR-TB, were studied. BCG scars were noted, and tuberculin skin test (TST), screening chest radiography, and sputum or gastric aspirate smear and culture for Mycobacterium tuberculosis in those with radiographic findings suggestive of PTB were done. RESULTS: For children in this study, the prevalences of latent TB infection (LTBI), radiographically diagnosed pulmonary TB, and bacillary pulmonary TB were 69.2%, 3.3%, and 0.65%, respectively. Only age > or = 5 years was found to be a significant predictor of LTBI (OR 3.17, 95%CI 1.43-7.01). CONCLUSION: Contact investigation for active case-finding and early treatment of TB in children from households of patients with active PTB is essential for TB control. Further study on a more precise definition of TB infection and strategies for control in this population will be pursued.

DOTS-Plus for multidrug-resistant tuberculosis in the Philippines: global assistance urgently needed.

SETTING: The Philippines, a high burden country for tuberculosis (TB). STUDY DESIGN: Health Operational Study. OBJECTIVE: To describe preliminary data from the Makati Medical Center (MMC)-DOTS Plus pilot project. METHODS: Patients were consecutively enrolled after confirmation of MDR-TB status. Individualized treatment regimens were based on drug susceptibility testing and history of previous intake for the other drugs that were not tested. Treatment outcome in those who had completed at least 18 months of therapy and interim outcome for those who received more than 12 months but less than 18 months were analyzed. RESULTS: One hundred forty-nine patients with MDR-TB were enrolled from April 1999 to 30 May 2002 at the MMC DOTS Clinic. Referrals were from private institutions and practicing physicians in 73.2% of cases. Approximately 30% of isolates tested were resistant to all five first-line drugs, 39.4% to four, 16.8% to three, 12.1% to two. Fluoroquinolone resistance was noted in 40.9% of all the isolates, including 54.5% of those resistant to five drugs and 34.6% of those resistant to four drugs. The outcome of 23 patients who completed therapy and 62 who have received more than 12 months therapy showed cure and likely cure in 73.4% of cases and failure in 3.8% and likely failure in 6.3%. Death occurred in 3.8% and default was observed in 11.4%. CONCLUSION: The MMC DOTS-Plus pilot project is a public-private collaboration in TB Control. Response to therapy was encouraging. Complete subsidy of medicines and laboratory and clinic services and DOT were essential in the successful implementation of the program. DOTS-Plus and DOTS should go hand in hand in TB control if MDR-TB is highly prevalent.

Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines.

SETTING: A hospital-based study at the Makati Medical Center, Makati City, Philippines, a hyperendemic area for tuberculosis (TB). OBJECTIVE: To determine the susceptibility of Mycobacterium tuberculosis to ciprofloxacin and ofloxacin. DESIGN: Retrospective analysis of drug susceptibility tests (DST) of M. tuberculosis isolated from 1995-2000. RESULTS: Resistance to ciprofloxacin was 26.8%, ofloxacin 35.3%, and multidrug resistance (MDR) was 17.2%. Of the MDR strains, 51.4% were resistant to ciprofloxacin and ofloxacin. Acquired resistance was significantly higher for all first-line drugs and for ciprofloxacin, but not for ofloxacin. A significant increase in resistance to ciprofloxacin and ofloxacin was noted compared to 1989-1994, while resistance to the firstline drugs was not significantly different. CONCLUSION: Ciprofloxacin and ofloxacin are now a significantly less effective alternative therapy in tuberculosis, particularly MDR-TB, due to a selection pressure from their widespread use in the treatment of TB and possibly other infections in the community, which is hyperendemic for tuberculosis.

BCG coverage and the annual risk of tuberculosis infection over a 14-year period in the Philippines assessed from the Nationwide Prevalence Surveys.

SETTING: A prevalence survey of tuberculosis (TB) infection was undertaken in the Philippines, a developing country in the Western Pacific region. OBJECTIVE: To determine the bacille Calmette Guerin (BCG) vaccination rate, the prevalence of TB infection and the annual risk of TB infection (ARTI). METHODS: A nationwide stratified multi-stage cluster survey of 21,960 individuals. BCG scar verification and tuberculin test were performed on those aged > or =2 months. The ARTI was calculated using the prevalence rates of TB infection in children aged 5-9 years. RESULTS: BCG scars were noted in 66% of the study population. The prevalence of TB infection was 63.4% among unvaccinated individuals. The prevalence rate was higher in males in both urban and rural areas. With both sexes combined, urban and rural communities had similar prevalence rates. In children aged 5-9 years, the prevalence rate was 16.1% (males 17.4%, females 14.9%), corresponding to an ARTI of 2.3% (males 2.5%, females 2.1%). CONCLUSION: BCG coverage increased substantially between 1981-1983 and 1997. The ARTI, however, was virtually unchanged, indicating that morbidity due to TB continued to be high.

Seroepidemiology of Hantavirus in the Philippines.

OBJECTIVE: This study was undertaken to determine the seroepidemiology of Hantavirus infection in the Philippines. METHODS: This is a cross-sectional study done in asymptomatic volunteers from various communities in the Philippines selected by a stratified multistage sampling design. Antibody to Hantavirus was detected by particle agglutination (PA) test using Hantadia high-density particle agglutination (HDPA) reagent kit. RESULTS: The prevalence of positive Hantavirus antibody among 461 subjects was the same in both males (6.1%) and females (6.1%) in rural (7.6%), urban (5.6%), and urban poor (5.1%) populations. CONCLUSIONS: The prevalence of Hantavirus infection in the Filipino population is comparable to that seen in other developing countries. The HDPA can be conveniently used as a rapid tool to detect the Hantavirus antibody for seroepidemiologic and diagnostic purposes.

Tuberculosis in the urban poor settlements in the Philippines.

SETTING: Urban poor settlements in the Philippines. OBJECTIVE: To determine the magnitude of the tuberculosis problem in urban poor settlements in comparison with urban areas studied in the Nationwide Tuberculosis Prevalence Survey. STUDY DESIGN AND METHOD: A multistage cluster survey of BCG scar, tuberculin test, chest radiography and sputum examination for bacillary disease, in urban poor areas. RESULTS: The prevalences of culture-positive and smear-positive tuberculosis were 17.5 +/- 2.3 (95% CI 13.3-22.4) and 7.9 +/- 2.3 per thousand (95% CI 2.611.5), respectively. Extrapolated to the total population, the rates in the urban poor settlements were 12.4 +/- 1.7 (95% CI 9.6-16.2) and 5.6 +/- 1.6 per thousand population (95% CI 1.3-8.3), respectively. The prevalence of active pulmonary tuberculosis in subjects aged 10 years or more was 66 +/- 5.6/1000 (95% CI 55-77). The BCG vaccination rate was 72%. The overall prevalence of tuberculosis infection was 66%, and 39% in those aged 5-9 years, corresponding to an annual risk of infection (ARI) of 6.5%. CONCLUSION: The problem of tuberculosis was substantial in the urban poor settlements, and was appreciably worse than that in the general urban population.

Bacillary disease and health seeking behavior among Filipinos with symptoms of tuberculosis: implications for control.

SETTING: Urban and rural communities and urban poor settlements in the Philippines. OBJECTIVE: To determine bacillary disease and action taking among individuals with symptoms of tuberculosis (TB), and to analyze their implications for TB control. STUDY DESIGN AND METHOD: Subjects aged 20 years and older were interviewed in the 1997 nationwide stratified multi-cluster survey. Sputum acid-fast smears and cultures were done in subjects with abnormal screening chest radiographs. RESULTS: Individuals with TB symptoms comprised 18.1% of the population studied. The prevalence of bacillary disease was 39/1000 in symptomatic subjects compared to 13/1000 in asymptomatic subjects. Symptom screening had a 14.3% positive predictive value and a 91.4% negative predictive value for bacillary disease. Significantly more symptomatic than asymptomatic subjects attended chest radiographic screening during the survey. However, in response to their symptoms, the majority (43.0%) took no action or self medicated (31.6%), while 11.8% consulted a private practitioner, 7.5% a public health center, 4.4% a hospital, and 1.7% a traditional healer. CONCLUSION: Sputum smear examination after symptom screening was acceptable for case finding. The health seeking behavior of subjects with TB symptoms was inappropriate. A health education program and public-private collaboration in directly observed therapy, short course (DOTS) are essential for TB control in the Philippines.

Quinolone use in the developing world: state of the art.

The development of bacterial resistance to previously recommended standard therapy for common childhood infections in developing countries, notably dysentery and invasive salmonellosis, has left treatment options limited to the quinolones. A number of randomised controlled trials of the quinolones in shigellosis have demonstrated their efficacy and safety in children. Strategies to make these drugs available in developing countries for specific indications should be devised. Quinolones, however, should be limited to specific indications in order to prevent the emergence of bacterial resistance and thus preserve their clinical efficacy for important childhood infectious diseases in developing countries.

The 1997 Nationwide Tuberculosis Prevalence Survey in the Philippines.

SETTING: The Philippines is a developing country where tuberculosis (TB) remains a significant public health problem. OBJECTIVE: To determine the prevalence of TB as a basis for setting the targets of the National Tuberculosis Control Program. STUDY POPULATION AND METHODS: A multi-stage cluster survey of a random sample of 21960 subjects from 36 clusters nationwide was undertaken from 2 April to 31 July 1997. BCG scar verification and tuberculin testing was performed for subjects aged 2 months and over, and chest radiography screening was done on subjects 10 years and older. Sputum samples were collected from individuals who were initially assessed to have abnormal chest radiographs to determine the prevalence of bacillary tuberculosis. Acid-fast smear by modified Kinyoun's technique and culture on Löwenstein Jensen were done to demonstrate Mycobacterium tuberculosis. RESULTS: The prevalence of active pulmonary TB was 42/1000 population. The prevalence of culture-positive and smear-positive cases was 8.1 and 3.1/1000, respectively. The prevalence was similar in urban and rural areas. CONCLUSION: Morbidity from TB remains high. Allowing for methodological differences from the survey in 1981-1983, the prevalence of active pulmonary TB was unchanged. There was only a minimal decrease, of 37% for smear-positive cases and 25% for culture-positive cases, in the 14-year interval.