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.

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.

Physico-chemical and solid-state characterization of secnidazole.

Secnidazole (hydroxy-2-propyl)-l-methyl-2-nitro-5-imidazole) is an antimicrobic agent. This drug has pharmacological activity against intestinal and hepatic amebiasis, giardiasis and vaginal trichomoniasis. This paper shows the physicochemical parameters of secnidazole determined during a preformulation study. The determination of the apparent partition coefficient and the profile of solubility in dependence of pH demonstrate the basic characteristic of the drug. The dissolution assay was performed to evaluate its behavior in water. For this purpose, a new spectrophotometric method, which was linear from 5 to 15 microg/ml, sensitive, precise, accurate and selective, was validated to assay the bulk drug. The evaluation of higroscopicity revealed that the drug is unstable above 54% of relative humidity. Rheological properties, such as porosity, tapped and bulk densities and percentage of compressibility were calculated. Results show a bad rheological characteristic for this drug. DSC curves do not show any physical interaction between the drug and the excipients in the compatibility studies.

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.

Rapid and improved recovery rate of Mycobacterium tuberculosis in Mycobacteria Growth Indicator Tube combined with solid Löwenstein Jensen medium.

SETTING: Clinical microbiology laboratory with limited resources in a developing country. OBJECTIVE: To determine the recovery rate of Mycobacterium tuberculosis (MTB) in Mycobacteria Growth Indicator Tube (MGIT) combined with Löwenstein Jensen (LJ) culture medium. DESIGN: Stock cultures and reference strains of mycobacteria and clinical specimens were inoculated into MGIT and onto LJ. The combined recovery rate was determined and time to positive culture in each medium was compared. RESULTS: All known stock and reference cultures of mycobacteria grew in both media. MGIT combined with LJ increased the recovery rate from 109 (63.4%) to 122 (70.9%) of 172 clinical specimens. Of those isolated, the yield in MGIT (99.2%) exceeded that in LJ (89.3%). The average day to detection of MTB in MGIT was earlier by 14.2 days compared to LJ (15.7 days vs. 29.9 days). For mycobacteria other than tuberculosis (MOTT), there was little difference in the recovery time, except for M. kansasii where growth in MGIT was earlier by one week and M. triviale where growth in MGIT was detected later than LJ. CONCLUSION: MGIT is an excellent system for the rapid isolation of mycobacteria. It increases the recovery rate of MTB when combined with LJ.