Detection of active tuberculosis by an MPB-64 transdermal patch: a field study.

The mycobacterial antigen MPB-64 was formulated for delivery in a transdermal patch and used as a diagnostic skin test reagent to detect active tuberculosis (TB) in patients attending a clinic in Manila, The Philippines. The MPB-64 Transdermal Patch was applied to 62 patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and to 28 non-TB but tuberculin-positive controls. The results were read at 72 h. The sensitivity of the Transdermal Patch was 87.8%, with an efficacy of 92.9% and a specificity of 100%. The 13 TB patients who had completed 6 months of TB chemotherapy showed different reactions to the MPB64 patch test: those who had completed chemotherapy < 4 months before testing were positive; 50% of patients who completed chemotherapy 5 months previously were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. Moreover, the MPB64 Transdermal Patch may be useful to monitor successful chemotherapy.

MPB64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis.

SETTING: A collaborative study between the Japan BCG Laboratory, Tokyo, Japan, and the Infectious Disease Section, Philippine General Hospital, Manila, the Philippines. Tuberculosis patients from four clinics in the vicinity of Manila, Our Lady of Grace Parish, Sto. Niño de Tondo Parish, the Canossa Health and Social Center, and the Health Care Development Center, were examined. OBJECTIVE: To develop a new, simple and rapid diagnostic method for active tuberculosis. Subjects were tested for skin reaction to a special antigen, MPB64, by the patch test method instead of intradermal injection of purified protein derivative (PPD). DESIGN: Fifty-three active tuberculosis patients and 43 healthy PPD-positive controls were tested to determine whether or not the reaction to MPB64 was positive only in active tuberculosis patients. RESULTS: Fifty-two of the 53 active tuberculosis patients showed a positive reaction to MPB64, while none of the 43 PPD-positive controls did. The specificity of MPB64 to active tuberculosis was 100%, and the sensitivity was 98.1%. The efficacy of the test was 98.9%. CONCLUSION: The patch test with MPB64 is a promising method for the diagnosis of active tuberculosis, distinguishing tuberculous patients from those who are infected but have not developed the disease, and also from BCG-vaccinated individuals. This new skin test is a subject for further evaluation and it is important to compare the results with PPD Mantoux.

Nature of drug resistance and predictors of multidrug-resistant tuberculosis among patients seen at the Philippine General Hospital, Manila, Philippines.

SETTING: This study was conducted at the University of the Philippines--Philippine General Hospital (UP-PGH), Manila, Philippines. OBJECTIVES: To determine the nature of drug resistance among patients with pulmonary tuberculosis (PTB), and to establish clinical predictors of drug-resistant tuberculosis. DESIGN: Descriptive, prospective study. METHODS: Patients with positive culture for Mycobacterium tuberculosis were interviewed regarding past history of anti-tuberculosis treatment, BCG vaccination, chest X-ray and family contact. M. tuberculosis isolates from 299 patients were tested for susceptibility to rifampicin, isoniazid (INH), ethambutol and streptomycin using the submerged disc proportion method. Pyrazinamide (PZA) susceptibility test was done with standard laboratory powder in 7H10 media. RESULTS: Of the 299 M. tuberculosis isolates, 17% were fully susceptible to the 5 primary drugs and 54% were resistant to 2 or more drugs (multidrug resistant TB [MDR-TB]). Initial drug resistance rate was high with ethambutol (39%) and INH (17%). Previous history of anti-tuberculosis treatment was significantly associated with MDR-TB (Odds Ratio [OR] 2.44, 95% confidence interval). Incomplete anti-TB treatment taken for longer than 3 months increased the likelihood of MDR-TB (OR 4.6, P < 0.0001). CONCLUSION: The high rate of MDR-TB was associated with previous anti-tuberculosis treatment. The chance of developing MDR-TB was significantly increased when inadequate prior treatment was given for more than 3 months.

Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C.

A conjugate vaccine against meningococcus A and C was prepared using the non-toxic mutant of diphtheria toxin CRM 197 as a carrier protein. Capsular polysaccharides of Neisseria meningitidis group A and C were hydrolysed and the resulting oligosaccharides were then coupled to CRM 197 in order to obtain conjugates with a carbohydrate content of 25-30%. The final vaccine that contained 11 micrograms of each oligosaccharide and 88 micrograms of CRM 197 was used to immunize mice and rabbits. After the preclinical studies which showed that the vaccine was safe and immunogenic in animal models, a pilot phase 1 clinical trial, blind versus placebo, was performed on adult volunteers. The difference between the incidence of adverse reactions associated with vaccine and placebo administration was not statistically significant. All the volunteers who received the vaccine had a significant increase in antibodies to group A and C meningococcal capsular polysaccharides after the first dose.

Determinants of morbidity and mortality due to acute respiratory infections: implications for intervention.

Acute respiratory infections (ARI) were monitored every two weeks in an urban community in Metro Manila, Philippines, to determine the incidence and risk factors for ARI morbidity. Hospitalized children with acute lower-respiratory-tract infection (ALRI) were studied to determine case-fatality rates (CFR) and predictors for mortality. Incidence rates were highest in infants, 3.2-4.0 per person, followed by children one to four years of age, with corresponding rates of 3.0-3.4 per person. The risk factors for ARI morbidity were low socioeconomic status and age less than one year. A CFR of 5% in children with ALRI was observed. Malnutrition and a positive culture of blood were significant risk factors for mortality. These identified risk factors underscore the value of primary health care interventions, such as the standard ARI case management, immunization, health education, promotion of breast-feeding, and vitamin A supplementation, as strategies for reducing ARI mortality in developing countries.

Norfloxacin in the treatment of infections caused by Salmonella typhi.

The bacteriological and clinical efficacy of norfloxacin 400 mg b.i.d. was studied in an open, non-comparative trial. Twenty-seven patients with clinical symptoms of typhoid fever were included and assigned to treatment for 14 days. Salmonella typhi was found in stools and/or blood cultures from 12 patients. Subsequent cultures from ten of these patients were negative during treatment and in the follow-up period. Two patients remained positive in stool cultures. Body temperature normalized within one week in 11 of the 12 evaluable patients. In conclusion, these results indicate the potential clinical value of norfloxacin for treatment of typhoid fever. Further controlled and comparative studies are needed.