Tranquilino T. Fajardo

Methods for the Classification of Leprosy for Treatment Purposes

The World Health Organization advocates 2 leprosy treatment regimens on the basis of disease classification (as multibacillary or paucibacillary) by skin lesion count. This method, which, in the Philippines, results in a high prevalence (78%) of patients with multibacillary leprosy, was directly compared with classification using standard histopathological and microbiological criteria in 264 currently untreated patients with leprosy. Of those whose leprosy was classified as paucibacillary, 38%-51% of patients had multibacillary leprosy according to classic criteria and were thus at risk of undertreatment according to World Health Organization recommendations.

Prevalence of IgM antibodies to phenolic glycolipid I among household contacts and controls in Korea and the Philippines.

Phenolic glycolipid I (PGL-I) is a Mycobacterium leprae-specific antigen and the antibodies to the antigen may suggest an M. leprae infection. To compare the M. leprae transmission among the populations, we compared the prevalence of anti-PGL-I IgM antibodies among household contacts and controls between Korea and the Philippines. In Korea (prevalence of leprosy--0.04: 1000), the prevalence of anti-PGL-I antibodies were 4.8% among controls and 8.0% among contacts, respectively. On the other hand, the seroprevalence rate was 10.8% among controls and 13.4% among contacts in the Philippines (prevalence of leprosy--0.70: 1000). Interestingly, a marked difference was noted in the prevalance of anti-PGL-I antibodies among children between the countries; 10-14% among children under 10 years old and 15-18% among those aged between 10 and 19 in the Philippines compared to 0% and 2.9-6.4% in Korea, respectively. This study, therefore suggests that a high prevalance of anti-PGL-I IgM antibodies among children may indicate an active transmission of M. leprae, resulting in a higher incidence of leprosy in the population.

Powerful Bactericidal Activity of Moxifloxacin in Human Leprosy

ABSTRACT In a clinical trial of moxifloxacin in eight multibacillary leprosy patients, moxifloxacin proved highly effective. In all trial patients, a single 400-mg dose of moxifloxacin resulted in significant killing (P ≤ 0.006) of Mycobacterium leprae, ranging from 82% to 99%, with a mean of 91%. In all instances, no viable bacilli were detected with an additional 3 weeks of daily therapy, this observed rapid bactericidal activity being matched previously only by rifampin. On moxifloxacin therapy, skin lesions cleared exceedingly rapidly with definite improvement observed consistently after eight doses and progressive resolution continuing for the 56 days of the trial. Side effects, toxicities, and laboratory abnormalities were mild, not requiring discontinuation of therapy.

Improvement in psoriasis after intradermal administration of heat‐killed Mycobacterium vaccae

Background New treatments for psoriasis are being developed, but many are associated with limited efficacy, side‐effects, or rapid recurrence after discontinuation. Thus, the aim of new agents is to induce longer term remissions with fewer side‐effects. Preliminary studies have shown that Mycobacterium vaccae, a nonpathogenic organism prepared as a heat‐killed suspension, may induce periods of remission in some psoriasis patients when administered intradermally.

Evaluation of Mycobacterium leprae antigens in the monitoring of a dapsone-based chemotherapy of previously untreated lepromatous patients in Cebu, Philippines

Thirty-five previously untreated lepromatous patients receiving dapsone-based therapy were monitored throughout their 5-year period of treatment by serology and by pathology. Sequentially collected sera were used to evaluate the usefulness of four Mycobacterium leprae antigens as used in ELISA to monitor the progress of their therapy. ELISA results were compared with each other and with bacterial load over the treatment period and with duration of treatment. The ELISAs, based on the measurement of IgM antibody reactivity to the two neoglycoproteins (NDO and NTO) representing the phenolic glycolipid antigen of M. leprae, were found to be the most effective in monitoring treatment. A whole M. leprae based ELISA was less efficient in monitoring treatment because it failed to measure antibodies in 8 out of 35 patients and because it provided consistently lower values than either NTO or NDO. The ELISA-inhibition test based on the detection of antibodies to a species-specific epitope on the 36 K antigen of M. leprae was less suitable because of persistent reactivity during therapy, consequently resulting in no significant correlation with ELISA reactivities to NTO or NDO.

Evaluation of Mycobacterium leprae antigens in the serological monitoring of a clofazimine-based chemotherapeutic study of dapsone resistant lepromatous leprosy patients in Cebu, Philippines.

Thirty-one dapsone resistant lepromatous leprosy patients receiving clofazimine based therapy were serologically monitored throughout their 5-year period of treatment. Sequentially collected sera were used to examine 4 Mycobacterium leprae antigens to evaluate their usefulness in ELISAs for monitoring the progress of their therapy. The ELISA results were compared with decline in bacterial load over the treatment period and with duration of treatment. In addition the ELISAs were compared with each other. The ELISAs based on the measurement of IgM antibodies to the two neoglycoproteins (NDO and NTO) representing the phenolic glycolipid antigen of M. leprae were found to be the most effective with regard to monitoring treatment. A whole M. leprae based ELISA was less efficient in monitoring treatment because it failed to measure antibodies in 5 out of 31 patients. The ELISA-inhibition test based on the detection of antibodies to a species-specific epitope on the 36 K antigen of M. leprae was less suitable because of persistent reactivity during therapy.

Clofazimine therapy for lepromatous leprosy:a historical perspective

The Leonard Wood Memorial (LWM), situated in the grounds of the Eversley Childs Sanitarium near Cebu City, Philippines, was among the first institutions in Southeast Asia to use clofazimine (B663, Lamprene®) to treat disseminated leprosy. In 1966, being aware of modest improvements in African patients treated with clofazimine,1 we used the drug for the first time in a moribund male patient with advanced leprosy unresponsive to dapsone and streptomycin. The response was dramatic. Within the first 2 years, the skin lesions markedly improved, paralleled by a steady fall in the bacterial index (BI). There was never any indication of resistance and, within 6 years, the BI was zero. Treatment continued for 17 years with gradually reduced doses, and today, more than 30 years later, there are no signs of active disease or sequelae from the disease or long-term administration of clofazimine. This single ‘‘index’’ case prompted formal trials at the LWM which showed that clofazimine was as effective as dapsone in improving both clinical and microbiologic parameters and, moreover, that clofazimine was effective for dapsoneresistant infections. Clearly, until rifampicin and other treatments became available, clofazimine provided a credible alternative for dapsone-resistant infections. Today, even though clofazimine’s mechanism of action is still unclear, an expanding list of clinical applications indicates that the drug is useful in many other conditions, particularly granulomatous diseases.2 New formulations with diminished cutaneous pigmentation and toxicity, better kinetic profiles, and heightened efficacy should continue to be developed.

Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1-19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration.