Efectividad del tratamiento farmacológico en la lepra multibacilar: un seguimiento de 34 pacientes multibacilares tratados con multiterapia hasta la negativización de los frotis cutaneos

Los ensayos sobre el terreno de la Organización Mundial de la Salud (OMS) con tratamientos farmacológicos combinados (MDT), se iniciaron en el Centro Schieffelin para Investigación y Formación en Lepra (SL R & IC), Karigiri, India en Diciembre de 1981. Se administraron a los pacientes 2 tratamientos farmacológicos distintos. El primero (régimen A) consistía en 600 mgr. de rifampicina y 300 mgr de clofazimina, administrada bajo supervisión mensualmente durante 2 días consecutivos, una inyección bimensual de 225 mgr de acedapsona y 100 mgr de dapsona diarios. El segundo (régimen: B) era el MDT convencional (OMS/MDT), rifampicina 600 mgr y clofazimin a 300 mgr, supervisada una vez al mes y 100 mgr dapsona y 50 mgr. clofazi- mina diarios no supervisados. Se administraron ambos tratamientos durante un período mínimo de 2 años o hasta la negatividad bacteriológica. Se reevaluaron 34 nuevos pacientes de lepra (MB) no tratados previamente , 16 de los cuales se les había administrado el régimen A y 18 el régimen B. Ambos regímenes resultaron bien tolerados y aceptados por los pacientes. La pigmentación por clofazimina fue el único efecto colateral adverso de la MDT. Después de completar la MDT, los pacientes se controlaron con un seguimiento durante un total de 466 personas/ año, con un promedio de 13.7ñ 1.4 paciente. No se detectaron recidivas (AU)

Effectiveness of multidrug therapy in multibacillary leprosy: a long-term follow-up of 34 multibacillary leprosy patients treated with multidrug regimens till skin smear negativity.

The World Health Organization (WHO) Field Trials of multidrug therapy (MDT) started at Schieffelin Leprosy Research and Training Centre (SLR & IC), Karigiri, India in December 1981. The patients were treated with two MDT regimens. The first (regimen A) consisted of 600mg rifampicin and 300mg of clofazimine given under supervision on 2 consecutive days monthly, 225mg injection of acedapsone bimonthly and dapsone 100mg daily. The second regimen (regimen B) was the conventional MDT (WHO/MDT), rifampicin 600mg and clofazimine 300mg supervised once a month, dapsone 100mg and clofazimine 50mg daily, unsupervised. Both the regimens were administered for a minimum period of 2 years or until skin smear negativity, whichever occurred later. Thirty-four newly detected previously untreated MB patients, 16 of whom received regimen A and 18 regimen B, were reassessed. Both regimens were well accepted and well tolerated by the patients. Clofazimine discolouration was the only adverse effect of MDT seen in these patients. After completion of treatment with MDT, the patients were followed up for a total duration of 466 person-years with a mean of 13.7 +/- 1.4 years per patient. No relapse was seen.

Activities of respository preparations of cycloguanil pamoate and 4,4'-diacetyldiaminodiphenylsulfone, alone and in combination, against infections with Plasmodium cynomolgi in rhesus monkeys.

The studies summarized in this report were concerned with the capacities of repository preparations of cycloguanil pamoate (CGT-P) to protect rhesus monkeys against infections with drug-susceptible and pyrimethamine-resistant strains of Plasmodium cynomolgi. Administered intramuscularly as a suspension in an oleaginous vehicle, CGT-P (i) provided long-term protection against single and repetitive challenges of rhesus monkeys with sporozoites of the drug-susceptible B and Ro strains, (ii) effected prompt clearance of parasitemia in established infections, and (iii) delayed relapse. Protection was equated to absence of parasites on thick blood films, negative results when blood was transferred to susceptible recipients, and inability to activate infection by splenectomy. Eventual loss of protection was not related to emergence of parasites resistant to cycloguanil (CGT). Although protection varied from monkey to monkey, its mean duration was related directly to size of CGT-P dose and size of particles in the suspension. Urinary excretion studies indicated that protection persisted as long as the daily output of CGT did not fall below that attained with the parenterally administered hydrochloride salt at a dose equivalent to 0.015 mg of CGT per kg. Studies on infections with the resistant Ro/PM strain showed that the activity of CGT-P was compromised severely by resistance to pyrimethamine. Attempts to minimize this liability by concomitant administration of 4,4'-diacetyldiaminodiphenylsulfone met with limited success. These results suggest that even the best of the repository preparations of CGT-P, with or without 4,4'-diacetyldiaminodiphenylsulfone, would be useful only in areas where Plasmodium falciparum and Plasmodium vivax are fully susceptible to chlorguanide and pyrimethamine.

Susceptibility of Mycobacterium leprae to dapsone as a determinant of patient response to acedapsone.

In the course of a clinical trial of acedapsone therapy in 17 patients with lepromatous leprosy, the rate of response to therapy was measured by inoculation of mice with Mycobacterium leprae recovered from biopsy specimens of skin lesions obtained before treatment and at intervals of 4, 12, and 24 weeks after institution of treatment. The susceptibility of each isolate of M. leprae to dapsone (4,4'-diaminodiphenylsulfone [DDS]) was measured by passaging organisms that had multiplied in mice to new groups of untreated mice and to mice treated with DDS incorporated in the mouse chow in concentrations of 10(-5), 3 x 10(-5), and 10(-4) g/100 ml. The rate of response to acedapsone therapy and the susceptibility of patient strains of M. leprae to DDS varied widely among patients. All isolates were inhibited from multiplication by treatment of mice with 10(-4) g of DDS per 100 ml; all but two isolates were susceptible to 3 x 10(-5) g of DDS per 100 ml; and 17 of 36 isolates, representing nine patient strains, were susceptible to 10(-5) g of DDS per 100 ml. Plasma levels of DDS measured in the mice administered these diets show that the minimal inhibitory concentration of DDS for M. leprae isolated from untreated patients is about 3 ng/ml. No relationship could be demonstrated between DDS susceptibility of pretreatment isolates of M. leprae and the rate at which patients responded to acedapsone therapy. Neither acedapsone treatment of patients nor DDS treatment of mice appeared to select genotypically more resistant M. leprae.