Description:

Studies on the primary drug resistance to the major anti-tuberculosis drugs in Japan were conducted by the Tuberculosis Research Committee (Ryoken) in 1966. Seventy-one institutions throughout the whole country participated. The prevalence of primary drug resistance to the major drugs among newly admitted patients with pulmonary tuberculosis to these institutions during the year 1966 was investigated. Drug sensitivity was rechecked by the reference laboratories of the Committee. Previously untreated patients comprised 35·1 % of the 10,983 newly admitted patients, and among them, 51·9% were culture-positive. The prevalence of primary drug resistance was 8·5 % according to the results of the sensitivity tests conducted at the reference laboratories. The prevalence was higher in the younger age groups, and it decreased with age. The prevalence was higher among patients with tuberculosis or previous tuberculosis deaths within the same household. The culture-negative conversion rate during treatment with streptomycin, isoniazid and PAS was compared among the sensitive and resistant groups and the group with reduced drug susceptibility. Among those with pretreatment culture (+) and (++), the rate was similar in the sensitive group, the group with reduced susceptibility and the group resistant to a single drug. The rate in the group resistant to two or three drugs was lower; and the difference was statistically significant at five months. Among those with pretreatment culture (+++) and (++++), the rate in the group resistant to a single drug was slightly lower, and the rate in the group resistant to two or three drugs was considerably lower than that of the sensitive groups and the group with reduced susceptibility. The differences were significant for the rate at six months in the former and at five and six months in the latter. Comparing the culture-negative conversion rate among 50 matched pairs composed of patients with sensitive and resistant cultures with similar background factors, the rate in the resistant group, especially those treated by the same regimen of chemotherapy throughout the six months period, was lower than that of the sensitive group; and the difference was significant for the rates from the third to the sixth month.

Treatment of intractable Pneumocystis jirovecii pneumonia (PCP) patients with primaquine (PQ) in combination with clindamycin (CLDM) was conducted by the Research Group on Chemotherapy of Tropical Diseases (RG-CTD), as a kind of compassionate use. Primaquine was not nationally licensed at the time but imported by RG-CTD for the use in a clinical research to investigate safety and efficacy in malaria treatment. Eighteen Japanese adult patients thus treated were analyzed. Prior to the treatment with PQ-CLDM, most of the patients had been treated with trimethoprim-sulfamethoxazole first, all of which being followed by pentamidine and/or atovaquone treatment. This combination regimen of PQ-CLDM was effective in 16 (89%) patients and developed adverse events (AEs) in five (28%) patients. AEs included skin lesions, methemoglobinemia, and hepatic dysfunction, though none of them were serious. As a second-line or salvage treatment for PCP, PQ-CLDM appears to be a better option than pentamidine or atovaquone. Currently in Japan, both PQ and CLDM are licensed drugs but neither of them is approved for treatment of PCP. Considering the potentially fatal nature of PCP, approval of PQ-CLDM for treating this illness should be urged. Toll-like receptor 1 (TLR1) genetic variant (rs5743551, − 7202A > G) has been reported to be associated with susceptibility to various infectious diseases. We retrospectively examined the impact of TLR1 variation on transplant outcomes in a cohort of 320 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. A multivariate analysis showed that the G/G genotype in the recipients and the donors was associated with a significantly lower 3-year transplant-related mortality (TRM). The recipient G/G genotype also resulted in a better 3-year progression-free survival. This study suggests that the recipient and donor TLR1 G/G genotypes are comparably associated with a reduced risk of death that was not related to relapse. Thus, TLR1 genotyping may be useful for selecting the donor, managing patients in a risk-adapted manner, and creating therapeutic strategies to prevent complications after hematopoietic stem cell transplantation.

With Regards
Jack
Journal Coordinator
Global Journal of Research and Review