Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China.

BACKGROUND: Clofazimine (Cfz) has shown activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to treat MDR tuberculosis in China. METHODS: We enrolled 105 patients who had sputum culture-positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in China. Patients were randomly assigned to either the Cfz therapy group (n = 53) or control group (n = 52). Patients in the 2 groups were given 21 months of individual-based chemotherapy regimens based on medication history and drug susceptibility test results. The Cfz therapy group regimens incorporated 100 mg of Cfz once daily for 21 months. RESULTS: Three patients in each group discontinued therapy because of side effects or other reasons. Sputum culture conversion to negative was earlier in patients who received Cfz compared with controls (P = .042 by log-rank test). Chest computed tomography showed cavitary changes in 46 patients in the Cfz therapy group and 45 in the control group. Cavity closure was earlier in patient who received Cfz compared with controls (P = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%, higher than that in control group (53.8%; P = .035). Side effects in skin only occurred in the Cfz group. The rates of skin discoloration and ichthyosis were 94.3% and 47.2%, respectively. CONCLUSIONS: Using Cfz to treat MDR tuberculosis promotes cavity closure, accelerates sputum culture conversion, and improves treatment success rates.

[Resistance of Anopheles sinensis to three common insecticides in Hainan Province].

Anopheles sinensis adults were collected by cow-baited trap in Haikou City, Sanya City, Lingshui County, Changjiang County and Qiongzhong County of Hainan Province during 2011-2013. The mosquitoes were exposed to insecticide impregnated papers with discriminating concentrations of DDT (4%), deltamethrin (0.05%), and malathion (5%) using WHO standard assays. Knockdown rate was recorded at 10, 15, 20, 30, 40, 50, and 60 min, and KT50 values were calculated. Mortality was recorded after 24 hours of exposure. The resistance level was graded as sensitive group (S) with a mortality rate of 98%-100%, preliminary resistance group (M) with mortality rate of 80%-97%, and resistance group (R) with mortality rate of lower than 80%. The results showed that the mortality rate of An. sinensis in Qiongzhong County in 24 h-post-exposure to 0.05% deltamethrin was 95.0% with a resistance degree of M. That to 0.05% deltamethrin in the other 4 sites was 17.0%-63.0%, all with a resistance degree of R. That to 4% DDT in Haikou, Sanya, Lingshui, Qiongzhong and Changjiang was 36.0%, 27.0%, 24.0%, 59.1%, and 82.0%, with a resistance level of R, R, R, R, and M, respectively. That to 5% malathion in Haikou, Sanya, and Lingshui was 16.0%-41.0%, all with a resistance degree of R, while that to malathion in Qiongzhong and Changjiang was 100% and 98.0%, respectively, with a resistance level of S.

[Resistance assay of malaria vectors to four kinds of common insecticides in some endemic areas of Hainan Province].

OBJECTIVE: To determine the resistance of malaria vectors to four kinds of common insecticides in some endemic areas of Hainan Province. METHODS: Anopheline mosquitoes were collected between 2008 and 2010 from malaria endemic areas where insecticides were used for years. Anopheles dirus were collected from human-baited trap in Wangxia Town of Changjiang County. An. minimus and An. sinensis were collected by cow-baited trap in Jiangbian Town of Dongfang City. F0 generation female An. sinensis, F1 generation of female An. dirus and An. minimus were selected and exposed to insecticide impregnated papers with discriminating concentrations of DDT (4%), deltamethrin (0.05%), cyfluthrin (0.15%), and malathion (5%) using WHO standard assays. Knockdown rate was recorded at 10, 15, 20, 30, 40, 50, and 60 min, and KTm values were calculated. Mortality was recorded after 24 hours of exposure. RESULTS: Mortality in An. dirus was 100% to DDT, deltamethrin and malathion. Knockdown rate of An. dirus exposed to DDT and deltamethrin was 82.0% and 100%, with a KT50 value of 46.9 and 18.4 min, respectively. Mortality of An. minimus to DDT, deltamethrin, cyfluthrin and malathion was 98.1%, 99.0%, 100%, and 100%, respectively. The knockdown rate of An. minimus to DDT, deltamethrin, and cyfluthrin was 96.3%, 99.0%, and 100%, respectively, and the KTs value was 31.3, 16.8, and 7.4 min, respectively. Mortality of An. sinensis to DDT, deltamethrin, and malathion was 19.8%, 22.9%, and 43.8%, respectively. Knockdown rate of An. sinensis to DDT and deltamethrin was 2.0%, the KT50 can not be calculated. CONCLUSION: An. dirus and An. minimus, the main malaria vectors in the survey sites of Hainan Province, are susceptible to the four insecticides, while secondary malaria vector An. sinensis showed resistance to DDT, deltamethrin, and malathion.

[Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in Hainan, China].

OBJECTIVE: To assess the therapeutic efficacy of the combinations dihydroartemisinin-piperaquine and artemether-lumefantrine in treating uncomplicated falciparum malaria cases in an area with high level resistance of Plasmodium falciparum to chloroquine in Hainan Province. METHODS: Patients aged 1 to 60 with uncomplicated P. falciparum infection and parasite density 1,000 to 200,000 parasites/microl were enrolled following an informed consent. Eligible patients were randomly assigned to 2 groups for receiving either a 3-day course of dihydroartemisinin-piperaquine (40/320 mg, DP, group A) or 6-dose course of artemether/lumefantrine (20/120 mg tablets, AL, group B) over three days. They were followed up with clinical and laboratory examinations until day 28 using standard WHO in vivo antimalarial drug test protocol. RESULTS: Altogether 107 eligible patients were enrolled but 106 completed the study. Adequate clinical and parasitological response (ACPR) was observed in 51 (100%) and 55 (100%) cases in groups A and B respectively. The mean time of fever clearance and mean time of asexual parasite clearance were (20.99 +/- 11.38) h and (36.45 +/- 12.60) h in AL and (22.35 +/- 13.26)h and (34.99 +/- 12.28) h in DP, respectively. There was no statistical difference on the mean time of fever clearance and asexual parasite clearance between AL and DP (P > 0.05). None of the participants showed recrudescence and serious adverse effect. CONCLUSION: Both combinations artemether-lumefantrine and dihydroartemisinin-piperaquine show a high cure rate and proper tolerability among the patients with uncomplicated falciparum malaria in Hainan.

Extensive Resistance of Anopheles sinensis to Insecticides in Malaria-Endemic Areas of Hainan Province, China.

Anopheles sinensis is one of the major malaria vectors and among the dominant species in Hainan Province, China. The resistance of An. sinensis to insecticides is an important threat to malaria control. However, few reports on insecticide resistance of An. sinensis were reported in this area. Eight districts in Hainan Province were selected as the study areas. Insecticide susceptibility bioassays were tested on wild-caught female mosquitoes of An. sinensis to 4% dichlorodiphenyltrichloroethane (DDT), 0.05% deltamethrin, and 5% malathion by using the World Health Organization standard resistance tube assay procedure. All the tested An. sinensis mosquitoes demonstrated resistance to 4% DDT, with less than 72% mortality in the standard assay. The populations from Baisha and Qiongzhong demonstrated possible resistance to 0.05% deltamethrin, with 94-95% mortality, whereas the populations from other districts demonstrated resistance to 0.05% deltamethrin in the standard assay. The populations from Baisha, Qiongzhong, and Dongfang demonstrated susceptibility to 5% malathion, but the populations from other districts demonstrated resistance. These results facilitate the improvement of effective control strategies for malaria vector mosquitoes in Hainan.

[Therapeutic effect of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria].

OBJECTIVE: To observe the therapeutic efficacy of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria. METHODS: Patients with Plasmodium falciparum were selected as the subjects, treated with a single dose of dihydroarteminisinin 160 mg combined with naphthoquine phosphate 400 mg (for adults) and followed up in preselective time by blood and temperature examination for 28 days after drug administration. RESULTS: 37 patients with falciparum malaria were treated and followed up. One patient had recrudescence and the cure rate in 28 days was 97.3%(36/37). The mean fever clearance time was (15.8 +/- 8.7) hours; the mean parasite clearance time was (27.6 +/- 13.2) hours; the mean reduction parasite rate in 24 hours was 96.7% +/- 26.5%. No apparent side effect was observed. CONCLUSION: A combination of dihydroartemisinin and naphthoquine is effective for the treatment of patients with falciparum malaria.