Chemotherapy Of Tropical Diseases Research Articles

Primaquine plus clindamycin as a promising salvage therapy for Pneumocystis jirovecii pneumonia: A retrospective analysis in Japanese patients

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.

Retrospective observational study of the use of artemether-lumefantrine in the treatment of malaria in Japan.

The Research Group on Chemotherapy of Tropical Diseases, Japan, introduced artemether-lumefantrine (AL) in late 2002, mainly for treating uncomplicated Plasmodium falciparum malaria. Because AL was on the market in Japan in March 2017, the effectiveness and safety of AL were analyzed to help medical personnel use AL optimally. Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information. Effectiveness analysis was performed for 62 cases and safety analysis was performed for 66 cases. In P. falciparum malaria, the overall cure rate was 91.1% (51/56), of which the cure rates for Japanese and non-Japanese patients were 82.1% (23/28) and 100% (28/28), respectively. The successfully treated cases included severe P. falciparum malaria, with parasite densities exceeding 500,000/μL. Adverse events were reported in 14 patients, including delayed hemolytic anemia which occurred in the top four highest parasitemic cases. AL treatment failure in P. falciparum malaria may not be rare among non-immune individuals, including Japanese. The possibility of delayed hemolytic anemia, which occurs preferentially in high parasitemic cases, should be considered following AL treatment.

Imported malaria in pregnant women experienced in Japan.

With ever-growing global exchanges, the number of travelers, including pregnant women, to the tropics is increasing, which poses a risk of contracting malaria. Although there are several reports on imported malaria in pregnancy from Western countries, those focusing on cases experienced in Japan are very limited. We searched for cases of malaria in pregnancy in the treatment records submitted to the Research Group on Chemotherapy of Tropical Diseases, Japan, during the period 1993-2016. Literature searches were also conducted using an American and a Japanese search system. Ten cases of malaria in pregnant women were identified, including four cases with Plasmodium falciparum. Of eight evaluable cases, only one practiced malaria chemoprophylaxis. Among the nine evaluable cases, eight resulted in uneventful delivery and one P.falciparum case developed severe hepatic disturbance, disseminated intravascular coagulation, and intrauterine fetal death. After the initial attack, none of the Plasmodium vivax/Plasmodiumovale cases practiced chloroquine prophylaxis until delivery. One P. ovale case received a lower dose regimen of chloroquine as acute-stage therapy. This study demonstrated additional cases of imported malaria in pregnant women to the literature and highlighted various epidemiological, demographic, and clinical characteristics. Some of the clinical issues raised need to be investigated. Due to the paucity of the cases worldwide, sharing information among various countries is indispensable, and international guidelines which are now increasingly recommending the use of artemisinins in pregnant women should be referred.

Malaria cases treated with artemether/lumefantrine in Japanese travelers

Artemisinin-based combination therapy (ACT) has been the standard treatment for uncomplicated malaria. Although not licensed in Japan, artemether/lumefantrine (AL), one type of ACT, has been administered to patients with malaria since 2002 by the Research Group on Chemotherapy of Tropical Diseases. Herein, we reviewed malaria cases treated with AL in Japanese travelers. A retrospective study was conducted at the National Center for Global Health and Medicine from October 2005 to March 2013. There were 19 malaria patients treated with AL, and 10 falciparum malaria patients treated with AL only. In these 10 patients treated with AL only, the median time of fever clearance was 25.0 hours (range:14-66 hours), and the median time of parasite clearance was 36.0 hours (range:16-62 hours). There was a positive correlation between parasitemia and time from the start of therapy to the disappearance of the parasites. Parasitemia was higher (4.05% vs. 0.24%; p = 0.044) and parasite clearance time was longer (55.5 hours vs. 31.5 hours; p = 0.044) in the cases of recrudescence than non-recrudescence, respectively. Three of the 19 malaria patients showed recrudescence of malaria after treatment with AL. The reason that treatment failure was more frequently observed in this study than in previous reports may be related to poor absorption of lumefantrine owing to gastrointestinal symptoms, insufficiently ingested fatty foods, or high parasitemia on admission. The World Health Organization recommends that intravenous antimalarials should be administered in cases of severe malaria however, this is not applicable in Japan. Further studies are needed to distinguish patients with malaria who are treatable with ACT from those who should be treated initially with other intravenous antimalarials.

The chemotherapy of tropical diseases. II. Diseases caused by rickettsiae, bacteria, spirochaetes and worms.

The chemotherapy of tropical diseases. II. Diseases caused by rickettsiae, bacteria, spirochaetes and worms.

Experience with Intravenous Metronidazole to Treat Moderate-to-Severe Amebiasis in Japan

Twenty-eight cases of either intestinal amebiasis, amebic liver abscess, or both, most of which were of moderate-to-severe intensity, were treated with intravenous metronidazole, pioneered by the Research Group on Chemotherapy of Tropical Diseases, Japan. This study was not conducted as a formal clinical trial, and all patients either underwent colectomy for intestinal amebiasis, received oral metronidazole, or both. Despite these limitations, intravenous metronidazole was shown to be well tolerated and seemed to be very effective. This agent should be more widely recommended than previously thought for treating moderate-to-severe amebiasis, especially its intestinal form.

Efficacy and safety of atovaquone-proguanil compared with mefloquine in the treatment of nonimmune patients with uncomplicated P. falciparum malaria in Japan

Malaria treatment is becoming increasingly difficult due to the widespread drug resistance of Plasmodium falciparum. In Japan, only three antimalarials are approved for treatment: oral quinine, sulfadoxine-pyrimethamine, and mefloquine. Recently, however, the Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil for treating drug-resistant P. falciparum malaria. This research group had also introduced mefloquine before it was licensed nationally. Using data obtained from the research group, we analyzed the efficacy and safety of atovaquone-proguanil, as compared with mefloquine, in nonimmune patients with uncomplicated P. falciparum malaria. Cures were attained in all (100%) of 20 atovaquone-proguanil-treated and 49 (98%) of 50 mefloquine-treated adults. The mean fever clearance time (FCT) and parasite clearance time (PCT) appeared to be longer in the atovaquone-proguanil group than in the mefloquine group, but the differences were not statistically significant. Three (15%) of the 20 atovaquone-proguanil-treated adults had adverse events (AEs), all of which were transient elevations of liver enzymes, while 19 (38%) of the 50 mefloquine-treated adults had AEs, including dizziness in 8 (16%) and nausea/vomiting in 7 (14%). All 3 children treated with atovaquone-proguanil were cured without developing AEs. Despite the limitations of this study in not being a formal clinical trial, atovaquone-proguanil seemed to be at least equal to, or even better than, mefloquine for the treatment of uncomplicated P. falciparum malaria in nonimmune patients, including children. Its marketing in Japan could be beneficial in offering an alternative therapeutic option. However, vigilance should be maintained on the possible occurrence of rare but severe AEs, and also of the possible spread of drug resistance.

Chemotherapy of Tropical Diseases, Volume 21, Clinical Reports on Applied Chemistry

Chemotherapy of Tropical Diseases, Volume 21, Clinical Reports on Applied Chemistry

Some reflections on the chemotherapy of tropical diseases: past, present and future.

Chemotherapy of tropical diseases is the prevention or cure by drugs of some major diseases, which are currently more or less confined to hot and often humid climates. In selective population-based chemotherapy its application is a good example of protection of health through technology. Regretfully, this area of health technology has suffered from fluctuating interests, for a variety of scientific, economic and political reasons. About five years ago, the question of a substantial lag in progress towards improved, efficacious, safe and cheap drugs became a matter of public interest and concern.KeywordsCutaneous LeishmaniasisVivax MalariaTropical DiseaseRetinyl PalmitateOcular InsertThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Reviews: The Chemotherapy of Tropical Diseases

Reviews: The Chemotherapy of Tropical Diseases

The Chemotherapy of Tropical Diseases

The Chemotherapy of Tropical Diseases

Chemotherapy of Tropical Diseases

This 164-page book gives a most useful and up-to-date summary of the chemotherapy of tropical diseases. The following chapter headings indicate the scope of this work: (1) Protozoal Diseases, (2) Spirochaetal Diseases, (3) Rickettsial Diseases, (4) Bacterial Diseases, (5) Fungal Infections, (6) Nutritional Diseases, (7) Climatic Diseases, (8) Metazoal Diseases, and (9) Venereal Diseases. There is a useful summary list of drugs employed in the treatment of tropical diseases. It is most convenient to have all of this material gathered together in one volume, for it saves searching through many books. For a number of diseases, several chemotherapeutic agents are mentioned, usually in historical order which means that the older discarded drugs come first. It is unfortunate that the author does not indicate the current drug of choice. This is not important to experts in the field, but for the internists or general practitioners it would be most valuable. One

Book Review: The Chemotherapy of Tropical Diseases

Book Review: The Chemotherapy of Tropical Diseases