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Introduction: 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., Methods: 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., Results: 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/Plasmodium ovale cases practiced chloroquine prophylaxis until delivery. One P. ovale case received a lower dose regimen of chloroquine as acute-stage therapy., Conclusion: 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., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Data on imported malaria in pregnant women are scarce., Method: A retrospective, descriptive study of pooled data on imported malaria in pregnancy was done using data from 1991 to 2014 from 8 different collaborators in Europe, the United States and Japan. National malaria reference centres as well as specialists on this topic were asked to search their archives for cases of imported malaria in pregnancy. A total of 631 cases were collated, providing information on Plasmodium species, region of acquisition, nationality, country of residence, reason for travel, age, gestational age, prophylactic measures and treatment used, as well as on complications and outcomes in mother and child., Results: Datasets from some sources were incomplete. The predominant Plasmodium species was P. falciparum (78.5% of cases). Among the 542 cases where information on the use of chemoprophylaxis was known, 464 (85.6%) did not use chemoprophylaxis. The main reason for travelling was "visiting friends and relatives" VFR (57.8%) and overall, most cases of malaria were imported from West Africa (57.4%). Severe anaemia was the most frequent complication in the mother. Data on offspring outcome were limited, but spontaneous abortion was a frequently reported foetal outcome (n = 14). A total of 50 different variants of malaria treatment regimens were reported., Conclusions: Imported cases of malaria in pregnancy are mainly P. falciparum acquired in sub-Saharan Africa. Malaria prevention and treatment in pregnant travellers is a challenge for travel medicine due to few data on medication safety and maternal and foetal outcomes. International, collaborative efforts are needed to capture standardized data on imported malaria cases in pregnant women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Recently, a dose of 30 mg (base) primaquine daily for 14 days is increasingly recommended for radical cure of Plasmodium vivax malaria. However, total primaquine doses, or those per body weight, are also recognized as important. In Japan, primaquine is not a licensed medicine, but has been used through the Research Group on Chemotherapy of Tropical Diseases for >3 decades., Methods: Based on clinical records submitted to the Research Group, patients with P. vivax and Plasmodium ovale malaria treated with primaquine were analyzed to determine the efficacy and safety of the antimalarial drug., Results: Seventy-five P. vivax cases, including 3 in children, and 19 P. ovale cases were enrolled. Five of the P. vivax cases demonstrated at least one relapse despite primaquine therapy. Total primaquine doses per body weight were obtained in 4 of the 5 relapsed patients, presenting 9 malaria episodes totally, and most of the primaquine failures were caused with a total dose ≤ 3.5 mg/kg. Liver function disturbance was reported in 2 cases., Conclusion: In order to optimize radical cure of P. vivax, the total primaquine dose per body weight should be considered, at least 3.5 mg/kg or even more if contracted in countries with significant drug resistance. Possibility of primaquine hepatotoxicity in chronic liver disease patients remains to be elucidated., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In cerebral malaria, the binding of parasitized erythrocytes to the cerebral endothelium and the consequent angiogenic dysregulation play a key role in pathogenesis. Because vascular endothelial growth factor (VEGF) is widely regarded as a potent stimulator of angiogenesis, edema, inflammation, and vascular remodeling, the plasma levels of VEGF and the soluble form of the VEGF receptor (sVEGFR)-1 and -2 in uncomplicated malaria patients and healthy adults were measured by enzyme-linked immunosorbent assay (ELISA) to examine their roles in malaria. The results showed that VEGF and sVEGFR-2 levels were significantly elevated in malaria patients compared with healthy adults. Moreover, it was confirmed that malarial parasite antigens induced VEGF secretion from the human mast cell lines HMC-1 or KU812 cell. This is the first report to suggest that the interaction of VEGF and sVEGFR-2 is involved in the host immune response to malarial infection and that malarial parasites induce VEGF secretion from human mast cells.

Background: Country-specific information on the incidence of malaria in travelers provides the most reliable data on which to base the pre-travel risk assessment. Some such studies have been conducted among Western travelers; however, to our knowledge, there have been no reports on Japanese travelers., Methods: Malaria cases that were diagnosed between April 1999 and December 2005 and were reported to the national infectious disease surveillance body were used as the numerators after grouped into countries of disease acquisition. The denominators, the numbers of Japanese travelers visiting individual countries were derived from the recipient countries and obtained through a Japanese organization., Results: In addition to the well-documented high risks in sub-Saharan countries, our study showed that travelers to Papua New Guinea were exposed to a significantly high risk of malaria. In Asia, Myanmar had the highest risk. Generally, malaria incidence rates among Japanese travelers were lower than those previously reported on Western travelers. However, the rates were rather comparable to the data obtained recently., Conclusions: These malaria incidence data in travelers should be taken into consideration for pre-travel risk assessment. They need to be constantly updated, and at the same time, limitations in data interpretation that are inherent in various study methodologies should also be clarified.

Background: There has been some concern that Japanese travelers are not adequately protected against malaria, especially when compared to Western travelers. Multi-national studies of knowledge, attitudes, and practices (KAP) regarding malaria risk have previously been conducted in travelers., Methods: We conducted a KAP study in Japanese travelers using the same standardized questionnaire as the previous studies. Unlike those studies, questionnaires could not be distributed at departure lounges/gates at international airports, and therefore, travelers were sourced from several different study sites, targeting different populations., Results: A total of 212 Japanese travelers who had visited malarious areas were enrolled, of which 63.2% had visited Asia and 28.3% visited sub-Saharan Africa. Significant shortcomings in KAP were noted with respect to lack of knowledge about symptoms of malaria, poor awareness of malaria risk at their destination, and non-adherence to adequate antimosquito measures. Chemoprophylaxis use was lower among Japanese travelers than travelers from other countries, even when confining to those traveling to sub-Saharan Africa., Conclusions: Japanese travel medicine providers and general practitioners who engage in pre-travel consultation should raise awareness of travelers about the seriousness of malaria, the need for improved compliance with chemoprophylaxis, and the importance of being properly prepared prior to departure.

Background: While chemoprophylaxis remains the safest option for most travelers to malaria high-risk areas, stand-by emergency treatment (SBET) may also be a sensible option especially for travelers to low-risk areas, due to the possible adverse effects (AEs) of prophylactic antimalarials. However, studies on the suitability of SBET actually implemented by travelers are scarce, especially those targeting Japanese travelers. We investigated to what extent malaria prevention measures are taken and how effectively SBET is used by Japanese travelers to malaria-endemic areas., Materials and Methods: A questionnaire study was conducted targeting Japanese travelers who visited quarantine stations for pre-travel health advice and who had previously visited malaria-endemic areas as defined by the World Health Organization (N = 160)., Results: The results showed that only a minority (13%) of travelers to malaria-endemic areas took chemoprophylaxis. Although most (89%) of the SBET users (N = 9) took antimalarial drugs when they experienced both fever and chills, characteristic of clinical malaria, there were several problems related to SBET. Some (22%) of the subjects conducted SBET less than 7 days after entering the area, most (89%) of them did so when a medical facility was readily accessible, and many (56%) failed to seek medical attention soon after SBET or did not at all., Conclusions: Japanese travelers to malaria-endemic areas seemed less protected with the use of chemoprophylaxis. Furthermore, problems related to SBET among Japanese travelers were identified. These should be taken into full consideration when educating both travelers and travel health professionals to avoid risks of malaria and possible AEs of antimalarial drugs.

Imported malaria remains an important problem in Japan. We have reviewed the medical records of 170 cases of malaria in our hospital, which corresponds to 14.9% of the total cases in Japan. The predominant malarial species was Plasmodium falciparum (52.3%), and the most frequent area of acquisition was Africa (54.2%), followed by Asia (20.9%) and Oceania (19.6%). The most common reason for travel among Japanese patients was business. A significant proportion (22.2%) of vivax malaria cases experienced relapse despite standard primaquine therapy. Most primaquine failures were from Oceania. We also found that a substantial number of Japanese patients contracted malaria without chemoprophylaxis and consulted medical facilities with an unfavorably long delay from initial symptoms (median: 3.0 days). Direct education of travelers and travel companies, in addition to health care providers, is likely necessary to improve outcomes of imported malaria.

Background 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. Methods Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Abstract: Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use — oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone–proguanil in 1999, and reported on its excellent antimalarial efficacy and safety for treating non-immune patients with uncomplicated Plasmodium falciparum malaria (20 adult and 3 pediatric cases) in 2006. In the present study, additional cases of malaria were analyzed to confirm the efficacy and safety of this antimalarial drug. Fourteen adult and 2 pediatric cases of P. falciparum malaria and 13 adult cases and 1 pediatric case of P. vivax/ovale malaria were successfully treated with atovaquone–proguanil, including 3 P. falciparum cases in which the antecedent treatment failed. Two patients with P. vivax malaria were treated twice due to primaquine treatment failure as opposed to atovaquone–proguanil treatment failure. Except for 1 patient with P. falciparum malaria who developed a moderate liver function disturbance, no significant adverse effects were observed. Despite the intrinsic limitations of this study, which was not a formal clinical trial, the data showed that atovaquone–proguanil was an effective and well-tolerated therapeutic option; licensure of this drug in Japan could greatly contribute to individually appropriate treatment options. [Copyright &y& Elsevier]

Background. Malaria poses a significant threat to military personnel stationed in endemic areas; therefore, it is important to examine the risks of military operations, particularly in areas where malaria-related data are scarce. The recent deployment of Japan Ground Self-Defense Force (JGSDF) for a peacekeeping operation in East Timor provided an opportunity to investigate these risks. The results of these studies may be translated into chemoprophylactic strategies for travelers. Methods. A total of 1,876 members were deployed between April 2002 and September 2003. They consisted of three battalions; each remained for 6 months and was put on mefloquine prophylaxis. Malaria infection was investigated, including exposure to Plasmodium falciparum sporozoites, assessed by seroconversion for anticircumsporozoite (anti-CS) protein antibodies. Adherence to and adverse events (AEs) of mefloquine were studied via questionnaires. Results. Four members were evacuated: one each with optic neuritis, lung cancer with brain metastasis, IgA nephropathy, and psychotic reactions that may have been precipitated by mefloquine. Six clinical episodes of Plasmodium vivax occurred, including one relapse, but there were no clinical cases of P falciparum, yielding a crude malaria attack rate of 0.32% for the 6-month period. Overall, 3.1% of the study population seroconverted for the anti-CS protein antibodies, with some regional differences noted. About 24% of questionnaire respondents, reported AEs; however, none of the AEs was severe. The AEs tended to emerge during the initial doses of chemoprophylaxis. Conclusions. The implementation of mefloquine prophylaxis among JGSDF personnel in East Timor, where P falciparum constitutes a moderate risk, appears to have been a success. Mefloquine prophylaxis was generally safe for Japanese unless predisposed to neuropsychiatric illness. However, given that mefloquine is the only chemoprophylactic agent available, a risk-benefit analysis tailored to the traveler is required for visits to countries such as East Timor. [ABSTRACT FROM AUTHOR]

Just after World War II, more than 10,000 malaria cases per year were reported in Japan, including indigenous, imported and induced malaria. Malaria has been successfully eradicated since 1961 in Japan and now only imported malaria cases are encountered. However, as the number of Japanese people who are going abroad and also the number of foreigners who are visiting Japan increases (about 16 and 5 millions, respectively, in 2001), so does the chance for Japanese doctors to see imported malaria or transfusion-transmitted malaria cases. In fact, the total number of the patients with acute malaria in Japan has been around 100–150 annually for the last 10 years. Of those, about 75% are Japanese and 25% are foreigners, and about 75% are male and 25% are female. The peak age is in the 20 s. Recently, about 45% of patients are Plasmodium falciparum and another 45% Plasmodium vivax infections. The former species is likely to be seen in travelers coming back from African countries and the latter is mainly from Asian countries. The important issue is that patients in Japan have not been diagnosed promptly nor treated properly because doctors in Japan are no longer familiar with tropical medicine. Therefore, some patients are dying from severe malaria as a consequence. As it is, most of the effective medicines for drug-resistant malaria or severe malaria have not been registered in Japan. There is now a need for medical practitioners to focus on travel medicine in Japan. [Copyright &y& Elsevier]