The Topic of This Month Vol.22 No.2(No.252)
Malaria is a disease caused by four different species of malarial parasites (protozoa); falciparum malaria, its etiological agent Plasmodium falciparum , vivax malaria P. vivax , ovale malaria P. ovale , and malariae malaria P. malariae . Malaria is transmitted by the bite of an Anopheles mosquito. It is estimated that 300-500 million malarial cases occur yearly worldwide with 1.5-2.7 million deaths. Falciparum malaria, the most serious one, may cause encephalopathy, pulmonary edema/acute respiratory distress syndrome (ARDS), renal failure, bleeding tendency, and metabolic acidosis, leading rapidly to the severe type ending in death. In addition, new epidemics have been reported in areas where there were no signs of epidemics previously. In Korea, vivax malaria has been reemerging in some areas since 1993 (WHO, WER, 74: 265-270, 1999) and since many Japanese people travel to malaria-endemic areas, antimalarial strategy in Japan will be increasingly important.
Case reporting in Japan: Most cases of malaria are imported ones infected in foreign countries; some blood transfusion-infected cases can also be seen (see IASR, Vol. 18, No. 11). Malaria used to be a notifiable disease under the Infectious Diseases Prevention Law (an outdated law). About 50-80 cases were notified yearly (Fig. 1), nevertheless the Research Group on Chemotherapy of Tropical Diseases grasped more, over 100 cases yearly (Table 1). In the National Epidemiological Surveillance of Infectious Diseases (NESID) under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999, malaria was placed under the category IV notifiable infectious diseases. During the nine months from April through December 1999, 110 cases were notified and all cases of 1999 totaled at 120, including 10 cases notified during January through March under the outdated law. The cases notified during January through December 2000 showed an increase to 152 (Fig. 1). The increased reports may have been due to not only the actually increased cases but also to the regular notification by the medical institutes adjusted, on the occasion of the amendment, to the new law. In addition, falciparum malarial cases are tending to increase gradually, outnumbering the rest in the years 1994, 1998, and 2000 (Tables 1 and Table 2).
Monthly malarial incidence during April 1999 through December 2000 was somewhat high during March-May and August-September. Vivax malarial cases tended to be large in number at the ages of 20s and falciparum malarial ones numbered the largest at the ages of 30s (Fig. 2). Male cases counted at 198 (76%) and female ones 64 (24%). The estimated regions of acquiring infection are shown in Fig. 3. A large number of vivax malarial cases were from Asian Pacific areas, while it is noticeable that some falciparum malarial cases were from sub-Saharan African countries.
Diagnosis: Diagnosis of malaria is dependent entirely on light microscopy of Giemsa-stained blood films, which has been followed and will be continued in the future. This method will, however, cause missing or erroneous identification of the parasites when practiced by unskilled workers. Therefore, right diagnosis using the auxiliary procedures is recommended in the following:
The acridine orange method includes staining on thin blood films. Parasite's nucleic acid with fluorescence can be observed in the dark field under a fluorescence microscope, which enables skilled workers to detect the parasites without missing in a short period of time. In addition, the PCR-MPH method is simple to perform, detecting sensitively each of the four species of the parasites (see p. 25 of this issue). In some foreign countries, simple and rapid antigen-detection kits with high sensitivity and specificity, particularly for falciparum malarial parasites, are marketed, and are in use by some medical institutes in Japan (see p. 26 of this issue).
At quarantine stations at New Tokyo (Narita), Kansai, since October 1997, Fukuoka, and Nagoya International Airports, since April 1998, tests for rapid diagnosis of malaria are offered at the entry formalities; 247 travelers were tested and 10 gave positive results so far. This system is exclusively unique to Japan (see p. 27 of this issue).
Therapy: There are only two approved antimalarial drugs in Japan; sulfadoxine/pyrimethamine combination (Fansidar) and oral quinine. The Research Group on Chemotherapy of Tropical Diseases possesses other antimalarials (see p. 28 of this issue).
In vivax malaria, however, chloroquine-resistant and primaquine-low sensitive cases have already appeared in Papua New Guinea and Indonesia. Falciparum malarial cases resistant to chloroquine and sulfadoxine/pyrimethamine combination are increasing. In the border districts Thailand/Cambodia and Thailand/Myanmar, mefloquine-resistant cases are often seen. For falciparum malaria, in vitro drug-sensitivity tests are possible to perform and may sometimes be clinically useful for selecting appropriate therapeutic drugs (see p. 29 of this issue).
Besides antimalarial parasite therapy, adequate supportive therapy in response to the disease conditions is indispensable.
Prevention: The following methods may be followed: (1) personal antimosquito measures (avoiding going out after dark, wearing long sleeves and pants, using insect repellents, installing air conditioners, using mosquito bed net and mosquito coils, (2) chemoprophylaxis, and (3) stand-by treatment (emergency treatment or self treatment when professional medical care is out of the reach within 24 hr). In Western countries, chemoprophylaxis is positively practiced with mefloquine in principle, chloroquine plus proguanil or doxycycline. Recently, attention is being paid to atovaquone/proguanil combination. Of these drugs, only doxycycline is marketed within Japan, not as a malaria-preventive drug but as a remedy for bacterial infections.
Problems: Experts of malaria prevention in Western countries have pointed out that chemoprophylaxis is not popular among Japanese travelers. The reasons for this may be (1) lack of knowledge of chemoprophylaxis availability, (2) difficulty in obtaining the drugs, (3) not willing to intake or recommend the drug, taking any possibility of side effects. Malaria prevention, particularly the efficacy and side effects of chemoprophylaxis, its appropriate application and adequate practice of stand-by treatment, is under active discussion in the field of travel medicine that has been developing also in Japan.
Falciparum malaria is accounted to be a curable disease when rapid diagnosis and early treatment are carried out, nevertheless severe illness and death still occur (Table 1). Such a tendency brings forth a problem not only for Japan but also for other countries in Europe and North America (WHO, WER 76: 25-27, 2001). The analysis of the present data from NESID revealed many cases of delayed initial consultation. In the case of unexplained fever among the returnees from tropical areas, rapid differential diagnosis of diseases including malaria is a must (see IASR, Vol. 18, No. 11). It is also necessary to consult infectious disease hospitals or university experts on infectious diseases/tropical medicine.