Background: Rapid diagnostic tests (RDTs) have widely been used in the diagnosis of malaria. Although the effectiveness of RDTs for malaria has previously been described in many reports, the low performance of RDTs particularly for Plasmodium ovale malaria in travellers have rarely been reported. Methods: This was retrospective cohort study conducted among Japanese travellers who were diagnosed with malaria at the National Center for Global Health and Medicine between January 2004 and June 2013. Diagnosis of malaria by microscopic examination, RDT, and polymerase chain reaction were performed for all the patients. The RDTs used in our study were Binax NOW Malaria (Binax Inc., Scarborough, Maine, USA) (BN) and SD Malaria Antigen Pf/Pan (Standard Diagnostics Inc., Korea) (SDMA). We compared the sensitivity of the RDTs of P. ovale malaria with that of Plasmodium vivax malaria. Results: A total of 153 cases of malaria were observed, of which 113 patients were Japanese travellers. Nine patients with P. ovale malaria and 17 patients with P. vivax malaria performing RDTs were evaluated. The overall sensitivity of RDTs for P. ovale malaria was 22.2% and that for P. vivax malaria was 94.1% (P < 0.001). The sensitivity of SDMA for P. vivax malaria was 100% and that for P. ovale malaria was 50%. The sensitivity of BN for P. vivax malaria was 90.0%; however, it was unable to detect the cases of P. ovale malaria. Conclusions: The sensitivity of RDTs was not high enough to diagnose P. ovale malaria in our study. Thus, microscopic examination is indispensable not to overlook P. ovale malaria.

Background: Rapid diagnostic tests (RDTs) are used widely in the diagnosis of malaria. Although the effectiveness of RDTs for malaria has been described in many previous studies, the low performance of RDT particularly for Plasmodium ovale malaria in traveller has rarely been reported. Methods: This was a retrospective cohort study conducted on Japanese travellers diagnosed with malaria at the National Center for Global Health and Medicine between January 2004 and June 2013. The diagnosis of malaria was confirmed by microscopic examination, RDT, and polymerase chain reaction in all patients. The RDTs used in our study were Binax NOW Malaria (Binax Inc., Scarborough, Maine, USA) (BN) and SD Malaria Antigen Pf/Pan (Standard Diagnostics Inc., Korea) (SDMA). We compared the sensitivity of the RDTs to P. ovale malaria and Plasmodium vivax malaria. Results: A total of 153 cases of malaria were observed, 113 of which were found among Japanese travellers. Nine patients with P. ovale malaria and 17 patients with P. vivax malaria undergoing RDTs were evaluated. The overall sensitivity of RDTs for P. ovale malaria and P. vivax malaria was 22.2% and 94.1%, respectively (P < 0.001). The sensitivity of SDMA for P. ovale malaria and P. vivax malaria was 50% and 100%, respectively. The sensitivity of BN for P. vivax malaria was 90.0%, but it was ineffective in detecting the cases of P. ovale malaria. Conclusions: The sensitivity of RDTs was not high enough to diagnose P. ovale malaria in our study. In order not to overlook P. ovale malaria, therefore, microscopic examination is indispensable.

Plasmodium falciparum is one of the causative agents of malaria in humans. This parasite causes the most severe forms of the disease. In order to combat the disease, it is important to have knowledge about the parasite and its interaction with its host. In this study, we profiled 74 patients admitted to hospital in Tagum, Davao, Philippines who were confirmed to be infected with P. falciparum. We correlated the age, sex and parasite load with malaria severity and show that among these, only sex is correlated with disease severity in this population. In addition, we profiled the MSP-1 block 2 allele distribution in the population and found that the most abundant allele form was K1, followed by MAD20. The RO33 allele form was the rarest allele in this population.

The NOW^® Malaria Test, an immunochromatographic test (ICT), was evaluated to determine its ability to quantitatively detect malaria parasites using 100 blood samples from Thailand, including 50 Plasmodium falciparum (Pf) infections and 50 P. vivax (Pv) infections. Intensities of the thickness of the visible bands of the positive ICT were compared with the parasite densities. In cases of Pf infection, the intensities of both HRP-2 bands (T1 bands: Pf specific bands) and aldolase bands (T2 bands: pan-Plasmodium bands) correlated with the parasite densities. The intensities of T2 bands in Pf positive samples showed better correlation with the parasite densities than the T1 bands. In the cases of Pv infection, the intensities of T2 bands were also well correlated with parasite density. These results suggest that the ICT is useful not only for rapid detection of malaria parasites but also for estimating parasite density.

Although Mefloquine is commonly used as a prophylactic drug for travelers to malaria endemic areas, there are only limited reports about its adverse effects in Japanese travelers. We carried out a prospective observation study of 107 travelers who were prescribed mefloquine as chemoprophylaxis against malaria prior to their departure from November 2004 to October 2006. We carefully sought the appropriate prescription for each client according to the guidelines for Japanese overseas travelers. The clients consisted of 71 men and 36 women of whom we were able to follow 65 travelers until the end of their prophylactic procedure. Of the 65, 47 travelers completed their full course of chemoprophylaxis. Different adverse effects were reported in 19 travelers of them such as fatigue (n=9), dizziness (n=6), headache (n=3), nausea (n=3), drowsiness (n=2), strange dreams (n=2), anxiety (n=2), fever (n=1) and skin rash (n=1). Three travelers were incapable of continuing chemoprophylaxis due to the adverse effects, but no serious events were noted. Through our study, mefloquine chemoprophylaxis seemed tolerable for Japanese travelers. We believe that our detailed consultation and careful monitoring reduced the incidence of severe adverse effects and maintained the high rate of adherence to chemoprophylaxis.

Mixed infections of Plasmodium falciparum and Plasmodium vivax is high (~30%) in some malaria hypoendemic areas where the patients present with P. falciparum malaria diagnosed by microscopy. Conventional treatment of P. falciparum with concurrent chloroquine and 14 days of primaquine for all falciparum malaria patients may be useful in areas where mixed falciparum and vivax infections are high and common and also with mild or moderate G6PD deficiency in the population even with or without subpatent vivax mixed infection. It will be possibly cost-effective to reduce subsequent vivax illness if the patients have mixed vivax infection. Further study to prove this hypothesis may be warranted.

Artemisinin-based combination therapy (ACT) is currently promoted as a strategy for treating both uncomplicated and severe falciparum malaria, targeting asexual blood-stage Plasmodium falciparum parasites. However, the effect of ACT on sexual-stage parasites remains controversial. To determine the clearance of sexual-stage P. falciparum parasites from 342 uncomplicated, and 217 severe, adult malaria cases, we reviewed and followed peripheral blood sexualstage parasites for 4 wk after starting ACT. All patients presented with both asexual and sexual stage parasites on admission, and were treated with artesunate-mefloquine as the standard regimen. The results showed that all patients were asymptomatic and negative for asexual forms before discharge from hospital. The percentages of uncomplicated malaria patients positive for gametocytes on days 3, 7, 14, 21, and 28 were 41.5, 13.1, 3.8, 2.0, and 2.0%, while the percentages of gametocyte positive severe malaria patients on days 3, 7, 14, 21, and 28 were 33.6, 8.2, 2.7, 0.9, and 0.9%, respectively. Although all patients were negative for asexual parasites by day 7 after completion of the artesunate-mefloquine course, gametocytemia persisted in some patients. Thus, a gametocytocidal drug, e.g., primaquine, may be useful in combination with an artesunate-mefloquine regimen to clear gametocytes, so blocking transmission more effectively than artesunate alone, in malaria transmission areas.
Adolescent ; Adult ; Animals ; Antimalarials/*pharmacology/therapeutic use ; Artemisinins/*pharmacology/therapeutic use ; Drug Evaluation ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Germ Cells/*drug effects/growth & development ; Humans ; Malaria, Falciparum/*drug therapy/parasitology ; Male ; Mefloquine/*pharmacology/therapeutic use ; Plasmodium falciparum/*drug effects/growth & development ; Severity of Illness Index ; Thailand ; Treatment Outcome

As malaria continues to be a public health problem in the Philippines, its control is now the responsibility of the Local Government Unit (LGU). In this set-up, social mobilization is believed to be the key strategy in effective and sustainable implementation of malaria prevention and control activities. Palawan has always been the most malarious province in the country. Despite untiring malaria control efforts and huge funds spent to curb this malady for which Palawan has become known, this province remains the largest contributor of malaria cases and deaths. Thus, Kilusan Ligtas Malaria (KLM: meaning Movement Against Malaria) has focused on social mobilization in the implementation of malaria prevention and control. Microscopic confirmation of malaria is done by trained village microscopists, while health education-promotion activities, advocacy and linkage building are carried out by trained village community organizers. The noticeable outcomes are the increase in malaria case finding as reflected in the total number of malaria smears done, the increase in microscopic confirmation of malaria, and the decline in clinical diagnoses. Other outcomes include policy development and implementation in the form of executive orders and community ordinances to support the village microscopists and community organizers. Now, the biggest challenge of KLM is maintaining the momentum and sustaining gains.

In vitro drug susceptibility testing of Plasmodium falciparum must be conducted immediately after collecting a sample of the patient‘s blood; otherwise the parasites may weaken and the culture fail. Collecting blood samples from individuals in areas far from the field station or clinic where in vitro testing is conducted requires a reliable method of sample preservation during transportation. We examined and compared three different methods used to preserve blood samples in endemic areas in the Philippines. The three methods are as follows: the on-site method (test is conducted soon after blood sampling), flask culture method (sample is taken to the laboratory in a culture flask with medium) and EDTA tube method (sample is taken to the laboratory in a blood collection tube). The WHO in vitro micro-test for susceptibility of P. falciparum to chloroquine was performed using an AnaeroPack® system and a portable thermostat incubator. Evaluation of the three methods was based on schizont maturation, ease of handling, and risk of contamination during the test. The on-site and flask culture methods, but not the EDTA tube method, were effective for keeping the parasites viable. Furthermore, schizont maturation appeared better with the flask method than with the on-site method, especially in the control wells (drug-free wells). In addition, it was easier to perform the flask method than the on-site method. No contamination was observed using any of the methods. The results of the study suggest that the flask culture method is the most effective and useful way to preserve blood samples for the in vitro test and, moreover, that it aids in providing detailed field evidence of drug-resistant malaria.

Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.
Adolescent ; Aged ; Animals ; Antimalarials/adverse effects/*therapeutic use ; Artemisinins/adverse effects/*therapeutic use ; Chloroquine/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Ethanolamines/adverse effects/*therapeutic use ; Female ; Fluorenes/adverse effects/*therapeutic use ; Humans ; Malaria, Vivax/*drug therapy ; Male ; Middle Aged ; Parasitemia ; Plasmodium vivax/drug effects ; Primaquine/therapeutic use ; Thailand ; Treatment Outcome