BACKGROUND: Chemoprophylaxis has been used to prevent malaria among soldiers and secondary transmission, as it effectively facilitates a decline in disease occurrence and secondary prevention. However, poor compliance and decreased risk of exposure to malaria necessitate that control strategies be reestablished. METHODS: To predict the incidence of malaria according to a control strategy, we proposed a mathematical model for its transmission using epidemiological data from 2010 to 2012. The benefit component included in the analyses was the averted cost with each control strategy, and the cost components were the cost of implementing chemoprophylaxis and early diagnosis. RESULTS: The chemoprophylaxis regimen with hydroxychloroquine sulfate and primaquine was Intervention 1, the regimen with primaquine only was Intervention 2, and diagnosis with a rapid diagnostic test (RDT) kit within 5 days of fever was Intervention 3. The simulation indicated that the combined control program with chemoprophylaxis and early diagnosis would be the most effective strategy, whereas sole early diagnosis would be the least effective strategy. However, the cost-benefit ratio of chemoprophylaxis was less than Intervention 1, irrespective of the varying range of chemoprophylaxis compliance, and that of early diagnosis was more than Intervention 1, regardless of the varying early diagnosis rate and demand for the RDT kit. Although chemoprophylaxis would be more effective at reducing the incidence of malaria than early diagnosis, it is less economical due to the higher cost. CONCLUSION: Our results support the introduction of early diagnosis with a RDT kit to control malaria in the Republic of Korea Army.
Chemoprevention* ; Compliance ; Cost-Benefit Analysis* ; Diagnosis ; Diagnostic Tests, Routine ; Early Diagnosis* ; Fever ; Humans ; Hydroxychloroquine ; Incidence ; Malaria* ; Military Personnel* ; Models, Theoretical ; Primaquine ; Republic of Korea ; Secondary Prevention

Primaquine is often administered for the hypnozoite stage of Plasmodium vivax and Plasmodium ovale. Primaquine (with clindamycin) is also an alternative drug for treatment of pneumocystis pneumonia when trimethoprim/sulfamethoxazole cannot be used. Primaquine may cause methemoglobinemia, an altered state of hemoglobin in which the ferrous state of heme is oxidized to the ferric state. We report a case of methemoglobinemia caused by a standard dose of primaquine plus clindamycin in a 27-year-old female recipient of a kidney transplant who was diagnosed with pneumocystis pneumonia.
Adult ; Clindamycin ; Female ; Heme ; Humans ; Kidney ; Methemoglobin ; Methemoglobinemia* ; Plasmodium ovale ; Plasmodium vivax ; Pneumonia, Pneumocystis ; Primaquine*

Acquaintance is scanty on primaquine (PQ) efficacy and Plasmodium vivax recurrence in Udupi district, Karnataka, India. We assessed the efficacy of 14 days PQ regimen (0.25 mg/kg/day) to prevent P. vivax recurrence. Microscopically, aparasitemic adults (≥18 years) after acute vivax malaria on day 28 were re-enrolled into 15 months’ long follow-up study. A peripheral blood smear examination was performed with participants at every 1–2 month interval. A nested PCR test was performed to confirm the mono-infection with P. vivax. Of 114 participants, 28 (24.6%) recurred subsequently. The median (IQR) duration of the first recurrence was 3.1 (2.2–5.8) months which ranged from 1.2 to 15.1 months, including initial 28 days. Participants with history of vivax malaria had significantly higher risk of recurrence, with hazard ratio (HR) (95% CI) of 2.62 (1.24–5.54) (P=0.012). Severity of disease (11.4%, 13/114) was not associated (P=1.00) with recurrence. Of 28 recurrence cases, the nPCR proved that P. vivax mono-infection recurrence rate was at least 72.7% (16/22) at first recurrence. In Udupi district, PQ dose of 0.25 mg/kg/day over 14 days seems inadequate to prevent recurrence in substantial proportion of vivax malaria. Patients with a history of vivax malaria are at high risk of recurrences.
Adult ; Follow-Up Studies ; Humans ; India* ; Malaria ; Malaria, Vivax* ; Plasmodium vivax* ; Plasmodium* ; Polymerase Chain Reaction ; Primaquine* ; Recurrence ; Tertiary Healthcare* ; Treatment Failure

INTRODUCTIONChloroquine, in combination with primaquine, is used as the firstline treatment for uncomplicated P. vivax malaria in Thailand. In view of the declining efficacy of chloroquine in many P. vivax endemic areas, the possibility of emergence of chloroquine- resistant P. vivax in Thailand is a concern. The aim of this study was to assess the trends in therapeutic efficacy of chloroquine and primaquine for the treatment of uncomplicated P. vivax malaria and to assess the utility of parasite clearance times as a measure of efficacy.

MATERIALS AND METHODSThis study consisted of: 1) review of medical records of patients who were hospitalised for a period during their treatment for uncomplicated P. vivax malaria at the Hospital for Tropical Diseases, Bangkok, Thailand between 2004 and 2013. Treatment consisted of chloroquine (1500 mg base administered over 3 days) or chloroquine (as before) plus primaquine (15 to 30 mg base/daily for 14 days from day 2); and 2) systematic review of the literature in English to assess current standards in the reporting of parasite clearance times.

RESULTSThe 28-day cure rate was 99.1%. The range of median parasite clearance time over the 10-year period was 46 to 59 hours, and there was statistical evidence for an increasing trend in parasite clearance times between 2009 and 2013. Heterogeneity was noted among previous chloroquine efficacy studies in the measurement and reporting of parasite clearance.

CONCLUSIONThe treatment of P. vivax infection with a combination of chloroquine and primaquine has remained efficacious in Thailand. Increasing rates of parasite clearance in a population over time may be a useful early warning mechanism for the emergence of chloroquine resistance. The utility of monitoring time-trends in parasite clearance to detect resistance may be enhanced if parasite clearance measurements are standardised.

Antimalarials ; therapeutic use ; Chloroquine ; therapeutic use ; Drug Resistance, Microbial ; Drug Therapy, Combination ; Humans ; Malaria, Vivax ; drug therapy ; Plasmodium vivax ; Primaquine ; therapeutic use ; Thailand ; Time Factors ; Treatment Outcome

Pneumocystis jirovecii pneumonia is a common opportunistic infection seen in patients with human immunodeficiency virus (HIV) infection. Dihydropteroate synthase (DHPS) is a target of sulfa drugs, and mutations in DHPS gene are associated with failure in treatment and prophylaxis of P. jirovecii infections in HIV-infected patients. Here, we report a case of a patient with P. jirovecii infection, harboring DHPS gene mutations, who had not been previously treated with trimethoprim/sulfamethoxazole (TMP/SMX). A 50-yr-old man was admitted to the hospital with symptoms such as fever, cough, sputum, and sore throat. Chest computed tomography scanning revealed diffuse ground glass opacity in both the lungs, and the patient was diagnosed as having HIV infection with a CD4+ T cell count of 22/µL. Immunohistochemical test results were positive for P. jirovecii. He was treated with TMP/SMX; however, his symptoms and laboratory findings did not improve. The treatment was changed to clindamycin and primaquine, and his symptoms improved after 3 days. Molecular testing of the sample for the detection of DHPS gene mutations and the typing of mitochondrial large subunit rRNA (mtlsurRNA) revealed DHPS gene mutations at codon 55 and 57, respectively, and the case had type 3 mtlsurRNA. This case study illustrates that DHPS mutation test results can be positive even in patients without previous exposure to TMP/SMX.
Cell Count ; Clindamycin ; Codon ; Cough ; Dihydropteroate Synthase ; Fever ; Glass ; HIV ; HIV Infections ; Humans ; Lung ; Opportunistic Infections ; Pharyngitis ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia* ; Primaquine ; Sputum ; Thorax

Primaquine was approved for treatment of malaria in 1952 by the United States Food and Drug Administration (FDA). It has remained the only FDA-licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. It is associated with serious hazards and side effects, such as hemolytic anemia and methemoglobinemia. However, there is no report of primaquine causing liver injury in Korea. We describe a case of acute liver failure following primaquine overdose in a 19-year-old man.
Anemia, Hemolytic ; Drug-Induced Liver Injury ; Humans ; Korea ; Liver ; Liver Failure, Acute* ; Malaria ; Methemoglobinemia ; Plasmodium vivax ; Primaquine ; Schizonts ; United States Food and Drug Administration ; Young Adult

Incidence of parasitic diseases in Korea has been changing recently. The incidence of some parasitic diseases such as toxocariasis and cryptosporidiosis has increased, while that of soil-transmitted helminthic diseases has drastically decreased. Malaria reemerged in 1993 but has decreased in the 2010s. Here, common parasitic diseases that can be encountered in the clinical field are introduced, along with therapeutic agents such as anthelmintics, anti-malarial drugs, and anti-protozoan drugs to help general physicians select the appropriate medicine for parasitic diseases. Currently, soil-transmitted helminths are not a public health problem. On the other hand, the egg positive rate of Clonorchis sinensis has not decreased rapidly due to the habit of eating raw fresh water fishes in endemic areas; however, due to low worm density, it is difficult to detect infected persons only by clinical symptoms. Toxocariasis and ocular acanthamoebiasis can be detected more frequently due to appropriate diagnostic tools and physicians' concern. Cases of intestinal trematodiases, intestinal protozoasis, and vaginal trichomoniasis have decreased year by year. Since enterobiasis, pediculosis, and scabies are contact-borne diseases, local transmission and resurgence are always possible. Only a few antiparasitic agents can be prescribed in the clinics: albendazole, praziquantel, metronidazole, chloroquine, primaquine, and crotamiton. It may be helpful to general physicians to be reminded of the indications, prescription methods, and side effects described briefly for each drug that can be prescribed for parasitic diseases. Further information can be gathered from the Korea Pharmaceutical Information Service (http://www.kpis.or.kr/). For accurate diagnosis and prescription, a parasitologist may be consulted.
Albendazole ; Animals ; Anthelmintics ; Antiparasitic Agents ; Chloroquine ; Clonorchis sinensis ; Cryptosporidiosis ; Eating ; Enterobiasis ; Fishes ; Fresh Water ; Hand ; Helminths ; Humans ; Incidence ; Information Services ; Korea ; Lice Infestations ; Malaria ; Metronidazole ; Ovum ; Parasitic Diseases ; Praziquantel ; Prescriptions ; Primaquine ; Public Health ; Scabies ; Toluidines ; Toxocariasis

BACKGROUND: Plasmodium vivax malaria is an acute debilitating illness characterized by recurrent paroxysmal fever and relapses from hypnozoites in the liver. Although a few studies reported clinical characteristics of vivax malaria in civilians after reemergence in the Republic of Korea, only a small group of patients was analyzed. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had been diagnosed with vivax malaria by peripheral blood smear in a university-affiliated hospital located in a malaria-endemic area between January 2005 and December 2009. RESULTS: During the study period, a total of 352 malarial cases from 341 patients were diagnosed. Vivax malaria was most commonly developed in July and August, 24.7% (87/352), and 21.9% (77/352), respectively. The mean (SD) age was 42.5 (14.7) years and the number of male patients was 243 (71.3%). Six patients had a previous history of vivax malaria from 6 months to 10 years before. A total of 337 patients (98.8%) had fever and the mean (SD) body temperature was 38.3 (1.4)degrees C. Common associated symptoms were chills (213/341, 62.5%), headache (115/341, 33.7%), and myalgia (85/341, 24.9%). Laboratory findings included thrombocytopenia (340/341, 99.7%), anemia (97/341, 28.5%), leukopenia (148/341, 43.4%), increase of aspartate transaminase (177/341, 51.9%), and increase of alanine transaminase (187/341, 54.8%). Hypotension (14/341, 4.1%), altered mentality (3/341, 0.9%), azotemia (3/341, 0.9%), spleen infarction (2/341, 0.6%), and spleen rupture (1/341, 0.3%) developed as complications. Chloroquine was administered to all patients and primaquine was administered with mean (SD) 3.39 (0.82) mg/kg to 320 patients. There were 11 recurrent infections during the study period. The median (range) time to recurrent infection was 100 (32-285) days. Platelet counts were higher (86,550 vs. 56,910/mm3) and time to treatment of malaria was shorter (5 vs. 7 days) in relapsed cases compared with first occurrence cases (P=0.046). CONCLUSIONS: The overall recurrence rate of vivax malaria was 3.2% (11/341) in this study. In recurred cases, malaria was diagnosed earlier and thrombocytopenia was less severe. To evaluate the risk factors associated with recurrence and adequate dose of primaquine in Korean patients, further large-scale prospective studies will be needed.
Alanine Transaminase ; Anemia ; Aspartate Aminotransferases ; Azotemia ; Body Temperature ; Chills ; Chloroquine ; Fever ; Headache ; Humans ; Hypotension ; Infarction ; Leukopenia ; Liver ; Malaria ; Malaria, Vivax ; Male ; Medical Records ; Platelet Count ; Primaquine ; Recurrence ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Rupture ; Spleen ; Thrombocytopenia ; Time-to-Treatment

In Korea, Plasmodium vivax (P. vivax) is the most common agent of malaria infection. However, as travel to regions where malaria is endemic increases, so do the numbers of Plasmodium falciparum and mixed infections. P. falciparum predominates, while P. vivax is rare in west-central Africa. We report on a case of mixed malaria infection with severe hemolytic anemia caused by P. falciparum and P. vivax in a 38-year-old man after traveling to Angola. A diagnosis of P. falciparum malaria was made by microscopic examination. However, both P. vivax and P. falciparum were detected by the polymerase chain reaction (PCR). As a radical cure P. vivax, the patient was treated with mefloquine, artemether, and primaquine. Both P. falciparum and P. vivax had disappeared from peripheral blood by admission day 4, however, low grade fever and headache persisted, and his hemoglobin and hematocrit levels were depleted. A peripheral blood smear was negative for both P. vivax and P. falciparum; however, a direct anti-globulin test and anti-nuclear antibody test were positive, suggesting immune hemolytic anemia. After conservative treatment, which included a transfusion with packed red blood cells (RBC), his symptoms and signs showed improvement and laboratory findings were normalized.
Adult ; Africa ; Anemia, Hemolytic ; Angola ; Artemisinins ; Coinfection ; Erythrocytes ; Fever ; Headache ; Hematocrit ; Hemoglobins ; Humans ; Korea ; Malaria ; Mefloquine ; Plasmodium falciparum ; Plasmodium vivax ; Polymerase Chain Reaction ; Primaquine

BACKGROUND: Inflammatory cytokines play an important role in human immune responses to malaria, although the role of these mediators in pathogenesis is unclear. In this study, we evaluated changes in cytokine levels following chemotherapy, and determined whether cytokine levels in serum correlated with the hematological parameters in the Korean vivax malarial patients. METHODS: The study population was composed of 31 patients in Inje University Ilsan Paik Hospital who were diagnosed with Plasmodium vivax infection. Cytokine profiles, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels, were assessed in serum samples obtained from the malaria patients three times, at the time of diagnosis (stage I) and after treatment with hydroxychloroquine (stage II) and primaquine (stage III). The level of each cytokine was measured using commercially available serum-based ELISA kits. Hematological parameters were simultaneously measured using a hematology autoanalyzer. RESULTS: At thetime of diagnosis, the TNF-alpha (mean, 62.9 pg/mL), IL-6 (mean, 45.5 pg/mL), and IL-10 (mean, 237.7 pg/mL) levels in the malaria patients were higher than the reference values. After treatment with hydroxychloroquine, these levels (TNF-alpha, P<0.01; IL-6, P<0.05; IL-10, P<0.01) significantly decreased to near-normal levels. Significant positive correlations were observed among the cytokine levels, but not between the cytokine levels and other hematological parameters. CONCLUSIONS: In this study, TNF-alpha, IL-6, and IL-10 levels increased at the time of diagnosis and rapidly decreased to normal levels after treatment the levels of these cytokines did not correlate with other hematological parameters.
Cytokines ; Enzyme-Linked Immunosorbent Assay ; Hematology ; Humans ; Hydroxychloroquine ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Malaria ; Malaria, Vivax ; Plasmodium vivax ; Primaquine ; Reference Values ; Tumor Necrosis Factor-alpha