Current status of vivax malaria among civilians in Korea

A result of national malaria surveillance in Korean civilians was described. Since a case of indigenous vivax malaria was detected in 1993, a total of 2,198 cases was confirmed by blood smear up to 1997. Of them, 1,548 cases were soldiers serving in the demilitarized zone (DMZ), while 650 cases were civilians. Number of civilian cases was 3 in 1994, 19 in 1995, 71 in 1996, and 557 in 1997. Of them, 239 were ex-soldiers who discharged after military service in the prevalent areas such as Paju, Yonchon, Kimpo, Kangwha, Tongduchon in Kyonggi-do and Chorwon in Kangwon-do while 308 patients were civilian residents in the prevalent areas. Seventy-two patients, living nationwide, had a history of visiting the prevalent areas during transmission season. Only 32 civilian patients denied any relation with the prevalent areas. As a whole, a half of the civilian cases was diagnosed when living in non-prevalent areas. Male patients in their twenties was the highest in number. Annual parasite index is steadily elevated in residents living in the prevalent areas. Monthly incidence showed an unimodal distribution, forming a peak in August. Ex-soldiers exhibited a delayed incubation ranging from 153 to 452 days (279 ± 41 days). The time required for diagnosis was shortened from 23.6 days in 1995 to 13.7 days in 1997. Although the current epidemic of vivax malaria started as a border malaria, it seems highly probable that vivax malaria is established in the local areas and responsible for at least a part of transmission.     

Incidence patterns of vivax malaria in civilians residing in a high-risk county of Kyonggi-do (province), Republic of Korea.

The characteristics of vivax malaria epidemics along the demilitarized zone (DMZ) in the Republic of Korea has been established by the early surveillance data. To further characterize the epidemic, data of civilian patients microscopically diagnosed with malaria from 1995 through 2000 were analyzed in Yonchon-gun (county). Malaria incidence was greater in male civilians > 30 years of age (p < 0.05). The annual parasite index was significantly higher in those living in the administrative areas (Myeon) traversed by DMZ than those living in Myons not traversed by DMZ (p < 0.05). Analysis according to the distance (4 to 14 km) from DMZ showed that people living in villages close to DMZ had higher annual parasite indices than those living in villages remote from DMZ (p for trend < 0.05). Civilians living in Myeons with plains and located in northwestern part of the county had higher annual parasite indices than those living in hilly Myeons located in southeastern part of the county (p for trend < 0.05). These findings suggest that the contraction of vivax malaria is related with night-time outdoor activities, and that the distance from DMZ is a risk factor. In this area, the flying distance of infected vector mosquitos can explain the annually repeating occurrence of civilian cases.     

A case of symptomatic splenic infarction in vivax malaria

Splenic infarction is a rare complication in malaria cases, and is caused primarily by Plasmodium falciparum. Recently in South Korea, only P. vivax has prevailed since 1993. Although the probability that symptomatic splenic infarction may occur in vivax malaria cases is considered relatively high, there have never been any case reports describing the occurrence of symptomatic splenic infarction in cases of vivax malaria. A 34-year-old man presented with fever that had persisted for 5 days. P. vivax infection was verified using a peripheral blood smear, and chloroquine was utilized to treat the fever successfully. Six days later, the patient developed pain in the left upper abdomen, which was diagnosed as splenic infarction by computed tomography.     

Border malaria characters of reemerging vivax malaria in the Republic of Korea.

Since 1993, the number of vivax malaria cases has increased every year in the northern part of the Republic of Korea (ROK). This study was designed to characterize factors related to the reemergence of malaria in the ROK. A total of 21 cases diagnosed in 1993 and 1994 distributed sporadically in the narrow zone along the demilitarized zone (DMZ). Of total 317 civilian inhabitant cases reported in 1994-1997, 287 cases were studied and 80.8% of them resided within 10 km from the southern border of the DMZ. The frequency distribution of anti-Plasmodium vivax antibody titers using indirect fluorescent antibody test was compared in three villages in relation with distance from the DMZ. The number of inhabitants with high antibody titers was larger in the village nearest to the border than that in more distant villages. The present results highly suggested that the reemerging vivax malaria start in the border area, most possibly caused by infected mosquitoes which flew across the border. This pattern of transmission repeated year after year.     

An Epidemiological Analysis of 28 Vivax Malaria Cases in Gimpo-si,Korea, 2020

Since 1993, vivax malaria has been recognized as a public health burden in Korea. Despite of pan-governmental malaria-control efforts and the dramatic reduction in the burden of this disease over the last 10 years, vivax malaria has not been well controlled and has remained continuously endemic. We focused interviewed and examined the charts of 28 confirmed vivax malaria patients given malarial therapy for whom daily records were kept from Gimpo-si, Gyeonggi-do of Korea. Various epidemiological characteristics of vivax malaria, including the incubation period, medication used, and recurrence, and an evaluation of the parasitic characteristics from the focused interviews of patients from this region are described here. Most of the participants indicated the 3 most common symptoms of malaria (headache, chills and fever). Of the 28 cases, 2 experienced a second attack and there were 17 and 11 cases with short- and long-term incubation periods, respectively, yielding a short-term to long-term ratio of 1.5. Based on the parasitemia stages, most of the participants were tested at 5 to 7 days (11 cases) and 7 to 15 days (11 cases) after initial wave of asexual parasites. In conclusion, public health authorities should consider developing management measures to decrease the time lag for diagnosis and drafting unified and robust guidelines for drug use for malaria and drawing up unified and robust guidelines on the use of medication for malaria. It also suggests that routine monitoring, surveillance, and precise medical surveys in high-risk vivax malaria endemic areas are pivotal to controlling this persistent public disease and finally eliminating it from Korea.     

Unstable vivax malaria in Korea

Korean vivax malaria had been prevalent for longtime throughout the country with low endemicity. As a result of the Korean war (1950-1953), malaria became epidemic. In 1959-1969 when the National Malaria Eradication Service (NMES) was implemented, malaria rates declined, with low endemicity in the south-west and south plain areas and high endemic foci in north Kyongsangbuk-do (province) and north and east Kyonggi-do. NMES activities greatly contributed in accelerating the control and later eradication of malaria. The Republic of Korea (South Korea) was designated malaria free in 1979. However, malaria re-emerged in 1993 and an outbreak occurred in north Kyonggi-do and north-west Kangwon-do (in and/or near the Demilitarized Zone, DMZ), bordering North Korea. It has been postulated that most of the malaria cases resulted from bites of sporozoite-infected females of An. sinensis dispersed from North Korea across the DMZ. Judging from epidemiological and socio-ecological factors, vivax malaria would not be possible to be endemic in South Korea. Historical data show that vivax malaria in Korea is a typical unstable malaria. Epidemics may occur when environmental, socio-economical, and/or political factors change in favor to malaria transmission, and when such factors change to normal conditions malaria rates become low and may disappear. Passive case detection is a most feasible and recommendable control measure against the unstable vivax malaria in Korea in cost-effect point of view.     

Reemerging vivax malaria: changing patterns of annual incidence and control programs in the Republic of Korea

Changing patterns of the reemerging Plasmodium vivax malaria in the Republic of Korea (South Korea) during the period 1993 to 2005 are briefly analyzed with emphasis on the control measures used and the effects of meteorological and entomological factors. Data were obtained from the Communicable Diseases Monthly Reports published by the Korea Center for Disease Control and Prevention, and webpages of World Health Organization and United Nations. Meteorological data of Kangwon-do (Province) were obtained from local weather stations. After its first reemergence in 1993, the prevalence of malaria increased exponentially, peaking in 2000, and then decreased. In total, 21,419 cases were reported between 1993 and 2005 in South Korea. In North Korea, a total of 916,225 cases were reported between 1999 and 2004. The occurrence of malaria in high risk areas of South Korea was significantly (P > 0.05) correlated with the mosquito population but not with temperature and rainfall. Control programs, including early case detection and treatment, mass chemoprophylaxis of soldiers, and international financial aids to North Korea for malaria control have been instituted. The situation of the reemerging vivax malaria in the Republic of Korea is remarkably improving during the recent years, at least in part, due to the control activities undertaken in South and North Korea.     

Re-emerging Plasmodium vivax malaria in the Republic of Korea.

Plasmodium vivax malaria, which was highly prevalent in the Republic of Korea, disappeared rapidly since 1970s. However, malaria re-emerged with the first occurrence of a patient in 1993 near the demilitarized zone (DMZ), the border between South Korea and North Korea. Thereafter, the number of cases increased exponentially year after year, totaling 6,142 cases (6,249 if United States Army personnels were included) by the end of 1998. Interestingly enough, the majority of cases (3,743; 61%) was soldiers aged 20-25, camping around the northern parts of Kyonggi-do or Gangwon-do (Province) just facing the DMZ. Among 2,399 civilian cases, 1,144 (47.7%) were those who have recently retired from their military services in the northern parts of the two Provinces. The re-emerging malaria characteristically revealed a combination type of short and long incubation periods with predominance of the long type. The course of illness was relatively mild, and the treatment was successful in most patients. Vector mosquitoes are Anopheles sinensis and possibly A. yatsushiroensis. Wide-scale preventive and control measures should be operated to eradicate this re-emerging disease. It has been suggested by many authors that the initial source of the re-emerging malaria was infected mosquitoes which had flown from the northern part of the DMZ.     

A recombinant Plasmodium vivax apical membrane antigen-1 to detect human infection in Iran

In Iran, Plasmodium vivax is responsible for more than 80% of the infected cases of malaria per year. Control interventions for vivax malaria in humans rely mainly on developed diagnostic methods. Recombinant P. vivax apical membrane antigen-1 (rPvAMA-1) has been reported to achieve designing rapid, sensitive, and specific molecular diagnosis. This study aimed to perform isolation and expression of a rPvAMA-1, derived from Iranian patients residing in an endemic area. Then, the diagnostic efficiency of the characterized Iranian PvAMA-1 was assessed using an indirect ELISA method. For this purpose, a partial region of AMA-1 gene was amplified, cloned, and expressed in pET32a plasmid. The recombinant His-tagged protein was purified and used to coat the ELISA plate. Antibody detection was assessed by indirect ELISA using rPvAMA-1. The validity of the ELISA method for detection of anti-P. vivax antibodies in the field was compared to light microscopy on 84 confirmed P. vivax patients and compared to 84 non-P. vivax infected individuals. The ELISA cut-off value was calculated as the mean+2SD of OD values of the people living in malaria endemic areas from a south part of Iran. We found a cut-off point of OD=0.311 that showed the best correlation between the sera confirmed with P. vivax infection and healthy control sera. A sensitivity of 81.0% and specificity of 84.5% were found at this cut off titer. A good degree of statistical agreement was found between ELISA using rPvAMA-1 and light microscopy (0.827) by Kappa analysis.     

Population dynamics of five anopheles species of the Hyrcanus group in northern Gyeonggi-do, Korea

To investigate the population densities of potential malaria vectors, Anopheles species were collected by light traps in malaria endemic areas, Paju and Gimpo, Gyeonggi-do of Korea. Five Anopheles Hyrcanus sibling species (An. sinensis, An. pullus, An. lesteri, An. kleini, and An. belenrae) were identified by PCR. The predominant species, An. pullus was collected during the late spring and mid-summer, while higher population consists of An. sinensis were collected from late summer to early autumn. These 2 species accounted for 92.1% of all Anopheles mosquitoes collected, while the other 3 species accounted for 7.9%. Taking into account of these population densities, late seasonal prevalence, and long-term incubation period (9-13 months) of the Korean Plasmodium vivax strain, An. sinensis s.s is thought to play an important role in the transmission of vivax malaria in the study areas.     

Imported Malaria over Fifteen Years in an Inner City Teaching Hospital of Washington DC

As endemic malaria is not commonly seen in the United States, most of the cases diagnosed and reported are associated with travel to and from the endemic places of malaria. As the number of imported cases of malaria has been increasing since 1973, it is important to look into these cases to study the morbidity and mortality associated with this disease in the United States. In this study, we would like to share our experience in diagnosing and treating these patients at our institution. We did a retrospective chart review of 37 cases with a documented history of imported malaria from 1998 to 2012. Among them, 16 patients had complicated malaria during that study period, with a mean length of hospital stay of 3.5 days. Most common place of travel was Africa, and chemoprophylaxis was taken by only 11% of patients. Travel history plays a critical role in suspecting the diagnosis and in initiating prompt treatment.     

Clinical efficacy of chloroquine versus artemether-lumefantrine for Plasmodium vivax treatment in Thailand

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.     

Control of epidemic malaria on the highlands of Madagascar

The Malagashy national malaria control programme ('Programme National de Lutte contre le Paludisme', PNLP) has been developing, since 1996, an epidemiological early warning system for malaria epidemics in the Central Highlands with the support of the Italian Development Cooperation. The system is based on the monitoring of malaria morbidity (clinical diagnosis) in 536 peripheral health centres (CSB) of the Highlands. The intervention area corresponds to 27 districts of the Antananarivo and Fianarantsoa provinces (4.7 million inhabitants) and spans around 100,000 square km. For each CSB a monthly warning threshold, defined as the 1993-1996 monthly mean number of malaria cases plus two standard deviations, was established. Three levels of epidemic alert have been defined according to the number of times the cases of presumptive malaria surpassed the threshold and according to the reported presence of severe malaria cases. The surveillance system relies also on the monitoring, in district hospitals of the Highlands, of the Plasmodium falciparum infection rate among clinically diagnosed malaria cases. A total of 185,589 presumptive malaria cases, corresponding to a 42/1000 malaria incidence, were recorded in 1997 by the surveillance system. During the same year 184 alerts of 2nd degree were reported. During 1998 173,632 presumptive malaria cases corresponding to a 38/1000 incidence were reported and 207 alerts of 2nd degree were detected; 75 of these alerts were investigated with ad hoc surveys and 3 initial malaria epidemics identified and controlled. Out of 6884 presumptive malaria cases diagnosed in the district hospitals during 1997-1998, only 835 (12.1%) have been confirmed by microscopy (P. falciparum 81.7%, P. vivax 15.0%, P. malariae 2.5%, P. ovale 0.2%, mixed infections 0.6%); 22.4% of these infections were imported cases from coastal endemic areas. The efficiency of the system in monitoring the trend of malaria morbidity and in the rapid detection and response to malaria epidemics is still being evaluated.     

Malaria: medical and surgical complications

The resurgence of malaria in Venezuela as an epidemic has caused an increase in the number of cases of this disease. 898 cases were registered in 1962 in contrast to 46,279 cases in 1988. This reality implies that all hospitals will have to face the increase of patients with this disease. Ten cases of malaria have been described and analyzed. These have been chosen for their medical and surgical complications, for which they were admitted to the "Hospital Universitario de Caracas" and "Hospital de Clínicas Caracas". Of these ten cases, eight were acquired in a natural way and two in an induced form. In six cases, the agent was P. falciparum; in three, P. vivax; in one, P. ovale and P.vivax combined. Five of the cases by P.falciparum were resistant to chloroquine, being necessary to treat them with a combination of quinine and other antimalaric drugs. Among the 10 described patients, there were: one case of splenic rupture in malaria by P. vivax, a severe case of anemia in a child with malaria by this same species and a case of relapse produced by P.vivax in another child with an insufficient radical treatment. The usual mistakes are observed in the management of malaria, such as a delay in the diagnosis and inappropriate radical treatment. As conclusion, publication of epidemiological, clinical and parasitological problems which are causing the actual epidemic, is recommended. This will be a guide in the fight against malaria, that must be considered again a national emergency.     

Temporal trends in severe malaria in Chittagong, Bangladesh

ABSTRACT: BACKGROUND: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division. METHODS: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh. RESULTS: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period. A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border. CONCLUSIONS: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be an important component of further reducing malaria-attributable disease and death in Bangladesh.     

Comparative study on longevity of Anopheles sinensis in malarious and non-malarious areas in Korea

An outbreak of vivax malaria has been occurring in northern part of Kyonggi-do and north-western part of Kangwon-do, where are located near the demilitarized zone, since 1993. For understanding of epidemiological features of malaria, the probability of daily survival of Anopheles sinensis, the vector species of malaria was compared in malarious and non-malarious areas in July-August, 2000. Total 915 females collected at three locations in malarious areas were dissected for ovaries, and 64.6% of the parous rate was found. Total 758 females collected at three locations in non-malarious areas were dissected, and 57.8% of the parous rate was observed. It was estimated from the parous rates that the probability of daily survival of An. sinensis females was 0.864 in malarious areas and 0.850 in non-malarious areas, which was not significantly different.     

Primaquine Administration after Falciparum Malaria Treatment in Malaria Hypoendemic Areas with High Incidence of Falciparum and Vivax Mixed Infection: Pros and Cons

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.     

Travelers' malaria among foreigners at the Hospital for Tropical Diseases, Bangkok, Thailand - a 6-year review (2000-2005)

We retrospectively examined the charts of travelers admitted to the Hospital for Tropical Diseases, Bangkok, Thailand, with malaria during the years 2000-2005. Twenty-one cases of malaria were identified, of which 12 (57%) were Plasmodium vivax infections and 9 (43%) were P. falciparum infections. There was one mixed case with vivax and falciparum infection. Only 1 P. falciparum case had complications. All cases were successfully treated with standard antimalarial drugs. Only 3 of the 21 cases were thought to be acquired in Thailand, the rest were regarded to be imported.     

Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of Plasmidium vivax malaria in Thailand

We conducted a study to compare the safety and tolerability of anti-relapse drugs elubaquine and primaquine against Plasmodium vivax malaria. After standard therapy with chloroquine, 30 mg/kg given over 3 days, 141 patients with P. vivax infection were randomized to receive primaquine or elubaquine. The 2 treatment regimens were primaquine 30 mg once daily for 7 days (group A, n = 71), and elubaquine 25 mg once daily for 7 days (group B, n = 70). All patients cleared parasitemia within 7 days after chloroquine treatment. Among patients treated with primaquine, one patient relapsed on day 26; no relapse occurred with elubaquine treatement. Both drugs were well tolerated. Adverse effects occurred only in patients with G6PD deficiency who were treated with primaquine (group A, n = 4), whose mean hematocrit fell significantly on days 7, 8 and 9 (P = 0.015, 0.027, and 0.048, respectively). No significant change in hematocrit was observed in patients with G6PD deficiency who were treated with elubaquine (group B, n = 3) or in patients with normal G6PD. In conclusion, elubaquine, as anti-relapse therapy for P. vivax malaria, was as safe and well tolerated as primaquine and did not cause clinically significant hemolysis.     

Surveillance of vivax malaria vectors and civilian patients for malaria high-risk areas in northern Gyeonggi and Gangwon Provinces near the demilitarized zone,Republic of Korea, 2003–2006

After re-emergence of malaria in 1993, a continued increase in Plasmodium vivax cases was observed from 1993 to 2006 in northern Gyeonggi and Gangwon Provinces adjacent to the demilitarized zone separating North from South Korea. Annual parasite incidence per 1000 people ranged from 0.33 in 2004 to 0.89 in 2006. While malaria case rates declined (22.6%) in 2004, they increased 75.1% in 2005 and 51.7% in 2006 from the previous years. An initial incorrect diagnosis of 46.8% of malaria cases as common cold resulted in a mean delay of 1.3 days for the detection malarial parasites. Of the total cases, 10.2% from December to May were due to latent intrinsic incubation infections acquired the previous malaria season and the rest of the cases from June to November were either latent or short incubation infections. Overall, the peak anopheline population occurred from July to September, resulting in a similar peak in malaria cases. While malaria cases increased during 2005–2006, anopheline populations, based on trap indices, were not significantly different during 4 years of surveillance. To decrease the malaria patient infective period to mosquitoes, public health centers in Paju and Cheorwon in 2006 prescribed chloroquine + primaquine at days 0–3 after initial malaria diagnosis followed by an additional 11 days of primaquine (early primaquine treatment), rather than chloroquine on days 0–3 and primaquine on days 4–17 (delayed primaquine treatment). A reduction in the malaria parasite incidence during 2007 was recorded for the two locations offering the early primaquine treatment relative to other locations using the delayed primaquine treatment.