Am. J. Trop. Med. Hyg., 77(4), 2007, pp. 609-611
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene
Two Cases of Plasmodium vivax Malaria with the Clinical Picture Resembling Toxic Shock
Joon Young Song,
Cheong Won Park,
You Mee Jo,
Jeong Yun Kim,
Jeong Hyun Kim,
Hyo Joong Yoon,
Chi Hoon Kim,
Chae Seung Lim,
Hee Jin Cheong*, AND
Woo Joo Kim
Division of Infectious Diseases, Department of Internal Medicine, and Department of Laboratory Medicine, Korea University, Seoul, Republic of Korea; Armed Forces Byeokje Hospital, Kyonggi Province, Republic of Korea
 |
ABSTRACT
|
Fatal complications of Plasmodium falciparum malaria have been reported. However, complicated P. vivax malaria is rare. We observed two unusual cases of P. vivax malaria who presented with clinical pictures of toxic shock. Both showed disseminated intravascular coagulation with marked thrombocytopenia, oliguric renal failure, and pulmonary edema. Examination of initial blood smears showed a P. vivax parasitemia of 2,352/µL and 12,376/µL, respectively. The patients were treated with hydroxychloroquine and primaquine without an antibacterial agent. These cases emphasize the importance of considering the possibility of P. vivax malarial infection in patients with a clinical picture resembling toxic shock if they have a travel history to malaria-endemic areas.
|
INTRODUCTION
|
Malaria is prevalent worldwide and remains a major health problem, accounting for up to 500 million febrile illnesses and several million deaths annually.1,2 In 1979, malaria was declared eradicated in the Republic of Korea, but it re-emerged in 1993.3 Since then, annual outbreaks of Plasmodium vivax malaria have occurred in northern Kyonggi Province and northwestern Kangwon Province near the demilitarized zone, which include Paju, Yeoncheon, Yangju, Gimpo, Gangwha, Cheorwon, and other areas (Figure 1
). In recent years, the annual case occurrence of P. vivax malaria in the Republic of Korea has been between 1,000 and 2,000 cases, half of whom are civilians and half of whom are military personnel and veterans.4
View larger version (37K):
[in this window]
[in a new window]
|
FIGURE 1. Plasmodium vivax malaria-endemic areas in the Republic of Korea in northern Kyonggi Province and northwestern Kangwon Province near the demilitarized zone (DMZ).
|
|
Generally, Korean P. vivax malaria is characterized by a mild clinical course and long incubation period. Although P. vivax malaria infections were sometimes associated with serious complications, including acute lung injury, retinal hemorrhage, and splenic rupture,5–7 shock due to malaria was extremely rare, which is contrary to P. falciparum malaria cases. We report two cases of P. vivax malaria who had a clinical picture of toxic shock as an early manifestation.
Case 1.
A 21-year-old soldier was admitted to the intensive care unit at Armed Forces Byeokje Military Hospital (Ky-onggi Province, Republic of Korea) in August 2005 because of high fever (up to 40°C), dizziness, and general weakness. Fever had begun six days earlier and relapsed every 48 hours despite hydration and anti-inflammatory medication. The interval between febrile episodes got shorter with time. He also had loose stool and right upper abdominal discomfort for two days. He has been performing his military service in Paju for the past three months. Paju is one of the most common areas endemic for P. vivax malaria in the Republic of Korea (Figure 1
).
On presentation, he was febrile (39°C) and pale, and his tongue was dehydrated. He was drowsy, but his neck was not stiff and no pathologic reflex was found. On physical examination, hypotension (70/40 mm of Hg), tachycardia (105 beats/minute), hepatosplenomegaly, and fine crackles in both lower lung fields were observed. Laboratory tests showed a low platelet count, an abnormal liver function test result, an abnormal disseminated intravascular coagulation profile, a high level of triglycerides, and mild metabolic acidosis (Table 1). Hepatic steatosis and gallbladder wall thickening were observed, but no abscess was found by abdominal ultrasonography. Microscopic examination of peripheral blood smears showed many ring forms, trophozoites, and schizonts. Some infected red blood cells were enlarged, and the parasitemia density was 2,352/µL (Figure 2).
View larger version (103K):
[in this window]
[in a new window]
|
FIGURE 2. Peripheral blood smears of case 1 on day 1. Parasites of all stages were observed: Shown are red blood cells containing ring forms (A), trophozoites (B), schizonts (C), and gametocytes (D) (magnification x 1,000). This figure appears in color at www.ajtmh.org.
|
|
We inserted a central venous catheter and a foley catheter. Initial central venous pressure (CVP) was 11cm of H2O and anuria persisted for approximately 1.5 hours. After hydration and vasopressor treatment, blood pressure returned to a normal level and urination occurred. These therapies were maintained and tapered over the next four days. A standard regimen of hydroxychloroquine (1,500 mg base) was used for P. vivax malaria and primaquine (15 mg base for 14 days) were given for the prevention of relapse. No antibacterial agent was administered. The level of parasitemia decreased to 112/ µL on the third day of hospitalization and was undetectable four days after hospitalization. Laboratory results were normal and the patient was discharged without complications. He has remained asymptomatic for one month during follow-up.
Case 2.
A 33-year-old engineer was admitted to Korea University Guro Hospital (Seoul, Republic of Korea) in August 2005. The patient was febrile with chills and dizziness. Fever had begun one week earlier and relapsed every two or three days. He also complained of nausea and abdominal discomfort. He worked at a broadcasting station and had been in Yangju and Dongducheon in the northeastern part of Ky-onggi province for the last two months (Figure 1).
His vital signs were unstable with hypotension (70/40 mm of Hg) and relative bradycardia (88 beat/minute). Hepatosplenomegaly was observed, and a fine crackle was heard in both lower lung fields. Initial CVP was 9.5 cm of H2O and oliguria (less than 30 ml/hour) persisted for approximately 2–3 hours. After hydration and management with a vasopressor, blood pressure returned to a normal level and urination occurred. Therapy was maintained and tapered over five days.
The results of laboratory tests were similar to those of case 1 (Table 1). Microscopic examination of peripheral blood smears showed many intracellular malarial parasites (12,376/ µL) compatible with P. vivax malaria. The patient was treated with hydroxychloroquine and primaquine. No antibacterial agent was given. He had no further complications and was discharged after seven days in the hospital; all laboratory results were normal.
Species identification.
In addition to microscopic examination, we performed rapid immunocapture assay (OptiMal test; Diamed, Morat, Switzerland) and a polymerase chain reaction (PCR) to identify the species of malaria in case 1. The OptiMal test is based on immunologic detection of Plasmodium lactate dehydrogenase. The assay was performed according to the manufacturer’s instruction. The result was recorded on the basis of the observation of the precipitated band: single band (positive for P. vivax), double band (positive for P. falciparum), absence of a band (negative). In case 1, a single band was obtained (Figure 3).
View larger version (82K):
[in this window]
[in a new window]
|
FIGURE 3. Additional studies to identify the species of malaria. A, Result of rapid immunocapture assay (OptiMal test). A single band indicates positivity for Plasmodium vivax, and no band indicates no malaria infection. B, Allele-specific polymerase chain reaction for detection of P. vivax and P. falciparum. The P. vivax malarial is between 400 and 500 basepairs (bp) and the P. falciparum malarial band is between 300 and 400 bp.
|
|
An allele-specific PCR was performed using previously described primers.8 It showed that only P. vivax was present in the patient’s blood (Figure 3). Thus, we could exclude co-infection with other Plasmodium species.
|
DISCUSSION
|
We described two cases of P. vivax malaria with a clinical picture of toxic shock as an early manifestation. Usually, P. vivax malaria is known to show a benign clinical course, whereas P. falciparum malaria is characterized by much more acute and severe clinical picture than malaria caused by other Plasmodium species. In P. falciparum malaria, the P. falciparum erythrocyte membrane protein 1 (PfEMP-1) is important in pathogenesis; the cytoadherence protein is also believed to be associated with pathogenesis.9 Moreover, P. falciparum can infect all stages of erythrocytes, which aids in producing heavy parasite burdens.10 In comparison, P. vivax malaria is devoid of PfEMP-1 and the parasite is selective for reticulocytes; therefore, the parasite burden is usually less than 1%.10,11 These facts explain why complications are rare in P. vivax malaria. Initial blood smears from both cases showed P. vivax parasitemias of 2,352/µL and 12,376/µL, respectively, which were not higher than those previously reported (32–52,000/µL).12 Nevertheless, shock was accompanied by metabolic acidosis, hepatic, and renal dysfunction developed in our cases. It is uncertain how and why the shock occurred in these P. vivax malaria infections.
Although serious complications of P. vivax malaria are rare, severe anemia, cerebral malaria, acute respiratory distress syndrome, and acute renal failure have occurred,5–7 and some risk factors such as a high level of parasitemia, old age, and co-infection of Salmonella typhi have been reported.13 However, shock due to P. vivax malaria has been extremely rare. As previously described, non-immune people tend to have a more severe clinical picture compared with those who are semi-immune to malaria.1 Our two cases lived in non-endemic areas and they were otherwise healthy people without any underlying diseases; case 1 was born and raised in Nonsan, which is located in south central Chungcheong Province, and case 2 have lived in southern Seoul for several years. Therefore, we assumed that the immune status of these host might be one of the factors causing shock, but their health status was believed to be a prognostic factor rather than the cause of the shock. Further studies are required to clarify the pathogenesis.
The levels of acute-phase reactants were relatively lower in the present cases compared with patients with bacterial infections. However, shock due to P. vivax malaria was clinically indistinguishable from septic shock caused by gram-negative bacteria. In both cases, the blood cultures were negative and the patients recovered without being treated with antibacterial agents.
These cases emphasize the importance of considering the possibility of P. vivax malarial infection when patients have a clinical picture of toxic shock if they have a history of travel to malaria-endemic areas. Of note, P. vivax hibernans, which has a long incubation period, is still found in northern china and adjacent countries.14 Thus, a detailed history is required for an accurate diagnosis.
Received January 18, 2006.
Accepted for publication March 2, 2006.
* Address correspondence to Hee Jin Cheong, Section of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, 97 Guro Dong-Gil, Guro Gu, (152-703) Seoul, Republic of Korea. E-mail: heejinmd{at}medimail.co.kr 
Authors’ addresses: Joon Young Song, Cheong Won Park, You Mee Jo, Jeong Yun Kim, Hee Jin Cheong, and Woo Joo Kim, Division of Infectious Diseases, Department of Internal Medicine, Korea University, Seoul, Republic of Korea. Jeong Hyun Kim, Hyo Joong Yoon, and Chi Hoon Kim, Armed Forces Byeokje Hsopital, Kyonggi Province, Republic of Korea. Chae Seung Lim, Department of Laboratory Medicine, Korea University, Seoul, Republic of Korea.
Reprint requests: Hee Jin Cheong, Section of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, 97 Guro Dong-Gil, Guro Gu, (152-703) Seoul, Republic of Korea, Telephone: 82-2-818-6649, Fax: 82-2-866-1643, E-mail: heejinmd{at}medimail.co.kr.
|
REFERENCES
|
- Greenwood BM, Bojang K, Whitty CJ, Targett GA, 2005. Malaria. Lancet 365: 1487–1498.[Web of Science][Medline]
- Guerin PJ, Olliaro P, Nosten F, Druilhe P, Laxminarayan R, Binka F, Kilama WL, Ford N, White NJ, 2002. Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development. Lancet Infect Dis 2: 564–573.[Web of Science][Medline]
- Ree HI, 2000. Unstable vivax malaria in Korea. Korean J Parasitol 38: 119–138.[Medline]
- Yeom JS, Ryu SH, Oh S, Lee WJ, Kim TS, Kim KH, Kim YA, Ahn SY, Cha JE, Park JW, 2005. Status of Plasmodium vivax malaria in the republic of Korea during 2001–2003. Am J Trop Med Hyg 73: 604–608.[Abstract/Free Full Text]
- Islam N, Qamruddin K, 1995. Unusual complications in benign tertian malaria. Trop Geogr Med 47: 141–143.[Web of Science][Medline]
- Torres JR, Perez H, Postigo MM, Silva JR, 1997. Acute non-cardiogenic lung injury in benign tertian malaria. Lancet 350: 31–32.[Web of Science][Medline]
- Kim SM, Kim KB, Jung HJ, Kim WJ, Kim MJ, Park SC, 1997. Retinal hemorrhage in an adult with P. vivax malaria. Korean J Infect Dis 29: 323–326.
- Cho D, Kim KH, Park SC, Kim YK, Lee KN, Lim CS, 2001. Evaluation of rapid immunocapture assays for diagnosis of Plasmodium vivax in Korea. Parasitol Res 87: 445–448.[Web of Science][Medline]
- Newbold C, Craig A, Kyes S, Rowe A, Fernandez-Reyes D, Fagan T, 1999. Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum. Int J Parasitol 29: 927–937.[Web of Science][Medline]
- Simpson JA, Silamut K, Chotivanich K, Pukrittayakamee S, White NJ, 1999. Red cell selectivity in malaria: a study of multiple-infected erythrocytes. Trans R Soc Trop Med Hyg 93: 165–168.[Web of Science][Medline]
- Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, Miller LH, 1993. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 261: 1182–1184.[Abstract/Free Full Text]
- Oh MD, Shin H, Shin D, Kim U, Lee S, Kim N, Choi MH, Chai JY, Choe K, 2001. Clinical features of vivax malaria. Am J Trop Med Hyg 65: 143–146.[Abstract]
- Gandapur AS, Khattak S, Khan H, 1988. A patient with vivax malaria and enteric fever presenting as a case of jaundice with leukaemoid reaction. Pak Med Assoc 38: 148–149.
- Nicholas J, 1996. Malaria. Gordon CC, ed. Manson’s Tropical Disease. 20th edition. London: W. B. Saunders, 1087–1163.
This article has been cited by other articles:
|
|
|
|
 
J. K. Baird
Resistance to Therapies for Infection by Plasmodium vivax
Clin. Microbiol. Rev.,
July 1, 2009;
22(3):
508 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION
