JAC Advance Access originally published online on November 12, 2005
Journal of Antimicrobial Chemotherapy 2006 57(1):160-161; doi:10.1093/jac/dki414
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Correspondence |
Thrombotic-thrombocytopenic purpura following malaria prophylaxis with mefloquine
1 Dipartimento di Clinica Medica, Nefrologia and Scienze della Prevenzione, Università degli Studi di Parma, Via Gramsci 14, 43100 Parma, Italy; 2 Bangkok Hospital, Internal Medicine Divisions, 2 Soi Soonvijai 7, New Petchburi Road, Bangkok 10320, Thailand
* Corresponding author. Tel: +39-0521-701367; Fax: +39-0521-292627; E-mail: enrico.fiaccadori{at}unipr.it
Keywords: antimalarial agents , neurological status , plasmapheresis
Sir,
Mefloquine, a quinoline-derivative compound structurally similar to quinine, is recommended for malaria prophylaxis in travellers directed to zones where chloroquine-resistant strains of Plasmodium vivax and susceptible strains of Plasmodium falciparum are endemic.1
Mefloquine is generally well tolerated. However, gastrointestinal side effects, such as nausea, late vomiting, abdominal pain and diarrhoea are noted frequently and tend to be dose-related. Neurological side effects, such as dysphoria, dizziness, ataxia, headache, alterations in motor function or consciousness and visual or auditory disturbances, occur in about half of individuals, and are apparently unrelated to the dose. Severe neuropsychiatric reactions, such as disorientation, seizures, encephalopathy and a range of neurotic and psychotic manifestations, have also been described, but they are usually reversible upon drug withdrawal and symptomatic therapy.2 The occurrence of thrombotic thrombocytopenic purpura (TTP) has never been described so far in subjects receiving mefloquine, though it has been reported with the use of quinine (the parent compound of mefloquine), or other quinoline-derivatives (such as quinidine).3 Here we report a case of severe TTP requiring plasmapheresis associated with the use of mefloquine for malaria prophylaxis.
A 56-year-old male Caucasian, who travelled to Thailand for a medical congress, and had planned to travel later also to Cambodia, was admitted to an ICU in Bangkok (Thailand) after the sudden appearance of fever, confusion, lethargy and blurred vision. His past medical history was unremarkable except for mild diastolic hypertension not requiring pharmacological treatment.
He had been working as a biologist in a laboratory of immunological research at an Italian university. Two weeks before admission he had started taking mefloquine (1 tab. 250 mg/week) for malaria prophylaxis.
One week before admission he developed weakness, followed some days later by anorexia, myalgia and lethargy, and, finally, by fever, confusion and blurred vision. He denied drug allergy, the use of any medication other than mefloquine or other medicines containing quinine or quinine-like compounds. Physical examination was normal except for fever (38.6°C), leg petechiae and scleral icterus. Lung fields on X-ray were clear. Electrocardiogram, abdominal ecography and cerebral CT scan did not reveal any abnormality. Laboratory tests showed thrombocytopenia (26 000 platelets/mm3), leucocytosis (18 450 white blood cells/mm3, neutrophils 81%), anaemia (haemoglobin 10.1 g/L, haematocrit 29.6%) with anisocytosis and schistocytes, increased reticulocyte count (240 480 reticulocytes/mm3), and high lactate dehydrogenase (LDH) (22.40 µkat/L) and bilirubin levels (total bilirubin 54.7 µmol/L, indirect 42.7 µmol/L). Coagulation parameters were normal. Serum creatinine was 97.2 µmol/L; urine examination was normal except for microhaematuria. A central venous catheter was placed in the right jugular vein and two plasmapheresis sessions (12 units of fresh-frozen plasma) were performed in the first 24 h. Neurological status improved at the end of the first plasmapheresis; haematological abnormalities disappeared in the first few days of treatment (Figure 1). Plasmapheresis was continued daily for another 6 days (a total of eight sessions), until the patient was transferred back to Italy, then every other day for another week in a Nephrology Unit. We ruled out either infective or autoimmune processes. The former because the search for pathogens in blood, urine and faeces and imaging studies were negative; the latter, on the basis of extensive serology assessment for systemic lupus erythematosus, antiphospholipid syndrome and other immunological diseases. The patient was discharged home after 14 days.
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To our knowledge this is the first report describing a case of TTP associated with the use of mefloquine, an antimalarial agent widely used for prophylaxis or treatment of malaria.
Palmer et al.4 reported eight cases of isolated thrombocytopenia following mefloquine administration, whereas Orlando et al.5 described a case of massive intravascular haemolysis, haemoglobinuria, oliguria and fever within 2 days of treatment with mefloquine and halofantrine for P. falciparum malaria. Finally, Palmer et al.4 reported five patients who developed haemolytic anaemia after taking doses of up to 1500 mg of mefloquine.
In our patient the presence of severe neurological symptoms together with fever, thrombocytopenia and microangiopathic anaemia suggests a more complex haematological abnormality, such as TTP.6 The causal relation between drug and disease is supported by the temporal relation of drug intake with the onset of the clinical symptoms and laboratory abnormalities, as well as by their prompt improvement after the apheretic treatment and drug withdrawal. Of note, the neurological abnormalities, which were the main clinical findings in our patient, appeared soon after the intake of the first dose of the drug, and worsened after each dose until the third dose. Lastly, the patient denied taking any other drug along with mefloquine, and other infectious or immunological diseases were ruled out.
Given the widespread use of mefloquine for malaria prophylaxis and therapy in Western countries, it is important to also include this drug among the assessment of previous drug exposure in any person manifesting acute neurological abnormalities associated with thrombocytopenia and microangiopathic haemolytic anaemia.
Transparency declarations
None to declare.
Acknowledgements
Financial support from departmental funds of the Dipartimento di Clinica Medica, Nefrologia and Scienze della Prevenzione.
References
1.
Wyler DJ. Malaria chemoprophylaxis for the traveler. N Engl J Med 1993; 329: 31–7.
2. Schwartz E, Potasman I, Rotenberg M et al. Serious adverse events of mefloquine in relation to blood level and gender. Am J Trop Med Hyg 2001; 65: 189–92.[Abstract]
3.
Kojouri K, Vesely SK, George JN. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Ann Intern Med 2001; 135: 1047–51.
4. Palmer KJ, Holliday SM, Brogden RN. Mefloquine: a review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1993; 45: 430–75.[Medline]
5. Orlando G, Isabella L, Atzori C et al. Blackwater fever after halofantrine. Lancet 1996; 347: 1408–9.[Medline]
6.
Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol 2003; 14: 1072–81.
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