Working Group on International and

1. Bell DM; World Health Organization Working Group on International and Community Transmission of SARS. Public health interventions and SARS spread, 2003. Emerg Infect Dis. 2004;10:1900–6. 2. Chen KT, Twu SJ, Chang HL, Wu YC, Chen CT, Lin TH, et al. SARS in Taiwan: an overview and lessons learned. Int J Infect Dis. 2005;9:77–85. DOI: 10.1016/j. ijid.2004.04.015 3. WHO global infl uenza preparedness plan 2005 [cited 2009 Feb 4]. Available from http://www.who.int/csr/resources/ publications/influenza/GIP_2005_5E web.pdf 4. Swiss Federal Offi ce of Public Health. Swiss infl uenza pandemic plan 2006 [cited 2009 Feb 4]. Available from http://www.bag. admin.ch/infl uenza/01120/01134/03058/ index.html?lang=en 5. Swiss Federal Offi ce of Public Health. Détection des personnes fébriles dans les lieux publiques par thermographie infrarouge: résultats d’une étude préliminaire. Bulletin Offi ce Fédéral de la Santé Publique. 2007;33:608–9. 6. Van Herck K, Van Damme P, Castelli F, Zuckerman J, Nothdurft H, Dahlgren AL, et al. Knowledge, attitudes and practices in travel-related infectious diseases: the European airport survey. J Travel Med. 2004;11:3–8. 7. DiGiovanni C, Conley J, Chiu D, Zaborski J. Factors infl uencing compliance with quarantine in Toronto during the 2003 SARS outbreak. Biosecur Bioterror. 2004;2:265–72. DOI: 10.1089/ bsp.2004.2.265 8. Sadique MZ, Edmunds WJ, Smith RD, Meerding WJ, de Zwart O, Brug J, et al. Precautionary behavior in response to perceived threat of pandemic infl uenza. Emerg Infect Dis. 2007;13:1307–13. 9. Blendon RJ, Benson JM, Weldon KJ, Herrmann MJ. Pandemic fl u survey, Harvard School of Public Health, September 28–October 5, 2006 [cited 2009 Feb 4]. Available from http://www.hsph.harvard. edu/panfl u/panfl u_release_topline.doc 10. Lau JT, Kim JH, Tsui HY, Griffi ths S. Anticipated and current preventive behaviors in response to an anticipated human-tohuman H5N1 epidemic in the Hong Kong Chinese general population. BMC Infect Dis. 2007;7:18. DOI: 10.1186/1471-2334 -7-18


Near-Fatal Multiple Organ Dysfunction Syndrome Induced by Plasmodium malariae
To the Editor: We report a case of Plasmodium malariae-related multiple organ dysfunction syndrome (MODS) in a healthy immunocompetent patient. Despite extensive investigation, P. malariae was the only pathogen identifi ed. The patient's isolates had a combination of mutant alleles that could possibly explain the severity of the infection.
Five weeks after returning to France in November 2006 from Côte d'Ivoire, a 28-year-old French soldier was admitted to our surgical intensive care unit (University Hospital, Rennes, France) because of fever and MODS of suspected infectious origin. The patient had stopped taking his doxycycline for antimalarial chemoprophylaxis 3 days before his admission. During those 3 days he began to experience myalgia, fatigue, nausea, and vomiting but no fever. He took no medication. He then became unable to move his lower legs and experienced paresthesia just before his condition rapidly deteriorated. He was found at home by the local Emergency Medical Service (EMS) in respiratory distress and shock and required immediate orotracheal intubation for mechanical ventilation. When admitted to the intensive care unit, he had severe acute respiratory distress syndrome (PO 2 / FiO 2 , 65 mm Hg; PCO 2 , 90 mm Hg; with positive end expiratory pressure of 12 cm H 2 O). Transthoracic echocardiography and pulmonary artery catheterization showed severe global hypokinesia with a left ventricular ejection fraction of <10%, right ventricular dilatation, and low pulmonary artery occlusion pressure. Blood tests showed disseminated intravascular coagulation with 30 × 10 9 /L platelets, an international normalized ratio of 3.54, an activated partial thromboplastin time >180 s, and D-dimers at 25.6 μg/mL. He had severe mixed acidosis (pH 6.9 and arterial lactate 4.2 mmol/L) and acute renal failure. Blood cultures were performed. A thin-blood fi lm showed Plasmodium spp. within the red blood cells (parasitemia 0.4%). Rapid fl uid resuscitation was carried out and epinephrine was given, along with intravenous quinine (1,000 mg over 4 h, then 1,500 mg/d) and broadspectrum antimicrobial drugs (cefotaxime and ofl oxacine).
Extensive microbiologic investigations included tests for common bacteria at usual sampling sites and tests for specifi c arboviruses, Lep-tospira spp., Rickettsia spp., and parasites other than Plasmodium spp. Results were negative. P. malariae was found in the thick-blood fi lm.
The patient's cardiac and pulmonary functions stabilized over the next week. Epinephrine and ECMO were stopped. Surgical exploration of extensive lower-limb necrosis showed arterial thrombosis and Serratia marcescens infection. Amputation was necessary of the right leg at the thigh and of the left lower leg after 1 month of hospitalization. The patient was discharged from intensive care 90 days after hospital admission. One year later he was fully recovered and was using prostheses.
Almost all deaths from malaria are related to P. falciparum infection. We are unaware of previous reports of near-fatal imported P. malariae infection (1). Although we cannot defi nitively exclude bacterial co-infection, results were negative from blood cultures drawn before the fi rst antimicrobial drug dose and from all other microbiologic tests. To look for factors that might explain the unusual disease severity, we conducted additional investigations. The thick blood fi lm showed P. malariae trophozoites, schizonts, and gametocytes (285/μL). Rapid diagnostic tests were positive for pan-Plasmodium lactate dehydrogenase (pLDH) and aldolase but negative for histidinerich protein 2, which is specifi c for P. falciparum. Nested PCR with specifi c primers for P. falciparum and P. malariae, followed by sequence analysis of the SSUrRNA gene, and nested PCR, followed by sequence analysis of the pLDH gene, were negative for P. falciparum, positive for P. malariae, and negative for P. knowlesi (2).
The patient gave written informed consent to tests for genetic polymorphisms associated with severe sepsis, coagulation disorders, and MODS (3). Several of these polymorphisms were found (Table). He had a mannose-binding lectin (MBL) haplotype associated with low MBL levels (2 variants in the promoter region [homozygous at -550 and heterozygous at -221] and 1 in the fi rst exon [heterozygous for codon 54 mutation]) (5). He was homozygous for 4 gene polymorphisms associated with higher susceptibility or severity of severe sepsis or both and ARDS: CD14, lymphotoxin alpha, TNF-alpha, IRAK-1, and IL-6 (6-9). Furthermore, he was homozygous for a PAI-1 variant associated with decreased fi brinolysis and a higher risk for amputation, skin grafting, and death in meningococcal disease and trauma (10). Of 11 patients with uncomplicated P. malariae whom we screened for these polymorphisms, none had such a combination of high-risk polymorphisms as did our patient. Thus, the genetic background of our patient may have contributed to the severity of P. malariae infection.

Pulmonary Involvement and Leptospirosis, Greece
To the Editor: Since the leptospirosis outbreak associated with pulmonary hemorrhage in Nicaragua in 1995 (1), pulmonary manifestations of leptospirosis are often recognized in many countries; reported incidence has ranged from 20% to 70% (2)(3)(4). The severe pulmonary form of leptospirosis is accompanied by pulmonary hemorrhage, which directly results in high death rates (2,5). In Greece (population 11 million), leptospirosis cases in humans occur every year, usually from June to November (summer and autumn), with a peak in August. The annual incidence rate of the disease is 3 cases per 1 million population (6). Clinical presentation varies from a fl u-like syndrome to Weil disease, which includes jaundice, renal failure, and hemorrhagic complications. Studies on leptospirosis in Greece have been limited, and no reports have focused on pulmonary involvement.
During 1998-2007, we tested samples from 650 patients with suspected leptospirosis or hemorrhagic fever with renal syndrome (i.e., hantavirus infection). Various hospitals of northern Greece sent these samples to our laboratory (a World Health Organization Collaborating Center for Reference and Research on Arboviruses and Hemorrhagic Fever) for analysis. Because both diseases are endemic to Greece and have similar clinical, epidemiologic, and seasonal characteristics (7), all samples sent to our laboratory for testing either for leptospirosis or for hantavirus infection are always tested for both (8).
Leptospirosis was confi rmed for 123 patients, 10 (8.1%) of whom died (Table). For 72 case-patients, paired samples were available. A commercial ELISA (Leptospira IgG/IgM, Institute Virion/Serion GmbH, Würzburg, Germany) was used to detect immunoglobulin (Ig) G and IgM against Leptospira spp.. A nested PCR, which amplifi es a 289-bp fragment of the 16S rDNA gene, was used to detect bacterial DNA (9). IgM concentrations >20 U/mL indicated acute infection. Samples with borderline results were tested in parallel with a second sample taken from the patient 1 week later. IgG concentrations were considered only for paired samples, and a case was considered as acute leptospirosis when a >4-fold titer rise of IgG, or IgG seroconversion, was detected. When samples were taken before the sixth day of illness, initial diagnosis was achieved by PCR. In 6 of 10 fatal cases, leptospirosis was diagnosed only by PCR because antibodies were not detectable. Epidemiologic and clinical information for patients was collected from chart review, following a protocol approved by the medical school review board.
All 123 patients resided in northern Greece. Most (82.1%) were male; patients were 6-83 years of age (me-