Announcements
Eurosurveillance remains in the updated list of the Directory of Open Access Journals (DOAJ). It was first added to the DOAJ on 9 September 2004. Eurosurveillance is also listed in the Securing a Hybrid Environment for Research Preservation and Access / Rights MEtadata for Open archiving (SHERPA/RoMEO) [2], a database which uses a colour‐coding scheme to classify publishers according to their self‐archiving policy and to show the copyright and open access self-archiving policies of academic journals. Eurosurveillance is listed there as a ‘green’ journal, which means that authors can archive pre-print (i.e. pre-refereeing), post-print (i.e. final draft post-refereeing) and archive the publisher's version/PDF.

ESCAIDE participants are invited to the fifth Eurosurveillance scientific seminar on 30 November 2016

Follow Eurosurveillance on Twitter: @Eurosurveillanc

Read our articles on Zika virus infection

Read our articles on mcr-1-mediated colistin resistance

Note of concern published for 'Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015', http://bit.ly/29QFXPp


In this issue


Home Eurosurveillance Edition  2013: Volume 18/ Issue 40 Article 2
Back to Table of Contents
Previous Download (pdf)
Next

Eurosurveillance, Volume 18, Issue 40, 03 October 2013
Rapid communications
Plasmodium knowlesi infection imported to Germany, January 2013
  1. Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany
  3. Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  4. Mahidol-Oxford Tropical Medicine Research Unit; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Citation style for this article: Orth H, Jensen BO, Holtfreter MC, Kocheril SJ, Mallach S, MacKenzie C, Müller-Stöver I, Henrich B, Imwong M, White NJ, Häussinger D, Richter J. Plasmodium knowlesi infection imported to Germany, January 2013. Euro Surveill. 2013;18(40):pii=20603. Article DOI: http://dx.doi.org/10.2807/1560-7917.ES2013.18.40.20603
Date of submission: 02 October 2013

Plasmodium knowlesi was known as a plasmodium of macaques until P. knowlesi transmission to humans was recognised in Borneo and later throughout South-East Asia. We describe here a case of a P. knowlesi infection imported to Germany from Thailand. The patient had not taken antimalarial chemoprophylaxis and suffered from daily fever attacks. Microscopy revealed trophozoites and gametocytes resembling P. malariae. P. knowlesi malaria was confirmed by PCR.


In January 2013, a 55 year-old German woman presented to her practitioner because of fever, nausea and vomiting ten days after a holiday in Thailand. She had not taken antimalarial chemoprophylaxis. She was referred to hospital, where laboratory abnormalities included a decreased platelet count (27,000x109/L), elevated aspartate aminotransferase (AST) (237 U/L; normal value (nv): <35 U/L), alanine aminotransferase (ALT) (277 U/L; nv: <45 U/L), gamma-glutamyltransferase (gamma-GT) (480 U/L; nv: <55 U/L), lactate dehydrogenase (LDH) (419 U/L; nv: <248 U/L) and C-reactive protein (CRP) levels (102 mg/L; nv: <5 mg/L). Red blood cell count, white blood cell count (7.360x109/L), electrolytes, urea, creatinine and CK were normal. Electrocardiography showed no abnormalities except for sinus tachycardia with a heart rate of 105 beats per minute Suspecting a bacterial infection, empirical antibiotic treatment with piperacillin and tazobactam was initiated. However, the patient continued to suffer from daily fever attacks. The serum creatinine rose to 3.45 mg/dL, while she became oliguric. The procalcitonine level rose to 3.71 ng/mL, interleukin-6 to 66.8 pg/mL, haematocrit fell to 29.7%, and microscopy of stained blood films revealed malaria parasites, but the hospital’s microbiologist reported that he felt unable to identify a specific Plasmodium species.

With a diagnosis of malaria and acute renal failure, the patient was referred to our Tropical and Infectious Diseases service. Rapid immunochromatography test (Malaria now Binax, United States) showed a negative result for P. falciparum-specific histidine-rich protein-2 but was positive for pan-plasmodial aldolase. In stained thin and thick blood films, plasmodia resembling P. malariae were present with 0.2% trophozoite parasitaemia and numerous gametocytes. P. knowlesi malaria was suspected because of the disease severity and the patient’s recent stay in Khao Sok National Park in southern Thailand. A multiplex real-time PCR for the species P. falciparum, P. ovale, P. vivax and P. malariae detected in addition the presence of plasmodial DNA on genus level. The sequence of the amplified genus-specific DNA was homologous with the species P. knowlesi. Infection by this parasite was confirmed by a specific PCR in the Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand. DNA was extracted from a dry blood spot using QIAamp blood mini kit (Qiagen, Germany). Plasmodium spp. infection were tested using three PCR protocols based on 18sRNA [1-2], mitochondrial DNA [3], the linker region of dihydrofolate reductase and thymidylate synthase [4]. Monoinfection of P. knowlesi was confirmed by all three techniques. Direct sequencing from PCR products were also performed and showed more than 98% identity to reference P. knowlesi.

Intravenous treatment with artesunate (2.4 mg/kg) was started on Day 3 after admission and switched to oral treatment with artemether/lumefantrine the following day. The patient recovered promptly and malaria parasites cleared within two days. With intravenous isotonic saline administration, urine output was restored and serum creatinine fell to 1.3 mg/dL on Day 4.

Discussion

P. knowlesi was first described in 1931 as a plasmodium of long tailed and pig-tailed macaques and one year later was shown to be transmissible to humans [5]. A naturally acquired human infection was reported 1965 in a citizen of the United States returning from Malaysia [6]. Thereafter, human P. knowlesi infections were reported only occasionally until 2004, when a study by Singh et al. revealed that P. knowlesi accounted for more than 50% of endemic human malaria cases in Kapit division of the Malaysian state of Sarawak, located on the island of Borneo [7].

With increasing awareness of this pathogen, P. knowlesi has been diagnosed frequently in human malaria cases on the island of Borneo, and has also been reported from Indonesia, the Malay peninsula, Myanmar, the Philippines, Singapore, Thailand and Vietnam [8].

As a cause for imported malaria, P. knowlesi has been identified only occasionally:
only five cases of P. knowlesi malaria imported to Europe have been published so far. The first case was a Swedish traveller to Malaysian Borneo in 2006, the second a Finnish traveller to peninsular Malaysia in 2007, the third was a Spanish traveller in 2009 who had spent six month in several south east Asian countries including Indonesia, Malaysia, Thailand and Vietnam, and the fourth was a French tourist who presumably acquired the infection on the island of Kho Phayam (Thailand) in 2010 [9-12] (Figure). The most recent case was reported in August 2013 and occurred in a German traveller with human immunodeficiency virus (HIV) co-infection who presumably acquired the infection in Ranong province in Thailand [13]. 

Figure. Presumable geographical site of acquisition of Plasmodium knowlesi infection, Thailand, 2010 and 2013

The retrospective analysis of blood samples from Thailand suggests that the prevalence of P. knowlesi infections has not changed significantly over time during the period from 1996 to 2008 [3]. Therefore, it is most likely that the increasing number of cases recognised is due to the awareness of the possibility of human P. knowlesi malaria and to the application of diagnostic molecular biology techniques to differentiate this parasite from other malaria parasites.

The prevalence of P. knowlesi infections in Thailand (1%) is very low compared with the highly endemic Kapit division (50%) in Borneo, Malaysia Thailand [3,7]. Therefore, large numbers of imported cases from Thailand are not to be expected in the near future. However, changing tourism patterns like the trend towards eco-tourism might increase the risk of infection with P. knowlesi even in low prevalence countries. In the present case for instance, the infection was most likely acquired during a stay in the forested Khao Sok National Park inhabited by the natural monkey host.

It is important to recognise P. knowlesi infections, especially in the late stage when the parasites resemble P. malariae, because P. knowlesi infections can sometimes be associated with complications and may be fatal. A study on 107 patients reported severe malaria in 6.5% of P. knowlesi infections, among these three cases presenting with acute renal impairment. Whereas these severe P. knowlesi cases reported were associated with hyperparasitaemia, acute kidney failure occurred in our case despite a low parasitaemia of 0.2% [14]. Because of the possibility of a severe course of P. knowlesi infections, physicians must be increasingly aware of this possibility and contact specialised centres as soon as possible to ensure early appropriate diagnosis and timely treatment.



Conflict of interest

None declared.

Authors’ contributions
HM O and JR treated the patient and wrote the paper. MC H, C MkC, B H and M I did the parasitological and molecular investigations and contributed to writing the manuscript. BEO J, SJ K, S M, I MS, and D H managed the patient and contributed to the manuscript. All authors participated in writing the manuscript and approved the final version.



References
  1. Snounou G, Singh B. Nested PCR analysis of Plasmodium parasites. Methods Mol Med. 2002;72:189-203. PMid:12125116.
  2. Imwong M, Tanomsing N, Pukrittayakamee S, Day NPJ, White NJ, Snounou G. Spurious amplification of Plasmodium vivax small subunit RNA gene using the primers currently used to detect P. knowlesi. J Clin Microbiol. 2009;47(12):4173–5. http://dx.doi.org/10.1128/JCM.00811-09. PMid:19812279. PMCid:PMC2786678.
  3. Jongwutiwes S , Buppan P, Kosuvin R, Seethamchai S, Pattanawong U, Sirichaisinthop J, et al. Plasmodium knowlesi malaria in humans and macaques, Thailand. Emerg Infect Dis. 2011;17(10):1799-806. http://dx.doi.org/10.3201/eid1710.110349. PMid:22000348. PMCid:PMC3310673.
  4. Tanomsing N, Imwong M, Theppabutr S, Pukrittayakamee S, Day NP, White NJ, et al. Accurate and sensitive detection of Plasmodium species in humans by use of the dihydrofolate reductase-thymidylate synthase linker region. J Clin Microbiol. 2010;48(10):3735-7. http://dx.doi.org/10.1128/JCM.00898-10. PMid:20702666. PMCid:PMC2953080.
  5. Knowles RM, Das Gupta B. A study of monkey–malaria and its experimental transmission to man. Ind Med Gaz. 1932; 67:301–320.
  6. Chin W, Contacos PG, Coatney GR, Kimball HR. A naturally acquired quotidian-type malaria in man transferable to monkeys. Science 1965; 149(3686):865. http://dx.doi.org/10.1126/science.149.3686.865. PMid:14332847.
  7. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet. 2004;363(9414):1017-24. http://dx.doi.org/10.1016/S0140-6736(04)15836-4.
  8. Kantele A, Jokiranta TS. Review of Cases with the Emerging Fifth Human Malaria Parasite, Plasmodium knowlesi. Clin Infect Dis. 2011;52(11):1356-62. http://dx.doi.org/10.1093/cid/cir180. PMid:21596677.
  9. Berry A, Iriart X, Wilhelm N, Valentin A, Cassaing S, Witkowski B, et al. Imported Plasmodium knowlesi malaria in a French tourist returning from Thailand. Am J Trop Med Hyg. 2011;84(4):535-8. http://dx.doi.org/10.4269/ajtmh.2011.10-0622. PMid:21460005. PMCid:PMC3062444.
  10. Ta TT, Salas A, Ali-Tammam M, Martínez Mdel C, Lanza M, Arroyo E, et al. First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia. Malar J. 2010;9:219. http://dx.doi.org/10.1186/1475-2875-9-219. PMid:20663184. PMCid:PMC2921078.
  11. Bronner U, Divis PC, Färnert A, Singh B. Swedish traveller with Plasmodium knowlesi malaria after visiting Malaysian Borneo. Malar J. 2009;8:15. http://dx.doi.org/10.1186/1475-2875-8-15. PMid:19146706. PMCid:PMC2634766.
  12. Kantele A, Marti H, Felger I, Müller D, Jokiranta TS. Monkey malaria in a European traveler returning from Malaysia. Emerg Infect Dis. 2008;14(9):1434-6. http://dx.doi.org/10.3201/eid1409.080170. PMid:18760013. PMCid:PMC2603100.
  13. Ehrhardt J, Trein A, Kremsner PG, Frank M. Plasmodium knowlesi and HIV co-infection in a German traveller to Thailand. Malar J. 2013;12(1):283. http://dx.doi.org/10.1186/1475-2875-12-283. PMid:23941258. PMCid:PMC3765117.
  14. Daneshvar C, Davis TM, Cox-Singh J, Rafa'ee MZ, Zakaria SK, Divis PC, et al. Clinical and laboratory features of human Plasmodium knowlesi infection. Clin Infect Dis. 2009;49(6):852-60. http://dx.doi.org/10.1086/605439. PMid:19635025. PMCid:PMC2843824.


Back to Table of Contents
Previous Download (pdf)
Next

The publisher’s policy on data collection and use of cookies.

Disclaimer: The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal. The information provided on the Eurosurveillance site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her physician. Our website does not host any form of commercial advertisement. Except where otherwise stated, all manuscripts published after 1 January 2016 will be published under the Creative Commons Attribution (CC BY) licence. You are free to share and adapt the material, but you must give appropriate credit, provide a link to the licence, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

Eurosurveillance [ISSN 1560-7917] - ©2007-2016. All rights reserved.
 

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information:
verify here.