Plasmodium falciparum in asymptomatic immigrants from sub-Saharan Africa, Spain.
Article Type: Letter to the editor
Subject: Plasmodium falciparum (Health aspects)
Plasmodium falciparum (Research)
Malaria (Diagnosis)
Malaria (Research)
Immigrants (Health aspects)
Authors: Monge-Maillo, Begona
Norman, Francesca
Perez-Molina, Jose Antonio
Diaz-Menendez, Marta
Rubio, Jose Miguel
Lopez-Velez, Rogelio
Pub Date: 02/01/2012
Publication: Name: Emerging Infectious Diseases Publisher: U.S. National Center for Infectious Diseases Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 U.S. National Center for Infectious Diseases ISSN: 1080-6040
Issue: Date: Feb, 2012 Source Volume: 18 Source Issue: 2
Topic: Event Code: 310 Science & research
Product: Product Code: E198450 Immigrants
Geographic: Geographic Scope: Spain Geographic Code: 4EUSP Spain
Accession Number: 281175432
Full Text: To the Editor: A range of infectious diseases have been described in asymptomatic immigrants (1), which may justify the implementation of screening after obtaining consent. In particular, asymptomatic malaria caused by Plasmodium falciparum parasitemia among recently arrived immigrants may be a major public health problem outside malariaendemic areas because these patients may be involved in autochthonous transmission cycles and may act as reservoirs capable of reintroducing malaria into areas where it had been previously eradicated.

In 2010, we reviewed the medical records of 314 asymptomatic (defined as patients with no symptoms at the time of consultation) immigrants from sub-Saharan Africa who had settled in Spain, had not traveled to their countries of origin since arrival, and had been examined at the Tropical Medicine Unit (TMU) of the Ramon y Cajal Hospital in Madrid during the previous 5 years. Systematic screening included a blood count; serum biochemistry; basic urine analysis; serologic tests for HIV infection, hepatitis B or C infection, syphilis, and schistosomiasis (if epidemiologic risk factors were present); tuberculin skin test; analysis of fecal samples for parasites; and PCR to identify Plasmodium spp. (2). Date of arrival in Spain was obtained from the patient and corroborated by the nongovernmental organizations caring for them.

PCR for Plasmodium spp. was performed for 216 patients, and 10 (4.6%) had positive test results for P. falciparum. Nine were men; median age was 27 years (interquartile range [IQR] 20-31 years). The median period from arrival in Spain to malaria diagnosis was 4.5 months (IQR 1.7512.5 months). Three men received a diagnosis of P. falciparum malaria >1 year after arrival.

Patient 1 was a 32-year-old man from Angola who came to the TMU for screening 13 months after arriving in Spain. He was treated with a standard regimen of artesunate plus sulfadoxine/pyrimethamine; latent tuberculosis (TB) infection and schistosomiasis were also diagnosed. Patient 2 was a 17-year-old man from Senegal, seen at the TMU 14 months after arrival. Malaria treatment was not prescribed because he was lost to follow-up. He was also diagnosed with latent TB infection. Patient 3 was a 28-year-old man from Guinea who visited the TMU 28 months after arrival in Spain. He was treated with a standard regimen of atovaquone/ proguanil and also received diagnoses of tuberculosis (TB) infection, schistosomiasis, and strongyloidiasis. No statistically significant association was observed between positive or negative PCR for P. falciparum and a diagnosis of tuberculosis (TB) infection, hepatitis B or C virus infection, HIV infection, syphilis, intestinal parasite infection, or schistosomiasis. None of the 3 patients had received a blood transfusion since arriving in Spain.

Reported prevalence of imported malaria among immigrants may be >10%, according to some studies (1), with higher rates among persons from sub-Saharan Africa (malaria caused by P. falciparum occurring mainly 3 months after arrival). Clinical symptoms of malaria in immigrants are typically mild, with low levels of parasitemia. Many immigrants may be asymptomatic (1,3), which has been explained by partial immunity acquired gradually after prolonged exposure in areas with stable malaria transmission. Because infected persons may initially have no symptoms, implementation of malaria screening for recently arrived immigrants from disease-endemic areas would seem advisable (4).

How long a low level of P. falciparum parasitemia may persist once exposure to malaria has been discontinued is not known. Mathematical models have estimated the maximum duration of P. falciparum infection after interruption of transmission at -4 years (5), although delayed clinical presentations of P. falciparum malaria have been described as long as 2 (6), 4 (7), or even 8 years (8) after patients have left malaria-endemic areas. These data highlight that low asymptomatic parasitemia may persist long after migration.

Determining in which patients with asymptomatic parasitemia clinical malaria will develop and when, or if, any external factors may act as triggers would also be useful. A study in France found that 2.3% of malaria cases among immigrants developed >1 year after their arrival and that pregnancy and co-infection with HIV were factors associated with late presentation of malaria caused by P. falciparum (9).

Asymptomatic malaria cases may affect public health in non-disease-endemic areas because persons with low-grade parasitemia are capable of infecting mosquitoes (10). These persons could act as unidentified reservoirs and contribute to transmission in areas where malaria has been eliminated. In addition, congenital transmission or transmission by blood transfusion or organ transplantation may occur even when the donor has lived for years outside the malaria-endemic area.

Our cases highlight how malaria parasites may persist in asymptomatic immigrants long after their arrival in the host country (up to 28 months). On the basis of published reports of symptomatic delayed cases, we believe that the prevalence of persistently low-level parasitemia among asymptomatic immigrants is probably higher than previous estimates. Screening for malaria among immigrants long after arrival would help determine if there are any factors that influence the development of clinical malaria. Delayed screening could also be particularly relevant in certain risk groups, such as pregnant women and persons who are HIV positive. As a public health measure, such delayed screening could play a role in preventing outbreaks or reintroducing malaria in countries where it has been eradicated.

Acknowledgments

We thank L. Velasquez for technical assistance and help with the database.

Support was provided by the Red de Investigacion de Centros de Enfermedades Tropicales (RICET). RD 06/0021/0020.

Begona Monge-Maillo, Francesca Norman, Jose Antonio Perez-Molina, Marta Diaz-Menendez, Jose Miguel Rubio, and Rogelio Lopez-Velez

Author affiliations: Ramon y Cajal Hospital. Madrid, Spain (B. Monge-Maillo, F. Norman, J.A. Perez-Molina, M. Diaz-Menendez, R. Lopez-Velez); and National Centre of Microbiology, Madrid (J.M. Rubio)

DOI: http://dx.doi.org/10.3201/eid1801.111283

References

(1.) Monge-Maillo B, Jimenez BC, Perez-Molina JA, Norman F, Navarro M, Perez-Ayala A, et al. Imported infectious diseases in mobile populations, Spain. Emerg Infect Dis. 2009;15:1745-52.

(2.) Rubio JM, Post RJ, van Leeuwen WM, Henry MC, Lindergard G, Hommel M. Alternative polymerase chain reaction method to identify Plasmodium species in human blood samples: the semi-nested multiplex malaria PCR (SnM-PCR). Trans R Soc Trop Med Hyg. 2002;96:S199204. http://dx.doi.org/10.1016/S00359203(02)90077-5

(3.) Mascarello M, Gobbi F, Angheben A, Concia E, Marocco S, Anselmi M, et al. Imported malaria in immigrants to Italy: a changing pattern observed in north-eastern Italy. J Travel Med. 2009;16:317-21. http://dx.doi.org/10.1111/j.1708-8305. 2009.00321.x

(4.) Monge-Maillo B, Lopez-Velez R. Is screening for malaria necessary among asymptomatic refugees and immigrants coming from endemic countries? Expert Rev Anti Infect Ther. 2011;9:521-4. http://dx.doi.org/10.1586/eri.11.37

(5.) Sama W, Killeen GF, Smith T. Estimating the duration of Plasmodium falciparum infection from trials of indoor residual spraying. Am J Trop Med Hyg. 2004;70:625-34.

(6.) Krajden S, Panisko DM, Tobe B, Yang J, Keystone JS. Prolonged infection with Plasmodium falciparum in a semiimmune patient. Trans R Soc Trop Med Hyg. 1991;85:731-2. http://dx.doi. org/10.1016/0035-9203(91)90434-Z

(7.) Greenwood T, Vikerfors T, Sjoberg M, Skeppner G, Farnert A. Febrile Plasmodium falciparum malaria 4 years after exposure in a man with sickle cell disease. Clin Infect Dis. 2008;47:e39-41. http://dx.doi. org/10.1086/590250

(8.) Szmitko PE, Kohn ML, Simor AE. Plas modium falciparum malaria occurring 8 years after leaving an endemic area. Di agn Microbiol Infect Dis. 2009;63:105-7. http://dx.doi.org/10.1016/j.diagmicro bio.2008.08.017

(9.) D'Ortenzio E, Godineau N, Fontanet A, Houze S, Bouchaud O, Matheron S, et al. Prolonged Plasmodium falciparum infection in immigrants, Paris. Emerg Infect Dis. 2008;14:323-6. http://dx.doi. org/10.3201/eid1402.061475

(10.) Schneider P, Bousema JT, Gouagna LC, Otieno S, van de Vegte-Bolmer M, Omar SA, et al. Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. Am J Trop Med Hyg. 2007;76:470-4.

Address for correspondence: Rogelio LopezVelez, Tropical Medicine and Clinical Parasitology, Infectious Diseases Department, Ramon y Cajal Hospital, Carretera de Colmenar Km 9,1, Madrid 28034, Spain; email: rlopezvelez.hrc@salud.madrid.org
Gale Copyright: Copyright 2012 Gale, Cengage Learning. All rights reserved.