Infectious Diseases in Clinical Practice:
Late Appearance of Malaria: Commentary
Wilson, Mary Elizabeth MD, FACP, FIDSA, FASTMH; Written as an editorial commentary regarding Jenks J, Heidari S, Watts L, Nader C. A Case of Plasmodium falciparum Malaria in a Man 6 Months After Visiting a Malaria-Endemic Region on pages 173–176 of the Journal.
From the Harvard Medical School, Washington, DC.
Correspondence to: Mary Elizabeth Wilson, MD, FACP, FIDSA, FASTMH, Department of Global Health and Population, Harvard School of Public Health, Boston, MA. E-mail: firstname.lastname@example.org.
The author has no funding or conflicts of interest to disclose.
A barrier to making the diagnosis of malaria is thinking of it. Most clinicians in the United States do not regularly see patients with malaria, so they do not consider it in the differential diagnosis of patients who seek care for acute febrile illnesses.
Lessons from this case reported by Jenks and colleagues1 are several. Malaria can first appear many months or even a year or longer after exposure. Although this is most common with infections caused by Plasmodium vivax, Plasmodium ovale, or Plasmodium malariae, infections with Plasmodium falciparum occasionally manifest long after exposure. Among 489 falciparum malaria patients reported to the Centers for Disease Control and Prevention in 2009 for whom dates were available, 5 reported onset of illness more than 6 months after return to the United States.2 The likelihood of late onset of symptoms is higher with all other species of malaria than with P. falciparum infections. Clinicians should keep this in mind because individuals who have traveled more than a few weeks earlier may be unaware of the importance of tropical exposures and may not offer that history.
Although the interval between exposure and onset of illness is longer than usual, there is ample evidence that viable parasites can persist, sometimes for years, in patients infected with P. falciparum. Long persistence has been documented in individuals who have transmitted infection through donated blood. One such case of falciparum malaria described in 2009 was linked to a donor from Nigeria who had lived in United States for 5 years.2 He gave a history of having had malaria 15 years earlier in Nigeria. In a review of transfusion-transmitted malaria in the United States between 1963 and 1999, 4 cases were caused by P. falciparum. The donors included a foreign-born donor who had immigrated to the United States 3.5 years before donation and 3 US-born donors who had traveled to a malarious area 1 to 5 years (median 13 months) before donation.3
On the basis of the information provided, the patient would have lived in Nigeria for almost 30 years. Given that malaria is endemic throughout the country, the patient presumably had repeated exposure to infection over 3 decades, sufficient to lead to partial immunity. The data collected by the US Centers for Disease Control and Prevention reveal that Nigeria accounted for more than a third (254) of all malaria cases imported into the United States from Africa in 2009.2 It also ranks among the countries with the highest estimated relative case rates of malaria among US residents.
Incomplete immunity to malaria develops after repeated infections.4 In highly endemic areas, malaria mortality occurs primarily in children younger than 5 years. Older individuals, although frequently parasitemic, typically do not develop severe symptoms of infection. This partial immunity, however, is not durable, and individuals who leave an endemic area can develop symptomatic infection after re-exposure. Infections can be fatal, although infection overall may be less severe. Christen and colleagues5 in Switzerland found that nonimmune Europeans had a significantly higher case fatality rate than individuals from endemic countries.
The appearance of a case that seems out of place (temperate area in winter and long after exposure) should raise the possibility of alternative routes of transmission. Careful sleuthing is required to identify alternate routes. Several that have been documented include transfusion of blood and blood products, other health care-associated transmission (involving patients and health care workers in various reports), shared injection equipment among drug users, and suitcase malaria (unintentional carriage of an infective mosquito in suitcase to temperate area where it is released and takes a blood meal).6 In the patient reported in this journal, autochthonous transmission is not a possibility—either airport or transmission locally from another person with malaria—because of the time and place (in Boston in January). Given the reports of “suitcase” or “luggage” malaria, it would be useful to know the exact date when the patient’s ex-wife and children returned from Nigeria relative to the date when the patient first developed symptoms—and whether suitcases were opened in his residence. Information provided is not sufficiently detailed to exclude the possibility of suitcase malaria. The most plausible explanation, however, is imported malaria that the patient acquired in Nigeria.
The patient denied taking mefloquine but the authors do not comment on whether the patient might have taken other drugs (other than antimalarials) that have some antimalarial activity—and might have contributed to the delay in clinical illness. For the sake of completeness, it would useful to know patient’s human immunodeficiency virus status. Human immunodeficiency virus impairs the immune response to malaria and is associated with increased prevalence and severity of clinical malaria and increased frequency of parasitemia.7 Ideally, it would have been useful to have confirmation of species identification by polymerase chain reaction. In this case, diagnosis was based on peripheral smears read by a microbiologist and pathologist. The authors acknowledge the possibility of infection by more than 1 species, although most infections in Nigeria are caused by P. falciparum.
In today’s world with frequent international travel and migration, clinicians should routinely include a travel history and history of prior residence as a part of the medical history. It becomes even more critical in acutely ill patients who may have rapidly progressive illness for which the correct diagnosis may be essential in providing the appropriate treatment. One way to minimize the likelihood that the diagnosis of post–travel malaria will be missed or delayed is to educate travelers at the time chemoprophylaxis is given that, in the event they become ill after return, they must seek care and inform their treating clinician about their travel. It is most important during the first month after return (when most infections will become apparent) but remains relevant up to a year (and very rarely longer). Education pre–travel depends on individuals seeking evaluation before travel to a malarious area. In general, persons who are visiting friends and relatives (often in country of birth) are less likely than others to seek evaluation before travel and are more likely to develop a number of infections, including malaria and enteric fever.8
1. Jenks J, Heidari S, Watts L, et al.. A case of Plasmodium falciparum malaria in a man six months after visiting a malaria-endemic region. Infect Dis Clin Pract. 2012.
2. Centers for Disease Control and Prevention. Malaria surveillance summary—United States, 2009. MMWR Morb Mortal Wkly Rep. 2011; 60 (No. SS-3): 1–15.
3. Mungai M, Tegtmeier G, Chamberland M, et al.. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med. 2001; 344 (26): 1973–1978.
4. Doolan DL, Dobano C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev. 2009; 22 (6): 13–36.
5. Christen D, Steffen R, Schlagenhauf P. Deaths caused by malaria in Switzerland. Am J Trop Med Hyg. 2006; 75 (6): 1188–1194.
6. Zoller T, Naucke T, May J, et al.. Malaria transmission in non-endemic areas: case report, review of the literature and implications for public health management. Malar J. 2009; 8: 71.
7. Whitworth J, Morgan D, Quigley M, et al.. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet. 2000; 356: 1051–1056.
8. Leder K, Tong S, Weld L, et al.. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis. 2006; 43: 1185–1193.
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