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Letter
Concurrent Dengue and Malaria
Remi N. Charrel,*
Philippe Brouqui,† Cedric Foucault,† and Xavier de Lamballerie*
*Université de la Méditerranée, Marseille, France; and †AP-HM Hôpital
Nord, Marseille, France
Suggested
citation for this article
To the Editor: A 37-year-old woman, a logistics director for a
nongovernment organization, returned to France in March 2004 from an 18-day
trip to Guinea, Senegal, and Sierra Leone. Fever, chills, and myalgia
developed in the woman 3 days before she returned to France, and she treated
herself with aspirin and paracetamol (acetaminophen). Malaria prophylaxis
was taken neither during nor after the trip.
The day after returning to France, the woman's condition progressively
worsened; diarrhea and extreme weakness that led to the inability to walk
developed. Ten days after her return, she was admitted to the local hospital
and treated with intravenous quinine and oral doxycycline (2 g per day)
after thick and thin blood films showed 3% parasitemia with Plasmodium
falciparum. Three days later, she was still febrile and had conjunctival
jaundice, vomiting, insomnia, and moderate hemorrhagic manifestations
(epistaxis, blood in urine and feces). Three days after initial hospitalization,
the patient was transferred to the Infectious Diseases Unit in Marseille;
fever (39.5°C) continued, and hepatosplenomegaly developed. Biologic
analyses showed disseminated intravascular coagulation with platelet count
of 22,000/mL, an elevated prothrombin time (54% higher than the control
value), a longer activated clotting time (51 seconds versus a control
value of 34 seconds), a fibrinogen level of 0.9 g/dL, exaggerated plasma
fibrin formation and degradation, and hepatic cytolysis with both aspartate
aminotransferase and alanine aminotransferase levels of 80 U/L.
Although acute malaria had been diagnosed, viral serologic tests were
performed because the patient had returned from a tropical country with
a fever. Persons in these circumstances are systematically administered
a series of tests to determine the cause of their fever. Serologic tests
for dengue performed on the acute-phase serum (collected 13 days after
onset of symptoms) and convalescent-phase serum (collected 23 days after
onset of symptoms) showed the presence of immunoglobulin (Ig) M (titers
1:800 and 1:3,200, respectively) and IgG (titers 1:400 and 1:3,200, respectively),
which suggested that the patient had dengue fever and malaria concurrently.
These results were obtained by using the Dengue Duo IgM-capture and IgG-indirect
enzyme-linked immunosorbent assay (Biotrin, PanBio Pty. Ltd., Brisbane,
Australia). The same acute-phase serum was tested for flavivirus RNA by
seminested reverse transcription–polymerase chain reaction (RT-PCR) by
using flavivirus consensus primers PF1S and PF2R as previously described
(1) in conjunction with the sense primer PF3S (GCIATHTGGTAYATGTGGYT).
Attempts to isolate viruses by using C6/36 and Vero cells were unsuccessful,
which might be expected given the delay between the onset of symptoms
and specimen collection.
Sequence analysis of the 163-bp (primers excluded) PCR product (GenBank
accession no. AY862501) showed 89%–99.4% range of homology with 34 dengue
3 virus strains by using the BLAST nucleotide program. Similarities obtained
with sequences of dengue virus 1, 2, and 4 were ≤87%. Phylogenetic
analysis performed with the patient sequence together with homologous
sequences from dengue viruses and other flaviviruses showed that it corresponded
to dengue 3 virus species. RT-PCR amplification on the convalescent-phase
serum was negative. Based on World Health Organization criteria, the patient
was diagnosed with dengue fever (2). The patient's interview
showed a previous dengue fever episode in Haiti in 1995 and a previous
malaria episode in Burundi in 2002, but biologic confirmation was not
available, and serum was not collected before this episode. Therefore,
we could not determine definitively whether this patient experienced primary
or secondary dengue. In light of virologic tests results, the diagnosis
of secondary dengue infection was more likely (3).
A PubMed search using the keywords dengue, mixed infections, dual infections,
simultaneous infections, and concurrent infections retrieved 14 references
published since 1958. In most cases, concurrent infection was with 2 dengue
virus strains from 2 different serotypes in a single patient (4,5).
Only 6 published studies reported concurrent infection with dengue virus
and a bacterium (Salmonella typhi, Shigella sonnei, Leptospira
spp.) (6–8) or with a virus such as Chikungunya virus
(9).
To our knowledge, this is the first report of mixed dengue–parasite infection,
dengue virus with P. falciparum. The authors previously questioned
the accuracy of a serologic test to diagnosis dengue fever in patients
experiencing malaria because reactivity was nonspecific on certain rapid
serologic assays (10); however, serologic tests used
in this study have demonstrated good specificity (10),
and molecular tests are not prone to such specificity problems. Classifying
this case as dengue hemorrhagic fever is questionable since some of the
hemorrhagic signs may have been caused by acute malaria. In cases of concurrent
infections involving a dengue virus, questions related to the influence
of mixed infection on severity and prognosis are, therefore, impossible
to address because of lack of information. Further investigations are
required because this situation likely occurs frequently in nature, despite
scant available data.
References
- Crochu S, Cook S, Attoui H, Charrel RN, De Chesse
R, Belhouchet M et al. Sequences
of flavivirus-related RNA viruses persist in DNA form integrated in
the genome of Aedes mosquitoes. J Gen Virol. 2004; 85:1971–80.
- World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment
and control. 2nd ed. Geneva: The Organization; 1997.
- Centers for Disease Control and Prevention. Case
definitions for infectious conditions under public health surveillance.
MMWR Morb Mortal Wkly Rep. 1997;46(RR-10):1–55.
- Lorono-Pino MA, Cropp CB, Farfan JA, Vorndam AV, Rodriguez-Angulo
EM, Rosado-Paredes EP, et al. Common
occurrence of concurrent infections by multiple dengue virus serotypes.
Am J Trop Med Hyg. 1999;61:725–30.
- Wang WK, Chao DY, Lin SR, King CC, Chang SC. Concurrent
infections by two dengue virus serotypes among dengue patients in Taiwan.
J Microbiol Immunol Infect. 2003;36:89–95.
- Sudjana P, Jusuf H. Concurrent
dengue hemorrhagic fever and typhoid fever infection in adult: case
report. Southeast Asian J Trop Med Public Health. 1998,29:370–2.
- Charrel RN, Abboud M, Durand JP, Brouqui P, de Lamballerie X. Dual
infection by dengue virus and Shigella sonnei in patient returning
from India. Emerg Infect Dis. 2003;9:271.
- Kaur H, John M. Mixed infection due to leptospira and dengue. Indian
J Gastroenterol. 2002;21:206.
- Myers RM, Carey DE. Concurrent
isolation from patient of two arboviruses, Chikungunya and dengue type
2. Science. 1967,157:1307–8.
- Charrel RN, de Lamballerie X. Low
specificity of an immunochromatographic serological assay for diagnosis
of dengue fever in travelers returning with malaria. Clin Diagn
Lab Immunol. 2002;9:1400.
Suggested citation
for this article:
Charrel RN, Brouqui
P, Foucault C, de Lamballerie X. Concurrent dengue and malaria [letter].
Emerg Infect Dis [serial on the Internet]. 2005 Jul [date cited].
Available from http://www.cdc.gov/ncidod/EID/vol11no07/04-1352.htm
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