Is dengue and malaria co-infection more severe than single infections? A retrospective matched-pair study in French Guiana

Epelboin Loïc, Hanf Matthieu, Dussart Philippe, Ouar-Epelboin Sihem, Djossou Félix, Nacher Mathieu, Carme, Carme Bernard

Description

Dengue and malaria are two major arthropod-borne infections in tropical areas, but dual infections were only described for the first time in 2005. Reports of these concomitant infections are scarce and there is no evidence of more severe clinical and biological pictures than single infections. Methods To compare co-infections to dengue alone and malaria alone, a retrospective matched-pair study was conducted between 2004 and 2010 among patients admitted in the emergency department of Cayenne hospital, French Guiana. Results 104 dengue and malaria co-infection cases were identified during the study period and 208 individuals were matched in two comparison groups: dengue alone and malaria alone. In bivariate analysis, co-infection clinical picture was more severe than separated infections, in particular using the severe malaria WHO criteria. In multivariate analysis, independent factors associated with co-infection versus dengue were: masculine gender, CRP level > 50 mg/L, thrombocytopaenia < 50 10 9 /L, and low haematocrit <36% and independent factors significantly associated with co-infections versus malaria were red cells transfusion, low haematocrit < 36%, thrombocytopaenia < 50 10 9 /L and low Plasmodium parasitic load < 0.001%. Conclusions In the present study, dengue and malaria co-infection clinical picture seems to be more severe than single infections in French Guiana, with a greater risk of deep thrombocytopaenia and anaemia.

Sujets

• Dengue
• Malaria
• French Guiana
• Thrombocytopenia
• Case-control study

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 11
• Langue: English

Extrait

Epelboin et al. Malaria Journal 2012, 11:142
http://www.malariajournal.com/content/11/1/142
RESEARCH Open Access
Is dengue and malaria co-infection more severe
than single infections? A retrospective
matched-pair study in French Guiana
1,2,3* 1,2 4 1 2,5Loïc Epelboin , Matthieu Hanf , Philippe Dussart , Sihem Ouar-Epelboin , Félix Djossou ,
1,2 1,2Mathieu Nacher and Bernard Carme
Abstract
Background: Dengue and malaria are two major arthropod-borne infections in tropical areas, but dual infections
were only described for the first time in 2005. Reports of these concomitant infections are scarce and there is no
evidence of more severe clinical and biological pictures than single infections.
Methods: To compare co-infections to dengue alone and malaria alone, a retrospective matched-pair study was
conducted between 2004 and 2010 among patients admitted in the emergency department of Cayenne hospital,
French Guiana.
Results: 104 dengue and malaria co-infection cases were identified during the study period and 208 individuals
were matched in two comparison groups: dengue alone and malaria alone. In bivariate analysis, co-infection clinical
picture was more severe than separated infections, in particular using the severe malaria WHO criteria. In
multivariate analysis, independent factors associated with co-infection versus dengue were: masculine gender, CRP
9level>50 mg/L, thrombocytopaenia<50 10 /L, and low haematocrit<36% and independent factors significantly
associated with co-infections versus malaria were red cells transfusion, low haematocrit<36%,
9thrombocytopaenia<50 10 /L and low Plasmodium parasitic load<0.001%.
Conclusions: In the present study, dengue and malaria co-infection clinical picture seems to be more severe than
single infections in French Guiana, with a greater risk of deep thrombocytopaenia and anaemia.
Keywords: Dengue, Malaria, French Guiana, Thrombocytopaenia, Case–control studies
Background Plasmodium falciparum and/or Plasmodium vivax in
Dengue fever and malaria are the most common India and Pakistan [2-5], Southeast Asia [6,7], French
arthropod-borne diseases in humans and represent Guiana [8] and Brazil [9]. This phenomenon seems to be
major public health problems. Dengue virus (family uncommon. In a study performed in Thailand among 194
Flaviridae,genus Flavivirus)and Plasmodium para- patients with dengue, no co-infection with malaria was
sites are widespread in American and Asian tropical found[10], butinFrenchGuiana, a retrospective study
regions and their endemic areas overlap extensively. performed in 2004–2005 on 1,723 consecutive febrile
emerNevertheless, reports of malaria and dengue dual in- gency patients found 17 co-infections, including six acute
fection are scarce. Since the first case reported in concurrent infections (e.g. 1% of dengue and 4% of malaria
2005 [1], only case-reports and two descriptive studies cases) [8]. The influence of co-infections on severity is not
have been published. They have been reported with straightforward, therefore, the aim of this study was to
differentiate clinical and biological picture of co-infections
from infections alone and determine whether patients* Correspondence: [e-mail]
1
CIC-EC Antilles Guyane CIE 802 Inserm, Centre Hospitalier Andrée Rosemon, infected by both malaria and dengue (MD) were more
Cayenne, French Guiana
2 severe than either infection alone (respectively M and D).
Research team EPaT EA 3593, University of French West Indies and French
Guiana, Cayenne, French Guiana
Full list of author information is available at the end of the article
© 2012 Epelboin et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.Epelboin et al. Malaria Journal 2012, 11:142 Page 2 of 8
http://www.malariajournal.com/content/11/1/142
Methods isolation, genome detection by Reverse
TranscriptaseStudy location Polymerase Chain Reaction (RT-PCR) or NS1 antigen
deFrench Guiana is a French Overseas territory located on tection introduced in 2006 in French Guiana. Indirect
the north-eastern coast of South America. About 90% of diagnosis was based on detection of specific anti-dengue
2its surface of 84,000 km is Amazonian rain forest; the IgM and/or IgA antibodies in patients’ sera [17]. When
remaining 10% in the north is a coastal plain where 90% NS1 antigen detection was available, RT-PCR, which
of the 215,000 inhabitants live and Cayenne and sur- allows serotype identification, was not systematically
roundings contain almost 50% of the population in 2009 performed.
[11]. Malaria and dengue fever (DF) represent two major Concerning dengue definition (groups MD and D),
public health concerns in French Guiana. Malaria is en- cases were separated in two groups: “confirmed acute
demic and the annual number of cases ranges from dengue cases” (CADC) were defined by direct biological
3,200 to 4,700 [12]. Until 2006, P. vivax represented 50% diagnosis (NS1 antigen and/or RT-PCR and/or virus
isoof annual cases. The current proportion of P. vivax mal- lation), IgM seroconversion (early serum sample negative
aria is 75%, as in the rest of the Americas [12-14]. Since for IgM but convalescent sample positive) or IgA
antithe first cases of DF were reported in French Guiana in bodies detection. “Likely dengue cases” (LDC) were
1943, an increase in the number of DF cases and DF out- defined by IgM antibodies detection. Indeed, IgM appear
rd th
breaks and the emergence of dengue hemorrhagic fever between the 3 and 5 day of fever but can persist for
(DHF) have been observed [15]. All four dengue virus over three months and IgA appear concomitantly with
serotypes circulate in French Guiana. The last two mains IgM but does not persist longer than five to six weeks
epidemics occurred in 2006 and 2009, and dengue is cur- [18,19]. There was no discrimination between dengue
rently endemic. Until 2005, dengue outbreaks were ex- primary infection and secondary infection, e.g., further
clusively described on the coast. Since 2006, outbreaks of infection(s) by dengue of a different serotype.
DF have been reported in interior villages where malaria
is endemic [16]. Covariates included, data collection and statistical analysis
Patients’ data, including socio-epidemiologic data,
previStudy population ous medical history, clinical symptoms, and biological
A matched retrospective study was conducted comparing results, were obtained from the computerized medical
W
patients infected with concurrent malaria and dengue to charts. Data were analysed using R version 2.10.0 and
Ws with either infection alone. The study popula- the Epicalc package.
tion included all patients admitted in the emergency de- The continuous variables of interest were categorized
partment of Cayenne hospital, between June 2004 and following the laboratory cut-off values, or published
February 2010. The diagnosis of dengue and malaria co- values. They generally were dichotomized because of the
infection was made on the basis of concomitant bio- small sample size.
logical diagnosis of dengue and malaria within seven Two analyses were performed comparing separately
days in patients with a compatible clinical picture. Two MD to D and MD to M. For categorical variables, a
control groups were constituted: the group M with posi- matched bivariate analysis using the Wald test was
pertive biological diagnosis for malaria and negative for den- formed to identify factors associated with co-infections.
gue, according to the criteria defined in the next Statistical significance was set at p<0.05. Variables with
paragraph, and the contrary for the group D. Control a p-value<0.2 in bivariate analyses were entered into
cases were matched on the date of biological diagnosis multivariate model to identify the factors independently
of infection. associated with dengue-malaria co-infections. As
bivariCase definitions were based on compatible clinical his- ate analysis were made in an exploratory way and used
tory and biological diagnosis. Malaria diagnosis relied on as a selection criterion for inclusion in the final
multithe identification of haematozoa on a thin blood film and/ variate model (p<0.20), we did not judge as a necessity
or on a thick blood film stained with Giemsa (group MD to adjust bivariate p-values for multiple comparisons.
and M). The screening sensitivity was6 plasmodia/μL Thus, bivariate p-values near to 0.05 must be relativized.
(1/1,000 leukocytes). The asexual parasite load (PL) was To obtain more powerful models, and because of the
classified in five classes: class 5:>1.25%; class 4: 0.125 to missing data inherent to retrospective studies, variables
1.25%; class 3 : 0.0125% to 0.125%; class 2: 0.00125 to obtained from anamnesis and clinical examination and
0.0125%; and class 1: ≤0.00125. Malaria rapid diagnosis variables with more than 5% of missing data were
tests were not systematically performed on the study excluded from the model. Thus, conditional multivariate
period. Due to the evolution of the techniques between backward stepwise logistic regression estimated the
2004 and 2010, the laboratory diagnosis of deng