Open Access

Atypical aetiology of a conjugal fever: autochthonous airport malaria between Paris and French Riviera: a case report

  • Christelle Pomares-Estran1Email author,
  • Pascal Delaunay1,
  • Annie Mottard2,
  • Eric Cua3,
  • Pierre-Marie Roger3,
  • Bruno Pradines4,
  • Daniel Parzy4,
  • Hervé Bogreau4,
  • Christophe Rogier4,
  • Charles Jeannin5,
  • Saïd Karch6,
  • Didier Fontenille7,
  • Dominique Dejour-Salamanca8,
  • Fabrice Legros9 and
  • Pierre Marty1
Malaria Journal20098:202

https://doi.org/10.1186/1475-2875-8-202

Received: 20 April 2009

Accepted: 23 August 2009

Published: 23 August 2009

Abstract

Endemic malaria has been eradicated from France, but some falciparum malaria cases have been described in patients who have never travelled outside the country. Ms. V. 21 year-old and Mr. M. 23 year-old living together in Paris were on holiday in Saint Raphaël (French Riviera). They presented with fever, vertigo and nausea. A blood smear made to control thrombocytopaenia revealed intra-erythrocytic forms of Plasmodium falciparum. The parasitaemia level was 0.15% for Ms. V and 3.2% for Mr. M. This couple had no history of blood transfusion or intravenous drug use. They had never travelled outside metropolitan France, but had recently travelled around France: to Saint Mard (close to Paris Charles de Gaulle (CdG) airport), to Barneville plage (in Normandy) and finally to Saint Raphaël. The most probable hypothesis is an infection transmitted in Saint Mard by an imported anopheline mosquito at CdG airport. The DNA analysis of parasites from Ms. V.'s and Mr. M.'s blood revealed identical genotypes. Because it is unlikely that two different anopheline mosquitoes would be infected by exactly the same clones, the two infections must have been caused by the infective bites of the same infected mosquito.

Background

In a recent paper, Doudier et al described two cases of possible autochthonous malaria contracted in Marseille area (southern France) during the summer 2006 [1]. Malaria is a common disease in tropical and sub-tropical areas of over 100 countries, but endemic malaria has been eradicated from France. Nevertheless, some falciparum malaria cases have been described in patients who have never travelled outside France [16]. In this case presentation, two autochthonous malaria cases are reported in French Riviera during summer 2008.

Case presentation

Ms. V. 21 year-old and Mr. M. 23 year-old living together in Paris were on holiday in Saint Raphaël (French Riviera) since of August 13th, 2008. In the evening of August, 18th Ms. V. and Mr. M. presented with fever, vertigo and nausea (Day 0). The man's symptoms were more pronounced. He was hospitalized on August 19th in Fréjus-Saint Raphaël Hospital (Day 1). His platelet count was normal (Mr. M. = 208 giga/l). No aetiology was found. The patient went back home the next day with a follow-up but no diagnosis.

On August 22nd (Day 4), his symptoms were still present. The couple returned to the same hospital and a blood cell count, done at that time, found a thrombocytopaenia (Mr. M. = 11 giga/l, Ms. V. = 31 giga/l). A blood smear made to control the thrombocytopaenia and stained by May-Grünwald Giemsa revealed intra-erythrocytic forms of P. falciparum. The parasitaemia level was 0.15% for Ms. V and 3.2% for Mr. M. Retrospectively, the Day 1 blood smear of Mr. M. revealed P. falciparum with a parasitaemia level of 0.1%. They were hospitalized in Nice University Hospital (French Riviera) and treated with intravenous quinine because of vomiting. Parasitaemia controls done on Day 3 and Day 7 post treatment were negative and clinical evolution was successful.

Parasite DNA was extracted from the blood samples and four P. falciparum microsatellite loci (C4M79, Pf2689, Pf2802, TRAP) were genotyped using the method previously described [1]. Length polymorphism analysis revealed that the two infections had exactly the same genotype profile at the four loci and were composed of at least four distinct clones as indicated in Table 1. An in vitro drug susceptibility assay was setup on blood samples collected before treatment, for P. falciparum drug resistance surveillance [7]. Only the isolate collected before treatment on the woman has an interpretable micro-isotopic test. Inhibitory concentrations 50% (IC50) were 2.3 nM, 23.8 nM, 9.1 μM and 2.0 nM for atovaquone, mefloquine, doxycycline and dihydroartemisinin, respectively [7, 8]. The isolate was susceptible to all the anti-malarial drugs tested. Unfortunately there weren't enough parasites to realize the test on the second line of antimalarial drug (quinine, chloroquine, lumefantrine and monodesethylamodiaquine). The analysis of resistance molecular markers of the isolates of the two patients revealed a high level of resistance to antifolate drugs (mutations on codons 51, 59 and 108 of the Pfdhfr-ts gene, and 436 of the Pfdhps gene), the presence of a lysine variant on codon 76 of the P. falciparum chloroquine resistance transporter (Pfcrt) and no mutation on cytochrome b gene.
Table 1

Microsatellite loci genotyping

 

C4M79

Pf2689

Pf2802

TRAP

Autochthonous 1*

187, 195, 206, 214

87, 80

133, 141, 148

133, 145

Autochthonous 2†

187, 195, 206, 214

87, 80

133, 141, 148

133, 145

3D7‡

221

87

138

137

W2‡

188

87

146

140

*Patient 1, Plasmodium falciparum diagnosed in Ms V.

†Patient 2, P. falciparum diagnosed in Mr M.

‡Two parasite strains (3D7 and W2) were genotyped as a positive control; water was used as a negative control.

This couple had no history of blood transfusion or intravenous drug use. They had never travelled outside metropolitan France, however they had travelled around France in the previous fortnight: from the 5th to the 7th to Saint Mard, from the 7th to the 12th to Barneville plage (Normandy) and, finally, from the 13th to the 22nd in Saint Raphaël. Entomological and environmental studies have been conducted in Saint Raphaël and Saint Mard on the 28th of August and the 9th of September. No Anopheles sp. mosquito has been collected in these towns. The mean of temperature during their stay in Saint Raphaël and Saint Mard was 23°4 C (30°4 to 17°8 C) and 22°9 C (32°4 to 17°4 C) respectively. However, Saint Mard is 7 kilometers away from International Paris Charles de Gaulle (CdG) airport, where many airport-workers live. Furthermore, a hotel 300 metres away from the couple's home is served daily by a frequent shuttle from CdG Airport. The environmental and climatologic studies showed that there were no international port or airport in the area of Barneville plage and the mean temperature was quite low during their stay (18°5 C). Despite the compatible malaria incubation period no entomological study has been done in that place.

Conclusion

Autochthonous malaria is defined as Plasmodium sp. in blood smears of patients who have never travelled to malaria-endemic areas in the previous 12 months [9]. Transfusion, organ transplantation, intravenous drug use, must also be excluded [9]. The latest case of autochthonous malaria due to P. falciparum described in France was in 2006 [1]. Among autochthonous malaria, airport malaria occurs when a Plasmodium-infected Anopheles sp. mosquito travels from an endemic area to a malaria-free airport [10]. Two cases are described in a couple. The diagnosis was made incidentally on Day 4, when blood smears were done manually for thrombocytopaenia control. In France, it is legally defined that all thrombocytopaenia detected by the analyzer (platelet count below 150 giga/l) have to be controlled. A blood clot has to be excluded and a blood smear is done. On Day 1, in view to the lack of context (no travel history) and of thrombocytopaenia, the diagnosis was not made, but the disease was obviously still ongoing. DNA analysis revealed identical genotypes at all the investigated loci. Because it is unlikely that two different anopheline mosquitoes would be infected by exactly the same four clones, the present data shows that the two infections were caused by the infective bites of the same infected vector specimen, possibly during an interrupted blood feeding. In non-immune individuals most clinical manifestations occur between 7 and 14 days after the infective bite [11]. According to this delay, the potential places of contamination are Saint Mard and Barneville plage and a contamination in Saint Raphäel is excluded. Moreover, 10 cases were described at CdG airport area during the summers 1994 and 1999 [6, 10]. In Europe, airport malaria occurred mainly in August when the climate in the vicinity of the origin and destination airport is suitable for the survival of malaria-carrying Anopheles [12]. However, an autochthonous anopheline vector infected by a gametocyte carrier in Paris suburb or Barneville plage cannot be excluded [13]. In continental France, nine Anopheles species are potential malaria vectors and among them Anopheles atroparvus is considered as the primary vector because of its abundance and its anthropophilous potential [14]. Nevertheless, the temperature during their stay in Barneville plage is not in favour of a contamination in this location. In this case, because of incubation period, climate and environmental studies, the most probable hypothesis is an infection acquired during their stay in Saint Mard transmitted by an imported anopheline mosquito at CdG airport.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Declarations

Acknowledgements

The authors would like to thank Lionel Bertaux for his precious collaboration and Sandy Jones for English proof reading.

Authors’ Affiliations

(1)
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire L'Archet
(2)
Laboratoire de Biologie, Hôpital de Fréjus-Saint Raphaël
(3)
Infectiologie CHU L'Archet
(4)
Institut de Médecine Tropicale du Service de Santé des Armées
(5)
Entente Interdépartementale de Démoustication Méditerranée
(6)
Entomologiste médical
(7)
Institut de la Recherche pour le Développement, Caractérisation et contrôle des populations de vecteurs
(8)
Département International et Tropical, Institut de Veille Sanitaire
(9)
Centre National de Référence du Paludisme, Université Pierre et Marie Curie

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Copyright

© Pomares-Estran et al; licensee BioMed Central Ltd. 2009

This article is published under license to 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.

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