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Case report
Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia Choc septique compliquant un paludisme à Plasmodium falciparum associé à une parasitémie faible chez une femme enceinte F. Boissier a,∗ , C. Vermersch a , S. Spagnolo a , F. Bruneel b , C. Brun-Buisson a , N. de Prost a a
Service de réanimation médicale, hôpital Henri-Mondor, 51, avenue de Lattre-de-Tassigny, 94010 Créteil, France b Service de réanimation médico-chirurgicale, centre hospitalier de Versailles, Le Chesnay, France Received 26 March 2014; received in revised form 22 July 2014; accepted 10 September 2014
Keywords: Malaria; Parasitemia; Septic shock; Pregnancy Mots clés : Paludisme ; Parasitémie ; Choc septique ; Grossesse
1. Introduction Parasitemia is one of the World Health Organization criteria for severe malaria, with a suggested threshold of 5% in the semiimmune adult. However, there is no consensus on the optimal threshold for predicting severity. 2. Case presentation We report the case of a 6-month pregnant patient, Ivory Coast native, hospitalized for septic shock. The 35-year-old HIV negative patient had a medical history of malaria 1 year before and had returned from a 15-day trip to Africa 5 days before admission. She had not taken any anti-malarial chemoprophylaxis. She reported fever and headache associated with vomiting and diarrhea, beginning a few hours before her arrival to the emergency room. She presented with severe shock, resistant to fluid resuscitation with 3500 mL of saline. She was transferred to the intensive care unit (ICU) and was given high doses of intravenous norepinephrine (2 g/kg/min). The left ventricle ejection fraction was normal. A blood smear was positive for Plasmodium falciparum with 0.55% of parasitemia. Intravenous quinine and empirical antibiotic treatment with cefotaxime and amoxicillin (as anti-Listeria therapy) was promptly administered. ∗
Corresponding author. E-mail address: [email protected] (F. Boissier).
Recent data suggests that artemisin derivatives could be associated with increased survival during severe malaria and could be used safely in pregnant women. But, official French guidelines supporting the use of artemisin derivatives during severe malaria were published in February 2013 [1], 4 months after our patient was admitted. Thus, we used quinine as a first line treatment for this patient because our local guidelines still recommended using quinine, and because artemisin derivatives were not available for emergency use in our hospital. The patient did not need mechanical ventilation and norepinephrine was discontinued on day 1. No associated bacterial infection was diagnosed. The patient was discharged from ICU at day 3 and from the hospital at day 7. There were no fetal complications. 3. Discussion The discrepancy between the severity of septic shock, as proven by the need for high doses of norepinephrine, and a concomitant low parasitemia (well below a recently proposed 2% threshold to predict poor outcomes [2]) was intriguing. The initial parasitemia in a previous series of patients with P. falciparum infection and shock was much higher than in our case (21 ± 6%), with an associated mortality of 50% [3]. Shock complicated the course of malaria in 27% of cases as reported for a recent series of patients requiring ICU admission with a median parasitemia of 7% (interquartile range: 2.7–15.0%) [4] and was associated with bacterial co-infections in 50% of cases
http://dx.doi.org/10.1016/j.medmal.2014.09.005 0399-077X/© 2014 Published by Elsevier Masson SAS.
Please cite this article in press as: Boissier F, et al. Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia. Med Mal Infect (2014), http://dx.doi.org/10.1016/j.medmal.2014.09.005
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ARTICLE IN PRESS F. Boissier et al. / Médecine et maladies infectieuses xxx (2014) xxx–xxx
[3]. P. falciparum may increase the risk of bacterial infection through several mechanisms including acquired immune dysfunction, complement activation, and hemolysis. P. falciparum may also contribute alone to shock, via the malarial glycoprotein, which exhibits some of the properties of bacterial lipopolysaccharide [5], and via cytokines and nitric oxide pathways. No other cause of sepsis was found for our patient and we concluded that shock was directly related to P. falciparum infection. The severity of shock requiring high doses of vasopressors despite massive fluid resuscitation ruled out the hypothesis of an isolated hypovolemic shock. Pregnancy might have contributed to the severity of shock; indeed, altered immune response against P. falciparum has been reported in pregnant patients and could increase the frequency and severity of malaria during pregnancy. Malaria is more frequent in primiparous and young women, and usually occurs in the second trimester of pregnancy [6]. P. falciparum-infected erythrocytes expression of a new antigenic variant of PfEMP1 (P. falciparum erythrocyte membrane protein 1) during pregnancy can impair the identification of P. falciparum by the immune system and make pre-existing immunity ineffective [7]. Moreover, P. falciparum avoids spleen clearance thanks to this protein that binds to chondroitin sulphate A in the placental intervillous space [8]. Consequently, pregnant patients can present with low or microscopically undetectable parasitemia in peripheral blood, which is a rather poor indicator of infection during pregnancy, compared to RT-PCR [9]. Other authors have already demonstrated that parasitemia of any density could be harmful for a pregnant patient and her fetus (stillbirth, low birth weight, and prematurity). One author reported a case of severe acute respiratory distress syndrome and septic shock in a pregnant patient with very low parasitemia, contrasting with the presence of parasitized erythrocytes in the broncho-alveolar lavage fluid and placental parasitic infestation, also demonstrating that severity and organ infestation can be dissociated from parasitemia during pregnancy [10].
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Authors’ contribution: FlB, CV, SS, and NDP managed the patient and wrote the case. FAB and CBB supervised and corrected the article. References [1] Paludisme grave chez l’adulte et chez l’enfant. Place de l’artésunate injectable. Rapport du Haut conseil de la santé publique; 2013. [2] Phillips A, Bassett P, Zeki S, Newman S, Pasvol G. Risk Factors for severe disease in adults with falciparum malaria. Clin Infect Dis 2009;48(7):871–8. [3] Bruneel F, Gachot B, Timsit JF, Wolff M, Bedos JP, Regnier B, et al. Shock complicating severe falciparum malaria in European adults. Intensive Care Med 1997;23:698–701. [4] Bruneel F, Tubach F, Corne P, Megarbane B, Mira JP, Peytel E, et al. Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One 2010;5(10.). [5] Schofield L, Hackett F. Signal transduction in host cells by glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 1993;177(1): 145–53. [6] Botolahy ZA, Randriambelomanana JA, Imbara E, Rakotoarisoa H, Andrianampanalinarivo HR. Aspects du paludisme à Plasmodium falciparum pendant la grossesse selon les cas observés au CHU de Toamasina Madagascar. Rev Anesth Med Urgence 2011;3(1):23–6. [7] Resende M, Nielsen MA, Dahlbäck M, Ditlev SB, Andersen P, Sander AF, et al. Identification of glycosaminoglycan binding regions in the Plasmodium falciparum endoced placental sequestration ligand, VAR2CSA. Malar J 2008;7:104. [8] Fried M, Duffy PE. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 1996;272:1502–4. [9] Mayor A, Serra-Casas E, Bardaji A, Sanz S, Puyol L, Cistero P, et al. Sub-microscopic infections and long-terme recrudescence of Plasmodium falciparum in Mozambican pregnant women. Malar J 2009;8:9. [10] Baud M, Bauchet E, Poilane I, Levacher S, Pourriat JL. Acute respiratory distress syndrome due to falciparum malaria in a pregnant woman. Intensive Care Med 1997;23:787–9.
4. Conclusion Physicians should be aware that septic shock exclusively related to severe P. falciparum malaria can occur during pregnancy, despite a low parasitemia.
Please cite this article in press as: Boissier F, et al. Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia. Med Mal Infect (2014), http://dx.doi.org/10.1016/j.medmal.2014.09.005
ARTICLE IN PRESS Disponible en ligne sur
ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses xxx (2014) xxx–xxx
Case report
Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia Choc septique compliquant un paludisme à Plasmodium falciparum associé à une parasitémie faible chez une femme enceinte F. Boissier a,∗ , C. Vermersch a , S. Spagnolo a , F. Bruneel b , C. Brun-Buisson a , N. de Prost a a
Service de réanimation médicale, hôpital Henri-Mondor, 51, avenue de Lattre-de-Tassigny, 94010 Créteil, France b Service de réanimation médico-chirurgicale, centre hospitalier de Versailles, Le Chesnay, France Received 26 March 2014; received in revised form 22 July 2014; accepted 10 September 2014
Keywords: Malaria; Parasitemia; Septic shock; Pregnancy Mots clés : Paludisme ; Parasitémie ; Choc septique ; Grossesse
1. Introduction Parasitemia is one of the World Health Organization criteria for severe malaria, with a suggested threshold of 5% in the semiimmune adult. However, there is no consensus on the optimal threshold for predicting severity. 2. Case presentation We report the case of a 6-month pregnant patient, Ivory Coast native, hospitalized for septic shock. The 35-year-old HIV negative patient had a medical history of malaria 1 year before and had returned from a 15-day trip to Africa 5 days before admission. She had not taken any anti-malarial chemoprophylaxis. She reported fever and headache associated with vomiting and diarrhea, beginning a few hours before her arrival to the emergency room. She presented with severe shock, resistant to fluid resuscitation with 3500 mL of saline. She was transferred to the intensive care unit (ICU) and was given high doses of intravenous norepinephrine (2 g/kg/min). The left ventricle ejection fraction was normal. A blood smear was positive for Plasmodium falciparum with 0.55% of parasitemia. Intravenous quinine and empirical antibiotic treatment with cefotaxime and amoxicillin (as anti-Listeria therapy) was promptly administered. ∗
Corresponding author. E-mail address: [email protected] (F. Boissier).
Recent data suggests that artemisin derivatives could be associated with increased survival during severe malaria and could be used safely in pregnant women. But, official French guidelines supporting the use of artemisin derivatives during severe malaria were published in February 2013 [1], 4 months after our patient was admitted. Thus, we used quinine as a first line treatment for this patient because our local guidelines still recommended using quinine, and because artemisin derivatives were not available for emergency use in our hospital. The patient did not need mechanical ventilation and norepinephrine was discontinued on day 1. No associated bacterial infection was diagnosed. The patient was discharged from ICU at day 3 and from the hospital at day 7. There were no fetal complications. 3. Discussion The discrepancy between the severity of septic shock, as proven by the need for high doses of norepinephrine, and a concomitant low parasitemia (well below a recently proposed 2% threshold to predict poor outcomes [2]) was intriguing. The initial parasitemia in a previous series of patients with P. falciparum infection and shock was much higher than in our case (21 ± 6%), with an associated mortality of 50% [3]. Shock complicated the course of malaria in 27% of cases as reported for a recent series of patients requiring ICU admission with a median parasitemia of 7% (interquartile range: 2.7–15.0%) [4] and was associated with bacterial co-infections in 50% of cases
http://dx.doi.org/10.1016/j.medmal.2014.09.005 0399-077X/© 2014 Published by Elsevier Masson SAS.
Please cite this article in press as: Boissier F, et al. Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia. Med Mal Infect (2014), http://dx.doi.org/10.1016/j.medmal.2014.09.005
+Model MEDMAL-3554; No. of Pages 2 2
ARTICLE IN PRESS F. Boissier et al. / Médecine et maladies infectieuses xxx (2014) xxx–xxx
[3]. P. falciparum may increase the risk of bacterial infection through several mechanisms including acquired immune dysfunction, complement activation, and hemolysis. P. falciparum may also contribute alone to shock, via the malarial glycoprotein, which exhibits some of the properties of bacterial lipopolysaccharide [5], and via cytokines and nitric oxide pathways. No other cause of sepsis was found for our patient and we concluded that shock was directly related to P. falciparum infection. The severity of shock requiring high doses of vasopressors despite massive fluid resuscitation ruled out the hypothesis of an isolated hypovolemic shock. Pregnancy might have contributed to the severity of shock; indeed, altered immune response against P. falciparum has been reported in pregnant patients and could increase the frequency and severity of malaria during pregnancy. Malaria is more frequent in primiparous and young women, and usually occurs in the second trimester of pregnancy [6]. P. falciparum-infected erythrocytes expression of a new antigenic variant of PfEMP1 (P. falciparum erythrocyte membrane protein 1) during pregnancy can impair the identification of P. falciparum by the immune system and make pre-existing immunity ineffective [7]. Moreover, P. falciparum avoids spleen clearance thanks to this protein that binds to chondroitin sulphate A in the placental intervillous space [8]. Consequently, pregnant patients can present with low or microscopically undetectable parasitemia in peripheral blood, which is a rather poor indicator of infection during pregnancy, compared to RT-PCR [9]. Other authors have already demonstrated that parasitemia of any density could be harmful for a pregnant patient and her fetus (stillbirth, low birth weight, and prematurity). One author reported a case of severe acute respiratory distress syndrome and septic shock in a pregnant patient with very low parasitemia, contrasting with the presence of parasitized erythrocytes in the broncho-alveolar lavage fluid and placental parasitic infestation, also demonstrating that severity and organ infestation can be dissociated from parasitemia during pregnancy [10].
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Authors’ contribution: FlB, CV, SS, and NDP managed the patient and wrote the case. FAB and CBB supervised and corrected the article. References [1] Paludisme grave chez l’adulte et chez l’enfant. Place de l’artésunate injectable. Rapport du Haut conseil de la santé publique; 2013. [2] Phillips A, Bassett P, Zeki S, Newman S, Pasvol G. Risk Factors for severe disease in adults with falciparum malaria. Clin Infect Dis 2009;48(7):871–8. [3] Bruneel F, Gachot B, Timsit JF, Wolff M, Bedos JP, Regnier B, et al. Shock complicating severe falciparum malaria in European adults. Intensive Care Med 1997;23:698–701. [4] Bruneel F, Tubach F, Corne P, Megarbane B, Mira JP, Peytel E, et al. Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One 2010;5(10.). [5] Schofield L, Hackett F. Signal transduction in host cells by glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 1993;177(1): 145–53. [6] Botolahy ZA, Randriambelomanana JA, Imbara E, Rakotoarisoa H, Andrianampanalinarivo HR. Aspects du paludisme à Plasmodium falciparum pendant la grossesse selon les cas observés au CHU de Toamasina Madagascar. Rev Anesth Med Urgence 2011;3(1):23–6. [7] Resende M, Nielsen MA, Dahlbäck M, Ditlev SB, Andersen P, Sander AF, et al. Identification of glycosaminoglycan binding regions in the Plasmodium falciparum endoced placental sequestration ligand, VAR2CSA. Malar J 2008;7:104. [8] Fried M, Duffy PE. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 1996;272:1502–4. [9] Mayor A, Serra-Casas E, Bardaji A, Sanz S, Puyol L, Cistero P, et al. Sub-microscopic infections and long-terme recrudescence of Plasmodium falciparum in Mozambican pregnant women. Malar J 2009;8:9. [10] Baud M, Bauchet E, Poilane I, Levacher S, Pourriat JL. Acute respiratory distress syndrome due to falciparum malaria in a pregnant woman. Intensive Care Med 1997;23:787–9.
4. Conclusion Physicians should be aware that septic shock exclusively related to severe P. falciparum malaria can occur during pregnancy, despite a low parasitemia.
Please cite this article in press as: Boissier F, et al. Septic shock complicating Plasmodium falciparum malaria in a pregnant patient with low parasitemia. Med Mal Infect (2014), http://dx.doi.org/10.1016/j.medmal.2014.09.005
