Correspondence
Case 32-2006: A Girl with Fever after a Visit to Africa
N Engl J Med 2007; 356:527-529February 1, 2007
- Article
To the Editor:
In the Case Record regarding severe falciparum malaria in a 3-year-old girl (Oct. 19 issue),1 Fraser et al. discuss the use of exchange transfusion and attribute the patient's clinical improvement to this treatment. Current evidence does not support this conclusion: a meta-analysis of eight comparative trials showed no significant benefit of adjunctive exchange transfusion over chemotherapy alone. Although there was systematic bias toward use of exchange transfusion in patients with severe malaria, subgroup analysis showed no additional benefit at any level of parasitemia.2
Treatment of severe malaria with artesunate, as compared with quinine, has been shown to reduce mortality by 35%.3 Unlike intravenous quinidine, artesunate is easy to administer and is well tolerated. Artesunate has not yet been approved by the Food and Drug Administration. Therefore, it is ironic that the drug is being used to great effect in much of Asia and Africa, even though in the United States, patients with severe falciparum malaria are denied the most effective treatment and may be exposed to unproven, potentially dangerous interventions.
3 ReferencesJohn Williams, M.R.C.P.
Tan Tock Seng Hospital, Singapore 308433, Singapore
john_williams@ttsh.com. sg 1
Case Records of the Massachusetts General Hospital (Case 32-2006). N Engl J Med 2006;355:1715-1722
Full Text | Web of Science | Medline2
Riddle MS ,Jackson JL ,Sanders JW ,Blazes DL . Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis. Clin Infect Dis 2002;34:1192-1198
CrossRef | Web of Science | Medline3
South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group
CrossRef | Web of Science | Medline
To the Editor:
In the Case Record, a 3-year-old child with severe malaria was treated with intravenous quinidine and exchange transfusion. Both the treatment protocols are potentially life-threatening, and better alternatives are available. A review of the currently available data from trials that have compared quinine with artesunate suggests a 9% absolute reduction in the risk of death with the use of artesunate (number of patients who would need to be treated to prevent one death, 11), where available.1 Also, the use of artesunate is associated with lower infusion volumes and can potentially reduce the incidence of fluid overload, which is a common complication in children. Furthermore, the parasite clearance time is faster with artesunate than with quinine, and its use might have obviated the observed increase in parasitemia in this case.1 Moreover, artesunate is not associated with hypoglycemia and cardiac toxicity, both of which are commonly encountered with the use of quinidine. In a systematic review, exchange transfusion was not associated with a higher survival rate than was antimalarial chemotherapy alone, and the procedure is fraught with complications.2 In fact, the recent guidelines of the World Health Organization (WHO) do not endorse the use of exchange transfusion, even in patients with severe parasitemia.3
3 ReferencesRitesh Agarwal, M.D., D.M.
Rajagopala Srinivas, M.D.
Alok Nath, M.D.
Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
ritesh@indiachest.org 1
South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group
CrossRef | Web of Science | Medline2
Riddle MS ,Jackson JL ,Sanders JW ,Blazes DL . Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis. Clin Infect Dis 2002;34:1192-1198
CrossRef | Web of Science | Medline3
Guidelines for the treatment of malaria. Geneva: World Health Organization, 2006. (Document no. WHO/HTM/MAL/2006.1108.) (Accessed January 11, 2007, at http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.)
To the Editor:
One must not generalize from the experience with the patient in the Case Record, especially in the developing world. The discussants state that there are risks involved in exchange transfusion but fail to mention an important risk in regions where malaria is prevalent: transfusion-transmitted infections such as human immunodeficiency virus (HIV) infection.
In the United States, the risk of acquiring HIV infection from blood transfusion is less than one case per 1 million units of blood.1 In sub-Saharan Africa, HIV infection coexists with malaria at hyperendemic rates, and some observers believe that many countries cannot ensure the biosafety of blood.2 In Guinea, the residual risk of acquiring HIV from transfusion is estimated at 1 per 8562 transfusions.2
The discussants state that there have been no prospective trials of exchange transfusion for severe malaria. In our meta-analysis,3 we found one,4 but it had limited data and small numbers. Although patients must be considered individually, we urge caution in the use of exchange transfusion and believe that it should not be recommended universally until the benefit has been prospectively proven to outweigh the risks.
David L. Blazes, M.D., M.P.H.
Naval Medical Research Center Detachment, Lima, Peru
blazes@nmrcd.med. navy. mil John W. Sanders, M.D., M.P.H.
National Naval Medical Center, Bethesda, MD 20889Mark S. Riddle, M.D., M.P.H.
Naval Medical Research Center, Silver Spring, MD 20889The views expressed in this letter are those of the authors and do not necessarily reflect the views or policies of the Department of the Navy or the Department of Defense.
4 References1
Blajchman MA ,Vamvakis EC . The continued risk of transfusion-transmitted infections. N Engl J Med 2006;355:1303-1305
Full Text | Web of Science | Medline2
Loua A ,Sow EM ,Magassouba FB ,Camara M ,Balde MA . Evaluation of residual infectious risk among blood donors in National Center of Blood Transfusion in Conakry. Transfus Clin Biol 2004;11:98-100
CrossRef | Web of Science | Medline3
Riddle MS ,Jackson JL ,Sanders JW ,Blazes DL . Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis. Clin Infect Dis 2002;34:1192-1198
CrossRef | Web of Science | Medline4
Treatment of severe malaria by exchange transfusion. N Engl J Med 1990;322:58-59
Full Text | Medline
To the Editor:
The nonimmune patient with 5% parasitemia, described in the Case Record, should have received parenteral treatment from the outset.1 Furthermore, there was no need to give the second antimalarial agent, doxycycline (which is contraindicated in children), with the quinine. Blood films in the first 24 hours with a rise in the parasite count are not indicative of therapeutic failure and may indicate a more favorable outcome.2
The article indicates that more mature forms and schizonts are not found in the peripheral blood in falciparum malaria. They can indeed be found and are of ominous prognostic significance.3 The authors do not distinguish between hemozoin found in malarial parasites, which may be present in late ring forms or more mature trophozoite forms and indicates a poor prognosis, and hemozoin found in neutrophils, which also indicates a poor outcome.4 Although in malaria there may be evidence of activation of coagulation, thrombocytopenia is more often caused by widespread sequestration than by disseminated intravascular coagulation.
4 ReferencesGeoffrey Pasvol, M.D., Ph.D.
Imperial College London, London HA1 3UJ, United Kingdom
g.pasvol@ic. ac. uk 1
Pasvol G . Management of severe malaria: interventions and controversies. Infect Dis Clin North Am 2005;19:211-240
CrossRef | Web of Science | Medline2
Gachot B ,Houze S ,Le Bras J ,Charmot G ,Bedos JP ,Vachon F . Possible prognostic significance of a brief rise in parasitaemia following quinine treatment of severe Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1996;90:388-390
CrossRef | Web of Science | Medline3
Silamut K ,White NJ . Relation of the stage of parasite development in the peripheral blood to prognosis in severe falciparum malaria. Trans R Soc Trop Med Hyg 1993;87:436-443
CrossRef | Web of Science | Medline4
Nguyen PH ,Day N ,Pram TD ,Ferguson DJ ,White NJ . Intraleucocytic malaria pigment and prognosis in severe malaria. Trans R Soc Trop Med Hyg 1995;89:200-204
CrossRef | Web of Science | Medline
Author/Editor Response
The responses to our Case Record highlight significant regional variations in the treatment of malaria. Both Williams and Agarwal et al. correctly identify the benefits of artemesin-based therapies in the treatment of severe malaria. As Williams points out, this class of drugs is not available in the United States, and our use of alternative therapeutic agents in this case reflected this reality.
Pasvol suggests that the patient should have received parenteral therapy from the outset on the basis of her parasitemia of 5%. Whereas the review he cites suggests the use of 2% parasitemia as a cutoff,1 we have used higher levels of parasitemia in making this determination, in part because of the toxicity of parenteral quinidine as compared with oral quinine. We recognize that doxycycline is not routinely used in children under the age of 8 years because of dental staining. Oral quinine plus clindamycin is an appropriate antimalarial combination for this age group, but oral clindamycin has significant gastrointestinal toxicity that may exacerbate the nausea and vomiting associated with malaria, thereby compromising oral therapy. Doxycycline is used to treat life-threatening infections in children of all ages, dosing is convenient, and short courses of therapy (as used in our case) carry a minimal risk of dental staining.2
We agree with Blazes et al. that the real value of exchange-transfusion therapy in severe malaria is unknown and that exchange transfusion should not be universally applied until any benefit is proven to outweigh the risks. In the case we reported, the decision to perform an exchange transfusion was based on individual risk–benefit considerations for that single child. Indeed, the recent WHO guidelines (referred to by Agarwal et al.) are noncommittal on the topic of exchange transfusion. The guidelines state, “There is no consensus on the indications, benefits and dangers involved, or on practical details such as the volume of blood that should be exchanged. It is therefore not possible to make any recommendation regarding the use of exchange blood transfusion.”3
Pasvol makes the point that the appearance of mature schizonts in the peripheral blood is an ominous sign in Plasmodium falciparum infection. In our patient, hemozoin was seen neither in the parasite nor in the neutrophils, and we agree that its presence portends a bad prognosis. We also agree with him that thrombocytopenia results principally from sequestration and rosette formation rather than from disseminated intravascular coagulation. According to the WHO, clinically significant disseminated intravascular coagulation develops in less than 5% of patients with severe malaria.3
3 ReferencesIain P. Fraser, M.B., Ch.B., D.Phil.
Massachusetts General Hospital, Boston, MA 02114Christine M. Cserti, M.D.
University Health Network, Toronto, ON M5G 2C4, CanadaWalter H. Dzik, M.D.
Massachusetts General Hospital, Boston, MA 021141
Pasvol G . Management of severe malaria: interventions and controversies. Infect Dis Clin North Am 2005;19:211-240
CrossRef | Web of Science | Medline2
Cale DF ,McCarthy MW . Treatment of Rocky Mountain spotted fever in children. Ann Pharmacother 1997;31:492-494
Web of Science | Medline3
Guidelines for the treatment of malaria. Geneva: World Health Organization, 2006. (Document no. WHO/HTM/MAL/2006.1108.) (Accessed January 11, 2007, at http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.)
- Citing Articles (1)
Citing Articles
1
Suresh G. Shelat, Jason P. Lott, Matthew S. Braga. (2010) Considerations on the use of adjunct red blood cell exchange transfusion in the treatment of severe Plasmodium falciparum malaria. Transfusion 50:4, 875-880
CrossRef
