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Tumor Necrosis Factor and Severe Malaria Nathan Shaffer,· Georges E. Grau, Katrina Hedberg,· Farzin Davachi, Bongo Lyamba, Allen W. Hightower, Joel G. Breman, and Phuc Nguyen-Dinh
Malaria Branch. Division of Parasitic Diseases, Centers for Disease Control, Atlanta, Georgia; Kbrld Health Organization (WHO) Immunology Research and Training Center, Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland; Department of Pediatrics. Mama ~mo Hospital, Kinshasa, Zaire
Thmor necrosis factor-a (TNFa), a cytokine produced by monocytes/macrophages and T lymphocytes, is thought to play an important role in the host response to inflammation and infection [1-3]. Among its wide range of systemic effects, it acts as an endogenous pyrogen [4] and has been found to mediate endotoxic shock [5]. Elevated levels have now been reported in a number of acute and chronic infectious processes, including several parasitic diseases [6], meningococcemia [7, 8], endotoxemia [9, 10], leprosy [11], and AIDS [12, 13]. In 1986, elevated TNFa concentrations were detected in patients with malaria [6]. Since then, interest has focused on the possible relation of TNFa to severe and cerebral malaria. Recently, elevated TNFa levels were reported in African children [14] and in European travelers [15] with severe Plasmodiumfalciparum infection. Many questions remain about the pathophysiologic relation of TNFa to different manifestations of severe malaria and about the prognostic significance of high TNFa levels. To further investigate the clinical features associated with elevated TNFa concentrations in P. falciparum malaria, we evaluated a group of Zairian children hospital-
Received 15 March 1990; revised 10 July 1990. Informed consent was obtained, and the study was approved by the Mama Yemo Hospital Ethical Committee. Financial support: US Agency for International Development (PASABAF 0421 PHC 22333); the Sandoz Research Foundation and the WHO/World Bank/United Nations Development Programme Special Program fur Research and Training for Tropical Diseases (for TNFa laboratory work). Reprints or correspondence: Malaria Branch, F-12, Centers for Disease Control, Atlanta, GA 30333. * Present addresses: Division ofHIV/AIDS, Centers for Disease Control, Atlanta (N.S.); University of Washington School of Public Health, Seattle (K.H.). The Journal of Infectious Diseases 1991;163:96-101 © 1991 by The University of Chicago. All rights reserved. 0022-1899/9116301-0017$01.00
ized with severe P. falciparum infections and compared them with children with mild malaria and with ill, aparasitemic children.
Patients and Methods Study population. The study was carried out in November 1988 in the pediatric emergency room of Mama Yemo Hospital (MYH), a large, urban community and referral hospital in Kinshasa, Zaire, where malaria is endemic. At MYH, fever is the most common pediatric complaint, and malaria is the most common diagnosis. After triage evaluation, ill children are treated as outpatients or admitted to an emergency perfusion room for parenteral therapy. After 12-24 h, those requiring continued parenteral therapy are admitted as inpatients. All children
Tumor Necrosis Factor and Severe Malaria Nathan Shaffer,· Georges E. Grau, Katrina Hedberg,· Farzin Davachi, Bongo Lyamba, Allen W. Hightower, Joel G. Breman, and Phuc Nguyen-Dinh
Malaria Branch. Division of Parasitic Diseases, Centers for Disease Control, Atlanta, Georgia; Kbrld Health Organization (WHO) Immunology Research and Training Center, Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland; Department of Pediatrics. Mama ~mo Hospital, Kinshasa, Zaire
Thmor necrosis factor-a (TNFa), a cytokine produced by monocytes/macrophages and T lymphocytes, is thought to play an important role in the host response to inflammation and infection [1-3]. Among its wide range of systemic effects, it acts as an endogenous pyrogen [4] and has been found to mediate endotoxic shock [5]. Elevated levels have now been reported in a number of acute and chronic infectious processes, including several parasitic diseases [6], meningococcemia [7, 8], endotoxemia [9, 10], leprosy [11], and AIDS [12, 13]. In 1986, elevated TNFa concentrations were detected in patients with malaria [6]. Since then, interest has focused on the possible relation of TNFa to severe and cerebral malaria. Recently, elevated TNFa levels were reported in African children [14] and in European travelers [15] with severe Plasmodiumfalciparum infection. Many questions remain about the pathophysiologic relation of TNFa to different manifestations of severe malaria and about the prognostic significance of high TNFa levels. To further investigate the clinical features associated with elevated TNFa concentrations in P. falciparum malaria, we evaluated a group of Zairian children hospital-
Received 15 March 1990; revised 10 July 1990. Informed consent was obtained, and the study was approved by the Mama Yemo Hospital Ethical Committee. Financial support: US Agency for International Development (PASABAF 0421 PHC 22333); the Sandoz Research Foundation and the WHO/World Bank/United Nations Development Programme Special Program fur Research and Training for Tropical Diseases (for TNFa laboratory work). Reprints or correspondence: Malaria Branch, F-12, Centers for Disease Control, Atlanta, GA 30333. * Present addresses: Division ofHIV/AIDS, Centers for Disease Control, Atlanta (N.S.); University of Washington School of Public Health, Seattle (K.H.). The Journal of Infectious Diseases 1991;163:96-101 © 1991 by The University of Chicago. All rights reserved. 0022-1899/9116301-0017$01.00
ized with severe P. falciparum infections and compared them with children with mild malaria and with ill, aparasitemic children.
Patients and Methods Study population. The study was carried out in November 1988 in the pediatric emergency room of Mama Yemo Hospital (MYH), a large, urban community and referral hospital in Kinshasa, Zaire, where malaria is endemic. At MYH, fever is the most common pediatric complaint, and malaria is the most common diagnosis. After triage evaluation, ill children are treated as outpatients or admitted to an emergency perfusion room for parenteral therapy. After 12-24 h, those requiring continued parenteral therapy are admitted as inpatients. All children
