Correspondence
JlD 1992; 166 (December)
w. Hugo C. Landivar, Tamotsu Nakasa, Hiroshi Tachibana, KiIma C. paz, and Seiki Tateno Santa Cruz General Hospital. Santa Cruz. Bolivia; Laboratorio de Imunopatologia Prof Keizo Asami. Universidade Federal de Pernambuco. Recife. Brazil
Falciparum Malaria Modulates Viremia in Chronic Hepatitis B Virus Infection Colleagues-During acute falciparum malaria there are both cellular and cytokine changes associated with altered immune responsiveness [I], but their influence on other host-pathogen relationships is poorly understood. With hepatitis B virus (HBV) and Plasmodium falciparum coendemic in vast areas of Africa and Asia, we investigated whether acute falciparum malaria perturbs viremia in persons with chronic HBV infection. We assumed that changes in viremia expressed as serum concentration of HBV DNA would inversely reflect altered antiviral immunity; that is, depressed viremia would result from enhanced immune responses to HBV and vice versa. During field studies ofmalaria in Thailand from 1986 to 1991 [2], sera were collected from a cross-section of male soldiers both in good health and during acute malaria infections. Sera were stored at -70°C. Of 104 men who had specimens collected before, during, and after microscopically documented attacks of falciparum malaria, 23 (22%) were found on repeated testing (Auszyme; Abbott, Abbott Park, IL) to be hepatitis B surface
Financial support: US Army Medical Research and Development Command. Reprints or correspondence (present address): Dr. Arthur E. Brown, WRAIR. Suite 20 I, 13 Taft Ct .. Rockville, MD 20850. The Journal of Infectious Diseases This article is in the public domain.
1992;166:1465-6
References I. Schmunis GA. Trypanosoma cruzi. the etiologic agent ofChagas' disease: status in the blood supply in endemic and non endemic countries. Transfusion 1991;31 :547-57. 2. Zuna H. La Fuente C, Valdez E, et al. Estudio prospectivo de la transmision del Trypanosoma cruzi por via sanguinea, en Bolivia. Ann Soc Belg Med Trop 1985;65:107-13. 3. Carrasco R. Miguez H. Camacho C, et al. Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia. Mem Inst Oswaldo Cruz 1990;85:69-73. 4. Tachibana H. Kobayashi S. Kato Y. Nagakura K, Kaneda Y, Takeuchi T. Identification of a pathogenic isolate-specific 30,000-M, antigen of Entamoeba histolvtica by using a monoclonal antibody. Infect Immun 1990;58:955-60. 5. Figueredo-Silva J, Kaneda Y. Tachibana H. et al. Epidemiological survey of Trvpanosoma cruzi infection in northeastern Brazil using different diagnostic methods. Rev Inst Med Trop Sao Paulo 1991;33: 1938. 6. Camargo ME. Amato Neto V. Anti-Trypanosoma cruzi IgM antibodies as serological evidence of recent infection. Rev Inst Med Trop Sao Paulo 1974;16:200-2. 7. Kirchhoff LV. Neva FA. Chagas' disease in Latin American immigrants. lAMA 1985;254:3058-60. ; 8. Grant IH. Gold lWM, Wittner M. et al. Transfusion-associated acute Chagas disease acquired in the United States. Ann Intern Med 1989; 111:849-51,
antigen (HBsAg)-positive. Sera from 19 of these 23 were then assayed for the presence of HBV DNA by hybridizing in liquid phase to a Il5I-labeled single-stranded probe (Hepatitis B Viral DNA; Abbott). HBV DNA was detectable in sera from 9 (47%) of the 19 men, with concentrations ranging from 4.4 to 122.0 pg/rnl., We quantitated HBV DNA in longitudinal serum sets (5 specimens each) from 4 of the individuals with hepatitis B antigenemia. The chronicity of their infections was confirmed by our failure to detect IgM to hepatitis B core (Corezyme-M EIA; Abbott) in any specimen. In 2 individuals with low titers ofHBsAg, HBV DNA was undetectable in serum collected before malaria, rose to low levels (2.4 and 4.3 pg/rnl.) on the day of malaria diagnosis, and became undetectable again 2 and 3 days later, when a response to chemotherapy was observed (figure I). About 2 months after this transient increase in HBV viremia in the subject (no, 132) with the lowest HBsAg titer, HBsAg became undetectable in his serum (figure I). We observed a different alteration of viremia in 2 individuals with high levels of HBsAg (reciprocal titers ~104) and HBV DNA (51 and 161 pg/mL) measured ~ 1 month before diagnosis offalciparum malaria. In them, levels ofHBV DNA fell (to 19 and 37 pg/ml., respectively) during the episodes of malaria but were again at high levels when next measured (3 days and 3 months later, respectively). Since detectable HBV DNA and virus particles in serum are associated with free or "replicative" forms ofHBV DNA in liver tissue [3], it is assumed that changes in concentration ofcirculating DNA reflect changes in hepatic viral replication. The data reported here suggest that altered immune responses during
Downloaded from http://jid.oxfordjournals.org/ at University of Exeter on July 23, 2015
Carrasco et al. [3]. It was extremely high in comparison with those from other locations in Latin America [I]. In spite of such high prevalence, trypanocides such as gentian violet, to eliminate the parasite in stored blood, are not commonly used in Bolivia except in a few blood banks. Because many Latin Americans have immigrated to nonendemic areas, Chagas' disease has become an increasingly important public health problem in several countries. Recently, in the United States, a number of cases of Bolivian immigrants developing symptomatic chronic Chagas' disease years after emigration were reported [7]. Grant et al. [8] described a case of severe acute transfusion-acquired Chagas' disease in a child who had received platelets from an asymptomatic Bolivian immigrant with later serologic proof of T. cruzi infection. Therefore, serologic screening must be considered in efforts to prevent transfusion-associated Chagas' disease in non endemic as well as endemic areas.
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JID 1992; 166 (December)
Correspondence
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Arthur E. Brown, Duangrat Mongkolsirichaikul, Bruce Innis, Rapin Snitbhan, and H. Kyle Webster*
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Departments of Immunology and Virology. US Army Medical Component, Armed Forces Research Institute of Medical Sciences. Bangkok, Thailand
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Tim. From Falclparum Malaria (DaYI)
Figure 1. Relationship over time between Plasmodiumfalciparum parasitemia (bars) and HBY DNA concentration in serum (line) in two Thai soldiers (nos. 682 and 132). Hepatitis B surface antigen (HBsAg) serology at specified dilutions is noted at top of each panel. Level of detection ofHBY DNA = 1.6 pg/mL. Day 0 is day of malaria diagnosis and onset of treatment.
acute malaria influence chronic hepatitis B viremia, in some instances decreasing and in others increasing it. A similar phenomenon has also been observed in chronic HBV carriers who
I. Ho M. Webster HK. Immunology of human malaria. A cellular perspective. Parasite ImmunoI1989;11:105-16. 2. Brown AE, Webster HK. Krinchai K, Chuenchitra C. Pipithkul J. Occupational malaria in Thai Rangers: epidemiological, clinical and immunological features. Mil Med 1990;155:406-10. 3. Hoofnagle JH, Shafritz DA. Popper H. Chronic type B hepatitis and the "healthy" HBsAg carrier state. Hepatology 1987;7:758-63. 4. Homann C. Krogsgaard K. Pedersen C. Andersson P. Nielsen JO. High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIY infection. J Acquir Immune Defic Syndr 1991;4:416-20. 5. Hoofnagle JH. Dusheiko OM, Schafer DF. et al. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med 1982;96:447-9. 6. Rosenberg R, Andre RO. Ngampatom S, Hatz C. Burge R. A stable. oligosymptomatic malaria focus in Thailand. Trans R Soc Trop Med Hyg 1990;84:14-21.
Downloaded from http://jid.oxfordjournals.org/ at University of Exeter on July 23, 2015
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became immunosuppressed by coinfection with human immunodeficiency virus [4]. Of particular interest was the response of subject no. 132, suggesting that transient, malaria-associated reactivation ofHBV may in turn lead to loss ofHBsAg positivity, possibly from antigen-mediated immune activation as described after cessation of chemotherapy for cancer [5]. The 4 patients with falciparum malaria we studied were treated promptly with curative chemotherapy. Yet among populations in which hepatitis B virus and malaria are coendemic, malaria parasitemias are often subclinical and thus frequently untreated for long periods of time [6]. Chronic falciparum malaria may be accompanied by intervals of immunomodulation leading to sustained periods of HBV reactivation, increased infectivity, and possible aggravation of hepatic pathology.
JlD 1992; 166 (December)
w. Hugo C. Landivar, Tamotsu Nakasa, Hiroshi Tachibana, KiIma C. paz, and Seiki Tateno Santa Cruz General Hospital. Santa Cruz. Bolivia; Laboratorio de Imunopatologia Prof Keizo Asami. Universidade Federal de Pernambuco. Recife. Brazil
Falciparum Malaria Modulates Viremia in Chronic Hepatitis B Virus Infection Colleagues-During acute falciparum malaria there are both cellular and cytokine changes associated with altered immune responsiveness [I], but their influence on other host-pathogen relationships is poorly understood. With hepatitis B virus (HBV) and Plasmodium falciparum coendemic in vast areas of Africa and Asia, we investigated whether acute falciparum malaria perturbs viremia in persons with chronic HBV infection. We assumed that changes in viremia expressed as serum concentration of HBV DNA would inversely reflect altered antiviral immunity; that is, depressed viremia would result from enhanced immune responses to HBV and vice versa. During field studies ofmalaria in Thailand from 1986 to 1991 [2], sera were collected from a cross-section of male soldiers both in good health and during acute malaria infections. Sera were stored at -70°C. Of 104 men who had specimens collected before, during, and after microscopically documented attacks of falciparum malaria, 23 (22%) were found on repeated testing (Auszyme; Abbott, Abbott Park, IL) to be hepatitis B surface
Financial support: US Army Medical Research and Development Command. Reprints or correspondence (present address): Dr. Arthur E. Brown, WRAIR. Suite 20 I, 13 Taft Ct .. Rockville, MD 20850. The Journal of Infectious Diseases This article is in the public domain.
1992;166:1465-6
References I. Schmunis GA. Trypanosoma cruzi. the etiologic agent ofChagas' disease: status in the blood supply in endemic and non endemic countries. Transfusion 1991;31 :547-57. 2. Zuna H. La Fuente C, Valdez E, et al. Estudio prospectivo de la transmision del Trypanosoma cruzi por via sanguinea, en Bolivia. Ann Soc Belg Med Trop 1985;65:107-13. 3. Carrasco R. Miguez H. Camacho C, et al. Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia. Mem Inst Oswaldo Cruz 1990;85:69-73. 4. Tachibana H. Kobayashi S. Kato Y. Nagakura K, Kaneda Y, Takeuchi T. Identification of a pathogenic isolate-specific 30,000-M, antigen of Entamoeba histolvtica by using a monoclonal antibody. Infect Immun 1990;58:955-60. 5. Figueredo-Silva J, Kaneda Y. Tachibana H. et al. Epidemiological survey of Trvpanosoma cruzi infection in northeastern Brazil using different diagnostic methods. Rev Inst Med Trop Sao Paulo 1991;33: 1938. 6. Camargo ME. Amato Neto V. Anti-Trypanosoma cruzi IgM antibodies as serological evidence of recent infection. Rev Inst Med Trop Sao Paulo 1974;16:200-2. 7. Kirchhoff LV. Neva FA. Chagas' disease in Latin American immigrants. lAMA 1985;254:3058-60. ; 8. Grant IH. Gold lWM, Wittner M. et al. Transfusion-associated acute Chagas disease acquired in the United States. Ann Intern Med 1989; 111:849-51,
antigen (HBsAg)-positive. Sera from 19 of these 23 were then assayed for the presence of HBV DNA by hybridizing in liquid phase to a Il5I-labeled single-stranded probe (Hepatitis B Viral DNA; Abbott). HBV DNA was detectable in sera from 9 (47%) of the 19 men, with concentrations ranging from 4.4 to 122.0 pg/rnl., We quantitated HBV DNA in longitudinal serum sets (5 specimens each) from 4 of the individuals with hepatitis B antigenemia. The chronicity of their infections was confirmed by our failure to detect IgM to hepatitis B core (Corezyme-M EIA; Abbott) in any specimen. In 2 individuals with low titers ofHBsAg, HBV DNA was undetectable in serum collected before malaria, rose to low levels (2.4 and 4.3 pg/rnl.) on the day of malaria diagnosis, and became undetectable again 2 and 3 days later, when a response to chemotherapy was observed (figure I). About 2 months after this transient increase in HBV viremia in the subject (no, 132) with the lowest HBsAg titer, HBsAg became undetectable in his serum (figure I). We observed a different alteration of viremia in 2 individuals with high levels of HBsAg (reciprocal titers ~104) and HBV DNA (51 and 161 pg/mL) measured ~ 1 month before diagnosis offalciparum malaria. In them, levels ofHBV DNA fell (to 19 and 37 pg/ml., respectively) during the episodes of malaria but were again at high levels when next measured (3 days and 3 months later, respectively). Since detectable HBV DNA and virus particles in serum are associated with free or "replicative" forms ofHBV DNA in liver tissue [3], it is assumed that changes in concentration ofcirculating DNA reflect changes in hepatic viral replication. The data reported here suggest that altered immune responses during
Downloaded from http://jid.oxfordjournals.org/ at University of Exeter on July 23, 2015
Carrasco et al. [3]. It was extremely high in comparison with those from other locations in Latin America [I]. In spite of such high prevalence, trypanocides such as gentian violet, to eliminate the parasite in stored blood, are not commonly used in Bolivia except in a few blood banks. Because many Latin Americans have immigrated to nonendemic areas, Chagas' disease has become an increasingly important public health problem in several countries. Recently, in the United States, a number of cases of Bolivian immigrants developing symptomatic chronic Chagas' disease years after emigration were reported [7]. Grant et al. [8] described a case of severe acute transfusion-acquired Chagas' disease in a child who had received platelets from an asymptomatic Bolivian immigrant with later serologic proof of T. cruzi infection. Therefore, serologic screening must be considered in efforts to prevent transfusion-associated Chagas' disease in non endemic as well as endemic areas.
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JID 1992; 166 (December)
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Arthur E. Brown, Duangrat Mongkolsirichaikul, Bruce Innis, Rapin Snitbhan, and H. Kyle Webster*
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Departments of Immunology and Virology. US Army Medical Component, Armed Forces Research Institute of Medical Sciences. Bangkok, Thailand
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Tim. From Falclparum Malaria (DaYI)
Figure 1. Relationship over time between Plasmodiumfalciparum parasitemia (bars) and HBY DNA concentration in serum (line) in two Thai soldiers (nos. 682 and 132). Hepatitis B surface antigen (HBsAg) serology at specified dilutions is noted at top of each panel. Level of detection ofHBY DNA = 1.6 pg/mL. Day 0 is day of malaria diagnosis and onset of treatment.
acute malaria influence chronic hepatitis B viremia, in some instances decreasing and in others increasing it. A similar phenomenon has also been observed in chronic HBV carriers who
I. Ho M. Webster HK. Immunology of human malaria. A cellular perspective. Parasite ImmunoI1989;11:105-16. 2. Brown AE, Webster HK. Krinchai K, Chuenchitra C. Pipithkul J. Occupational malaria in Thai Rangers: epidemiological, clinical and immunological features. Mil Med 1990;155:406-10. 3. Hoofnagle JH, Shafritz DA. Popper H. Chronic type B hepatitis and the "healthy" HBsAg carrier state. Hepatology 1987;7:758-63. 4. Homann C. Krogsgaard K. Pedersen C. Andersson P. Nielsen JO. High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIY infection. J Acquir Immune Defic Syndr 1991;4:416-20. 5. Hoofnagle JH. Dusheiko OM, Schafer DF. et al. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med 1982;96:447-9. 6. Rosenberg R, Andre RO. Ngampatom S, Hatz C. Burge R. A stable. oligosymptomatic malaria focus in Thailand. Trans R Soc Trop Med Hyg 1990;84:14-21.
Downloaded from http://jid.oxfordjournals.org/ at University of Exeter on July 23, 2015
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became immunosuppressed by coinfection with human immunodeficiency virus [4]. Of particular interest was the response of subject no. 132, suggesting that transient, malaria-associated reactivation ofHBV may in turn lead to loss ofHBsAg positivity, possibly from antigen-mediated immune activation as described after cessation of chemotherapy for cancer [5]. The 4 patients with falciparum malaria we studied were treated promptly with curative chemotherapy. Yet among populations in which hepatitis B virus and malaria are coendemic, malaria parasitemias are often subclinical and thus frequently untreated for long periods of time [6]. Chronic falciparum malaria may be accompanied by intervals of immunomodulation leading to sustained periods of HBV reactivation, increased infectivity, and possible aggravation of hepatic pathology.
