Smith, Tom

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TID 1996; 173 (January) Correspondence 275We do not believe that disease is caused by one streptococcalsuperantigen, and it is quite possible that the 2 cases analyzed byMichie represent true expansion ofV(32T cells; however, it wouldbe helpful to increase the number of cases analyzed and to deter-mine the changes in the entire V(3 repertoire of these patients.It should be emphasized that the majority of studies that haveinvestigated the in vivo effects of superantigens have documentedthe deletion of superantigen-specific V(3bearing cells following abrief window of V(3 expansion [3-6]. In some cases, expansionwas not detected and only V(3 depletion was seen [6]. I believethat this is related to the type of superantigen and the magnitudeof the inflammatory cytokine response elicited in the host duringthe infection. Thus, it should not be surprising to observe V(3depletion in STSS, which is consistent with the severe inflamma-tory response in these patients. However, as we indicated in [2],we cannot rule out that earlier expansion of these V(3-bearing Tcells may have taken place.As to the method used to analyze the T cell receptor (TCR)repertoire, we agree that this method is quite difficult and if notdone properly can generate misleading results. However, we haveused this method for > 5 years and optimized the conditions tothe point that the technique is quite reliable and reproducible [7].We [8, 9] and others [10] have compared the results with thoseobtained by flow cytometry and found very good correlation. Fur-thermore, because the number of anti-V(3 antibodies is limited, itis not possible to analyze the entire repertoire by flow cytometryand consequently it is not possible to determine changes in otherV(3 elements. We agree with Michie that multiple methods shouldbe used to analyze the TCR repertoire; however, because of thelimited amount of blood that can be obtained from patients, thisoption is not always available. In addition, we fully agree thatanalysis of the repertoire in CD4 versus CD8 cells and in activatedversus naive T cells is important, and we are developing methodsto allow us to address this point in STSS patients.Finally, although Michie reported the repertoire of only 2 STSScases, his finding of a possible V(32 expansion and our finding ofV(3I, V(35.1, and V(3l2 depletion underscores the importance ofDistinction between Parasitologic and Clinical Efficacy ofAntimalarial AgentsTo the Editor-Weiss et al. [I] compared the effect of differentprophylactic regimens against Plasmodium falciparum malaria in9- to l4-year-old children in Saradidi in western Kenya. Theyconsidered two outcome measures, the cumulative incidence ofparasitemia and the cumulative incidence of "symptomatic fal-ciparum malaria."A diagnosis of symptomatic falciparum malaria in that studyrequired the presence of malaria parasites in a thick smear andReprints or correspondence: Dr. Tom Smith, Swiss Tropical Institute, Dept.of Public Health & Epidemiology, Socinstrasse 57, CH-4002 Basel, Switzer-land.The Journal of Infectious Diseases 1996;173:275-6© 1996by The Universityof Chicago. All rights reserved.0022-1899/9617301-0046$01.00analyzing the TCR repertoire of STSS patients in the context ofthe superantigen profile of their respective isolates. Such studiesare currently underway in our laboratory and should help us betterunderstand the mechanism of pathogenesis of severe streptococcalinfections.Malak KotbDepartment of Surgery, College ofMedicine, University of Tennessee,and VA Medical Center, Memphis, TennesseeReferencesI. Michie C, Scott A, Cheesbrough J, Pasvol G, Beverley PCL. Streptococcaltoxic shock-like syndrome: "its effects on T cells in vivo." Clin ExpImmunoll994;98:101-5.2. Watanabe-Ohnishi R, Low DE, McGeer A, et al. Selective depletion ofV,6-bearing T cells in patients with severe invasive group A streptococcalinfections and streptococcal toxic shock syndrome. J Infect Dis1995; 171:74-84.3. Kawabe Y, Ochi A. Programmed cell death and extrathymic reduction ofV,68+CD4+T cells in mice tolerant to Staphylococcusaureus enterotoxinB. Nature 1991; 349:245-8.4. Lussow AR, Crompton T, Karapetian 0, MacDonald HR. Peripheral clonaldeletion of superantigen-reactive T cells is enhanced by cortisone. Eur JImmunoll993;23:578-81.5. Ochi A, Yuh K, Migita K. Not every superantigen induces tolerance invivo. Semin Immunoll993;5:57-63.6. McCormack IE, Callahan IE, Kappler J, Marrack PC. Profound deletionof mature T cells in vivo by chronic exposure to exogenous superantigen.J Immunol 1993; 150:3785-92.7. Kotb M, Watanbe-Ohnishi R, Wang B, et al. Analysis of the TCR V,6specificities of bacterial superantigens using PCR. Immunomethods1993;2:33-40.8. Tomai M, Kotb M, Majumdar G, Beachey EH. Superantigenicity of strep-tococcal M protein. J Exp Med 1990; 172:359-62.9. Tomai MA, Aelion JA, Dockter ME, Majumdar G, Spinella DG, Kotb M.T cell receptor V gene usage by human T cells stimulated with thesuperantigen streptococcal M protein. J Exp Med 1991; 174:285-8.10. Hall BL, Finn OJ. T cell receptor V,6 gene usage in allograft-derived celllines analyzed by a polymerase chain reaction technique. Transplantation1992;53:1088-99.at least one of the following: history of fever or chills, axillarytemperature>37.5°C, headache, musculoskeletal aches, or abdom-inal pains.The authors acknowledge that ~20% of all blood smears werepositive for P. falciparum, and hence that other illnesses wouldoccur along with an incidentally positive smear leading to an over-diagnosis of malaria. In fact, it is well known that in children ofthe age range studied, clinical malaria attacks in areas of highendemicity are infrequent [2]. It is possible to estimate the propor-tion of clinical episodes attributable to malaria by considering theexcess risk among the infected persons. When we did an analysiswith data from areas of malaria endemicity comparable to Saradidi,we found that only a small proportion of the clinical episodes wereattributable to malaria in children> 10 years old [3, 4].It seems likely that the vast majority of the clinical episodesreported by Weiss et al. are not in fact of malarial etiology. Theauthors are to be congratulated on their well-designed study andimportant contribution to the study of malarial prophylaxis in EastAfrica; however, it is doubtful that their analyses give a validcomparison of the clinical efficacy of the different regimens. It

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