PROGNOSTIC VALUE OF ANTI-PLASMODIUM FALCIPARUM SPECIFIC IMMUNOGLOBULIN G3, CYTOKINES, AND THEIR SOLUBLE RECEPTORS IN WEST-AFRICAN PATIENTS WITH SEVERE MALARIA

Forty-one African patients suffering from clinically defined severe ma laria were studied in the intensive medical care unit of the main hosp ital in Dakar, Senegal, West Africa, All of these individuals lived in Greater Dakar, an area of low and seasonal Plasmodium falciparum ende micity, Twenty-seven patients (mean age +/- I standard deviation, 19.2 +/- 12.7 years) survived this life-threatening episode, but 14 (30.8 +/- 16.2 Sears old) died despite initiation of adequate treatment, On the day of admission (day 0) and 3 days later, one to two blood sample s (i.e., approximately 10 to 15 mi) were obtained from each subject, a nd different biological parameters were evaluated in the two groups, P lasma samples were tested for their content in tumor necrosis factor a lpha (TNF-alpha), soluble receptors I and II for TNF-alpha (TNF-alpha sRI and TNF-alpha sRII), interleukin-6 (IL-6), IL-6 sR, IL-10, and IL- 2 sR, The concentrations of all these cytokines and/or their receptors was significantly elevated in patient plasma samples on day 0, and it rapidly decreased in the group of individuals who survived, By compar ison, the mean concentration of the same parameters decreased slowly i n the group of patients who died (except for IL-10, which dramatically fell in all patient plasma samples soon after initiation of antimalar ial treatment). The TNF-alpha sRI level remained significantly elevate d among the patients who died, and the highest levels of soluble TNF-a lpha sRI receptor were found among the older patients, Parasite-specif ic immunoglobulin M (IgM), total IgG, IgGl, IgG2, IgG3, and IgG4 were evaluated by enzyme-linked immunosorbent assay using a crude extract o f a local P. falciparum isolate as antigen and human class- and subcla ss-specific monoclonal antibodies, Parasite-specific IgM, total IgG, a nd IgG1 were detectable in the plasma samples of most of these African patients, whereas IgG2 and IgG4 mean values were low, The mean level of parasite-specific IgG3 was different (P = 0.024) at day 0, i.e., be fore initiation of intensive medical care, between the group of the 27 surviving subjects and the group of 1J patients dying of severe malar ia, As a consequence, most of the African patients who died had only t race amounts or almost no detectable level of parasite-specific IgG3 a t the time of admission, In contrast, the presence of even limited Igc 3 activity at day 0 was found to be associated with a significantly in creased probability of recovering from severe malaria, Therefore, in o ur study, both an elevated level of TNF-alpha sRI and absence of IgG3 activity were of bleak prognostic significance, whereas a favorable ou tcome was usually observed when parasite-specific IgG3 activity was de tectable, This finding was strongly suggestive of a prime role for the se parasite-specific immunoglobulins in the capacity to help recovery from severe malaria.