The sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria in young African children. We investigated the extent of the association between HbAS and antibodies directed to parasite-derived variant surface antigens (VSAs) on the membrane of infected erythrocytes. We measured immunoglobulin G (IgG) responses with specificity for VSAs of 2 heterologous parasite isolates in 458 Gabonese children aged between 6 months and 11 years. Logistic regression analyses showed a highly significant independent association (P<.001) between carriage of HbAS and the presence of IgG anti-VSA responses; this association was related specifically to IgG1 and IgG4 subclasses in the anti-VSA profile. IgG2 and IgG3 anti-VSA responses were both independently associated with older age, consistent with the pattern observed in semi-immune adults. The results imply that enhanced levels of cross-reactive anti-VSA responses in children with HbAS may be intimately associated with the protection they have against malaria.

Abstract. The fucose-mannose ligand (FML)-ELISA assay showed a sensitivity of 100% and a specificity of 100% in diagnosis of canine visceral leishmaniasis (CVL) (kala-azar) in sera from naturally infected dogs from São Gonçalo do Amaranto, Rio Grande de Norte, Brazil. The overall prevalence of antibodies to Leishmania in the endemic area was 23% (79 of 343). Seroreactivity detected by a Leishmania chagasi immunofluorescent (IF) assay was much lower (2.9%) and similar to the percentage of dogs with kala-azar symptoms (2.6%). Twenty-one of 21 asymptomatic, FML-seropositive animals died of kala-azar in a period ranging from 0 to 6 months after diagnosis. The predictive value was 100% for the FML-ELISA, 43% for an L. mexicana ELISA, and 24% for the L. mexicana and L. chagasi IF assays, respectively. In experimentally infected dogs, all assays detected seropositivity between 90 and 120 days after infection. Since the current strategy for control of CVL is based on detection and destruction of infected dogs, the highly predictive, sensitive, and specific FML-ELISA represents a useful tool for field control of the disease.Zoonotic visceral leishmaniasis (ZVL) is one of the most important emerging diseases. 1 Its etiologic agent, (Leishmania chagasi or L. infantum) is introduced into the domestic cycle when infected foxes visit houses to scavenge poultry. Peridomestic sand flies acquire the parasite by feeding on the skin of foxes and transmitting it to dogs. The subsequent transmission to humans causes human visceral leishmaniasis (kala-azar), a severe disease that is lethal if not treated soon after the onset of symptoms. About 500,000 human cases of kala-azar are recorded annually worldwide. The current strategy for control of ZVL, as recommended by the World Health Organization, is based on detection and destruction or treatment of infected dogs and vector control. 1 The control of visceral leishmaniasis in northeastern Brazil involves the detection of infected dogs by serologic analysis using an immunofluorescent (IF) assay and elimination of seropositive dogs. 2 Seropositivity detected by the IF assay usually shows a good correlation with parasitologic evidence of infection. 2-4 However, due to its low sensitivity, this method underestimates the true prevalence of canine infection. More recently, an ELISA, 5 a dot-ELISA, 6 Western blotting, 7 rapid immunochromatographic tests, 8 and DNA molecular tools 2,9 have also been compared with conventional serology and proposed as alternative methods. No information is available concerning the predictive value of these tests. However, it is known that in human and canine kala-azar, antibodies to Leishmania appear in the circulation soon after infection, leading to an early subclinical period. 10 The early detection of infected dogs in the field could improve the control program since it would identify dogs that are still subclinical but already infective for sand flies. 3 We have recently tested the diagnostic and predictive value of the fucose-mannose ligand (FML)-ELISA f...

We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individual isolate-specific antibody profiles differed markedly in terms of their isotype content but were similar for healthy adults and healthy uninfected children. In healthy adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3 and IgG4 predominated. A transiently elevated IgG1 response was observed during the second of two successive malaria episodes in children, signaling P. falciparum infection-induced cross-reactive anti-VSA responses. Our findings highlight the prominence of IgG3 in the overall profile of these responses but also indicate a marked age-related increase in the prevalence of anti-VSA antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the high frequency of the histidine-131 variant of Fc␥RIIA in the Gabonese population.

We used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant surface antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1alpha (DBL-1alpha ) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) DBL-1alpha domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens' history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin.

Abstrucr.A lymphocytotoxic serum with unknown non-HL-A specificity was shown to detect Lea antigen on the lymphocytes of Le(a +) individuals. Hemagglutinating anti-Lea was present as well. The reactions of both antibodies were in complete agreement when tested against the red cells and lymphocytes of random donors and in family analyses.Lymphocytotoxic antibodies of Lea specificity were observed in five of six samples of anti-Lea sera, but three anti-Leb failed to demonstrate cytotoxic activity. The optimal thermal activity for anti-Lea cytotoxins was 22°C as compared to two examples of cold cytotoxins reactive at 15 "C. The possible presence of cytotoxic Lewis antibodies in HL-A typing sera should be considered, particularly when a 22°C phase is empoyed in the technique.The majority of human leukocyte cell antigens belong to the HL-A antigenic complex. Exceptions have been described by VAN ROOD et al. [14], LALEZARI [9], and their colleagues. SINGAL et al. [I21 have suggested that anomalous reactions observed in cytotoxicity testing were due to non-HL-A antibodies, and GROTHAUS et al. [6]have detected a number of reactions against neuraminidase-treated cells which clearly fall outside the HL-A system. Of these non-HL-A antigens, only the 5a and 5 b antigens of VAN ROOD and the NA series antigens of LALEZARI have been described in any detail. The 5 b antigen is known to be chemically distinct from the HL-A antigens, and the 5 system antigens are also distinguished on the basis of their different tissue distribution and lack of effectiveness in graft rejection [5, 151. LALEZARI'S neutrophil antigens are also distinctive in being restricted to this cell type and in being implicated in neonatal neutropenia [8]. This l Supported in part by funds from USPHS grants GM 10356, A1 00285, and A1 18399.