We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-phase, pretreatment plasma IL-12 and alpha interferon (IFN-alpha) levels, as well as the acute-phase mitogen-stimulated whole-blood production capacity of IL-12, were significantly lower in children with severe rather than mild malaria. IL-12 levels, in addition, showed strong inverse correlations both with parasitemia and with the numbers of circulating malaria pigment containing neutrophils. Acute-phase plasma tumor necrosis factor (TNF) and IL-10 levels were significantly higher in those with severe malaria, and the concentrations of both of these cytokines were positively correlated both with parasitemia and with the numbers of pigment-containing phagocytes in the blood. Children with severe anemia had the highest levels of TNF in plasma. In all the children, the levels in plasma and production capacities of all cytokines normalized when they were healthy and parasite free. The results indicate that severe but not mild P, falciparum malaria in young, nonimmune African children is characterized by down-regulated IL-12 activity, contrasting markedly with the up-regulation of both TNF and IL-10 in the same children. A combination of disturbed phagocyte functions resulting from hemozoin consumption, along with reduced IFN-gamma responses, may contribute to these differential effects.

We measured sporozoite- and total parasite antigen-specific IgG and IgM antibodies before and after treatment in matched groups of Gabonese children who presented with either mild or severe Plasmodium falciparum malaria. We investigated the influence of various parameters on these antibody responses, including clinical presentation, age, and post-treatment reinfection profiles. IgG but not IgM responses were strongly influenced by both clinical and parasitological status. IgG responses to the repeat region of the circumsporozoite protein, which were low at admission, particularly so in those with severe anemia, increased after treatment but showed no association with either age or reinfection profiles. Total parasite antigen-specific IgG responses were strongly influenced by parasitological status, and also differed significantly when segregated according to clinical status at admission, age, and reinfection histories. Most notably, anti-parasite IgG responses measured when children were parasite-free were higher and a good indicator of recent reinfections in those who presented with mild rather than with severe malaria. The profile of responses in the latter group suggests some immune system dysfunction, which may reflect the induction of tolerance to parasite antigens.

1. Sam DeRosa-Farag 1. Director of global high-yield portfolio strategy at Donaldson, Lufkin & Jenrette in New York. 2. Jonathan Blau 1. Senior vice president at Donaldson, Lufkin & Jenrette in New York. 3. Peter Matousek 1. An associate at Donaldson, Lufkin & Jenrette in New York. 4. Indra Chandra 1. A research assistant at Donaldson, Lufkin & Jenrette in New York. The author draws comparisons among three studies of default rates in the high–yield markets. Using data through December 1998, they show how the different methodologies of the three studies can produce very different results. While default rates increased during 1998, they remain below historical averages, and spreads as of the end of 1998 more than adequately compensated investors for the likelihood of a recession. Default rates by security type, rating, industry, seniority, and size of issue are examined in detail.

The contribution of T cell-mediated responses was studied with regard to resistance to reinfection in groups of Gabonese children participating in a prospective study of severe and mild malaria due to infection with Plasmodium falciparum. In those admitted with mild malaria, but not in those with severe malaria, production of IFN-gamma by peripheral blood mononuclear cells (PBMC) in response to either liver-stage or merozoite antigen peptides was associated with significantly delayed first reinfections and with significantly lower rates of reinfection. Proliferative or tumor necrosis factor responses to the same peptides showed no such associations. Production of interferon-gamma by PBMC in response to sporozoite and merozoite antigen peptides was observed in a higher proportion of those presenting with mild malaria. Differences in the Th1/Th2 cytokine balance may be linked to the ability to control parasite multiplication in these young children, helping to explain the marked differences observed in both susceptibility to infection as well as in clinical presentation.

In regions highly endemic for Plasmodium falciparum malaria, red cell polymorphisms that confer resistance to severe disease are widespread. Sickle cell trait, alpha-thalassemia, glucose-6-phosphate dehydrogenase deficiency, and blood groups were determined in 100 children from Gabon with severe malaria who were matched with 100 children with mild malaria and followed up for evaluation of reinfections. The sickle cell trait was significantly associated with mild malaria and blood group A with severe malaria. During follow-up, the original severe cases had significantly higher rates of reinfection than the original mild cases, with higher parasitemia and lower hematocrit values. Incidence rates did not differ in the context of erythrocyte polymorphisms, but patients with sickle cell trait presented with markedly lower levels of parasitemia than those without. Thus, the severity of malaria is partly determined by the presence of blood group A and the sickle cell trait. The different presentation of reinfections in severe versus mild cases probably reflects different susceptibility to malaria.

Using strict inclusion criteria, we conducted a hospital-based, case-control study in which 100 Gabonese children with severe Plasmodium falciparum malaria were matched for age, gender and provenance with 100 children presenting with mild malaria. Parasite antigen-specific cellular and humoral immunological responses were measured and compared with post-treatment parasite clearance times in each group. Significantly faster parasite clearance times were associated with in vitro production of IL-10 by acute-phase peripheral blood mononuclear cells (PBMC) in response to both liver and asexual stage parasite antigens, but not with proliferative, IFN-gamma, or TNF responses to the same antigens. In addition, in those children with mild malaria, higher levels of acute-phase antibody responses to liver stage antigen-1 (LSA-1) were associated with faster parasite clearance times, and were correlated with the presence of IL-10 responses to the same antigen. No such associations were found for IL-10 or antibody responses to a range of asexual blood stage antigens. Those with severe malaria had significantly lower levels of anti-LSA-1 antibodies compared to their counterparts with mild malaria. In conclusion, the results of this study suggest that parasite antigen-specific IL-10-mediated antibody responses may play a role in the control of asexual stage parasite multiplication in P. falciparum malaria.

We present a case-control study to investigate the distribution of Plasmodium falciparum genotypes in patients with severe and mild malaria. We compared clinical and parasitological data with the parasites' genotype and rosetting. The study group consisted of 100 children suffering severe malaria, defined as severe anaemia and hyperparasitaemia. These children were matched by age, sex and provenance with 100 children with mild malaria. For characterization of the parasites we used the polymerase chain reaction to determine merozoite surface antigen (MSA) 1 and 2 genotypes and the phenomenon of rosette formation. We found a significant association between rosette formation and disease severity, and a significant association of severe anaemia with the presence of the MSA-1 allele K1. Infections with 2 genotypes in the severely affected group were significantly associated with severe anaemia and the presence of MSA-1 allele K1. Comparison with the findings of other groups led to the conclusion that the occurrence of P. falciparum genotypes seems to differ geographically.

Journal Article Pyrimethamine/sulfadoxine for treating uncomplicated Plasmodium falciparum malaria in young children in Gabon Get access Ruprecht Schmidt-Ott, Ruprecht Schmidt-Ott 1Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon Search for other works by this author on: Oxford Academic PubMed Google Scholar Doris Luckner, Doris Luckner 2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon3Department of Infectious Diseases, Internal Medicine I, University of Vienna, Vienna, Austria Search for other works by this author on: Oxford Academic PubMed Google Scholar Leopold G. Lehman, Leopold G. Lehman 1Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon Search for other works by this author on: Oxford Academic PubMed Google Scholar Bertrand Lell, Bertrand Lell 1Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Matousek, Peter Matousek 2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon3Department of Infectious Diseases, Internal Medicine I, University of Vienna, Vienna, Austria Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernhard Greve, Bernhard Greve 2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter G. Kremsner Peter G. Kremsner 1Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany2Laboratoire de Recherches, Hôpital Albert Schweitzer, Lambaréné, Gabon Address for correspondence: Peter G. Kremsner, Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany. phone +49 7071 2987179, fax +49 7071 295189. peter.kremsner@uni-tuebingen.de Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 91, Issue 5, September-October 1997, Pages 578–579, https://doi.org/10.1016/S0035-9203(97)90033-X Published: 01 October 1997 Article history Received: 17 March 1997 Revision received: 28 April 1997 Accepted: 29 April 1997 Published: 01 October 1997