Serums from 90 individuals from three areas in Sudan were tested for inhibitory activity against cultures of Plasmodium falciparum. In addition to inhibitory activity against merozoite invasion, all of the serums demonstrated, in varying degrees, the ability to retard intraerythrocyte development, leading to crisis forms and parasite deterioration. These retardation factors could be removed by absorption of immune serum with parasite-infected erythrocytes and were demonstrable in purified immunoglobulin fractions. Serum from donors in hypoendemic Khartoum did not retard parasite development.

Clinical histories with regard to falciparum malaria were collected from adults living in holo-, hyper-, and hypoendemic areas of Sudan and matched to serum samples which were assayed for antiparasitic activity in cultures of Plasmodium falciparum. The adult population of the endemic areas could be divided into three groups based on oral histories: those who never experience falciparum malaria; those with a childhood history of malaria, who experience only mild occasional malaria as adults; and those who suffer serious recurring malaria symptoms. In vitro parasite inhibition was greatest with sera from individuals with no clinical histories of malaria, and generally, more inhibition was noted in sera from holoendemic versus hyperendemic areas. Serum from hypoendemic urban Khartoum was not inhibitory. There was no relationship between serum indirect fluorescent antibody titers and parasite inhibition, but there was strong association between clinical immunity and intraerythrocytic parasite inhibition resulting in "crisis" forms. Purified immunoglobulin G was not strongly associated with crisis forms, which were consistently associated with fractions of immune serum remaining after immunoglobulin removal. Thus, it appears that clinical immunity to malaria in Sudan is based on nonantibody serum factors, possibly associated with cell-mediated immunity. Human leukocyte alpha-interferon had no inhibitory effects on cultured P. falciparum. Some umbilical cord sera were profoundly inhibitory, producing crisis forms, whereas others were not inhibitory, suggesting that factors that induce crisis forms may play a role in protecting neonates from falciparum malaria.

Immunity to falciparum malaria was compared in two populations from malarious areas of southern Sudan and Flores, Indonesia. In Sudan, splenomegaly in adults was rare and anti-plasmodium indirect fluorescent antibody (IFA) titers were low to moderate, 1:1,280 being the modal titer. Sudanese serum was profoundly inhibitory to cultured Plasmodium falciparum, reducing incorporation of radiolabeled hypoxanthine by 63-93% and severely retarding intraerythrocytic parasite development, resulting in moribund crisis-form parasites and virtually no healthy schizonts. In Flores, 64% of the serum donors had splenomegaly 2 Hackett spleen grade 4 or 5, and the modal IFA titer was 1:10,240. Sera from Indonesia did not retard intraerythrocytic parasite development, but inhibited merozoite erythrocyte invasion 22-87%. Anti-merozoite activity did not correlate with IFA titers. The differences in principal modes of anti-parasitic activity suggest that immunity to malaria in Sudan is based on cellmediated immune mechanisms associated with crisis forms, merozoite neutralization being of secondary importance. In contrast, malaria immunity in Flores appears to be principally based on anti-merozoite antibody, which does not cause crisis forms and allows for development of reduced numbers of healthy schizonts. This less efficient mechanism may lead to a continuous low-grade parasitemia, which could explain the high specific malaria antibody titers and adult splenomegaly in Flores as compared to Sudan. This latter approach to immunity, being less efficient than the former, apparently results in chronic malaria infections with associated high Ig titers and splenomegaly.Recent studies on human immune responses to falciparum malaria in Sudan have shown that serum from,adults who live in malarious areas and are clinically immune to malaria contains a factor, or factors, that retard intraerythrocytic parasite development in cultured Plasmodium falciparum, leading to abnormal parasites known as crisis forms (1). Sera containing high titers of this factor can inhibit metabolic activity of the cultured parasites by more than 90% over a single 48-hr developmental cycle, as determined by scintillation spectrometry of the incorporation of [3H]hypoxantbine ([3H]Hyp) into parasite nucleic acids; schizogony, if it occurs in the presence of immune serum, rarely results in the production of invasive merozoites (2). Further studies correlating medical histories with regard to clinical malaria and the parasite-inhibition properties of corresponding serum samples have shown that serum factors responsible for induction of crisis-form parasites in vitro are not associated with immunoglobulins G or M but (i) are strongly associated with clinical immunity to malaria, (ii) are found in the umbilical cord blood of neonates born to immupe mothers, (iii) are highly associated with malaria endemicity, and (iv) thus appear to be part of the acquired immunity to falciparum malaria (3). We have coined the term crisis-form factor (CFF) for convenience; althoug...

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Chloroquine-resistant Plasmodium falciparum is endemic in many areas. Saudi Arabia was considered to have chloroquine-susceptible P. falciparum. During the 1997-1998 season, an outbreak of malaria occurred in the southwestern region. Over a 4-month period, 32 cases (6.2%) of 520 malaria admissions met the World Health Organization criteria for cerebral malaria. The mean patient age was 28 years. Thirteen male and 19 female patients were admitted in coma. The mean duration of coma was 4.3 days; the case fatality rate was 41%. Compared with those who recovered, patients who died had a lower mean admission diastolic blood pressure and hemoglobin level, higher mean blood urea nitrogen and blood glucose levels, and thrombocytopenia. Logistic regression analysis identified treatment with quinine rather than chloroquine to be associated with survival. These findings show the potential of P. falciparum to emerge as chloroquine resistant in previously susceptible areas, resulting in significant morbidity and mortality in spite of sophisticated medical care.