Course Of Malarial Infection Research Articles

Identification and characterization of autoantibody-producing B220 low B (B-1) cells appearing in malarial infection

Mice with malaria showed unique immunological responses, including the expansion of NK1.1 −TCR int cells (extrathymic T cells). Since TCR int cells with autoreactivity and autoantibody-producing B cells (B-1 cells) are often simultaneously activated under autoimmune conditions, it was examined whether B-1 cells were activated in the course of malarial infection. From days 14 after infection, B220 low B-1 cells appeared in the liver and spleen. The number of B220 low B cells was highest at day 14, but the ratio was highest at days 28–35. In parallel with the appearance of B220 low cells, autoantibodies against HEp-2 cells and double-stranded DNA were detected in sera. These B220 low cells had phenotypes of CD44 high, CD23 − and CD62L −. In sharp contrast, conventional B220 high B cells (B-2 cells) were CD44 low, CD23 + and CD62L +. These results suggested that malaria immune responses were not mediated by conventional T and B cells but resembled the responses during autoimmune diseases.

Immune responses during helminth-malaria co-infection: a pilot study in Ghanaian school children

Malaria and helminth infections have a shared geographical distribution and therefore co-infections are frequent in tropical areas of the world. Human populations of helminth and malaria co-infection have shown contradictory results for the course of malarial infection and disease, possibly depending on the type of helminth studied, the intensity of helminth infection and the age of the study population. Although immunological studies might clarify the underlying mechanisms of protection or increased susceptibility, there are very few studies that have looked at immunological parameters in helminth and malaria co-infection. After discussing the available immunological data on co-infection, we describe a pilot study performed in Ghanaian school children where we compare anti-malarial responses in children living in an urban area, where the prevalence of helminth and Plasmodium falciparum infections was low, with that of children living in a rural area with high prevalence of helminth and Plasmodium falciparum infections.

Plasma 25-hydroxyvitamin D does not vary over the course of a malarial infection

Assessment of the status of some micronutrients is complicated by the acute phase response to infection. We investigated whether 25-hydroxyvitamin D (25OHD) is an acute phase reactant by measuring the effect of a malarial infection on plasma 25OHD level. Blood samples were taken from patients with Plasmodium falciparum malaria daily during the course of their stay in hospital and at a follow-up session 2-6 weeks after discharge. 25OHD was measured by radioimmunoassay. Time course data for the 14 subjects who provided samples for at least the first 2 d in hospital showed no change in 25OHD level during the acute infection. For the 14 subjects with follow-up results, there was no difference between median 25OHD level at admission (25.6 ng/ml, interquartile range (IQR) 23.0, 40.2) and at follow-up (25.2 ng/ml, IQR 19.2, 32.1; P=0.084). 25OHD level appears to be unaffected during the course of a severe malarial infection and thus can be used as a measure of vitamin D status even in subjects who are currently ill.

Influence of CD4 +CD25 + T cells on Plasmodium berghei NK65 infection in BALB/c mice

CD4 + T cells co-expressing CD25 (CD4 +CD25 + T cells) have been identified as immunoregulatory suppressors modulating autoimmune response. Beside that, autoimmune response was supposed to be associated with malaria infection. Based on these data, we hypothesised that CD4 +CD25 + T cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. To test this possibility, we evaluated the kinetics of CD4 +CD25 + T cells during malaria infection and investigated the influence of CD25 depletion by anti-mouse CD25 monoclonal antibody (PC61) on the infection, using a mouse model of premunition to Plasmodium berghei NK65 malaria. The results showed that, during exacerbation of P. berghei NK65 infection, the proportion of CD4 +CD25 + T cells among CD4 + T cells decreased, although that of CD4 + T cells increased. CD25 depletion clearly delayed the growth of parasitaemia during parasite challenge, particularly in immunised mice. These findings demonstrated that CD4 +CD25 + T cells are able to influence protective immunity underlying premunition to P. berghei NK65 parasites.

Serum Vitamin A and E Concentrations in Acute Falciparum Malaria: Modulators or Markers of Severity?

1. To assess the association between vitamin A, vitamin E and the clinical course of severe malaria, serial morning blood samples were taken from 24 Vietnamese patients, aged 18-62 years, receiving intensive treatment for complicated Plasmodium falciparum infections. A single fasting blood sample was also taken from 10 control subjects aged 22-45 years. Serum retinol, carotene and vitamin E concentrations were measured by h.p.l.c. 2. Admission serum retinol concentration was depressed relative to that of the control subjects (0.69 +/- 0.35 versus 1.86 +/- 0.41 mumol/l mean +/- SD, P < 0.001) and correlated inversely with indices of hepatic function, but positively with the simultaneous serum creatinine concentration (P < 0.05). During the first week of treatment, serum retinol concentration increased in parallel with improving liver function, whereas serum creatinine concentration remained elevated in the majority of patients. Serum alpha- and beta-carotene concentrations remained depressed throughout. 3. Serum vitamin E concentration, corrected for total serum cholesterol concentration in the form of a ratio, was also depressed at presentation (3.1 +/- 1.8 x 10(3) versus 4.2 +/- 0.8 x 10(3) in control subjects; P < 0.05), but tended to be higher than the control value at the time of discharge (0.1 > P > 0.05); there was a significant correlation between admission ratio and parasite clearance time (P = 0.04). 4. On the basis of this and previous studies, vitamin A replacement could be considered in selected severely ill patients without renal impairment. As found previously in animal models, depressed vitamin E levels may have a beneficial effect on the course of malarial infection.

Malarial parasites and antioxidant nutrients.

Susceptibility to oxidative stress is a well-established feature of the malarial parasite. Pharmacologists have taken advantage of this property to design highly effective pro-oxidant antimalarial drugs. Less well appreciated is the fact that nutritional manipulation of host oxidative stress status by dietary means can have a profound effect on the growth of the parasite. In particular, rapid induction of vitamin E deficiency in mice by feeding highly unsaturated fatty acids (fish oil) strongly suppresses plasmodial growth. Likewise, the status of other antioxidant nutrients (e.g., riboflavin or vitamin C) may also influence the course of malarial infection under certain conditions. A combined nutritional pharmacology approach may offer some promise in controlling malaria.

Variation in the cytoadherence characteristics of malaria parasites: is this a true virulence factor?

The sequestration of Plasmodium falciparum-infected erythrocytes to the endothelial cells of brain capillaries is believed to represent one of the determining factors in the pathogenesis of cerebral malaria. In vitro studies of cytoadherence provide an experimental approach to understand the mechanism of sequestration and the respective roles played by parasite and host components in this interaction. This paper critically reviews current studies on cytoadherence, with particular emphasis on the nature of the information provided by such studies and their limitations. The paper also describes how cytoadherence studies using the patient's own monocytes can provide original information on the level of receptor up-regulation in the course of malarial infection.

Influence of Pregnancy on the Course of Malaria in Mice Infected with Plasmodium berghei

The course of malarial infection was compared in pregnant mice inoculated with Plasmodium berghei at different stages of gestation. When 12-14 wk old, pregnant BALB/c mice were inoculated with 1 x 10(6) of P. berghei NK65-infected red cells at gestation day 0, 2, 4, 6, 8, 10, 12, 14 or 16, the mice inoculated on gestation days 6-12 expired 6.5 days after inoculation compared to 9.5 days in non-pregnant mice. Parasitemia in these pregnant mice increased rapidly on day 4 after inoculation and anemia also developed earlier on day 5. However, the degree of parasitemia and anemia in the terminal stage of infection in these pregnant mice was milder than that of non-pregnant controls. Blood urea nitrogen increased at the terminal stage although the degree of increase in mice inoculated on gestation days 6-10 was comparatively small. Pregnant malarial mice died earlier with less physiological changes than non-pregnant controls. It was concluded that pregnancy makes the host susceptible to physiological changes caused by malaria.

The influence of dietary protein on the development of malaria.

In the course of malarial infection in an animal model, the dietary level of protein proved to be important. Synthetic diets were used, identical in every respect other than the type and amount of protein. Reducing the protein content of the diet led to a decrease in the level of infection and a protein-free diet almost totally suppressed the disease. These findings were obtained in rats infected with either Plasmodium berghei or Plasmodium vinckei; when the dietary protein was in the form of casein or albumin; and when well-nourished or previously undernourished animals were used. The study indicates that acute and chronic undernutrition may protect a host against severe malarial infection.

Rural hyper-endemic malaria in Tanganyika Territory

1. 1. There is a real need for a detailed study of hyper-endemic malaria in African villages, in order to provide the necessary background to more summary observations in other parts. 2. 2. A survey of previous work shows that, while a few careful studies of this nature have been made in other parts of the world, Africa is not so fortunate. The previous observations recorded show that the findings in different countries cannot be fitted into a coherent whole. 3. 3. A description is given of the people studied, their diet, and their conditions of life, with some indication of the diseases to which they are subject and of the birth and death rates. 4. 4. There is a high prevalence of A. gambiae in. houses, and a mean sporozoite infectivity of 12-2 per cent. The infectivity has a seasonal rise to 24 per cent., at a time when there is an average of nearly 15 female anopheles to a house. 5. 5. In a detailed clinical description of the course of malarial infection in this untreated population, it is shown that all babies are infected within 5 months of birth, and that all have severe infections. 6. 6. This stage of acute infestation has passed its zenith after 18 months, and is succeeded by a period of malarial instability, during which the parasite count rises and falls irregularly. But symptoms are absent. 7. 7. After puberty symptoms are completely absent, and the general parasite level is a fiftieth or less of that which is present during infancy. 8. 8. The spleen rate is high, being 85 per cent., but it decreases with the parasite rate, as immunity is acquired. The largest spleens are found in babies soon after their first infection. 9. 9. There is a seasonal rise in the parasite infestation of man, which is chiefly confined to the non-immune and partially immune children. 10. 10. Gametocytes are found predominantly in children, at the time when immunity is just beginning to be established. Even if they are present in adults, they occur in very small numbers only. There is a great seasonal rise in the frequency and number of gametocytes in children under 5 years of age. 11. 11. P. falciparum is the dominant infection at all ages, but the other species (including P. ovale) are also present during the first few years of life, and more rarely later. The immunity acquired to P. falciparum is less complete than that acquired to the other species. 12. 12. While children suffer from malaria during the first 2 years of life, and a few die during the first few months, older children cannot be said so to suffer, and no evidence was obtained of any harmful effects from malaria during adult life.

Notes on the association of malaria with nephritis

Summary 1. The irritation of epithelial cells and capillaries of the kidney in the course of a malarial attack in mostly slight and transient. But a copious production of toxins in an acute-attack of subtertian fever may more often give rise to a grave kidney lesion in the form of toxic nephritis. 2. Any form of malarial infection, if not treated or if inadequately treated, when in due course it becomes chronic or sub-chronic in character gives rise to prolonged toxin action on the kidney. This may account for the occurrence of chronic nephritis of the hydr˦mic type in all forms of malarial infection. In a small number of cases this form is associated with the azot˦mic type. 3. Kidney complication occurs more frequently in quartan infection, this being mostly mild in character, often insufficiently treated, and so more likely to lapse into the latent chronic stage. 4. Cases of kidney complications, acute or chronic, in the course of malarial infection are completely cured by specific malarial treatment.