Falciparum malaria and pregnancy.

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortion, still births, intra uterine growth retardation (IUGR), and pre-mature labour. Two hundred eighty-eight admitted female patients of falciparum malaria were included in the study out of which 45 were pregnant. The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%); (p < 0.001). The incidence of various pernicious syndromes including cerebral malaria, severe anaemia (Hb < 5 g%) hepatic and renal failure were more in pregnant females in comparison to non-pregnant females. The incidence of infection was higher among primigravida and second gravida 30/45 (66.66%) as compared to multigravida 15/45 (33.33%) and the greater incidence of infection was seen during 14-28 wk of gestation 23/45 (51.11%). Pregnancy related complications in the form of preterm live birth (20%). Intra uterine death (IUD 31.11%), still births (13.33%) and abortions (11.11%) were more pronounced in primiparous women as compared to multiparous. Weight of placenta in majority of patients ranged between 200-400 g (22/31; 70.96%). Normal pregnancy continued in only 11 out of 45 pregnant females, out of which seven had low birth weight body (63.63%). As the pregnancy is associated with increased incidence and adverse outcome of falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemic therapy to reduce the risk of serious maternal and fetal complications.     

Falciparum malaria parasitemia index for predicting severe malaria

Introduction: While hyperparasitemia is considered an important indicator for the development of severe malaria, there is currently no consensus on the quantitative definition of hyperparasitemia. This study was conducted to establish a cutoff point for peripheral parasitemia among patients with Plasmodium falciparum malaria, to define severe malaria. Methods: The clinical presentations of 200 uncomplicated P. falciparum malaria, and 189 severe P. falciparum malaria, patients, admitted to the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, were analyzed. Results: A peripheral parasitemia of 0.5% was found to be the optimal cutoff point for defining severe malaria, demonstrating highest sensitivity (85.1%), specificity (62.0%), and accuracy (73.2%). Conclusion: Symptoms of severe falciparum malaria depend on many factors. For the definition of hyperparasitemia in areas of low or seasonal transmission, peripheral parasitemia of 0.5% might be considered a cutoff point for discrimination between severity levels. This value might be useful for the clinical management of malaria, particularly in hypo‐endemic areas, unstable transmission areas, and other areas with similar transmission patterns.     

Falciparum malaria presenting with pruritic rashes

Rash is not generally believed to be a symptom of malaria. Two cases of acute falciparum malaria in non-immune residents of Mozambique who presented with pruritic rashes are reported. One case exhibited classical urticaria, the other a pruritic papular rash. Review of the literature reveals cases of malaria from India, East Africa, France, and the USA presenting with urticaria or a pruritic rash. Previous exposure to malaria may be a factor in these presentations. Physicians should not discount the diagnosis of malaria in patients with a history of exposure if they present with a rash. This may be of particular importance in travellers returned from malarious areas to developed countries.     

Falciparum malaria: current therapeutic challenges

PURPOSE OF REVIEW: Malaria remains a major cause of death in much of the world. The routine treatment of malaria is currently threatened by rising rates of drug resistance. Moreover, mortality among children with severe and complicated malaria remains unacceptably high. Here we review trends in antimalarial drug resistance and report on the progress of newer drugs and drug combinations. We then review some recent literature regarding the pathological processes involved in the aetiology of severe malaria that may lead to improvements in the management of children with severe disease. RECENT FINDINGS: Resistance to first line therapies, including chloroquine and sulphadoxine/pyramethamine, continues to rise in many parts of the world. The availability of newer and more effective drugs and fixed drug combinations is hampered by financial and political considerations. Nevertheless, a number of promising drugs and supportive treatments for both mild and severe malaria are at various stages of development. SUMMARY: A range of newer drugs and fixed drug combinations are now available that are safe and effective. However, these drugs remain expensive and their introduction will require political and financial support at every level. Considerable work is still required to achieve a better understanding of the processes involved in the pathogenesis of severe and complicated malaria. Only then will it be possible to develop new and appropriate therapies that will be widely applicable.     

Falciparum malaria and beta-thalassaemia trait in northern Liberia

In a study in northern Liberia of the malaria and beta-thalassaemia hypothesis, the frequencies of beta-thalassaemia and HbS traits were 9.1 and 3.4% in the Mano and 9.5 and 1.7% in the Gio tribal samples. HbC and HbN were present at low frequency. G6PD deficiency was found in 16% of males. An observed increase with age of beta-thalassaemia trait frequencies was consistent with the selection hypothesis. However, we could not entirely exclude that associated iron deficiency influenced the results in the six to 11 month age group. Malaria was holoendemic; Plasmodium falciparum predominated, P. malariae and P. ovale were also identified. Plasmodium falciparum prevalence rates were similar in normal and beta-thalassaemia trait children but parasite densities were consistently lower in the latter. Using the criterion of a falciparum parasite density of 1 x 10(9) 1(-1) or greater to indicate a potentially important infection, the relative risk in beta-thalassaemia traits one to four years old from the cross-sectional study was 0.45 (upper 95% confidence interval 0.79) and 0.41 (0.61) in two to nine year trait carriers from a longitudinal study. Plasmodium falciparum gametocyte rates were lower in beta-thalassaemia trait children (P less than 0.005). The geometric mean titre of P. falciparum antibodies was lower in beta-thalassaemia trait children from the one to four year group (P less than 0.05). Otherwise immunological studies showed little difference between the different Hb types. Parasitological findings were consistent with relative resistance of HbS trait carriers towards P. falciparum infection. We found no evidence for relative resistance of beta-thalassaemia traits towards P. malariae infection nor that G6PD deficient males were more resistant to P. falciparum than those with normal activity. We conclude that the results are consistent with relative resistance of beta-thalassaemia trait carriers to P. falciparum malaria.     

Parasite multiplication potential and the severity of Falciparum malaria

The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.     

Cholesterol and apolipoprotein B metabolism in Tangier disease.

Tangier disease (TD), caused by mutations in the gene encoding ATP-binding cassette 1 (ABCA1), is a rare genetic disorder in which homozygotes have a marked deficiency of high density lipoproteins (HDL), as well as concentrations of low density lipoproteins (LDL) that are typically 40% of normal. Although it is well known that the reduced levels of HDL in TD are due to hypercatabolism, the mechanism responsible for the low LDL levels has not been defined. Recently, it has been reported that intestinal cholesterol absorption is altered in ABCA1 deficient mice, suggesting that aberrant cholesterol metabolism may contribute to the LDL reductions in TD. In order to explore this possibility, as well as to define the role that ABCA1 plays in the metabolism of apolipoprotein (apoB)-containing lipoproteins, we determined the kinetics of apoB-100 within lipoproteins, and cholesterol absorption, biosynthesis, and turnover, in a compound heterozygote for TD. The levels of HDL cholesterol, LDL cholesterol and LDL apoB-100 in this subject were 7, 27 and 69% of normal, respectively, the latter of which was due to a two-fold increase in LDL catabolism (0.54 vs. 0.26+/-0.07 poolsday(-1)) relative to controls (n=11). NMR analysis of plasma lipoproteins revealed that 91% of the LDL cholesterol in the TD subject was contained within small, dense LDL, as compared with only 20% for controls (n=70). Cholesterol absorption was 97% of the value for controls (n=15) in the TD subject, at 45%, with cholesterol synthesis and turnover increased modestly by 17 and 25%, respectively. Our data are consistent with the concept that the reductions of LDL observed in TD are due to enhanced catabolism, secondary to changes in LDL composition and size, with neither cholesterol absorption nor metabolism significantly influenced by mutations in ABCA1.     

Ocular complications of Tangier disease

Tangier disease, or familial high-density lipoprotein deficiency, is an inherited disorder resulting in tissue deposition of excessive cholesterol esters. Although associated corneal clouding has been reported to produce little visual impairment, this patient with Tangier disease had corneal clouding, decreased corneal sensation, and cicatricial ectropion and experienced slowly progressive marked visual impairment. All ocular cases of Tangier disease are reviewed. Ectropion and incomplete eyelid closure may precede corneal clouding and should be recognized as signs associated with Tangier disease. The combination of exposure keratopathy and corneal infiltration can cause significant visual impairment.     

Haemoglobinuria in a case of Falciparum malaria treated with co-artemether

The first reported case of haemoglobinuria in a patient treated with co-artemether for falciparum malaria is described.     

Tangier disease: a disorder of intracellular membrane traffic.

The interaction of human high density lipoproteins (HDL) with isolated human monocytes from control and Tangier patients was studied in tissue culture experiments. It was observed that normal monocytes, similar to mouse peritoneal macrophages, bind HDL to a cell surface receptor, internalize the bound HDL particles, transport the internalized HDL intracellularly through the cytoplasmic compartment without significant degradation, and ultimately resecrete intact HDL. The cellular interaction of Tangier monocytes with normal HDL was markedly different from control monocytes. HDL binding to Tangier monocytes was moderately increased and cell-associated HDL radioactivity was 6- to 10-fold enhanced in Tangier monocytes. The bulk of the internalized HDL, however, was detected in secondary lysosomes. Only minor amounts of the internalized HDL were resecreted from the Tangier monocytes, and most of this was degraded. These data suggest that the cellular metabolism of HDL is abnormal in Tangier monocytes. It is postulated that Tangier disease may be a disorder of intracellular membrane traffic in which HDL is diverted into the lysosomal compartment and degraded instead of being secreted through its regular transcellular route.     

Tangier disease: a structural defect in apolipoprotein A-I (apoA-I Tangier).

Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins apo-A-I and apoA-II in patients with Tangier disease are approximately 1% and 7% of those in normal subjects, respectively. Previous studies have shown that the low plasma concentrations of apoA-I and apoA-II are due to increased fractional catabolism with a relatively normal apoA-I and apoA-II synthesis. Plasma apoA-I and apoA-II were isolated to electrophoretic homogeneity from delipidated plasma lipoproteins from a patient with Tangier disease. ApoA-I Tangier differed from apoA-I from control subjects in amino acid composition, electrophoretic mobility, apparent molecular weight on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and heterogeneity of isoforms on isoelectric focusing. ApoA-II Tangier, however, appeared to be identical to normal apoA-II in amino acid composition and in immunological as well as chemical properties. These results have been interpreted as indicating that apoA-I Tangier has a different covalent structure than does normal apoA-I, and apoA-II Tangier is identical to normal apoA-II. This structural change in apoA-I Tangier is associated with rapid catabolism of apoA-I Tangier-and apoA-II Tangier-containing plasma lipoproteins, and it leads to the deficiency in high density lipoproteins, abnormal chylomicron remnants, and the intracellular accumulation of cholesterol ester characteristic of Tangier disease.     

Falciparum malaria transmitted by a thick blood smear negative kidney donor

This report describes a case of P. falciparum transmission by a recent-immigrant renal donor. The donor tested negative upon microscopy of a thick blood smear. The diagnosis was made after analysis of a Quantified Buffy Coat. In our opinion, a renal donor from a malaria endemic country should be pre-treated with antimalarials.