Acute Malaria Infection Research Articles

Role of DNA-binding antibodies in kidney pathology associated with murine malaria infections

We performed a series of studies to examine the sequential development of nephritis during murine malaria infections and to define the role of DNA-binding antibodies in the associated pathology. Serum levels of these antibodies were assessed throughout acute and chronic malaria infections. Increased levels of double-stranded DNA- and single-stranded DNA-binding antibodies were initially detected in mice infected with Plasmodium vinckei or Plasmodium yoelii nigeriensis during the middle stages of infection, and these levels were maintained until death. Infection with the more chronic organism Plasmodium berghei clone RC also resulted in increased single-stranded DNA-binding antibody titers, which fluctuated as the infection progressed. All three species caused kidney damage and dysfunction, as assessed by changes in morphology, blood urea nitrogen, and excreted albumin; this damage correlated with the extent of parasitemia and was observed before the levels of DNA-binding antibodies were detectably elevated in the serum. However, the results of immunohistochemical studies demonstrated that DNA-binding monoclonal antibodies bound ex vivo to glomeruli within kidneys prepared from mice at late stages of infection, after the initial damage had been incurred. Our findings suggest how DNA-binding antibodies could contribute to the kidney pathology associated with both malaria and certain autoimmune diseases, such as systemic lupus erythematosus.

High Frequency of Antibody Response to Plasmodium falciparum Gametocyte Antigens during Acute Malaria Infections in Papua New Guinea Highlanders

Sera from 62 adult Papua New Guinea highlanders with suspected acute malaria were tested by competitive ELISA for the presence of antibodies capable of inhibiting binding of 8 monoclonal antibodies (Mabs) directed against epitopes on gametocytes of Plasmodium falciparum. Between 33% and 72% of the malaria cases were inhibitory, depending on the Mab. There was no difference between the proportion of persons with P. falciparum (asexuals or gametocytes) and P. vivax whose sera inhibited Mab binding, but all 3 categories had a significantly higher proportion of inhibitors than persons who were malaria negative. The amount of gametocyte antibody recognizing epitopes on Pfs 48/45 and Pfs 230 increased with increasing numbers of previous malaria episodes. The proportion of sera from these relatively nonimmune adults which had gamete antibodies was similar to the proportion seen in sera from a highly endemic area, suggesting that antibody responses to these epitopes are a part of the initial response observed after a limited number of malaria episodes.

Reversible defect in cAMP metabolism in lymphocytes in malaria infection

Peripheral blood lymphocytes were observed to have a defect in adenosine 3′,5′-monophosphate (cAMP) metabolism during acute malaria infection which reversed once parasites were eliminated from the host circulation. The defect was characterized by decreased intracellular cAMP levels in lymphocytes and by hyporesponsiveness to adenosine or forskolin stimulation of cAMP production. These biochemical changesappeared to correlate functionally with a reduction in the proliferative response of lymphocytes to concanavalin A. A defect in the second messenger role of cAMP in immune effector cells may underlie immunosuppression in malaria infection.

THE CIRCULATING PLATELET IN ACUTE MALARIA INFECTION

British Journal of HaematologyVolume 74, Issue 1 p. 122-122 THE CIRCULATING PLATELET IN ACUTE MALARIA INFECTION B. Paul, Department of Haematology, Victoria Hospital, Worksop, Notts. S80 2BNSearch for more papers by this author B. Paul, Department of Haematology, Victoria Hospital, Worksop, Notts. S80 2BNSearch for more papers by this author First published: January 1990 https://doi.org/10.1111/j.1365-2141.1990.00118.x-i1Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume74, Issue1January 1990Pages 122-122 RelatedInformation

Suppression of in-vitro lymphoproliferative responses in acute malaria patients can be partially reversed by indomethacin.

In-vitro lymphoproliferative responses to malaria antigens are suppressed in patients with acute Plasmodium falciparum infection. Studies with other parasitic diseases have suggested that monocyte/macrophage-derived prostaglandins may be responsible for immunosuppression. Since acute malaria infection is characteristically associated with fever it is likely that prostaglandin E production will also be enhanced in these patients. In this study, indomethacin, a cyclooxygenase inhibitor which blocks the synthesis of prostaglandins, was added to the culture medium during assays of lymphoproliferative responses to malaria antigens and other soluble proteins. Responses to several antigens were enhanced in the presence of indomethacin, indicating that prostaglandins may have a generalized immunosuppressive role in malaria-infected individuals. However, responses to malaria antigens were particularly enhanced by indomethacin, suggesting that malaria-specific T-cells are especially sensitive to the effects of prostaglandin, possibly due to prior activation in vivo by circulating malaria antigens.

Platelet reactions after interaction with cultured Plasmodium falciparum infected erythrocytes

SummaryAn in vitro model for studying the interaction between normal human platelets and Plasmodium falciparum infected erythrocytes in culture is described. After the interaction, changes in platelet function such as enhanced aggregation response to exogenous ADP and increased secretion of dense granule contents were reproduced. Some of these responses represented manifestations of platelet hypersensitivity described earlier in acute malaria infections in man and mice. Preliminary investigations of the mechanisms involved in such reactions revealed that ADP and thromboxane A2 mechanisms contributed about 79% and 18.5% of the enhanced aggregation response to exogenous stimuli in the system.

Platelet reactions after interaction with cultured Plasmodium falciparum infected erythrocytes.

An in vitro model for studying the interaction between normal human platelets and Plasmodium falciparum infected erythrocytes in culture is described. After the interaction, changes in platelet function such as enhanced aggregation response to exogenous ADP and increased secretion of dense granule contents were reproduced. Some of these responses represented manifestations of platelet hypersensitivity described earlier in acute malaria infections in man and mice. Preliminary investigations of the mechanisms involved in such reactions revealed that ADP and thromboxane A2 mechanisms contributed about 79% and 18.5% of the enhanced aggregation response to exogenous stimuli in the system.

Clinical epidemiology, not seroepidemiology, is the answer to Africa's AIDS problem.

The shortcomings of the "seroepidemiology" approach as opposed to the traditional "clinical epidemiology" approach in answer to Africa's acquired immunodeficiency syndrome (AIDS) problem, are discussed. Investigators with a knowledge of tropical medicine have observe that recurrent malaria and other infectious diseases are associated with excessively high rates of false-positivity with H9/HTV-III, enzyme linked immunoabsorbent assay (ELISA), leading to a dichotomy between seroepidemiology and clinical epidemiology in tropical Africa. In addition, patients with alcoholic liver disease have a high incidence of false positive results on tests for HTLV-III antibodies, while acute malaria infections have produced false positivity even with the Western blot. When the conclusions of clinical epidemiology differ from those of seroepidemiology, clinicians should always believe the former. Serological work should be limited to assessing the specificity and sensitivity of the various kits under African conditions, screening all blood before transfusion, and serving as a back up procedure when clinical features are not clear cut. In his Krobo tribe, in southeastern Ghana, Dr. Konotey-Ahulu suggests that the bulk of any available funds should be resourcefully utilized in answering the questions: how, when, who, which, why and where?

The bone marrow of non-immune Europeans in acute malaria infection: a topical review.

(1987). The bone marrow of non-immune Europeans in acute malaria infection: a topical review. Annals of Tropical Medicine & Parasitology: Vol. 81, No. 5, pp. 567-576.

The mode of action of chloroquine and related malarial schizontocides

Use of fast-acting blood schizontocidal drugs such as chloroqune, amodiaquine, mepacrine or quinine, is essential for the treatment of acute malaria infections. The spread of resistance in Plasmodium falciparum to chloroquine, the most useful of these drugs, has been a serious problem since the 1960s, and the resistant strains show various degrees of cross-resistance to other drugs. Design of replacement drugs requires knowledge of their modes of action and mechanisms of resistance. At present, there are two theories to explain the mode of action of chloroquine (Box 1). In this debate, Coy Fitch advances the hypothesis that chloroquine acts by delaying the sequestration of Ferriprotoporphyrin IX (FP) into malaria pigment, thereby allowing FP to exert its intrinsic cellular toxicity. In contrast, David Warhurst proposes a new ‘Permease theory’ suggesting that chloroquine is imported into the parasite cytoplasm on a membrane carrier (the permease) under the influence of a proton gradient; the drug would then interfere with lysosomal digestion of haemoglobin, thus starving the parasite of amino acids for protein synthesis.

Antibodies to acquired immune deficiency syndrome (AIDS)-associated virus (HTLV-III/LAV) in Venezuelan populations.

Serum samples from 850 individuals from Venezuela were tested for the presence of antibodies to HTLV-III/LAV virus, the probable etiological agent of acquired immune deficiency syndrome (AIDS). At the time of the study, none of the individuals tested had symptoms indicative of AIDS or related disorders. Viral antibodies were assayed by indirect immunofluorescence (IF) assay, using a chronically infected, HTLV-III/LAV producer cell line CEM/LAV-NIT established in our laboratory. Twenty individuals (2.5%), 8 of them (40%) female, were seropositive by IF and by confirmatory Western blotting and radioimmunoprecipitation assays. The seropositivity rate ranged from 2.4% (11 of 465) in the general healthy population, 4% (2 of 50) among patients with Chagas' disease, and up to 29.2% (7 of 24) among patients with acute malaria infection. The titers of HTLV-III/LAV antibodies ranged from 1:40 to 1:640. In addition, 2 of 36 patients with hemophilia A (5.5%) also had antibodies to HTLV-III/LAV. Two of 7 patients with acute malaria had specific antibodies both to HTLV-III/LAV and HTLV-I, as determined by IF and Western blotting. None of over 169 randomly chosen, healthy blood donors from seven major Venezuelan cities, as well as none of 99 patients with leukemia/lymphoma, had antibodies to HTLV-III/LAV. The presence of specific antibodies among various Venezuelan populations indicates that HTLV-III/LAV, or a closely related cross-reactive virus, is indigenous in Latin American subjects as was previously indicated for tropical populations of central Africa. Isolation and characterization of this virus will help to understand the origin and etiology of AIDS.

Parasite antigens in protection, diagnosis and escape: Plasmodium.

In the hundred years since Laveran first described the malaria parasite as the cause of intermittent fevers, the basic biological questions posed at the end of his paper have been answered. The pathology of acute or chronic malaria infection is however still far from being fully understood and despite the accumulated knowledge of a century, the disease persists as one of the world’s major health problems. Optimism about worldwide eradication by organised vector control and chemotherapy was maintained up until the early 1960s. Since this time there has been a resurgence of malaria in many areas of the world due to a number of factors many of which are outside the scope of this discussion. Deterioration in control of malaria has however been associated with a rapid spread of both insecticide resistance among mosquitos and drug resistance of the parasites. Such chemical weapons remain as the major means of controlling malaria so that for the reasons outlined above, research in recent years has begun to focus on possible means of immunoprophylaxis. This chapter will be devoted mainly to work which has attempted to define and characterise parasite antigens important in the induction of protective immunity, and evasion of the host’s immune response.

Platelet Hypersensitivity in Acute Malaria (Plasmodium falciparum) Infection in Man

During acute malaria infection, platelets in human platelet-rich plasma re hypersensitive to the addition of ADP between 1.0 micro M and 5.0 micro M, or adrenaline 0.11 micro M as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 micro M) , 39.8 +/- 27 (1SD), was significantly greater than the value in 6 controls (5.2 +/- 6.7 (1SD); t = 3,51 P less than 0.005). A similar pattern of response was obtained with higher ADP concentrations (2,4, 4.5 or 5.0 micro M) in 22 patients and 20 control subjects (89.9 +/- 14.9 % vs 77.8 +/- 16.5% (1SD) t = 2,45, P less than 0.02). Addition to 4.5 microM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls. Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 +/0 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2 +/- 15.7 ng/ml; t=13.44, P less than 0.002).

The effect of Plasmodum berghei and Trypanosoma brucei infections on the immune expulsion of the nematode Trichuris muris from mice

The effects of concurrent P. berghei or T. brucei infections on the immune expulsion of primary and challenge infections of T. muris from CFLP strain mice have been examined. CFLP mice usually expel the nematode 18–21 days after a primary infection and within 4–6 days after a challenge infection. Both acute malaria and trypanosome infections initiated at the same time as the T. muris infection suppressed worm expulsion; when the protozoal infections were started 7 days after the T. muris infection worm expulsion was suppressed in a proportion of the mice. Acute trypanosome and malaria infections delayed the expulsion of a challenge infection from immune mice, but in the case of P. berghei the delay was short-lived.

Physiopathological changes in primary acute blood-transmitted malaria andBabesiainfections

(1965). Physiopathological changes in primary acute blood-transmitted malaria and Babesia infections. Annals of Tropical Medicine & Parasitology: Vol. 59, No. 2, pp. 153-158.

Hormone Treatment of Prostatic Hypertrophy

<h3>Objective:</h3> To report a case of Post-Malaria Neurological Syndrome presenting in the US in a returning Peace Corps volunteer <h3>Background:</h3> Post-Malaria Neurological Syndrome (PMNS) is a rare post-infectious encephalitis which occurs 4 to 60 days after recovery from severe <i>falciparum</i> malaria. There is a proclivity for non-immune travelers visiting endemic areas. <h3>Design/Methods:</h3> A 24-year-old man presented with acute onset fever, impaired consciousness, tremors and generalized tonic-clonic seizures. One month prior he had successfully completed treatment for P. <i>falciparum</i> malaria contracted while working in Togo, Africa. On exam temperature was 38.0 C. He exhibited neck rigidity with Kernig’s and Brudzinski’s signs. Glasgow Coma Scale was 6. There was generalized hyper-reflexia. Babinski signs were absent. Peripheral WBC 15.3, Neutrophils 76%. Cerebrospinal fluid (CSF) analysis: WBC 65, lymphocytes 91%, protein 65, Glucose 64. Four malaria smears, DNA PCR and malaria antigen were negative. CSF infectious panel was also negative. Patient received empiric antibiotics with no improvement. After initiation of high dose glucocorticoids he demonstrated rapid improvement with complete recovery in seven days. <h3>Results:</h3> PMNS must be distinguished from relapse of malaria or cerebral malaria (CM). CM is an encephalopathy occurring during acute malaria infection where parasitemia and other manifestations of malaria such as acidosis, hemolysis, renal and hepatic failure are also present. In PMNS, there is a disease-free interval between treated malaria and the onset of neurological symptoms, parasitemia is absent and other organ systems are not involved. MRI abnormalities consist of increased T2-weighted signal in periventricular area, internal capsule, pons, thalamus and corona radiata. It is usually self-limited, lasting 2–14 days, and requires no specific treatment. Steroids may play a role in severe cases. <h3>Conclusions:</h3> It is prudent to consider and distinguish the diagnosis of Post Malaria Neurological Syndrome in a patient who presents with new onset neurological symptoms with recent malaria infection in the background. <b>Disclosure:</b> Dr. Waseem has nothing to disclose. Dr. Singh has nothing to disclose. Dr. Bradshaw has received research support from Cytokinetics, Catalyst.