Naturally-occurring anti-α-galactosyl antibodies in human Plasmodium falciparum infections — a possible role for autoantibodies in malaria

Naturally-occurring antibodies with a distinct α-galactosyl specificity (anti-gal) have been earlier implicated in opsonization and elimination of human senescent erythrocytes from circulation. In the present study a cell-ELISA was developed for quantification of anti-gal antibodies in human sera. Using the test, titres of anti-gal were found to be significantly elevated in many of the sera collected from subjects living in malaria endemic areas or patients with acute Plasmodium falciparum malaria, in comparision to the titres in subjects living in areas where the incidence of P. falciparum malaria was scarce. IgG subclass typing by cell-ELISA revealed IgG3 to be the predominant type with anti-gal activity in P. falciparum infected patients' serum while IgG2 was found to be dominant in the non-endemic control serum. These findings appear to have implications in P. falciparum malaria, since putative antigens with α-galactosyl determinants have been identified in the erythrocytic stage parasites of P. falciparum. [5].     

Blood coagulation in immunothrombosis—At the frontline of intravascular immunity

While hemostasis is the physiological process that prevents blood loss after vessel injury, thrombosis is often portrayed as a pathologic event involving blood coagulation and platelet aggregation eventually leading to vascular occlusion and tissue damage. However, recent work suggests that thrombosis can also be a physiological process, termed immunothrombosis, initiated by the innate immune system providing a first line of defense to locally control infection. Fibrin forms the structural basis of immunothrombotic clots and its assembly involves the concerted action of coagulation factors, platelets and leukocytes. Here, we summarize the cellular and molecular events that initiate fibrin formation during the innate immune response and discuss how aberrant activation of these pathways fosters pathologies associated with thrombosis, including disseminated intravascular coagulation and atherothrombosis.     

Clinico-pathological studies of Plasmodium falciparum and Plasmodium vivax — malaria in India and Saudi Arabia

Malaria is one of the most devastating diseases of tropical countries with clinical manifestations such as anaemia, splenomegaly, thrombocytopenia, hepatomegaly and acute renal failures. In this study, cases of thrombocytopenia and haemoglobinemia were more prominent in subjects infected with Plasmodium falciparum (Welch, 1897) than those with Plasmodium vivax (Grassi et Feletti, 1890). However, anaemia, jaundice, convulsions and acute renal failure were significantly high (3–4 times) in subjects infected with P. falciparum than those infected with P. vivax. The incidence of splenomegaly and neurological sequelae were 2 and 6 times higher in P. falciparum infections compared to the infections of P. vivax. Both in P. vivax and P. falciparum malaria, the cases of splenomegaly, jaundice and neurological sequelae were almost double in children (<10 years) compared to older patients. The liver enzymes were generally in normal range in cases of low and mild infections. However, the AST, ALT, ALP activities and serum bilirubin, creatinine, and the urea content were increased in P. falciparum and P. vivax malaria patients having high parasitaemia, confirming liver dysfunction and renal failures in few cases of severe malaria both in India and Saudi Arabia.     

P. falciparum malaria prevalence among blood donors in Bamako,Mali

Aim

Malaria parasite is usually transmitted to humans by Anopheles mosquitoes but it can also be transmitted through blood transfusion. Usually malaria transmission is low in African urban settings. In West Africa where the P. falciparum is the most predominant malaria species, there are limited measures to reduce the risk of blood transfusion malaria. The aim of this study was to evaluate the prevalence of P. falciparum malaria carriage among blood donors in the National Blood Center of Bamako, capital city of Mali.

Decreased serum levels of TGF-β in patients with acutePlasmodium falciparum malaria

Apart from cellular immunity and immunopathology, various cytokines have been implicated in malaria-associated immunosuppression. In this study, serum levels of transforming growth factor- (TGF-) were determined with an enzyme-linked immunosorbent assay in 37 patients with acutePlasmodium falciparum malaria prior to, during, and after therapy and in 17 healthy controls in Bangkok, Thailand. Patients were treated with artesunate and mefloquine. TGF- serum levels were found decreased prior to treatment (14±11 pg/ml versus 63±15 pg/ml in healthy controls;P<0.05). The serum concentrations of TGF- increased after initiation of treatment and were within normal range on day 21. Serum levels of both tumor necrosis factor-ga (TNF-) and soluble TNF-receptor 55 kDa were inversely correlated to serum levels of TGF- (r= –0.667 andr=}-0.592, n=37; respectively,P < 0.05 for both). No correlation between parasitemia and serum levels of TGF- could be found. The results are compatible with a decreased production and release, an enhanced clearance or utilization, or tissue accumulation of TGF- in acuteP. falciparum malaria.     

Blood compatibility — a perspective

This perspective on blood-materials interactions is intended to introduce the set of papers stemming from the symposium, ''Devices and Diagnostics in Contact with Blood: Issues in Blood Compatibility at the Close of the 20th Century,'' organized on August 4-6, 1999 at the University of Washington by the University of Washington Engineered Biomaterials (UWEB) Engineering Research Center. This article outlines some of the history of blood contacting materials, overviews the work that has originated at the University of Washington over the past 28 years, speculates on the origins of the controversies on blood compatibility and considers the issues that should be addressed in future studies.     

Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: a threat to diagnosis of P. falciparum malaria

BackgroundPfHRP2-based rapid diagnostic tests (RDTs), based on the recognition of the Plasmodium falciparum histidine-rich protein 2, are currently the most used tests in malaria detection. Most of the antibodies used in RDTs also detect PfHRP3. However, false-negative results were reported. Significant variation in the pfhrp2 gene could lead to the expression of a modified protein that would no longer be recognized by the antibodies used in PfHRP2-based RDTs. Additionally, parasites lacking the PfHRP2 do not express the protein and are, therefore, not identifiable.AimsThis review aims to assess the pfhrp2 and pfhrp3 genetic variation or the prevalence of gene deletion in areas where malaria is endemic and describe its implications on RDT use.SourcesPublications of interest were identified using PubMed, Google Scholar and Google.ContentMore than 18 types of amino acid repeats were identified from the PfHRP2 sequences. Sequencing analysis revealed high-level genetic variation in the pfhrp2 and pfhrp3 genes (>90% of variation in Madagascar, Nigeria or Senegal) both within and between countries. However, genetic variation of PfHRP2 and PfHRP3 does not seem to be a major cause of false-negative results. The countries that showed the highest proportions of pfhrp2-negative parasites were Peru (20%–100%) and Guyana (41%) in South America, Ghana (36%) and Rwanda (23%) in Africa. High prevalence of pfhrp2 deletion causes a high rate of false-negatives results.ImplicationsPresence of parasites lacking the pfhrp2 gene may pose a major threat to malaria control programmes because P. falciparum-infected individuals are not diagnosed and properly treated.     

Resolution of inflammation pathways in preeclampsia—a narrative review

Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality worldwide. This disease is believed to occur in two stages with placental dysfunction in early pregnancy leading to maternal clinical findings after 20 weeks of gestation, as consequence of systemic inflammation, oxidative stress, and endothelial dysfunction. Much evidence suggests that PE women display an overshooting inflammatory response throughout pregnancy due to an unbalanced regulation of innate and adaptive immune responses. Recently, it has been suggested that dysregulation of endogenous protective pathways might be associated with PE etiopathogenesis. Resolution of inflammation is an active process coordinated by mediators from diverse nature that regulate key cellular events to restore tissue homeostasis. Inadequate or insufficient resolution of inflammation is believed to play an important role in the development of chronic inflammatory diseases, like PE. In this narrative review, we discuss possible pro-resolution pathways that might be compromised in PE women, which could be targets to novel therapeutic strategies in this disease.     

Oxytocin and depression in the perinatal period—a systematic review

Postpartum depression (PPD) is the most common postnatal psychiatric disorder, and it represents a considerable problem to the health and well-being of women and their families. Several pathogenic mechanisms have been identified in PPD, and recently, oxytocin (OT), known to be involved in childbirth and lactation, has drawn attention as a possible diagnostic and therapeutic tool in this disorder. The aim of this review was to assess and summarize the current literature on the relationship between OT as a potential depressive biomarker and depression in the perinatal period. We conducted a literature search on four electronic databases (Pubmed, PsycINFO, Web of Science, and Science Direct) by applying the following search terms: oxytocin AND (postpartum OR postnatal OR perinatal OR peripartum) AND (depression OR depressive). Six studies were included and a total of 620 pregnant women were recruited and completed the follow-up. Depressive symptoms were evaluated using self-report scales, and in three studies, the diagnosis of major depression was additionally confirmed using semi-structured interviews. Peripheral OT levels and depression were assessed during pregnancy and/or after delivery. Higher OT levels were associated with lower depressive symptoms, even if this association lacked statistical significance in two studies. Although some studies are beginning to shed light upon the complex nature of OT’s effect in depression, its role as a diagnostic and therapeutic tool in PPD is still unclear. Future research is needed to clarify the neuroendocrinological and psychosocial particularities of mothers with PPD and to define a specific profile associated with OT dysfunction.     

Endothelium—role in regulation of coagulation and inflammation

By its strategic position at the interface between blood and tissues, endothelial cells control blood fluidity and continued tissue perfusion while simultaneously they direct inflammatory cells to areas in need of defense or repair. The endothelial response depends on specific tissue needs and adapts to local stresses. Endothelial cells counteract coagulation by providing tissue factor and thrombin inhibitors and receptors for protein C activation. The receptor PAR-1 is differentially activated by thrombin and the activated protein C/EPCR complex, resulting in antithrombotic and anti-inflammatory effects. Thrombin and vasoactive agents release von Willebrand factor as ultra-large platelet-binding multimers, which are cleaved by ADAMTS13. Platelets can also facilitate leukocyte-endothelium interaction. Platelet activation is prevented by nitric oxide, prostacyclin, and exonucleotidases. Thrombin-cleaved ADAMTS18 induces disintegration of platelet aggregates while tissue-type plasminogen activator initiates fibrinolysis. Fibrin and products of platelets and inflammatory cells modulate the angiogenic response of endothelial cells and contribute to tissue repair.     

Advances in avian immunology—prospects for disease control: a review

In order to develop novel solutions to avian disease problems, including novel vaccines and/or vaccine adjuvants, and the identification of disease resistance genes which can feed into conventional breeding programmes, it is necessary to gain a more thorough understanding of the avian immune response and how pathogens can subvert that response. Birds occupy the same habitats as mammals, have similar ranges of longevity and body mass, and face similar pathogen challenges, yet birds have a different repertoire of organs, cells, molecules and genes of the immune system compared to mammals. This review summarises the current state of knowledge of the chicken's immune response, highlighting differences in the bird compared to mammals, and discusses how the availability of the chicken genome sequence and the associated postgenomics technologies are contributing to theses studies and also to the development of novel intervention strategies againts avian and zoonotic disease.     

Antidepressant combination for major depression in incomplete responders—a systematic review

BackgroundAntidepressant combination has been suggested as a strategy to increase treatment efficacy. The objective of this study was to perform a systematic review and meta-analysis of studies that assessed the effect of antidepressant combination for major depression in patients with incomplete response to an initial antidepressant.MethodsStudies were retrieved from PubMed (1966–February, 2012), Cochrane Library (–February, 2012), Embase (1980–February, 2012), PsycINFO (1980–February, 2012), Lilacs (1982–February, 2012), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. Included studies had an open label phase in which an initial antidepressant was used for the treatment of major depression and a double blind phase for the incomplete responders that compared monotherapy with the first antidepressant versus the association of a second antidepressant to the first one.ResultsOut of the 4,884 studies retrieved, only five satisfied the inclusion criteria. The total number of patients included was 483. Only two small trials reported benefits of adding a second antidepressant to the initial antidepressant. Dropouts due to side effects were not reported in three studies. Meta-analysis was not performed due to the small number of studies, the inconsistency in the direction of effect and the possible instability of effect size. Only limited kinds of combination, involving mianserin, mirtazapine and desipramine were studied. Some properties of the first two drugs such as the anxiolytic, sedative, and orexigenic effects, can mimic depression improvement.LimitationsPublication bias cannot be ruled out. Only one study included a monotherapy arm with the antidepressant used for augmentation of the first antidepressant.ConclusionsThe practice of using a combination of antidepressants for major depression in incomplete responders is not warranted by the literature.     

Hormone therapy in the menopause and breast cancer risk—a review

To evaluate the association between use of hormones in the menopause and breast cancer risk. Methods: A qualitative review of reports published between 1970 and 1995. Results: The risk of breast cancer starts to increase after 5 or more years of hormone use and remains elevated while taking hormones. Use for 10 or more years may be associated with a 30–80% increase in risk. From 2 to 5 years after stopping taking hormones, the risk seems to return to unity. There is no difference in risk between different types of oestrogens and the addition of progestins does not lower the risk. Conclusions: Short term use (less than 5 years) seems safe with respect to breast cancer risk, while longer durations of use may be associated with a small, but significant increase in risk.     

Interactions between coagulation and complement—their role in inflammation

The parallel expression of activation products of the coagulation, fibrinolysis, and complement systems has long been observed in both clinical and experimental settings. Several interconnections between the individual components of these cascades have also been described, and the list of shared regulators is expanding. The co-existence and interplay of hemostatic and inflammatory mediators in the same microenvironment typically ensures a successful host immune defense in compromised barrier settings. However, dysregulation of the cascade activities or functions of inhibitors in one or both systems can result in clinical manifestations of disease, such as sepsis, systemic lupus erythematosus, or ischemia–reperfusion injury, with critical thrombotic and/or inflammatory complications. An appreciation of the precise relationship between complement activation and thrombosis may facilitate the development of novel therapeutics, as well as improve the clinical management of patients with thrombotic conditions that are characterized by complement-associated inflammatory responses.     

Entomological characteristics of malaria transmission in Manhiça, a rural area in southern Mozambique

From October 1997 to September 1998, an entomological survey was carried out in Manhi?a, Mozambique, to describe the anopheline population and intensity of malaria transmission. Ten different huts were randomly selected for entomological surveillance throughout the year. CDC light trap collections were conducted during three nights each month. Additional knockdown spraying catches were carried out in the morning, after the last catch. A total of 17,245 Culicinae and 1,251 Anophelinae were collected during the study. There was substantial house to house variation and seasonality in the distribution of Anophelinae population, with a peak in April towards the end of the warm and rainy season. Four species of genus Anopheles (Diptera: Culicidae) were described: Anopheles funestus Giles, Anopheles tenebrosus D?nitz, Anopheles arabiensis Patton, and Anopheles merus D?nitz. An. funestus constitutes 72.3% of the anopheline population. The estimated sporozoite rate was 1.2% and the average entomological inoculation rate for the area was 15 infective bites per person per year.     

Efficacy of chloroquine in treatment of non-complicated malaria with Plasmodium falciparum in children at the San Pedro dispensary in Côte d'Ivoire

A survey has been carried out in south-west of C?te d'Ivoire in order to study chloroquine resistance in treatment of malaria according to 14 days protocol of WHO (World Health Organisation) (1996) for evaluation of antimalarial drugs activity; 63 children, aged from 6 months to 15 years and suffering from noncomplicated malaria due to Plasmodium falciparum, received by oral way 25 mg/kg of chloroquine over three days (10-10-5). During the survey, they were subjected to a clinic and parasitologic (thick and thin blood film) follow up. We obtained, for 51 children (81%), a satisfactory clinical answer, for 8 children (13%) an early therapeutic failure and for the other 4 (6%) a late therapeutic failure. Moreover, we obtained 40% of failure in children of less than 24 months old, 25% between 24 months and 59 months and 7% beyond 6 years old.     

Leishmaniasis treatment—a challenge that remains: a review

Leishmaniasis is a disease caused by flagellate protozoan Leishmania spp. and represents an emergent illness with high morbidity and mortality in the tropics and subtropics. Since the discovery of the first drugs for Leishmaniasis treatment (i.e., pentavalent antimonials), until the current days, the search for substances with antileishmanial activity, without toxic effects, and able to overcome the emergence of drug resistant strains still remains as the current goal. This article reports the development of new chemotherapies through the rational design of new drugs, the use of products derived from microorganisms and plants, and treatments related to immunity as new alternatives for the chemotherapy of leishmaniasis.