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Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.

The anti-Trypanosoma brucei brucei activity in vitro and in vivo of a lactone-rich fraction of Vernonia blumeoides leaves (VBLF) and its potential in alleviating trypanosome-induced anemia and organ damage were investigated. Gas chromatography-mass spectrometry (GC-MS) analysis of VBLF revealed the presence of a number of lactone-containing compounds. In an in vitro study, VBLF showed concentration-dependent activity and was further used to treat T. brucei brucei-infected rats. The VBLF treatments, especially at 300 mg/kg body weight (BW), significantly (P < 0.05) kept the parasites reduced during the entire experimental period compared with the infected untreated group. At the end of the experiment, the trypanosome-induced anemia and hepatic damage were significantly (P < 0.05) alleviated in all the VBLF treatment groups, but renal damage was only prevented in the 200 and 300 mg/kg BW treatment groups. Furthermore, the trypanosome-induced increase in the relative weights of liver, spleen and kidney were significantly (P < 0.05) alleviated by the 300 mg/kg BW VBLF treatment. It was concluded that orally administered VBLF, especially at 300 mg/kg BW, possessed antitrypanosomal activity and could alleviate parasite-induced anemia and organ damage.

It is believed that most of the serious and life threatening complications are caused only by P falciparum infection while P vivax infections are relatively mild and run a benign course and usually not required hospitalisation but in the last few years hospitalisation rate and complications are also increasing in P vivax infection; so we planned this study to evaluate the severity and complicated presentation of P vivax malaria. This hospital-based study conducted in Jawahar Lal Nehru Hospital Ajmer, India. One hundred and two indoor patients with isolated P vivax malaria were included in this study with exclusion of other causes of fever including P falciparum malaria. All patients of severe and complicated P vivax malaria were admitted and treated as severe P falciparum malaria. Severe complications like significant hepatomegaly, thrombocytopenia, acute renal failure, severe anaemia, leucopoenia, electrolyte disturbance, acute respiratory distress syndrome, cerebral malaria, multiorgan dysfunction, hepatic dysfunction, pancytopenia, and death seen in 21.57%, 18.63%, 11.76%, 8.82%, 5.88%, 5.88%, 3.92%, 2.94%, 1.96%, 1.96%, 0.98%, 1.96% patients respectively. A significant proportion of morbidity and mortality in malaria also observed in P vivax infection as seen in P falciparum infection and require hospitalisation.

Recently, while studying erythrocytic apoptosis during Plasmodium yoelii infection, we observed an increase in the levels of non-parasitised red blood cell (nRBC) apoptosis, which could be related to malarial anaemia. Therefore, in the present study, we attempted to investigate whether nRBC apoptosis is associated with the peripheral RBC count, parasite load or immune response. To this end, BALB/c mice were infected with P. yoelii 17XL and nRBC apoptosis, number of peripheral RBCs, parasitaemia and plasmatic levels of cytokines, nitric oxide and anti-RBC antibodies were evaluated at the early and late stages of anaemia. The apoptosis of nRBCs increased at the late stage and was associated with parasitaemia, but not with the intensity of the immune response. The increased percentage of nRBC apoptosis that was observed when anaemia was accentuated was not related to a reduction in peripheral RBCs. We conclude that nRBC apoptosis in P. yoelii malaria appears to be induced in response to a high parasite load. Further studies on malaria models in which acute anaemia develops during low parasitaemia are needed to identify the potential pathogenic role of nRBC apoptosis.

Background: High seroprevalence of parvovirus B19 (B19V) coinfection with Plasmodium falciparum has been previously reported. However, the impact of B19V-infection on the clinical course of malaria is still elusive. In this study, we investigated the prevalence and clinical significance of B19V co-infection in Gabonese children with malaria., Methods: B19V prevalence was analyzed in serum samples of 197 Gabonese children with P. falciparum malaria and 85 healthy controls using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct DNA-sequencing., Results: B19V was detected in 29/282 (10.28%) of Gabonese children. B19V was observed more frequently in P. falciparum malaria patients (14.21%) in comparison to healthy individuals (1.17%) (P<0.001). Notably, the mild-malaria group revealed significantly lower hematocrit levels in B19V/P. falciparum co-infection than in P. falciparum mono-infection (P<0.05). Genetic analysis revealed a predominance of B19V genotype-1 (71.43%) in the studied population. However, B19V-genotype 2 was observed significantly more often in children with severe-malaria than in mild-malaria (P=0.04)., Conclusion: Our findings reveal that B19V-infection is frequent in Gabonese children with P. falciparum malaria and signifies a possible contribution of B19V on the clinical course of malaria in a genotype-dependent manner. B19V co-infection should be considered as a additional diagnostic measure in malaria patients with life threatening anemia.

Trypanosomal infection-induced anaemia is a devastating scourge for cattle in widespread regions. Although Trypanosoma vivax is considered as one of the most important parasites regarding economic impact in Africa and South America, very few in-depth studies have been conducted due to the difficulty of manipulating this parasite. Several hypotheses were proposed to explain trypanosome induced-anaemia but mechanisms have not yet been elucidated. Here, we characterized a multigenic family of trans-sialidases in T. vivax, some of which are released into the host serum during infection. These enzymes are able to trigger erythrophagocytosis by desialylating the major surface erythrocytes sialoglycoproteins, the glycophorins. Using an ex vivo assay to quantify erythrophagocytosis throughout infection, we showed that erythrocyte desialylation alone results in significant levels of anaemia during the acute phase of the disease. Characterization of virulence factors such as the trans-sialidases is vital to develop a control strategy against the disease or parasite., (© 2013 John Wiley & Sons Ltd.)

Context: The stem bark of Khaya senegalensis A. Juss (Meliaceae) is currently used for the treatment of trypanosomiasis by traditional practitioners in Nigeria., Objectives: The present study investigated the anti-Trypanosoma brucei brucei activity of phenolics-rich fraction of K. senegalensis (pfks) and its ameliorative effects on trypanosome-induced pathological changes., Materials and Methods: The fraction was initially analyzed by gas chromatography-mass spectrometry (GC-MS). A 60 min time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique and was further used to treat T. brucei infected rats at 100, 200 and 300 mg/kg body weight (BW). Indices of anemia as well as hepatic and renal functions were analyzed in all experimental animals at the end of the experiment., Results: The GC-MS analysis of the pfks revealed that the most abundant phytochemicals are phloroglucinol (40.56%) and 3,4-(dihydroxyphenyl) acetic acid (41.76%). The fraction showed a concentration dependent in vitro antitrypanosomal activity. Interestingly, the fraction completely eliminated the parasites from the bloodstream of infected rats without relapse during the experimental period at the dose of 300 mg/kg BW and also kept the parasites consistently lower at 100 and 200 mg/kg BW than that was recorded in the untreated infected rats. Furthermore, the severity of T. brucei-induced anemia and hepatic damage was significantly (p < 0.05) ameliorated in the 300 mg/kg BW treatment group whereas the parasite-induced renal damage was significantly (p < 0.05) ameliorated in all treatment groups., Conclusion: Data from this study may suggest that phenolics play an important role in the antitrypanosomal activity of K. senegalensis.

Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies.

Polymorphisms of ATP2B4 encoding an ubiquitous Ca(2+) pump protect against severe childhood malaria. We assessed the influence of a main polymorphism (rs10900585) on malaria among 834 delivering Ghanaian women. In homozygous primiparae, the odds of placental Plasmodium falciparum infection were reduced by 64%. No influence of the polymorphism on parasite density, low birth weight, or preterm delivery was discernible. However, malarial anemia was greatly reduced in primiparous carriers of the variant allele, paralleling the reduced impact of malaria on hemoglobin levels in this group. A common ATP2B4 polymorphism protects against malaria in pregnancy and related maternal anemia, suggesting ATP2B4 variant associated protection not to be limited to severe childhood malaria.

Background: Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates., Methodology/principal Findings: Rosetting and adhesion to CSA, CD36, ICAM1, placental and brain cryosections were determined in P. vivax peripheral isolates from 12 pregnant women, 24 non-pregnant women and 23 men from Manaus (Brazil). P. falciparum co-infection was excluded by PCR and P. vivax isolates were genotyped by assessing the size polymorphism of microsatellites ms2, ms20 and msp1F3 through capillary electrophoresis of PCR products. P. vivax monoinfection was confirmed by PCR in 59 isolates, with 50 (85%) of them being single-clone infections. One P. vivax haplotype was more frequently found among pregnant women (33%) than in non-pregnant women (0%) and men (4%; p=0.010). Rosetting was observed in 64% of the isolates, adhesion to CSA in 15%, to ICAM1 in 12% and to placental cryosections in 9%, being similar among pregnant and non-pregnant groups. Intensity of rosetting was higher among anaemic individuals compared to non-anaemic (p=0.010) and decreased with increasing haematocrit (p=0.033) and haemoglobin levels (p=0.015)., Conclusions/significance: P. vivax peripheral isolates from pregnant women do not exhibit a prominent adhesion to CSA, although other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones observed among pregnant hosts. Rosetting is a frequent cytoadhesive phenotype in P. vivax infections that may contribute to the development of anaemia.

The prevalence and pathogenic effects of trypanosomosis were determined in cattle, goats and pigs reared in Kasese, Jinja and Rakai districts, Uganda; presence of trypanosomes was detected by buffy coat technique (BCT). The overall prevalence of trypanosomosis in cattle was 7.6% (144/1,891), 0.7% in goats (4/573) and 2.3% in pigs (9/386). Internal transcribed spacer 1 (ITS1) of ribosomal DNA polymerase chain reaction was utilised to identify trypanosomes to species level and revealed infections in 108 of the 144 trypanosome-positive cattle while all infected goats and pigs gave amplicons. Trypanosoma vivax was the most prevalent trypanosome species in cattle in single and mixed infections compared to infections involving Trypanosoma congolense and Trypanosoma brucei; in pigs, eight were mixed infections with one single T. vivax infection. No predominant trypanosome species was detected in goats. Anaemia, the main trypanosomosis pathological feature, was investigated by determining packed cell volume (PCV). Mean PCV values by t test in infected individuals were significantly lower than non-infected individuals (P<0.05) for all animal species. However, the proportion of anaemic animals was not significantly different in infected and non-infected individuals. In addition, the percent of infected animals by Fisher's exact test depended on district of origin and species but not sex. These findings show that trypanosomosis is a major cause of anaemia in livestock in endemic areas. Cattle were the major animal species affected by trypanosomosis; similar genotypes of trypanosomes were detected in the three animal species. BCT was more effective than ITS1 rDNA detecting trypanosomes in naturally infected cattle.

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov).

Severe malaria is characterized by a massive release of proinflammatory cytokines in the context of sequestration of parasitized and normal red cells (RBCs). High-mobility group box 1 (HMGB1) is a DNA- and heparin-binding protein that also acts as a cytokine when released from cells in the extracellular milieu after a proinflammatory stimulus. In this study, we have measured the circulating levels of HMGB1 in 76 children with severe or uncomplicated malaria. Sera from both severe (P = 0.0022) and uncomplicated (P = 0.0049) patients had significantly higher circulating HMGB1 levels compared with healthy controls. Elevated HMGB1 in patients with ongoing Plasmodium falciparum infections might prolong inflammation and the febrile state of malaria and could offer a potential target for therapeutic intervention.

In recent years, the emergence of highly pathogenic Trypanosoma evansi strains in the Philippines has resulted in substantial losses in livestock production. In this study, we isolated T. evansi from infected-water buffaloes in the Philippines and analyzed their virulence using mice and cattle. A total of 10 strains of T. evansi were isolated. Evaluation of the virulence of each strain using mice depicted significant differences among the strains in the prepatent period, the level of parasitemia, and the survival time of the infected animals. In mice infected with the highly pathogenic T. evansi, signs of excessive inflammation such as marked splenomegaly and increase more than 6-fold in the number of leukocytes were observed at 8 days post-infection. To study the virulence of the parasite strains in cattle (which are the common T. evansi hosts in Philippines), cattle were infected with the T. evansi isolates that showed high and low virulence in mice. The rate of parasite growth and the length of the prepatent periods were found to be similar to those observed in mice for the respective strains. The cattle infected with the highly pathogenic strain developed anemia and a marked decrease in leukocyte counts. To determine the cause of the pathological changes, we analyzed the expression levels of inflammatory cytokines and observed up-regulation of tumor necrosis factor-α in anemic infected cattle. Our findings suggest that the epidemic of T. evansi in the Philippines is characterized by T. evansi strains with varying virulences from low to very high pathogenicity in cattle.

Rangeliosis is a hemoparasitosis that affects dogs in Brazil. The disease has similar clinical and pathological characteristics to other hemo-protozoan infections. So, this paper has aimed to report a clinical case of infection by Rangelia vitalii in one dog, focusing on the need for the differential diagnosis to other infectious diseases. The animal showed apathy, anemia, thrombocytopenia, alteration of leucogram, and bleeding. The first difference was the observation of parasites in blood smears, where R. vitalii was visualized within leukocytes and erythrocytes. The confirmation of the clinical diagnosis was made by molecular test to R. vitalii. The dog was debilitated, and died a few hours after treatment at the veterinary hospital. At necropsy, splenomegaly, lymphadenopathy, and mild jaundice in the abdominal viscera were found. This article draws attention to the need for the parasitological, serological, and molecular to differential diagnosis in order to differentiate from other clinically similar disorders.

Hookworms are bloodfeeding intestinal nematodes that are a major cause of anemia in resource-limited countries. Despite repeated exposure beginning in early childhood, humans retain lifelong susceptibility to infection without evidence of sterilizing immunity. In contrast, experimental infection of laboratory animals is typically characterized by varying degrees of resistance following primary infection, although the mechanisms underlying this phenomenon remain unknown. In this study, hamsters subjected to a single drug-terminated infection with 100 third stage hookworm larvae were confirmed to be resistant to pathological effects following a subsequent challenge. In a second experiment, hamsters infected twice-weekly with 10 third stage larvae (low inoculum) exhibited clinical and parasitological evidence of continued susceptibility, while those given 100 L3 (high inoculum) developed apparent resistance within 3 days following the initial exposure. The kinetics of parasite-specific IgA, IgM, and IgG antibody production varied by group, which suggests that the humoral immune response to hookworm infection is stimulated by the nature (frequency and intensity) of larval exposure. These results suggest that intermittent low-inoculum larval exposure, which is characterized by prolonged susceptibility to infection, may serve as a more representative model of human hookworm disease for studies of pathogenesis, as well as drug and vaccine development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determin the extent to which parvovirus B19 (B19V) and co-infection of B19V and malaria contribute to risk of anaemia in children., Methods: B19V DNA and malaria parasites were screened for 234 children at the PML Children's Hospital in Accra. The role of B19V and co-infection with B19V and malaria in anaemia was evaluated by analysing full blood cell counts, malaria and B19V DNA results from these children., Results: The prevalence of B19V, malaria and co-infection with B19V and malaria was 4.7%, 41.9% and 2.6%, respectively. Malaria posed a greater risk in the development of mild anaemia compared to severe anaemia (OR=5.28 vrs 3.15) whereas B19V posed a higher risk in the development of severe anaemia compared to mild anaemia (OR=4.07 vrs 1.00) from a non-anaemic child. Persons with co-infection with B19V and malaria had 2.23 times the risk (95% CI=0.40-12.54) of developing severe anaemia should they already have a mild anaemia. The degree of anaemia was about three times affected by co-infection (Pillai's trace=0.551, P=0.001) as was affected by malaria alone (Pillai's trace=0.185, P=0.001). B19V alone did not significantly affect the development of anaemia in a non-anaemic child. Microcytic anaemia was associated with B19V and co-infection with B19V and malaria more than normocytic normochromic anaemia., Conclusions: B19V was associated with malaria in cases of severe anaemia. The association posed a significant risk for exacerbation of anaemia in mild anaemic children. B19V and co-infection with B19V and malaria may be associated with microcytic anaemia rather than normocytic normochromic anaemia as seen in cases of B19V infection among persons with red cell abnormalities.

Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2) were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR) and transcription factors (GATA1, GATA2, FOG1) were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL), was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by cytokine-mediated apoptosis of erythroblasts.

Objective: To evaluate the contribution of poses screen pre-impregnated (PSP) installed at openings and eaves of dwellings in the reduction of malaria transmission in the commune of Aguégués in Bénin., Methods: The PSP were manufactured from preimpregnated Olyset Net. They were installed at windows, eaves and doors of 70 dwellings. 320 children aged 6-59 months were treated and 311 children were recruited in the control zone. Variables measured are: plasmodic index (IP), gametocyte index, parasite density (PD), fever, hemoglobin, anemia., Results: The global IP was 16.62% with PSP and 72.20% without PSP. Gametocyte index did not differ significantly between the treated zone (27.8) and the control zone (29.1). The total geometric mean of DP was 309 in the treated zone and 600 in the control zone. Hemoglobin level is 8.7 in the control zone and 9.5 in the treated zone. We noted a predominance of anemia in the control zone compared to the treated zone., Conclusions: The PSP have contributed to a significant reduction in morbidity in the commune of Aguégués., (Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Background: Severe falciparum malaria anaemia (SMA) is a frequent cause of mortality in children and pregnant women. The most important determinant of SMA appears to be the loss of non-parasitized red blood cells (np-RBCs) in excess of loss of parasitized (p-) RBCs at schizogony. Based on data from acute SMA where excretion of haemoglobin in urine and increased plasma haemoglobin represented respectively less than 1% and 0.5% of total Hb loss, phagocytosis appears to be the predominant mechanism of removal of np- and p-RBC.Estimates indicate that np-RBCs are cleared in approximately 10-fold excess compared to p-RBCs. An even larger removal of np-RBCs has been described in vivax malaria anaemia. Estimates were based on two single studies both performed on neurosyphilitic patients who underwent malaria therapy. As the share of np-RBC removal is likely to vary between wide limits, it is important to assess the contribution of both np- and p-RBC populations to overall RBC loss, and disclose the mechanism of such variability. As available methods do not discriminate between the removal of np- vs p-RBCs, the purpose of this study was to set up a system allowing the simultaneous determination of phagocytosis of p- and np-RBC in the same sample., Methods and Results: Phagocytosis of p- and np-RBCs was quantified in the same sample using double-labelled target cells and the human phagocytic cell-line THP-1, pre-activated by TNF and IFNγ to enhance their phagocytic activity. Target RBCs were double-labelled with fluorescent carboxyfluorescein-succinimidyl ester (CF-SE) and the DNA label ethidium bromide (EB). EB, a DNA label, allowed to discriminate p-RBCs that contain parasitic DNA from the np-RBCs devoid of DNA. FACS analysis of THP-1 cells fed with double-labelled RBCs showed that p- and np-RBCs were phagocytosed in different proportions in relation to parasitaemia., Conclusions: The assay allowed the analysis of phagocytosis rapidly and with low subjective error, and the differentiation between phagocytosed p- and np-RBCs in the same sample. The presented method may help to analyse the factors or conditions that modulate the share of np-RBC removal in vitro and in vivo and lead to a better understanding of the pathogenesis of SMA.

Background: Anaemia is known to be one of the outcomes of parasitic infection and it may result in impaired cognitive development, reduced physical work capacity and in severe cases increased risk of mortality, particularly during the prenatal period. The aim of this study was to determine the prevalence and associated risk factors of anaemia among pregnant women in Gilgel-Gibe dam area, southwestern Ethiopia., Methods: A cross-sectional community based study was conducted on 388 pregnant women living in three districts around Gilgel Gibe Dam area, southwestern Ethiopia. Socio-demographic and socio-economic data were collected from each participant. A single stool sample was also collected from each selected pregnant woman. Haemoglobin concentration was determined by the cyanmethemoglobin method. Plasmodium infection prevalence and intensity were assessed with thin and thick blood film examination., Results: Of the total 388 study participants, 209 (53.9%) were anaemic. Pregnant woman who were rural residents (Adjusted odds ratio (AOR) = 1.62, 95% C.I: 1.02-2.62, P= 0.042), not using insecticide treated nets (ITNs) during the study period (AOR = 2.84, 95% C.I: 1.33-6.05, p = 0.007), those who were Plasmodium malaria infected (AOR = 11.19, 95% C.I: 3.31-37.7, p= 0.01) and those with Soil Transmitted Helminth (STH) infections (AOR=1.82, 95% C.I: 1.16-2.87, p=0.001) had higher odds of being anaemic than those who were urban residents, using ITNs, free of Plasmodium malaria and Soil transmitted helminth infection, respectively. There was a significant correlation between increasing hookworm parasite load (r = -.110, P< 0.001), Ascaris lumbricoides (r = -.122, P < 0.001) and Trichuris trichiura (r = -.025, P < 0.001) and decreasing hematocrit values., Conclusion: The high prevalence of anaemia indicates it is currently a serious health problem of pregnant women living in Gilgel Gibe Dam area. Plasmodium malaria and soil transmitted helminth infections were significantly associated with anaemia. Antenatal care should promote de-worming and education on personal hygiene. Therefore, there is a need to design strategies that help to diagnose pregnant women for malaria and STH infections during their antenatal care (ANC) visit instead of testing for only haemoglobin (Hgb) levels and blood group.

Purpose: The aim was to assess whether impaired cardiac function contributes to symptoms of severe malaria in general or to metabolic acidosis in particular in children living in endemic regions., Methods: In a prospective observational investigation, 183 children with severe malaria were investigated for hemodynamic status and cardiac function upon admission (day 0) and after recovery (day 42). Cardiac function parameters were assessed by cardiac ultrasonography. Blood gas analyses and cardiac enzymes were measured at hospitalization and follow-up. Differences in subgroups with and without metabolic acidosis as well as other severe malaria-defining symptoms and conditions were assessed., Results: Cardiac index (CI) was significantly increased on day 0 compared to day 42 (5.8 ml/m(2), SD ± 1.8 ml/m(2), versus 4.7 ml/m(2), SD ± 1.4 ml/m(2); P < 0.001). CI correlated negatively with hemoglobin levels but not with parameters indicating impaired tissue perfusion or metabolic acidosis. Parasite levels had a significant influence on metabolic acidosis but not on CI. Alterations related to cardiac function, hemoglobin levels and metabolic acidosis were most prominent in children younger than 2 years., Conclusion: Increased CI reflecting high output status is associated with low hemoglobin levels while metabolic acidosis is linked to parasite levels.

Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4⁺ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4⁺ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8⁺ and human leukocyte antigen-DR expression on CD3⁺ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.

This study aimed to evaluate the utilization of FAMACHA(©) method as an auxiliary strategy to use the individual identification for the selective control of gastrointestinal helminthiasis in naturally infected dairy goats. The experiment was conducted on 63 farms in the towns of Passagem, Quixabá and Cacimba de Areia, semiarid region of the Paraíba state, Brazil. Fifty animals were used on each farm, being visited tree farms per month, totaling 1800 animals, between May 2009 and April 2010. The animals received no anthelmintic treatment for at least four months prior to the farm visits. All animals were subjected to parasitological faecal collection, blood sampling for packed cell volume and the visual/selective exam of the eye colour through the FAMACHA(©) method. Larvae culture was performed in every assessment on each farm. Haemonchus sp. was the most prevalent helminth (80.1%) on larval cultures. The use of this method allowed a reduction of 79.2% on anthelmintic application in dairy goats. The FAMACHA(©) method proved to be a viable auxiliary strategy to control gastrointestinal helminthiasis of dairy goats from a resource-poor area in the semiarid region of the Paraíba state, Northeastern Brazil., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Sheep and goats are the species of farm animal with the highest growth rate in Paraná State. The main problems facing Paraná State flocks are gastrointestinal parasites and anthelmintic resistance. One of the newest resources used to slow down the development of anthelmintic resistance is the FAMACHA(©) system, a selective method useful for controlling gastrointestinal verminosis in small ruminants. The purpose of the present research was to evaluate the sensitivity and specificity of the FAMACHA(©) system in sheep and goats and to compare the results for both species. The conjunctivae of 83 Suffolk ewes and 60 adult crossbred Boer does were evaluated by the same trained person using the FAMACHA(©) system. The packed cell value (PCV) served as the gold standard for clinical FAMACHA(©) evaluation. To calculate the sensitivity and specificity of the FAMACHA(©) system, different criteria were adopted in turn: animals classified as FAMACHA(©) (F(©)) 4 and 5, or 3, 4 and 5, were considered to be anemic (positive test), and animals classified as F(©)1, 2 and 3, or 1 and 2 were considered to be non-anemic (negative test). Three standard values of PCV, namely ≤19%, ≤18% or ≤15%, were used to confirm anemia. At all cut-off levels, the sensitivity increased if F(©)3 animals were included as being anemic. However, changes in levels of sensitivity were associated with reciprocal changes in specificity. The sensitivity was higher for sheep than for goats, excepting when the criteria included PCV≤18 and F(©)3, F(©)4 and F(©)5 were considered positive. In contrast, the specificity was always lower in sheep for any criteria adopted. Other than in goats, using the ≤15 cut-off level for sheep, it is possible to opt not to drench the animals that were shown to be F(©)3 because the sensitivity is still high, indicating that few animals that should have been drenched were overlooked. In goats, in contrast, the low sensitivity at all cut-off levels made it too risky to leave F(©)3 animals undrenched. Even though the number of correct treatments for goats was always higher than that for sheep, the opposite was true for the kappa index for all the criteria tested. Therefore, the FAMACHA(©) system is suitable for the identification of anemic animals of both species. It is necessary that all small ruminants classified as FAMACHA(©) level 3 are also treated to increase the sensitivity of the method., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To assess the prevalence of malaria helminth co-infections and their contribution for aneamia in febrile patients attending Azzezo health center, Gondar, Northwest Ethiopia., Methods: A cross section study was conducted among febrile patients attending Azezo health center from February-March 30, 2011. Convenient sampling technique was used to select 384 individuals. Both capillary blood and stool were collected. Giemsa stained thick and thin blood film were prepared for identification of Plasmodium species and stool sample was examined by direct wet mount and formalin-ether concentration technique for detection of intestinal helminthes parasites. Haemoglobin concentration was determined using a portable haemoglobin spectrophotometer, Hemocue Hb 201 analyzer., Results: Out of 384 febrile patients examined for malaria parasites, 44 (11.5%) individuals were positive for malaria parasites, of which Plasmodium vivax accounted for 75.0% (33), Plasmodium falciparum for 20.5% (9) infectious, whereas two person (4.5%) had mixed species infection. Prevalence of malaria was higher in males (28) when compared with prevalence in females (16). More than half (207, 53.9%) of study participants had one or more infection. Prevalence was slightly higher in females (109, 52.7%) than in males (98, 47.3%). About helminths, Ascaris lumbricoides was the predominant isolate (62.1%) followed by hookworms (18.4%). Only 22 participants were co-infected with malaria parasite and helminths and co-infection with Ascaris lumbricoides was predominant (45.0%). The prevalence of anemia was 10.9% and co-infection with Plasmodium and helminth parasites was significantly associated with (P< 0.000 1) higher anemia prevalence compared to individuals without any infection., Conclusions: Prevalence of malaria and soil transmitted helminths is high and the disease is still major health problem in the study area. Hence, simultaneous combat against the two parasitic infections is very crucial to improve health of the affected communities in economically developing countries., (Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Older patients referred for further investigation of anaemia are common in a geriatric medicine clinic and it is important to consider a wide range of underlying diagnoses. We present an unusual case of anaemia in an octogenarian in whom a diagnosis of visceral leishmaniasis was made. This is a rare and unusual diagnosis in this cohort of patients, especially within the UK; however, it is important to identify it, given its high mortality if left untreated. Our case, presumably contracted while in Andalucia, Spain, highlights the need for awareness in this group of patients, especially when travel within Europe is becoming commonplace.

Insect-borne diseases exact a high public health burden and have a devastating impact on livestock and agriculture. To date, control has proved to be exceedingly difficult. One such disease that has plagued sub-Saharan Africa is caused by the protozoan African trypanosomes (Trypanosoma species) and transmitted by tsetse flies (Diptera: Glossinidae). This presentation describes Trypanosoma evansi (T. evansi) which causes the disease known as trypanosomosis (Surra) or trypanosomiasis in which several attempts have being made to unravel the clinical pathogenic mechanisms in T. evansi infections, yielding various reports which have implicated hemolysis associated to decrease in life span of erythrocytes and extensive erythrophagocytosis being among those that enjoy prominence. T. evansi generates Adenosine Triphosphate (ATP) from glucose catabolism which is required for the parasite motility and survival. Oxidation of the erythrocytes induces oxidative stress due to free radical generation. Lipid peroxidation of the erythrocytes causes membrane injury, osmotic fragility and destruction of the red blood cell (RBC) making anemia a hallmark of the pathology of T. evansi infections., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI(95%): 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group O was demonstrated with a decreased risk of severe malaria OR=0.743 (CI(95%): 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI(95%): 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In holoendemic Plasmodium falciparum transmission areas, severe malaria primarily occurs in children aged <48 months and manifests as severe malarial anemia [SMA; hemoglobin (Hb) < 6.0 g/dL]. Induction of high levels of prostaglandin-E(2) (PGE(2)) through inducible cyclooxygenase-2 (COX-2) is an important host-defense mechanism against invading pathogens. We have previously shown that COX-2-derived PGE(2) levels are reduced in children residing in hyperendemic transmission regions with cerebral malaria and in those with mixed sequelae of anemia and hyperparasitemia. Our in vitro studies further demonstrated that reduced PGE(2) was due to downregulation of COX-2 gene products following phagocytosis of malarial pigment (hemozoin, PfHz). However, as COX-2-PGE(2) pathways and the impact of naturally acquired PfHz on erythropoietic responses have not been determined in children with SMA, plasma and urinary bicyclo-PGE(2)/creatinine and leukocytic COX-2 transcripts were determined in parasitized children (<36 months) stratified into SMA (n = 36) and non-SMA (Hb ≥ 6.0 g/dL; n = 38). Children with SMA had significantly reduced plasma (P = 0.001) and urinary (P < 0.001) bicyclo-PGE(2)/creatinine and COX-2 transcripts (P = 0.007). There was a significant positive association between Hb and both plasma (r = 0.363, P = 0.002) and urinary (r = 0.500, P = 0.001)] bicyclo-PGE(2)/creatinine. Furthermore, decreased systemic bicyclo-PGE(2)/creatinine was associated with inefficient erythropoiesis (i.e., reticulocyte production index; RPI < 2.0, P = 0.026). Additional analyses demonstrated that plasma (P = 0.031) and urinary (P = 0.070) bicyclo-PGE(2)/creatinine and COX-2 transcripts (P = 0.026) progressively declined with increasing concentrations of naturally acquired PfHz by monocytes. Results presented here support a model in which reduced COX-2-derived PGE(2), driven in part by naturally acquired PfHz by monocytes, promotes decreased erythropoietic responses in children with SMA., (Copyright © 2012 Wiley Periodicals, Inc.)

Copy number variation can contribute to the variation observed in susceptibility to complex diseases. Here we present the first study to investigate copy number variation of the chemokine gene CCL3L1 with susceptibility to malaria. We present a family-based genetic analysis of a Tanzanian population (n=922), using parasite load, mean number of clinical infections of malaria and haemoglobin levels as phenotypes. Copy number of CCL3L1 was measured using the paralogue ratio test (PRT) and the dataset exhibited copy numbers ranging between 1 and 10 copies per diploid genome (pdg). Association between copy number and phenotypes was assessed. Furthermore, we were able to identify copy number haplotypes in some families, using microsatellites within the copy variable region, for transmission disequilibrium testing. We identified a high level of copy number haplotype diversity and find some evidence for an association of low CCL3L1 copy number with protection from anaemia., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The effective application of targeted selective treatment (TST) against gastro-intestinal nematodes depends on the accurate identification of those animals in need of anthelmintic treatment. Finding cost and labour effective measures to identify such animals is paramount. This study tested the efficacy of three indicators on lambs in a farm in Eastern Algeria: anaemia score (FAMACHA(©)), diarrhoea score (DISCO) and weight gain. These were contrasted against traditional parasitological infection measures (nematode eggs per gram of faeces: EPG). Thirty lambs were used in the study; every second month they were sampled (FAMACHA(©), faecal samples for EPG and DISCO, weight gains) and two of the original 30 lambs were necropsied for adult worm counts. The main gastro-intestinal nematodes were Teladorsagia circumcincta, Marshallagia marshalli, Nematodirus helvetianus, Trichostrongylus vitrinus, and Haemonchus contortus. DISCO proved to be the most effective indicator correctly identifying 80% of the sheep in need of treatment. This was followed by FAMACHA(©) with a 50% accuracy level and finally weight gains, which were not found to be a useful indicator at all., (Copyright © 2012. Published by Elsevier B.V.)

Strongyloides stercoralis can affect humans in the form of asymptomatic infections, Strongyloidal hyperinfection syndrome and disseminated Strongyloidiasis depending on the immune response of the host. We report a case of strongyloidial hyperinfection syndrome that subsequently tested positive for HTLV infection.

The present study aimed to assess antioxidant status and oxidative stress in sheep naturally infected with Babesia ovis. Red blood cell (RBC) count, hemoglobin (Hb) concentration, packed cell volume (PCV), piroplasm parasitemia percentage, malondialdehyde (MDA) concentration, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities and total antioxidant capacity (TAC) were determined in 52 sheep naturally infected with B. ovis as well as same number of healthy sheep in West-Azerbaijan province, Iran. Microscopic examination of Giemsa-stained peripheral blood smears revealed B. ovis infection. The parasitological diagnosis was confirmed using polymerase chain reaction (PCR) analysis by amplifying a partial small subunit ribosomal RNA (ssu rRNA) gene sequence of B. ovis of 52 diseased sheep, 18 (34.61%), 11 (21.15%), 16 (30.76%) and 7 (13.48%) had <1%, 1-2%, 2-3% and >3% parasitemia, respectively. Compared to controls, the activities of erythrocyte GSH-Px, SOD, TAC and CAT showed a significant decrease, whereas the concentration of MDA in erythrocytes of infected sheep increased significantly. Parasitemia rate was positively correlated with MDA and negatively correlated with PCV, SOD, CAT, GSH-Px and TAC. Also, MDA was negatively correlated with PCV, SOD, catalase, GSH-Px and TAC. The study demonstrated that B. ovis plays an important role in the occurrence of oxidative damage to RBCs and anemia in ovine babesiosis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Plasmodium yoelii 17XL was used to investigate the mechanism of Plasmodium falciparum-caused cerebral malaria, although its histological effect on other mouse organs is still unclear. Here, histological examination was performed on mice infected with P. yoelii 17XL; the effect of P. yoelii 17XL infection on anemia and body weight loss, as well as its lesions in the brain, liver, kidney, lung, and spleen, also was investigated. Plasmodium yoelii 17XL-infected red blood cells were sequestered in the microcirculation of the brain and in the kidney. Compared with the nonlethal P. yoelii 17XNL strain, infection by P. yoelii 17XL caused substantial pulmonary edema, severe anemia, and significant body weight loss. Although P. yoelii 17XNL and 17XL produced a similar focal necrosis in the mouse liver, infection of P. yoelii 17XL induced coalescing of red and white pulp. Mortality caused by P. yoelii 17XL may be due to cerebral malaria, as well as respiratory distress syndrome and severe anemia. Plasmodium yoelii 17XL-infected rodent malaria seems to be a useful model for investigating severe malaria caused by P. falciparum.

Background: Strongyloidiasis, endemic in tropical areas, may be asymptomatic in immunocompetent subjects or may cause potentially fatal hyper-infection in immunocompromised patients., Methods: Of the 13,885 patients referred to the parasitology laboratory at our tertiary care referral center for stool microscopy, 15 were diagnosed as strongyloidiasis over a 6 year period. We assessed these patients retrospectively., Results: Most patients were young (median age 32 years, range 3-66) males (12, 80%). Seven patients (46.6%) were immunocompromised. All patients were symptomatic, and symptoms included chronic diarrhea (4, 26.7%), acute diarrhea (1,6.7%), abdominal pain (6, 40%), weight loss (3, 20%), cough (2, 13.33%), vomiting (1, 6.7%), anemia (10, 66.7%) and eosinophilia (3, 20%). Thirteen patients (86.6%) were diagnosed on first stool microscopy. Duodenal biopsy showed normal histology in twelve (80%) and partial villous atrophy in one (6.7%) patient. Stool microscopy also revealed giardiasis and cryptosporidiosis in one patient each. Nine patients responded well to ivermectin and albendazole, one died and five were lost to follow-up., Conclusions: In endemic areas, even immunocompetent subjects may suffer from symptomatic strongyloidiasis and associated eosinophilia is uncommon.

Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden., (© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Severe anaemia is a life-threatening complication of falciparum malaria associated with loss of predominantly non-parasitized red blood cells (npRBCs). This poorly elucidated process might be influenced by (i) rosettes, i.e. npRBCs cytoadherent to haemozoin-containing parasitized RBCs (pRBCs) and (ii) generation in pRBCs of 4-hydroxynonenal (4-HNE) through haemozoin-catalysed lipid peroxidation. We explored whether close proximity in rosettes may facilitate 4-HNE transfer to npRBCs, which is likely to enhance their phagocytosis and contribute to malaria anaemia. Fluorescence microscopy and flow cytometry data indicated 4-HNE transfer to npRBCs in rosettes. Rosettes were formed by 64·8 ± 1·8% varO-expressing pRBCs, and 8·7 ± 1·1% npRBCs were positive for 4-HNE-protein-conjugates, while low-rosetting parasites generated only 2·4 ± 1·1% 4-HNE-conjugate-positive npRBCs. 4-HNE transfer decreased after blocking rosetting by monoclonal antibodies. A positive linear relationship between rosette frequency and 4-HNE-conjugates in npRBCs was found in 40 malaria patients, a first indication for a role of rosetting in npRBCs modifications in vivo. Children with severe malaria anaemia had significantly higher percentages of 4-HNE-conjugate-positive npRBCs compared to children with uncomplicated malaria. In conclusion, 4-HNE transfer from pRBCs to npRBCs in rosettes is suggested to play a role in the phagocytic removal of large numbers of npRBCs, the hallmark of severe malaria anaemia., (© 2012 Blackwell Publishing Ltd.)

Background: A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery., Methods: Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality., Results: Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection., Conclusion: Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy.

Background: Recent studies implicate deficiency of red blood cell (RBC) complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial anaemia. This study explored the involvement of B cell CD21, which has an analogous role to RBC CR1., Methods: In a case control study conducted in Kisumu District hospital, western Kenya, children with severe malaria anaemia (SMA) and those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA for soluble CD21 (sCD21). Paired t tests were used to determine statistical significance at a = 0.05., Results: Children with SMA had significantly higher lymphocyte count (9,627.7 ± 8786.1 SD vs. 5,507 ± 2436 SD, P = 0.04 in the UM group) and the computed geometric mean of mature B-cell numbers based on the absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to 2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P = 0.003). SMA group also had a higher percentage of CD20+ B cells (26.8 ± 9.7SD vs 20.9 ± 9.01 SD in the UM) (P = 0.03), indicating considerable polyclonal B-cell activation. The CD21 median flourescence intensity was lower in the SMA (246.4 ± 87.4 SD vs 369 ± 137.7 SD) (P <0.0001), probably due to complement mediated shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher levels of the complement split product C3dg (18.35 ± 10 SD vs 11.5 ± 6.8 S.D), (P = 0.0002), confirming possible role of complement in CD21 removal. Unexpectedly, the SMAs had lower levels of sCD21 (226.5 ± 131.5 SD vs 341.4 ± 137.3 SD in the UM) (P < 0.0001), indicating that the shaved CD21 is not released to peripheral circulation., Conclusions: These results implicate B-cell in pathophysiology of severe malaria that involves increased B-cell proliferation, increased complement deposition and subsequent loss of membrane-bound CD21. The loss of CD21 is not by the classical enzmatic cleavage.

WHO estimates that 80% of mortality due to malaria occurs among infants and young children. Though it has long been established that malaria disproportionately affects children under age five, our understanding of the underlying biological mechanisms for this distribution remains incomplete. Many studies use age as an indicator of exposure, but age may affect malaria burden independently of previous exposure. Not only does the severity of malaria infection change with age, but the clinical manifestation of disease does as well: younger children are more likely to suffer severe anaemia, while older children are more likely to develop cerebral malaria. Intensity of transmission and acquired immunity are important determinants of this age variation, but age differences remain consistent over varying transmission levels. Thus, age differences in clinical presentation may involve inherent age-related factors as well as still-undiscovered facets of acquired immunity, perhaps including the rates at which relevant aspects of immunity are acquired. The concept of "allometry" - the relative growth of a part in relation to that of an entire organism or to a standard - has not previously been applied in the context of malaria infection. However, because malaria affects a number of organs and cells, including the liver, red blood cells, white blood cells, and spleen, which may intrinsically develop at rates partly independent of each other and of a child's overall size, developmental allometry may influence the course and consequences of malaria infection. Here, scattered items of evidence have been collected from a variety of disciplines, aiming to suggest possible research paths for investigating exposure-independent age differences affecting clinical outcomes of malaria infection., (© 2012 Billig et al; licensee BioMed Central Ltd.)

Animal African trypanosomiasis is a major constraint to livestock productivity and has an important impact on millions of people in developing African countries. This parasitic disease, caused mainly by Trypanosoma congolense, results in severe anaemia leading to animal death. In order to characterize potential targets for an anti-disease vaccine, we investigated a multigenic trans-sialidase family (TcoTS) in T. congolense. Sialidase and trans-sialidase activities were quantified for the first time, as well as the tightly regulated TcoTS expression pattern throughout the life cycle. Active enzymes were expressed in bloodstream form parasites and released into the blood during infection. Using genetic tools, we demonstrated a significant correlation between TcoTS silencing and impairment of virulence during experimental infection with T. congolense. Reduced TcoTS expression affected infectivity, parasitaemia and pathogenesis development. Immunization-challenge experiments using recombinant TcoTS highlighted their potential protective use in an anti-disease vaccine., (© 2011 Blackwell Publishing Ltd.)

The spleen is a complex organ that is perfectly adapted to selectively filtering and destroying senescent red blood cells (RBCs), infectious microorganisms and Plasmodium-parasitized RBCs. Infection by malaria is the most common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection. Here, the role of the spleen in malaria is reviewed with special emphasis in lessons learned from human infections and mouse models., (© 2011 Blackwell Publishing Ltd.)

We studied anemia and bleeding risk among hematologic-oncologic pediatric patients with dengue infection. A total of 907 patients suspected of having dengue infection were included in the study. They were categorized into 2 groups: 1) patients with confirmed dengue infection (n=843) and 2) patients with other febrile illnesses (n = 64). Both groups included patients with underlying hematologic-oncologic diseases (55 vs 14) and without underlying disease (788 vs 50). Patients with underlying diseases were divided into 3 subgroups by risk: Subgroup A, anemia risk, including patients with thalassemia and hemoglobinopathies (n = 39) and G6PD deficiency (n=6); Subgroup B, patients with bleeding risk, including hemophilia (n = 7), von Willebrand disease (n = 1) and thrombocytopenia (n = 4); and Subgroup C, patients with anemia and bleeding risk, including oncologic diseases (n =12). Acute hemolysis in Subgroup A started during the febrile stage and required packed red cell transfusions. Bleeding risk in Subgroup B started during the early febrile stage with vasculopathy and continued to the late febrile stage with thrombocytopenia. These patients required factor concentrate and platelet concentrate transfusions. Anemia and bleeding risk in Subgroup C was greater among patients undergoing chemotherapy than those who had discontinued treatment. The greater the length of time since discontinuation of treatment, the lower risk. The case-fatality rate among dengue infected patients with underlying disease (2/55 = 3.64%) was significantly higher than those without underlying disease 0.63% (5/788).

In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum-positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts.

Background: Malaria control campaigns have reduced malaria transmission to very low levels in many areas of Africa. Yet the extent to which malaria interruption or elimination might decrease the prevalence of anemia in areas of low malaria transmission is unknown., Methods: Kapsisiywa and Kipsamoite, highland areas of Kenya with low, unstable malaria transmission, experienced a 12-month interruption in malaria transmission from April 2007 to May 2008, following high-level coverage (>70% of households) with indoor residual insecticide spraying in 2007. Hemoglobin levels were tested in 1697 randomly selected asymptomatic residents of Kapsisiywa (n = 910) and Kipsamoite (n = 787) at the beginning of a 12-month period of interrupted transmission (in May 2007) and 14 months later (in July 2008)., Results: From May 2007 to July 2008, only 1 of 1697 study cohort members developed clinical malaria. In this period, the prevalence of anemia decreased in Kapsisiywa in all age groups (from 57.5% to 37.9% in children aged <5 years [P < .001], from 21.7% to 10.5% in children aged 5-14 years [P < .001], and from 22.7% to 16.6% in individuals aged ≥ 15 years [P = .004]). The prevalence of anemia in Kipsamoite also decreased in children aged <5 years (from 47.2% to 31.3%; P = .001) but was unchanged in children aged 5-14 years and in individuals aged ≥15 years. Among children <5 years, anemia prevalence was reduced by 34% in both Kapsisiywa (95% confidence interval [CI], 21%-45%) and Kipsamoite (95% CI, 16%-48%)., Conclusions: Successful malaria elimination or interruption may lead to substantial reductions in anemia prevalence even in areas of very low transmission.

Objective: To determine the range and incidence of complications associated with Plasmodium vivax (P. vivax) malaria., Methods: A retrospective analysis was performed of all patients of P. vivax malaria admitted in Kasturba Medical College, Manipal between January and December, 2010. Patients with mixed malarial infection were excluded by appropriate tests. Clinical presentation and laboratory parameters were studied., Results: Medical records of 213 individuals who satisfied the inclusion criteria were reviewed. Anaemia was seen in 65 (30.5%), leucopenia in 38 (17.8%) and thrombocytopenia in 184 (86.4%) patients. Aspartate and alanine aminotransferases were elevated in 86 (40.4%), and 89 (41.9%) patients respectively. Hypoalbuminemia was observed in 157 (73.6%) cases. Elevated serum creatinine was noted in in 59 (27.5%) patients. Creatine kinase was elevated in 30 out of 59 patients (50.8%). Overall, 107 (50.2%) patients fulfilled WHO criteria for severe malaria. None of the patients succumbed to the disease., Conclusions: P. vivax malaria is a potentially severe disease, and the term "benign" tertian malaria is a misnomer. Despite significant morbidity, with timely and appropriate treatment P. vivax malaria has an excellent outcome., (Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Background: Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis., Methods: A cross sectional study was conducted in the north-east coast of Tanzania to investigate whether the changes in glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins (CD55 and CD59) contributes to malaria anaemia. Blood samples were collected from a cohort of children under intensive surveillance for Plasmodium falciparum parasitaemia and illness. Levels of CD55 and CD59 were measured by flow cytometer and compared between anaemic (8.08 g/dl) and non- anaemic children (11.42 g/dl)., Results: Levels of CD55 and CD59 decreased with increased RBC age. CD55 levels were lower in anaemic children and the difference was seen in RBC of all ages. Levels of CD59 were lower in anaemic children, but these differences were not significant. CD55, but not CD59, levels correlated positively with the level of haemoglobin in anaemic children., Conclusion: The extent of CD55 loss from RBC of all ages early in the course of malarial anaemia and the correlation of CD55 with haemoglobin levels support the hypothesis that CD55 may play a causal role in this disorder.

Background: Malaria in pregnant women has been shown to be associated with low birth weight, stillbirth and mortality in newborns. The WHO has adopted the use of sulphadoxine-pyrimethamine (SP) to control malaria, a disease which worsens the plight of pregnant women leading to low birth weight, stillbirths and increased neonatal mortality. The present study assessed the effectiveness of SP and perception of its use in pregnant women in Offinso district (Ashanti Region), Ghana., Method: Pregnant women, gestational age 32 weeks prior to term, were studied from November 2006 to October 2007. Their haemoglobin levels (Hb), parasitaemia and other quantitative determinants were assessed. In-depth interviews (IDIs) and focus group discussions (FGDs) were used to assess the perception of SP usage and its effectiveness., Results: Of the 306 study participants, 92 (30%) took one dose, 100 (33%) two doses and 114 (37%) three doses of SP, respectively. There was significant association between gravidity and SP dosage taken (Pearson χ2 = 18.9, p < 0.001). Although adverse effects were produced in 113 (i.e. 37%) of the pregnant women, no significant difference was observed with regard to the dosage of SP taken (Pearson's χ2 = 2.3, p ≥ 0.32). Peripheral parasitaemia was present in 47 (15%) of the subjects. There was a poor negative relationship of doses of SP with parasitaemia (r = -0.07, p ≥ 0.24). Mean Hb was 11.3 ± 1.6 g/dl, with 118 (39%) of the subjects anaemic (Hb < 11.0 g/dl), whilst 187 (61%) were normal (Hb ≥11.0 g/dl). Significant positive correlation of SP use with Hb level (r = 0.15, p < 0.008) was observed. SP use reduced malaria and anaemia prevalence, contributed to reduced maternal morbidity with mild side effects being reported., Conclusions: This study points to the effectiveness of IPTp using SP as an evidence-based measure for control of malaria and malaria-related anaemia in pregnancy. Therefore, the Ghana Health Service should improve current programme strategies to increase the proportion of pregnant women who take three doses of SP, paying attention to improved face-to-face health education, focussed antenatal care and better social mobilization.