Malaria-infected Group Research Articles

Expression of 4-Hydroxynonenal (4-HNE) and Heme Oxygenase-1 (HO-1) in the Kidneys of Plasmodium berghei-Infected Mice.

Acute kidney injury (AKI) is one of the most serious complications of severe Plasmodium falciparum malaria, but the exact pathogenic mechanisms of AKI in P. falciparum infection have not been clearly elucidated. We hypothesized that oxidative stress is a potential mediator of acute tubular necrosis in P. falciparum-infected kidneys. Therefore, this study aimed to investigate the histopathological changes and markers of oxidative stress in kidney tissues from mice with experimental malaria. DBA/2 mice were divided into two groups: the mice in the malaria-infected group (n = 10) were intraperitoneally injected with 1 × 106P. berghei ANKA-infected red blood cells, and the mice in the control group (n = 10) were intraperitoneally injected with a single dose of 0.85% normal saline. Kidney sections were collected and used for histopathological examination and the investigation of 4-hydroxynonenal (4-HNE) and heme oxygenase-1 (HO-1) expression through immunohistochemistry staining. The histopathology study revealed that the P. berghei-infected kidneys exhibited a greater area of tubular necrosis than those of the control group (p < 0.05). The positive staining scores for 4-HNE and HO-1 expression in tubular epithelial cells of the P. berghei-infected group were significantly higher than those found for the control group (p < 0.05). In addition, significant positive correlations were found between the tubular necrosis score and the positive staining scores for 4-HNE and HO-1 in the kidneys from the P. berghei-infected group. In conclusion, this finding demonstrates that increased expression of 4-HNE and HO-1 might be involved in the pathogenesis of acute tubular damage in the kidneys during malaria infection. Our results provide new insights into the pathogenesis of malaria-associated AKI and might provide guidelines for the future development of a therapeutic intervention for malaria.

The Effects of Plasmodium Falciparum Parasitaemia on Liver Synthetic Fidelity and Oxidative Stress Markers

Malaria has for century’s defiled eradication due to pathophysiological and environmental complexities. The study was aimed at revealing the effect of malaria parasitaemia on hepatic synthetic fidelity and oxidative stress markers individually and synergistically. A total of five hundred subjects constituted the sample size, out of which two hundred comprised the control and three hundred the test group with grades of parasitaemia. Serum aspartate aminotransferases (AST), alanine aminotransferase (ALT), iron, malonaldehyde and glutathione were analysed using WHO approved methods. The results obtained indicated a significant increase (p&lt;0.05) in AST, ALT, malonaldehyde, and glutathione levels in malaria infected subjects when compared to the control group respectively. The result further showed a significant decrease (p&lt;0.01) in serum iron concentration in malaria infected groups when compared to the control. In conclusion, malaria infection has a significant impact on the hepatic synthetic capacity and oxidative indicators. It is suggested that these observed biochemical change should be considered when malaria infected individuals are treated and managed.

Impact of malaria on haematological parameters of urban, peri-urban and rural residents in the Ashanti region of Ghana: a cross-sectional study.

Background: We aimed at investigating the impact of malaria on the haematological parameters of residents from different demographic settlements in the Ashanti Region of Ghana. Malaria parasites trigger changes in certain haematological parameters, which may result in a number of clinical manifestations. Differences in demographic settlements, such as rural, peri-urban and urban settlements may also influence these changes, but this has not been extensively studied in Ghana. Methods: We conducted a hospital-based, cross-sectional study from January to December 2018 in three different settlements. A total of 598 participants were recruited. Blood smears were examined to detect and quantify malaria parasitaemia, while haematological parameters were measured using a haematology analyser. Results: Participants from the rural settlement had the highest malaria prevalence (21.3%) compared to urban (11.8%) and peri-urban areas (13.3%); however, the peri-urban area had the highest median parasite density (568; IQR=190.0-1312.0). Age was significantly associated with the odds of malaria positivity (OR: 0.97; CI:0.96 - 0.99; p=4.96*10 -4). When haematological parameters of the malaria-infected study participants were compared to the parameters of uninfected participants, red blood cell count (p=0.017), haemoglobin (p=0.0165), haematocrit (p=0.0015), mean corpuscular volume (p=0.0014), plateletcrit (p<0.0001) and platelet count (p<0.0001) were all significantly lower in the malaria infected group. In addition to age, haemoglobin and plateletcrit levels were also inversely correlated with the odds of testing positive for malaria, suggesting that children who were anaemic and/or thrombocytopaenic were likely to be infected. After fitting the data to a logistic regression model comprising the three variables, the model correctly categorised 78% of uninfected study participants, but only 50% of the malaria-positive participants. Conclusions: Study participants who were positive for malaria were younger and had low haemoglobin and plateletcrit levels compared to uninfected individuals. Further studies are needed to more precisely elucidate the relationship between malaria infection,demographic and haematological parameters.

Malaria Parasitaemia and Variations in Haematological Parameters among Pregnant Women in Buea

Background: Malaria is a life threatening parasitic disease that is entirely preventable and curable. Pregnant women are among the most vulnerable groups to this deadly disease. Prompt diagnosis and treatment is needed to reduce morbidity and mortality. Haematological changes that occur during malaria infection have been suggested as a potential predictor that can aid in the diagnosis of malaria infection.&#x0D; Methods: A cross sectional study involving 276 pregnant women with signs and symptoms of malaria was conducted at Regional Hospital Buea (RHB) from April to July 2018. Baselines characteristics of the study population were collected. Blood (4 ml) was collected from each pregnant woman and dispensed into an EDTA tube. Identification of malaria parasite was done using a rapid diagnostic test (Care StartTM). Complete blood count was performed using an automated haematology analyzer (Mindray®, BC-5300).&#x0D; Results: Out of the 276 pregnant women, 98 (35.51%) had malaria. A total of eighty eight (31.88%) of the pregnant women were anaemic, with forty eight (17.4%) being malaria infected and forty (14.5%) non-malaria. The mean (± SD) of total white blood cell count in the malaria infected group was 5.9 (±2.4) and was significantly different (p = 0.039) from that of non-malaria infected (6.7[±1.9]) population. Red blood cells significantly (p = 0.001) decreased in malaria infected patients (3.7 [± 0.6]) as compared to non-malaria infections (4.2 (±1.0). The mean (± SD) of platelets counts in malaria infected group was significantly different from that of non-malaria infected pregnant women.&#x0D; Conclusion: Pregnant women infected with malaria exhibited changes in haematological parameters with low platelets (thrombocytopenia) and Haemoglobin concentration being the most significant predictors of malaria in our study area. These parameters could improve malaria diagnosis when used in combination with other clinical diagnosis.

Impact of malaria on haematological parameters of urban, peri-urban and rural residents in the Ashanti region of Ghana: a cross-sectional study

Background: We aimed at investigating the impact of malaria on the haematological parameters of residents from different demographic settlements in the Ashanti Region of Ghana. Malaria parasites trigger changes in certain haematological parameters, which may result in a number of clinical manifestations. Differences in demographic settlements, such as rural, peri-urban and urban settlements may also influence these changes, but this has not been extensively studied in Ghana. Methods: We conducted a hospital-based, cross-sectional study from January to December 2018 in three different settlements. A total of 598 participants were recruited. Blood smears were examined to detect and quantify malaria parasitaemia, while haematological parameters were measured using a haematology analyser. Results: Participants from the rural settlement had the highest malaria prevalence (21.3%) compared to urban (11.8%) and peri-urban areas (13.3%); however, the peri-urban area had the highest median parasite density (568; IQR=190.0-1312.0). Age was significantly associated with the odds of malaria positivity (OR: 0.97; CI:0.96 — 0.99; p=4.96*10 -4). When haematological parameters of the malaria-infected study participants were compared to the parameters of uninfected participants, red blood cell count (p=0.017), haemoglobin (p=0.0165), haematocrit (p=0.0015), mean corpuscular volume (p=0.0014), plateletcrit (p<0.0001) and platelet count (p<0.0001) were all significantly lower in the malaria infected group. In addition to age, haemoglobin and plateletcrit levels were also inversely correlated with the odds of testing positive for malaria, suggesting that children who were anaemic and/or thrombocytopaenic were likely to be infected. After fitting the data to a logistic regression model comprising the three variables, the model correctly categorised 78% of uninfected study participants, but only 50% of the malaria-positive participants. Conclusions: Study participants who were positive for malaria were younger and had low haemoglobin and plateletcrit levels compared to uninfected individuals. Further studies are needed to more precisely elucidate the relationship between malaria infection,demographic and haematological parameters.

Impact of malaria on haematological parameters of urban, peri-urban and rural residents in the Ashanti region of Ghana: a cross-sectional study.

Background: We aimed at investigating the impact of malaria on the haematological parameters of residents from different demographic settlements in the Ashanti Region of Ghana. Malaria parasites trigger changes in certain haematological parameters, which may result in a number of clinical manifestations. Differences in demographic settlements, such as rural, peri-urban and urban settlements may also influence these changes, but this has not been extensively studied in Ghana. Methods: We conducted a hospital-based, cross-sectional study from January to December 2018 in three different settlements. A total of 598 participants were recruited. Blood smears were examined to detect and quantify malaria parasitaemia, while haematological parameters were measured using a haematology analyser. Results: Participants from the rural settlement had the highest malaria prevalence (21.3%) compared to the urban (11.8%) and peri-urban areas (13.3%); however, the peri-urban area had the highest median parasite density (568; IQR=190.0-1312.0). Age was significantly associated with the odds of malaria positivity (OR: 0.97; CI:0.96 - 0.99). When haematological parameters of the malaria-infected study participants were compared to the parameters of uninfected participants, red blood cell count (p=0.017), haemoglobin (p=0.0165), haematocrit (p=0.0015), mean corpuscular volume (p=0.0014), plateletcrit (p<0.0001) and platelet count (p<0.0001) were all significantly lower in the malaria infected group. In addition to age, haemoglobin and plateletcrit levels were also inversely correlated with the odds of testing positive for malaria, suggesting that children who were anaemic and/or thrombocytopaenic were likely to be infected. After fitting the data to a logistic regression model comprising the three variables, the model correctly categorised 78% of uninfected study participants, but only 50% of the malaria-positive participants. Conclusions: Study participants who were positive for malaria were younger and had low haemoglobin and plateletcrit levels compared to uninfected individuals. Further studies are needed to more precisely elucidate the relationship between malaria infection,demographic and haematological parameters.

PO 8571 CYTOKINE PROFILE IN ASYMPTOMATIC SCHOOL CHILDREN CO-INFECTED WITH HELMINTHS ANDPLASMODIUM FALCIPARUMIN IBADAN, SOUTH-WEST NIGERIA

BackgroundIntestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of co-infections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms.MethodsA total of 78 afebrile school children (20 helminth/malaria-co-infected, 17 helminth-infected, 19 malaria-infected and 22 uninfected) and 75 febrile children (14 helminth/malaria-co-infected, 16 helminth-infected, 20 malaria-infected and 25 uninfected) were recruited into the study. Helminths were screened using Kato Katz method while malaria parasite screening was done using Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance.ResultsAmong the afebrile school children, IL-10 was significantly increased in helminth-infected children compared with helminth/malaria-co-infected, malaria-infected and uninfected groups (p&lt;0.05). IFN-γ was significantly elevated in malaria and malaria/helminth-co-infection relative to helminth alone (p&lt;0.05). IL-1 level was significantly higher in single infection of helminth and malaria relative to co-infection and the uninfected groups (p&lt;0.05). An insignificant difference was observed for IL-6 and TNF-α concentrations across all the four groups while among febrile children. IL-6 was significantly increased among helminth alone and helminth/malaria-co-infection relative to malaria-infected group (p&lt;0.05). IL-10 was significantly elevated in co-infected group compared with helminth- or malaria-infected group while TNF-α was significantly increased in helminth and helminth-malaria co-infection compared with uninfected or malaria-infected group (p&lt;0.05). IFN-γ level was insignificant in the infection groups relative to uninfected group (p&lt;0.05); IL-1 level similar across the groups.ConclusionHelminth infection seems to upregulate the Th2 immune response among children with symptomatic uncomplicated malaria while there were no significant changes in Th immune response among afebrile children.

Induction of Angiogenesis by Malarial Infection through Hypoxia Dependent Manner.

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×106 parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia-induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.

Alterations in T-helper cell type 1 and blood cell parameters in malaria-infected patients

Malaria is a global public health disease. Haematological and cytokine alterations are the major sources of its pathological conditions. Therefore, blood and serum of patients attending health centres were screened to investigate the effects of Plasmodium falciparum on the T-helper cell type 1 and blood cell parameters using Enzyme linked immunosorbent assay and automatic hematology analyzer respectively. Approximately 55% of malaria-infected patients with average parasitaemia of 2523.64parasite/μl of blood concurrently suffered anaemia, thrombocytopenia, leucopenia, microcytosis and hypochromasia. However, thrombocytopenia and leucopenia were age-specific and their prevalences in children within ≤10years were higher. These disease conditions significantly vary with severity of malaria infection (p<0.05). Blood parameters with the exception of RBC and MCHC were significantly lower in the infected patients (p<0.05) with 12.9% and 41.2% reduction in haemoglobin and platelet counts respectively. A high plasma concentration of IL-10, IL-12, INF-γ and TNF-α, ratio of IL-10/TNF-α (1.86) and IL-10/INF-γ (1.55) were recorded among the malaria-infected groups. This study revealed that unregulated interaction of the parasite with host immune response has important consequences in disease progression and thus relevant for therapeutic and vaccine development.

Extensive genetic diversity of CD14 promoter gene (rs2569190) polymorphism is associated with regulation of Plasmodium falciparum parasitemia but not susceptibility to infection

Abstract CD14 is a multifunctional receptor expressed on many cell types, and has been shown to mediate immune response resulting in the activation of an inflammatory cascade. Genetic polymorphisms of the CD14 promoter (rs2569190) has been found to be associated with susceptibility to several diseases. In malaria infection, CD14 gene demonstrates a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of malaria patients, with no definitive conclusions. We present a detailed analysis of genetic diversity of CD14 promoter gene polymorphism between a malaria-infected group and uninfected controls, and its association with clinical parameters of disease. Genomic DNA samples obtained from 107 Plasmodium falciparum-infected (microscopy and PCR-confirmed) patients and 380 uninfected controls were subjected to a PCR-RFLP analysis. Our results show a significant diversity (p=3.32E-06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between infected and uninfected controls respectively, with the mutant allele less frequent in infected group. Mean parasitemia (parasites/μl of blood) was significantly regulated based on CD14 genetic profile (19,855 vs 37,041 vs 49,396 for mutants, heterozygotes and wild type alleles respectively), but showed no association with other markers of disease severity (fever, age of patients or anemia). Our results show the mutant variant pushed Th1 cell differentiation resulting in interferon-γ response leading to reduced parasitemia. How this affects disease severity between sub-regional or continental malaria groups deserves elucidation, including extending this results among cerebral malaria patients.

Genetic Diversity of CD14 Promoter Gene Polymorphism (rs2569190) is Associated With Regulation of Malaria Parasitemia and Susceptibility to Plasmodium falciparum Infection.

CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp −159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease. Genomic DNA samples obtained from 106 Plasmodium falciparum malaria–infected patients and 277 uninfected controls were elucidated with a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Our results show a significant diversity (P = 3.32E−06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between the malaria-infected group and controls, respectively. The mutant allele had the lowest frequency among the malaria-infected group demonstrating its necessity for infection. Mean parasitemia (parasites/μL of blood) was significantly regulated based on CD14 polymorphic profile (19 855 versus 37 041 versus 49 396 for homozygote mutants, heterozygotes, and homozygote wild type, respectively). Interestingly, we found no association between CD14 genetic variants with fever, age of patients, or anemia. How this affects disease severity between subregional and continental groups deserves further clarification, including extending these studies in a larger group and among severe and asymptomatic patients with malaria.

Altered renal immune complexes deposition in female BWF1 lupus mice following Plasmodium chabaudi infection.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that has a mysterious relationship with malaria infection. The current study was designated to compare between the effect of the live and the gamma irradiated Plasmodium chabaudi infection on BWF1 lupus murine model. A total of 30 female BWF1 mice were randomly divided into three groups (10 mice/group) as follows: group (I) lupus group (lupus non infected); group (II) live malaria infected group (lupus + live malaria infection); and group (III) irradiated malaria-infected group (lupus + gamma irradiated malaria infection). Live P. chabaudi infection was accompanied with a decrease in survival rate and food consumption in comparison to the control group of mice while gamma irradiated P. chabaudi -infection was unable to do this effect. Additionally, live P. chabaudi infection was accompanied with an increased level of proteinuria and increased rate of immune complexes deposition in kidney. Moreover, infection with live, but not gamma-irradiated P. chabaudi was accompanied with an increase in nitric oxide (NO), hydrogen peroxide (H2O2), and malondialdehyde (MDA) levels in plasma of lupus mice. The levels of both total cholesterol and triglycerides in plasma of lupus mice after live P. chabaudi infection were obviously decreased in comparison to the control group. On the other hand, gamma-irradiated P. chabaudi infection resembled the control group. Our data revealed that infection of lupus mice with live but not gamma-irradiated P. chabaudi has several histological and biochemical effects.

Correlation between Thrombocytopenia and Anaemia in Plasmodium falciparum malaria among patients in Kisumu County-Western Kenya

Background: Malaria is associated with haematological complications which may be avoided by early diagnosis and treatment. Microscopic diagnosis showing presence of malarial parasites is needed for confirmation which requires technical expertise. The study was therefore carried out determine the correlation between thrombocytopenia and anaemia in P.falciparum malaria. Methods: The study was conducted in Kisumu County-Kenya which is a highly endemic malaria region. Both thick and thin blood smears were used to determine P. falciparum infection status in a total of 228 patients presenting with acute febrile illness. All participants’ demographics and Haematological parameters i.e. Haemoglobin level, platelet count, Mean platelet volume and platelet distribution width were analysed. Results: Haemoglobin and platelet count were significantly lower in the malaria infected group (p<0.001 in both cases). Conversely, mean platelet volume and platelet distribution width were higher in comparison to non-infected group (p<0.001). Severe to moderate anaemia was present in 78 %( n=122) of malaria infected patients against 47 %( n=33) of the non-infected group. Thrombocytopenia was present in 87 %( n=137) of the infected patients against 10 % (n=7) of the non-infected group. There was a positive correlation between anaemia and thrombocytopenia in malaria(r= 0.26, p<0.001). Conclusion: Low platelet count and Haemoglobin levels positively correlate and are important predictors of P .falciparum malaria. This could to avoid performing unnecessary expensive tests to rule out other febrile conditions. The above findings also have therapeutic implications of avoiding unnecessary platelet infusion in malaria. Keywords: thrombocytopenia, pseudo-thrombocytopenia, anaemia and haemoglobin. Afr J Health Sci . 2016; 29(2):76-88

Evaluation of In-vivo Antimalarial Activity of Methanol Leaf Extract of Glyphaea brevis in Plasmodium berghei-Infected Mice

Purpose: To evaluate the in-vivo antimalarial activity of the methanol extract of the leaves of Glyphaea brevis in Plasmodium berghei infected mice.Methods: The phytochemical profile of ethylacetate, n-butanol, and residual aqueous fractions of the methanol extract of G. brevis were determined using standard procedures. Mice, weighing between 15 - 30 g, were used for this study. Plasmodium berghei infected blood (0.2 ml) was used to infect each of 55 mice (5 in 11 groups) intraperitoneally. Animals in the infected groups were treated orally with varying doses (200, 300 and 400 mg/kg body weight) of the ethylacetate, n-butanol and residual aqueous fractions daily, using artemisinin (5 mg/kg body weight per day) as standard drug, over a period of four days. The non-infected (normal control, n = 5) received distilled water (0.2 ml) while the infected control group (n = 5) was administered 0.2 ml normal saline. The suppressive antiplasmodial properties of the fractions as well as the serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined.Results: Alkaloids, carbohydrates, cardiac glycosides, flavonoids, saponins, tannins, steroids and triterpenes were present in the extract fractions. The suppressive antiplasmodial activity of n-butanol, residual aqueous portion and ethylacetate fractions was 76.64, 73.25 and 72.99 %, respectively, while that of artemisinin was 86.13 %. The serum concentrations of AST, ALT, and ALP in the infected control group were significantly higher (p &lt; 0.05) than those of the treated malaria-infected groups treated with the three fractions.Conclusion: Glyphaea brevis possesses significant antiplasmodial properties and could be a source of lead molecules for the development of new antimalarial agents.Keywords: Antimalarial, Glyphaea brevis, Plasmodium berghei, Artemisinin

Nutritional status and malaria infection in primary school-aged children

Background The most common nutritional problem affecting the pediatric population in developing countries is protein energy malnutrition (PEM). The nutritional problem may be caused by a variety of factors, most of which are related inadequate food intake and infection. One of the highest causes of morbidity and mortality in endemic areas is malaria. Malaria infection and nutritional status have been suggested to be interrelated.Objective To assess for a relationship between nutritional status and malaria infection in children.Methods This cross-sectional study was conducted in October and November 2010 in primary school children at Panyabungan City, North Sumatera Province. Peripheral thick and thin blood smear examinations were done to confirm the diagnosis of malaria. Participants were divided in two groups (malaria-infected and uninfected) by consecutive sampling. Nutritional status was determined by body weight and height measurements based on the 2000 Centers for Disease Control and Prevention (CDC) chart. The mild and moderate malnutrition classification was further sub-divided into stunted and wasted, based on the 2007 NCHS/WHO chart. Chi-square test was used to analyze the relationship between nutritional status and malaria infection.Results There were 126 children in each group. Significant differences in mild-moderate malnutrition were found between the malaria-infected and uninfected groups (23.8% vs. 46.8%, respectively; P= 0.011). There were also significant differences between the malaria-infected and uninfected groups with regards to chronic malnutrition type: stunted (20.0% vs. 37.3%, respectively; P=0.042) and stunted-wasted (6.7% vs. 28.8%, respectively; P= 0.008) in both groups of the children with mild-moderate malnutrition.Conclusion There are significantly more children with mild-moderate malnutrition in the uninfected group than in the malaria-infected group, furthermore, of those with mild-moderate malnutrition, there are significantly more stunted and stunted-wasted children who were uninfected than malaria-infected.

Endoglin Expression and the Level of Tgf-? Are Increased In the Placental Tissue and Correlated with Low Fetal Weight in Malaria Infected Mice

Malaria infection during pregnancy can cause accumulation of infected-red blood cells in placental intervillous space and induces placental tissue inflammation and hypoxia. This condition triggers endoglin expression, and release of soluble endoglin which can interfere TGF-β binding to its receptor. The aim of this study was to investigate the correlation between placental endoglin expression and TGF-β level with low fetal weight (LFW) in malaria-infected mice. Nine pregnant mice infected with Plasmodium berghei on the day 9th post mating (malaria infected group) and eight normal pregnant mice (non-infected group) were used in this study. The mice were sacrificed on the day 18th post mating, and all fetal body weights were measured by analytical scale. Enzyme Link Immunosorbent Assay (ELISA) was done to determine the level of placental TGF-β while immunohistochemical staining was performed to examine endoglin expression in placental tissue. The mean of fetal body weights of malaria infected group was significantly lower than non-infected group (p=0,002), while the expression of placental endoglin in malaria infected group was significantly higher than non-infected group (p=0.003). The level of placental TGF-β in malaria infected group was also higher than non-infected group but the difference was not significant (p=0.064). Pearson correlation test showed that there were significant negative correlations between fetal body weights with the level of placental TGF-β (p=0.017, r=-0.568) and the expression of placental endoglin (p=0.002, r=-0.694). Malaria infection in pregnant mice will increase both TGF- β and endoglin in placenta tissue and correlate with low fetal weight.  Â

Endoglin Expression and The Level of TGF- β are Increased in The Placental Tissue and Correlated with Low Fetal Weight in Malaria Infected Mice

Malaria infection during pregnancy can cause accumulation of infected-red blood cells in placental intervillous space and induces placental tissue inflammation and hypoxia. This condition triggers endoglin expression, and release of soluble endoglin which can interfere TGF-β binding to its receptor. The aim of this study was to investigate the correlation between placental endoglin expression and TGF-β level with low fetal weight (LFW) in malaria-infected mice. Nine pregnant mice infected with Plasmodium berghei on the day 9 th post mating (malaria infected group) and eight normal pregnant mice (non-infected group) were used in this study. The mice were sacrificed on the day 18 th post mating, and all fetal body weights were measured by analytical scale. Enzyme Link Immunosorbent Assay (ELISA) was done to determine the level of placental TGF-β while immunohistochemical staining was performed to examine endoglin expression in placental tissue. The mean of fetal body weights of malaria infected group was significantly lower than non-infected group (p=0,002), while the expression of placental endoglin in malaria infected group was significantly higher than non-infected group (p=0.003). The level of placental TGF-β in malaria infected group was also higher than non-infected group but the difference was not significant (p=0.064). Pearson correlation test showed that there were significant negative correlations between fetal body weights with the level of placental TGF-β (p=0.017, r=-0.568) and the expression of placental endoglin (p=0.002, r=-0.694). Malaria infection in pregnant mice will increase both TGF- β and endoglin in placenta tissue and correlate with low fetal weight.

Malaria Infection Alters the Expression of Hepatobiliary and Placental Drug Transporters in Pregnant Mice

Preventing and treating malaria in pregnancy is a global health priority. However little is known regarding the impact of malaria infection on the maternal and fetal disposition of pharmaceuticals and other xenobiotics. Our objective was to characterize expression of key determinants of drug-disposition in maternal and fetal tissues in a validated murine model of experimental placental malaria. Balb/c mice were infected with Plasmodium berghei at mid gestation [gestational day (GD) 13] and maternal, placental, and fetal tissues were collected at GD19. Expression of key ABC drug transporters and Cyp3a11 was examined by quantitative polymerase chain reaction. Western blotting was used to examine the protein expression of multidrug resistance protein 1 (MDR1, ABCB1). Compared with controls, placental mRNA expression of Abcb1a, Abcb1b, Abcc1, Abcc2, Abcc3, and Abcg2 were significantly downregulated in the malaria-infected group (P < 0.05), as was placental MDR1 protein (P < 0.05). Significantly decreased hepatic expression of Abcc2, Abcg2, and Abcb11 and significantly increased expression of Abcb1b, Abcc1, and Abcc3 were seen in malaria-infected dams (P < 0.05) in comparison with uninfected controls. The expression of Abcb1a and Abcg2 was significantly decreased in fetal liver of infected dams, whereas levels of Abcb1b were increased (P < 0.05). Maternal and fetal hepatic expression of Cyp3a11 was significantly downregulated in the malaria group (P < 0.05). Together, malaria-induced alterations in the expression of transporters and drug-metabolizing enzymes in maternal and fetal tissues may alter the disposition of endogenous and therapeutic substrates, potentially impacting maternal and fetal outcomes.

Pharmacokinetics, Pharmacodynamics, and Allometric Scaling of Chloroquine in a Murine Malaria Model

Chloroquine (CQ) is an important antimalarial drug for the treatment of special patient groups and as a comparator for preclinical testing of new drugs. Pharmacokinetic data for CQ in animal models are limited; thus, we conducted a three-part investigation, comprising (i) pharmacodynamic studies of CQ and CQ plus dihydroartemisinin (DHA) in Plasmodium berghei-infected mice, (ii) pharmacokinetic studies of CQ in healthy and malaria-infected mice, and (iii) interspecies allometric scaling for CQ from 6 animal and 12 human studies. The single-dose pharmacodynamic study (10 to 50 mg CQ/kg of body weight) showed dose-related reduction in parasitemia (5- to >500-fold) and a nadir 2 days after the dose. Multiple-dose regimens (total dose, 50 mg/kg CQ) demonstrated a lower nadir and longer survival time than did the same single dose. The CQ-DHA combination provided an additive effect compared to each drug alone. The elimination half-life (t(1/2)), clearance (CL), and volume of distribution (V) of CQ were 46.6 h, 9.9 liters/h/kg, and 667 liters/kg, respectively, in healthy mice and 99.3 h, 7.9 liters/h/kg, and 1,122 liters/kg, respectively, in malaria-infected mice. The allometric equations for CQ in healthy mammals (CL = 3.86 × W(0.56), V = 230 × W(0.94), and t(1/2) = 123 × W(0.2)) were similar to those for malaria-infected groups. CQ showed a delayed dose-response relationship in the murine malaria model and additive efficacy when combined with DHA. The biphasic pharmacokinetic profiles of CQ are similar across mammalian species, and scaling of specific parameters is plausible for preclinical investigations.

Impact of schistosome infection on Plasmodium falciparum Malariometric indices and immune correlates in school age children in Burma Valley, Zimbabwe.

A group of children aged 6–17 years was recruited and followed up for 12 months to study the impact of schistosome infection on malaria parasite prevalence, density, distribution and anemia. Levels of cytokines, malaria specific antibodies in plasma and parasite growth inhibition capacities were assessed. Baseline results suggested an increased prevalence of malaria parasites in children co-infected with schistosomiasis (31%) compared to children infected with malaria only (25%) (p = 0.064). Moreover, children co-infected with schistosomes and malaria had higher sexual stage geometric mean malaria parasite density (189 gametocytes/µl) than children infected with malaria only (73/µl gametocytes) (p = 0.043). In addition, a larger percentage of co-infected children (57%) had gametocytes as observed by microscopy compared to the malaria only infected children (36%) (p = 0.06). There was no difference between the two groups in terms of the prevalence of anemia, which was approximately 64% in both groups (p = 0.9). Plasma from malaria-infected children exhibited higher malaria antibody activity compared to the controls (p = 0.001) but was not different between malaria and schistosome plus malaria infected groups (p = 0.44) and malaria parasite growth inhibition activity at baseline was higher in the malaria-only infected group of children than in the co-infected group though not reaching statistical significance (p = 0.5). Higher prevalence and higher mean gametocyte density in the peripheral blood may have implications in malaria transmission dynamics during co-infection with helminths.