Acute Malaria Infection Research Articles

Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children

BackgroundThe effects of Plasmodium falciparum on B-cell homeostasis have not been well characterized. This study investigated whether an episode of acute malaria in young children results in changes in the peripheral B cell phenotype.MethodsUsing flow-cytofluorimetric analysis, the B cell phenotypes found in the peripheral blood of children aged 2–5 years were characterized during an episode of acute uncomplicated clinical malaria and four weeks post-recovery and in healthy age-matched controls.ResultsThere was a significant decrease in CD19+ B lymphocytes during acute malaria. Characterization of the CD19+ B cell subsets in the peripheral blood based on expression of IgD and CD38 revealed a significant decrease in the numbers of naive 1 CD38-IgD+ B cells while there was an increase in CD38+IgD- memory 3 B cells during acute malaria. Further analysis of the peripheral B cell phenotype also identified an expansion of transitional CD10+CD19+ B cells in children following an episode of acute malaria with up to 25% of total CD19+ B cell pool residing in this subset.ConclusionChildren experiencing an episode of acute uncomplicated clinical malaria experienced profound disturbances in B cell homeostasis.

Cell-mediated pathology during murine malaria-associated nephritis.

We have studied the cellular mechanisms involved in the development of nephritis during acute and chronic murine malaria infections induced by Plasmodium vinckei petteri and P. berghei respectively. Albuminuria and uraemia were observed during the early stages of both types of infection, and were associated with glomerular and interstitial hypercellularity. There was a gradual increase in numbers of CD45+ cells from the early stages of both infections onwards. These infiltrates contained CD4+ and CD8+ cells and mononuclear phagocytes. The interstitial and glomerular hypercellularity was due to an influx of inflammatory cells rather than an increase in renal cell division. These findings indicate the importance of cell-mediated immune mechanisms in the development of nephritis during murine malaria and illustrate an example of naturally occurring infection-induced nephritis.

Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity

Splenic microarchitecture is substantially altered during acute malaria infections, which may affect the development and regulation of immune responses. Here we investigated whether engagement of host Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adaptor protein MyD88 is required for induction of the changes and whether antibody responses are modified when immunization takes place during the period of splenic disruption. The alterations in splenic microarchitecture were maximal shortly after the peak of parasitemia and were not dependent on engagement of TLR2, TLR4, or TLR9, and they were only minimally affected by the absence of the MyD88 adaptor molecule. Although germinal centers were formed in infected mice, they did not contain the usual light and dark zones. Immunization of mice with chicken gamma globulin 2 weeks prior to acute Plasmodium chabaudi infection did not affect the quantity or avidity of the immunoglobulin G antibody response to this antigen. However, immunization at the same time as the primary P. chabaudi infection resulted in a clear transient reduction in antibody avidity in the month following immunization. These data suggest that the alterations in splenic structure, particularly the germinal centers, may affect the quality of an antibody response during a malaria infection and could impact the development of immunity to malaria or to other infections or immunizations given during a malaria infection.

The dynamics of acute malaria infections. I. Effect of the parasite's red blood cell preference

What determines the dynamics of parasite and anaemia during acute primary malaria infections? Why do some strains of malaria reach higher densities and cause greater anaemia than others? The conventional view is that the fastest replicating parasites reach the highest densities and cause the greatest loss of red blood cells (RBCs). Other current hypotheses suggest that the maximum parasite density is achieved by strains that either elicit the weakest immune responses or infect the youngest RBCs (reticulocytes). Yet another hypothesis is a simple resource limitation model where the peak parasite density and the maximum anaemia (percentage loss of RBCs) during the acute phase of infection equal the fraction of RBCs that the malaria parasite can infect. We discriminate between these hypotheses by developing a mathematical model of acute malaria infections and confronting it with experimental data from the rodent malaria parasite Plasmodium chabaudi. We show that the resource limitation model can explain the initial dynamics of infection of mice with different strains of this parasite. We further test the model by showing that without modification it closely reproduces the dynamics of competing strains in mixed infections of mice with these strains of P. chabaudi. Our results suggest that a simple resource limitation is capable of capturing the basic features of the dynamics of both parasite and RBC loss during acute malaria infections of mice with P. chabaudi, suggesting that it might be worth exploring if similar results might hold for other acute malaria infections, including those of humans.

Macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of Plasmodium yoelii parasitemia.

In most models of blood-stage malaria infection, proinflammatory immune responses are required for control of infection and elimination of parasites. We hypothesized therefore that the fulminant infections caused in mice by the lethal strain of Plasmodium yoelii (17XL) might be due to failure to activate a sufficient inflammatory response. Here we have compared the adaptive CD4+ T-cell and innate immune response to P. yoelii 17XL with that induced by the self-resolving, nonlethal strain of P. yoelii, 17X(NL). During the first 7 to 9 days of infection, splenic effector CD4+ T-cell responses were similar in mice with lethal and nonlethal infections with similar levels of activation in vivo and equivalent proliferation in vitro following mitogenic stimulation. Nonspecific T-cell hyporesponsiveness was observed at similar levels during both infections and was due, in part, to suppression mediated by CD11b+ cells. Importantly, however, RAG-/- mice were able to control the initial growth phase of nonlethal P. yoelii infection as effectively as wild-type mice, indicating that T cells and/or B cells play little, if any, role in control of the primary peak of parasitemia. Somewhat unexpectedly, we could find no clear role for either NK cells or gamma interferon (IFN-gamma) in controlling primary P. yoelii infection. In contrast, depletion of monocytes/macrophages exacerbated parasite growth and anemia during both lethal and nonlethal acute P. yoelii infections, indicating that there is an IFN-gamma-, NK cell-, and T-cell-independent pathway for induction of effector macrophages during acute malaria infection.

ABO blood group system and placental malaria in an area of unstable malaria transmission in eastern Sudan

BackgroundUnderstanding the pathogenesis of malaria in pregnancy and its consequences for both the mother and the baby is fundamental for improving malaria control in pregnant women.AimThe study aimed to investigate the role of ABO blood groups on pregnancy outcomes in an area of unstable malaria transmission in eastern Sudan.MethodsA total of 293 women delivering in New Half teaching hospital, eastern Sudan during the period October 2006–March 2007 have been analyzed. ABO blood groups were determined and placental histopathology examinations for malaria were performed. Birth and placental weight were recorded and maternal haemoglobin was measured.Results114 (39.7%), 61 (22.1%) and 118 (38.2%) women were primiparae, secundiparae and multiparae, respectively. The ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128 (O). Placental histopathology showed acute placental malaria infections in 6 (2%), chronic infections in 6 (2%), 82 (28.0%) of the placentae showed past infection and 199 (68.0%) showed no infection. There was no association between the age (OR = 1.02, 95% CI = 0.45–2.2; P = 0.9), parity (OR = 0.6, 95% CI = 0.3–1.2; P = 0.1) and placental malaria infections. In all parity blood group O was associated with a higher risk of past (OR = 1.9, 95% CI = 1.1–3.2; P = 0.01) placental malaria infection. This was also true when primiparae were considered separately (OR = 2.6, 95% CI = 1.05–6.5, P = 0.03).Among women with all placental infections/past placental infection, the mean haemoglobin was higher in women with the blood group O, but the mean birth weight, foeto-placental weight ratio was not different between these groups and the non-O group.ConclusionThese results indicate that women of eastern Sudan are at risk for placental malaria infection irrespective to their age or parity. Those women with blood group O were at higher risk of past placental malaria infection.

Role of TGF‐β and PGE2 in T cell responses during Plasmodium yoelii infection

During an acute blood-stage malaria infection, T cell responses to malaria and other bystander antigens are inhibited. Plasmodium infection induces strong cytokine responses that facilitate parasite clearance but may interfere with T cell functions, as some of the soluble immune mediators induced are also general inhibitors of T cell responses. Using a malaria mouse model, we have analyzed the cytokines produced by dendritic cells in response to P. yoelii infection that have potential T cell inhibitory activity. We found that during acute infection DC migrate to the spleen and secrete TGF-beta, prostaglandin E2 (PGE2) and IL-10. We have analyzed the role of these general T cell inhibitors in a particular T cell response of evident importance in malaria infections: the CD8+ T cells generated against the liver-stage of the disease. During blood-stage infection, inhibition of the activity of TGF-beta and PGE2 restores the CD8+ T cell responses generated by sporozoites, increasing protection against re-infection. Our findings suggest that the strong cytokine response induced by blood-stage P. yoelii infection affects host T cell responses, inhibiting protective CD8+ T cells against the liver-stage of the disease.

Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice.

Investigation of the role of regulatory T cells (Treg) in model systems is facilitated by their depletion using anti-CD25 Abs, but there has been considerable debate about the effectiveness of this strategy. In this study, we have compared the depletion and repopulation of CD4+CD25+Foxp3+ Treg in uninfected and malaria-infected mice using 7D4 and/or PC61 anti-CD25 Abs. We find that numbers and percentages of CD25(high) cells, but not Foxp3+ cells, are transiently reduced after 7D4 treatment, whereas treatment with PC61 alone or in combination with 7D4 (7D4 plus PC61) reduces but does not eliminate Foxp3+ cells for up to 2 wk. Importantly, all protocols fail to eliminate significant populations of CD25-Foxp3+ or CD25(low)Foxp3+ cells, which retain potent regulatory capacity. By adoptive transfer we show that repopulation of the spleen by CD25(high)Foxp3+ cells results from the re-expression of CD25 on peripheral populations of CD25-Foxp3+ but not from the conversion of peripheral Foxp3-) cells. CD25(high)Foxp3+ repopulation occurs more rapidly in 7D4-treated mice than in 7D4 plus PC61-treated mice, reflecting ongoing clearance of emergent CD25+Foxp3+ cells by persistent PC61 Ab. However, in 7D4 plus PC61-treated mice undergoing acute malaria infection, repopulation of the spleen by CD25+Foxp3+ cells occurs extremely rapidly, with malaria infection driving proliferation and CD25 expression in peripheral CD4+CD25-Foxp3+ cells and/or conversion of CD4+CD25-Foxp3- cells. Finally, we reveal an essential role for IL-2 for the re-expression of CD25 by Foxp3+ cells after anti-CD25 treatment and observe that TGF-beta is required, in the absence of CD25 and IL-2, to maintain splenic Foxp3+ cell numbers and a normal ratio of Treg:non-Treg cells.

Disruption of CD36 Impairs Cytokine Response to Plasmodium falciparum Glycosylphosphatidylinositol and Confers Susceptibility to Severe and Fatal Malaria In Vivo

CD36 is a scavenger receptor that has been implicated in malaria pathogenesis as well as innate defense against blood-stage infection. Inflammatory responses to Plasmodium falciparum GPI (pfGPI) anchors are believed to play an important role in innate immune response to malaria. We investigated the role of CD36 in pfGPI-induced MAPK activation and proinflammatory cytokine secretion. Furthermore, we explored the role of this receptor in an experimental model of acute malaria in vivo. We demonstrate that ERK1/2, JNK, p38, and c-Jun became phosphorylated in pfGPI-stimulated macrophages. In contrast, pfGPI-induced phosphorylation of JNK, ERK1/2, and c-Jun was reduced in Cd36(-/-) macrophages and Cd36(-/-) macrophages secreted significantly less TNF-alpha in response to pfGPI than their wild-type counterparts. In addition, we demonstrate a role for CD36 in innate immune response to malaria in vivo. Compared with wild-type mice, Cd36(-/-) mice experienced more severe and fatal malaria when challenged with Plasmodium chabaudi chabaudi AS. Cd36(-/-) mice displayed a combined defect in cytokine induction and parasite clearance with a dysregulated cytokine response to infection, earlier peak parasitemias, higher parasite densities, and higher mortality rates than wild-type mice. These results provide direct evidence that pfGPI induces TNF-alpha secretion in a CD36-dependent manner and support a role for CD36 in modulating host cytokine response and innate control of acute blood-stage malaria infection in vivo.

Depression of platelet counts in apparently healthy children with asymptomatic malaria infection in a Nigerian metropolitan city

Asymptomatic malaria infection is a common feature of malaria endemic regions in the tropics. In this prospective cross sectional survey, involving 240 children aged 1 to 8 years (Boys = 117, Girls = 123; Ratio 1:1.05), the median platelet count was 115 × 109/L (IQR 97.5–190). Thirty-three out of 240 (13.75%) of the children had thrombocytopenia (platelet count < 100 × 109/L). Malaria parasite was found to exert significant reduction in platelet count. This reduction was more pronounced in children under 5 years and also at higher parasite counts. An inverse relationship was established between parasite density and platelet count (y = −0.017x + 96.2, r = −0.2). Thrombocytopenia is not only a feature of acute malaria infection but also that of asymptomatic malaria infection in the tropics and might be a useful indicator of malaria in children.

Laboratory indicators of the diagnosis and course of imported malaria

When travellers return from malaria-endemic areas and present to hospital with fever, microscopy of blood smears remains the leading method to verify a suspected diagnosis of malaria. Additional laboratory abnormalities may, however, also be indicative of acute malaria infection. We monitored prospectively a group of patients with imported Plasmodium falciparum (n=28) or P. vivax/P. ovale (n=12) infection, respectively, and assessed haemoglobin, leucocytes, thrombocytes, C-reactive protein, coagulation factor II-VII-X, lactate dehydrogenase and bilirubin during 7 d of admission and weekly until d 28. For comparison, admission values of a group of febrile patients with suspected malaria, but with negative blood slides, were also assessed (n=66). The thrombocyte, leucocyte counts and coagulation factor II-VII-X were significantly lower in the malaria group compared to the non-malaria group, whereas the C-reactive protein, lactate dehydrogenase and bilirubin were significantly higher in the malaria group. The differences were particularly strong with falciparum malaria. By contrast, haemoglobin levels were not affected. In conclusion, our study emphasizes the role of a few commonly analysed laboratory parameters, in particular thrombocyte counts, in guiding the clinician managing a returning traveller with fever.

Characterization of Peripheral Blood Lymphocyte Subsets in Patients with AcutePlasmodium falciparumandP. vivaxMalaria Infections at Wonji Sugar Estate, Ethiopia

We investigated the absolute counts of CD4+, CD8+, B, NK, and CD3+ cells and total lymphocytes in patients with acute Plasmodium falciparum and Plasmodium vivax malaria. Three-color flow cytometry was used for enumerating the immune cells. After slide smears were stained with 3% Giemsa stain, parasite species were detected using light microscopy. Data were analyzed using STATA and SPSS software. A total of 204 adults of both sexes (age, >15 years) were included in the study. One hundred fifty-eight were acute malaria patients, of whom 79 (50%) were infected with P. falciparum, 76 (48.1%) were infected with P. vivax, and 3 (1.9%) were infected with both malaria parasites. The remaining 46 subjects were healthy controls. The leukocyte count in P. falciparum patients was lower than that in controls (P=0.015). Absolute counts of CD4+, CD8+, B, and CD3+ cells and total lymphocytes were decreased very significantly during both P. falciparum (P<0.0001) and P. vivax (P<0.0001) infections. However, the NK cell count was an exception in that it was not affected by either P. falciparum or P. vivax malaria. No difference was found in the percentages of CD4, CD8, and CD3 cells in P. falciparum or P. vivax patients compared to controls. In summary, acute malaria infection causes a depletion of lymphocyte populations in the peripheral blood. Thus, special steps should be taken in dealing with malaria patients, including enumeration of peripheral lymphocyte cells for diagnostic purposes and research on peripheral blood to evaluate the immune status of patients.

Elevated total and isoenzyme forms of acid phosphatase in falciparum malaria

The activities of total serum acid phosphatase (E.C. 3.1.3.2) and of two of its isoenzymes, tartrate-resistant acid phosphatase and erythrocyte-specific acid phosphatase were measured in 109 adult male and female patients presenting acute falciparum malaria infection, and a normal, healthy control group comprised of 82 subjects. All the three forms of acid phosphatase were found to be significantly ( p < 0.05 ) higher during infection as compared to their activity in the control group. This result suggests that the measurement of acid phosphatase, particularly the erythrocyte isoenzyme, in serum could be potentially used as a biomarker of acute falciparum malaria infection. To cite this article: I.H. Garba et al., C. R. Biologies 329 (2006).

Potential Role of Serum Magnesium Measurement as a Biomarker of Acute Falciparum Malaria Infection in Adult Patients

Serum magnesium concentration was measured in 80 adult patients (age range: 18-40 yr) presenting with acute, uncomplicated falciparum malaria infection and a control group of 20 age-matched, healthy individuals. The mean serum magnesium concentration in the patients was 1950.0 +/- 10.0 microg/dL. The control serum magnesium was 640.0 +/- 40.0 microg/dL. This represents an over threefold increase in serum magnesium levels above normal value, p < 0.01. The key pathogenic event in acute falciparum malaria infection is the hemolysis of both infected and uninfected red blood cells. Therefore, the increased serum magnesium concentration might occur because of the hemolysis arising from erythrocytic merogony because red blood cells contain high amounts of magnesium. In conclusion, the increased serum magnesium has potential application as a biomarker of acute falciparum malaria infection in adults.

Serum L-Ascorbic Acid Concentration And Its Potential For Scavenging Of Reactive Oxygen Species In Acute, Uncomplicated, &lt;italic&gt;Falciparum&lt;/italic&gt; Malaria Infection

Introduction: Reactive oxygen species (ROS) are produced during falciparum malaria infection leading to serum lipid peroxidation which is known to overwhelm some of the body's major antioxidant defenses including vitamin A, vitamin E, iron, catalase, glutathione peroxidase and superoxide dismutase. Methods: The serum concentration of L-ascorbic acid was measured in 252 patients comprising of 90 adult males and 90 adult females (age range = 18-35 years), 34 male children and 34 female children (age range = 3-5years), presenting with acute, uncomplicated falciparum malaria infection and a control group of 76 healthy age-matched adults and 19 children. Results: Serum L-ascorbic acid concentration was found to be significantly elevated in all the patient groups relative to the control L-ascorbic acid concentration. The male and female adult patients had a serum L-ascorbic acid concentration of 1.07 ± 0.03 mg/dl and 1.24 ± 0.03 mg/dl, while the value was 0.53 ± 0.03 mg/dl in healthy adult controls, p < 0.05. Serum L-ascorbic acid concentrations in male and female children were 1.18 ± 0.03 mg/dl and 1.23 ± 0.02 mg/dl. These values are all higher than the serum L-ascorbic acid concentration of 0.55 ± 0.03 mg/dl in healthy children, p< 0.05. Conclusion:The increased serum L-ascorbic acid may arise as result of the mobilization of leukocyte L-ascorbic acid since leukocytes are known to increase in response to acute falciparum malaria infection. It could also be a compensatory homeostatic mechanism by the patients to offset the failure of the other antioxidant defenses during the disease.

Effects of antifolates - co-trimoxazole and pyrimethamine-sulfadoxine - on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS--but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrollment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

Malarial Hepatitis Simulating Fulminant Hepatic Failure–Reply–I

We thank Dr Padda for his interest in our article and for the thoughtful questions he raised. Splenomegaly, not seen in any patient with viral FHF in our study but present in 48% of our patients with MHsFHF, does appear to have the same significance as hepatomegaly. However, when we used stepwise discriminant function analysis to identify variables predictive of discriminating MHsFHF vs viral FHF, prothrombin time and hepatomegaly were identified as the best predictors. During the review process, we deleted the discriminant analysis as suggested because prothrombin time alone had a concordance of 98%. In our study, none of the patients in the MHsFHF group had serologic markers of hepatitis B infection. Therefore, we did not discuss malaria and hepatitis B coinfection. As reported, 19 patients in the viral FHF group had serologic markers of acute hepatitis B infection without smears positive for malarial parasites. As Dr Padda stated, hepatitis B may affect the outcome of severe malaria, although currently there is no clear evidence that it does. In the study by Barcus et al,1Barcus MJ Hien TT White NJ et al.Short report: hepatitis B infection and severe Plasmodium falciparum malaria in Vietnamese adults.Am J Trop Med Hyg. 2002; 66: 140-142PubMed Google Scholar hepatitis B surface antigen positivity alone did not affect mortality; thus, other factors may play a role. In another study,2Brown AE Mongkolsirichaikul D Innis B Snitbhan R Webster HK Falciparum malaria modulates viremia in chronic hepatitis B virus infection [letter].J Infect Dis. 1992; 166: 1465-1466Crossref PubMed Scopus (13) Google Scholar among 4 patients with acute malaria who were also positive for hepatitis B surface antigen, levels of hepatitis B virus DNA became detectable in 2 with undetectable hepatitis B virus DNA before malaria. In the remaining 2 patients with high levels of hepatitis B virus DNA, there was a transient decrease in DNA titer during episodes of malaria. These findings suggest that altered immune responses during acute malaria may influence hepatitis B viremia. However, there is no convincing evidence of exacerbation of underlying hepatitis B-related liver disease during acute falciparum malaria infection. Further studies are needed to clarify the effect of underlying hepatitis B infection on acute falciparum malaria and vice versa. Furthermore, both of the aforementioned studies suffered from selection bias and lacked a control arm. The levels of alkaline phosphatase were high in both groups we reported, and the difference was not statistically significant (263.1 ± 29.32 vs 321.48 ± 61.57; P=.14). Malarial Hepatitis Simulating Fulminant Hepatic FailureMayo Clinic ProceedingsVol. 80Issue 6PreviewTo the Editor: I read the article on malarial hepatitis by Devarbhavi et al,1 published in the March 2005 issue of the Mayo Clinic Proceedings, with much interest because I live in southern California, where unexpectedly heavy rainfall this year is anticipated to result in increased numbers of cases of mosquito-related illnesses. Their valuable study helps differentiate cases of malarial hepatitis simulating fulminant hepatic failure (MHsFHF) from viral-associated FHF. However, I have a few concerns. Full-Text PDF

Plasma Zinc Concentrations Are Depressed during the Acute Phase Response in Children with Falciparum Malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.

AST/ALT Ratio In Acute, Uncomplicated Falciparum Malaria Infection: Comparison In Relation To The AST/ALT Ratios In Diseases Of The Liver

Introduction: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assayed in 110 adult patients (age range 18-40 years) presenting with acute, uncomplicated falciparum malaria infection and a control group of 80 age and sex-matched adults. Methods: Patient selection was done by simple random sampling of adult males and females presenting at the Bauchi State Specialist Hospital with a history of fever and malaise not lasting more that seven days and who were subsequently confirmed to be malaria-positive by microscopic examination of Giemsa-stained thin blood slides. Results: The mean serum AST and ALT activities were found to increase significantly relative to the AST and ALT values in the control group. Serum AST activity was 38.29 ± 1.37 IU in the falciparum malaria patients and 30.19 ± 1.37 IU in the healthy controls, p < 0.05. Similarly serum ALT activity was 31.06 ± 0.58 IU in falciparum malaria patients and 24.96 ± 0.92 IU in the control group, p < 0.05. The mean AST/ALT ratio in acute falciparum malaria infection was found to be 1.22 ± 0.14. This ratio differs significantly from the AST/ALT ratios reported for patients with Non-alcoholic steatohepatitis, chronic hepatitis C, alcoholic liver disease, hepatitis B and cirrhosis, p < 0.05. Conclusion:An AST/ALT ratio greater than 1 during acute falciparum infection contradicts earlier reports that the ratio is highly specific to cirrhosis alone or has application as marker of liver disease only. Therefore the application the AST/ALT ratio as a non-invasive means of assessing liver disease must be done with caution in the tropics where P. falciparum malaria infection is among the leading causes of hospital attendance.

Serum Alkaline Phosphatase Activity As A Potential Biomarker For The Intergrity Of The Hepatic Drainage System In Acute Falciparum Malaria Infection

Introduction: The serum activity of the tissue-specific, membrane-bound enzyme alkaline phosphatase (Orthophosphoric monoester phosphohydrolase, alkaline optimum (E.C. 3.1.3.1))was assayed in the sera of 110 adult patients comprising of 50 males and 60 females (age range, 18 – 40 years) presenting with acute falciparum malaria infection and a control group of 48 healthy adults. Methods: Serum samples were collected from a randomly selected group of individuals confirmed to be infected with the falciparum malaria parasite by microscopic examination of Giemsa stained thin blood slides. Results:Serum alkaline phosphatase activity was significantly increased (6.35 ± 0.39 IU) in female patients relative to the normal females (4.33 ± 0.23 IU), p = 0.003. Serum alkaline phosphatase activity was also higher in male patients (5.85 ± 0.36 IU) when compared to the control activity of (4.83 ± 0.35 IU) in males, p = 0.001. Conclusion: The increased serum alkaline phosphatase activity among the patients indicates that the liver stage of falciparum malaria infection is accompanied by a perturbation of the host hepatocytes drainage pathways where alkaline phosphatase is localized on the membrane. This makes alkaline phosphatase a potentially important biomarker for the assessment of the integrity of the hepatic drainage system in acute falciparum malaria infection.