Manifestations Of Severe Malaria Research Articles

Synthetic angiotensin II peptide derivatives confer protection against cerebral and severe non-cerebral malaria in murine models

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.

Malarial Pigment Hemozoin in Neutrophils: A Manifestation of Severe Malaria

Malarial Pigment Hemozoin in Neutrophils: A Manifestation of Severe Malaria

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.

Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.

Clinical impact of vivax malaria: A collection review.

BackgroundPlasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade.Methods and findingsWe describe the main clinical impacts of vivax malaria, incorporating a rapid systematic review of severe disease with meta-analysis of data from studies with clearly defined denominators, stratified by hospitalization status. Severe anemia is a serious consequence of relapsing infections in children in endemic areas, in whom vivax malaria causes increased morbidity and mortality and impaired school performance. P. vivax infection in pregnancy is associated with maternal anemia, prematurity, fetal loss, and low birth weight. More than 11,658 patients with severe vivax malaria have been reported since 1929, with 15,954 manifestations of severe malaria, of which only 7,157 (45%) conformed to the World Health Organization (WHO) diagnostic criteria. Out of 423 articles, 311 (74%) were published since 2010. In a random-effects meta-analysis of 85 studies, 68 of which were in hospitalized patients with vivax malaria, we estimated the proportion of patients with WHO-defined severe disease as 0.7% [95% confidence interval (CI) 0.19% to 2.57%] in all patients with vivax malaria and 7.11% [95% CI 4.30% to 11.55%] in hospitalized patients. We estimated the mortality from vivax malaria as 0.01% [95% CI 0.00% to 0.07%] in all patients and 0.56% [95% CI 0.35% to 0.92%] in hospital settings. WHO-defined cerebral, respiratory, and renal severe complications were generally estimated to occur in fewer than 0.5% patients in all included studies. Limitations of this review include the observational nature and small size of most of the studies of severe vivax malaria, high heterogeneity of included studies which were predominantly in hospitalized patients (who were therefore more likely to be severely unwell), and high risk of bias including small study effects.ConclusionsYoung children and pregnant women are particularly vulnerable to adverse clinical impacts of vivax malaria, and preventing infections and relapse in this groups is a priority. Substantial evidence of severe presentations of vivax malaria has accrued over the last 10 years, but reporting is inconsistent. There are major knowledge gaps, for example, limited understanding of the underlying pathophysiology and the reason for the heterogenous geographical distribution of reported complications. An adapted case definition of severe vivax malaria would facilitate surveillance and future research to better understand this condition.

Perfusion Index as an Indicator for Mortality in Children with Plasmodium falciparum Severe Malaria

Background:Severe malaria (SM) remains a major global health problem causing ~275,000 pediatric deaths annually, worldwide. Continuous, non-invasive monitoring of peripheral perfusion can help detect abnormalities in systemic circulation, a common problem in critically ill patients, and can improve outcomes in children hospitalized with SM. Perfusion index (PI), an indicator of peripheral perfusion measured using a point-of-care pulse oximeter, is the ratio of pulsatile blood flow to static blood in peripheral tissue. &#x0D; Objective: To investigate the role of PI as an indicator of adverse outcomes including mortality in children hospitalized with SM. &#x0D; Methods: We measured PI in a prospective cohort study of 600 children &lt;5 years of age with 5 different clinical manifestations of SM, and 120 healthy community children (CC) at two hospitals in Uganda. PI was measured at 6-hr intervals during hospitalization using a Masimo Rad 57 pulse oximeter.&#x0D; Results: Children with SM had significantly lower admission PI values (1.2 [IQR: 0.58, 2.2] compared to CC (2.8 [1.7, 4.3], p&lt;0.001). Children with SM manifesting as respiratory distress syndrome or severe malarial anemia had lower median PI compared to other manifestations including cerebral malaria, the deadliest form of SM in children. In children with SM, a log decrease in admission PI was associated with 2.7 higher odds of in-hospital mortality (p=0.01). A log reduction in PI was also associated with in-hospital clinical complications associated with SM, including circulatory shock, deep acidotic breathing and acidosis, hypoglycemia, and severe anemia (all P&lt;0.03). In survivors of SM, there were no significant associations between PI and cognitive outcomes at 12-month follow-up.&#x0D; Conclusion: The role of PI as an indicator of mortality in children with SM and the use of point-of-care tools for continuous monitoring of PI warrants further investigation in the management of SM to prevent or reduce the incidence of adverse outcomes.

Mixed Infection of Vivax and Falciparum Malaria with Severe Manifestations of Malaria at the General Hospital of the Christian University of Indonesia: A Case Report

Malaria is still a health problem in Indonesia. The number of malaria cases according to the 2018 RISKESDAS reached 8076 cases, and the highest number was obtained from Papua province with 3,334 cases. Multiple infection malaria in Indonesia according to RISKESDAS 2018, has a rate of 0.01% of the total cases, namely Plasmodium Falciparum malaria and Plasmodium non Falciparum malaria. A 47 year old man was referred from the clinic with complaints of high fever preceded by chills 10 days before being admitted to the hospital. Accompanied by shortness of breath, unable to get off the treatment bed due to feeling very weak, nauseous, sick and having a bulging stomach. Physical examination revealed a pale conjunctiva, ronkhi in the lower field of the right lung, dim percussion in the basal of the left lung, hepatomegaly, splenomegaly, shifting dullness. ring form vivax, on chest X-ray found a left pleural effusion. It is known that the patient previously lived in Papua from September 2018 to May 2019. During treatment, the patient was given artesunate injection therapy, dihydroartemisin + piperaquine and primaquin for seven days of treatment. At the end of the treatment, another chest X-ray was performed and re-examination of the peripheral blood smear, no more pleural effusions were found and no parasites were found on re-examination of the peripheral blood smear. Mixed infection of vivax and falciparum malaria, is a rare case that may occur in endemic areas where both plasmodium can be found. The prevalence in Indonesia according to RISKESDAS is only about 0.01% of all malaria cases in Indonesia.

Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology.

Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6-9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.

Investigating Differences in Nutritional Parameters in Ugandan Children with Plasmodium falciparum Severe Malaria

Background: In 2018, malaria produced an estimated 272,000 deaths in children &lt;5 years of age, accounting for 67% of all malaria deaths worldwide, with a majority in the WHO African Region. Malnutrition is an important risk factor for malaria. Wasting, Stunting and Underweight are crucial indicators of malnutrition. Annually, 14 million children &lt;5 are classified as wasted and 59 million children are classified as stunted. &#x0D; Objective: The objective of this study is to determine the association between each of the major manifestations of severe malaria (SM) and nutritional parameters – weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) – in children from the Ugandan cities Mulago and Jinja. &#x0D; Methods: To assess differences in WAZ, HAZ, and WHZ by the five types of SM and community controls (CC), we evaluated Z-scores from children &lt;5 years old enrolled in a prospective cohort study (NDI, Neurodevelopmental Impairment in Children with Severe Malaria) at enrollment and 12-month follow-up. &#x0D; Results: WAZ and WHZ at baseline were significantly lower among SM groups than in CC (p&lt;0.001), but there were no significant differences observed at 12-month follow-up. There were no major differences in HAZ between the SM and CC groups. WAZ and HAZ at baseline were significantly lower among High Mortality (HM) versus Low Mortality (LM) groups (p&lt;0.01). At 12-month follow-up, HAZ remained significantly lower in HM versus LM (p&lt;0.01). There were no major differences in WHZ between the HM and LM groups. Compared to those who survived, the 27 children who died had significantly lower WAZ (p&lt;0.05), but no major differences in HAZ or WHZ. &#x0D; Conclusion: Underweight, stunting, and wasting may be risk factors for SM. Overall, a more comprehensive understanding of how SM elicits adverse effects in children is necessary. Nutrition intervention programs must be implemented to prevent child stunting, wasting, underweight, and mortality.

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

Severe vivax malaria trends in the last two years: a study from a tertiary care centre, Delhi, India

BackgroundPlasmodium vivax, once considered benign species, is recently being recognised to be causing severe malaria like Plasmodium falciparum. In the present study, the authors report the trends in malaria severity in P. vivax among patients from a Delhi government hospital. The aim of the study was to understand the disease severity and the burden of severe vivax malaria.MethodsA hospital based study was carried out from June 2017 to December 2018 at a tertiary care centre from Delhi, India. Patients were tested for malaria using peripheral blood smear (PBS) and/or rapid malaria antigen test (RMAT). The severe and non-severe vivax malaria categorization was done as per the WHO guidelines. Sociodemographic, clinic and paraclinical data were collected from patients and their medical records.ResultsOf the 205 patients, 177 (86.3%) had P. vivax infection, 22 (10.7%) had P. falciparum infection and six (2.9%) had mixed infection with both the species. Out of 177 P. vivax cases included in this study one or more manifestations of severe malaria was found in 58 cases (32.7%). Severe anaemia (56.9%), jaundice (15%) and significant bleeding (15%) were the most common complications reported in most of patients, along with thrombocytopenia.ConclusionsIn this study, it is evident that vivax malaria is emerging as the new severe disease in malaria patients, a significant shift in the paradigm of P. vivax pathogenesis. The spectrum of complications and alterations in the laboratory parameters in P. vivax clinical cases also indicate the recent shift in the disease severity.

Clinico-epidemiological profile of malaria cases admitted in a tertiary care hospital, in South India

Background: Malaria is a global health problem leading to huge morbidity and mortality. India accounts for 4% of global malaria cases and 52% of malaria deaths outside the African region. A disease that was relatively unknown in Mangaluru till 1990, has shown consistent rise till 2015 killing nearly 300 people. Though, declining trends are being observed since 2015, yet its incidence continues to be high. Present study was undertaken to study clinical as well as epidemiological factors associated with malaria transmission in Mangaluru.Methods: A record based retrospective study was conducted in A J Institute of Medical Sciences and Research Centre Mangaluru tertiary care hospital. The data was retrieved from the Medical Record Department of the hospital for three years i.e. 2015 to 2017 and analysed.Results: A total of 1779 confirmed cases of malaria were admitted during the study period. Out of these 1309 (73.58%) cases were due P. vivax, 73 (04.10%) cases due to P. falciparum 306 (17.20%) cases had mixed infections while species of remaining 91 (05.11%) cases remained unspecified. A peak in the number of inpatients was seen in June while mean duration of hospital stay was 5.17±3.31 days. A total of 252 (14.16%) patients had one or more severe manifestations of malaria as per WHO guidelines.Conclusions: The present study reveals that majority of admitted malaria cases were young adult males belonged to urban area. Majority of the cases were infected by Plasmodium vivax or had mixed infections.

Clinico-epidemiological profile of patients admitted with Plasmodium vivax malaria in a tertiary care hospital, Delhi

Background: Malaria is an important public health problem in India. Severe and complicated forms of malaria are usually associated with Plasmodium falciparum species. But recently published literature suggests that Plasmodium vivax infection also presents as severe malaria. The objective was to study clinical and epidemiological profile of patients with P. vivax malaria admitted in Safdarjung hospital.Methods: A record based retrospective study was conducted in Vardhman Mahavir Medical College &amp; Safdarjung Hospital, a tertiary care hospital in Delhi. Data were collected from all case records with ICD 10 codes for Malaria (B50-B54) for the year 2011 obtained from Medical Records Department, Safdarjung Hospital and analyzed using SPSS 21.0.Results: A total of 147 case records which had information about the test results for type of malaria infection were reviewed. Out of 147, 89 (60.5%) had P. vivax malaria. Of the 89 patients with P. vivax malaria, 47 (53%) were children and 63 (70.7%) were males. A peak in the number of inpatients was seen in September with median duration of hospital stay of 4 days and case fatality rate of 9%. A total of 56 (63%) patients had one or more severe manifestations of malaria as per WHO criteria. The most common severe manifestation was bleeding 27 (30%) followed by impaired consciousness 18 (20%).Conclusions: In more than half of the malaria patients admitted at the tertiary care centre the diagnosis was P. vivax malaria. Of them 63% patients had severe malaria as per WHO criteria.

Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains.

Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR‐binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full‐length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1‐EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.

Prevalence and pattern of severe malaria seen in children at a specialist hospital in Gusau, Nigeria

Aims : Malaria continues to cause high morbidity and mortality in children. This study determined the prevalence of severe malaria, pattern of presentation and outcome at the emergency paediatric unit of Yariman Bakura Specialist Hospital, Gusau, Nigeria. Materials and methods : A descriptive retrospective cross sectional study of children aged 1 month to 12 years who fulfilled the 2000 WHOsevere malaria criteria admitted over a one year period at the emergency paediatric unit. Children with positive malaria parasite were included in the study. Children presumed to have severe malaria but with negative malaria parasite test or malaria parasite test not done were excluded. Children with sickle cell anaemia and those with features of meningitis or confirmed to have meningitis were also excluded from the study. All patients were treated with injectable artesunate followed by oral artemeter lumefantrine. Results : A total of 844 children were admitted into the paediatric wards of which 262 were managed for severe malaria but only 164(19.4%) were confirmed to have positive malaria parasitaemia. Fifty seven percent were males with M: F ratio of 1.1:1. Majority of the children were under fives (62.8%). Fever, multiple convulsions and pallor were the commonest presenting symptoms. Multiple convulsions, hyperpyrexia and prostrations were the commonest manifestations of severe malaria. Jaundice, haemoglobinuria and shock were uncommon. Only 11.6% of the children had severe anaemia warranting blood transfusion. Our case fatality rate was 8.5% while 86.6% were discharged and 4.9% left against medical advice. Conclusion : The high prevalence reflects the malaria burden in children especially under fives, despite the measures carried out to reduce malaria morbidity and mortality in the country. However our mortality is lower than what has been found in many studies which shows a decrease in mortality from malaria as has been shown by the latest WHO report.

Sickle Cell Trait (HbAS) is Associated with Increased Expression of Erythrocyte Complement Regulatory Proteins CR1 and CD55 Levels in Children

Aims: Erythrocyte complement regulatory proteins, complement receptor 1 (CR1) and decay accelerating factor (CD55) protect red blood cells (RBCs) from complement mediated damage by controlling complement activation cascade and potentially protect RBCs from complement mediated damage that may occur when immune complexes are Research Article International Journal of TROPICAL DISEASE & Health, 3(2): 133-147, 2013 134 formed following malaria infection. Given the important role of RBCs in regulation of complement activation, we considered the competence of sickle cell trait RBCs in these functions. Methods: Children (age 0-192 months; n=116) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu west District between October and December 2004. Based on hemoglobin (Hb) type, children were stratified into those with HbAS (n=47) and HbAA (n=69). The 47 HbAS individuals were matched to the 69 HbAA individuals of similar age (± 2 months or ± 24 months for those below or more than 192 months, respectively) at a ratio of 1:1 or 1:2. Circulating CR1 levels and CD levels were quantified using a FACScan cytometer under normal and reduced oxygen saturation. Results: The mean CR1 copy numbers per RBC was comparable in the two groups. However, between the ages of 49-192 months, the mean CR1 copy numbers per erythrocyte was significantly higher in children who had HbAS compared to those with HbAA (P=0.0332). The mean CD55 levels were comparable between the two groups but after deoxygenation, the mean CD levels in RBCs of individuals with HbAS was significantly higher than in the HbAA (P=0.011). Conclusion: The mean CR1 and CD55 copy numbers per RBC were comparable between the two groups under normal and reduced oxygen saturation. Beyond the age of 49 months, the CR1 copy numbers was higher in the HbAS compared to HbAA and this was also true for CD55 levels under deoxygenated conditions. Taken together, these results demonstrate that in the younger age groups, the protection afforded by HbAS against severe manifestations of malaria may be due to other factors other than complement regulatory proteins but beyond the age of 49 months, this protection may be partly due to the high CR1 copy numbers in the HbAS individuals.

Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya

Aims: Malaria infection leads to the formation of circulating immune complexes (CICs) which have been implicated in the pathogenesis of complicated malaria which includes severe malarial anemia. Children with sickle cell trait (HbAS) are less predisposed to getting severe manifestations of malaria. We carried out a study to determine the competence of the red blood cells (RBCs) of children with HbAS to bind immune complexes (ICs) and compared this with normal hemoglobin (HbAA). Methods: Children (aged 0-192 months) were enrolled in a nested case controlled study

Relationship between Serum C-reactive Protein Levels and Severity of Plasmodium falciparum Malaria in Children Seen in South-South Nigeria

Aim: To determine the relationship between serum C-reactive protein levels and severity of malaria infection in children aged six months to five years in a malaria endemic setting. Study Design: A prospective cross-sectional study. Place and Duration of Study: This study was carried out in the Children Out-patient (CHOP) Clinic, Children Emergency Unit (CHEU), Child Welfare/Growth Monitoring Clinic, Immunization Centre and main Paediatric Ward of the University of Uyo Teaching Hospital (UUTH), Uyo in Akwa-Ibom State. It was conducted over a six month period. Methodology: We studied three hundred and sixty (360) children with microscopically confirmed Plasmodium falciparum malaria and three hundred and sixty (360) healthy controls matched for age and gender. Their serum C-reactive protein levels were measured using the highly sensitive Enzyme Linked Immunosorbent assay (ELISA). Data analysis was done using the Statistical Package for Social Sciences (SPSS) version 17.0. Original Research Article International Journal of TROPICAL DISEASE & Health, 4(10): 1078-1087, 2014 1079 Results: The serum C-reactive protein levels showed a positive correlation with the malaria parasite count (r = 0.55; p < 0.001). Children presenting with severe manifestations of malaria had significantly higher mean serum C-reactive protein levels (33.3± 6.88mg/l) than the 8.12±9.09mg/l obtained in those with uncomplicated malaria (t = -15.57; p = 0.001. Conclusion: This study shows that C-reactive protein levels are increased in children with malaria, especially in severe malaria. Its estimation therefore holds potential usefulness as an adjunct for assessment of malarial severity.

Prediction of outcome of severe falciparum malaria in Koraput, Odisha, India: A hospital-based study.

Background and Objectives:Infection with Plasmodium falciparum, caused 627,000 deaths in 2012 in the world. P. falciparum infection causes myriads of clinical manifestations. Exact clinical manifestation resulting in poor prognosis in hyper-endemic epidemiological settings need to be ascertained to save human lives. A hospital-based study was conducted to elucidate the different severe clinical presentations of falciparum malaria and to examine the critical clinical and laboratory parameters on the prognosis of these severe manifestations in a stable hyper-endemic falciparum area in the state of Odisha, India.Materials and Methods:Consecutive patients admitted in a tertiary care hospital with severe manifestations of malaria as per WHO criteria and confirmed by parasitological examination were included in the study. A detailed clinical and biochemical parameters were examined. Clinical data were reviewed before being double entered into a computer and analyzed. Statistical analyses were carried out using Epi Info 6.04. Continuous and normal distributed data were compared by two-tailed Student's t-test and proportions compared with χ2 tests with Yates’ correction or Fisher's exact test.Results and Discussion:A total of 1320 patients with clinical malaria, diagnosed at outpatients’ department were admitted in the hospital during the 1 year study period of which, 292 (22.1%) were children under 14 years of age. The major clinical categories on admission were hyperpyrexia (70.7%), cerebral malaria (9.4%), malarial anemia (7.7%), algid malaria (1.5%), and malaria associated categories were respiratory infection (2.2%), hepatitis (2.0%), urinary tract infection (1.8%), enteric fever (3.3%), and sickle cell disease (1.2%). The overall case fatality rate (CFR) was 4.3 (57/1320). The CFR in children 12.3 (36/292) was significantly higher when compared to adults, that is, 2.0 (21/1028). The major causes of death were cerebral malaria (45.6%), malaria along with a respiratory infection (19.3%) and anemia (10.5%). Malarial anemia along sickle cell disease accounted for 19.3% of all malaria related deaths. Proportion of mortality due to acute renal failure was higher in adults. Biochemical parameters suggest involvement of multiple organs. The findings suggest that the area can be effectively managed by sustained and continuous preventive and curative efforts.

Anaemia and severe malarial anaemia burden in febrile Gabonese children: a nine-year health facility based survey

Anaemia remains a major cause of poor health in children and pregnant women living in sub-Saharan Africa. Malaria is one of the main causes of anaemia in endemic countries. At the time of decreasing Plasmodium falciparum infection prevalence among children, it was essential to analyze the evolution of anaemia and severe malarial anaemia (SMA), the most frequent clinical manifestation of severe malaria, in Gabon. Yearly recorded haemoglobin levels of febrile children aged below11 years, who benefitted from microscopic malaria diagnosis, were retrospectively analyzed to determine the evolution of anaemia and SMA prevalence throughout a nine-year period between 2000 and 2008. Anaemia prevalence remained high both in P. falciparum-infected children (between 87.6% and 90.7%) and in uninfected children (between 73.5% and 82.6%). Although the risk of developing severe anaemia ranged between 1.9 [0.9-3.8] in 2000 and 3.0 [1.3-6.5] in 2007, SMA prevalence did not significantly change during the study period, varying from 6.0% to 8.0%. From 2001, the frequency of SMA was comparable between children younger than five years of age and children older than five years of age. The decreasing malaria prevalence previously observed in Gabon between 2000 and 2008 was not associated with a significant reduction of anaemia and SMA burden among children. Furthermore, other factors such as nutritional deficiencies, which may not be negligible, must be investigated in this vulnerable population.

Manifestations of Severe Malaria among the Under-five Children Attending Kampala International University Teaching Hospital, Bushenyi, Western Uganda: Pilot Study

The clinical spectrum of severe malaria has not been described in Bushenyi, hence; this study was carried out to document the prevalence, major clinical features, contributing factors and immediate outcome of this number one killer disease of under-five children, at Kampala International University Teaching Hospital (KIUTH). This is a pilot study. Study design was retrospective; carried out in the records department of KIUTH; the study population were files of children, 5 years of age and below who attended KIUTH between August and October 2009, sample size was 100 using systematic random sampling. Ethical clearance and permission were obtained. Data was collected using checklist, entered into Epi-Info version 3.2 and analysed with SPSS 16 statistical software. Prevalence of complicated malaria was 29.8%. Male: female ratio was 1.33:1. Peak age was 3years, 78% of the children had no wasting and 62% slept under treated bed nets. The three most common presentations were febrile multiple convulsions (69%), hyperparasitemia (67%) and circulatory shock (59%), prolonged coma was the least presentation (30%). The infants most commonly present with severe anaemia (60%), while the older ones manifest usually with febrile multiple convulsions (76.9%). Mortality rate was 14%, higher in the malnourished (27.3%), boys (19.3%), age 5year bracket (23.1%), with hypoglycaemia (18.8%), respiratory distress (17.9%) and multiple febrile convulsions (17.4%). The prevalence and mortality from severe malaria was high. The most common presentations were multiple febrile convulsions, hyperparasitaemia and circulatory shock. Immediate outcome was significantly affected by the nutritional status. A larger study will be done in future for a more complete picture of this problem.