What kind of anemia does malaria cause

Emphasis was laid on the voluntary participation of the children in the study and on the point that their refusal to participate in the study will in no way affect the treatment quality the children were to receive. For each child a general clinical evaluation was carried out by the medical personnel in charge. Symptoms and the duration of the symptoms were recorded. Anthropometric parameters such as height and weight were measured using a measuring tape and a weighing scale, respectively.

A structured questionnaire was administered to parent or guardian of the child in order to obtain information on demography, socioeconomic status SES , type of accommodation, health-seeking behaviour, access to health facilities, malaria control measures, knowledge on the signs of anaemia, and feeding practices. The socioeconomic status was classified as poor, average, and rich as described by Kimbi et al.

Thin and thick blood films were prepared and the remaining blood sample dispensed into labelled ethylenediaminetetraacetate EDTA tubes. The thick and thin blood films prepared on glass slides at the time of blood sampling were stained with Giemsa and examined following standard protocols [ 24 ]. If gametocytes were seen, the count was extended to leukocytes [ 25 ]. Malarial anaemia MA was defined as children with a malaria-positive smear for P.

Continuous variables were summarized into means and standard deviations and categorical variables reported as frequencies and percentages were used to evaluate the descriptive statistics. Parasite density was log transformed before analysis. A multinomial logistic regression model analysis was conducted to evaluate potential determinants of M d SA and M d SMA with age, sex, SES, level of education, altitude, fever, and nutritional status as independent variables. The odd ratios OR computed was used to evaluate the risk factors.

The consent of children at presentation to the general outpatient department in the Regional Hospital Annex-Buea was sought for their participation in the study of the burden of malaria, M d SA, and M d SMA. As revealed in Table 1 , Majority of the children resided in the middle belt The proportion of mosquito bed net MBN use in the studied population was Fever, splenomegaly, malarial anaemia, and malnutrition were observed in The prevalence of anaemia in the studied population was The difference was statistically significant.

Wasting occurred in 6. While the prevalence of wasting was significantly higher in females Plasmodium falciparum occurred in The prevalence of malaria was highest in patients from the lowland A greater proportion of the children had high parasite densities In addition, the prevalence of malaria was significantly higher , in children with fever On the other hand, the high prevalence of malaria observed in malnourished children The prevalence of fever was highest in the month of July However, only the monthly difference in prevalence of MA was statistically significant ,.

The prevalence of anaemia as influenced by the morbid state is shown in Figure 4. Children with both fever and detectable malaria parasitaemia had a higher prevalence of anaemia Mild, moderate, and severe anaemia were prevalent in While the prevalence of M d SA and M d SMA was comparable amongst age group, gender, SES, family size, splenic, and nutritional status, and statistically significant differences were observed with the level of education of head of household , altitude of residence , and fever status and as shown in Table 2.

Explicitly, in comparison with their contemporaries, the prevalence of M d SA was significantly higher in children who came from homes where the head of household had no formal education On the other hand, M d SMA was significantly higher in children who had fever only The multinomial logistic regression model demonstrated that the altitude, more specifically the lowland , and being febrile were significant predictors of M d SA, while being febrile was the only significant factor associated with M d SMA as shown in Table 3.

The AR of anaemia caused by malaria in the studied population was 7. On the other hand, the AR of moderate to severe anaemia caused by malaria was 9. In addition, the AR of moderate to severe anaemia due to malaria was higher in children of the 11—14 years age group A nonsignificant negative trend was observed between platelet count and malaria parasitaemia ,. This cross-sectional study examines P.

The overall malaria parasite prevalence of The equatorial climate in the Mount Cameroon area is characterized by abundant rainfall and constant humidity, all of which are factors that favour intense and perennial transmission of the malaria parasite [ 2 ], which may be a contributing factor in the higher prevalence of malaria in spite of the intensification of control measures.

Against the backdrop of a decline, the increased prevalence of malaria parasite observed with age culminating in children of the 11—14 years age group having the highest prevalence Similar observation of a change in malaria morbidity following control measures had been reported earlier in the region [ 4 ].

While this trend may be linked to the effective use of mosquito bed nets observed in children of the 1—5 years age group when compared with the other age groups, the significantly higher prevalence of malaria in febrile children highlights fever as one of the symptoms characteristic of malaria infection.

Similar significant association between malaria and fever has been reported in the same region [ 5 , 30 ] even though fever may be a poor indicator of malaria where infection with other pathogens is possible [ 31 ]. Nevertheless the confirmed malaria case in febrile children The significantly higher prevalence of anaemia in feverish children compared to nonfeverish ones is in line with other studies [ 4 , 7 , 34 , 35 ].

Similarly, the significantly higher prevalence of anaemia in malaria-positive individuals is consistent with findings of several studies [ 34 , 36 , 37 ]. However, worthy of note, the This regional drop in prevalence of anaemia in children with malaria may be accredited to the sustained malaria control measures and its impact on the outcome measure.

More so, frequent research and sensitization campaigns carried out in this study area raise awareness on the condition. Observation from the study revealed no significant differences in the categorisation of anaemia severe, mild, and moderate when the various groups were compared. Hence, the moderate and severe groups of anaemia were lumped together for comparison with such other studies. However, the intention of the paper was to report on moderate to severe anaemia with or without malaria.

Findings revealed a Furthermore, the logistic regression analysis revealed febrile children were two times at odds of being moderate to severely anaemic than their afebrile counterparts.

This is not unusual as fever is not specific to infection with malaria parasite only but could be indicative of other anaemia-causing infections [ 38 ]. On the other hand, above secondary schooling may facilitate better feeding practices and habits gained through knowledge on nutritional composition of foods and health education.

The highest prevalence of M d SA observed in children who came from the lowland This cohort of children may have been exposed to the impact of repeated infections with malaria parasites even though they were negative at the time of examination. However, in a combination of factors in the logistic regression analysis, our findings revealed to a certain extent a significant protection against moderate to severe anaemia in children from the lowland.

The prevalence of M d SMA In the context of a decline in the prevalence of malaria in the region, the moderate prevalence of malarial anaemia Even though the study had as limitation the length of the period in which the investigation was carried out and the number of children examined, that notwithstanding, the investigation was carried out during the peak season of malaria transmission to ensure probability of encountering malaria parasite positive cases.

However, the contribution of malaria to the public health problem of anaemia should be interpreted with caution and further study in different ecological settings and a larger population should be carried out.

In conformity with Leite et al. The constraints of large family size may not only be the number of individuals to provide adequate diet in terms of nutrients and proportions, but the lack of resources to provide adequate health care such as providing appropriate malaria treatment. Delayed treatment-seeking and inappropriate medication, both of which are common among people in the Mount Cameroon area, have been reported earlier as risk factors of anaemia [ 7 ].

The low estimate of the risk of anaemia 7. Why females had a higher attributable risk of anaemia and moderate to severe anaemia due to malaria is unclear as no significant gender differences were observed in prevalence and density.

Even though studies on the attributable risk of anaemia and moderate to severe anaemia due to falciparum malaria have seldom been carried out in Cameroon, previous studies in the Mount Cameroon area, in apparently healthy children, revealed a moderate This process lowers the amount of red blood cells and can in a severe stage cause severe anemia.

Malaria, how is it treated? Malaria is an entirely preventable and treatable disease. HemoCue in relation to Malaria Patients with suspected malaria should have parasitological confirmation of diagnosis with either microscopy or rapid diagnostic test RDT before antimalarial treatment is started.

Hemoglobin testing in parallel with i. Coinfections with other parasites may increase SMA susceptibility as they aggravate malaria-associated inflammation. A normocytic and normochromic RBCs' morphologic appearance is a common presentation of anemia in malaria, which is characterized by the absence of spherocytes and schistocytes although there may be abundance of fragmentocytes and eliptocytes typifying increased hemolysis.

High frequencies of hemoglobinopathies and iron deficiencies in areas of high malarial prevalence may change the picture to microcytytosis and hypochromasia [ 15 ]. Severe malarial anemia displays inadequate reticulocytosis in the presence of the anemia signifying that there is reduced synthesis of RBC's and not just increased hemolysis. In malaria, hematocrit gradually decreases, after an apparent initial steady state even with the onset of fever, showing either an increase in reticulocytosis or an absence of hemolysis within the first 24 h after infection.

The decrease in hematocrit is independent of treatment initiation and may even occur in the absence of overt parasitemia on peripheral blood films, blood transfusion and adequate antimalarial treatment. These parasites continue to shed soluble antigens, hemoglobin metabolites and derivatives that drive various syndromes of malaria like SMA.

This may explain the continued decline in hematologic indices despite the evidently low parasitemia and the malarial anemia pathogenesis, which implicates bone marrow dysfunction as displayed by low reticulocytosis [ 16 , 17 ]. When Hb decreases, the normal body physiology upregulates the bone marrow erythroid progenitors and reticulocytes are increased as an indicator of this process.

Bone marrow suppression of the erythroid blast cells has been evidenced in children exposed to multiple reinfections, receiving inadequate treatment or experiencing treatment failure that tend to become asymptomatic during acute P.

Inadequate erythropoietin production or effectiveness, the effect of the inflammasome on erythropoiesis, concomitant parasitic and bacterial infections contribute to the complex milieu culminating in SMA as well.

Red blood cell membrane modifications by attached parasite ligands remodel the cells to a phenotype tagged for destruction through phagocytosis. Anemia is described as a decrease in Hb concentration, which is directly related to RBC's mass within the circulation. Infection with P. Cytoadherence of pRBC's to the microvasculature, rosetting and cell-cell agglutination are processes facilitated by several ligands of P. These ligands such as P.

Some of these ligands are necessary for the formation of the host cell-parasite connection, which allows invagination of the erythrocyte bilayer leading the parasite engulfed into the RBC. As a result, an intracellular parasite vacuole is formed and provides an environment for parasitic multiple stage growth.

During the process of parasite-protein-mediated internalization as well as during the intracellular proliferation, several other parasite proteins bearing a host-targeting HT or plasmodial expert element PEXEL are also exported into RBCs [ 22 , 23 ], providing a myriad of host cell-parasite communication paradigms. The ability of RBCs to change shape allows them to pass through the spleen filtration mechanisms. Infection in the cell membranes causes them to be more rigid and unable to change shape when passing through capillaries and become prone to phagocytosis and hemolysis.

Some of the exported parasite ligands adhere to the membranes of npRBCs. Parasite ligand deposition on npRBC's tags these cells and pRBCs for rapid reticuloendothelial system pooling and sequestration by the spleen, which removes them from circulation resulting in SMA.

Cytoadherence and auto-agglutination, emanating from the various ligand-epitope interactions, also removes a considerable amount of cells from circulation exacerbating SMA. However, such tagging only occurs on a subset of erythrocytes to account for the rapid setting of SMA encountered in malaria meaning that host cell-parasite ligand interactions along with other mechanisms play profound role in the creation of overt SMA.

The interaction between host cell and parasite ligands is a complex process of an inefficient invasion mechanism that may be completed in a small fraction of infection-targeted RBCs. As a result, many ligands need to be secreted and shed off into plasma resulting in many of these pRBC-adhesive proteins being present in high concentrations in plasma.

Subsequently, cells binding immunoglobulin Ig and complements are cleared from circulation through phagocytosis by macrophages and hemolysis. This results in a critical hemoglobin reduction.

These processes are repeated over and over again as the parasite intracellular cycle ends, concomitantly increasing the disease. Aberrant signaling circuits are also increased in the affected cells heralding their apparent need for removal from circulation by macrophages and exacerbating SMA. Parasite proteins in rhoptries and merozoites surface membranes are candidates associated with SMA development.

As these parasites are intracellular, they invade new cells for the continued propagations of more asexual and sexual forms.

To execute invasion, the parasite aligns its apical surface to the surface on RBCs. Rhoptries are structures protruding from the parasites. The merozoite uses the rhoptry proteins for anchoring on the surface of the RBC targeted for invasion.

During the invasion processes, merozoites use rhoptries, which are also secretory structures on the merozoites apical end, to release their contents at the junction between the parasite and the erythrocyte.

The P. The presence of these proteins on the surface of npRBCs is possibly a result of failed invasion or when they adhere to the surface of these cells, they shed off from the merozoites into the plasma. Proposed model of dysregulation in innate immune responses in severe malarial anemia. Based on concomitant measurement of innate inflammatory mediators using multiplex technologies in children with varying severities of malarial anemia, a model to describe how dysregulation in innate inflammatory mediators promotes suppression of erythropoiesis in children with SMA was developed.

Phagocytosis of hemozoin Pf Hz by monocytes causes of altered production of innate inflammatory mediators. Elevated inflammatory mediators are shown with an arrow facing up against text, those that are decreased in children with SMA are shown with arrow facing down. MIF is suppressed in children with falciparum malaria, which is associated with phagocytosis of Pf Hz by monocytes and enhanced SMA severity.

Reduced NO and reactive oxygen species ROS generation in children with falciparum malaria may promote ineffective parasite killing and, thereby, prolong parasitemia, and children with malarial anemia have elevated levels of NO and ROS that can directly inhibit erythropoiesis adapted from open access source: Perkins et al. The RSP-2 is transferred to the surface of the host cell around the site of contact with the merozoite. Gradually, the protein spreads over the entire surface of the cell by slow, lateral movements in both the npRBCs and pRBCs, leading to their premature identification and destruction by the reticuloendothelial system.

These changes are not observable by the light microscope as there are no obvious cell membrane morphologic abnormalities that have been noted. The subtle changes are due to oxidative damage of cell membranes, phosphatidylserine PS externalization or exposure and reduced deformability, which contribute to increased RBC's clearance leading to SMA.

The involvement of ligands in RBC's clearance is mediated through stimulation of the inflammasome and its role in erythropoiesis in malaria [ 27 ]. Despite massive RBC's destruction in malarial infection, there is also a delayed compensation of RBCs in overt anemic individuals due to defective erythropoiesis. Acute infection in children shows a picture of normal to small erythroid precursors in bone marrow BM.

There is considerable change noted on the erythroid cells morphology in malaria induced anaemia. These include multinucleated erythroid cells, karyorrhexis, incomplete or unequal mitotic divisions, intercytoplasmic bridges and cytoplasmic budding. A higher proportion of the erythroid progenitors are held in G 2 phase in SMA as compared with healthy individuals. RSP-2 has been observed to be transferred to erythroid precursors only when there has been a direct contact with merozoites, in vitro.

In vivo, these proteins are also known to be tagged to these cells [ 28 ]. Subsequently, erythroid precursors tagged with RSP-2 are destroyed through complement activation and cytokine oxidative stress linked apoptosis processes. Noteworthy is that colony-forming units CFU's and other stages of the erythroid lineage suffer the same fate in the presence of cytophilic antibodies accounting for their reduced numbers in SMA. The antibody-RSP-2 complex on the surface of erythroblasts triggers the decline of these cell lines through phagocytosis or morphologic alterations observed in erythroid cells in the BM and the mediators of this process are closely linked to the inflammasome in SMA.

RPI is a measure of the extent to which the reticulocyte count has risen or not in response to the level of anemia, which indicates that SMA is the result of erythroid suppression [ 30 ], arbitrated by inflammatory molecules. Concomitant erythroid hyperplasia and reduced RPI signifies a cellular maturation check point or bottleneck that is introduced in SMA. Inflammation is a process that tends to control the proliferation of hostile entities and foreign bodies when the physiologic aspect of the body is invaded by pathogens or when there is a physical injury at both macroscopic and microscopic levels.

The inflammasome is composed, among other mediators, of both pro-inflammatory cytokines typically denoted as T-helper cells type 1 Th1 and anti-inflammatory cytokines denoted as T-helper cells type 2 Th2 , which tend to counteract each other into a balance state under normal physiologic states. In falciparum malaria, anemia can develop rapidly due to profound hemolysis.

The degree of anemia correlates with parasitemia and schizontemia. It is also associated with high serum bilirubin and creatinine levels. Pregnancy, secondary bacterial infections and bleeding disorders like disseminated intravascular coagulation can aggravate the anemia. Children may have severe anemia even with low parasitemia and in such cases the reticuloendothelial cells exhibit abundant malarial pigments.

Anemia in malaria is multifactorial. The causes include obligatory destruction of red cells at merogony, accelerated destruction of non-parasitised red cells major contributor in anemia of severe malaria , bone marrow dysfunction that can persist for weeks, shortened red cell survival and increased splenic clearance. Massive gastrointestinal haemorrhage can also contribute to the anemia of malaria.