Determining The Serum Protein Levels And CIC Level In Cerebral Malaria Patients

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Determining The Serum Protein Levels And CIC Level In Cerebral Malaria Patients


Chapter One


1.0 Introduction

Malaria is a febrile illness characterized by fever and related symptoms (WHO, 1990). It is a disease caused by a blood borne protozoan parasite which is an intracellular parasite belonging to the class Sporozoa and of the genus Plasmodium and it is transmitted through the bite of an infected female anopheles mosquito (CDC, 2002). There are four different parasites of this genus which may give rise to malaria in man. Malaria is probably one of the oldest diseases known to mankind that has profound impact on our history. History of malaria and its terrible effects is as ancient as the history of civilization, therefore history of mankind itself (Ray et al., 1992). This ancient disease is still the scourge of the tropic and subtropics Africa, the Middle East, Asia and China and Central and South America are all endemic zones with tens of Ilion cases annually (Lucas, 1992).

Plasmodium falciparum is one of the genus and cause the most ere and virulent form of the disease and the only one to cause acute ality. In this study Plasmodium falciparum will be on focus since it is most prevalent in Nigeria. This genus of malaria spend a part of their cycle in the red cell of the host where the erythrocyticschizogony. They develop into merozoites and undergo a cycle producing schizonts. Each cycle terminates when the red cell rupture releasing merozoites into the circulation to infect new red cells eliciting an immune response. Malaria infection leads to the formation of circulating immune complexes (Mibeiet al., 2005).

The importance of circulating immune complexes (CIC) and their relationship to various diseases has been the subject of investigation for number of years. Formation of immune complexes is a protective, on-going and usually benign process of a normally functioning immune system. However, in some individual CIC are deposited in the walls of blood vessels, especially in the glomerular capillaries where they cause tissue damage. The biospecific binding between sites of the antibody and the determinant group of the antigen result in the formation of antigen-antibody complex (AgAb) known as immune complexes (McDougal and McDuffie, 1985). Since malaria has been known to cause mortality this study is aimed at assessing the magnitude of circulating immune Complexes and some biochemical parameters which include serum total rein, albumin and globulin.


1.1 Justification

The science of immunology have suggested the use of CIC to measure variety of clinically oriented condition, this current studies ,suggest that CIC determination can be important in the evaluation of in disease and sometimes in monitoring the efficiency of therapy. Studies have suggested that plasma protein pattern is frequently abnormal in patients with acute malaria and disturbance in immune responses makes the disease a major cause of morbidity and mortality in patients with malaria. There is therefore need to determine CIC and serum proteins in patients suffering from malaria with a view to understand the pathology of the infection.


1.2 Objectives of this Study

This study is aimed at:

  1. Determining the serum protein levels and CIC level in cerebral malaria patients, those currently on treatments, severe malaria and apparently healthy individuals.
  2. Comparing the level among the different groups studied. Making recommendations based on the results obtained and use of CIC in the diagnosis of malaria.
  3. Making recommendations based on the results obtained and use of CIC in the diagnosis of malaria.

Chapter Five


5.0 Discussion and Conclusion

5.1 Discussion

Immune complexes formation is the normal consequence of an immune response to an antigen and low levels of circulating immune complexes occur transiently in normal individual without producing tissue injury. However, in some individual circulating immune complexes are deposited at the walls of blood vessels, especially in the glomerular capillaries where they cause tissue damage (Whaley, 1992).

Table 1 showed that the mean serum CIC level in different malaria patients is higher than that of apparently healthy individual although this value lies within the normal range. This observation is however in conformity with the earlier work of Erick et al., (2005). Similarly, according to Adam et al., (1981), cerebral malaria are associated with high level of serum circulating immune complexes most of which are always presented with some clinical features like neurological symptoms (Stupor, delirium, light coma, meningeal symptoms and deep coma), renal failure and anaemia due to the destruction of erythrocyte by the plasmodia. In addition, the other malaria patients showed a significant ise of serum CIC level, these values are statistically significant when ompared with apparently healthy individual.

Imman, (1981) reported a significant elevation of CIC in apparently healthy individual, this fact is however confirmed in this work. However, these were not as high as those of cerebral malaria, severe malaria patient and malaria patients on treatment. This suggests that the presence of immune complexes does not prove its pathogenicity, as such many variables are taken into account while interpreting the concentration of CIC (Imman, 1981). He also reported that methods presently available do not distinguish between complexes related to specific diseases and thus formed in other more common conditions, e.g. Viral infections It is therefore not surprising that circulating AgAb complexes are also formed in some apparently healthy subjects. However, the general picture of our finding still indicates the detection of elevated concentration of CIC in severe malaria patients on treatment. Despite this treatment, some antimalaria (sulfadoxine) is known to aggravate the serum CIC concentration (Adam et al., 1981).

Increased level of CIC could also be due to an increased rate of production or decrease rate of clearance of the formed complexes (McDougal and McDuffie, 1985). The clearance of AgAb complexes is mainly by the reticuloendothelial system taking place primarily in the liver and spleen. The former is mediated predominantly by C3b receptors, while the latter by FC receptors (Hakestand and Mannok, 1974). At the cellular level, immune complexes are cleared by macrophages.

Rheumatoid factors enhance binding of immune complexes to macrophages whereas compliment promotes the ingestion of the complexes (Vansnick and Mason, 1978).

The immunological consequence of immune complexes formation reflects a balance between effects that are detrimental and those that are useful to the body (Inman, 1981). The multi effect of complement activation by circulating AgAb complexes include increased vascular permeability release of hydrolytic enzyme from polymorphonuclear leucocyte attack of cellular membranes. Large immune complexes can cause inhibition of antibody-dependent cell mediated cytotoxicity (Aspice et al., 1977). Regulation of immune response by immune complexes may also occur by the blockage of antigen reactive B-cell in which immune complexes binding to Fc receptor causes selective inhibition of antibody formation by blocking antigen receptor (Oberbarnsheidt and Kolsch, 1978).

However, the presence of immune complexes does not suggest pathogenicity but considerable evidence has been gathered to implicate immune complexes in the presence of joint inflammation and destruction (Inman, 1981). Caution should be taken when interpreting the result of CIC concentration. This caution should include the type of malaria, the different types of treatment, the time of diagnosis, the degree of metabolic control and severity of complications. Moreover, due to the variability of these complexes, several test methods may be used as most immune assay has not yet been standardized (McDougal and McDuffie, 1985).

Studies have showed that the serum or plasma protein in malaria have shown that there is a depression of albumin and a relative rise of globulin following paroxysm (Gosh and Sinton, 1935). However, from table II, III, IV and figure I which shows the total protein, albumin, globulin and the mean (SD) concentration respectively. The results obtained from this studies is slightly different from the classical protein pattern in malaria as earlier reviewed (Gosh and Sinton, 1935). Although the total protein concentration remain within the normal range, the albumin are also within the normal range. But the globulin were slightly elevated.

According to Philip, (1971), total protein estimation is of clinical value. Acute changes in concentration, like those of all proteins, reflect the ratio of protein to fluid in the vascular compartment. As in the case of sodium, acute changes are more likely to be due to loss from or gain by the vascular compartment of protein free fluid. In this present study, serum total are within normal range although the value are limited.

Serum albumin concentration in this present study was shown to be within the normal range although slightly lower in malaria patient on treatment. Alteration in albumin haemostasis in the vascular and fluid compartment ar not too consistent (Adam et al., 1973).

The globulin level, in this work are generally significant in cerebral malaria and severe malaria when compared with that of apparently healthy individual. Surveys of serum protein patterns in different population have shown that some communities have a higher mean concentration gama-globulin than others (Van Oye and Charles, 1951; Holmes, Stanier, Semambo, and Jones, 1951; Arens and Brock, 1954; Vera and Roche, 1956; Edozien, 1957). Race, nutrition and immune antibody response to certain endemic. Infections are some of the factors which are thought to be significant in producing these differences. Of the endemic disease, malaria has been the most frequently associated with high serum globulin. From this current study, cerebral malaria patients are infants and are from communities where there is an imbalance in nutritional status. Hence with treatment this pattern in total protein, albumin and globulin tend to return to normal.


5.2 Conclusion

The result shows a significant increase in serum protein and albumin concentration in patients with cerebral malaria and severe malaria patients on treatment. The CIC of the different types of malaria increased significantly as compared to apparently individual.

Consequently, the determination of these parameters may serve as a diagnostic value in the immune related diseases.


5.3 Recommendation

We propose the integration of some of these parameters in routine malaria care investigation, so as to guide against complications associated with them. This of course will further strengthen our health care delivery system and allow patients with this disease to have more data at their disposal, so as to closely monitor their state of health.
However, further work should be carried out on a large population; so as to have a standardized reference range for this parameter (CIC).


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