|Keywords (Extracted from title, table of contents and abstract of thesis)
tumor necrosis factor, biochemical changes, haematological profile, falciparum malaria, plasmodium falciparum, plasmodium vivax, falciparum malaria, sma groups, mma groups, smc groups, mmc groups, cm groups, plasma tnf α
To investigate the relationship of TNF α levels to P. falciparum infection, 1575 patients suspected to be suffering from malaria were examined. The slides of these patients were seen for the detection of malarial parasites. The slide positivity rate was found to be 48 percent. The predominant species infecting the people was Plasmodium falciparum (98.7%) while in 1.3% cases Plasmodium vivax was present. Out of these a total of 100 patients (74 adults and 26 children) were enrolled for further clinical and laboratory evaluations. All these subjects were identified to be suffering either from mild, severe, cerebral and chronic falciparum malaria and accordingly were divided into SMA, MMA, SMC, MMC and CM groups. Plasma TNF α concentrations were measured in all these patients as well as 25 healthy control subjects.
The mean plasma TNF α concentration in control group was 108.08 pg/ml. The mean TNF α level in SMA, MMA, SMC, MMC and CM groups were 373.85 pg/ml, 117.8 pg/ml, 356.2 pg/ml, 149.0 pg/ml and 206.3 pg/ml respectively. The difference in TNF α level between control group and SMA,SMC and CM groups was statistically significant (P < .001, P < .001 and P < 0.01 each respectively). Although the mean TNF α concentration in mild malaria groups (MMA and MMC) was higher than control group, the difference was statistically non significant.
The geometric mean plasma concentration of TNF α in SMA, MMA, SMC, MMC and CM groups was 234.2 pg/ml, 81.5 pg/ml, 239.6 pg/ml, 75.6 pg/ml and 134.9 pg/ml respectively. The TNF α levels were significantly higher in SMA and CM groups than MMA group (P <.001, P < 0.05) respectively. Although the TNF ex. concentration was higher in SMC than MMC group, the difference between the two groups was statistically non significant.
The TNF α levels were not correlated to parasite density, cerebral malaria, young age, or fatal outcome. However, TNF IX levels were associated with severe anemia, hypoglycemia and hepatic and kidney dysfunction. TNF levels were significantly elevated in chronic falciparum malaria patients.
The mean values of hemoglobin (13.95 g/dl) blood sugar (97.9 mg/dl). and serum albumin (5.4 g/dl) in control group were much higher. than the severe malaria (SMA. SMC and CM) groups and tlle difference between control and these groups was allnosl highly significant (P < .00 I). The difference in haemoglobin level and these biochcmicat parmneters between control group and mild malaria groups (MMA and MMC)/ was non significant.
The difference in blood sugar, bilirubin and ALT levels between SMA and MMA group was statistically significant (P < .001, P < .001 and P < .05 each, respectively). The difference in serum bilirubin levels between SMC and MMC group was also significant (P < .02). The difference in serum creatinine levels between CM and MMA group was also significant (P < .02).
This study showed that falciparum malaria was associated with a number of haematological changes like anaemia, leukocytosis, leukopenia, thrombocytopenia, elevation of fibrin degradation products and erythrocyte sedimentation rate. The TNF a. levels were not correlated to these haematological parameters except anaemia.
Forty one percent (41 %) cases of our enrolled patients had complicated falciparum malaria. TNF α. levels were independently elevated in patients with anaemia, hypoglycaemia and hepatic and kidney dysfunction. In this study ,high TNF α. levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria and hyperparasitaemia.
This study showed that plasmodium falciparum and vivax also invade the bone marrow, in endemic areas like Pakistan. The bone marrow reports of 1966 patients were retrospectively analysed during 39 months period from January 1992 to April 1995. The study showed that P.vivax malaria was not associated with any significant pathology in the bone marrow, except mild megaloblastic erythropoesis. The bone marrows with the P. falciparum malaria showed myeloid hyperplasia, erythroid hyperplasia, megaloblastosis and hypoplasia in different proportions. No evidence of dyserythropoesis was found in our series.