| Abstract|| |
Malaria is a disease of tropical regions and both types of plasmodia, i.e. Plasmodium falciparum and Plasmodium vivax, cause significant morbidity and mortality. P. vivax was thought to be benign and cause less morbidity and mortality. Many reports showed the devastating effect of vivax malaria too. We compared the clinical symptoms, laboratory markers, treatment and outcome of both the plasmodia. This is a retrospective analysis of 95 patients admitted to The Kidney Center, Karachi in a duration of 15 years (1997-2012); 45 patients with falciparum malaria and 50 patients with vivax malaria, and compared the clinical presentation, laboratory workup, treatment and outcome in both groups. The two groups constitute a mixed population of diabetes, chronic kidney disease (CKD) and hemodialysis patients. Both plasmodia have an equal clinical impact in terms of fever and rigors, anorexia, nausea, feeling of dyspnea, change in the mental status, changes in the urine color, diarrhea, volume depletion and pedal edema. However, patients with falciparum had significantly more vomiting (P = 0.02), oliguria (P = 0.003) and jaundice (P = 0.003). Laboratory parameters also showed a severe impact of falciparum, as there was more severe anemia and kidney and liver dysfunction. More patients were treated with dialysis and blood transfusion in the falciparum group. The outcome in the two groups was not significantly different in terms of death and days of hospitalization. Falciparum malaria has a higher clinical impact than the vivax malaria, but vivax is not as benign as it was once thought to be. It also has devastating effects on vulnerable populations like patients with CKD and diabetes.
|How to cite this article:|
Imtiaz S, Drohlia MF, Nasir K, Hussain M, Ahmad A. Morbidity and mortality associated with Plasmodium vivax and Plasmodium falciparum infection in a tertiary care kidney hospital. Saudi J Kidney Dis Transpl 2015;26:1169-76
|How to cite this URL:|
Imtiaz S, Drohlia MF, Nasir K, Hussain M, Ahmad A. Morbidity and mortality associated with Plasmodium vivax and Plasmodium falciparum infection in a tertiary care kidney hospital. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 Aug 3];26:1169-76. Available from: http://www.sjkdt.org/text.asp?2015/26/6/1169/168598
| Introduction|| |
The Eastern Mediterranean region ranked third after Africa and South East Asia in terms of burden of malaria, where 55% of the populations (295 million) live at risk with 38,000 deaths annually.  Pakistan has been categorized by the World Health Organization (WHO) in the group 3 (estimated burden of 1.5 million cases annually) countries of the WHO Eastern Mediterranean region along with Afghanistan, Djibouti, Somalia, South Sudan, Sudan and Yemen. These countries account for sharing 95% of the total regional malarial burden.  Malaria is no more confined only to tropical areas; the effect of international traveling and globalization has enabled malaria to reach the non-endemic places as well. 
Malaria with Plasmodium falciparum has momentous morbidity and mortality due to its novel pathogenesis,  as revealed in many reports. ,,,, On the other hand, Plasmodium vivax, so far considered benign and named "benign tertian malaria," seems to be no more benign because of the associated complications reported in the recent past. The vivax malaria is also linked with significant morbidity and mortality and is somehow difficult to eradicate. , Analogues to falciparum malaria, vivax is also shown to cause anemia,  thrombocytopenia,  acute lung injury, , cerebral malaria, , acute kidney injury,  malnutrition  and severe infection of such an extent that leads to multiple organ involvement. 
Most of these reports are anecdotal and are either case series or case reports. This research presents a comparison of clinical presentation, laboratory markers and outcome of both types of plasmodia.
| Subjects and Methods|| |
The study includes all the adult patients admitted to The Kidney Center, Karachi between a span of 15 years (1997-2012), with fever and other constitutional symptoms and diagnosed to have malaria on the peripheral blood smear stained with Giemsa and rapid diagnostic test of malaria (immunochromatographic test malaria). Those patients who were treated as out-patients for malaria and those who were found to have some other cause of fever as well were excluded from the study. Most of the patients referred to The Kidney Center were due to a combination of reduced urinary output, change in the color of urine, increase in urea and creatinine or any of the electrolyte and acid base abnormalities like hyponatremia, hyperkalemia and metabolic acidosis. The other laboratory tests performed included complete blood count, liver and kidney function tests, urinalysis and ultra-sound kidneys for all of the admitted patients, while chest X-ray for those who had difficulty in breathing or had clinical findings on the chest examination and LDH for those who had a significant drop in hemoglobin were proposed.
A total number of 102 patients were admitted, four (3.9%) of them were only positive on the immunochromatographic test and three (2.9%) patients had both falciparum and vivax on microscopy; seven (6.8%) patients were excluded and 95 patients were included in study. Of these 95 patients, falciparum was seen in 45 (47.4%) and vivax was seen in 50 (52.6%) patients. Both groups were equal in terms of age, gender and associated comorbid conditions like diabetes, hypertension and chronic kidney disease (CKD) [Table 1].
|Table 1: Comparison of patients characteristics and co-morbids in falciparum and vivax parasites.|
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The severity of malaria was judged by the WHO criteria, i.e. presence or absence or respiratory distress, spontaneous bleeding, coma, circulatory collapse, acidosis and renal failure.
All the patients were treated with Chloroquine, Quinine or Artemisinin-based combination therapy. Hemodialysis was performed for those who had acute indication on arrival, like pulmonary edema, metabolic acidosis, advanced uremia and hyperkalemia.
| Statistical analysis|| |
Data were entered and analyzed in SPSS v. 18. Mean ± standard deviation and median (interquartile range) were computed for quantitative variables. Categorical variables were described in terms of frequencies and percentages. Association of symptoms and co-treatments with two parasites was checked by the Chi-square test. Odds ratio with its 95% confidence interval were assessed for measuring the effect of the same. Symmetric and skewed biochemical markers were compared in two parasites, respectively, using the t test and the Mann-Whitney U test. Normality of the quantitative variables was computed via the Shapiro-Wilk's test. Significance of the results was set to be at least 5% type I error.
| Results|| |
The clinical impact and reported symptoms and observed signs were almost equal in both groups. There were no differences in fever and rigors, anorexia, nausea, feeling of dyspnea, change in the mental status, changes in the urine color, diarrhea, volume depletion and pedal edema. There was a significantly higher incidence of vomiting (P = 0.02), oliguria (P = 0.003) and jaundice (P = 0.003) in falciparum-infected patients [Table 2].
|Table 2: Comparison of clinical markers in falciparum and vivax parasites.|
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Similarly, the laboratory parameters showed a notable devastating effect of falciparum over vivax. There was a remarkable drop in hemoglobin (P <0.0001) along with high urea (P <0.0001), creatinine (P <0.0001) and serum glutamic pyruvic transaminase (SGPT) (P = 0.02). Patients with falciparum infestation had a higher incidence of hyperkalemia (P = 0.09), hyponatremia (P = 0.05), acidosis (P = 0.001) and microscopic hematuria (P = 0.03). The two groups were equally affected with low platelet and white cell count and there was no significant difference in terms of change in blood sugar levels and oxygen saturation. LDH was not checked in every patient; therefore, its significance does not reveal a true picture [Table 3].
|Table 3: Comparison of laboratory parameters in falciparum and vivax parasites.|
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Likewise, patients with falciparum malaria required more blood transfusions (P = 0.001), intravenous hydration (P = 0.001) and hemodialysis (P = 0.05). Amazingly, the duration of the hospital stay and outcome of the patients had no significant difference [Table 4].
|Table 4: Comparison of treatment characteristics in the falciparum and vivax parasites.|
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| Discussion|| |
The severity of malaria depends on the state of immunity of the effected person.  Besides immunity, the other important factor determining the morbidity and mortality is the effect of parasite of the human RBCs. The falciparum infects all stages of erythrocytes, which causes heavy parasitemia and severe breakdown of the RBCs as compared with other species of malaria, like vivax that infects only young RBCs. The pathophysiology of falciparum is unique, which makes it different and more dangerous from other types of plasmodia. The infected RBCs provoke a hemodynamic, immunologic and metabolic effect. 
The state of immunity plays an important role in severe manifestation of vivax malaria. Most of the reported patients with severe vivax malaria leading to organ damage were either children who did not develop immunity even in endemic areas , or persons who came from non-endemic areas. , Barcus et al discussed the demographic effect of severe fatal vivax and falciparum malaria in the Indonesian population and showed a significant effect of severe disease among young adults and those patients who came from non-endemic areas where they suffered less exposure precluding development of protective immunity. 
Because this is a retrospective analysis, we cannot comment on the effect of demography on patient outcome, but one thing of note is that almost one-third of our patients were either diabetic or with CKD, who are well known to have a compromised immune status. This might be the reason for the relatively high morbidity and mortality even in this small group.
The symptomatology of either infection was not different from each other and both groups were equal in terms of fever, anorexia and nausea. Later on, most of the patients from the falciparum group developed jaundice and decrease in urinary output. This sequence of symptoms could be explained by the pathophysiology of falciparum infection causing more hemolysis leading to a higher frequency of hepatic and renal dysfunction.
Furthermore, the laboratory parameters also directed toward the severity of the falciparum malaria as compared with the vivax malaria. The clinical and laboratory parameters indicating severity of the malaria is defined by the WHO severity index of malaria. According to these criteria, the severity and complications of malaria can be assessed by the presence or absence of ten defining clinical or laboratory criteria, supported by five additional non-defining criteria. The defining criteria include coma, severe malarial anemia, respiratory distress, hypoglycemia, circulatory collapse, renal failure, spontaneous bleeding, repeated convulsions, acidosis and hemoglobinuria while supporting criteria include impaired consciousness, jaundice, prostration, hyperpyrexia and hyperparasitemia.
In our patients, both groups were equal in terms of respiratory distress, hypoglycemia, spontaneous bleeding, convulsion, impaired consciousness, jaundice and hyperpyrexia. However, the impetus of severe disease was toward falciparum malaria as there was a significant drop of hemoglobin along with renal and hepatic dysfunction, electrolyte abnormalities and acidosis [Table 4].
The outcome of both groups in terms of recovery, hospital stay and death was not significantly different, although most of the patients from the falciparum group required blood transfusions and intravenous hydration. More patients in the Falciparum group required hemodialysis, but the difference did not reach a significant level. In the falciparum group, 18 patients were dialyzed, six were those who were on maintenance hemodialysis while the remaining 12 developed acute kidney injury, while in the vivax group 11 patients were dialyzed, five were those who were on maintenance dialysis and the remaining were those who developed acute kidney injury.
There were more deaths in the falciparum group. Four of seven patients died due to acute kidney injury while one patient had end-stage renal disease (ESRD), one had CKD but died before dialysis and one had a non-renal death due to disseminated intravascular coagulation DIC. In the vivax group, three patients died, one was diabetic, one had CKD and one had ESRD. All patients who developed acute kidney injury recovered completely, and all patients who were on HD also recovered from the malarial insult, except one. However, it is difficult to make any inference from the mortality due to few deaths in both groups, but all patients who died in the vivax group had comorbid conditions and healthy patients recovered completely, while most of the deaths in the falciparum group were among those who developed acute kidney injury.
In summary, both types of plasmodia have significant morbidity. Although patients with falciparum developed more severe disease, the outcome was not much different in the two groups. Vivax has this effect on vulnerable populations, especially diabetics and patients with CKD.
| Acknowledgment|| |
The authors acknowledge Mr. Mohammad Zafar, Mr. M. Ali Qureshi and Dr. Beena Salman for their help in preparing and arranging this manuscript.
Conflict of interest: None declared.
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Department of Nephrology, Dorab Patel Post Graduate Training and Research Center, The Kidney Center Post Graduate Training Institute, Karachi
[Table 1], [Table 2], [Table 3], [Table 4]