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   Table of Contents     
ORIGINAL ARTICLE  
Year : 2017  |  Volume : 9  |  Issue : 2  |  Page : 60-65
Analysis of the clinical profile in patients with Plasmodium falciparum malaria and its association with parasite density


1 Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
2 Department of Pathology, Mahaveer Institute of Medical Sciences and Research, Bhopal, Madhya Pradesh, India
3 Department of Biochemistry, Mahaveer Institute of Medical Sciences and Research, Bhopal, Madhya Pradesh, India
4 Department of Anatomy, Mahaveer Institute of Medical Sciences and Research, Bhopal, Madhya Pradesh, India
5 Department of Pharmacology, Veer Surendra Sai Medical College, Sambalpur, Odisha, India
6 Department of Pharmacology, Mahaveer Institute of Medical Sciences and Research, Bhopal, Madhya Pradesh, India

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Date of Web Publication24-May-2017
 

   Abstract 

Background: Malaria remains a major health hazard in the modern world, particularly in developing countries. In Plasmodium falciparum malaria, there is a direct correlation between asexual erythrocytic stage parasite density and disease severity. Accordingly, the correlations between parasite density and various clinical presentations, severity, and outcome were examined in falciparum malaria in India. Materials and Methods: The study was conducted in a tertiary health-care center in North India. Of 100 cases of falciparum malaria, 65 patients were male and 35 were female. A total of 54 patients were in the uncomplicated group and 46 patients were in the complicated malaria group. Results: Fever, anemia, icterus, splenomegaly, hepatomegaly, and hepatosplenomegaly were common clinical findings. All clinical findings were significantly more common in the complicated malaria group and patients with a high parasite density than in the uncomplicated group and those with a low parasite density. All patients in the uncomplicated malaria group had a parasite density of <5% while most patients in the complicated malaria group had a parasite density of >5%, and the difference between groups was statistically significant. The incidence of cerebral malaria was significantly higher in cases with a high parasite density; 58.33% mortality was observed in these cases. Cerebral malaria and hyperbilirubinemia was the most frequently encountered combination of complications. Conclusions: In P. falciparum malaria, parasite density was associated with complications and poor clinical outcomes. These results may inform treatment decisions and suggest that a threshold parasite density of 5% is informative.

Keywords: Malaria, parasite density, Plasmodium falciparum

How to cite this article:
Mangal P, Mittal S, Kachhawa K, Agrawal D, Rath B, Kumar S. Analysis of the clinical profile in patients with Plasmodium falciparum malaria and its association with parasite density. J Global Infect Dis 2017;9:60-5

How to cite this URL:
Mangal P, Mittal S, Kachhawa K, Agrawal D, Rath B, Kumar S. Analysis of the clinical profile in patients with Plasmodium falciparum malaria and its association with parasite density. J Global Infect Dis [serial online] 2017 [cited 2019 Oct 16];9:60-5. Available from: http://www.jgid.org/text.asp?2017/9/2/60/201626



   Introduction Top


Malaria remains, as it has been for centuries, one of the most serious parasitic diseases worldwide, affecting 300–500 million people and causing over 1 million deaths annually.[1]Plasmodium falciparum accounts for nearly 50% of reported malaria cases. The major endemic areas in India are in the Northeastern states. P. falciparum infection can lead to cerebral malaria, acute renal failure, acute malarial hepatitis, hypoglycemia, hyperpyrexia, noncardiogenic pulmonary edema, adult respiratory distress syndrome, adrenal insufficiency-like syndrome, hyperparasitemia, blackwater fever, cardiac arrhythmias, and gastrointestinal syndromes.[2],[3],[4] Typically, a higher parasite count is associated with a more severe infection [5] and increased mortality. Accordingly, correlations between P. falciparum density and various clinical presentations, complications, and outcome were examined in malaria patients.


   Materials and Methods Top


This open prospective study was conducted in the Department of Medicine in a tertiary healthcare center in North India. The study included 100 consecutive patients with P. falciparum malaria who were admitted to the department between June 2009 and May 2010. Adult patients of >18 years old, either male or female, presenting with fever, headache, body ache, and confirmed P. falciparum based on the detected of the asexual form of P. falciparum in a blood smear were included in the study. Those with a negative peripheral smear for P. falciparum, mixed plasmodium infection, or evidence of any coexisting morbid disorder that could affect the outcome, for example, diabetes mellitus, chronic renal disease, chronic liver disease, rheumatic heart disease, and coronary artery disease were excluded from the study.

Written consent was obtained from all patients. A detailed history was obtained, and a clinical examination was performed for all patients. Various parameters were investigated in all patients, including a complete blood count, peripheral blood smear (thin and thick), blood sugar, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, serum proteins, serum electrolytes, chest X-ray, and arterial blood gas, if needed. The parasite density was estimated by an experienced pathologist. All slides obtained for all patients were examined by the same pathologist to prevent observation error.

Microscope examination of blood films is the current gold standard for the diagnosis of malaria. Blood obtained by pricking a finger or earlobe is ideal because the density of developed trophozoites or schizonts is greater in blood from these capillary-rich areas. Both thick and thin smears were prepared separately for each patient. The blood films were air dried, and thin blood films were fixed with methanol. Blood films were stained with Field's/Giemsa stain. The initial thick smear was declared negative only if no malarial parasites were seen after the examination of a 100 × 1.25 oil immersion high-power field. After the detection of malarial parasites, thin smears were used to identify the parasite species. Parasite density was then estimated from the thin blood smears. All patients were followed in the hospital until recovery or death.

Parasite density was estimated as follows:

Parasite density = Number of parasitized RBCs × X/200 WBCs

Where X = Total WBC count/200; WBC: White blood cell; RBC: Red blood cell.

Parasite density was calculated as the % parasitemia. All patients were categorized into three groups based on parasite density as follows:

  1. Group A: Parasite density <5%
  2. Group B: Parasite density 5%–10%
  3. Group CL Parasite density >10%.


The parasite density was estimated daily for 3 days. Mean parasite density was calculated and used to estimate correlations with clinical manifestations, complications, and outcome in P. falciparum malaria patients.

Statistical analysis

Data were analyzed usingSPSS version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). Quantitative variables are described as mean ± standard deviation. Analyses of variance (Fisher's test) were performed to compare mean values among the groups of patients. The categorical data are presented as percentages and differences among groups were evaluated using Chi-square test of proportions. Differences in mean values between groups for two variable strata were evaluated using t-tests. A P < 0.05 was considered significant for all statistical analyses.


   Observations Top


A total of 100 patients with P. falciparum malaria who fulfilled the inclusion criteria were enrolled in the study. There were 65 males and 35 females. Blood films were observed for parasite species [Figure 1] and [Figure 2]. All cases of uncomplicated malaria had a parasite density of <5%. Most cases of complicated malaria had a parasite density of 5%–10%. The difference between groups was statistically significant [Table 1] and [Chart 1].
Figure 1: Ring form of Plasmodium falciparum (100×, Leishman stain)

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Figure 2: Gametocyte of Plasmodium falciparum (100×, Leishman stain)

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Table 1: Severity of Falciparum Malaria with Respect to Parasite Density

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Fever was the most common symptom and was present in all patients at the time of admission, irrespective of parasite density. Nausea and vomiting (66%), headache (62%), jaundice (22%), impaired consciousness (17%), oliguria or anuria (13%), and bleeding (4%) were also observed. Convulsions were not present in any case.

The impact of increasing parasite density on clinical disease parameters in the three groups is summarized in [Table 2] and [Chart 2]. Impaired consciousness and oliguria or anuria were more common in patients with a parasite density of >10% than in patients with lower parasite densities, and this difference was statistically significant. Hepatosplenomegaly and hypotension were significantly more common in patients with a parasite density of >10% than in the other groups [Table 3].
Table 2: Association between Parasite Density and Clinical Characteristics of 100 Studied Patients

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Table 3: Comparisons between Parasite Density and Laboratory Parameters of 100 Studied Patients

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The hemoglobin (Hb), platelets, serum total protein, serum albumin, and random blood sugar levels decreased as parasite density increased from <5% to >10%. Total leukocyte count, blood urea, serum creatinine, serum aspartate aminotransferase, and serum alanine aminotransferase increased as parasite density increased from <5% to >10% [Table 3].

Patients with P. falciparum malaria developed complications at a parasite count of >5%, and the severity of complications increased when the parasite count was >10%. The difference between groups was statistically significant [Table 4] and [Chart 3].
Table 4: Complications with Respect to Parasite Density

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Mortality was most commonly associated with cerebral malaria (58.33%), followed by hypotension (57.14%) [Table 5] and [Chart 4]. All patients who died had a parasite density of >10%. The majority of patients who died had cerebral malaria and hyperbilirubinemia as complications.
Table 5: Distribution of Complicated form of Falciparum Malaria with Mortality

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   Discussion Top


Infection with P. falciparum is more serious than infections with other malarial species owing to the high frequency of severe complications. In P. falciparum malaria, parasite density is directly correlated with the severity of clinical disease. Patients with high parasite counts have more severe and complicated courses.[6],[7]

In this study, the major symptoms observed were fever, followed by nausea and vomiting, headache, jaundice, cough, pain in the abdomen, impaired consciousness, and oliguria or anuria.

Shaikh et al.[8] reported fever in all patients, rigor in 96% of patients, and vomiting and headache in 62% of patients. Ali et al.[9] also observed fever in 100% of cases. Murthy et al.[6] reported fever with chills and rigor (98.10%), altered sensorium (48.10%), algid malaria (18.35%), and jaundice (27.12%).

In the present study, anemia was found in 58% of cases, hepatomegaly in 32% of cases, splenomegaly in 66% of cases, and hepatosplenomegaly in 27% of cases. Anemia results from accelerated RBC removal by the spleen, obligatory RBC destruction during parasite schizogony, and ineffective erythropoiesis. Enlargements of the liver and spleen result from the inflammatory response to plasmodia and are more severe in cases of P. falciparum infection.

Shaikh et al.[8] reported anemia in 58% of cases, disseminated intravascular coagulation in 4% of patients, hepatosplenomegaly in 20% of patients, and bacterial septicemia in 18% of patients. Murthy et al.[6] and Ali et al.[9] reported similar results, but Muddaiah and Prakash [10] reported anemia in 14.27% of cases.

The relationship between the severity of falciparum malaria and parasitemia is complex. In the present study, 68% of patients had a parasite density of <5% (Group A), 18% had a parasite density of 5%–10% (Group B), and 14% had a parasite density of >10% (Group C). All the uncomplicated malaria cases had a parasite density of <5% while most of the complicated malaria cases (32/46) had a parasite density of >5%. The difference between these groups was statistically significant.

As per WHO criteria, in the present study, out of 100 cases, 46 were complicated malaria. Among these 46 patients, 22 had hyperbilirubinemia (serum bilirubin >3 mg%), 12 had cerebral malaria, 7 had hypotension (systolic blood pressure <80 mmHg), 6 had acute renal failure, and 5 patients had severe anemia (Hb <5 mg%).

Cerebral malaria may be defined strictly as an unarousable coma (i.e., a nonpurposeful response or no response to a painful stimulus) in falciparum malaria. Cerebral malaria was present in 12 out of 46 cases (26.08%) of complicated malaria. All patients with cerebral malaria had a parasite density of >5%, and 9 out of 12 (75%) patients had a parasite density of >10%. This difference was statistically significant (P = 0.000). In total, 7 out of 12 patients (58.33%) with cerebral malaria in the study died. The mortality rate was highest in patients with cerebral malaria.

Murthy et al.[6] observed cerebral malaria in 45.56% of cases. Bajiya and Kochar [11] reported a mortality rate of 33.5% while Ahmad et al.[12] reported a mortality rate of 23%, which was similar to the results of our study.

Hyperbilirubinemia was found in 22 out of 100 cases in the study. These patients were in the complicated malaria group. No patient in the uncomplicated malaria group had serum bilirubin levels exceeding 3.0 mg%. The incidence of hyperbilirubinemia increased from 10.29% in Group A to 57.14% in Group C as parasite density increased from <5% to >10%. This difference between groups was statistically significant (P = 0.00096) [Table 3]. Seven out of 22 patients (58.33%) with hyperbilirubinemia died in the study.

Wasnik et al.[13] observed hyperbilirubinemia in 35% of patients while Muddaiah and Prakash [10] observed it in 14.73% of cases.

Thrombocytopenia is a common observation in falciparum malaria. Thrombocytopenia is thought to be caused by increased splenic sequestration, immune-mediated destruction, and shortened platelet survival. The degree of thrombocytopenia is associated with the severity of falciparum malaria. In the present study, the incidence of severe thrombocytopenia was significantly higher in the complicated malaria group than the uncomplicated malaria group (P = 0.000).

Wasnik et al.[13] observed thrombocytopenia in 46 (57.5%) patients while Ali et al.[9] reported thrombocytopenia in 95.65% of patients with a parasite density of >10% and 58.06% of patients with a parasite density of <5%.

P. falciparum malaria is one of the most common causes of acute renal failure in adults. In the present study, 92.64% (63 out of 68) of cases in the uncomplicated malaria group had serum creatinine levels of <1.5 mg/dL while only 62.5% (20 out of 32) in the complicated malaria group had serum creatinine levels of <1.5 mg%. This difference between groups was statistically significant (P = 0.0001). The occurrence of renal failure in cases of complicated falciparum malaria was also reported previously. Bajiya and Kochar [11] reported a high incidence (21.7%), and similar results were observed by Gopinathan and Subramanian,[14] Hazra et al.,[15] and Prakash et al.[16]

P. falciparum is the most dangerous form of malaria, with a mortality exceeding 20% depending on the degree of parasitemia and the development of complications. High parasitemia, even without complications, can lead to high mortality.

In the present study, an overall mortality of 10% was observed. All cases of mortality were in the complicated malaria group. No death occurred in the uncomplicated malaria group. All patients who died had a parasite density of >10%.


   Conclusions Top


The detection of P. falciparum in a peripheral smear can be used to diagnose malaria, but the assessment of the malaria parasite index helps determine the prognosis. It can serve as a good prognostic marker combined with other established factors. Owing to its low cost and effectiveness, the parasite index should be evaluated in all malaria patients. The results of study are consistent with those of previous studies. The parasite index of P. falciparum is a good prognostic marker.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
World Health Organization. World malaria situation in 1992. Wkly Epidemiol Rec 1994;69:309-32.  Back to cited text no. 1
    
2.
Kochar DK, Kochar SK, Agrawal RP, Sabir M, Nayak KC, Agrawal TD, et al. The changing spectrum of severe falciparum malaria: A clinical study from Bikaner (Northwest India). J Vector Borne Dis 2006;43:104-8.  Back to cited text no. 2
    
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Bhalli MA. P. falciparum malaria – A review of 120 cases. J Coll Physicians Surg Pak 2001;11:300-3.  Back to cited text no. 3
    
4.
Mohapatra MK. The natural history of complicated falciparum malaria – a prospective study. J Assoc Physicians India 2006;54:848-53.  Back to cited text no. 4
    
5.
Field JW, Niven JC. Anote on prognosis in relation to parasite count in acute sub tertian malaria. Trans R Soc Trop Med Hyg 1937;30:569-74.  Back to cited text no. 5
    
6.
Murthy GL, Sahay RK, Srinivasan VR, Upadhaya AC, Shantaram V, Gayatri K. Clinical profile of falciparum malaria in a tertiary care hospital. J Indian Med Assoc 2000;98:160-2, 169.  Back to cited text no. 6
    
7.
McElroy PD, Beier JC, Oster CN, Beadle C, Sherwood JA, Oloo AJ, et al. Predicting outcome in malaria: Correlation between rate of exposure to infected mosquitoes and level of Plasmodium falciparum parasitemia. Am J Trop Med Hyg 1994;51:523-32.  Back to cited text no. 7
    
8.
Shaikh MK, Lohana RK, Abbasi P, Gill FA, Devrajani BR, Shah SZ, et al. Clinical features and complications of Plasmodium falciparum malaria at Liaquet University Hospital Hyderabad. World Appl Sci J 2001;13:651-4.  Back to cited text no. 8
    
9.
Ali H, Ahsan T, Mahmood T, Bakht SF, Farooq MU, Ahmed N. Parasite density and the spectrum of clinical illness in falciparum malaria. J Coll Physicians Surg Pak 2008;18:362-8.  Back to cited text no. 9
    
10.
Muddaiah M, Prakash PS. A study of clinical profile of malaria in a tertiary referral centre in South Canara. J Vector Borne Dis 2006;43:29-33.  Back to cited text no. 10
    
11.
Bajiya HN, Kochar DK. Incidence and outcome of neurological sequelae in survivors of cerebral malaria. J Assoc Physicians India 1996;44:679-81.  Back to cited text no. 11
    
12.
Ahmad SH, Moonis R, Kidwai T, Khan TA, Khan HM, Shahab T. Cerebral malaria in children. Indian J Pediatr 1986;53:409-13.  Back to cited text no. 12
    
13.
Wasnik PN, Manohar TP, Humaney NR, Salkar HR. Study of clinical profile of falciparum malaria in a tertiary referral centre in Central India. J Assoc Physicians India 2012;60:33-6.  Back to cited text no. 13
    
14.
Gopinathan VP, Subramanian AR. Pernicious syndromes in Plasmodium infections. Med J Aust 1982;2:568-72.  Back to cited text no. 14
    
15.
Hazra BR, Chowdhury RS, Saha SK, Ghosh MB, Mazumder AK. Changing scenario of malaria: A study at Calcutta. Indian J Malariol 1998;35:111-6.  Back to cited text no. 15
    
16.
Prakash J, Gupta A, Kumar O, Rout SB, Malhotra V, Srivastava PK. Acute renal failure in falciparum malaria – Increasing prevalence in some areas of India – A need for awareness. Nephrol Dial Transplant 1996;11:2414-6.  Back to cited text no. 16
    

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Correspondence Address:
Praveen Mangal
Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-777X.201626

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