|Year : 2019 | Volume
| Issue : 4 | Page : 360-366
Comparative assessment of clinic-laboratory profile of different species of severe malaria in a tertiary care institute in southern India
Thomas Kuncheria1, Nithyananda K Chowta1, Deepak Madi1, Mukta N Chowta2, A Basavaprabhu1
1 Department of Medicine, Kasturba Medical College, Mangalore, Manipal Academey of Higher Education, Manipal, Karnataka, India
2 Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academey of Higher Education, Manipal, Karnataka, India
|Date of Submission||25-Jul-2018|
|Date of Acceptance||05-Apr-2019|
|Date of Web Publication||30-Nov-2020|
Dr. Mukta N Chowta
Department of Medicine, Kasturba Medical College, Mangalore, Manipal Academey of Higher Education, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Background & objectives: Majority of the studies on severe malaria in India have concentrated on falciparum and have been done in northern part. The objective of the study was to compare the clinical spectrum and laboratory profile among severe Plasmodium vivax, P. falciparum and mixed malaria patients admitted at a tertiary care center in southern India.
Methods: This prospective, observational study was done in adult patients with severe malaria hospitalized in a tertiary care centre in southern India. Malaria was diagnosed by either quantitative buffy coat test or peripheral blood smear. In the cases of P. vivax malaria, an antigen detection test was done to rule out coexistent falciparum infection. Severe malaria was defined as per the WHO guidelines. The malaria severity score (MSS) was calculated for all patients based on the clinical features and laboratory parameters.
Results: A total of 204 cases of severe malaria were studied. Among them, 105 (51.5%) had vivax infection, 30 (14.7%) had falciparum and 69 (33.8%) patients had mixed malaria. The mean age of the study population was 39.8±15.7 yr. The majority were males (71.6%). Hypotension and prostration were the most common complications noted in the patients, irrespective of species. The maximum mean MSS was found to be highest in falciparum malaria, followed by mixed malaria and vivax. In vivax malaria, majority of patients (71.4%) had one or two complications and only 28.57% of patients had three more complications, whereas in falciparum malaria, the majority (53.33%) had three or more complications. Around 44.93% of mixed infection malaria patients had three or more complications. The number of patients with multi-organ dysfunction (>2 complications) was significantly more in patients with falciparum infections compared to the remaining patients.
Interpretation & conclusion: Severe malaria in south India is predominantly due to vivax. Hypotension and prostration were the most common complication of severe malaria irrespective of the plasmodium species. The entire spectrum of severe malaria complications described for falciparum are seen in severe vivax malaria.
Keywords: Mixed malaria; Plasmodium falciparum; P. vivax; severe malaria; south India
|How to cite this article:|
Kuncheria T, Chowta NK, Madi D, Chowta MN, Basavaprabhu A. Comparative assessment of clinic-laboratory profile of different species of severe malaria in a tertiary care institute in southern India. J Vector Borne Dis 2019;56:360-6
|How to cite this URL:|
Kuncheria T, Chowta NK, Madi D, Chowta MN, Basavaprabhu A. Comparative assessment of clinic-laboratory profile of different species of severe malaria in a tertiary care institute in southern India. J Vector Borne Dis [serial online] 2019 [cited 2021 Jul 23];56:360-6. Available from: https://www.jvbd.org/text.asp?2019/56/4/360/302040
| Introduction|| |
Malaria remains to be one of the causes as well as the consequence of poverty. Globally, there were about 216 million estimated cases of malaria and 4,45,000 deaths due to malaria in 2016. There was an increase of about 5 million cases of malaria over 2015. India had 13 million estimated cases and 331 reported deaths due to malaria in 2016 (Estimated deaths 23,990).
The clinical spectrum of malaria ranges from mild or uncomplicated malaria to severe malaria. Patients with uncomplicated malaria generally present with fever associated symptoms like headache, vomiting etc. Whereas in severe malaria, clinical features and laboratory parameters are suggestive of major organ dysfunction. Over the years the spectrum of severe malaria in India has changed. Definitions of severe malaria have changed in the last decade. Studies have used the old WHO definition to classify severe malaria,,. There is hardly any data documenting severe malaria from south India using 2012 WHO guidelines.
It was thought earlier that vivax malaria is having a benign course. However, the recent studies have shown that typical complications which were seen in falciparum malaria are also observed in vivax malaria,,. The risk of severe vivax malaria is found to be maximum among children and patients with other comorbidities.
It is necessary to describe the spectrum of severe malaria from various parts of India for health policy and research purpose. Majority of the studies on severe malaria have concentrated on falciparum, and most of these studies on severe malaria are from north and central India,,. This study was planned with the objective of comparing the clinical spectrum and laboratory profile among severe Plasmodium vivax, P. falciparum and mixed malaria patients admitted at a tertiary care centre.
| Material & Methods|| |
This prospective, observational study was done in the private hospitals attached to Kasturba Medical College, Mangalore, which is a tertiary care referral hospital in southern India.The study was conducted from September 2014 to September 2016 after the approval of the study protocol. All the patients (age >18 yr) with severe malaria hospitalized during the study period were included. Patients with other infections (typhoid, dengue fever, seizure disorder, chronic renal failure, congenital hyperbilirubinemia, anaemia and patients receiving chemotherapy were excluded. After obtaining informed consent, patients were evaluated clinically and investigated for features of severe malaria. Malaria was diagnosed by either quantitative buffy coat test (QBC) or peripheral blood smear. In cases of P. vivax malaria, an antigen detection test was done to rule out coexistent falciparum infection (Falcivax test). Severe malaria was defined as per the WHO 2012 guidelines. Demographic details, clinical features, haematological and biochemical investigations were recorded from the hospital records. All the patients were managed by the clinicians as per national guidelines. Malaria severity score was calculated for all patients for assessing the severity of disease and to predict the risk of severe malaria. The severity score is calculated based on the clinical features and laboratory parameters.
Severe malaria was defined as one or more of the followings, occurring in the absence of an identified alternative cause. The features of severe malaria as per WHO guidelines include:
- Impairment of consciousness or unarousable coma: Glasgow coma score <11.
- Prostration, i.e. generalized weakness rendering a patient to be unable to sit, stand or walk without help.
- Multiple convulsions; >2 episodes within 24 h.
- Deep breathing and respiratory distress; acidotic breathing.
- Acute pulmonary oedema (radiologically confirmed) or acute respiratory distress syndrome.
- Circulatory collapse or shock; systolic BP<80 mm Hg in adults.
- Abnormal bleeding, including recurrent bleeding or prolonged bleeding from the nose, gums or venipunc- ture sites; haematemesis or melaena.
- Hypoglycemia (<2.2 mmol/l).
- Metabolic acidosis (plasma bicarbonate <15 mmol/l).
- Severe normocytic anaemia (in adults Hb <4.34 mmol/L, packed cell volume <20%).
- Jaundice (serum bilirubin >51.3 μmol/l).
- Renal Impairment (serum creatinine >51.3 (imol/l).
Data collected were analysed using SPSS Version 11.5. Qualitative data is presented in the form of frequency and percentage whereas quantitative data expressed as a mean ± standard deviation.The categorical variables were compared using the chi-square test. Malaria severity scores were compared between the groups using the Mann Whitney test. A p-value of <0.05 indicates statistical significance.
Ethical statment: The study protocol was approved by the Institutional Ethics Committee (IEC) of the Kasturba Medical College, Mangalore (No. KMC MLR 09-14/175). Patients were included after obtaining written informed consent.
| Results|| |
A total of 204 cases of severe malaria were studied. Among them, 105 (51.5%) had vivax infection, 30 (14.7%) had falciparum and 69 (33.8%) patients had mixed malaria. The mean age was 39.8±15.7 yr, being 43.9±16.5 yr in females and 39.2±15.6 yr in males. The age of patients ranged from 18-70 yr, a majority belonging to <50 yr ([Table 1], p <0.05). There are no significant differences in the distribution of patients based on age among different species of plasmodia [Table 1]. The male: female ratio for P. vivax, P. falciparum and mixed infections were 74: 31, 22: 8 and 50:19 respectively, with a majority of patients being males (71.6%).
The presence of complications in P. vivax, P. falciparum and mixed infections are described in [Table 2]. Hypotension was the most common complication noted in the patients. The mean systolic blood pressure was 76.16±4.9 mmHg and the mean diastolic blood pressure was 55.13±6.47 mmHg. The hypotension improved with IV fluids in 161 patients whereas the remaining 17 patients required inotropes.
|Table 2: The distribution of complications in P. vivax, P. falciparum and mixed infections|
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Jaundice with vital organ dysfunction was seen in 83 patients. Conjugated hyperbilirubinemia was predominantly seen in these patients. The mean total bilirubin among these patients was 4.63±2.12 mg/dl and the mean direct bilirubin was 3.29±2.0 mg/dl.
Bleeding manifestations in the form of haematuria or bleeding gums were seen in 42 patients. All these patients had thrombocytopenia and the mean platelet count of these patients was 27357± 18217.95 cells/mm. All these patients with bleeding manifestations and platelet count <20,000 received a platelet transfusion.
Acute respiratory distress syndrome (ARDS) was noted in 17 patients of vivax and mixed malaria. Patients with falciparum infection did not have ARDS. The difference between the groups was statistically significant (p = 0.038). Out ofthese 17 patients, 12 were treated with non-invasive ventilation under ICU care while five patients required invasive ventilation. All these five patients expired during the course of hospital stay.
Renal failure was significantly more common in falciparum and mixed malaria (p = 0.001). Also comparison between falciparum and vivax groups showed statistical significance, being more in falciparum group (p = 0.001 among all three groups, p = 0.0004 for vivax vs. falciparum, [Table 3]). The mean serum creatinine level in patients with renal failure was 3.69±0.92mg/dl.
|Table 3: Distribution of severe malaria patients based on the number of complications|
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A total of 28 patients had anaemia. The mean haemoglobin level in these patients with anaemia was 6.82±0.34g%. Peripheral smear of these patients showed normocytic anaemia and all of the received packed RBC transfusion.
The degree of severity of malaria was quantitatively assessed in all patients using the malaria severity score (MSS). The mean MSS was found to be highest in falciparum malaria (4.17±1.95), followed by mixed malaria (3.9±2.72) and vivax (2.98±1.8). In vivax malaria, four patients had MSS >6 ([Figure 1]; 7 in one patient, 8 in two patients and 11 in one patient) whereas in falciparum malaria 2 patients had MSS >6 ([Figure 2]; 7 in one patient, 10 in 1 patient) and in mixed infection 12 patients had MSS >6 ([Figure 3]; 7 in four patients, 8 in two patients,11 in two patients and 12 in one patient). The difference between the three groups with regard to MSS score was statistically significant (p = 0.005, Mann-Whitney test).
|Figure 1: Histogram showing malaria severity score (MSS) in cases of severe vivax malaria (n = 105; mean = 2.98; SD = 1.797).|
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|Figure 2: Histogram showing malaria severity score (MSS) in cases of severe falciparum malaria (n = 30; mean = 4.17; SD = 1.949).|
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|Figure 3: Histogram showing malaria severity score in cases of severe mixed malaria (n = 69; mean = 3.9; SD= 2.718).|
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[Table 3] shows the distribution of severe malaria patients based on the number of complications. In vivax malaria, a majority of patients had one or two complications (71.4%) and only 28.57% of patients had >3 complications whereas in falciparum malaria, a majority had >3 complications (53.33%). Around 44.93% of mixed infection malaria patients had >3 complications. The number of patients with multi-organ dysfunction (>2 complications) was significantly more in patients with falciparum infections compared to the remaining patients (p = 0.015 among all three groups,p = 0.02 for vivax vs. falciparum, [Table 3]).
[Table 4] shows the comparison of clinic-laboratory profile among patients with different species of malaria. Diastolic blood pressure was significantly lower in patients with vivax and mixed malaria compared to those with falciparum malaria (p = 0.04). Serum creatinine level was significantly higher in patients with falciparum and mixed malaria compared to those with vivax malaria (p = 0.001 for P. vivax vs. P. falciparum, p = 0.017 for P. vivax vs. mixed malaria).
|Table 4: Comparison of clinic-laboratory profile among patients infected with different species of malaria|
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Six patients included in the study died during the course of hospital stay, i.e. mortality was 2.94%. Of these. two patients were suffering from vivax malaria, while the remaining four had mixed malaria. All these patients had multi-organ dysfunction. The mean MSS among these six patients was found to be 10.17±1.72 whereas in the remaining patients (alive) MSS was 3.27±1.92. This difference between the two groups was statistically significant (p = 0.001, Mann-Whitney test).
| Discussion|| |
Malaria is one of the common causes of mortality and morbidity in India. The presentation of complicated malaria is variable and mimics that of many other illnesses. The present hospital-based study compares the clinical and relevant laboratory spectrum among severe P. vivax, P. falciparum and mixed malaria patients. The pattern of complications among these patients was also analysed.
As observed by other studies, we too noted that mainly young and middle-aged patients were affected by malaria. Males were more commonly affected than females, as noted in earlier studies,.
This study showed that a little more than 50% of total cases of severe malaria admitted in the tertiary care center were having P. vivax malaria, indicating the non-benign nature of P. vivax malaria. This observation is similar to the studies done by Jadhav et al and Erhart et al. Many other studies done within and outside India also indicated the severe nature of vivax malaria,,,. Nandwani et al studied the manifestations of severe mlalaria in 160 patients of western Uttar Pradesh and reported that patients infected with P. vivax also present with manifestations of severe malaria like serum bilirubin >3 mg/dl, serum creatinine >3 mg/dl, severe anaemia (haemoglobin <5 mg/dl), acute kidney injury, metabolic injury, shock, generalized tonic-clonic convulsions and hypoglycemia.
A recent study conducted in Mangalore by Gai et al, showed that severe malaria was rare and seen in 3.5% of malaria patients. They have also reported that parasite species did not significantly affect the proportion of severe malaria. As our study included patients of severe malaria only, we could not assess the prevalence rate of severe malaria among patients tested positive for ma- laria. Another study conducted in south India showed the prevalence of severe P. vivax as 23.9% (122/511). In the study conducted by Kocher et al, it was found that patients with severe vivax and severe mixed infections had similar phenotypic features as in cases of severe isolated falciparum malaria.The exact reason behind the pathophysiology of complicated vivax malaria is not fully understood. Sequestration is not considered to play a role in the pathogenesis of severe vivax malaria as in the case of falciparum malaria. Plasmodium vivax infections are thought to cause a greater inflammatory response with a marked increase in the plasma levels IFN-y and TNF,.
As observed in this study, the complications in severe malaria in the decreasing order of frequency are hypotension, prostration, jaundice, renal failure, bleeding manifestations, anaemia, ARDS and cerebral malaria. The study done at Vellore (south India) by Mitra et al showed jaundice (total bilirubin >3 mg/dl) and acidosis (bicarbonate < 15 mEq/dl) as the main manifestations of severe malaria. A study done in Sudan also described hypotension as the most common complication in severe malaria of hypotension, although the frequency of hypotension was much lesser compared to our study (87.3 vs. 27.3%). This study reported a higher number of cerebral malaria in comparison with the present study (1.96 vs. 16.5%). They have also described hypoglycaemia as one of the frequently encountered complications which was not seen in our study.
Very few studies compared the complications of vivax malaria with that of mixed and falciparum malaria,. This study also showed that the pattern of complications was almost similar in all three types of malarial infections, except with regard to ARDS which was more common in mixed infection and renal failure which was seen predominantly in falciparum malaria. Most of the earlier studies on malaria showed an increased association of falciparum malaria with ARDS and there is limited data about the association of ARDS with mixed malaria,. However, there are multiple studies which show that falciparum malaria is associated with more risk of renal failure,, Saravu et al have found spontaneous bleeding and ARDS in severe vivax malaria and renal failure in severe falciparum malaria as the most common complications. The findings of the study done by Kocher et al at Bikaner showed jaundice, anaemia, thrombocytopaenia and renal failure as the common complications in severe falciparum malaria as well as severe vivax malaria whereas severe mixed species malaria patients had mainly jaundice and thrombocytopaenia. Hyperparasitaemia, jaundice and impaired consciousness/coma were the main manifestations of severe falciparum malaria in a study done in Europe.
The mortality rate in the present study was 2.94% (six patients). All those patients who died during the course of hospital stay had evidence ofmulti-organ dysfunction. The study done by Kocher et al reported higher mortality compared to our study with 34 deaths among 539 severe malaria patients (6.31% mortality). The mortality due to severe malaria has come down significantly in the past 5 yrs in India due to the improvement in the health care facility and better intensive care therapy. There are studies from Europe also showing that with prompt and proper interventions, the mortality rate in malaria can be reduced. These studies throw light into the fact that early diagnosis, as well as early initiation of treatment in case of complicated malaria, will help in improving the outcome.
The quantitative assessment of the degree of severity of malaria was not done in the above mentioned studies, whereas our study has estimated the severity of malaria quantitatively using MSS, which was devised by Mohapatra and Das. This score is designed to assess the severity of malaria and to predict the risk of mortality in adults with severe falciparum malaria. On analyzing the severity with the MSS, it was found that falciparum was more severe than mixed which in turn was more severe than vivax malaria. Thus, even though vivax malaria can cause severe malaria, the degree of severity is less compared to mixed or falciparum malaria. However, among the six patients who died during the course of hospital stay belonged to the groups of vivax (two patients) and mixed infection (four patients). Thus, though the mean MSS was less in vivax and mixed infection, compared to falciparum, mortality was seen vivax and mixed infection groups. This could be explained by the fact that patients with MSS >6 were more in mixed infection (12 patients) and vivax group (four patients) compared to falciparum group (two patients). Thus, though the mean MSS was lower, the number of patients having higher MSS being more in these groups contributed to higher mortality .These findings suggest that MSS may be used to predict the mortality in malaria patients. These facts raise the questions that whether vivax malaria is as or more severe as falciparum or mixed infection, which needs to be answered by further large-scale multicentric clinic-epidemiological studies.
Also, when we noted the number of complications associated with these severe cases, only 28.6% of vivax malaria patients had more than two complications, whereas 44.9% of mixed malaria cases and 53.3% of falciparum malaria patients had more than two complications. Sarkar et al studied 900 cases of vivax malaria in Kolkata and found severe disease in 200 (22.2%) cases. They reported that 54% of patients had a single complication and 46% of patients had multiple complications.
The study had some limitations. Being a hospital-based single-center study, the findings cannot be generalized to the community level. We did not use PCR to confirm the species. Hyperparasitaemia was not assessed in our study. We did not include the paediatric population. During the study period, new WHO guidelines on severe malaria were published, but we followed the 2012 guidelines in our study, as the study was initiated in 2014.
| Conclusion|| |
The results data shows that severe malaria in south India is predominantly due to vivax. The entire spectrum of complications of severe malaria which was described for falciparum was seen in severe vivax malaria. However, on quantifying the severity of malaria using MSS and assessing the number of complications, vivax malaria was found to be less severe as compared to mixed and falciparum malaria. Risk of mortality was more in mixed species malaria. The MSS may be used to predict mortality. Hypotension was the most common complication of severe malaria irrespective of the plasmodium species. ARDS seems to be more prevalent in mixed species malaria and renal failure was more prevalent in falciparum malaria.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]