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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 2  |  Page : 57-62

Pattern of severe malaria with special reference to Plasmodium vivax in pediatric population of the most aspirational region of North India


1 Department of Microbiology, Shaheed Hasan Khan Mewati Government Medical College, Nuh, Haryana, India
2 Department of Paediatrics, Shaheed Hasan Khan Mewati Government Medical College, Nuh, Haryana, India

Date of Submission23-Jan-2021
Date of Decision30-May-2021
Date of Acceptance26-Aug-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Jyoti Sangwan
Professor, Department of Microbiology, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijamr.ijamr_21_21

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  Abstract 

Introduction: Malaria is one of the major life-threatening health problems in most of the tropical countries. Children are the most vulnerable group accounting for 67% of all malaria-associated deaths worldwide. Southern Haryana is typically endemic for malaria. Therefore, the present study was undertaken to describe the clinical presentation of complicated malaria and correlate clinical complications with malarial species. Materials and Methods: It was an observational cross-sectional study conducted in the Department of Microbiology along with Department of Pediatrics, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Haryana. A total of 100 children with severe malaria admitted in the pediatric ward, confirmed by peripheral blood smear and rapid diagnostic test, were included. Results: Out of 100 cases admitted, majority were due to Plasmodium vivax (73%), followed by mixed (18%) and Plasmodium falciparum (9%) infection. Children below 5 years were more infected (57%). Male preponderance was seen (55%). Fever was the most common symptom observed (95%). Pallor was the most common sign observed (85%). Among severity parameters, the most common were severe anemia (41%), jaundice (17%), abnormal bleeding (17%), convulsions (15%), and acute respiratory distress syndrome (7%). The case fatality rate was 3%. Conclusion: P. vivax was previously known to cause benign malaria. The present study found that P. vivax mono-infection can cause severe malaria in children and should no longer be considered as benign malaria.

Keywords: Pediatric population, Plasmodium vivax, severe malaria


How to cite this article:
Minhas A, Mane P, Sangwan J, Dhingra A. Pattern of severe malaria with special reference to Plasmodium vivax in pediatric population of the most aspirational region of North India. Int J Adv Med Health Res 2021;8:57-62

How to cite this URL:
Minhas A, Mane P, Sangwan J, Dhingra A. Pattern of severe malaria with special reference to Plasmodium vivax in pediatric population of the most aspirational region of North India. Int J Adv Med Health Res [serial online] 2021 [cited 2022 Sep 29];8:57-62. Available from: https://www.ijamhrjournal.org/text.asp?2021/8/2/57/334367




  Introduction Top


Malaria is one of the major life-threatening health problems in most tropical countries.[1] It is a mosquito-borne infection caused by a protozoan parasite of genus Plasmodium, transmitted through bite of an infected female Anopheles mosquito.[2],[3] Five species of Plasmodium causing malaria in humans are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri), Plasmodium malariae, and Plasmodium knowlesi.[4] According to the World Health Organization (WHO) report 2019, 3.2 billion people were at risk, 228 million cases were reported, and 405,000 people died of malaria – most of these were children from the African region in 2018. Globally, 53% of the Plasmodium vivax burden is in the South-East Asia Region, majority being in India (47%). India accounts for 2% of malaria cases. P. falciparum and P. vivax are the most common species causing malaria in India. Children under 5 years of age are the most vulnerable group accounting for 67% of all malaria deaths worldwide.[5]

Previously, P. falciparum was known as the leading cause of severe malaria.[6] Recent studies from South-East Asia had reported P. vivax malaria as the major cause of morbidity and mortality in infants and children. Previously, it was known to cause benign tertian malaria, which is rarely fatal.[7],[8] In children, cerebral malaria, thrombocytopenia, and severe anemia are the most common manifestations seen.[1]

This study was taken up to study complicated malaria cases and different malaria species causing complicated malaria, with an objective to describe the clinical presentation of complicated malaria and correlate these clinical complications with malaria species in the region. As per the recent NITI Aayog report, the Mewat region was declared the most backward/aspirational region of India.[9] The local population here depends on agriculture, skill jobs, and cattle rearing. The sources of drinking water are wells and ponds. There is a lack of awareness about hygiene, education regarding prevention of diseases, and nutrition. All the indicators reflecting health, general well-being, and education are way below than anywhere in India. The pediatric population is highly malnourished. Giardiasis is common and largely nonvaccinated, making them much more vulnerable than other regions of country.[10],[11],[12]

Given the changing disease pattern and clinical presentations, the disease needs to be studied extensively. There are wide variations of disease severity in the pediatric and adult population from region to region. There is a paucity of such studies in the highly endemic backward area of southern Haryana.


  Materials and Methods Top


This was an observational cross-sectional study conducted in the Department of Microbiology in collaboration with Department of Pediatrics, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Haryana, after obtaining IEC permission vide letter no. EC/OA-35/2018 from February 1, 2019, to January 31, 2020. The sample size was calculated as 97 and rounded 100. The sampling technique was convenience sampling. Patients/guardians not willing for admissions, patients lost to follow-up, and patients with iron-deficiency anemia were excluded from the study.

Severe malaria was classified according to recent National Vector Borne Disease Control Programme India guidelines.[13] Severe malaria is a confirmed case of malaria with any one or more complications such as cerebral malaria, convulsions, pulmonary edema/acute respiratory distress syndrome (ARDS), severe anemia (hemoglobin <5 g/dl), renal failure (serum creatinine >3 mg/dl), jaundice (serum bilirubin >3 mg/dl), hypoglycemia (plasma glucose <40 mg/dl), metabolic acidosis, circulatory collapse/shock (systolic blood pressure <80 mmHg and <50 mmHg in children), abnormal bleeding and laboratory evidence of disseminated intravascular coagulation, hemoglobinuria, hyperthermia (temperature >106°F or >42°C), and hyperparasitemia (>5% parasitized red blood cells [RBCs]). All patients fulfilling these criteria were included in the study.[14]

Written informed consent was taken from parents. Two to five milliliters of blood sample was collected and processed for peripheral blood smear (PBS), rapid diagnostic tests (RDTs), biochemical tests, and hematological tests.

PBS was taken as gold standard for the diagnosis of malaria. Thick and thin smears were prepared and stained by Giemsa stain, which was then observed under 100X oil immersion field.

RDT kits used were MALARIGEN malaria rapid card kits for Pf/Pan Ag (Aspen Laboratories Pvt. Ltd, Delhi, India) for detection of antigens of P. falciparum and Pan malaria (P. vivax/P. malariae/P. ovale) in whole human blood.

The cases were included in the study after confirming with both PBS and rapid card antigen test.

Biochemical tests such as kidney function tests (blood urea and serum creatinine), liver function tests (serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, alkaline phosphatase, and total bilirubin), serum electrolytes (sodium and potassium), and random blood sugar were assessed.

Complete blood count was done using automated hematology analyzers based on Coulter's concept of electronic impedance.

All results so obtained were compiled in MS Excel. The data were analyzed using Epi Info. Bivariate analysis was done using Chi-square test. Odds ratio was also calculated for association between the categorical variables. P < 0.05 was set as significant.


  Results Top


A total of 1367 children were screened for malaria during the study period. Of these, 127 (9.29%) children were positive for malaria by either PBS or RDT or both. Among these, 109 (85%) cases were of severe malaria admitted in the pediatric ward, and a total of 100 cases were included in the study. The rest had to be excluded as per exclusion criteria.

Out of 100 positive cases of severe malaria, P. vivax infection was the most common, accounting for 73%, followed by mixed infection that was 18% and P. falciparum that was 9% of cases. Mixed infection was found to be either due to P. vivax and P. falciparum or P. vivax and P. ovale or P. falciparum and P. malariae.

Most of the cases (57%) were below 5 years of age. Among infants, out of 14 cases, P. vivax was the only species of Plasmodium causing severe malaria (100%). Among the age group of 1–5 years, out of 43 cases, the highest number was seen with P. vivax (62.8%) followed by mixed infection (30.2%) and P. falciparum was seen in three (7%). Similarly, in the age group of 6–10 years, P. vivax (80.8%) was the most common species responsible for severe malaria, followed by P. falciparum (11.5%) and mixed infection (7.7%). In children of more than 10 years also, P. vivax was seen in 11 (64.7%) cases, P. falciparum was seen in three (17.7%) cases, and mixed infection was seen in three (17.7%) cases [Table 1].
Table 1: Age-wise distribution of malaria species

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[Table 2] shows the common symptoms and signs among 100 cases of malaria. Fever was the most common symptom (95%), followed by chills and rigors (43%), vomiting (24%), convulsions (15%), breathing difficulty (10%), abdominal pain and epistaxis (8% each), altered sensorium (7%), diarrhea (5%), cough (4%), and headache (4%). Among signs observed, pallor was the most common (85%), followed by hepatosplenomegaly (28%), abdominal distension (24%), icterus (17%), hepatomegaly (15%), splenomegaly (13%), and edema (3%).
Table 2: Common symptoms and signs observed in children with malaria

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[Table 3] shows that, among all the severity parameters of malaria, severe anemia was most common (41%), followed by jaundice (17%), abnormal bleeding (17%), convulsions (15%), acute respiratory distress syndrome/pulmonary edema (7%), hypoglycemia (4%), metabolic acidosis (4%), cerebral malaria (3%), shock (2%), renal failure (2%), hemoglobinuria (2%), and hyperthermia (1%).
Table 3: Clinical manifestations of severe malaria

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In the present study, three deaths were reported: one was seen in case of P. vivax infection and two in cases of mixed infection (P. vivax and P. falciparum). All these deaths were seen in females.


  Discussion Top


In the present study, 109/127 (85%) children had severe malaria. Kaushik et al. from Delhi have reported the prevalence of severe malaria in children as 77.1%.[1] Among 100 study subjects with severe malaria, maximum (73%) cases were positive for P. vivax, followed by 18% for mixed infection and 9% for P. falciparum infection. Similarly, Kaushik et al. (Delhi, India) and Singh et al. (Uttarakhand, India) also reported P. vivax to be the most common species of malaria, the estimates were 88.9% and 71.8%, respectively.[1],[14] Poespoprodjo et al. (Indonesia) and Genton et al. (Papua New Guinea) also reported P. vivax malaria as more common compared to other species of Plasmodium. The reason could be a higher prevalence of P. vivax in South-East Asia as compared to African countries where P. falciparum is the major culprit.[7],[8] The higher prevalence of P. vivax malaria in India may be due to variations in climatic conditions, breeding places of mosquitos, and genetic resistance of mosquitoes to P. falciparum.[15] In contrast to the present study, Verma et al. (Bhopal, India) and Jain et al. (Bhopal, India) reported more cases of severe malaria due to P. falciparum.[16],[17]

Various studies conducted across India show a variable incidence of types of malarial species and its severity and mortality.[18] In the present study, 57 children less than five years of age and 43 more than five years were found to have severe malaria. This may be due to the immature immune system and thus being prone to repeated infections. Also, perhaps because, the Mewat region is the most backward area in India, people here lack awareness about basic hygiene and cleanliness leading to breeding of mosquitoes in stagnant water and more risk for malaria. Majority of newborns are pre term and hence again more prone to severe malaria manifestations. The presence of protozoal and helminthic infections and malnutrition further adds to the plight.[10],[11] Similarly, other studies from Mumbai and Punjab have reported greater involvement of less than-year-old children compared to older children.[19],[20] In contrast, Singh et al. reported children above 10 years as the most common age group affected.[18] Kochar et al. (Bikaner, India) reported an equal incidence of malaria in the age group of 0–5 years, 5–10 years, and >10 years.[21] Furthermore, the clinical manifestations of severe malaria were seen more commonly in infants and young children compared to those aged more than 10 years.[6]

Males were more affected (55%) as compared to females (45%) [Figure 1]. A similar male preponderance was reported by Hassan et al., Patel et al., and Kumari et al.[6],[19],[22] This may be due to the increased outdoor activities in males, and thus more exposure to mosquitoes. Since this is a backward area, female children would be wearing clothes that cover a larger proportion of body surface area.[6],[19]
Figure 1: Gender distribution of children with severe Malaria

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Fever was the most common symptom seen, followed by chills and rigor, vomiting, convulsions, and others in the present study. Similar findings were reported by many authors.[18],[21],[23],[24]

The most common sign observed in the study was pallor, followed by hepatosplenomegaly, abdominal distension, icterus, and others [Table 2]. Pallor occurs due to decrease in hemoglobin. Hepatomegaly occurs due to more invasion of liver parenchyma cells by the parasites, thus damaging the liver. Splenomegaly occurs due to an increased destruction of both infected and noninfected RBCs. Similar to our study, Kumari et al. and Hassan et al. also reported pallor as the most common sign, followed by hepatomegaly and splenomegaly.[6],[19] In contrast, Kaushik et al. reported hepatomegaly as the most common sign, followed by splenomegaly, pallor, and other signs.[1]

In the present study, severe anemia, jaundice, abnormal bleeding, convulsions, and ARDS were the most common manifestations of severe malaria. Various other studies also found similar results.[16],[21],[25] In contrast to the present study, Ragini et al. found cerebral malaria as the most common complication seen.[14] Metabolic acidosis, cerebral malaria, shock, renal failure, and hemoglobinuria were observed in less than five % of individuals in the present study compared to other studies that showed a higher percentage of such symptoms.[14],[16],[21],[25]

As shown in [Table 3], severe anemia, jaundice, abnormal bleeding, ARDS, metabolic acidosis, renal failure, and hemoglobinuria were found more in P. vivax infections as compared to P. falciparum and mixed infection; however, the difference was not significant (P > 0.05). At the same time, central nervous system involvement in the form of convulsions was also seen more in P. vivax infection as compared to other species infection, the difference being significant (P = 0.05). Similarly, Nagaraj et al. also reported the above findings to be more common in P. vivax infection,[25] whereas Verma et al. reported these findings to be more common in P. falciparum infection.[16] However, clinical manifestations such as hypoglycemia, cerebral malaria, and shock were found more often in mixed infections (P < 0.05).

In the present study, multiple complications were seen in 13% of cases. Females presented more with multiple complications (69.2%) compared to males (30.8%). This could be due to lower immunity among females due to various sociodemographic reasons. Another reason is lack of priority with regard to female child health in this backward area; consequently, they are not taken to hospital during early stages of the disease. Out of these 13 cases, seven had P. vivax malaria, one had P. falciparum malaria, and five had mixed malaria by P. vivax and P. falciparum.

Atypical presentation encountered in this study was hyperglycemia in a single patient diagnosed with convulsions due to P. vivax infection. Hyperglycemia could be stress induced. Stress responds with increase in counter-regulatory hormones similar to critically ill patients. Tombe et al. from Kenya also reported one case of severe malaria with hyperglycemia in their study.[26] Similarly, Dass et al. also reported hyperglycemia in severe malaria cases.[27] Verma et al. had reported that 15 out of 102 (14.7%) children with severe malaria had hyperglycemia seen mostly with P. falciparum infection followed by mixed malaria, but not with P. vivax infection.[16]

In the present study, three out 100 (3%) patients died within few hours of hospitalization. All were females. Out of three, one patient had P. vivax infection and was diagnosed with meningitis and convulsions. The other two cases had mixed malaria infection by P. vivax and P. falciparum infection, and both presented with more than one complication. Out of these two cases, one patient was diagnosed with hypoglycemia and died due to shock, whereas the other patient was diagnosed with cerebral malaria and severe anemia and also died due to shock. The case fatality rate was 3%. Hassan et al. reported a case fatality rate of 1.73%.[6] These patients had severe anemia, multi-organ dysfunction, and shock. Kumari et al. reported a 4% case fatality rate.[19]

The present study has certain limitations as the present study represents only those cases that were admitted in the hospital. Thus, these data cannot be generalized for whole population in this area; for this, further pilot studies are required. Nevertheless, this study provides evidence that P. vivax is an important agent in the region, resulting in severe morbidity in vulnerable population.


  Conclusion Top


The present study highlights the presence of Plasmodium vivax in children of this backward region. Children present with severe complications such as severe anemia, jaundice, abnormal bleeding, convulsions, ARDS, hypoglycemia, cerebral malaria, and shock. Previously considered benign, P. vivax can result in all these complications, especially in children. Therefore, a child presenting with malaria is at risk of developing complications irrespective of species and therefore needs urgent medical attention.

Ethical clearance

Ethical Clearance was obtained from Institutional Ethics Committee wide letter no SHKM/IEC/2018/61 DATED 30.11.2018.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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