European Journal of Cardiovascular Medicine

Malaria is caused by Plasmodium parasites, which are spread by female Anopheles species mosquitoes. As they eat, infected mosquitoes release infectious sporozoites.   After reaching the liver, sporozoites enter hepatocytes asymptomatically and multiply the infection. This discharge marks the start of the asexual erythrocytic replication stage, which causes malaria. Only two Plasmodium species—P. vivax and P. ovale—produce hypnozoites, which are dormant parasite forms that can remain in the liver for months or years before relapsing and causing clinical illness. Malaria symptoms are brought on by the asexual replication of red blood cells. Fever is caused by erythrocyte rupture and the release of parasites every two to three days, depending on the species of Plasmodium. Severe anemia and hemolysis can result from high parasite burdens, while end organ damage from vascular adhesion of infected erythrocytes and micro blockage can cause malaria, which can be fatal. Controlling mosquito vectors has been essential to the fight against malaria globally, and improving antimalarial treatment and controlling mosquito vectors have been top priorities.  Between 2000 and 2013, the incidence of malaria decreased by 37% and the number of fatalities decreased by 60% ^(1,2). Global control efforts are hampered by drug resistance, particularly to sulfadoxine-pyrimethamine and chloroquine. The rapid parasiticidal artemisinin-based combination treatments (ACTs), which are powerful tools against antimalarial resistance, were made possible by Nobel Laureate You Tu's discovery of artemisinin.  Unfortunately, just a few years after the ACT was adopted, artemisinin-resistant P. falciparum appeared in Southeast Asia, underscoring the need to continue antimalarial development and access while maintaining control measures ⁽³⁾.

The study was carried out in the tertiary care teaching hospital, Saraswathi Institute of Medical Sciences, Hapur over a one-year period. In accordance with NVBDCP guidelines, ethical council approval was obtained for the same. Every child under the age of 12 who had symptoms suggestive of malaria and tested positive for the disease using a rapid diagnostic test, a peripheral smear, or both underwent a thorough history, clinical examination, and basic investigations as specified in the proforma. All of these patients had electrocardiograms, echocardiograms, and chest X-rays. The study will include patients who have been verified to have these and whose parents will provide informed consent. Data must be gathered, entered into an Excel spreadsheet, and examined for demographic factors, clinical manifestations, and medications administered. The dosage, method, and reaction to antimalarial therapy in terms of fever resolution and microbiological clearance will be recorded. To document resolution, smears are performed every 24 hours in cases of severe malaria. After data was collected, it was processed to draw conclusions. Study design, setting, and length. An analytical and prospective study was conducted at Saraswathi Institute of Medical Sciences, Hapur. As required, MS Excel and Sofa Statistics were used for the data analysis. Over the course of one years, from September 2012 to September 2013, this study was carried out at the teaching institute. Inclusion criteria: Children with fever who were admitted to the hospital and diagnosed with malaria in the age group of less than 12 years, as demonstrated by a positive result from a peripheral smear, rapid diagnostic test, or both, must be included with the parent's informed consent. Exclusion criteria: neonates, those older than twelve, and those who do not consent to participate. Out of all those admitted, a total of 90 patients will be included in the sample. Until there was enough data for analysis, the study was carried out. Objectives: To investigate the prevalence of malaria in children under the age of twelve, the wide range of clinical manifestations of the disease in this age group, the prevalence of severe malaria in this age group, the morbidity and mortality rates of malaria in this age group, and the correlation between treatment response to antimalarial medications.

It was discovered that 3.1% of the children admitted to our center had malaria. The most common type of malaria among all patients diagnosed was vivax malaria, accounting for 64.4% of cases, followed by falciparum infection, which accounted for 28.8%. Only 6.6% of the patients had a mixed infection. The most prevalent etiological agent for malaria in our investigation was vivax (64.4%).  28.8% of children had falciparum, and 6.6% had mixed infections. To determine the infectivity of each group, the entire study population was split up into four groups. The group of children aged 5 to 10 had the highest prevalence of vivax infection (37.9%; 22), while the group of children aged 1 to 5 had the highest infestation rate (34.4%).  The majority of patients had fever, which was the most prevalent symptom of malaria and ranged from high to moderate.  94.54% of patients with vivax infection and 96.5% of patients with falciparum infection had fever.  Just 48.6% of patients with vivax infection, 14.03% with falciparum infection, and 5% with mixed infection exhibited the classic symptoms of chills and rigor. Only 1% of patients with vivax infections had altered sensorium, compared to 25% of patients with falciparum infections.  The least common clinical symptom presentation in children with bleeding diathesis was 5.5% (5 patients), followed by vivax (5.1%; 3 patients) and falciparum infection (7.7%; 2 patients). Our study revealed that, among the 35 patients (38.8%), anaemia or pallor was the most prevalent clinical finding overall. Of the patients with pallor, 21 had Vivax species infestation (36.2%), 13 had falciparum infestation (50%) and only 6.6% had mixed infection. Pallor was frequently observed in patients with falciparum infections. Splenomegaly was the second most frequent finding in these patients, occurring in 18 patients (20%) in total, of whom 33.3% had a mixed infection, 15.5% had a vivax infection, and 26.2% had a Falciparum infection. The third most frequent finding, hepatomegaly, was discovered in 17 patients overall, accounting for 18.8% of the total. Only nine patients (15.5%) had vivax, five patients (19.2%) had falciparum parasite, and 50% of the hepatomegaly patients had mixed infections. Just 14% (6patients) of all anaemia patients with vivax infection had severe anaemia, followed by moderate anaemia (18 patients) and mild anaemia (44.4%).

Table 1: Types of malaria and symptoms

chi square test = 76.3 p = 0.001 highly significant Therefore, we discovered that patients with falciparum infections had a higher overall incidence of severe anaemia in our study population. The results of our study showed that 16.6% (4) of patients had splenomegaly even in the absence of anaemia, while 22.7% (15) of patients with anaemia had splenomegaly and 77.27% did not. Anaemia and splenomegaly were highly significantly correlated in malaria patients. Assessment of hepatitis and liver function tests in patients with various malarial species Eight out of 26 patients (30.7%) had severe malaria with icterus, four out of 58 patients (6.89%) had vivax, and two out of six patients (33.33%) had mixed infections. Nine (34.6%) falciparum patients, twenty-four (42.8%) vivax patients, and three (50%) mixed infection patients had moderately elevated SGPT, whereas fifty percent (13) falciparum patients had SGPT in the range of 100IU.The total bilirubin levels were altered in six patients (23%), four patients (6.8%) with falciparum, and two patients (33.3%) with mixed infections.  Two patients (33.3%) with mixed infection, 31.4% (18) with vivax, and 23% (6) with falciparum were found to have significant hypoalbuminemia.  One (16.6%) child with mixed infections, seven (12%) vivax patients, and six (23%) children with falciparum infections had altered ALP with values higher than 100IU suggestive of hepatitis.

Three (50%) of patients with mixed infection, nine (34.6%) of falciparum patients, and twenty-four (42.8%) of vivax patients had moderately elevated SGPT, whereas fifty percent (13) of falciparum patients had SGPT in the range of 100IU. Two patients (33.3%) with mixed infections, four patients (6.8%) with falciparum, and six patients (23%), all had altered total bilirubin levels.  In two (33.3%) patients with mixed infection, 31.4% (18) with vivax, and 23% (6) with falciparum, significant hypoalbuminemia was found.  ALP values greater than 100IU, suggestive of hepatitis, were altered in six (23%) children with falciparum infection, seven (12%) vivax patients, and one (16.6%) with mixed infections.

Table 2: distribution according to severity of malaria

Neither hyperparasiten or hypoglycaemia were observed in any of the patients. Out of 90 patients, 2 patients died, and both had severe acute respiratory distress syndrome (ARDS) and altered sensorium, as indicated by a GCS of less than 9.  One patient had circulatory collapse. In our study population, repeated convulsions were the least common symptom, occurring in just 1 patient (4%). The most prevalent parasite linked to severe anaemia in our study population was falciparum, which was detected in 60% (15) of patients with severe malaria. The second most common parasite was vivax, which was found in 32% (8) of patients.

In our study population, the least common pathogen for severe malaria was mixed infection (2, or 8%). The prevalence of severe malaria in the population under study: Total cases of severe malaria divided by the population under study over the study period equals the incidence, which is 25 cases per 6000 person-years. Pulmonary edema/ARDS was the primary predictor of death among these predetermined WHO severity criteria, with a 100% fatality rate,

In contrast to vivax (32%) or mixed infection (8%), a greater proportion of patients with falciparum infection (60%) experienced severe malaria in our study. Clinical improvement in malaria species in response to antimalarial therapy and medication Reaction to ACT: Of all the children with falciparum infection, 21 required ACT therapy, while the remaining 6 received Quinine as first line treatment for severe falciparum malaria or as second line treatment for non-responders. Eight more children required additional intravenous treatment, while 13 children with falciparum were cured with oral medications alone.  Out of all the patients who had a repeat PS examination, only one patient had PS clearance within 24 hours, whereas the most notable parasite clearance in falciparum occurred in 1-3 days with a total of 6 patients. Five patients had defervescence in falciparum for longer than three days, thirteen patients had it for one to three days, and three children had it for less than twenty-four hours. In contrast to children with vivax, seven patients in total were given artesunate due to severe malaria.  Five received parenteral treatment, and two were given oral medication.   Two children had parasite clearance in less than twenty-four hours, three in one to three days, and two in more than seventy-two hours.  In five children with ACT, defervescence took an average of one to three days. Two children with mixed infections who were placed on ACT showed documented parasite clearance in 1-3 days, while the other two took more than 3 days.  Seven children required intravenous treatment, while 42 children with vivax infestation were cured with oral treatment alone.16 children had PS clearance in vivax within 1-3 days, 4 children within 24 hours, and 1 patient within >3 days. In contrast, defervescence was achieved in 10 children within 24 hours, in 20 within 1–3 days, and in 19 within more than 3 days. Quinine was used as a second line antimalarial treatment for patients who did not respond to first line antimalarials. Individual patients with simple P. falciparum malaria become much less contagious when treated with ACTs.8-10They have the potential to lessen the spread of parasites because they are more effective against gametocytes than earlier first-line antimalarials.  In lower-transmission environments, ACTs may be able to reduce transmission by amounts comparable to those attained by insecticide-treated nets.11Case mortality rate The study's case fatality rate was 2.2%.  Few death reports or brief descriptive clinical series without denominators make up the majority of the previously published literature. P. vivax and P. falciparum were found to be responsible for 1.6% and 2.2% of case fatalities, respectively, in a recent study conducted in Papua, Indonesia.12The case fatality rate in the aforementioned studies emphasizes that, when compared to P. falciparum, P. vivax infections are nearly as serious and can result in significant mortality. However, the current study found that vivax had a CFR of 0% and falciparum-related fatalities were 7.6%. This can be explained by the fact that the study center, a tertiary care facility, received a complicated case of falciparum malaria. The remaining patients were all successfully discharged, and there was only one total expiry among the admitted patients.  In order to check for any long-term organ damage, patients with severe malaria were first monitored every 15 days for a month, and then once a month for the following six months.

Over the past ten years, there has been a shift in the epidemiology of falciparum malaria, with fewer clinical cases reported worldwide. Over the past ten years, malaria deaths have decreased by one-third in Africa; in contrast, 35 of the 53 malaria-affected countries have seen a 50% decrease in cases during the same time frame (4,5).  Overall child mortality rates have decreased by roughly 20%, 3 a percentage more than twice that of all childhood deaths attributable to malaria, in nations where access to malaria control interventions has improved the most.  The fact that malaria is now known to be a significant risk factor for other serious infections, specifically bacteraemia, may be partially to blame for this decrease. According to a study done in Bikaner, the age-stratified composition of various malaria species showed that P. vivax mono infection was 33.9% (103/303) in children aged 0–5 years, 42.3% (41/97) in children aged 5–10 years, 30.1% (44/146) in children aged 5–10 years, and 30% (18/60) in those aged >10 years.  61.01% (185/303) (children aged 0-5 years 51.5% (50/97); 65.1% (95/146) in 5-10 years; >10 years 66.7% (40/60); and mixed (Pf Pv) infection 4.95% (15/303) (children aged 0-5 years 6.2% (6/97); in 5-10 years 4.8% (7/146); > 10 years 3.3% (2/60).One Another Mumbai-based study  The age distribution was nearly the same across all age groups, with 33.9% of people in the 0–5 age group, 30.1% in the 5–10 age group, and 30% in the >10 age group(6). According to our research, vivax was the most prevalent etiological agent for malaria (64.4%). 28.8% of children had falciparum, and 6.6% had mixed infections. In contrast to our findings, Tarkeshwar et al.'s study identified falciparum as the most prevalent etiological agent (64%). Even within the same nation, the species that infect children can differ due to varying environmental conditions that lead to the breeding of distinct vectors (7,8).   A study on the prevalence of malaria in Andhra Pradesh's agency areas revealed that P. falcifarum was a common cause of infection throughout the year. P vivax was identified as the most prevalent etiological agent in a study conducted in Bikaner by Kocher et al.(1,13) The only parasite species found in African nations such as Camerron was P. falciparum. This brings to mind the WHO report that P. falciparum is the cause of all (100%) of the malaria cases in Cameroon. (14,15) The most frequent clinical presentation in our study was fever (95.5%), which was followed by vomiting (57.6%).  The Mumbai-based study and the Tarakeshwar et al. study both showed similar results. In every case that was admitted, fever was the presenting complaint (9,10). The average time from fever onset to admission was five days. Studies conducted by Kaushik et al. and Taksande et al. made similar findings. Malaria pallor is caused by a confluence of several factors. The primary causes are ineffective erythropoeisis and the spleen's quick destruction and removal of RBC. Compared to 66.6% of mixed infections, pallor was seen in 74.14% of vivax and 73.03% of falciparum. This was consistent with research conducted in Thailand, which showed that the risk of developing pallor was 1.8 times lower in cases of mixed malaria than in cases of falcifarum malaria. In their study, Gohiya et al. found that pallor was present in 96% of cases of falcifarum malaria. There are several ways that thrombocytopenia in malaria develops. Thrombocytopenia is thought to be caused by a number of factors, including oxidative stress, bone marrow changes, coagulation abnormalities, splenomegaly, antibody-mediated platelet destruction, and the part platelets play in precipitating severe malaria. Increased blood levels of a particular immunoglobulin G (IgG) in malaria patients bind to malaria antigens attached to platelets, potentially accelerating platelet destruction. According to earlier research, the analyzer miscalculated platelet aggregation—the clumping of platelets—as a single platelet, which resulted in pseudothrombocytopenia (11).  Furthermore, endothelial activation is triggered during malaria infection, which may lead to organ dysfunction and a loss of endothelium barrier function. In our study, the percentage of patients with severe malaria was higher among those with falciparum infection (60%) compared to those with vivax infection (32%), or mixed infection (8%). Cross-sectional and longitudinal surveys conducted in Melanesia have demonstrated negative correlations between the prevalence of different Plasmodium species, and mixed-species infections are significantly less common in symptomatic patients compared to asymptomatic patients (12,13). Epidemiologic evidence from Thailand has also demonstrated that the incidence of severe malarial illness, but not mortality, is lower in patients with P. falciparum when there is a mixed infection with P. vivax.  Furthermore, P. vivaxco-infection seems to prevent the hemoglobin nadir following falciparum malaria treatment. These findings have been interpreted as proof that P. vivax guards against the clinical illness caused by P. falciparum (14,15) . Findings from Africa show that AS + AQ and AS + SP combinations are very effective, though their effectiveness might be hampered in regions with moderate to high levels of SP and AQ resistance.  The crude efficacy of AS+AQ was 75.9% in randomized comparative trials. In many, but not all, of the sub-Saharan African nations where it was studied, AS+AQmeets the WHO efficacy criteria for use against P. falciparum malaria and compares favourableto other treatments (16,17).

The current study focuses on the epidemiology of P. vivax malaria in pediatric age groups. There are few reports of P. vivax since it was thought to be a benign condition. The study emphasizes that Plasmodium vivax can cause serious sickness and should no longer be regarded a benign condition. The current study shows that some manifestations of WHO severity criteria were not seen in severe P. vivax malaria (renal impairment, hypoglycemia, jaundice, and hyperparasitemia), whereas leukopenia and thrombocytopenia, which are not part of WHO severity criteria, were frequently present and associated with mortality. This suggests the necessity for different severity measures for P. vivax malaria. However, bigger investigations must be conducted to determine the particular severity. The rise of severe malaria caused by P. vivax may have important consequences for community malaria control strategies. The extensive use of ACT treating severe malaria as per WHO guidelines may result in the establishment of resistant parasite strains. Because P. vivaxin chloroquine-sensitive regions exist, it may be prudent to continue using chloroquine to treat malaria. In areas where both P. vivax and P. falciparum coexist, initiatives to reduce morbidity and death from severe malaria must be equally focused at P. vivax.

1. Fernando SD, Rodrigo C, Rajapakse S. The “hidden” burden of malaria: cognitive impairment following infection. Malar J. 2010;9:366.

2. Kochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A. Plasmodium vivaxmalaria. Emerg Infect Dis. 2005 Jan;11(1):132-134. doi:10.3201/eid1101.040519.

3. Gehlawat VK, Arya V, Kaushik JS, Gathwala G. Clinical spectrum and treatment outcome of severe malaria caused by Plasmodium vivax in 18 children from northern India. Pathog Glob Health. 2013;107(4):210-4.

4. Messina JP, Taylor SM, Meshnick SR, Linke AM, Tshefu AK, Atua B, et al. Population, behavioural and environmental drivers of malaria prevalence in the Democratic Republic of Congo. Malar J. 2011;10:161.

5. Macintyre K, Keating J, Sosler S, Kibe L, Mbogo CM, et al. Examining determinants of mosquito-avoidance practices in two Kenyan cities. Malar J. 2002;1:1-14.

6. Guyatt HL, Corlett SK, Robinson TP, Ochola SA, Snow RW. Malaria prevention in highland Kenya: indoor residual house spraying vs insecticide-treated bed nets. Trop Med Int Health. 2002;7:298-303.

7. Beeching NJ, Fletcher TE, Wijaya L. Returned travellers. In: Zuckerman JN, editor. Principles and Practice of Travel Medicine. 2nd ed. Chichester: John Wiley & Sons; 2013. p. 260–286.

8. Takshande A, Vilhekar K, Jain M, Atkari S. Clinico-hematological profile of cerebral malaria in a rural hospital. J Indian Acad Clin Med. 2006;7:308-12.

9. Price RN, Simpson JA, Nosten F, Luxemburger C, Hkirjaroen L, Ter Kuile F, et al. Factors contributing to anemia after uncomplicated falciparum malaria. Am J Trop Med Hyg. 2001;65(5):614-22.

10. D'Acremont V, Landry P, Darioli R, Stuerchler D, Pecoud A, Genton B. Treatment of imported malaria in an ambulatory setting: prospective study. BMJ. 2002 Apr 13;324(7342):875-877. doi:10.1136/bmj.324.7342.875.

11. Rasheed A, Saeed S, Khan SA. Clinical and laboratory findings in acute malaria caused by various Plasmodium species. J Pak Med Assoc. 2009;59(4):220-3.

12. Taviad PP, Javadekar TB, Selot BA, Chaudhary VP. Sociodemographic and clinical features of malaria cases. Nat J Community Med. 2012;3(1):94-6.

13. Zimmerman PA, Mehlotra RK, Kasehagen LJ, Kazura JW. Why do we need to know more about mixed Plasmodium species infections in humans? Trends Parasitol. 2004;20(9):440-7.

14. Anstey NM, Handojo T, Pain MC, Kenangalem E, Tjitra E, Price RN, Maguire GP. Lung injury in vivax malaria: evidence for pulmonary vascular sequestration and post-treatment alveolar-capillary inflammation. J Infect Dis. 2007;195(4):589-96.

15. Sodeinde O. Glucose-6-phosphate dehydrogenase deficiency. Baillieres Clin Haematol. 1992;5(2):367-82.

16. Taviad PP, Javadekar TB, Selot BA, Chaudhary VP. Sociodemographic and clinical features of malaria cases. Nat J Community Med. 2012;3(1):94-6.

17. Phillips A, Bassett P, Zeki S, Newman S, Pasvol G. Risk factors for severe disease in adults with falciparum malaria. Clin Infect Dis. 2009 Apr 1;48(7):871-878. doi:10.1086/597258.