Diagnostic value of ferritin for the severity of dengue infection in children

The study was conducted to evaluate whether the severity of dengue fever can be predicted by serum ferritin level or not. This prospective observational study was conducted during the endemic period of dengue fever in 2019. A total of 30 diagnosed cases of dengue fever who presented with bicytopenia during febrile phase of the disease were enrolled in this study. Pearson’s correlation coefficient was calculated to compare ferritin levels with lowest platelet count and highest hematocrit level and it showed that there was significant correlation. There was no difference between the lowest total count of white blood cell and serum ferritin level. The severity of dengue fever can be predicted by raised level of serum ferritin.


Introduction
2][3] Now-a-days, it is endemic in more than 100 countries in Western Pacific, Latin America, Southeast Asia, Eastern Mediterranean regions and Africa.[6][7] The severity of dengue fever depends on the interactions between virus and host's immune response. 8w-a-days, many hematological parameters have been suggested to evaluate the severity of the disease including decreased platelet count, raised hematocrit level, prolonged prothombin time and activated partial thromboplastin time, liver transaminases, muscular enzymes, cytokines such as IL-6 and IL-10,  19 concluded that high hematocrit, thrombocytopenia and leukopenia were associated with severity of the disease.One of the effects of inappropriate activation of tissue macrophages is macrophage activation syndrome and could be responsible for morbidity and mortality in dengue fever.Serum ferritin, an acute phase reactant protein, is a surrogate marker of macrophage activa-tion. 20Elevated level of serum ferritin during the febrile phase of dengue fever might predict the severity of dengue fever during critical phase which would help physicians to prepare for the prevention and treatment of extended dengue fever.Thus, it can reduce the morbidity and mortality in dengue fever 20.
During the endemic period of dengue outbreak in Bangladesh, it was rational to conduct this study to early pickup of lethal cases which was helpful for the prevention of mortality and morbidity.
In this study, we assessed the relationship of serum ferritin concentration with the highest hematocrit, lowest platelet and total white blood cell count.

Materials and Methods
This study was conducted from June to August, 2019.In total 30 diagnosed cases of dengue fever (Dengue NS 1 positive) who developed bicytopenia during febrile phase of the illness 7,8 were included for the study.All participants later developed features of volume overloads in the form bilateral pleural effusions and ascites which resolved at variable period of time.The serum ferritin level was measured from 1 mL venous blood sample during the 4 th or 5 th day of onset of febrile phase of the illness (by electrochemiluminescence immunoassay-COBAS e411).

Abstract
The study was conducted to evaluate whether the severity of dengue fever can be predicted by serum ferritin level or not.This prospective observational study was conducted during the endemic period of dengue fever in 2019.A total of 30 diagnosed cases of dengue fever who presented with bicytopenia during febrile phase of the disease were enrolled in this study.Pearson's correlation coefficient was calculated to compare ferritin levels with lowest platelet count and highest hematocrit level and it showed that there was significant correlation.There was no difference between the lowest total count of white blood cell and serum ferritin level.The severity of dengue fever can be predicted by raised level of serum ferritin.
On a daily basis, disease progression and complete blood count were monitored carefully.
The patients were classified as having non-severe and severe infection as per National guideline of dengue fever. 21

Statistical analysis
The chi-squared test was done to compare the values of serum ferritin concentration with other parameters of the blood.Additionally Two-tailed, unpaired student's t test was done to compare the means of different variables Proportions were compared by means of the two-tailed, Fisher's exact test.Correlations between the variables were analyzed by Pearson correlation.

Results
Figure 1A shows the positive correlation of serum ferritin and high hematocrit value.Pearson correlation value was 0.661.The result was statically significant (p=0.000).
Figure 1B shows the negative correlation of serum ferritin and lowest platelet count.Pearson correlation value was -0.348.The result was statically significant (p=0.05).
Figure 1C shows negative correlation of serum feritin and lowest total count of white blood cell count.Pearson correlation value was -0.132.the result was not statically significant (p=0.486).

Discussion
In the present study, we found that higher serum ferritin level during febrile phase, significantly associated with lower platelet count and higher hematocrit level during critical period of dengue fever which ultimately correlate with the severity of the disease.Similar findings were noted in other studies as well.In South India, Soundravally et al. ( 2015) 22 conducted a research work on 96 febrile patients equally divided into dengue and nondengue groups.The plasma ferritin levels were monitored on 4th and 8th day of the onset of fever.Ferritin level was significantly raised in severe dengue fever both in febrile and afebrile phases (p value 0.000).In the current study, although we did not compare serum feritin level between the severe and nonsevere dengue fever, we found that higher the level of serum feritin, lower the level of platelet count (p value 0.000).

Conclusion
High serum ferritin level significantly associated with severe dengue fever.

Ethical Issue
The research protocol was approved by the ethical committee of the United Hospital LTD.Dhaka, Bangladesh.
Recently published another study by Petchiappan et al. (2019) 23 at Tamilnaru, India also described similar finding on 119 patients with dengue fever.Evalda et al. (2017) 24 at Indonesia described the association of high serum ferritin level with dengue shock syndrome in children.

Figure 1 :
Figure 1: Correlation of serum ferritin level with serum haematocrit level (A), lowest platelet count (B) and lowest total count of white blood cell (C)

9-15 but
there is paucity of researches which can predict bad outcome in dengue fever.Studies conducted by Zhang et al. (2014) 16 at the Caribbean island Aruba; Chaiyaratana et al. (2008) 17 at Thailand concluded that elevated ferritin level in serum is a distinguishing feature of dengue fever.Thanachartwet et al. (2015) 18 and Chaloemwong et al. (2018)