An Evaluation of Haematological Changes in Paediatric Dengue Fever Patients at a Tertiary Care Hospital Rawalpindi during 2019 Outbreak

Objective: The study aimed to evaluate the hematological parameters of patients with dengue fever in order to increase the sensitivity of screening for early diagnosis and as an aid to the early institution of appropriate


Introduction
Dengue is a public health concern as it is a global lifethreatening infection. In more than 100 countries it affects about 2.5 billion people. 1 Dengue is transmitted by mosquitos and leads to arthropod-born viral diseases. 2 Dengue virus is a member of the Flaviviridae family and has four different antigenic types (dengue 1, 2, 3 & 4). The principal vector is Aedes agypti which bites during the daytime. 3 The main presenting features are fever, headache, myalgia, arthralgia, and minor haemorrhagic manifestations. 4 A wide range of manifestations can occur in infection with any of the dengue virus infections and vary from mild fever to haemorrhage and shock which is life-threatening. 5 Correct and early diagnosis can help improve patient management and optimized the use of resources such as hospital staff, beds, and equipment. 6 The laboratory test for dengue is of two types, Nonspecific tests like complete blood count and definitive tests like dengue serology and NS1 antigen test. 7 The epidemiological aspects of the disease, the kit, and the method used may result in variations in these tests results. 8 During the disease process, a series of haematological and biochemical changes occur which depend upon the clinical disease. 9 The clinical features of dengue infection may resemble other infections. The serological tests are expensive and are not available in many hospitals. 10 Awareness of clinical features, as well as laboratory findings like haematological and biochemical parameters, are the most important guides to therapy and prognosis of dengue fever. The haematological and biochemical findings reported are thrombocytopenia, anemia, leukopenia, elevated levels of AST & ALT. 11 Other findings are activated lymphocytes on a peripheral blood smear. 12 Lymphocytosis and neutrophilia and raised bilirubin can also occur. 13 Changes in haematocrit, albumin, and cholesterol can also occur. 9 Other changes are hemoconcentration 12 , a raised blood urea and serum creatinine 14 , hypokalemia, DIC 15 hypocalcemia. 16 The study aimed to evaluate the hematological parameters of patients with dengue fever to increase the sensitivity of screening for early diagnosis and as an aid to the early institution of appropriate treatment.

Materials and Methods
This prospective descriptive study was conducted at the Department of Pediatrics, Benazir Bhutto Hospital, Rawalpindi for a period of 6 months from July to December 2019. One month to 12 years old children presenting with clinical signs and symptoms of dengue fever were admitted to the paediatric dengue ward and were included in the study. Patients with age more than 12 years or suffering from previously known blood disorders were excluded. All children attending the hospital with symptoms and signs suggestive of dengue fever were tested for NS1 antigen and IgM/IgG dengue antibody serology (depending on the day of fever) by enzyme-linked immunosorbent assay (ELISA) technique. Every admitted case with confirmed dengue fever was enrolled in a structured protocol that included relevant hematological investigations. The diagnosis of dengue fever was based on the WHO criteria. All this data was recorded and entered in the predesigned, pre-tested, and semi-structured questionnaire. The relevant data was recorded, entered, and analyzed by SPSS version 24 for descriptive statistics and bivariate analysis.

Results
During the study period of 6 months, 438 confirmed dengue patients were admitted, amongst which 254 were male (58%), and 184 were female (42%). The age of the children ranged from 04 months to 12 years, with a mean age of 8.03 years (SD + 3.13 years), In our study, out of 438 children, 254 (58%) were reported as uncomplicated dengue fever, 119 children (27%) developed dengue hemorrhagic fever and were managed accordingly. 65 children (15%) were into dengue shock syndrome and treated for this complication.

Discussion
Dengue infections are asymptomatic in 75% of infected humans. A spectrum of disease, from self-limiting dengue fever to haemorrhage and shock may be seen. A complex interaction of host and viral factors occur and determine whether the infection will be asymptomatic, typical, or severe. 2 CBC parameters such as hemoglobin (Hb), hematocrit (Hct), WBC count, differential percentages of WBCs, and platelet count alter each day of fever in patients infected with dengue. 10 Pancytopenia may develop after 3-4 days of illness. 3 Early and accurate laboratory diagnosis of dengue virus infection is critical to effective patient management. 5 Amongst the age and sex ratio, the majority of the children are in the age group of 8-12 years, boys more commonly affected than girls with male to female ratio of 1.2:1. A similar age group with a mean age (standard deviation) of 6.9+3.3 years and a higher male to female ratio of 1.2:1 was found in a study by Potha pregada S et al. 18 A study by Manoj Kumar et al. also shows a higher number of males affected with a male to female ratio of 1.54:1 among all seropositive cases. 19 The most significant laboratory abnormality seen in our study was thrombocytopenia. A study has shown thrombocytopenia in 59.8%. 11 Another study has found thrombocytopenia in 67% of the cases. 20 Significant derangements in platelets were found in yet another study. 21 A study by Adel Hamed has documented thrombocytopenia in 74.45% of the patients. 22 As platelet counts decrease the complication rate increase and duration of hospital stay increase with decreasing platelet count. Platelet count can therefore be used to predict the complication and duration of hospital stay and hence better use of resources. 23 In our study concomitant presence of leucopenia, raised haematocrit and low platelet count were commonly associated with dengue fever with warning signs. Leucopenia and differences in WBC count in dengue fever & dengue haemorrhagic fever have been found in a study by Juthatip Chaloemwong et al., demonstrating leucopenia (WBC count<5000 cells/mm) in 70.9% of the patients during the acute febrile phase (day 2, 3) of illness with the average value in the acute febrile phase of 4.38 and 4.49 in those who progressed to dengue haemorrhagic fever.
Other studies have documented leucopenia in 66% of patients 22 and 26.5% of patients. 11 In our study liver enzymes were in the range of 10 -3500, with three children having a value of more than 3000. ALT& AST levels were significantly increased among severe dengue cases compared to uncomplicated dengue fever cases. An elevation in AST (45.1%) and ALT (17.6%) were found in a study by Ferede et al. (11). Kularatam et al. has found that AST and ALT levels begin to rise in the early febrile phase with the median concentration of AST of 746 u/L and ALT median concentration of 118 u/L. 9 In our study, hemoglobin levels varied between 4.9 mg/dl and 16.9 mg/dl with a mean of 11.59 mg/dl (+ 2.32), while hematocrit varied between 18 24 Rise in Hct is more distinct, rapid, and significantly higher in DHF than in DF. 9 In a study on various dengue syndromes a raised Hct was seen in 13.2% of patients at the time of presentation. 20 Endothelial dysfunction leading to increased vascular permeability is a hallmark of severe dengue leading to leakage of fluid into pleural and peritoneal cavities and shock. 25

Conclusion
Careful assessment and interpretation of hematological changes in pediatric dengue patients not only allow early diagnosis but also aid in adopting appropriate treatment.