EPIDEMIOLOGICAL AND CLINICAL SPECTRUM OF DENGUE FEVER AT TERTIARY CARE HOSPITAL IN CHITWAN: A HOSPITAL BASED STUDY

Background: Dengue fever is one of the most common tropical diseases caused by an arbovirus. This virus is a member of genus Flavivirus and flaviviradae family, is transmitted by bite of Aedes aegypti mosquito. Its outbreak is being reported from different parts of the world including Nepal. This disease is prevalent throughout Nepal mostly in terai regions. The aim was to study the epidemiological and clinical spectrum of dengue fever at tertiary care hospital in Chitwan.


INTRODUCTION
Dengue fever is a dreadful disease caused by the Dengue virus. Dengue virus is an RNA virus, a member of flaviviradae family with 4 different serotypes (DENV1-4). It is transmitted to humans by a bite of a female mosquito called Aedes (Ochlerotatus) aegypti. It has an incubation period of 4-10 days.
In the late 18 th century, Benjamin Rush termed dengue as "Break Bone Fever". In 2001, there was a global epidemic and by the year 2010, it was one of the 17 neglected tropical diseases. WHO estimates more than 50 to 100 million infections worldwide every year. 3  The aim was to study the epidemiological and clinical spectrum of dengue fever admitted in tertiary care center of Central Nepal, hence our effort is to improve the diagnostic facilities and preventive measures and alert the citizens against this disease.

METHODS
This prospective study was carried out in Chitwan Medical College (CMC), Bharatpur, Chitwan from 1 st of September 2019 to 30 th of February 2020. Chitwan Medical College (CMC), being a tertiary multidisciplinary hospital, people of undiagnosed fever come from various nearby districts. The approval for the research was taken from the Ethical Review Committee of CMC. After taking informed consent, a prospective consecutive study was carried out during this six-month period. All the patients admitted in tropical ward with diagnosis of dengue fever was included during the study period.
Inclusion criteria were patients above 18 years of age, who had fever with either Dengue NS1 antigen test, IgM or IgG ELISA test positive. Exclusion criteria were age below 18 years or any coinfection with tropical diseases like Scrub typhus, Malaria, Leptospirosis, Enteric fever or other bacterial infections.
Detailed history, clinical examinations were performed in these patients. Laboratory investigations such as complete Blood count, liver function tests and ultrasound abdomen was done. Dengue NS1 test was done to those who had fever for less than 5 days, Immunoglobulin M (IgM), Immunoglobulin G ISSN 2091-2889 (Online) ISSN 2091-2412 (Print) (IgG) ELISA was done in patients having fever for more than 7 days and both antigen test and ELISA was done who had fever between 5 and 7 days. These patients were categorized as Dengue fever, Dengue hemorrhagic fever and Dengue Shock syndrome and managed according to the WHO protocol.
Laboratory investigations such as complete blood count and liver function tests were done at the time of admission, during hospital stay and a day before discharge to look for the improvements in leucocytes, platelet counts and transaminases level. Patients were followed up in OPD after 1 week of discharge. Data were collected by using a predesigned proforma and entered in a SPSS 16.0 (Statistical Package for Social science) version. Demographic, clinical, hematological, biochemical, and radiological parameters were assessed. Mean and standard deviation was calculated for continuous variables and frequencies for categorical variables.

RESULTS
In our study, a total of 241 patients admitted were diagnosed with dengue fever during the six months period. The age and sex distribution of the patients is depicted in Table 1. The mean age of the patients was calculated as 34.44 years on the basis of descriptive statistics. More than half (56%) of the dengue patients belonged to the age group of 25-44 years. Dengue was more commonly seen in male than in females (61.4% Vs 38.6%) with male: female ratio of 1.6:1.

Figure 1: Distribution of dengue cases according to symptoms
As the clinical features are concerned, all the patients had come with fever with one or more associated symptoms as shown in Figure 1 below. The mean duration of the fever was 3.58 days.
Another common complaint in our study was retro-orbital pain present in 203 patients (84.2%) followed by headache (80.1%), myalgia (61%) and vomiting (39%). Table 2 showed most patients being admitted were from Chitwan district (68.46%), followed by Makwanpur (13.27%) and Nawalparasi district (10.37%).  Table 3 showed the laboratory parameters of the patients. The most common hematological abnormality was leucopenia (71.8%).  The Table 4 showed the days when patients presented to the hospital with fever. More than 60% of patient presented be- fore fifth day of onset of fever so as per protocol these patients were tested for NS1 antigen only. From 5 to 7 th day around 39 % of patients presented with fever. None presented after 7 th day. This corrugates well with the positivity of serological test done depending on the days of duration of fever. Serological profile of the patient is depicted below in Figure 2.

Figure 2: Serological Profile of Dengue Fever Patients
The most common type of serology which was positive was NS1 Antigen test (84%). 23 patients (9.5%) were positive for both NS1 and IgM antibody.  Around 68% of patients with dengue fever were from Chitwan followed by neighboring districts such as Makwanpur, Nawalparasi, Gorkha, Butwal, Bara and Tanahu respectively which imply that this virus is not limited to terai regions only. This may be due to travel to an endemic area, urbanization and prevalence of marshy areas where mosquitoes breed and multiply easily.⁵ The mean duration of hospital stay in our study was 3.86 days conflicting with the study done by Mehta et al. 10 This could be because of non-availability of beds in our hospital during the outbreak of dengue fever and early improvement of patients leading to early discharge of the patients. The severity of dengue fever is predicted by severe thrombo- cytopenia. In a study done by Mandal et al there was severe thrombocytopenia in 38% of patients. We have found only 21 patients (8.7%) having severe thrombocytopenia (<50000/ cu.mm) suggestive of lesser severity and low mortality rate in our study.
Liver enzymes such as Aspartate Transaminase (AST) and Alanine Transaminase (ALT) was elevated in more than 45% of cases in our study. Similar results was seen in the studies by Laul et al. 27 Jayadas et al. 20 found elevated AST than ALT level in accordance to our study and this may be secondary to release of AST from the parts other than liver (heart and striated muscles). Deranged liver function in dengue infection can be a result of the direct attack of the virus on liver cells or the unregulated host immune response against the virus. Fulminant hepatic failure occurs because of acute severe hepatitis and massive necrosis of the liver, causing hepatic encephalopathy and even death. 22 The most common peak season for dengue infection in this study was in the month of mid-August to last week of September. This kind of seasonal response was seen in research conducted by Gupta et al. and studies from tropical countries like India, China and Philippines ., These months are the post monsoon period in Nepal where mosquitoes have a favourable climate to breed and multiply thus serving as a vector for transmission of virus in humans.⁵ The most common type of serological test to be positive in this study was Dengue NS1 antigen test. NS1antigen test was positive in 201 patients (84%) followed by combined NS1 and IgM positivity in 23 patients (9.5%). Similar result was shown in North Indian study and a study conducted by Chhotala et al. 4 The higher NS1 positivity may be because many patients came to our hospital and got admitted within two or three days of fever when this particular test is specifically done aiding for early identification and prompt notification. There are also evidences that sensitivity of NS1 antigen test is higher in primary infection(>90%) and even correlated with higher levels of viral load.
Dengue IgM antibody test was positive in only 11 patients (4.5%) in our study. A study published in 2012 by Shah et al. 6 showed seropositivity of Dengue IgM cases to be 9% which was twice than our study.
The ultrasound findings in our study simulated with the study done by Laul et.al. 27 Hepatomegaly and GB edema may be due to direct viral invasion of gall bladder and liver leading to protein rich plasma leak causing increase in severity. 24 Out of 241 dengue cases admitted for a certain period in the ward there was only 1 death with a case fatality rate of 0.41% similar to the research conducted by Antony

CONCLUSION
Dengue, an arthropod borne viral disease poses a significant morbidity and a high financial burden. With each outbreak, the number of confirmed cases have increased significantly. In our analysis, Leucopenia, rather than thrombocytopenia was the most common laboratory finding. Furthermore, the study also showed cases from the hilly areas implying that dengue was not limited to terai regions only. Hence, there should be a proper surveillance of the infection, start an integrated vector control programme, make an awareness programme and emergency preparedness for this cyclical outbreak.