Clinical and seasonal pattern of dengue in a tertiary care hospital of South West India

Background Dengue is an emerging global viral disease with an increase 30-fold in incidence in the past fifty years. In the past decade it was restricted to only few a states of South and Northern India but in the recent past it has affected almost all the states in India. The objective of this study was to assess the clinical profile, trends and outcome of dengue cases. Methods This retrospective record based cross-sectional study was conducted in tertiary hospital, Mangaluru in Southern India. The study population included all dengue positive cases diagnosed either by IgM Capture ELISA or Dengue Non-structural Protein NS1 antigen over a period of five years. Information from pre-recorded case sheets were used for data collection. The data was analyzed using SPSS Version 20. Results from the analysis have been expressed in percentages, means and graphs. Results The study included 401 dengue cases. Most cases were in the age range of 20-40 years with a male to female ratio of 3:2. Overall seropositivity rate was 23.94% with High IgM prevalence. Monthly distribution showed a maximum cases were in the months of June and July and minimum were in January and February. Among the study participants, 91.5% of patients recovered completely and 1.7% of patients had died. 6.8% of patients were discharged against medical advice. Conclusions Dengue continues to be major public health problem in this part of the globe affecting mainly the working age group. Low seropositivity with High IgM prevelance makes dengue an important differential for febrile illness of vague nature and invokes the need for robust public health response to curb the hyper-endemicity.


Introduction
Dengue is an emerging global viral disease with an increase in incidence of 30 times in the past fifty years.Nine countries were affected before the 1970s but now more than 100 counties have severely been affected with dengue epidemics with the Southeast Asian region and the Western Pacific region being the most severely affected.390 million cases of dengue occur annually with 96 million showing clinical manifestation. 1 The first case of dengue was reported by Benjamin Rush in 1789.Up until the middle of 20 th century it was restricted to few geographical locations, but with the population movement during the Second World War there were recurrent epidemics with the re-emergence of the disease. 2 Even though the first epidemic of dengue was reported from Chennai in India, the virologically proven epidemic occurred in Kolkata in the 1950s.There were cases of dengue hemorrhagic fever and dengue shock syndrome in Delhi and Lucknow in the year 1996, thereafter with a cyclical pattern occurring every 2-3 years. 2 In the past 20-30 years it was mostly restricted to only a few states of South and Northern India but in the last decade it has affected almost all the states of India. 3ngue is viral vector borne disease spread by the day-biting endophilic Aedes mosquito.Its clinical features tend to be vague and nonspecific, ranging from fever to hemorrhage to shock with no specific treatment but supportive care. 4,5ographically, dengue is more prevalent in tropical countries like India.With that background understanding, we conducted our study in the coastal part of South India where developmental activities are on a rise with rapid urbanization where the study population is at a high risk of being affected with dengue.Our study was conducted to determine the socio-demographic and clinical profile along with the disease outcome of dengue patients.As information regarding the trend, burden and distribution of the disease is vital to plan disease control strategies and optimum utilization of the resources, our study aims to further contribute to the knowledge base regarding this disease.

Study location
The study was conducted at Government Wenlock Hospital, a tertiary care teaching hospital affiliated to Kasturba Medical College, Mangalore.
Being a hospital which receives a confluence of patients from neighbouring districts of Karnataka and from northern parts of Kerala.However, this being a district hospital and suggest that the trend in this hospital could reflect what is happening in and around this location.

Study population
All dengue patients admitted to Government Wenlock Hospital within the time frame of five years from 2013 to 2017 were included in the present study.This includes patients from Dakshina Kannada district of Karnataka, northern Kerala districts such as Kasargod, Kannur and Wayanad with minimal number of patients from other districts of Karnataka as well.
Inclusion criteria: Clinically confirmed Dengue cases admitted at the above-mentioned time period.IgM Capture ELISA and Dengue Non-structural Protein NS1 antigen test which is a rapid test kit, were used for the diagnosis of Dengue in the study participants.
Exclusion criteria: All case sheets with inadequate or incomplete data were excluded from the study.

REVISED Amendments from Version 2
All the comments by the reviewer were addressed and necessary changes have been done.

Ethics and consent
The IEC (Institutional Ethics Committee) of Kasturba Medical College, Mangalore (Manipal Academy of Higher Education) has reviewed the study and has granted approval prior to the onset of the study.Owing to the nature of study design as retrospective record based study, informed consent was waived by the Ethics Committee.Confidentiality of the present study data was maintained in accordance with the Declaration of Helsinki.

Data collection
Case sheets of Dengue positive patients fitting the inclusion criteria were carefully analyzed.Relevant demographical, clinical and biochemical parameters were recorded onto the data collection sheet.

Analysis
Data collected was then analyzed with SPSS version 20.Results have been expressed in means, proportions and standard deviations.

Demographic profile
Our study was able to reinforce the prevalence of certain demographic trends that has been observed among patients affected with Dengue.Out of the 401 patients studied, 245 (61%) were males with a male to female ratio of 3:2.Majority of the cases fell under the age bracket of 20-40 years (169 cases, 42.1%) (Table 1).Certain demographic details such as occupation, marital status, place of residence were not available for all the patients and hence were not reported upon in our results.

Clinical and laboratory findings
The most common and consistent clinical feature with which most of the patients presented with was fever (398, 99.3%) proceeded by chills and rigor (256, 63.8%) followed by myalgia (194, 48.4%) (Table 2).
In line with expected trends, it was observed that most of our cases (n=368, 95.8%) had thrombocytopenia.81.6% of patients had elevated SGOT and 48% had elevated SGPT enzyme levels indicating certain degree of hepatocyte injury during the acute phase of the infection.However, a closer look at the seropositivity rate amongst the study population posed some interesting queries.Out of the 401 cases, only 96 cases showed elevated IgG or IgM (total seropositivity rate of 23.94%).Separately, seropositivity rate of IgM was 22.9% and of IgG was 2.7%.Sex wise distribution shows 25.7% seropositivity in males and 22.72% seropositivity among females.Dengue Non-structural Protein NS1 antigen test which is a rapid test kit, was used for the diagnosis in the remaining cases.

Clinical outcome
Our study revealed that regardless of the initial presentation and clinical progression, the majority tended to recover, with a recovery rate of 92%.(n=367).Case fatality rate was recorded to be 1.7% (Table 4).

Seasonality
Dengue being a vector borne disease was expected to boom in accordance with the monsoon seasons and our study was able to confirm this.As depicted by Figure 1 [Month wise distribution of dengue cases (n=401)], most of the cases were found to have been admitted during the months of June and July with a declining trend both pre-and post-monsoons.The months of January to April were shown to have a consistently lower admitted case load.Figure 2 represents the year wise distribution of Dengue cases admitted in the hospital.

Discussion
Dengue is an upcoming and swiftly spreading vector borne disease that has taken strong hold in India. 4Owing to the complicated interplay between the host, agent, vector, and environmental conditions, the number of cases in India has consistently increased substantially over the past ten years. 6It is now even considered as a hyper endemic disease in certain parts of India.As Das et al. demonstrated in their study, the available data on dengue prevalence in India is just the tip of the iceberg and that further weighs down the preventive measures taken to reduce the brunt of the burden. 7Having recognized the need for comprehensive stratified data on dengue prevalence and its trends to further the knowledge database in Indian population, we focused our study to assess the various clinical, sociodemographic and climactic factors.
Our study was able to demonstrate a significant male preponderance (male = 61%, females = 39%) in cases of dengue reporting to this hospital with a male to female sex ratio of 1.5:1.Similar observations have been made by a multitude of studies, yet a conclusive reasoning has not yet been attributed to this trend. 8Doke and Pawar has attributed this finding to the nature of dressing among women which reduces the amount of skin exposure. 9Other studies have explained this as a product of reporting bias among females as it has been seen that traditional practitioners are the first point of contact for the large majority of symptomatic female population. 10A few studies even postulated that this disparity could be due to the skewed sex ratio leaning towards the side of males in the general population. 11 Apart from the male preponderance, our research found that the productive working class aged 20-40 years was the age group most affected.Owing to the declining rate of incidence with advancing age, it could be said that infants, adolescents and young adults are at higher risk of developing dengue.[14][15] Combined, the age and sex distribution findings could be attributed to the complex interplay between outdoor nature of work (among men), 9 dressing patterns (among women), skewed sex ratio and diurnal feeding habbits of Aedes aegypti. 4st of the cases were found to have occurred in the months of June and July, with the maximum being 120 cases.A study conducted by Kumar et al. in a coastal city of Karnataka revealed the maximum cases were found to have occurred in the month of September while a meta-analysis conducted by Ganeshkumar et al. found that most cases were seen in the monsoon and post monsoon seasons. 13,16The peri-monsoon seasonality of dengue has also been promptly emphasized by a number of studies which implicates that there is a strong correlation that exists between temperature and humidity to the favourable breeding conditions for the mosquitoes. 3,13,14During rainy season environmental changes such as artificial water stagnation, especially in low lying areas, labour settlements and small collection of water in tyres and flowerpots act as favourable breeding grounds for the vector which conclusively explains the precipitous climb of dengue cases during June to September. 14e clinical picture of patients in our study revealed that fever was present in almost all cases (99.3%) followed by chills and rigor (63.8%).Haematological symptoms included hematemesis and haematuria which were present in 12% and 7% of cases respectively.A meta-analysis conducted on a global scale on dengue outbreaks came to an almost similar picture with fever (98.1), chills (65.3), myalgia (64.2), arthralgia (53.6), body pain (67.2), vomiting (39.8) etc. with similar haematological symptoms like haematuria and hematemesis which were seen in 5% and 13.4% of cases respectively. 17ver functions test showed abnormal rise in almost 99% of patients of SGPT and SGOT levels but SGOT levels were more prominent in most patients as compared to SGPT, similar research done in Punjab in 2007 had similar results with 98.9% of patients showing a rise in either of SGPT or SGOT levels indicating a strong heptic predeliction for dengue virus. 18A dedicated study regarding dengue and hepatopathy also revealed similar results of elevated SGOT and SGPT with the former being more elevated than the latter. 19rombocytopenia is the most common laboratory finding in dengue patients and is referred to as an early marker and prognostic factor for the management and recovery of dengue fever. 20Of 384 dengue patients studied, 368 patients had thrombocytopenia (platelet count less than 100,000 per mm 3 ).
Our study revealed a seropositivity rate of 23.94% which is similar to another study conducted by Kalita et al.where they repoted a seropositivity of 14.85%. 21Along with having a low seropositivity rate, it was seen that High IgM prevelance was noted in our study.As concluded by Eshetu et al., high IgM prevelance is indicative of active transmission of dengue which could account for the hyperendemic status of dengue in Southern India. 22r study included 401 serologically confirmed dengue cases out of which 367 cases (91.5%) were found to have recovered completely.Seven deaths were recorded (1.7%), and 27 cases (6.8%) were found to have been discharged against medical advice.A meta-analysis conducted in India, found that the pooled CFRs of the studies was 2.6% which was in line with findings of the present study. 16

Conclusion
Dengue remains to be a major public health problem in this part of the globe, affecting mainly the working age group.With vague nonspecific clinical features combined with low seropositivity rate, it is of paramount importance to keep dengue as a key differential when a patient presents with febrile illness of nonspecific nature.High IgM seropositivity also hints at the fact that a strong and robust vector control programme must be implemented to at least make a dent in the hyperendemic status of dengue especially during the monsoon seasons.

Biju Soman
Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India This is a good attempt at looking at the data from a prominent tertiary care hospital in Mangalore.However, the inference drawn by the authors conflicts with the hospital-based nature of the data.The manuscript should be rewritten as a hospital-based study, and the authors should refrain from giving statements on hyperendemicity, etc.The following detailed comments should be kept in mind while revising the paper."The study population included all clinical dengue positive cases over a period of five years."(p.Author's Response: We agree that it would be better to represent our data as a hospitalbased study that reflects the Dengue burden in the coastal districts of Kerala and Karnataka.We will also take into consideration the note to add year wise distribution of Dengue cases.Action Taken in the manuscript: Study title has been changed as per the suggestion.The results obtained have been rephrased to be a representation of a hospital-based survey.Year wise distribution of Dengue case load has been added as a graph.
4.Comment: This sentence is also unclear; the manuscript will benefit from thorough copy editing.
Author's Response: We agree that a thorough copy editing would help communicate the conclusions better to the reader.Action Taken in the manuscript: Necessary grammatical changes have been made

Zinia Nujum
Department of Community Medicine, Government Medical College, Kollam, Kerala, India

General Comment
The study is a single centre study done on a topic of public health relevance, but the information presented is not new.In order to bring in an analytic perspective, I would suggest classification of dengue cases into severe and not severe based on the need for hospitalization or shock and look at the determinants of severity.Since the number of deaths is small, they may also be included as severe dengue.
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5 .
Comment: "The data collected was entered and analyzed in SPSS Version 20" (p. 1) Please copy edit Author's Response: We agree that this statement could be rephrased better.Action Taken in the manuscript: This sentence has been rewritten 6. Comment: "Results were expressed in percentages, means and graphs."(p. 1) Please copy edit Author's Response: We agree that this statement could be rephrased better.Action Taken in the manuscript: This sentence has been rewritten Competing Interests: None to declare.Reviewer Report 25 October 2023 https://doi.org/10.5256/f1000research.139295.r187595© 2023 Nujum Z.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Table 3 .
Laboratory profile of dengue patients.

Table 2 .
Distribution pattern of the chief presenting complaints (n=401).

the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests:
1)Give the exact period and the jurisdiction.If it is the Mangalore town, define it; if it is the district, specify it.This assumption cannot be justified.Try to present this as a hospital study; at the most, you can claim this hospital as a sentinel hospital and suggest that the trend in this hospital could reflect what is happening in and around this location.However, please remember that Wenloc Hospital can no longer claim to cater to all or even a good majority of Dengue cases in the locality.There are many other government and private hospitals in the area.Also, it would help if you did a trend analysis to state the increase, decrease or other status of Malaria cases coming to the hospital.The Yearwise distribution should be used.No competing interests were disclosed.
○"Results were expressed in percentages, means and graphs."(p. 1) Please copy edit ○ "Among the study participants, 91.5% of patients recovered completely, and 1.7% of patients had died.8.7% of patients were discharged against medical advice."(p. 1) Better round the decimal figures to 100% ○ "Being a hospital which receives a confluence of patients from neighbouring districts of Karnataka and northern parts of Kerala, our study population well represents the burden of dengue in the South Western part of India."(p.3)○Is

have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.
We are in complete agreement with your observation.Our subset of patients are mainly residents of Dakshina Kannada district of Karnataka, Northern Kerala districts such as Kasargod, Kannur and Wayanad with a minority group of patients from other districts of Karnataka as well.

Action Taken in the manuscript:
Necessary changes have been done in the Materials and Methods section of the manuscript.We concur that it is better to round the decimal figures as pointed out.This assumption cannot be justified.Try to present this as a hospital study; at the most, you can claim this hospital as a sentinel hospital and suggest that the trend in this hospital could reflect what is happening in and around this location.However, please remember that Wenlock Hospital can no longer claim to cater to all or even a good majority of Dengue cases in the locality.There are many other government and private hospitals in the area.Also, it would help if you did a trend analysis to state the increase, decrease or other status of Malaria cases coming to the hospital.The Year wise distribution should be used.