A Review on Epidemiology of Dengue Viral Infection as an Emerging Disease

 

Rouhullah Dehghani1, Hamid Kassiri2

1Social Determinants of Health (SDH) Research Center and Department of Environment Health,

Kashan University of Medical Sciences, Kashan, Iran.

2Department of Medical Entomology, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

*Corresponding Author E-mail: Hamid.Kassiri@yahoo.com

 

ABSTRACT:

Dengue Virus (DENV) is transmitted by mosquito bite. This paper discusses the importance of Dengue Fever (DF) as an emerging disease in the world. In this study, some keywords such as break bone fever, dengue fever, dengue hemorrhagic fever, epidemiology, transmission methods, clinical manifestations, treatment, prevention, reservoirs, vectors, and Iran were searched on the Internet and reputable medical journals in order to find the papers published from 1988 to 2020. Until the mid-20th century, Dengue fever was restricted to special parts of the tropics and subtropics. Climate changes, increasing international travels and urban population, ineffective vector control methods, the lack of safe and effective antiviral drug and vaccine to prevent the disease are among the various factors contributing to the global distribution of DF. Dengue fever is a serious global threat to the lives of over 2.5 billion people in over 100 countries. Today, DF is endemic to Asia, Africa, South America, and the Caribbean. In fact, approximately 40% of the world's population is now living in countries with a high risk of DF transmission. The disease is endemic to urban and suburban areas across the tropics and subtropics of the world. It has been reported as an imported disease in Iran in recent years. Due to the appropriate climatic conditions and the presence of vectors, DF is likely to become endemic to Iran and put a large proportion of the population at risk of transmission. Therefore, the DF vectors' control should be precisely and consistently included in the Iranian health system’s agendas.

 

KEYWORDS: Break bone fever, Dengue fever, Dengue hemorrhagic fever, Epidemiology, Treatment, Vectors, Reservoirs, Control, Iran.

 

 


1. INTRODUCTION:

Dengue Fever (DF) is a major mosquito-borne disease and the most common arboviral infection among travelers. It is considered a dangerous global threat to human life and public health. There has been no report of the Dengue Virus (DENV) in some regions of the world before. However, the virus and its associated disease are now spreading in some of the world’s countries, including Iran. The annual incidence of DF has increased by 50 times over the last 50 years. The number of DF cases reported has increased from 2.2 million in 2010 to 3.2 million in 2015.

 

 

 

 

About half of the world's population (3.9 billion people) in 128 countries are at risk of DF. Only 9 countries had experienced severe dengue epidemics before 1970; however, DF is currently endemic in more than 100 countries (including Europe and the US). It is estimated that 390 million cases of dengue infection occur worldwide every year, 96 million of which result in clinical manifestations. The mortality rate of DF has been reported to be 5-20% in some regions. According to WHO estimates, 500000 cases of DHF annually occur worldwide, 22000 of which cause death. The American, Southeast Asian, and Western Pacific countries are the world’s most DF-affected areas. There have been numerous DF epidemics so far in China, Pakistan, Saudi Arabia, Japan, Yemen, Taiwan, Malaysia, Brazil and Mexico1-6.

 

The causative agent of DF belongs to the family Flaviviridae and the genus Flavivirus. There are other mosquito-borne viruses in the family, such as West Nile virus, Japanese encephalitis, Zika fever and yellow fever, all of which are single-stranded RNA viruses. Other Flaviviruses are transmitted by ticks and are responsible of encephalitis and hemorrhagic diseases: tick-borne encephalitis, Kyasanur Forest disease, Alkhurma hemorrhagic fever, and Omsk hemorrhagic fever7,8. Dengue virus is a spherical particle, 40-50nm in diameter and 11 kb in size. The virus encodes 3 structural proteins, namely capsid (C), envelope (E), and membrane (M), and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). Dengue fever virus is classified into four serotypes (DEN1, DEN2, DEN3, and DEN4). It is generally stated that these four serotypes were originated from monkeys and then transmitted to humans in Southeast Asia and some parts of Africa about 100 – 800 years ago3. Infection with one serotype cannot protect humans against the other three serotypes. DENV causes a wide range of diseases in humans, from a self-limiting DF to a life-threatening syndrome called Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS). Once a person is infected with one serotype and recovers, the person will acquire lifelong immunity to that serotype. Cross-immunity following a viral serotype infection may provide partially and temporally immunity to other serotypes. The first infection with DF causes mild symptoms, but the second infection may cause severe illness (DHF or DSS) in children or adults. This phenomenon is called antibody-dependent enhancement. Mild DF causes fever above 40°C, headache, rashes, eye pain, vomiting, swollen lymph nodes, and muscle and joint pain. A severe form of DF can cause severe ecchymosis, hematemesis, severe abdominal pain, nosebleeds and bleeding in the mouth, permanent nausea, pulmonary, cardiac and hepatic problems, hypertensive shock, and death. It is difficult to diagnose the disease because there are many diseases with symptoms similar to those of DF. ELISA test (for antibody or antigen detection) and PCR are available for detecting DHF. DF is transmitted with a virus, so there is no drug or antibiotic to be prescribed for its treatment. Treatment for DF involves relieving the symptoms. Supportive care is the preferred strategy for disease management through the use of analgesics like acetaminophen, hydration with electrolyte fluid replacement, drinking fluids, and adequate rest. There is no vaccine available to treat DF. The only method of controlling or preventing DF is to control the vector mosquitoes3,9-11. Until the mid-20th century, DF was restricted to special parts of tropics and subtropics. DHF was first reported in the 1950s and two epidemics occurred in the Philippines and Thailand. The World Health Organization (WHO) considers dengue as a major global public health challenge in the tropics and subtropics. Dengue has undergone a 30-fold upsurge worldwide between 1960 and 2010, due to the increased population growth rate, global warming, unplanned urbanization, inefficient mosquito control, frequent air travels, and lack of health care facilities. The increasing international travel and climate change have recently changed the geographical distribution and increased the number of DF cases5,7,12,13.

 

India is one of the countries where DENV is endemic and DF has been a major health crisis over the last 50 years. The first case of DF in India was reported from Madras in 1780. The first epidemic of DF in India occurred in Calcutta and the Eastern Coast of India in 1963-196414. DENV infection exhibit a variety of clinical manifestations ranging from asymptomatic infection and DF to severe hemorrhagic fever and Dengue Shock Syndrome (DHF/DSS)10,15. DF has been endemic in Pakistan for many years because of the temperate climate of this country16,17. In this country, several outbreaks of DF serotypes have been reported since 200618, mainly due to extensive farmlands, rich animal biodiversity, water reservoirs behind dams for power generation, open irrigation canals, and heavy floods and rainfall. These factors provide suitable conditions for the breeding of DENV- vector mosquitoes. The biological and seasonal activities of mosquitoes vary widely in different geographical areas. However, in most cases, the incidence of DF increases after the rainy seasons13.

 

There are currently several epidemics of DF in neighboring countries of Iran, including India and Pakistan, which both infect a large number of people in these countries every year and take the lives of many of them. Thousands of Iranians travel to India and Pakistan every year for various reasons. In addition, many people of these countries also travel to Iran who may be exposed to DENV in some cases. On the other hand, the emergence of DF in Iran, probably from eastern borders, makes it crucial to study the status of the disease and effective ways of its prevention and treatment. The present review study hence aimed to do so.

 

2. MATERIALS AND METHODS:

In this study, some keywords such as break bone fever, dengue fever, dengue hemorrhagic fever, epidemiology, transmission methods, clinical manifestations, treatment, prevention, reservoirs, vectors, and Iran were searched on the internet and reputable medical journals in scientific databases including Web of Science, Ovid, PubMed, SID, Iran Medex, Scirus, Google Scholar, and Medline to find Persian and English papers published from 1988 to 2020. A total of 99 papers were found and finally 56 of which, were selected for further analysis considering the study objectives and emphasis on DF in Iran. Ethical subjects (Including plagiarism, double submission and/or publication, redundancy, misbehavior, information fabrication and/or falsification, etc.) have been entirely considered by the researchers. All data were analyzed according to the relevant laws and guidelines of the ethical standards of the Declaration of Helsinki.

 

3. RESULTS AND DISCUSSION:

Dengue fever begins suddenly with an influenza-like syndrome and sometimes develops more severe forms. Sometimes the disease lacks clinical symptoms. High fever, muscular and articular pain, rashes, bleeding, and shock are common symptoms observed. Oral manifestations are rarely seen in dengue infection. However, some patients may present oral manifestations as the only clinical symptom. Early and accurate diagnosis is crucial to reduce mortality. Although DENV infections are usually self-limiting, dengue infection is considered a public health challenge in the tropics and subtropics19,20.

 

The first case of DF infection in Pakistan was reported from Punjab in 1982. Since then, about 8–10 outbreaks of DF have been reported from this country. DF has been a major public health problem in Pakistan since 2005, and almost 71649 cases and 757 deaths caused by DF were reported until 201616,21-23. A major DF epidemic was reported from Punjab in 2011 with an estimated 50,000 cases reported from Lahore only by the end of November 201124. A review study indicated that the estimated number of DF cases in District Swat in Khyber Pakhtunkhwa (KP) Province, Pakistan, in 2013 was 8546, including 33 deaths. The prevalent serotypes that caused the outbreak were serotypes 1, 2 and 325. Another study reported the number of DF cases in Swat to be around 6000, out of which 69% of patients were male. Random cases of DF infection were also reported from 3 other provinces of Pakistan. About 2165 cases of DF were reported from Punjab in 2013 by various health departments, 50% of which were related to Rawalpindi. In a study conducted during 2016 and 2017, 34% of the population in Faisalabad, Pakistan was infected with DF 16, 26-28.

 

Iran is highly at risk because of its proximity to DF-affected regions. Due to its geographical and critical situation and being in close proximity to countries undergoing DF epidemics, southern regions of Iran, i.e. Sistan – Baluchestan and Hormozgan Provinces, are more at risk. The southeastern borders of Iran are the center of commercial activities and commute of many people between Iran and the neighboring countries that may be undergoing DF epidemics. Hence, Iran is at the probable risk of a DF epidemic. In 2008, the first case of DF was reported in Iran and the patient had previously traveled to Malaysia2,29. In 2013, a 58-year-old woman who had traveled to Malaysia was diagnosed with DF. The patient visited Mehr Hospital of Tehran with dermal symptoms such as rashes, body pain, and fever2. In 2016, a 52-year-old man, suffering from hyperglycemia and hyperlipidemia, who was a shopkeeper in Bahrain, visited a doctor after traveling to Iran with DF clinical manifestations and positive DENV test results30. In another case reported in 2016, a young woman with cold-like symptoms visited Vasei Hospital of Sabzevar. The patient had traveled to Malaysia, as mentioned in her history. She was hospitalized with high fever, headache, and lethargy. Then, she underwent supportive therapy. The following day, symptoms such as bone pain, myalgia, shortness of breath, abdominal pain, severe headache, eyestrain, and maculopapular lesions appeared along with nausea, vomiting and diarrhea. Laboratory findings showed high-grade fever, leukopenia, and severe thrombocytopenia. According to the findings, DF was diagnosed and the patient's serum sample was sent to a reference laboratory for IgM analysis31. In a study conducted in Iran, among 300 sera tested negative for CCHF between 2000 and 2012, 5% were seropositive and 1% of both serum and PCR were positive for DF. Of the 15 seropositive cases, 8 had traveled to India, Malaysia, and Thailand and 7 had no history of traveling abroad. Of these, 6 were from Sistan–Baluchestan Province32. In another study, five patients with acute DENV infection were diagnosed in Sistan – Baluchestan Province during 2013-20151. The possible reaction between this virus and other Flaviviruse in this area, that cause West Nile fever, Saint Louis encephalitis, Japanese encephalitis, and yellow fever, should be addressed by researchers. Although West Nile virus has been present in the area, no encephalitis symptoms have been reported in any of the patients under study32-34. Iran is exposed to DF from two geographic regions. There is a risk of infection from Pakistan and the terrestrial spread of the disease and its vectors to Sistan – Baluchestan Province. There is also a risk of infection of the islands and coastline from the south and the Persian Gulf and the Oman Sea. The southeastern region of Iran and its southern coastline are zoo geographically lied into the oriental zone, including South Asia, India, and Pakistan, and are considered subtropical in terms of climatic conditions. As a result, their climatic features are different from other regions of Iran located in the Palearctic realm. According to reports of potential vectors, DF outbreaks are likely to occur in the south of Iran35, 36.

 

The animal reservoir of DF is unknown. Researchers have found that humans are the main reservoir of the virus. Mosquitoes are vectors of the disease. The infected female Aedes mosquitoes infect humans by biting them and sucking their blood. Aedes feeds blood throughout the day especially in the early morning and near sunset before dark. The yellow fever mosquito Aedes aegypti (Stegomyia) (L.) and the Asian tiger mosquito A. albopictus (Stegomyia) (Skuse) are two main vectors of DF. Aedes albopictus is the DF vector in southeastern Asia. Ae. aegypti and Ae. albopictus are container-breeding and invasive mosquitoes. Aedes aegypti rests in internal places and feeds blood mainly on humans during daylight. Aedes albopictus alternatively feeds blood on animals and humans and desires to rest in external places but has also been shown to exhibit strongly anthropophagic behavior like Ae. aegypti. Aedes albopictus has the largest global distribution among these mosquitoes. Lately, Ae. albopictus caused public threats by spreading its range to the Americas, Europe and Africa through active transportations, human activities and the international trade of used tires37-41. Iran, as an Asian country, has several DF vectors. The virus can be passed to the next generation through the eggs. So, the mosquito also plays the role of a reservoir for the disease. The mosquito will remain infected with the virus for its entire life. In order to transmit the disease, the virus must be able to replicate in the mosquito's blood and then migrate to the mosquito's mouth parts. As a mosquito bites an infected human, the virus requires an 8-12-day period before the mosquito can pass it to another person. Approximately 4-7 days after an infected mosquito bites, symptoms appear in the person, which last between 3-10 days. Most people do not show symptoms (80-70%) but some (10-20%) show flu-like clinical symptoms or sometimes severe forms of the disease (DHF or DSS) occur. In the severe form of the disease, severe vomiting, uncontrolled bleeding in the skin, blood in the urine and stool, enlargement of the liver and spleen, hepatitis, abdominal pain, bleeding, severe hypotension and coma are the main manifestations. About 30% of patients have oral mucosal involvement, although oral symptoms are mostly related to DHF rather than DF3,4,7,15,19.

 

Seventy species of mosquitoes from Culicidea family have been reported in Iran. Studies suggest that there are either seven or eleven genera depending on the classification used for aedines and 40 species of Culicinae mosquitoes in Iran. There are thirteen species of Aedes in Iran, including Ae. geniculatus, Ae. unilineatus, Ae. echinus, Ae. vexans, Ae. vittatus, Ae. caballus, Ae. flavescens, Ae. caspius, Ae. pulcritarsis, Ae. detritus, Ae. leucomelas, Ae. albopictus and Ae.aegypti. In Iran, Ae. albopictus and Ae.aegypti have recently been caught in small numbers in Sistan – Baluchestan and Hormozgan Provinces, respectively35,36, 42-45. Aedes mosquitoes are easily distinguishable from other mosquitoes by having white stripes on their body. Aedes aegypti and Ae. albopictus are easily recognizable by their dorsal thoracic patterns. The DF mosquito vector has a tendency to lay eggs in used tires. The water that accumulates beneath evaporative coolers in southern regions of Iran is also a good place for egg laying the Aedes mosquitoes. Pots of ornamental and bamboo plants imported to Iran can move vectors into the country. Other ways of transporting vectors to Iran is through cargoes; so, trade with other countries should be done with great care. The mosquitoes of the Culicinae family are one of the most common household pests in Iran42,46-51.

 

Iran is in a climatic and geographical condition suitable for the transmission of DF arbovirus and some other Flaviviruses. According to available evidence, the geographical distribution of potential outbreaks will be in the eastern border regions and southern coasts of        Iran 50. Immigrants from neighboring countries for economic and tourist reasons could increase the risk of disease transmission in Iran35,36,52. DENV is transmitted in endemic areas often by the blood feeding of Aedes mosquitoes, and all Aedes species are capable of transmitting the disease; so, preventing mosquitoes from blood feeding with personal-protection, and use of repellents and insecticides in emergencies is essential. Increasing the level of awareness of people about controlling vectors and the proper application of disease prevention methods is a priority. Also, sleeping in common mosquito nets or preferably the ones covered with insecticides, having air conditioning available, full covering of the body (wearing long-sleeved shirts and long pants), applying insecticide spray in the room, closing windows and doors two hours after sunrise and two hours before sunset, performing larval control operations, removing stagnant water, improving the environment (filling gaps between rocks and bricks, sanitary disposal of waste and sewage), covering surfaces of water storage containers, development of drinking water pipeline system and spraying walls of indoors with residual insecticides can prevent DF 53,54. Traveling, especially to endemic areas, increases the risk of entering the virus to the country and may make the disease endemic to Iran. Iranians who travel specifically to Southeast and East Asian countries are at DF risk. Most trips also occur during summers, when the virus is more likely to be transmitted and cause DF55, 56.

 

4. CONCLUSIONS:

Dengue fever is a serious global threat and may threaten the lives of over 2.5 billion people in over 100 countries. Implementing surveillance and control programs is essential to know about dengue status and take emergency control measures. Health care policymakers should pay particular attention to the disease and provide training to health professionals and physicians so that they can observe symptoms such as high fever, rashes, headache and muscle pain to diagnose and treat the disease. Future directions for tackling the disease include mosquito control, vaccine development, and antiviral drug regimens.

 

5. ACKNOWLEDGEMENTS:

Authors would like to thank Research vice-chancellery of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran and Kashan University of Medical Sciences, Kashan, Iran for their cooperation.

 

6. CONFLICT OF INTEREST STATEMENT:

The authors declare that they have no competing interests.

 

7. FINANCIAL DISCLOSURE:

There were no sources of extra-institutional commercial findings.

 

8. AUTHORS’ CONTRIBUTION:

All authors participated in the research design and contributed to different parts of the research.

 

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Received on 30.04.2020            Modified on 24.06.2020

Accepted on 29.07.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(4):2296-2301.

DOI: 10.52711/0974-360X.2021.00406