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RESEARCH

IMD 21 SECTION A

Group no :08
Topic: Dengue Fever
Members of the group

76. Pranav k

77. Thaslima k

78. K harishantanu

79. Deepti k

80. Nishantini k

81. Pranjali k

82. Sanwad k

83. Guddi k

84. Ayush k

85. Prajwal k

86. Saurabh k.

87. Blessy k

88. Akash k

89. Haripriya k

90. Krishna k.

91. Kishore k

92. Maharajan M

93. Manesadevi M

94. Shriaarthiga M

95. Ilakiya M

97. Samrudhi M

98. Arya M

99. Asarudheen M

100. Anand M

101. Abishek M
Current Dengue Fever Research

Introduction

Dengue has become a serious health problem worldwide, and scientists are focusing their

attention on understanding how the dengue virus causes disease. As they learn more about how

dengue affects the body, researchers hope to diagnose and treat dengue better. Current dengue

research also aims to provide better surveillance to limit the effect of dengue epidemics.

Basic Research on Dengue

What does basic dengue research involve? Basic research includes a wide range of studies

focused on learning how the dengue virus is transmitted and how it infects cells and causes

disease. This type of research investigates many aspects of dengue viral biology, including

exploration of the interactions between the virus and humans and studies of how the dengue

virus replicates itself.One important field of basic research is dengue pathogenesis, the study of

the process and mechanisms of dengue in humans. Scientists want to understand how the dengue

virus causes damage to the human body and how the immune system responds to a dengue

infection so that they can develop new treatments for the disease. For example, researchers want

to understand why bleeding and vascular leakage occur in patients with severe dengue illnesses.

Knowledge of the disease pathway may help doctors and clinicians diagnose dengue at earlier

stages. Researchers want to find out whether there are genetic factors that result in an increased

or decreased risk of infection for individuals. Some people may be genetically susceptible to

develop more severe symptoms than other people.

Scientists are also studying the dengue viruses to understand which factors are responsible for

transmitting the virus to humans. Researchers are investigating how the dengue virus replicates

itself and the structure of the viral components, such as the capsid, membrane, and envelope
proteins. Scientists also want to know — how do the dengue viruses manage to avoid detection

by the immune system? Because viruses can evolve and gain mutations over time, researchers

are examining dengue viral genetics and evolution to investigate changes in viral genomes over

time. These variations may help the virus hide from the immune system. Scientists know that

particular viral sequences are associated with more severe dengue symptoms. In addition, certain

dengue sequence variations may produce more deadly viruses with a greater potential for causing

epidemics. This kind of information can help scientists monitor the regional spread of

particularly dangerous dengue strains to help communities prevent or prepare for dengue

outbreaks.

Other dengue research focuses on vector biology. What is vector biology? This field of dengue

research studies the disease vector, Aedes mosquitoes. Vector biology studies mosquito ecology,

population biology, genetics, and behaviors to understand how mosquitoes transmit the dengue

viruses. Researchers can also study dengue transmission patterns. As one example, researchers

studied dengue infections in children living in Nicaragua and saw that patterns of dengue

transmission depended on changes in climate and changes in the dengue serotypes in the area.

Large-scale studies of patterns in dengue transmission can provide essential information to resist

the disease, identify and diagnose dengue cases, and implement mosquito-control efforts.
Dengue is a mosquito-borne, acute febrile illness that is an important public health problem in

tropical countries. In the early 1950’s, the disease was described in the Philippines as

hemorrhagic fever or infectious acute thrombocytopenic purpura [1, 2]. Dengue continues to

cause considerable concern in the country because of its widespread endemicity, the minimal

success of vector control strategies, the possibility of severe disease caused by sequential

infection by a different serotype, the potential for fatal outcomes and the consequent social and

economic burden. The four dengue virus serotypes circulate in the country where the disease is

predominantly reported among children.

Findings from dengue studies could provide policy-makers with information needed for rational

decision-making regarding dengue preventive and control efforts. The focus of dengue research

may vary widely. This could include basic laboratory research, the estimation of dengue

seroprevalence and incidence; the assessment of risk factors for severe disease; the quantification

of its economic burden; the elucidation of local transmission and epidemiology; the development

of improved diagnostic tests or the evaluation of interventions.

We reviewed published studies on dengue research in the Philippines during the past 60 years.

The objective of the review is to better understand the trends in dengue research and the findings

from these studies. The results of the review could provide an impression of local capacity and

infrastructure for dengue research and help determine important knowledge gaps. These gaps

need to be identified since research interest and support for funding can only be achieved if

scientists, decision makers and other stakeholders are able to understand developments related to

the disease and recognize it areas where more information is needed.

Climate and dengue incident


Dengue is a major public health concern for over half of the world’s population and is a leading

cause of hospitalization and death, particularly for children in endemic countries. A

comprehensive analysis of the impacts of climate change on the incidence of dengue should

consider the changes in a range of social, behavioral, economic, environmental, and health

systems factors, including human mobility, vector control interventions, and potential

vaccination coverage. These factors are important for determining the changes in exposure and

susceptibility to the dengue virus in the face of climate variability and change. Many studies

have found associations between climatic conditions and dengue transmission. The transmission

of dengue is highly sensitive to climatic conditions, especially temperature, rainfall and relative

humidity. Dengue is climate sensitive as the virus has to complete part of its development in the

mosquito vectors that transmit the disease. The major vector is Ae. aegypti whose life cycle is

directly influenced by ambient temperature and rainfall. Increased temperature could increase

dengue risk by increasing the rate of mosquito development and reducing virus incubation time

in areas where the vector presently exists, thereby increasing the rate of transmission. The major

vector is Ae. aegypti whose life cycle is directly influenced by ambient temperature and rainfall.

Increased temperature could increase dengue risk by increasing the rate of mosquito

development and reducing virus incubation time in areas where the vector presently exists,

thereby increasing the rate of transmission.


CLINICAL AND LABARATORY FACTORS ASSOCIATED WITH MORTALITY IN

DENGUE

BACKGROUND:

Dengue fever is a common mosquito borne disease of humans transmitted by the

bite of an infected female adult mosquito namely the ADES AEGYPTI as the primary vector and

AEDES ALBOPICTUS as the secondary vector .

Dengue remains a major public health concern in tropical and sub tropical areas.

The study site is located in Davao region which is situated at the south eastern portion of the

third largest island in the Philippines.

From 2016-2018,there were 38,169 dengue increased from 4115 cases in 2016 to 9507

cases in 2017 and reached a peak in the year 2018 with 10,762 cases , the highest reported

number of dengue cases within the study period.

According to DOH, Davao city which is located near Davao region , has always highest

number of dengue comprising around 70% of the cases while the rest from neighbouring

provinces.

The metrological variables , though may have varying effects on dengue incidence, exhibit

associations which coincide with the plausible biological pathways. Risks were particularly

higher in metrological events with moderate rain, low temperature and high dew point.

This study could help improve the dengue surveillance system in the country. Furthermore

,we also acknowledge some limitations in this study. First ,the weekly dengue data used in this

study were notified suspected dengue cases from clinics and hospitals and are not laboratory

confirmed. Second, we did not take into account the mosquito density , population immunity, age

classification, social behaviour for these data are un available.


Dengue virus life cycle

Aedes agypty is a so-called holometabolous insect. This means that the insects goes through a

complete metamorphosis with an egg, larvae, pupae, and adult stage. The adult life span can

range from two weeks to a month depending on environmental conditions. The life cycle of

Aedes aegypti can be completed within one-and-a-half to three weeks.

Egg

After taking a blood meal, female Aedes aegypti mosquitos produce on average 100 to 200 eggs

per batch. The females can produce up to five batches of eggs during a lifetime. The number of

eggs is dependent on the size of the bloodmeal. Eggs are laid on damp surfaces in areas likely to

temporarily flood, such as tree holes and man-made containers like barrels, drums, jars, pots,

buckets, flower vases, plant saucers, tanks, discarded bottles, tins, tyres, water cooler, etc. and a

lot more places where rain-water collects or is stored. The female Aedes aegypti lays her eggs

separately unlike most species. Not all eggs are laid at once, but they can be spread out over

hours or days, depending on the availability of suitable substrates. Eggs will most often be

placed at varying distances above the water line. The female mosquito will not lay the entire

clutch at a single site, but rather spread out the eggs over several sites.

The eggs of Aedes aegypti are smooth, long, ovoid shaped, and roughly one millimeter long.

When first laid, eggs appear white but within minutes turn a shiny black. In warm climates eggs

may develop in as little as two days, whereas in cooler temperate climates, development can take

up to a week. Laid eggs can survive for very long periods in a dry state, often for more than a

year. However, they hatch immediately once submerged in water. This makes the control of the

dengue virus mosquito very difficult.


Larvae

After hatching of the eggs, the larvae feed on organic particulate matter in the water, such as

algae and other microscopic organisms. Most of the larval stage is spent at the water's surface,

although they will swim to the bottom of the container if disturbed or when feeding. Larvae are

often found around the home in puddles, tires, or within any object holding water. Larval

development is temperature dependent. The larvae pass through four instars, spending a short

amount of time in the first three, and up to three days in the fourth instar. Fourth instar larvae are

approximately eight millimeters long. Males develop faster than females, so males generally

pupate earlier. If temperatures are cool, Aedes aegypti can remain in the larval stage for months

so long as the water supply is sufficient.

Pupae

After the fourth instar, the larvae enters the pupal stage (figure 3). Mosquito pupae are mobile

and respond to stimuli. Pupae do not feed and take approximately two days to develop. Adults

emerge by ingesting air to expand the abdomen thus splitting open the pupal case and emerge

head first.
Diagnostics

Patients with severe dengue illnesses can be treated successfully if they are diagnosed as early as

possible. Scientists are working on improving dengue diagnostics so that patients infected with

dengue can be treated quickly. What would the ideal diagnostic test for dengue do? The ideal

diagnostic test would be able to distinguish dengue from other diseases with similar symptoms

and distinguish one dengue serotype from another. An ideal diagnostic test would be highly

sensitive during the acute stage of the infection, quick and easy to use, and affordable.

How is dengue diagnosed? A number of laboratory methods are used to diagnose dengue,

including detection of the dengue virus, viral RNA, viral antigens, and antibodies against the

virus in the patient's blood or tissues (Figure 1). The virus can be detected in the blood for only

four to five days after the onset of symptoms. During this early stage of the disease, isolation of

the virus, viral RNA, and viral protein can be used to diagnose dengue.

Direct diagnostic methods such as dengue virus isolation, genome detection, and antigen

detection are more specific ways to diagnose dengue than indirect methods that detect IgM and

IgG antibodies against dengue. There is a greater opportunity for diagnosis with the indirect tests

because these diagnostic methods are typically the most practical options ava 

The detection of antibodies (IgM and IgG) in the blood of an infected individual is an indirect

method to diagnose dengue. This method is commonly used to diagnose dengue in the later stage

of the disease, after the viral levels have decreased. Antibodies against dengue can be detected in
most patients five days after the onset of symptoms, and IgG can be detected for many months

and even years after an infection (Figure 2). During a primary (first) dengue infection, IgM

levels are very high, but during a secondary infection, IgM levels are lower. The levels of IgG

actually increase during a secondary infection. Therefore, clinicians can measure the amounts of

IgM and IgG to decide whether a patient has a primary or a secondary dengue infection. This test

can be useful because patients with secondary infections are more likely to have severe dengue

than those who have not had a previous infection. Because dengue can be mistaken for other

diseases such as yellow fever, measles, and influenza, it is best to confirm a diagnosis of dengue

by detecting the antibody response and testing for direct evidence of the virus.

Figure 2: Major diagnostic markers for dengue infection

The major diagnostic markers for dengue infection include detection of the dengue virus, viral

RNA, and viral antigens such as the NS1 protein when the patient has viremia (high levels of the

dengue virus in the blood). IgM and IgG antibodies against the dengue virus can be detected in

most patients five days after the onset of symptoms. IgG can be measured for many months and

even years after a dengue infection. The amounts, or titres, of the IgM and IgG antibodies

depend on whether the infection is a primary or a secondary infection. During a primary (first)

dengue infection, IgM levels are very high, but during a secondary infection, IgM levels are

lower. The levels of IgG actually increase during a secondary infection. Clinicians can measure

the amounts of IgM and IgG to tell whether a patient has a primary or a secondary dengue

infection.
Have researchers developed any new diagnostic tests to diagnose dengue? Recently, scientists

developed a rapid, one-step test to detect and distinguish all four dengue serotypes. This test is

based on reverse transcription polymerase chain reaction amplification of the viral RNA, and it is

a sensitive, rapid, and cost-effective tool to diagnose patients with dengue. A second approach

involves diagnosing dengue infections by detecting NS1, one of the seven nonstructural dengue

proteins. NS1 is produced in large quantities during dengue viral replication, and it can be

detected as early as the first day the patient experiences a fever.

Is there a way to know which patients might develop severe dengue? Scientists want to find ways

to quickly identify patients who are the most likely to develop severe dengue illnesses. To

identify these patients, researchers must first discover predictive factors for severe dengue. One

way researchers can discover these factors is to monitor the progression of the disease and look

for factors that predict severe illness by taking frequent blood samples and ultrasound images

from patients with dengue. Ultrasound can measure indicators of severe dengue, including the

thickening of the gall bladder wall and excess fluids around the tissues and organs in the

abdomen and chest cavity. Knowledge of additional predictive factors could help researchers

design more effective diagnostic tests. Another strategy involves applying decision-making

computer models to diagnose patients with dengue and predict their prognoses by using clinical

data, such as the patient's platelet count and the presence of preexisting IgG antibodies against

dengue in the blood.

Dengue Surveillance

What can other fields of research do to prevent and control dengue? In addition to performing

basic research and improving diagnostics, improving dengue surveillance is an essential way to

prevent and control dengue transmission. The World Health Organization — in partnership with
ministries of health, research centers, and laboratories around the world — has developed a

dengue surveillance system called DengueNet, a database that can be continuously updated to

share current and historical data on dengue cases. The goals of DengueNet are to standardize

reporting of dengue cases and to improve the preparedness of public health officials by providing

early warnings prior to epidemics, which can help reduce fatality rates.

Monitoring mosquito populations is a first line of defense against dengue. Vector surveillance

allows for a prompt response to control mosquito populations and limit dengue transmission.

Studying vector competence, the ability of Aedesmosquitoes to acquire and transmit the dengue

virus, can provide important information about variations in the transmission of the different

dengue serotypes. Researchers have shown that delayed mosquito-control responses can lead to

an exponential increase in both the number of infected people and health costs. Public health

officials can prevent large dengue outbreaks by using surveillance information to plan mosquito-

control efforts and interventions and to provide resources to affected areas. Vector surveillance is

crucial for public health officials so that they can provide a prompt and preventative response to

dengue.

Summary

Scientists are investigating the mechanisms by which the dengue virus causes disease by

focusing on understanding dengue pathogenesis, the virus itself, and vector biology. Researchers

also aim to improve diagnostics for patients with dengue so that they can receive effective

treatments sooner. In addition, by improving surveillance of dengue cases and mosquito vectors,

researchers hope to reduce the effect of dengue epidemics.

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