What is Dengue Infection?

INTRODUCTION

Dengue is a vector-borne viral infection and a globally important public health problem. The dengue viruses (serotypes 1, 2, 3 and 4) are enveloped, single-stranded RNA viruses of the Flaviviridae family. Transmission from human to human is predominantly by the mosquito Aedes aegypti, which bites in the daytime, is adapted to human habitats and has a preference for human blood meals. More than 1 billion people are at risk of dengue infection in over 100 countries.

Any of the four serotypes of dengue virus can result in dengue, which is a systemic febrile illness lasting 3–7 days and characterized by viremia, fever, rash, headache, muscle and joint ache. Occasionally, dengue manifests as dengue hemorrhagic fever (DHF), a potentially life-threatening illness associated with capillary leakage, hemorrhagic manifestations and, in severe cases, hypovolemic shock.

DIAGNOSIS

Cautious attention should be directed at DF if a patient suffers from high fever within 2 weeks of being in the tropics or subtropics.[43] A decreased number of white blood cells (leukopenia), accompanied by a decreased number of platelet count (thrombocytopenia) and metabolic acidosis are the initial changes on laboratory examinations. Microbiological laboratory testing confirms the diagnosis of DF. Virus segregation in cell cultures, nucleic acid demonstration by polymerase chain reaction (PCR), and serological detection of viral antigens (such as NS1) or particular antibodies are the preferred microbiological assays.[5] Viral segregation and nucleic acid demonstration provide precise diagnosis, although the high cost limits the availability of these tests.

Transmission

Mosquito-to-human transmission

The virus is transmitted to humans through the bites of infected female mosquitoes, primarily the Aedes aegypti mosquito. Other species within the Aedes genus can also act as vectors, but their contribution is secondary to Aedes aegypti.

After feeding on an DENV-infected person, the virus replicates in the mosquito midgut, before it disseminates to secondary tissues, including the salivary glands. The time it takes from ingesting the virus to actual transmission to a new host is termed the extrinsic incubation period (EIP). The EIP takes about 8-12 days when the ambient temperature is between 25-28°C ^[4-6]. Variations in the extrinsic incubation period are not only influenced by ambient temperature; a number of factors such as the magnitude of daily temperature fluctuations^{[7, 8]}, virus genotype^[9], and initial viral concentration^[10] can also alter the time it takes for a mosquito to transmit virus. Once infectious, the mosquito is capable of transmitting virus for the rest of its life.

Human-to-mosquito transmission

Mosquitoes can become infected from people who are viremic with DENV. This can be someone who has a symptomatic dengue infection, someone who is yet to have a symptomatic infection (they are pre-symptomatic), but also people who show no signs of illness as well.

Disease characteristics (signs and symptoms)

The World Health Organization classifies dengue into 2 major categories: dengue (with / without warning signs) and severe dengue. The sub-classification of dengue with or without warning signs is designed to help health practitioners triage patients for hospital admission, ensuring close observation, and to minimise the risk of developing the more severe dengue (see below).

Dengue

Dengue should be suspected when a high fever (40°C/104°F) is accompanied by 2 of the following symptoms during the febrile phase:

severe headache
pain behind the eyes
muscle and joint pains
nausea
vomiting
swollen glands
rash.

Severe dengue

A patient enters what is called the critical phase normally about 3-7 days after illness onset. It is at this time, when the fever is dropping (below 38°C/100°F) in the patient, that warning signs associated with severe dengue can manifest. Severe dengue is a potentially fatal complication, due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.

Warning signs that doctors should look for include:

severe abdominal pain
persistent vomiting
rapid breathing
bleeding gums
fatigue
restlessness
blood in vomit.

If patients manifest these symptoms during the critical phase, close observation for the next 24–48 hours is essential so that proper medical care can be provided, to avoid complications and risk of death.

Treatment

There is no specific treatment for dengue fever.

Fever reducers and pain killers can be taken to control the symptoms of muscle aches and pains, and fever.

The best options to treat these symptoms are acetaminophen or paracetamol.
NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen and aspirin should be avoided. These anti-inflammatory drugs act by thinning the blood, and in a disease with risk of hemorrhage, blood thinners may exacerbate the prognosis.

For severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20% to less than 1%. Maintenance of the patient's body fluid volume is critical to severe dengue care. Patients with dengue should seek medical advice upon the appearance of warning signs.

Vaccination against dengue

The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 and has now been approved by regulatory authorities in ~20 countries. In November 2017, the results of an additional analysis to retrospectively determine serostatus at the time of vaccination were released. The analysis showed that the subset of trial participants who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue and hospitalizations from dengue compared to unvaccinated participants. As such, use of the vaccine is targeted for persons living in endemic areas, ranging from 9-45 years of age, who have had at least 1 documented dengue virus infection previously.

Key facts

Dengue is a mosquito-borne viral infection, found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas.
The virus responsible for causing dengue, is called dengue virus (DENV). There are four DENV serotypes, meaning that it is possible to be infected four times.
While many DENV infections produce only mild illness, DENV can cause an acute flu-like illness. Occasionally this develops into a potentially lethal complication, called severe dengue.
Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries. It requires management by medical professionals.
There is no specific treatment for dengue/severe dengue. Early detection of disease progression associated with severe dengue, and access to proper medical care lowers fatality rates of severe dengue to below 1%.
The global incidence of dengue has grown dramatically in recent decades. About half of the world's population is now at risk. There are an estimated 100-400 million infections each year.
Dengue prevention and control depends on effective vector control measures. Sustained community involvement can improve vector control efforts substantially.

Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent years. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus. These mosquitoes are also vectors of chikungunya, yellow fever and Zika viruses. Dengue is widespread throughout the tropics, with local variations in risk influenced by rainfall, temperature, relative humidity and unplanned rapid urbanization.

Global burden of dengue

The incidence of dengue has grown dramatically around the world in recent decades. A vast majority of cases are asymptomatic or mild and self-managed, and hence the actual numbers of dengue cases are under-reported. Many cases are also misdiagnosed as other febrile illnesses^[1].

One modelling estimate indicates 390 million dengue virus infections per year (95% credible interval 284–528 million), of which 96 million (67–136 million) manifest clinically (with any severity of disease) ^[2]. Another study on the prevalence of dengue estimates that 3.9 billion people are at risk of infection with dengue viruses. Despite a risk of infection existing in 129 countries ^[3], 70% of the actual burden is in Asia ^[2].

The number of dengue cases reported to WHO increased over 8 fold over the last two decades, from 505,430 cases in 2000, to over 2.4 million in 2010, and 5.2 million in 2019. Reported deaths between the year 2000 and 2015 increased from 960 to 4032.

This alarming increase in case numbers is partly explained by a change in national practices to record and report dengue to the Ministries of Health, and to the WHO. But it also represents government recognition of the burden, and therefore the pertinence to report dengue disease burden. Therefore, although the full global burden of the disease is uncertain, this observed growth only brings us closer to a more accurate estimate of the full extent of the burden.

Distribution and outbreaks of dengue

Before 1970, only 9 countries had experienced severe dengue epidemics. The disease is now endemic in more than 100 countries in the WHO regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific. The America, South-East Asia and Western Pacific regions are the most seriously affected, with Asia representing ~70% of the global burden of disease.

Not only is the number of cases increasing as the disease spreads to new areas including Europe, but explosive outbreaks are occurring. The threat of a possible outbreak of dengue now exists in Europe; local transmission was reported for the first time in France and Croatia in 2010 and imported cases were detected in 3 other European countries. In 2012, an outbreak of dengue on the Madeira islands of Portugal resulted in over 2000 cases and imported cases were detected in mainland Portugal and 10 other countries in Europe. Autochthonous cases are now observed on an almost annual basis in many European countries. Among travellers returning from low- and middle-income countries, dengue is the second most diagnosed cause of fever after malaria.

Transmission

Mosquito-to-human transmission

Human-to-mosquito transmission

Mosquitoes can become infected from people who are viremic with DENV. This can be someone who has a symptomatic dengue infection, someone who is yet to have a symptomatic infection (they are pre-symptomatic), but also people who show no signs of illness as well (they are asymptomatic) ^[11].

Human-to-mosquito transmission can occur up to 2 days before someone shows symptoms of the illness^{[5, 11]}, up to 2 days after the fever has resolved ^[12].

Risk of mosquito infection is positively associated with high viremia and high fever in the patient; conversely, high levels of DENV-specific antibodies are associated with a decreased risk of mosquito infection (Nguyen et al. 2013 PNAS). Most people are viremic for about 4-5 days, but viremia can last as long as 12 days ^[13].

Other modes of transmission

The primary mode of transmission of DENV between humans involves mosquito vectors. There is evidence however, of the possibility of maternal transmission (from a pregnant mother to her baby). While vertical transmission rates appear low, with the risk of vertical transmission seemingly linked to the timing of the dengue infection during the pregnancy ^[14-17]. When a mother does have a DENV infection when she is pregnant, babies may suffer from pre-term birth, low birthweight, and fetal distress ^[18].

Vector Ecology

The Aedes aegypti mosquito is considered the primary vector of DENV. It lives in urban habitats and breeds mostly in man-made containers. Ae. aegypti is a day-time feeder; its peak biting periods are early in the morning and in the evening before sunset ^[19] Female Ae. aegypti frequently feed multiple times between each egg-laying period ^[20]. Once a female has laid her eggs, these eggs can remain viable for several months, and will hatch when they in contact with water.

Disease characteristics (signs and symptoms)

Dengue is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. Symptoms usually last for 2–7 days, after an incubation period of 4–10 days after the bite from an infected mosquito ^[25]. The World Health Organization classifies dengue into 2 major categories: dengue (with / without warning signs) and severe dengue. The sub-classification of dengue with or without warning signs is designed to help health practitioners triage patients for hospital admission, ensuring close observation, and to minimise the risk of developing the more severe dengue.

Dengue

Dengue should be suspected when a high fever (40°C/104°F) is accompanied by 2 of the following symptoms during the febrile phase:

severe headache
pain behind the eyes
muscle and joint pains
nausea
vomiting
swollen glands
rash.

Severe dengue

Warning signs that doctors should look for include:

severe abdominal pain
persistent vomiting
rapid breathing
bleeding gums
fatigue
restlessness
blood in vomit.

Diagnostics

Several methods can be used for diagnosis of DENV infection. These include virological tests (that directly detect elements of the virus) and serological tests, which detect human-derived immune components that are produced in response to the virus). Depending on the time of patient presentation, the application of different diagnostic methods may be more or less appropriate. Patient samples collected during the first week of illness should be tested by both serological and virological methods (RT-PCR).

Virological methods

The virus may be isolated from the blood during the first few days of infection. Various reverse transcriptase–polymerase chain reaction (RT–PCR) methods are available.

The virus may also be detected by testing for a virus-produced protein, called NS1. There are commercially-produced rapid diagnostic tests available for this, because it takes only ~20 mins to determine the result, and the test does not require specialized laboratory techniques or equipment.

Serological methods

Serological methods, such as enzyme-linked immunosorbent assays (ELISA), may confirm the presence of a recent or past infection, with the detection of IgM and IgG anti-dengue antibodies. IgM antibodies are detectable ~1 week after infection and are highest at 2 to 4 weeks after the onset of illness. They remain detectable for about 3 months. The presence of IgM is indicative of a recent DENV infection. IgG antibody levels take longer to develop than IgM, but IgG remain in the body for years. The presence of IgG is indicative of a past infection.

Treatment

There is no specific treatment for dengue fever.

Fever reducers and pain killers can be taken to control the symptoms of muscle aches and pains, and fever.

The best options to treat these symptoms are acetaminophen or paracetamol.
NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen and aspirin should be avoided. These anti-inflammatory drugs act by thinning the blood, and in a disease with risk of hemorrhage, blood thinners may exacerbate the prognosis.

Vaccination against dengue

The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 and has now been approved by regulatory authorities in ~20 countries. In November 2017, the results of an additional analysis to retrospectively determine serostatus at the time of vaccination were released. The analysis showed that the subset of trial participants who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue and hospitalizations from dengue compared to unvaccinated participants. As such, use of the vaccine is targeted for persons living in endemic areas, ranging from 9-45 years of age, who have had at least 1 documented dengue virus infection previously.

WHO position on the CYD-TDV vaccine

As described in the WHO position paper on the Dengvaxia vaccine (September 2018) the live attenuated dengue vaccine CYD-TDV has been shown in clinical trials to be efficacious and safe in persons who have had a previous dengue virus infection (seropositive individuals). However, it carries an increased risk of severe dengue in those who experience their first natural dengue infection after vaccination (those who were seronegative at the time of vaccination). For countries considering vaccination as part of their dengue control programme, pre-vaccination screening is the recommended strategy. With this strategy, only persons with evidence of a past dengue infection would be vaccinated (based on an antibody test, or on a documented laboratory confirmed dengue infection in the past

Dengue test and control

If you know you have dengue, avoid getting further mosquito bites during the first week of illness. Virus may be circulating in the blood during this time, and therefore you may transmit the virus to new uninfected mosquitoes, who may in turn infect other people.

The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for dengue as well as for other diseases that Aedes mosquito transmit. At present, the main method to control or prevent the transmission of dengue virus is to combat the mosquito vectors. This is achieved through:

Prevention of mosquito breeding:
- Preventing mosquitoes from accessing egg-laying habitats by environmental management and modification;
- Disposing of solid waste properly and removing artificial man-made habitats that can hold water;
- Covering, emptying and cleaning of domestic water storage containers on a weekly basis;
- Applying appropriate insecticides to water storage outdoor containers;
Personal protection from mosquito bites:
- Using of personal household protection measures, such as window screens, repellents, insecticide treated materials, coils and vaporizers. These measures must be observed during the day both inside and outside of the home (e.g.: at work/school) because the primary mosquito vectors bites throughout the day;
- Wearing clothing that minimises skin exposure to mosquitoes is advised;

Dengue test report:

CBC dengue test consist on four(4) parameters:

1_HB

2_HCT

3_TLC

4_PALTELETS

Here is link of report preview

Community engagement:
- Educating the community on the risks of mosquito-borne diseases;
- Engaging with the community to improve participation and mobilization for sustained vector control;
Reactive vector control:
- Emergency vector control measures such as applying insecticides as space spraying during outbreaks may be used by health authorities;
Active mosquito and virus surveillance:
- Active monitoring and surveillance of vector abundance and species composition should be carried out to determine effectiveness of control interventions;
- Prospectively monitor prevalence of virus in the mosquito population, with active screening of sentinel mosquito collections;

Pakistan:34 dead as dengue cases in Pakistan cross 15,000

Pakistan has recorded 15,719 cases of dengue fever this year to date, while 34 people have died, as per the official data.

Of the total cases, recorded till October 13, the majority, 5,382, were recorded in Punjab, as per data provided to Geo.tv by the federal ministry of health.

In Punjab, 12 people have died so far. In Khyber Pakhtunkhwa, 3,300 cases of mosquito-borne disease have been recorded and four deaths.

Over in Sindh, 2,530 dengue infections have surfaced this year, while the virus has claimed 12 lives. In Balochistan, 1,841 cases have been recorded while there have been no deaths. In Azad Jammu and Kashmir as well no deaths have been reported but the tally of cases in the federating unit is 905 to date.

In Lahore, 1,761 cases have been recorded of the virus and six people have died.

Of the cases reported in Punjab, the majority, 74%, have been from the city of Lahore alone, notes the data of Punjab’s primary and secondary healthcare department.

In fact, in the last 24 hours, 231 dengue patients were recorded in the province, of which 146 were reported from Lahore, 39 from Rawalpindi, six from Sheikhupura, five from Nankana and Sargodha, amongst others.

Director General Health Dr Rana Muhammad Safdar has warned of the situation worsening in the coming year.

"The last outbreak was seen in 2019, largely in north Punjab and KP. 2020 was silent and we have this surge again. Typically, in endemic countries you expect large dengue outbreaks with a 3-year cycle. Hence, 2022 is likely to be severe," he said.

Imran Sikander, the secretary of the primary and healthcare department, has advised citizens to avoid letting water accumulate in residential areas. He added that to date, across the province, health officials have inspected 421,151 indoor places in order to eradicate the virus.