The origin of word “dengue” is derived from the Swahili phrase ka-dinga pepo which describes the disease is being caused by an evil spirit. The Swahili word Dinga had its origin from Spanish word dengue, meaning fastidious or careful which would describe the gait of a person suffering the bone pain of dengue fever. The term dengue fever came into use after 1828. The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from Jin Dynasty (265-420AD) which referred to a “water poison” associated with flying insects.  The first confirmed outbreak of dengue fever in Pakistan was in 1994, but a sudden rise in cases and the annual epidemic trend first occurred in Karachi in November 2005. The three provinces facing the epidemic are Khyber Pakhtunkhwa, Punjab and Sindh.

  In 1906, Aedes mosquitoes transmitting the dengue fever was confirmed and in 1907, Dengue was the second disease after “yellow fever” that was shown to be caused by virus. Dengue hemorrhagic fever is first reported in Philippines in 1953, and in 1981 in South America.

Dengue fever is caused by dengue virus (DENV) is a mosquito-borne viral infection that has become a major public health concern globally. The virus is primarily transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Dengue is prevalent in tropical and subtropical regions, especially in urban and semi-urban areas. Dengue is believed to infect 50 to 100 million people worldwide in a year. 1 The mortality is 1-5% without treatment and less than 1% with treatment. Severe disease (dengue haemonhagic fever, D. S. S) carry a mortality of 26%. The incidence of dengue in increased 30-fold between between 1960 and 2010. This increase is believed to be to be due to multiple factors like, rapid urbanization, population growth, increase is believed international travel from endemic areas and lastly global warming. The geographical distribution is around the equator mainly affecting Asia and pacific regions.

Dengue is endemic in Pakistan, with the last notable outbreak, with 53,498 cases and 95 deaths, being reported between September to December 2019.

From 1 January to 25 November 2021, to a total of 48,906 cases including 183 deaths (case fatality ratio (CFR): 0.4%) have been reported from four provinces including Punjab, Khyber Pakhtunkhwa, Sindh, Balochistan, and the federally administered Islamabad Capital Territory (ICT), and Azad Jammu and Kashmir autonomous territories (AJK), Pakistan.

As of 25 November, Punjab province reported the highest number of cases with 24,146 cases and 127 deaths (CFR: 0.5%) accounting for 49.4% and 69.4% of all cases and deaths, respectively. The deaths were mainly reported from Lahore district.

Khyber Pakhtunkhwa, a border province with Afghanistan, reported the second largest number of cases with 10,223 cases, accounting for 21% of all cases, and 10 deaths (CFR: 0.1%). 

Sindh province reported 5,548 cases with 24 (CFR:0.4%) deaths followed by the federally administered ICT with 5,261 cases and 21 (CFR: 0.4%) deaths, Balochistan province with 2,054 cases, and AJK reported 1,674 cases with one (CFR:0.1%) death.

Table 1: Dengue cases & death since 2019 (Govt. of pak).

Pakistan J MED RES, March 2011:

Table 2a: Year-wise and gender-wise distribution of suspected cases of dengue fever and dengue IgM positive cases over a three-year period (2006-2008).

Table 2b: Year-wise and age-wise (children and adults) distribution of suspected cases of dengue fever and dengue IgM positive cases over a three-year period (2006-2008).

Dengue fever outbreak are influenced by a combination of environmental biological, social, and human factors

Here is the key factor

Climate and Weather

Warm temperature and high humidity create ideal condition for the aedes mosquitoes the primary vectors of dengue, to breed and survive. Rainfall can increase mosquito breeding sites by creating standing water.

Urbanization and Population Density

Rapid urbanization, especially in tropical and subtropical regions, often leads to overcrowded living conditions with poor sanitation, which can enhance mosquito breeding and facilitate the spread of dengue.

Global Travel and Trade

Increased movement of people and goods can introduce the dengue virus to new areas. Travelers from endemic regions can carry the virus to non-endemic regions, where local mosquitoes can then spread it. 

Water Storage Practices

 In areas with inconsistent water supply, people often store water in containers, which can become breeding sites for Aedes mosquitoes if not properly covered or treated.

Clinical Presentation and Diagnosis

Dengue fever can present with a range of clinical symptoms, and its diagnosis typically involves a combination of clinical evaluation and laboratory testing. Here’s an overview of the clinical presentations and diagnostic methods:

Clinical Presentations

Asymptomatic or Mild Symptoms

Many dengue infections are asymptomatic or result in mild, flu-like symptoms.

Classic Dengue Fever

• High Fever: Sudden onset of high fever (40°C/104°F).
• Severe Headache: Particularly behind the eyes.
• Retro-orbital Pain: Pain behind the eyes.
• Myalgia and Arthralgia: Muscle and joint pain, often severe, leading to the nickname "breakbone fever".
• Rash: Maculopapular or petechial rash, which may appear after the fever subsides.
• Nausea and Vomiting: Gastrointestinal symptoms are common.
• Fatigue and Weakness: Persistent fatigue can last for weeks after the acute phase.

Severe Dengue (Dengue Hemorrhagic Fever and Dengue Shock Syndrome):

• Plasma Leakage: Leading to ascites, pleural effusion, and hypovolemic shock.
• Severe Abdominal Pain: Persistent and severe.
• Bleeding: Manifestations include petechiae, mucosal bleeding (e.g., nose or gums), gastrointestinal bleeding, and easy bruising.
• Hepatomegaly: Enlarged liver.
• Hypotension and Shock: Dengue Shock Syndrome (DSS) can be fatal without prompt treatment.

Diagnosis

Clinical Evaluation

• History and Physical Examination: Assessment of symptoms, travel history, and exposure to mosquito bites.
• Tourniquet Test: May be used to assess capillary fragility and bleeding tendency.

Laboratory Tests

• Complete Blood Count (CBC): Typically shows leukopenia, thrombocytopenia, and hemoconcentration.
• Liver Function Tests: Elevated transaminases (AST, ALT).

Specific Dengue Tests

• NS1 Antigen Test: Detects the dengue virus nonstructural protein 1 (NS1) and is useful in the early phase of infection.
• RT-PCR: Polymerase chain reaction test to detect viral RNA, most effective in the first few days of illness.

Serology Tests

• IgM and IgG Antibodies: IgM appears around 4-5 days after the onset of symptoms and indicates recent infection. IgG appears later and indicates past infection or secondary infection.

Imaging

• Ultrasound: May be used to detect plasma leakage such as pleural effusion or ascites in severe cases.

Clinical Management

• Supportive Care: Hydration, fever management, and pain relief are critical.
• Monitoring: Close monitoring for signs of severe dengue, particularly during the critical phase (typically days 3-7 of illness).
• Hospitalization: Required for severe dengue to manage complications like bleeding, shock, and organ failure.

Transmission and Vector Control

Virology

Dengue (pronounced Den’ gee) is a disease caused by any one of closely related dengue viruses (DEN1, DEN 2, DEN 3 & DEN 4).3 The viruses are transmitted to human by the bite of an infected mosquito, Aedes Aegypti but 2001 outbreak in Hawaii was transmitted by Aedes Albopictus. The Asian genotypes of DEN-2 and DEN-3 are frequently associated with severe disease.

Dengue virus is a RNA virus of the family flaviviridae3; they are otherwise called arboviruses. The dengue virus genome contains 11,000 nucleotide bones. They have 3 different protein molecules that form virus partied (C, prM and E) and 7 other types of protein molecules (NSI, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are found in infected host cells and are required for replication of virus. There are 4 strains of virus, ex; DEN1, DEN2, DEN3, DEN4. ALL 4 serotypes can cause full blown disease. Infection with 1 serotype is believed to produce lifelong immunity to that serotype, but he can be infected with other serotypes in future.

Strategies for Vector Control

The controlling of dengue fever involves a combination of strategies at the reduce the transmission of virus by its primary vector “Aedes Aegypti” mosquito.

Here some controlling measures

Source Reduction

• Locating and eliminating water-collecting and mosquito-breeding habitats, such as abandoned tires, flower pots, and water storage containers.
• Putting coverings or lids on containers that fit snugly to keep mosquitoes out
• Applying insecticides to "productive" containers—those where mosquitoes lay their eggs.
• Surveying pups in human habitations to determine which containers are most productive.

Larvicides 

Chemicals known as larvicides are created expressly to destroy mosquito larvae. They can be used to effectively lower mosquito populations by being administered to water sources where mosquitoes breed.

Adulticides

Adult mosquitoes are eliminated by using adulticides. Insecticides (such adulticide and larvacide) sprayed in open areas can aid in the management of adult mosquito populations.

Environmental Management

This entails modifying or getting rid of natural larval homes and water-holding containers. We lessen the possibility of mosquito reproduction by eliminating or altering these locations

Human Self-Protection

Using insect repellent is one way that people can shield themselves from mosquito bites.
Making use of window screens.
sleeping beneath bed nets sprayed with pesticide.
putting on long sleeves to reduce insect exposure.

Dengue Fever Prevention and Control Measure

The dengue virus, along with its vectors, is extensively spread throughout tropical and subtropical nations, such as Nigeria. Reducing dengue-associated morbidity and mortality requires a strategic focus on effective vector prevention and control techniques. Aedes aegypti is the primary arthropod vector used to transmit the dengue virus (DENV). Furthermore, Aedes albopictus, a less efficient vector, feeds on a variety of vertebrate species but has not yet been proven to be accountable for some dengue transmission. Interestingly, Aedes mosquitoes are more active during the day, which makes managing the vector challenging. Despite the substantial disease, social, and economic burden that dengue places globally, it has historically received little political will, coordinated efforts, or research attention, leading to its classification as a "neglected topical disease."This categorization has promoted.

One technical component of the Global Strategy for Dengue Prevention and Control, 2012–2020, is sustainable vector control. In light of the restricted treatment options and lack of dengue vaccination in the majority of endemic nations, efficient vector control techniques are a crucial part of the strategic plan to lower dengue-related mortality and morbidity. Living close to waste disposal sites is associated with an increased chance of contracting DENV infection, as determined by environmental factors. Artificial water containers, which are present in many households and trash disposal sites, are the nesting places for DENV vectors in the urban cycle. People who live in such communities are inevitably at a higher risk of catching dengue because of this behavior, which also promotes the growth and population of vectors.

Vaccination Effect and Challenges

Dengue virus (DENV) infection is the world's most quickly spreading virus spread by mosquitoes. Any of the four DENV serotypes can cause dengue, and the disease's clinical spectrum varies from mild, self-limiting dengue fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). During epidemics, higher hospitalization rates from severe dengue cause enormous financial losses and overburden the health system. The only way to reduce dengue-associated morbidity when there is no targeted antiviral medication is to manage vectors to prevent DENV transmission. Given that vector control techniques have not been sufficient in reducing viral transmission, the introduction of a dengue vaccine that is safe, effective, and affordable as a supplemental strategy is necessary. significant priority for public health. However, the development of a vaccine has been hampered by the peculiar and intricate immunopathology of dengue. Critical problems such as the lack of appropriate indicators of protective immunity and animal models for the disease have also raised doubts about dengue vaccinations. Several vaccine candidates, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines, and viral-vectored vaccinations, are in various stages of development despite the lack of an approved dengue vaccine at this time. While certain vaccine candidates have advanced from phase I and II studies in animals to phase II and III trials in people, there are still a number of concerns about the dengue vaccine's deployment in nations like India. Despite the present restrictions, the World Health Organization and other regulatory agencies' cooperative efforts with vaccine.

Impact of Dengue Fever Outbreak

Your blood vessels become compromised and leaky with severe dengue. Additionally, your blood's supply of platelets—cells that form clots—decreases. Shock, internal bleeding, organ failure, and even death are possible outcomes of this. Serious dengue fever warning signs, which are an emergency that might be fatal, can appear suddenly.

This study details the effects of a dengue fever outbreak on those who contracted the illness in the Puerto Rican village of Lares. The symptoms associated with the fever that have been observed match the clinical picture of the dengue virus's mild strain. A mixed quantitative and qualitative methodological approach is used in the study. The results show that a person's socioeconomic standing has a big impact on who gets dengue fever. The epidemic had a more severe effect on underprivileged urban and semi-rural communities, especially on women who identified as housewives and mothers and their offspring. The caregiving role that these women were expected to play by their families and society took precedence over their own illness. Furthermore, they suffered the most from the pandemic in terms of lost time. The incapacity of adult females in the household to carry out their regular tasks in order to support family life was the primary impact of the outbreak on work activities that are not often compensated with money, such as housework. Furthermore, a sizeable portion of the family's monthly income was consumed by the financial burden of health care. The stress caused by the clinical, social, and economic ramifications of the pandemic for women had an effect on psychological well-being. The subject of applied medical anthropology and dengue fever prevention and control are both affected by the noteworthy findings, which are presented.

Health and Economic Burden

Over 100 nations in Asia, the Pacific, the Americas, Africa, and the Caribbean are home to dengue, a mosquito-borne illness. A mild to moderate acute fever is the most common presentation of a symptomatic infection. However, up to 5% of dengue patients progress to severe dengue, a potentially fatal illness.

approximately the past 50 years, dengue has become more commonplace worldwide. In 2015, the World Health Organization (WHO) received reports of approximately 3.2 million illnesses from the Americas, South-East Asia, and Western Pacific regions. To determine the actual dengue burden, further methods are required as many cases remain unreported to national health systems. Between 58 and 101 million cases of symptomatic dengue fever are estimated to occur annually worldwide. Precise understanding of the financial and health costs associated with an illness is crucial for informing the creation of effective public health programs and directing the distribution of scarce medical resources. According to the Global impact of Disease (GBD) 2013 study, dengue caused 1.14 million disability-adjusted life years (DALYs) worldwide in 2013. This translated into a corresponding global economic impact of US$8.9 billion at current exchange rates. However, estimates of the economic and health effects of dengue vary throughout studies, and the methodologies employed have evolved over time. The purpose of this review is to present a critical summary of the most recent figures found in the literature about the health and economic costs of dengue in Vietnam.

Controlling on Dengue Fever Outbreak

The primary preventative measure to reduce dengue infections is the control of mosquito populations. Because the transmission of dengue requires mosquitoes as vectors, the spread of dengue can be limited by reducing mosquito populations. What can people at risk of dengue infections do to reduce the size of mosquito populations? One practical and recommended environmental management strategy is to eliminate unnecessary container habitats that collect water (such as plastic jars, bottles, cans, tires, and buckets) in which Aedes aegypti can lay their eggs . This strategy is called source reduction. When container habitats are removed and water storage containers are covered with a fine mesh to prevent mosquitoes from getting inside them, mosquitoes have fewer opportunities to lay eggs and cannot develop through their aquatic life stages. Source reduction can be effective when performed regularly, especially when members of a community are mobilized and educated about vector control.

Chemical Control of Dengue Mosquitoes

Chemical control can be effective in controlling mosquito populations. For instance, insecticides can be used to kill mosquito larvae or adult mosquitoes. Can insecticides be widely and routinely used? The use of insecticides is recommended in emergency situations during dengue epidemics or when there is evidence that an epidemic is emerging. On a regular basis, however, sustainable, coordinated, community-based environmental approaches are favored over chemical methods for controlling mosquitoes, and limited reliance on these chemicals is preferred. Why are environmental management approaches favored? One reason is that mosquitoes can develop resistance to insecticides. In addition, insecticides are expensive, and high doses can be toxic to humans and other species. Therefore, it is best to be cautious about applying these chemicals.

Bioinsecticides

Could safer insecticides be used to kill mosquitoes? Bioinsecticides are a combination of biological controls and insecticides. One example of a bioinsecticide is Bacillus thuringiensis israelensis (Bti), which is a naturally occurring soil bacterium that can effectively kill mosquito larvae present in water. There are many strains of Bacillus thuringiensis, each having unique toxicity characteristics, and Bti is very specific for mosquitoes. Bti is available in small, slow-release bricks called "mosquito dunks" that float on the water surface and are effective in treating deep water. Other bioinsecticides, such as pyriproxyfen and methoprene, act as juvenile hormone analogues that prevent mosquito larvae from metamorphosizing into adults.

Biological Control of Dengue Mosquitoes

Biological approaches are also being considered as alternatives to control mosquito populations. For example, predatory crustaceans called copepods and many varieties of fish, including mosquitofish and goldfish, eat mosquito larvae (Figure 3). When these organisms are placed in container habitats, decorative ponds, and pools, they prey on mosquito larvae, effectively preventing mosquito development. The addition of copepods into large water-storage tanks was successful in limiting dengue transmission in Vietnam. Other live predators- such as dragonflies, small aquatic turtles, and beetle larvae — have also been shown to be effective in killing Aedes aegypti.

Future Direction and Research

In order to evaluate drugs against dengue, animal model systems are required for drug development. It has been established and proven that a dengue mouse model is an appropriate test method for antiviral medications. In one investigation, the delivery of an antiviral medication that targets dengue RNA-dependent RNA polymerase dramatically and dose-dependently decreased viremia.

Prevention

The greatest risk for dengue virus infection is in individuals residing in endemic areas and not in travelers. Public health efforts in endemic areas: Control of the Aedes aegypti mosquito, which transmits dengue virus, and the development of vaccines are two potential approaches in preventing dengue virus infections.

Mosquito Control

Mosquito control is the most effective approach to the prevention of dengue transmission. Programs targeting the Aedes aegypti mosquito as a means to eliminate urban yellow fever in the Americas from the 1940s through 1970s were quite successful. These programs were also effective at reducing dengue transmission in the region. These programs were based on a "top down" approach involving aggressive mosquito surveillance and insecticide use. However, lack of attention and funding of these programs in the 1970s led to re-emergence of A. aegypti throughout its former region and the corresponding re-emergence of dengue. Insecticide spraying, in response to dengue outbreaks, is not highly effective against A. aegypti mosquitoes, which frequently breed inside houses. Community-based approaches involving education of the population in efforts to reduce breeding sites, such as discarded tyres and other containers that accumulate standing water. In one study, a comprehensive community and governmental control strategy, including the seeding of water vessels with Copepods (Fish) that feed on mosquito larvae, was successful in eliminating A. aegypti and dengue transmission in 32 communities in rural areas of Vietnam.

Vaccination

 Infection with dengue provides long-term protection against the particular serotype that caused the disease, supporting the feasibility of a dengue vaccine. However, it provides only short-lived immunity to the other three dengue serotypes. In view of the association of DHF with previous exposure to dengue viruses and the recognition that all four serotypes are capable of inducing DHF it is the general consensus in the scientific and public health communities that any candidate vaccine should produce protective immunity against DEN 1-4. Since waning immunity might also increase the risk for DHF in vaccinees, vaccine-induced protective immunity should also be long-lived. Animal studies indicate that protective immunity against dengue can be mediated by neutralizing antibodies, especially those directed against the envelope (E) glycoprotein. However, natural dengue infection induces low levels of cross-reactive antibodies that are detected in neutralization assays, but do not prevent infection with the other dengue serotypes. Studies have shed light on the molecular basis for antibody neutralization of virus infection; however, until improved assays are available the cross-reactivity will continue to complicate the laboratory assessment of vaccine-induced immunity. Tetravalent vaccines that induce immunity against all four serotypes are in development. In a rhesus monkey model, one tetravalent live attenuated dengue virus vaccine demonstrated seroconversion rates of 100, 100, 90 and 70 percent against dengue serotypes 1, 2, 3, and 4. In addition, vaccination resulted in complete protection against viremia from inoculation with serotype 2; challenge with the other dengue serotypes demonstrated protection in 50 to 80 percent of animals compared to controls. Recommendations for travelers: Most travelers from non-endemic countries are at exceedingly low risk for DHF because they lack previous exposure to dengue viruses.14 Avoidance of exposure to infected A. aegypti mosquitoes is the primary approach to prevention of dengue virus infections in travelers. These mosquitoes predominantly live in urban areas in and around houses.

Development of New Vaccine

Research and Discovery

Researchers are currently investigating possible vaccination concepts. Ten to fifteen years of laboratory work are often required, frequently in conjunction with academic institutions or the commercial sector. The goal of research is to find a vaccine candidate that shows promise.

Proof of Concept

Researchers use small animals like mice to investigate the vaccine's capacity to elicit an immunological response before testing it on humans. The vaccine advances to clinical trials if positive outcomes are seen.

Testing the Vaccine (Clinical Trials)

Phase 1: The trial vaccination is administered to a limited sample of individuals (20–100). Researchers evaluate immunological response and safety.
Phase 2: The trial is expanded to hundreds (100–300) of volunteers who share the intended recipients' characteristics. Data on efficacy and safety are gathered.
Phase 3: The vaccine is administered to thousands of individuals in order to assess its safety and efficacy.
Phase 4: Post-approval monitoring is ongoing, if approved.

Large-scale production of a vaccine starts after it has been shown to be both safe and effective. This stage guarantees that there are adequate dosages for general distribution.

Approval and Recommendation

After examining results from clinical studies, the FDA in the United States grants approval for the vaccine. Advisory groups advise using it because of its effectiveness and safety.

Reference

No Reference