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Introduction

Dengue fever epidemics have lately taken the front headlines in WHO reports, as they have become rampant throughout the world. Dengue, a disease transmitted through a mosquito vector by the name Aedes, is reported to be rampant in humid and sub-humid parts of the world. This means that more or less 2-3 billion citizens living in these areas are at high risk of contracting this disease. Despite the various attempts made to develop a vaccine against this disease, there is no vaccine, which is yet licensed for human use. The problem is that the disease has four existing stereotypes, which must be eliminated in order to curb the disease. The aim of the paper is to explain dengue fever and its history. The research explores how the disease has affected mankind throughout history. Finally, the development of dengue fever and the clinical trials that have been carried out on any vaccine that has been developed are explained in detail.

Dengue Fever History

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According to Whitehorn and Farrar (2010), Dengue Fever is a highly infectious disease caused by a group of viruses. The disease is passed to humans through mosquito bites. Up to date, the exact origin of this peculiar disease remains uncertain. However, recent research done in this field indicates that dengue fever may have originated from forests in Asia. The communicable cycle of this disease revolves around mosquitoes and primates. It is argued that an epidemic with characteristics similar to dengue fever was first recorded between 265 and 420 AD in a Chinese medical information bank. According to Rigau-Pérez (1998), the disease was referred to as ‘water poison’ and was argued to be highly infectious and communicable through flying insects.

Arguably, an outbreak, which looked similar to dengue fever, was recorded in 1992 in China. Following this outbreak, other dengue-like outbreaks were recorded in French, West Indies around 1635, and later on in 1699 it was reported in Panama. Two years after the report of dengue in Panama, a doctor by the name Sabater Jose, who was by then a physician at a military hospital, claimed to have treated the disease with small amounts of rum. During this period, the disease was commonly referred to as break-bone disease, as it mainly affected the bones. According to scientists, this disease causes severe pain in the bones and joints, which makes the patient feel like the bones are breaking.

Scientists point out that there have been several endemics of dengue fever, but the most credible early reports of this disease were recorded in late 1700s when serious dengue epidemics swept nations such as Africa, Asia, and North America. In 1780, a doctor in Pennsylvania by the name Rush Benjamin recorded an epidemic of dengue fever. This doctor tried to describe some symptoms of the disease, which he collectively called ‘bilious remitting fever’. Some of the symptoms listed by Dr. Rush included fever, pain, especially in the bones and muscles, headache, weakness, nauseating and hemorrhage. Many modern scientists argue that Dr. Rush made a spectacular contribution to the study of dengue and its effects on human beings. Most of the symptoms that Dr. Rush listed are similar to the symptoms of this disease even in the modern clinical practice context.

The name dengue was developed as early as 1801. Spain’s queen Luisa in 1801 fell a victim of this disease and in her statement after recovery, she said that she felt uncomfortable and her throat hurt because of suffering from a disease by the name dengue. After the formulation of the name dengue for the disease, many scientists tried to explain the meaning of the name. In Spanish, the name dengue means vigilant or careful. The patients suffering from this disease move in a cautious manner, because the disease mainly affects bones and joints making them become stiff and highly painful. Some other scientists have evolved the meaning of this name from a Swahili expression “ka dinga pepo,” which means that the illness is from an evil spirit. In West Indies, the disease mainly affected the slaves who are said to have had a dandy walking style and, hence, the disease came to be known as the dandy fever.

In 1818, a serious epidemic of this disease was recorded in Peru, whereby approximately 50, 000 people were affected. However, according to Halstead (2008), this is not the first recorded dengue epidemic. In fact, the first endemic of this disease was recorded between the year 1827 and 1828. During this period, the disease affected many regions including the United States, Cuba, Mexico, Virgin Islands, and Jamaica. Dengue plague is argued to have affected many countries around the world. In mid and late 1800s, the disease is said to have seriously hit such nations as the United States, Brazil, and the Caribbean. In early 1900s, the disease occurred more frequently compared to mid and late 1800s. In 1906, a mosquito genus by the name Aedes was established to be the means of transmission of dengue fever. A year after this, studies on this disease and its mode of transmission by two scientists namely John Burton Cleland and Joseph Franklin Siler revealed that dengue followed yellow fever in order of emergence of the diseases believed to be transmitted by a virus. It is argued that the study carried out by these two scientists contributed significantly in understanding dengue fever and its mode of transmission.

As Gubler (2011) explains, dengue epidemics became rampant during the World War II. During this period, the disease is argued to have spread to new regions all over the globe. The main reason for its spread is the fact that soldiers were distributed the entire world and the ones who carried the viruses infected people in the regions where they were stationed. According to Chakraborty (2008), the spread of dengue fever throughout this period is also credited to ecological disruption. It is argued that during this period, various serotypes of dengue fever spread to new areas and it is during this time that dengue hemorrhagic fever surfaced. The first outbreak of another serotype of dengue by the name severe dengue was reported in 1953 in a region called Manila in Philippines. Following this epidemic, the disease continued spreading to countries like Southeast Asia during the subsequent 20 years. Scientists point out that the spread and occurrence of this disease took a pattern as the epidemics became more rampant. The epidemics were characterized by more cases of hemorrhage fever. During this period, dengue hemorrhagic fever epidemics became more frequent and it was established through studies that its outbreaks occurred after every three years. This pattern of outbreaks is argued to have spread to other new regions.

The spread of this disease forced countries like America to come up with various initiatives of ensuring the disease was eliminated. Therefore, during the period between 1960s and 70s, few occurrences of dengue epidemics were recorded in both Central and South America. However, according to Gubler (2011), after the occurrences reduced, America and other countries that had started initiatives of fighting the disease relaxed. This led to more dengue epidemics all over the world. As Gubler (2011) explains, dengue fever continued affecting many nations and by the late 1970s, child mortality in the Pacific and America was mainly attributed to this disease. Two serotypes of dengue namely, “hemorrhagic fever and shock syndrome” were initially reported in 1981 in Central as well as South America. Scientists point out that people who had previously contracted dengue fever virus DENV-1 became vulnerable to virus DENV-2, because their immunity to this disease had decreased following their first infection.

The spread of dengue fever has continued over time and recently, World Health Organization (WHO) has reported a number of epidemics of this disease. According to WHO reports, dengue fever endemics have increased over time. Research shows that dengue fever has become a national threat in many countries, posing greater risk to civic health compared to the past. Dengue epidemics have affected almost all the humid and sub-tropical parts of the planet. New countries that have never been affected by this disease, such as Nepal and Bhutan have been affected greatly starting from 1960s. The increasing spread of the disease has evolved many questions, such as why have the epidemics of dengue fever become so frequent? Scientists working on this have tried to answer this question with a variety of suppositions. Some argue that population increase is the main cause of this, as people are becoming more congested, especially in urban areas, allowing the disease to spread more easily and faster. Other factors that have been pointed as the main causes of the  increase of dengue epidemics include poor mosquito management, poor sanitation, especially in urban areas of developing nations, and long distance journeys. It is also argued that the decrease in the spread of this disease is attributed to better examination and footage of this disease in modern days compared to the old days when the disease was poorly monitored. According to Guzman (2010), the increasing epidemics of this disease pose a serious international challenge that should be given a priority by all nations.

How Dengue Fever Has Affected Humans over the Course of History

According to Guzman (2010), dengue fever is one of the most widespread illnesses, which is affecting many people all over the world. Worldwide, approximately 2-3 billion people reside in regions established to experience dengue fever transmission every year. Recent WHO reports on diseases and their rate of infection indicate that about 50-100 million people are infected with this disease all over the world. In recent years, WHO reports indicate that dengue cases have increased considerably. According to Halstead (2008), dengue epidemics have been reported in almost all tropical and sub-tropical areas of the world. Dengue fever has spread to many parts of the world including countries, such as Nepal and Bhutan. Incidences of Dengue Fever are argued to have multiplied almost 30 times since 1960s. According to Gubler (2010), dengue fever is believed to be caused by any of its four viruses. Researchers point out that infection with any of its four viruses lowers the immunity of a person against all other dengue serotypes. This means that a person who has been infected with any dengue serotype is highly vulnerable to an infection with the other dengue serotypes. As Gubler (2010) explains, in a single epidemic, all the four dengue viruses might be in circulation.

According to WHO reports, there are approximately 50 million people infected with this disease annually all over the world. However, some researchers argue this figure may be even higher than 100 million. According to Chakraborty (2008), it has been established that dengue infection brought about another serious disease known as severe dengue. This form of dengue hospitalizes around 500, 000 people annually, most of which are children. Research indicates that about 5% of patients, suffering from this disease, eventually die. As Chakraborty (2008) explains, currently, around 2-3 million people all over the planet are at the risk of contracting the disease. Tropical areas are said to have good climatic conditions for the transmission of this disease and, hence, many people suffering from this disease live in the tropical areas. Tropical areas include Africa, Southeast of Asia, Central, and North America among many others. Researchers also point out that dengue and severe dengue are more rampant in urban areas compared to rural areas.

According to Gubler (2010), the first dengue epidemics were reported concurrently in North America, Asia, and Africa in early 1780s, following the identification and naming of the disease in 1779. A dengue endemic was reported in South East Asia in 1950 and by late 1970s, Dengue Hemorrhagic Fever (DHF) had become a principal cause of children fatality in the region. Since 1980s, dengue epidemics have become rampant throughout the world. According to scientists, by late 1990s, dengue fever had been established as the second leading disease after malaria, transmitted by mosquito and affecting over 40 million people. WHO reports that dengue outbreaks tend to reoccur after every five to six months.        

It has been established that dengue infections sometimes increase and other times decrease because of the influence of cross-immunity in its transmission cycle. According to World Health Organization (2009), when the immunity goes down, human population becomes highly vulnerable to infection. This means that over time, there are always large numbers of people who remain vulnerable even in infected populations despite having been hit by previous outbreaks. Another factor that makes human population susceptible to infection by dengue fever is that it has four types of viruses, which are believed to circulate at the same time during an outbreak. As Halstead (2008) points out, people who have never been exposed to the disease before or children born during an outbreak and people migrating during an outbreak are highly susceptible to an infection.

Researchers argue that the case of dengue fever outbreaks that have been reported do not represent the exact figure of people who have been affected by the disease since it was established. There are cases in which a person suffering from dengue fever does not get a chance to seek treatment from a medical institution. This means that such information is left out of national medical records on the spread and outbreaks of this particular disease. In 2002, a serious outbreak was reported in Rio de Janeiro, in which around one million people were infected and sixteen others died. According to the statement of Rio de Janeiro’s state secretary, there were around 23,555 dengue cases, which had been recorded and 30 fatalities in a period of less than three months following the outbreak. In his statement, the state secretary stated that he was considering the cases as an epidemic, because their numbers were high. The federal Minister of Health at that time approved the seriousness of the endemic and promised the nation that he would form a committee to lay immediate strategies of dealing with the public health issue. However, by 2008, the numbers of dengue cases increased to around 55,000.

In 2004, Singapore reported around 4,000-5,000 cases of dengue fever and seven deaths in the same year attributed to dengue shock syndrome. Recently, an outbreak was recorded in Puerto Rico in 2010 in which around 5000 people were confirmed to have been infected with the disease and 20 others were left dead. In the same year, in the French Caribbean regions, such as Guadeloupe and Martinique, 40, 0000 clinical cases were documented in each of these highlands. It is also during this time that dengue fever endemics were reported in French and Dutch island of St.Martin. During this 2010 wave of dengue epidemics, 5,000 infections were reported in Pakistan and around 31 people were reported dead.

According to WHO 2009 reports, a region by the name Cairns in the tropical north of Queensland Australia reported a dengue outbreak in December 2008. Four months after the outbreak, there were around 500 cases of dengue that were confirmed in a population of around 150, 000 people. Following this outbreak, it is reported that the disease spread subsequently to the surrounding towns such as Townsville, and Port Douglas and Rock Hampton among many others. In Queensland, an elderly woman died from the disease on March 4, 2009. In the statement given by the hospital, it was stated that despite the fact that the woman was suffering from other health problems, she was tested positive for dengue fever, and this most probably had contributed to her death.

According to WHO reports of the year 2009, many Argentina’s northern provinces such as Catamarca, Salta, Jujuy, and Chaco reported dengue infection. In all these provinces, over 9,500 dengue cases were reported by April 2009. It is argued that some travelers from these infected regions spread the disease to regions as far as Buenos Aires. Following these epidemics, major interventions to control and manage the disease were formulated such as preventing the vector mosquito from replicating. Such efforts include campaigns that sensitize people on the need of emptying all possible water reservoirs, as they form the breeding sites for the disease vector. The government also came up with initiatives of purchasing up-to-date insecticides to control mosquito population. It has been reported that Sri Lanka is one of the countries, which is currently suffering from dengue epidemic

In Texas, United States, the first significant transmission of dengue fever was reported in 1986. According to historical research, the population who was later established as the carrier of the dengue virus was argued to have crossed the American border through Mexico. Immediately the carriers crossed the border, the virus infected the local population. Following this initial infection, it has been established that seasonal outbreaks of dengue fever have since been reported both in Texas ad Hawaii. In Hawaii, the first dengue fever outbreak to be reported since the conclusion of Second World War was in 2000-2001. The outbreak was caused by DENV-1, and it affected both children and adults. 122 cases were reported, and the disease gradually spread to other areas, such as Maui, Kauai, and Oahu. Scientists established that the epidemic came about because of visitors who had come from Tahiti to Hawaii, who are believed to have been infected with the virus, since Tahiti had been hit with a severe dengue epidemic.

Since the first dengue epidemic in America, seasonal and other epidemics have been reported in many parts of America, such as New Mexico, Mississippi, Alabama, Texas, and Georgia among many others. Dengue outbreaks were also reported in West Florida in 2009 and 2010. It is argued that these outbreaks were comparable to the 2005 outbreak in Texas and the 2001 outbreak in Hawaii. However, the outbreaks occurred and were sustained on American soil and not because of people traveling from areas reported with dengue epidemics. It is argued that American visitors traveling to and from countries with reported dengue epidemics create possible trails, through which dengue serotypes enter America and infect populations, which have never been exposed to the disease for many decades. Medical researchers point out that it is highly important that American government monitors its travelers, both legal and illegal, to control the spread of this disease and come up with strategies of ensuring that its citizens are protected from this deadly disease.

The dengue fever does not occur naturally in continental Europe and the whole of European Union. The main reason attributed to this observation is that this part of the world does not have an appropriate vector population adequate to allow the spread of dengue from any visitors traveling from areas reported with dengue epidemics. However, dengue occurs in numerous other regions of European Union. According to recent researches done in this field, dengue epidemics have been reported in tourists, settlers, and military personnel in many parts of the European Union.

Development of Dengue Vaccines and Their Trials

According to World Health Organization (2009), despite the much effort applied by medical scientists to develop a dengue vaccine for many decades, there is not yet a vaccine that has been licensed for prevention of this disease. Many scientists have argued that the main obstacle faced in developing a dengue vaccine stems from the virus itself. Just as explained, dengue is caused by four types of viruses and this means that a vaccine, which is developed, has to offer full immunity to all the four types of viruses. Research has shown that infection with a dengue virus offers long-lasting immunity, but only to that particular dengue virus. If a person is infected with more than one virus, one becomes vulnerable to attacks by “dengue hemorrhagic fever or dengue shock syndrome,” which is more deadly than normal dengue.

Research points out that an epidemic caused by one dengue virus is followed by another caused by any of the other three serotypes within a period of three months. It is argued that within a single epidemic, all the four serotypes might be present. Recently, it has been reported that a doctor by the name Claire Huang and her team in Fort Collins have succeeded in developing a vaccine candidate currently being tested in the United States and Colombia for protection and effectiveness. The first Phase-1 trial showed that the vaccine was safe and moderately effective. The vaccine was reported to have produced enough antibodies that could protect against all the four serotypes of dengue. After these encouraging results, a Phase-II trial was done to assess whether the vaccine could aggravate sufficient immunity response for all the four types of viruses. After the phase-II trials, a phase-III trial would be carried out to evaluate the efficacy of the vaccine. This shows that the development of any vaccine against human diseases takes several steps to ensure it is highly effective.

Dr. Claire’s technology has received approval from many scientists all over the world. Another CDC’s team, working on the development of a dengue vaccine, has collaborated with a Colorado based manufacturer and has managed to develop a dengue vaccine by the name DENVax. It is undergoing clinical testing to evaluate whether it is safe for human use. The goal of developing a dengue vaccine is to ensure it is effective and affordable to all in order to protect billions of people vulnerable to dengue infection all over the world. In Thailand, a group of scientist by the name BANGKOK has been recently reported to have come closer to developing a dengue vaccine. This group of scientists is argued to have developed a dengue vaccine candidate, which is safe and effective, but it still needs more trials to prove its safety and efficiency for immunizing against dengue fever.

The second clinical trial of this particular vaccine candidate proved to be 30% effective in protecting all the four dengue viruses. AsGubler (2010) explains, the CYD-TDV vaccine developed earlier by the drug company Sanofi Pasteur has been tested using a sample of 4, 000 children between the age of 4 and 11, from 57 schools in Thailand. The trial results of this vaccine can protect against infections by DENV 1, 3 and 4, but cannot protect against DENV 2. During its clinical trial, the vaccine proved to be safe and well tolerated by the sample of people used in testing its efficacy. However, many scientists, uninvolved in the study, criticized the trial results pointing that the data gathered was inadequate to prove that the vaccine was effective for vaccinating against dengue and therefore, it needed thorough trials.

Following the development and trial of this vaccine, a leading physician at the International Institute in Seoul in Korea stated that the results were both shocking and devastating. The physician argued that the results were devastating, as they could not protect against DENV-2, which was the most common in Thailand compared to all other types of dengue viruses. In conclusion, he pointed out that it was too early for any clear conclusions to be drawn on the development of an effective dengue vaccine. Sutee Yoksan, the director of the center for vaccine development at Mahidol University in Thailand, who sensitized the need for more investigations to be carried out in order to ensure the vaccine was effective and safe for human use, supported the sentiments of this physician. According to Gubler (2010), currently, Phase-III clinical trials are being carried out on this vaccine using a sample population of 31,000 children and teenagers in many parts of Latin America such as Mexico, Brazil and many others, where many dengue epidemics have been reported. The Phase-III trial results on this particular vaccine are expected to be out by 2014. If the results are proved successful in immunizing against dengue fever, they will be distributed by 2015 to many countries where dengue is a priority public health issue.

According to World Health Organization (2009), due to the lack of permitted vaccines for this disease, the main means of deterrence are the effective control and protection of mosquito bites, believed to be the main means of transmission. The World Health Organization has formulated an Integrated Vector Control program, aimed to prevent against dengue infection. The program is based on five main elements, namely:

  • Support, community enlistment, and proper legislation to guarantee civic health agencies and the community are reinforced
  • Teamwork amid the public and private sector
  • Effective use of resources to ensure effective approach to disease control
  • Decision-making based on evidence to ensure that any initiatives are targeted suitably.
  • Capability building to ensure a sufficient response, especially to local dengue situations

Researchers have argued that the main method of controlling DENV-1 is eliminating all its possible habitats, such as pools of water or introduction of biological control agents in the area believed to have been infected with the mosquito responsible for its spread. Elimination of mosquitoes through spraying insecticides is said to be ineffective. Therefore, the most preferred method of controlling this disease is through reduction of all possible open water collections through environmental campaigns. Eradication of this disease using insecticides has been proven to pose various negative health and environmental impacts, such as air and water pollution. Scientists also point out that people can effectively protect themselves by wearing clothes covering all parts of the body, sleeping under treated mosquito nets and use of insect repulsive, such as DEET.

Conclusion

It is quite clear that dengue fever has become one of the leading causes of fatalities in many nations all over the world. The disease is believed to be transmitted through a mosquito vector by the name Aedes, affecting around 2-3 million people globally. Research points out that this disease is common in the humid and sub-humid parts of the world. Historically, the disease was first recorded between the period 265 and 420 AD in a Chinese medical encyclopedia. Back then, the disease was referred to as water poison and was believed to be spread through flying insects. The first outbreak of this disease was recorded around 992 in China, and by late 1690s the disease is believed to have spread to such areas as French West Indies and Panama. After these epidemics, the disease is said to have spread to new regions, including Central and North America and most of the tropical regions of Africa. Many scientists have tried coming up with an effective vaccine against this disease, but none have so far succeeded. It is argued that the main reason why it has been difficult to develop an effective dengue vaccine is that four types of viruses cause the disease. Therefore, the vaccine developed has to be highly effective in vaccinating against all the four serotypes of dengue. Many scientists point out that it is important for nations to ensure their citizens are protected from this deadly disease their priority. Citizens should also take personal responsibility of prevention and reporting any signs of the disease.

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