Dengue Fever: Re-emergence, DHF Emergence in America - A Report

This report provides a comprehensive historical overview of the re-emergence of dengue fever and the emergence of dengue hemorrhagic fever (DHF) in America. It begins with the first reported case in Philadelphia in 1780 and traces subsequent epidemics throughout the 19th and 20th centuries, focusing on the Caribbean and southern United States. The report details the re-emergence of dengue in the 1960s, highlighting the introduction of different strains like DEN-1, DEN-2, DEN-3, and DEN-4, and the geographical spread of the disease across various countries including Cuba, Venezuela, Brazil, and Mexico. It also examines the emergence of DHF, particularly the first major outbreak in Cuba in 1981, and the subsequent outbreaks in the Americas, including the significant impact of the DEN-2 virus. The report explores the varying incidence rates, age distributions, and gender patterns associated with the disease, offering a detailed analysis of the historical context and public health implications of dengue and DHF in the Americas.

RUNNING HEAD: RE-EMERGENCE AND EMERGENCE OF DHF IN AMERICA 1
Re-emergence of Dengue and Emergence of DHF in America
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RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 2
Historical overview
In 1780 in the region of Philadelphia United States of America, there was the first ever
case of dengue disease among the Americas. However, there were four epidemics of the same
condition in the following century. The epidemics took place in 1827-28, 1850-51, 1879-80 and
finally 1897-99 (Aubry et al., 2011).The regions that were adversely affected by this epidemics
are countries from Caribbean and the southern United States. During the dengue outbreak of
1827-1880, the clinical manifestation of the disease was similar to those of chikungunya and the
Mayaro viruses. The clinical manifestations exhibited include small joints arthritis and swelling.
The four epidemics of the dengue virus occurred in the same countries during the first half of the
century with the last epidemic occurring between 1941-1946 (Aubry et al., 2017).This epidemic
affected cities within the Texas Gulf, Caribbean islands such as Cuba, Puerto Rico and Bermuda.
Other countries that were affected include Mexico, Panama and Venezuela.
In Brazil, the dengue epidemics have been reported during 1846-1848 and between 1851
to 1853.However, it is not until 1982 that two outbreaks have been reported, one in 1916 and the
other in 1923 (Añez & Rios, 2013).Peru on the other hand has only reported a single epidemic of
the dengue disease back in 1953 with no single case in the last three decades.
It was not until 1953 that the first case of dengue virus which was described as DEN-2
was isolated among the Americas. The case was isolated in Trinidad (Brathwaite Dick et al.,
2012). During this same period, several isolates were also obtained within the same island of
Trinidad though there was no single outbreak that was reported during the same period or any
other Caribbean island.

RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 3
Re-emergence of dengue
In 1960s, there were two dengue pandemics with large magnitude that affected Caribbean
regions and Venezuela. The initial pandemic took place in 1963 and was described as DEN-
3.This pandemic really affected the Caribbean regions after almost 20 years of silence (Cao-
Lormeau et al., 2011). Among the countries affected by the DEN-3 pandemic were
Jamaica, Puerto Rico and the islands of Lesser Antilles and Venezuela. The most interesting thin
with this pandemic however the fact was that some countries within the same region were
spared. They include Cuba, Hispaniola as well as Trinidad.
The second dengue epidemic occurred between 1968 to 1969.It occurred in Caribbean
islands and the Venezuela. The most common strain isolated during this second outbreak was
DEN-2.However, some DEN-2 strains were also isolated among some people in some of the
Caribbean islands. In 1970s the two strains of dengue virus (DEN-2 and DEN-3) were reported
in Colombia a region where no single case had been reported from 1952 (Dupont-Rouzeyrol et
al., 2014).The initial outbreak occurring between 1971 and 1972 which was DEN-2.During the
year 1975 and 1977,dengue disease epidemic due to the DEN-3 strain was reported in the same
country. During this second epidemic, studies argue that more than one million people were
affected. During the two outbreaks however, the disease was silent while in some regions, it was
confused with other diseases and therefore there was no much attention from the different health
authorities.
One of the greatest milestone in the re-emergence of dengue disease was back in 1971
when a new strain was discovered. This strain was named DEN-1.The DEN-1 was followed up
with another disgusting pandemic which lasted until1980.The initial strain of DEN-1 was
discovered in Jamaica and scientists argue that it must have been imported from African

RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 4
Countries. Since then, the virus rapidly across Caribbean countries (Fares, Souza, Añez, & Rios,
2015). In 1978, there was another pandemic that hit South America with countries such as
Venezuela, Colombia, Guyana, Suriname and French Guinea being the most affected. During the
same year, another epidemic was detected in Central America which initially affected Honduras
followed by El Salvador, Guatemala and finally Belize. Since this epidemic was spreading
towards the North, it reached Mexico during 1979-1980.It continued to affect major cities within
Mexico and reached the state of Texas during the second half of 1980.According to reports by
the Pan American Health Organization, 702,000 cases were reported between 1977-1980
(Forshey et al., 2009).The incidence in this epidemic were also high since statistics indicate that
more than 5 million people were infected in Colombia, Cuba as well as Venezuela.
In 1981, a second milestone in the re-emergence of dengue was noted. The milestone was
recording of a new strain the DEN-4 that scientists established its source being the pacific
islands. This strain was then followed by a series of outbreaks in the Caribbean, Northern South
America, Central America and finally Mexico. However, this strain has been associated with
mild diseases apart from some few exceptions.
Five countries that previously had never experienced dengue disease experienced
explosive epidemics during the 1980s.The five countries affected include Brazil, Bolivia,
Paraguay, Ecuador and finally Peru. These countries had been free of the disease for many
decades (Gubler, 2012). The epidemic in this case was due to the DEN-1 strain. However, DEN-
4 was also isolated in parts of Peru. In Brazil, the first epidemic noted in Roraima in 1982 was
due to the DEN-s 1 and 4 strains. During the outbreaks, vector control measures were
implemented and no single outbreak was reported in the same region until 1996 (Gubler,
2010).The DEN-1 was isolated in Rio de Janeiro in 1986 and it was responsible for majority of

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the outbreaks in the region. After the introduction of dengue in the five countries in South
America, DEN-1 has led to most of the epidemics in those countries especially Brazil, Ecuador
and Peru in subsequent years.
There were two Latin American countries in which no single outbreak of dengue virus
had been reported for many decades. The countries in question include Costa Rica and Panama.
In 1993 however, indigenous transmission of dengue disease were reported in the two countries
(Heringer et al., 2015). The agent for the outbreaks in the two countries was DEN-1.Scientists
link the outbreak in Costa Rica to the severe outbreaks in the same region.
DEN-3 was re-introduced in in the Americas after a 16 year absence since being last
isolated in Puerto Rico in 1978.The same strain was detected in Panama and Nicaragua initially.
In subsequent years, the strain spread to other Central American countries and Mexico leading to
numerous epidemics of dengue within the same region (Heringer et al., 2017).DEN-3 was
introduced in 1994 and scientists state that this was due to the countrywide outbreak of dengue.
However, DEN-1 was also present.DEN-3 was then introduced in Mexico in
1995.Coincidentally, this was the same time the number of DHF cases increased. However,
research only associate DHF with DEN-1 and DEN-2 (Rodriguez-Barraquer et al., 2011).It
should be noted however that the DEN-3 genotype isolated in Nicaragua in 1994 is similar to the
one that caused major epidemics of DHF in Sri Lanka and India back in 1996.From then (1997),
no single DEN-3 genotype has been isolated beyond Central America and Mexico.
There has been a variation in the number of DHF cases reported among the Americas
between 1980-1996.Statistics indicate that the cases vary between 39,307 in 1984 to 388,591 in
1991.There has been a surge in the cases from 1994 with the highest number recorded in 1995 as
315,000.In 1997,270,000 cases were reported.

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The emergence of DHF
The first major outbreak of DHF in America was reported in 1981 in Cuba. However,
there had been suspected cases of the condition in five countries that include Venezuela,
Jamaica, Honduras, Curacao and Puerto Rico (Rodríguez-Barraquer et al., 2015). Few of the
cases could however fulfil the World Health Organization criteria for the diagnosis of dengue
hemorrhagic fever. Most of this cases were also not confirmed by laboratory tests. According to
statistics, the initial outbreak in Cuba is estimated to have infected more than 344203 people. Out
of these numbers, 10,312 were classified as being severe cases (Salje et al., 2014). According to
the World Health Organization, the severe cases are those that fall within grades ii-iv. 158 cases
were fatal during the same outbreak while 116143 were hospitalized. Scientists link this Cuban
epidemic to the DEN-2 virus which took place years after DEN-1 had been introduced in the
same region leading to the dengue virus epidemic that infected more than half of the country’s
population.
The department of health with the help of the world health organization acted swiftly to
eradicate aedes aegypti which is the vector responsible for the virus. The last cases were reported
in October 1981.Since then, the island was free of the virus until 1997 when an outbreak was
reported in Santiago Province which is in the east of Cuba. By August 1997, 2946 cases of
dengue virus were reported with 205 DHF cases and the Cuban Ministry of Health report that 12
people died from the condition.
In the history of dengue virus among the Americas, the Cuban outbreak was the most
significant. This is due to the fact that there was subsequent outbreak of the condition in the
country in each year except 1983 (San Martín et al., 2010).There was a marked annual increase
in the incidence of DHF in 1989 and this was due to the countrywide epidemic in the

RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 7
neighboring country Venezuela. This 1989 epidemic is believed to be the second largest
epidemic ever with 3108 reported cases and 73 deaths which were reported between 1989 and
1990.The predominant strain during this second largest outbreak was DEN-2.However, DEN-1
and 4 were also isolated from some of the patients. However, no latter strains were isolated form
the fatal cases (Shepard, Halasa, Zambrano, Dayan, & Coudeville, 2011). The only genotypes
obtained from the fatal cases were DEN-2 and this was carried out through
immunohistochemically analysis that was carried out through formalin fixed paraffin embedded
tissues obtained from the fatal cases. Results were positive for DEN-2 antigens from four of the
fatal cases. A similar epidemic recurred in 1990 and from there, Venezuela has been hit by the
epidemic on an annual basis.
42246 cases of DHF have been reported between 1981 and 1996 with 582 deaths reported
within the same period among 25 countries in America. According to statistics, 535 of the cases
were from Venezuela. Colombia, Nicaragua and Mexico each reported more than 1000 cases
each during the same period (Soto-Garita, Corrales-Aguilar, Somogyi, & Vicente-Santos, 2016).
From 1986 to 1987, 4 fatal cases were reported in Brazil and they were linked to DEN-1
genotype.24 cases and 11 deaths were also recorded in Rio de Janeiro between 1990 and
1991.When a comparison is made about the distribution of the disease according to age, it was
established that the disease occurred across all age groups in Cuba and Venezuela. The fatal rates
were however higher in children below 15 years since they contributed to two thirds of the fatal
cases (Souza et al., 2017). There was a modal age range of 31-45 years in DHF cases that
fulfilled WHO criteria in Brazil. In Puerto Rico, there was a distinct age distribution patterns for
the cases that meet the WHO criteria. Regarding distribution of the epidemic with gender, there
was no significant female predominance in Cuba as opposed to that observed in Asia.

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Both the two epidemics that took place in Cuba and Brazil were linked to the DEN-2
virus.DEN-1 had previously been introduced in the two countries four years later after a long
absence of the disease. It was Cuba that the impact of DHF outbreak was large as opposed to
Brazil in which only few cases were reported (Stoddard et al., 2014). There are other countries
that have experienced a similar sequence of infections with the two serotypes. The countries in
picture include Peru and Ecuador. However, no DHF epidemic has been reported in the said
countries.
There was a rare epidemiological pattern of DHF in Venezuela as well as the French
Guiana whereby the DHF had been endemic for more than 20 years prior to the emergence of the
initial epidemic between 1989 and 1990 and between 1990 and 1991 (Tapia-Conyer, Betancourt-
Cravioto, & Méndez-Galván, 2012).The most predominant genotype of the virus observed in
Venezuela and French Guiana was the DEN-2.This was still the same genotype observed in fatal
cases in Venezuela. There was an interesting discovery of the DEN genotype that was discovered
among the cases in French Guiana. The genotypes were genetically identical to the one that
belongs to the Jamaican genotype which was had a genome sequence similar to the DEN-2 strain
from the Vietnam where cases of DHF are highly endemic. This new findings illustrate the
complexity of different factors that contribute to the DHF. According to studies conducted
during the outbreak in Cuba however, it was established that some of the factors that trigger
DHF include chronic diseases like diabetes mellitus, sickle cell anemia and race. Race is thought
to be a risk factor since DHF is more common in white than the black persons.
The case fatality rate of DHF among the Americas remain relatively high
(1.4%).However, there is still variation in this rates with CFR rate of 8.35 in 1995 in Puerto Rico
and 0.8% in Venezuela. Studies link the variation in the case fatality rates to different factors

RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 9
such as reporting criteria, the genotype of the virus, how the cases are managed, the genetic
make-up of the host and finally other possible causes.
Causes of emergence and re-emergence
Scientists’ link different factors to the re-emergence and emergence of dengue disease in
America. The different factors include a rapid increase in urbanization among the Latin America
and the Caribbean islands. There is also increased travel of people and this has been associated
with dissemination of the virus from one region to another (Wilder-Smith, 2012). The other
factor is increased circulation of all the four strains of dengue viruses that increase the risk of
DHF in the region. Finally, inadequate vector control programs have also contributed to the
increased cases of DHF.
Vector control
The vector responsible for spreading dengue virus is the Aedes aegypti. PAHO is the
body that was entrusted with the mandate to control the vector. This took place in 1947 where
the Directing Council of PAHO entrusted it to set up hemispheric campaigns to eliminate the
aedes aegypti vector. By 1962, 18 continental countries had successfully eradicated the vector
(Vasconcelos & Nunes, 2011). This was attributed to the establishment of highly organized,
centralized vertical programs that had super vision with adequate funding. After 1962 however,
only three countries managed to eradicate the vector. There was another serious problem in that
after several countries had achieved eradication, they were again re-infested with the vector in
1960s as well as the subsequent decades.
Scientists argue that re-infestation of the vectors is due as a result of countries that are
still infested. The countries in picture include United States of America, Venezuela, Cuba and

RE-EMERGENCE OF DENGUE AND EMERGENCE OF DHF IN AMERICA 10
other countries within the Caribbean islands. At a time when re-infestation took place, majority
of the countries were reluctant with surveillance programs as well as insufficient funding and
manpower (Tapia-Conyer, Méndez-Galván, & Gallardo-Rincón, 2009). Other notable reasons
for re-infestations include reduced political support that led to poor management and scarce
qualified personnel. Resistance of the vector aedes aegypti to the chlorinated insecticides,
expensive nature of materials to be used and increased wages are other reasons for re-infestation
of the vector responsible for transmitting dengue virus.
Re-infestation contributed to the progressive dissemination of the disease such that by
1997, all the American Countries were infested with the disease with an exception of Canada,
Chile and Bermuda. Since the vector is known to breed around water reservoirs, scientists argue
that the increased exercise of storing water in tanks due shortage of water in this countries as
well as the increased use of containers such as tyres might have greatly contributed to the
increased densities of the vector.
The primary vector of dengue virus is aedes aegypti while aedes albopictus is the
secondary vector for the same. This secondary vector was initially reported in Texas USA in
1985.Since then, there have been similar infestations in 1986 in Brazil, in 1993 in Mexico while
in Dominican Republic, the infestation of the secondary vector took place in 1995 (Tapia-
Conyer, Méndez-Galván, & Burciaga-Zúñiga, 2012).In Bolivia, Cuba, El Salvador and the
Caymans Islands, infestation of the secondary vector took place in 1995,1995,1995,1996 and
1997 respectively. Despite the fact that the aedes albopictus has been confirmed as a laboratory
vector of dengue, yellow fever as well as different arboviruses, studies are yet to confirm if it is a
real vector of the dengue virus in America and as a result, there have been very minimal efforts
to eradicate this species in Brazil.

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Since dengue virus was increasingly becoming a public health threat in America, there
was the need for strategies to reduce its incidence. It is for this reason that PAHO came up with a
resolution that gave countries an option to eradicate aedes aegypti. The solution was to involve
maintaining the quantity of the vector at levels that are not a public health threat. This was to be
primarily achieved through integrating the chemical, biological as well as physical methods.
There was also the need of education as well as public participation (San Martín et al., 2010). All
this strategies were later documented into an article that was named “Dengue and Dengue
Hemorrhagic Fever in the Americas: Guidelines for prevention and control.” Despite the
mentioned solutions, dengue virus was still spreading in America. Brazil therefore proposed that
there should be reconsideration of the hemispheric eradication. The Directing council had a task
to draw national plans that advocated for expansion as well as increasing the intensity of efforts
to reduce Aedes aegypti in America. This plan was set up in 1997 and in September of the same
year, there was another resolution to that needed countries to carry out Hemispheric Plan through
five steps that include avoiding epidemics of dengue, DHF as well as urban yellow fever,
avoiding the outbreaks of dengue, Interruption of transmission of dengue, eradicating Aedes
aegypti and finally establishing sustainable surveillance against re-infestation of areas that are
free from Aedes aegypti.

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