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Epidemiology

Mosquitoes: the danger advances

Specialists predict that urban yellow fever and malaria will once more attack the South East

EDUARDO CESARIn 1989, the epidemiologist Oswaldo Paulo Forattini, of the School of Public Health of the University of São Paulo (USP), used to say that the population must be vaccinated against yellow fever as a routine. He was considered an alarmist, even by his colleagues. Time has proven that he was right to worry. Yellow fever has returned to be a public health problem throughout all of Brazil.

Today, Forattini is sending out two new alerts about the probable return of tropical diseases, specifically to the South East region. They are urban yellow fever, which swept the country in the beginning of the 20th century until it was considered to be eradicated in 1942, and malaria, which was also of epidemic proportions until the middle of the 20th century. The warning is being given in a calm voice by this 77 year-old professor, the Coordinator of the Center for Taxonomic and Systematic Research in Medical Entomology of the School of Public Health of USP (Nuptem). Far from wishing to alarm, he is worried about how to go about prevention.

For ten years he has been studying the adaptation of the insects, potential vectors (transmitters) of the disease to the environmental conditions created by man’s interference, a phenomenon called synanthropy or domiciliation. One of them is the mosquito Aedes aegypti, transmitter of dengue fever which is laying waste to the country and urban yellow fever, officially considered to be eradicated.

Slave trading ship
The mosquitoes that are locally called “pernilongos” (long-legged), “muriçocas” or “carapanãs” belong to the family of the culicids (Culicidae), in the majority hematophagus, blood sucking. Before the adult phase, they live as larvae in a water environment, into which the female puts her eggs. Among the culicids are the transmitters of yellow fever, of dengue fever and of malaria. Dr. Forattini reveals that the Aedes aegypti arrived in Brazil during the colonial period. Their eggs made the journey in the water casks of slave trading ships. Being able to resist for months before being hatched in the water, these eggs remained stuck in the internal walls of the empty recipients, until they were again filled, which gave them the possibility of hatching.

Until the 50s, the culicids of the genre Aedes, which attack in the early hours of the morning and in late afternoon, and suck blood shortly after landing, had found a fertile environment to proliferate. By their importance as a vector of yellow fever, they suffered unyielding combat in the first decades of the 20th century by armies of health agencies commanded by the health workers Oswaldo Cruz, in Rio de Janeiro, and Emílio Ribas, in São Paulo, until they were officially considered to have been eradicated in 1957.

Nevertheless, years later they would be observed yet again in Pará and in Salvador, and would dramatically reappear in 1986 in Rio de Janeiro, now as a transmitter of dengue fever, which from that point on became a nationwide epidemic, with yearly outbreaks. Only in the State of São Paulo 45,000 cases have been registered during the last five years.

Now the specialists are asking themselves: what is the risk of a city that has been hit by the dengue, being again the target of urban yellow fever? A researcher in Dr. Forattini’s team has made the estimates. Dr. Eduardo Massad, professor of Medical Informatics and Quantitative Methods in Medicine and Vice-Director of the School of Medicine of USP, constructed graphs of risk potential that include mosquito population, rate of bites and viremia – risk period in which an infected person can transmit the disease. In the case of dengue fever, for example, as the virus remains for more time in the blood stream (close to one week) the viraemia period is greater than that of yellow fever (close to two days).

Dr. Massad and his team carried out a comparative study of towns in the state of São Paulo which was accepted for publication in the magazine Transactions of the Royal Society of Tropical Medicine and Hygiene. He says: “To estimate the risk of an epidemic of urban yellow fever in an area infected by the dengue mosquito, we calculated an index of the intensity of the transmission of the disease, a threshold above which any individual infected by wild yellow fever could begin an epidemic of urban yellow fever.” That is to say, the person can become a transmitter by being bitten by non-infected urban mosquitoes, which produces a chain reaction. Significantly, two autochthonous cases of yellow fever were registered in the region of Araraquara, which presented a high index of “dengue”.

Man makes things easier
The risk of the return of the vectors of these illnesses is explained through human action on the environment. “In the decade of the 50s, there were few recipients in which the larvae could develop”, recalls Forattini. “We didn’t have any plastic containers and cars were the privilege of the rich. Today we have an enormous quantity of tires and bottles or plastic pots thrown out on open space.”

Besides this discarded material, he has detected a type of breeding place even more difficult to eliminate. The beautiful bromeliads in the residences of Rio de Janeiro, one of the cities most seriously hit by “dengue”, and whose leaves and flowers function like a chalice for water. “The bromeliads are recipients watered every day and which the owner doesn’t want to get rid of.” Recently, authorities estimated that 90% of the outbreaks of Aedes in Rio de Janeiro take place in residences and at least 70% come from the plant vases.

Environmental alterations in rural zones have also favored the insects that, on adapting to the humanized environment as a result of human activity, can turn themselves into transmitters. This was what the researchers verified in the Ribeira Valley in a thematic project developed between 1991 and 1995. “The new techniques of artificial irrigation with for agricultural production, added to an rise in the cases of Anopheles albitarsis, the vector mosquito of malaria”, says Forattini. This insect is joined by the Anophelescruzii and Anopheles bellator, already present in the environment and recognized as endemic vectors of malaria in the region.

For now, malaria in the Ribeira Valley is hypoendemic – there are few cases there and only of a mild form, transmitted by insects that had contact with the protozoan of the genre Plasmodium, which causes the disease. However, the presence of one more important vector and plus the fact that transport is so easy these days could bring the malaria rapidly from the north to the south of the country.

“The artificial irrigation also generates an increase in the population of Culex nigripalpus, a transmitting mosquito of a type of ornithological brain fever, and of Aedes scapularis, the mosquito which has a great tendency to enter homes”, states the researcher. “For me, this was the great transmitter of rocio encephalitis in the Ribeira Valley close to 20 years ago, though we didn’t find contaminated insects on that occasion”. The time at which the rocio encephalitis claimed human lives coincided with the works on the highway named the Rodovia dos Imigrantes. “Huge quantities of sand from the Santos area (on the coast of the state) were taken away for the construction of bridges, forming holes that filled with rain water, favoring the proliferation ofAe. scapularis. Not surprisingly, the first cases sprung up around Santos, and then afterwards hit the region of the Ribeira Valley.”

Ilha Comprida (Long Island)
In a second project, Dr. Forattini did an in-depth study of culicids in areas modified by human action. He researched localities on the north coast of the State of São Paulo and the valleys of Paraíba and Ribeira, especially Ilha Comprida, which separated itself from Iguape in1992 and is subject to rapid and profound alterations.

On the southern coast, at a distance of 220 kilometers from the capital, this municipality has 296 m², of which 70% is an Environmentally Protected Area. The island suffers the impact of tourists, the population of 6,000 inhabitants grows tenfold during the high season. “The result one can see in the amount of garbage thrown on the beaches” , sums up Dr. Forattini. This population fluctuation facilitates the entrance of infectious agents, that use the biological vectors already installed there, and this increases the risk of outbreaks of disease. In this way, more than trying to prove an increase in the population of the insects, in the first thematic project, the team wanted to evaluate the competency of the vectors, their capacity for survival and reproduction.

Traps
From 1996 until 2000, the team worked on the collection, identification and study of the vector capacity of various species, above all the Aedes aegypti, Ae. albopictus, Ae. scapularis, Anopheles albitarsis, An. bellator, An. cruzii and Culex quinquefasciatus. In order to collect the insectsalive, the researchers used various traps. Shannon, a tent of white cloth where the insects settle and are captured manually; CDC, a trap with dry ice which, on the liberation of the carbon dioxide gas, imitates human respiration and attracts the insects to an aspirator; and human bait, a commonly used term which Dr. Forattini does not like. Bait suggests the risk of contamination, that is not present, since the collector works all dressed up and captures the insect with a hand aspirator, even before it lands.

Only between May of 1995 and November of 1996, the team collected in Ilha Comprida and Cananéia 66,769 insects, of which 40,362 were immature and 26,407 adult, with a predominance towards Aedes albopictus, Ae. scapularis and Culex quinquefasciatus. The next step was to begin the comparison of these populations, a tool for epidemiological vigilance.

Asian scare
Their attention was called to the Aedes albopictus, which arrived from Asia close to 20 years ago and is commonly called the “Asian tiger”, with its high rate index of synantrophy, the ability to adapt to a human environment. Dr. Forattini identified it for the first time in Rio de Janeiro and verified that it has traveled west, pushing out the Ae. Aegypti. “The larvae pleases itself with less food and proliferates more”.

The Asiatic species is not yet responsible for a single case of dengue fever in Brazil. However, it is still being studied to see if it can be a vector of yellow fever. This could mean that its eventual victory in competition with the Aedes aegypti, transmitter of the two diseases, might be positive. The researcher prefers not to believe in this. “I would not trust a blood sucking species (hematophagous). Furthermore, in Asia the Aedes albopictus is a vector of dengue and, in the United States, transmits a type of human encephalitis. Here, it appears in large quantities in urban areas. Could it be that there already arealbopictus among the Aedes which transmits dengue in Brazil?”, he questions.

Consequently, he believes that it is more prudent to think that the Asiatic species may turn into a vector even more resistant and dangerous to human health than that of the Aedes aegypti.

Potential infector
To eliminate this doubt is one of the objectives of the current project, which he is coordinating until 2004. The focus, now, is the potential synantropy (adaption to human environment) of the culicids and their capacity to transmit infections. One of the team’s researchers, Zoraida Fernandez, of the National Institute of Hygiene Rafael Rangel, of Caracas, is at the University of Texas carrying out rehearsals on the capacity of transmission of viruses with populations of Aedes albopictus. First, they are tested with the virus of the Venezuelan equine encephalitis, isolated during the epidemic of 1995 in that country. Afterwards, she will use the virus of dengue fever subtype 1C, recentlyisolated in São Paulo. “This objective, combined with the estimation of longevity, would permit an evaluation for our populations, of the vector competence of this species”, assures Dr. Forattini.

Also, the third thematic project is continuing in the valleys of the Ribeira, the Paraíba and on the northern coast. Ilha Comprida was chosen as a natural ecosystem. In the Paraíba valley, the town of Taubaté exemplifies semi-industrialized environment. Ilhabela, on the northern coast, comes in as a tourist center, and in the center of the State, Araraquara represents the highly rural ecosystem modified by farming .

To study the immature forms, above all those of Aedes aegypti and albopictus, the team examined natural and artificial breeding grounds. Recipients of three sizes, up to 1 liter, 10 liters and more than 10 liters, are examined every 15 days. To prevent the production of adults, larvae and pupas are collected while still in the aquatic stage.

Equation
“Through this experiment we might determine a possible preference for the volume of the artificial recipient”, explains Dr. Forattini. “Our objective is to identify and evaluate the productivity of the breeding places, to estimate the competition between the populations, the relationship anthropic in the environment, and finally to propose what we might call as an index of synantropy” (adaptability to human environment). In order to arrive at this number, he adapted an equation created in the decade of the 60s by the Finnish entomologist Pekka Nuorteva for ecological studies on mosquitoes: S = 2a + b – 2c/2. The equation is based on the percentages of insects collected in a home environment (a), partially altered anthropic environment (b) and residual forests (c).

The researcher considers to be scarce the studies which focus on the process of domestication, since the public health system has never had any resources for this. Nevertheless, he believes that there lies the solution to the problem of infectious diseases in the human population. He thinks that the attempts of biological control, through the use of natural predators such as the dragon fly, have not yet produced the expected results. Also, experiments in genetic engineering to produce populations of sterile insects are at a beginning stage. Therefore what remains to be done is to understand how to live with the insects, which presupposes a consistent understanding about their characteristics. About viruses, it will be necessary to domesticate it. “We managed to control poliomyelitis because the population is inoculated with the weakened virus. The study of the genome could result in the taming of the virus of the dengue fever and of the parasite of malaria.”

Besides vaccination, he is betting on an improved distribution of wealth and in education to minimize these and other impacts of the transformation of the environment by man. He believes that one of the great difficulties in combating the dengue is to produce a conscience in the population about avoiding deposits of still water, a problem which comes more from ignorance than from carelessness. To confirm this idea, he tells an episode that took place nearly 100 years ago. “During the construction of the Panama canal, the nuns who looked after the bedridden used to place glasses of water at the foot of the beds in order to prevent their patients from getting ant bites. Protected from the ants, by the compassion of the nuns, many ended up dying from yellow fever.”

A graduate in 1949 in medicine at USP, Dr. Forattini retired in 1994, but goes daily to the Public Health School of USP to teach, give guidance on theses, organize the collection of references of the school – 35,00 examples of insects, some with his name such as Lutzomyia forattinii and Anopheles forattinii, as well as the protozoa Leishmania forattinii. For the first volume of Medical Culicidology, edited by Edusp in 1996, he received the Jabuti Award in Natural Sciences, from the Brazilian Book Chamber. The second volume is at the printing plant. While the first focused on the morphology of insects, this one is more directed towards epidemiology. On comparing the present moment with that of the three first volumes of Medical Entomology, which were published in 1962 and 1965, he laments: “At that time dengue fever only existed in Venezuela and yellow fever was a settled question.”

A trio ready to attack

Previously considered eradicated in the most populous regions of the country and confined above all to forest areas, the tropical diseases such as yellow fever, dengue and malaria, have some basic characteristics.

Dengue
It is caused by an arbovirus also of the genre Flavivirus, transmitted by Aedes aegypti, originally from Africa and which lives next to human households. Of the four types of virus, the most common in Brazil are: the 1 – responsible for the weakest form of the illness; and the 2, which causes hemorrhagic fever, which can lead to death. Also, there have been people found who have been infected with the type 3. The oldest reports in the country are of an epidemic in 1846, in São Paulo, Rio de Janeiro and Salvador, but the first documented case was in 1981 in the State of Roraima. In 1986, a strong epidemic broke out in Rio de Janeiro with close to 1 million cases. Today, the illness has spread to urban centers through almost all of the country.

Malaria
Known popularly as “maleita”, its characteristics are intermittent fever, shivering, sweating, pain, vomiting, jaundice and lack of appetite. Caused by protozoa of the genre Plasmodium, whose most common forms are the vivax, most benign and the falciparum, most serious, it is transmitted by the Anopheles mosquito. In Brazil, there are five vectors of malaria: Anopheles darlingi, An. aquasalis, An.albitarsis, An. cruzii and An.bellator. The endemic area is the Amazon basin. It is an illness known since ancient times, when, as it was typical of hot and humid environments, it was believed that it was caused by emanations and miasma coming from the swamps. Only during the last decades of the 19th century was it discovered that it was transmitted by mosquitoes, until that time only viewed badly by the discomfort of their bites.

Yellow fever
Acute infectious disease, that can be almost asymptomatic or can evolve into a serious form, with fever, progressive jaundice, hemorrhages and death. It is caused by the yellow fever virus – an arbovirus of group B, genre Flavivirus. There are two types: wild and urban. In the wild type the vectors are females of culicids of genre Haemagogus, which infect themselves on sucking disease-carrying monkeys. This is what today is hitting Brazil, above all the states of Amazônia, Goiás and Distrito Federal. The urban form comes up when a person infected by the wild type is bitten by females of the blood sucking Aedes aegypti, which makes the infection spread more rapidly.

Considered to be eradicated, at the beginning of the 20th century, today the urban form claims many victims. Between 1900 and 1902, one thousand six hundred and twenty seven (1,627) people died in Rio de Janeiro alone. In 1903, President Rodrigues Alves asked the sanitarian Oswaldo Cruz to lead an intensive campaign against the mosquito, which was done public awareness, provoked disturbances and repression. Nevertheless, the campaign was effective and since 1942, Brazil has only registered wild yellow fever. According to the Center of Epidemiological Vigilance, 446 cases and 241 deaths between 1980 and 1999. The main means of control is through the vaccination of the residents and those traveling to endemic areas.

The Projects
1. Culicidae of an Irrigated Agro-Ecosystem and its Epidemiologic Meaning (nº 90/03371-6); Modality Thematic Projects; Coordinator Dr. Oswaldo Paulo Forattini – Public Health Faculty of USP; Investments US$ 175,300.00
2. Culicidae in the Area of Human Transformation and its Epidemiologic Meaning (nº 95/00381-4); Modality Thematic Projects; Coordinator
Dr. Oswaldo Paulo Forattini – Public Health Faculty of USP; Investments R$ 179,485.00
3. Studies on the Domestication of Culicidae Mosquito (nº 99/10517-1); Modality Thematic Projects; Coordinator Dr. Oswaldo Paulo Forattini – Public Health Faculty of USP; Investments US$ 8,412.00

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