Dengue

Paul R. Earl

Facultad de Ciencias BiológicasUniversidad Autónoma de Nuevo LeónSan Nicolás de los Garza, Nl, Mexico

Generalities. DENGUE (DEN) is a positive-stranded RNA virus that is spread by the bite of an infected female mosquito which carries dengue virus after feeding on the blood of an infected person. Dengue is a mosquito-borne disease, and the objective is to stop the transmission of the pathogen.

The infected mosquito is commonly Aedes (Stegomyla) aegypti, and depending on the geographic area A. albopictus and A. polynesiensis are also seriously involved. Replication of positive strand flaviviruses is mediated by the viral RNA-dependent RNA polymerases (RdRP). The mosquito vectors and 4 DEN viruses are found throughout the subtropics and tropics where over 2.3 billion human hosts are at risk, especially children.

Dengue can be prevented by

1) elimination of mosquito breeding places, 2) prevention of mosquito bites and3) vaccination of all persons against all 4 serotypes, DEN 1-4.

Annually, over 100 million cases of primary dengue fever and over 450,000 cases of dengue hemorrhagic fever (DHF) and shock syndrome (DSS) occur DHF/DSS many fatal) is the leading cause of hospitalization of children in Asia.

A sick person needs to be diagnosed and treated early, and a rise in vector population must be controled early. Much of the essential knowledge on dengue fever has now been presented. Health education is the crucial aspect.

Symptoms. As soon as the public understands the mosquito transmission of dengue, they should learn the symptoms. Dengue fever has 1) sudden high fever, 2) severe frontal headache, 3) pain behind the eyes that worsens with eye movements, 4) muscle and joint pains, 5) loss of sense of taste and appetite, 6) measles-like rash over the chest and upper arms, and 7) nausea and vomiting. Breakbone fever is one name for dengue.

DHF/DSS has 1) severe and continuous stomach pains, 2) pale, cold or clammy skin, 3) Bleeding from the nose, mouth and gums ± skin bruising, 4) vomiting often ± blood, 5) sleepiness and restlessness, 6) constant crying, 7) excessive thirst, 8) rapid weak pulse, 9) difficulty in breathing, and 10) fainting.

DHF is the most fever form of dengue with hemorrhage and the tendency to develop shock. DHF presents a high continuous fever of 2-7 days after 5-8 days of incubation, hemorrhagic diathesis, hepatomegaly and circulatory disturbance as shock.

Live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (JE; strain SA14-14-2) viruses, and inactivated vaccines have been developed for JE and tick-borne encephalitis viruses. YF live attenuated 17D vaccine are efficacious and safe current vaccines been used to immunize more than 300 million people. Tetravalent live attenuated dengue vaccines are undergoing clinical trials.

Flaviviridae viruses. This family contains about 70 RNA viruses, the most important of which might be yellow fever (YF). or dengue. Flaviviruses are among the most important emerging viruses. Most are arboviruses (arthropod-borne) being transmitted by mosquitoes or ticks. Many are spreading to new geographical areas and causing increased numbers of infections. Many RNA viruses have these essential genes: pol, env and gag that are major protein coding regions.

Viremia and immune responses. Dengue virus is present in the blood of infected patients for about 6 days after which it is cleared by antibodies. Many parts of the world do not have the laboratory facilities required for virus diagnosis or even the equipment and skill for proper diagnosis of bacteria. Nonetheless in some communities, the political will to protect the public is not evinced.

IgM antibody rises during acute illness. Serological tests become positive by day 6. IgM lasts 60-90 days, thus indicates recent infection. However, IgM antibodies may crossreact with other flaviviruses. In primary dengue. IgG develops a few days later than IgM antibody. Tests measuring IgG antibody generally depend on paired sera that show a difference in the course of the infection, e. i., acute and convalescent sera are compared.

Although secondary antibody responses are broadly crossreactive, there can be a higher response to the primary infecting agent. Distressing allergic reactions are caused by crossreactions among the 4 dengue serotypes. Still, other flaviviruses might be involved.

Cultivation of the virus. Animal viruses can be grown only in cells, therefore the choices of hosts are in vivo and in vitro mammalian and insect hosts. Virus culture of isolates will yield the needed data on the virus and serotypes.

Many mammalian cells have long been available for culturing various viruses, whereas mosquito culture is more limited. The 3 common cell lines are 1) C6/36 clone of Aedes albopictus, 2) AP-61 line of A. pseudoscutellanis and 3) the TRA-284 line of Toxorhynchities amboinensis, C6/36 being the most popular. The presence of virus is often determined by fluorescent antibody (FA). The monoclonal antibodies DEN 1 (1F1), DEN 2 (3H5), DEN 3 (8A1) and DEN 4 (1H10). Also, an antigen capture ELISA test may be used.

Vector control and surveillance. Mosquito control involves only the vectors Aedes aegypti and A. albopictus, the former thoroughly domesticated. Vector control begins with favorable political will and public health financing, and can extend to the education of schoolchildren. Community cooperation can be the next step. The objective is the prevention of vector breeding. Without a good garbage and collection system, control will fail. Also, without a good piped water system, people will have to store water for household use, usually

in 200 liter drums.

Cleanup campaigns and clean neighborhoods are keynotes for successful control and depend on minimum health education. The main breeding sites are softdrink plastic and glass containers, and old discarded rubber tires. A. aegypti breeds in and around houses. Cleanup activity should reduce the necessity for insecticide applications. Incriminating mosquito breeding sites as propogating diseases is the main target of community communication.

Recycling is obviously beneficial, especially via reducing the burning of fuels, therefore available profit from garbage collection requires reassessment to provide maximum incentive for final disposal of waste. Can the metal and even glass in containers be transformed? Can paper and plastics be recycled? The profitable restoration of tires must lead to the reduction of breeding sites.

Insecticide applications. In some districts, the larvicide Abate (temephos) is the most important of 4 chemicals. Abate, often well recognized by the public, is popular and sometimes delivered by public health water trucks. Other chemicals are the insect growth regulator IGR, another IGR pyriproxyfen and methoprene. These larvicides are effective with Aedes aegyptyi and less so with mosquitoes that breed in natural environments.

Space sprays can be applied to neighborhoods as thermal fogs containing a low concentration of organophosphate (OP) life malathi-one, or pyrethroid insecticide with diesel oil droplets as the carrier. Doors and windows should be open for the spray as so many mosquitoes are inside houses. Spray cans with various insecticides can help to control dengue, yet at some expense.

Evaluations of vector densities of Aedes aegypti and all other mosquitoes should be continually carried out. The use of ovitraps is helpful, either with paddles for egg-laying and counts, or sticky ones that glue visiting mosquitoes and other pests.

Biological control. Both parasitic bacteria and predatory copepods are enemies that affect mosquito population densities. Cyclopoids of the genus Mesocyclops prey on the larvas of several species of mosquitoes. Not to be cleaned out, cyclopods require replacement and care by the public managing the barrels. Bacillus thuringiensis H-14 (BT) can control Aedes aegypti. Granules and tablets of BT mixtures are popular.

Impregnated materials. Insecticide impregnated curtains are efficient for reducing mosquitoes in houses. The natural repellents dimethylphthalate (DMP) and diethyltoluamide (DEET) at 35-50 % are used as on clothing. Some repellents on fabrics are efficient and long lasting, e. g., pyrethroid permethrin. Nonetheless, to repell rather than kill, seems to fail in logic!

Some countries like Mexico have DDT for use against malaria, but it has not been incorporated into paint or used much for impregnation. OtherOP compounds include diazinon, malathion, fenitrothion, fenthion, dimethoate and dichlorvos. The safety aspects of insecticides must be well advertized.

Health communication and public relations.Control activities may contain research results interesting for the target audience. Good public communication is influenced by the “knowledge, attitude and practices” (KAP) studies that have been made like questionaires. Television notices are of course effective, true also for health lessons to schoolchildren.

Geographical Information Systems (GIS). The daily, monthly and annual weather cycles are crucial factors in dengue epidemiology. In the Americas, virus dispersal is influenced by the Atlantic and the Eastern Pacific hurricane centers. Only climate in North America is noted here. Mexico has over six month of drought through winter with convection current rains in May, then cyclonic storms from July into October. Climatic changes in one year or decade to the next are not well studied.

Budgetary consideration.

Political will and public appreciation of vector control measures are expected. These measures likely include application of larvicide or adulticide space sprays. Much of this information is taken from Key Issues. . ., WHO, 1995. Health education should lead to public particioation as in cleanup campaigns, and then to political financing.

In order to estimate the costs of a control program, the following information must be collected: a) The size of the geographical area to be controlled, b) the human population of the targeted area,c) distribution, incidence and transmission,d) length of time of transmission, e) vector population density and seasonal variation, f) perferred larval habitats, g) resting sites of adults, and h) epidemiological pattern.

Dengue mainly affects children therefore most expenses fall on the adults of the family. In Thailand costs average US $ 128 per case. If the patient has grade IV DHF/DSS, cost can be $ 135. Private care costs about $ 400. Funeral costs are about $ 400. Income loss per year was $ 2,000. Epidemics in Thailand have cost $5-11 million (1994). Vector control can cost $ 2 million at $ 10/capita with 73.2 % for insecticides and 17.5 % for wages of personnel. How do these figures apply to your municipal situation? Are West Nile virus infections carried by culicine vectors complicating the situation?

Summary. Important points can now be summarized. a) Aedes aegypti is fully domesticated so that its biology is unlike that of other mosquitoes. b) Containers and tires have to be reduced as breeding sites via public appreciation of vector control (try cleanup campaigns coupled with schoolchild health education), c) symptoms just like dengue transmission should be advertized, and d) the realistic calculation of risk and then the possible need of a tetravalent vaccine should be monitored.