Dengue: An emerging arboviral disease Gary G. Clark, Ph.D. Mosquito and Fly Research Unit CMAVE, ARS, USDA Gainesville, Florida 1

My “emergence” at Balboa Naval Hospital San Diego, California First interaction with a Navy physician

Discussion topics Epidemiology of dengue and DHF Emergence of dengue in the Americas Aedes aegypti and its development Adult control methods for Ae. aegypti Evaluation of emergency control studies (CDC and the military) Dengue and the US military

Dengue virus An arbovirus; transmitted by mosquitoes Four virus serotypes (DEN-1, 2, 3, 4); single-stranded RNA Family Flaviviridae (WNV, SLE, YF, JE) Causes dengue (headache, fever, joint/retrorbital pain, rash, bleeding) and dengue hemorrhagic fever (DHF) 3

Dengue viruses Each serotype provides specific lifetime immunity and short-term cross-immunity All serotypes can cause severe and fatal disease Genetic variation within serotypes; some appear to be more virulent or have greater epidemic potential Can produce outbreaks/epidemics in urban areas 4

Transmission of dengue virus by Aedes aegypti Mosquito feeds / Mosquito refeeds / acquires virus transmits virus Extrinsic incubation period Intrinsic incubation period Viremia Viremia 5 8 12 16 20 24 28 Illness Illness Days Human #1 Human #2 5

Dengue: A global perspective* Most important arboviral disease of humans; 2.5- 3 billion people (40% of the world) at risk of infection 10’s of millions of cases of dengue and 100’s of thousands of DHF cases annually A leading cause of hospitalization and death among children in Asia DHF mortality rate averages about 5% * Source: WHO, 1996

World distribution of dengue 2006 Areas infested with Aedes aegypti Areas with Ae. aegypti and recent dengue epidemics

Dengue/DHF cases reported to the World Health Organization 1955-2005* Ave. annual no. cases * Source: WHO, Sep. 2006

Dengue in the Americas 1980 – 2006* Year * Source: PAHO (Jan. 19, 2007)

Dengue hemorrhagic fever in the Americas 1980 – 2006* Cases * Year * Source: PAHO (Jan. 19, 2007)

Why has dengue emerged in the Americas? Presence of competent mosquito vector Large, susceptible human population Conditions supporting abundant mosquito population Frequent introduction of dengue viruses Ineffective vector control programs

Emergence of dengue Socio-economic factors Population increase Billion 1830 1930 2000 Unprecedented population increase Uncontrolled and unplanned urbanization Inadequate environmental conditions 6 5 4 3 2 Entre 1950 y 1960 ocurrió el mayor crecimiento de la población de la tierra, la pob se duplico en 15 anos El tercer mundo duplica su población cada 43 anos. 1

Reinfestation of the Americas by Aedes aegypti* * Source: CDC/PAHO

Emergence of dengue Uncontrolled urbanization* In 1954, 42% of the population of Latin America lived in urban areas, increasing to 75% in 1999. “Informal” communities proliferated as a result of poverty. Scarcity of basic services: running water, sewage and collection of garbage. * High population density Sources: Gubler, 1998. PAHO, 1997.

Emergence of dengue Inadequate environmental conditions* Insufficient collection of disposable containers Non-biodegradable containers Discarded tires Insufficient and inadequate water service Increased number of “pilas” and water storage containers Inadequate water and sewer conditions * Increase in production sites

Production sites for Aedes aegypti Buckets and pails

Production sites for Aedes aegypti Water storage tanks

Production sites for Aedes aegypti Discarded tires

Emergence of dengue Population movement* Migrations International Tourism More than 750 millon people cross frontiers annually Increase of migration from rural areas to cities 1.4 billion international passengers in 1999 697 million international tourist arrivals in 2000. 715 million in 2002, an increase of 3.1% * Traffic of microorganisms Source: WTO

Why has dengue emerged in Latin America? Reinfestation by Aedes aegypti Ineffective mosquito control programs Deteriorated public health infrastructure Uncontrolled population growth and unplanned urbanization Increased air travel by humans

Aedes aegypti 8

Aedes aegypti Lives in and around human habitations in urban areas Lays eggs and produces larvae preferentially in artificial containers Strong preference for human blood; primarily a daytime feeder and bites several times in her life Most important vector of dengue viruses in the world 9

Life cycle of Aedes aegypti 4. Adult 3. Pupae 1. Eggs 2. Larvae

Personal protection against mosquitoes Apply repellent (20-30% DEET) to exposed skin- avoid eyes, mouth, and children’s hands Spray clothing with repellents with DEET or permethrin Use treated mosquito netting over bed Spray insecticide in room before going to bed, follow label instructions Wear long-sleeved shirts and long pants

Dengue vaccine? No licensed vaccine at present Effective vaccine must be tetravalent Field testing of an attenuated tetravalent vaccine currently underway Effective, safe and affordable vaccine will not be available in the immediate future Vector control continues to be key to dengue prevention

Vector control methods: Biological and environmental control Biological control Largely experimental Option: place fish in containers to eat larvae Environmental control Elimination of larval habitats Method most likely to be effective in the long term

Spraying to control adult Aedes aegypti Thermal fog Aerosols – Cold fog and ultra low volume (ULV) Inside of residences with portable equipment From the ground with vehicle-mounted equipment Aerial application

CDC evaluations: Emergency control in Puerto Rico* Ground ULV applications versus Aedes aegypti C-130 (Hercules transporter) with USAF Reserve Unit from Columbus, OH US Navy (DVECC) with PAU-9 from JAX Mosquitoes susceptible to naled (Dibrom 14) and insecticide reached the ground but did not penetrate houses Limited, transitory impact on wild population * Other projects with US Army in Honduras and the Dominican Republic

Ground ULV application

Ground ULV application

Aerial application in San Juan with C-130

Aerial application in San Juan with PAU-9

US Navy’s PAU-9 unit

Indoor application with thermal fog unit

Indoor application with portable ULV unit

Operation Restore Hope Somalia- 1992-1993 30,000 troops deployed; 530 were studied - 289 hospitalized with fever- 129 with “unspecified illness”- 41 with DEN virus and 18 with anti-dengue ABs= 59/129 (46%) with DEN infections. Study of unit in Baardera: 9% (44) of 494 with dengue infections 70% used DEET < 1 time/day, 22% never treated uniforms, 61% did not use bed nets and only 25% kept sleeves rolled down at all times Poor compliance with PPMs vs. insects

Operation Uphold Democracy Haiti- 1995 249 with fever- 79 (32%) with DEN infection - 44/79 participated in survey - 73% with mosquito bites daily - 50% used repellents < 1/week or never - 48% did not use a bed net 10/14 (71%) of Army units did not have deployed, functional field sanitation teams 31% of soldiers indicated PPMs emphasized “some but not enough or not at all” Low unit readiness to perform VC activities Command enforcement of PM doctrine is essential for dengue prevention

DHF in Venezuela 1989-1990 PAHO-Venezuela requested that CDC-San Juan test specimens from suspected fatal case (12 year-old girl) of DHF from Venezuela Dengue etiology was confirmed; epidemic was spreading from Maracay to Caracas Minister of Health sought epidemic response recommendation. Discussed results of USAF and Navy trials. “Aerial control… limited impact, dangerous, could not recommend aerial control as the solution.” Minister “… must take action and intended to spray using helicopters with booms attached” With Minister’s decision, I changed hats and recommended that he seek “professional assistance such as from the US Navy” No aerial spray experience in Venezuela. Venezuelan Air Force transported DVECC personnel and equipment to Venezuela.

MMART* Preventive Medicine Assists Venezuela Preparing to spray with Venezuelan helicopter MMART* Preventive Medicine Assists Venezuela LCDR Mark T. Wooster, MSC, USN Navy Medicine (Mar-Apr 1991) * Mobile Medical Augmentation Readiness Team

DHF in Venezuela 1989-1990 DVECC’s “equipo de expertos rociadores aereos” LCDR Mark Wooster LT Joseph Conlon LT Stanton Cope LT David Claborn LT Rafael del Vecchio U.S. Navy personnel performed 60 aerial spray missions (malathion @ 3 oz/acre) during 135 flight hours over Maracay and Caracas.

Aterriza de emergencia helicóptero de fumigación (Newspaper report) MARACAY (Especial) – Uno de los helicópteros de la Fuerza Aérea, que participa en las operaciones de fumigación contra el dengue, aterrizó de emergencia en el estacionamiento del centro comercial “El Castaño”, de esta ciudad, resultando gravemente herido el piloto de la unidad, que no fue identificado por las autoridades. En la aeronave viajaban dos oficiales [LT Joseph Conlon and LT Stanton Cope] de la Marina de los Estados Unidos, quienes habrian sufrido lesiones. Tambien iban dos oficiales de la Fuerza Aérea Venezolana, y tres guardias nacionales. La aeronave arrancó una linea de alta tensión y dejo al sector “El Castaño” sin electricidad.

Venezuelan helicopter After mission! Venezuelan helicopter

Fortunately, the injuries to the crew and US Navy personnel were minor. And, some of our “expertos” developed a new feeling for helicopters on the ground.

“Private parking space” for AFPMB RLO Silver Spring, Maryland “I love my choppers!” “Private parking space” for AFPMB RLO Silver Spring, Maryland

CAPT Stanton E. Cope- “Dengue fighter” b s CAPT Stanton E. Cope- “Dengue fighter”

Take home messages Importance of command emphasis for personal protection measures Critical that you lead by example and use repellents Be prepared to respond to requests for help in dealing with dengue and other VBD in support of US military or in humanitarian missions There is no “magic bullet” to solve the emerging problem of dengue/DHF You are part of unique national/international vector control resources; challenges and danger may accompany your work USDA is anxious to support US military in protecting deployed personnel and in responding to humanitarian missions

Walter Reed Army Medical Center PSA Washington, D.C. My last interaction with an Army physician