A retrospective study by researchers at the Baylor College of Medicine’s National School of Tropical Medicine at Houston, covering three years of blood and cerebrospinal fluid samples submitted for West Nile virus testing in the Houston area, found that 47 of the samples were positive for dengue virus. Their report was published October 9 in the journal Vector-Borne and Zoonotic Diseases.
“We looked at clinical specimens that were banked at the city laboratory to see if there were potentially any other viruses that we could detect that weren’t known to be circulating in Houston but have the high potential to do so,” says Dr. Kristy Murray, associate professor and associate vice chair of research in the department of pediatrics at BCM and director of the Laboratory of Viral and Zoonotic Diseases at Texas Children’s Hospital in a BCM release. “We started with dengue virus since it was highest on the list of possible transmission here in Houston because we have the right kind of mosquitoes and a very large, densely populated city full of frequent travel to endemic areas, including Mexico and Central and South America.” Dengue may be expected to occur about as often or even more often than malaria in persons returning from South and Central America, the Caribbean and Asia according to The Committee to Advise on Tropical Medicine and Travel (CATMAT).
Dr. Murray is an associate professor of Pediatrics in the section of Pediatric Tropical Medicine at Baylor College of Medicine, and is also a member of the National School of Tropical Medicine.
Dengue fever is endemic to most tropical and subtropical areas of the world, predominantly in urban and semi-urban areas, and widespread in regions of Central and South America; the Caribbean; South and Southeast Asia; Western, Eastern and Middle Africa; and Oceania. Global incidence of dengue has grown dramatically in recent decades, and about half of the world’s population is now at risk.
Dengue fever is the most common viral disease transmitted to humans through the bite of infected mosquitos — particularly species Aedes aegpyti and Aedes albopictus — carrying any one of four distinct, but closely related, serotypes of the virus that cause dengue (DEN-1, DEN-2, DEN-3 and DEN-4). After virus incubation for 4–10 days, an infected mosquito is capable of transmitting the Dengue virus for the rest of its life. Unlike other mosquitoes, Ae. aegypti is a daytime feeder; its peak biting periods being early morning and in the evening before dusk. A female Ae. aegypti bites multiple people during each feeding period.
Dengue-carrying mosquitoes, which breed in standing water and are often found in urban and semi-urban areas, typically bite during the daytime, indoors and outdoors, particularly two to three hours after dawn and during the early evening. In recent years, transmission has increased, and Dengue has become a major international public health concern. Aedes aegpyti larvae develop in relatively clean standing water found in the peri-domestic habitat, for example, in flower pots, tires, cisterns or other artificial containers. Aedes aegpyti tends to take most of its meals from humans, and infected humans are the main carriers and multipliers of the virus, serving as a source of the virus for uninfected mosquitoes. The incubation period of DEV in humans is 3 to 14 days (typically 5 to 7 days), and infected humans may remain viremic for up to 12 days (typically 4 to 5 days) after their first symptoms appear, during which time they can infect susceptible female Aedes mosquitoes that feed on them.
The World Health Organization (WHO) says Aedes albopictus, popularly referred to a the “Asian tiger mosquito.” a secondary dengue vector in Asia, has also spread to North America and Europe largely due to the international trade in used tires (a breeding habitat) and other goods (e.g. lucky bamboo). They note that Ae. albopictus is highly adaptive and therefore can survive in cooler temperate regions of Europe. Its spread is due to its tolerance to temperatures below freezing, hibernation, and ability to shelter in microhabitats.
WebMD News HealthDay’s Alan Mozes reports that experts now warn that Ae. albopictus has the potential to cause havoc across the United States, although as yet it hasn’t led to widespread disease in the country. Mozes cites Dr. Gabriel Hamer, a Clinical Assistant Professor at the Department Of Entomology at Texas A&M University observing that “What we have here is an invasive daytime-feeding, disease-carrying mosquito that, since it first arrived on the East Coast in the 1980s, has been pretty aggressive in mowing down its natural competitors. And now it’s really starting to move through the country in full force. That makes it, at the very least, a nuisance and an annoyance, and at worst, a serious vector for major pathogens.”
Developing a vaccine against dengue/severe dengue has been challenging, and there is currently no vaccine or medication that protects against the disease, and although there has been recent progress in vaccine development, the WHO says licensure of a vaccine is not imminent. There is no specific treatment for the disease but medically treating the symptoms can help with recovery. The WHO has set out guidelines for management of the severe disease, i.e. DHF and DSS. and critical in this regard is early and effective plasma replacement, but notes that debate exists as to the specific approach to be used for severe disease , e.g. use of colloid or crystalloid solutions in patients with worsening shock. Most commonly after being bitten by an infected mosquito symptoms will take four to seven days to appear, and usually include flu-like symptoms such as high fever (40°C/ 104°F), severe headache, joint and muscle pain, bone pain, pain behind the eyes, nausea, vomiting, swollen glands, and often a rash, but some people infected with the virus will show no symptoms.
The disease is usually self-limiting. Most people recover from Dengue Fever in two to seven days, after an incubation period of 4–10 days after the bite from an infected mosquito. However, in about one percent of cases, dengue fever victims will develop potentially lethal complication called Severe Dengue, or Dengue Haemorrhagic Fever (DHF) — also variously known as ‘O’nyong-nyong Fever; Dengue-Like Disease; Breakbone Fever, Hemorrhagic Dengue, Dengue Shock Syndrome, Philippine Hemorrhagic Fever, Thai Hemorrhagic Fever, and Singapore Hemorrhagic Fever — an incredibly severe form of the disease first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Symptoms of DHF include high fever, plasma leakage, fluid accumulation, respiratory distress, severe bleeding under the skin, severe abdominal pain, vomiting, rapid breathing, bleeding gums, fatigue, restlessness, blood in vomit or organ impairment such as encephalopathy and fulminant liver failure. DHF can lead to shock, but for severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20 percent to less than 1 percent. Infants between 5 and 8 months of age are at a high risk for severe disease, and Severe Dengue is a leading cause of serious illness and death among children affecting most Asian and Latin American countries, and has become a leading cause of hospitalization and death among children in these regions, with 2.5 percent of such cases proving fatal.
Before 1970, only nine countries had experienced Severe Dengue epidemics, but the disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. The American, South-east Asia and the Western Pacific regions are the most seriously affected. Over 2.5 billion people — over 40% of the world’s population-– are now at risk from dengue, and the WHO currently estimates there may be 50–100 million dengue infections worldwide every year.
Recovery from infection by one provides lifelong immunity against that particular causative serotype. However, cross-immunity to the other serotypes after recovery is only partial and temporary. Subsequent infections by other serotypes increase the risk of developing severe Dengue and Dengue Haemorrhagic Fever.
The WHO says threat of a possible outbreak of dengue fever now exists in Europe, and local transmission of Dengue was reported for the first time in France and Croatia in 2010 with imported cases detected in three other European countries. In 2012, an outbreak of dengue on Madeira islands of Portugal resulted in over 2 000 cases and imported cases were detected in 10 other countries in Europe apart from mainland Portugal. In the past decade, Dengue has been identified in Hawaii, south Florida and along the Texas-Mexico border, and in 2013, cases have occurred in Florida and in China’s Yunnan province. In Asia, Singapore has reported an increase in cases after a lapse of several years and outbreaks have also been reported in Laos.
Dengue Fever In Houston
In their Houston study, Dr. Murray and her colleagues first checked the clinical samples for immunoglobulin M (IgM) antibodies, the antibodies that represent acute dengue infection, and found that 47 of the 3,768 samples were positive for IgM antibodies specific to the dengue virus. Two of those samples were positive for the actual virus in their blood, which happened to be dengue 2 (DEN-2), a strain of dengue virus can be associated with severe illness, including hemorrhagic fever.
When researchers looked at the medical records of these patients and conducted interviews, they found that most did not have a history of travel to endemic areas, indicating that the virus is being transmitted locally. Most cases occurred in the summer months of 2003 and showed the typical characteristics of an outbreak.
Medical record review identified two fatal cases, one of whom had been bed-bound for two years, so clearly had no history of travel outside of Houston. The other fatal case did have a history of recent travel to Mexico, and clinical symptoms were compatible with dengue hemorrhagic fever and shock syndrome. None of the medical records of any of the cases listed dengue as a possible cause of the illness.
“Dengue virus is one of those diseases for which we suspected some low level of ongoing virus activity, and certainly Houston is a prime spot for these types of viruses to circulate,” says Dr. Murray.
“Many times, dengue virus is overlooked because a lot of doctors don’t know how to recognize the symptoms”, she added. Dr. Murray is now working to educate physicians on how to recognize the disease.
Results of the Murray study, which was supported in part by a grant from the United States Department of Defense, Army (Grant W81XWH-04-2-0031) and by the National Institutes of Health (Grant AI069145), entitled “Identification of Dengue Fever Cases in Houston, Texas, with Evidence of Autochthonous Transmission Between 2003 and 2005” (doi:10.1089/vbz.2013.1413) is co-authored by Liliana F. Rodriguez, Emily Herrington, Vineetkumar Kharat, Nikolaos Vasilakis and Christopher Walker of The University of Texas Health Science Center at Houston; Cynthia Turner, Salma Khuwaja and Raouf Arafat of the City of Houston Department of Health and Human Services; Scott C. Weaver of The University of Texas Medical Branch in Galveston; and Diana Martinez, Cindy Kilborn, Rudy Bueno and Martin Reyna of Harris County Public Health and Environmental Services. published in the journal Vector-Borne and Zoonotic Diseases, and available here.
The study abstract notes that Houston maintains an environment conducive to Dengue virus emergence; but surveillance is currently passive, and diagnostic testing is not readily available. To determine whether Dngue virus (DENV) is present in the Houston area, the researchers tested 3768 clinical specimens collected from patients with suspected mosquito-borne viral disease between 2003 and 2005, and identified 47 immunoglobulin M (IgM)-positive dengue cases, including two cases that were positive for viral RNA in serum for dengue serotype 2 (DEN-2).
The co-authors note that the majority of cases did not report any history of travel outside the Houston area prior to symptom onset, and the epidemic curve suggests an outbreak occurred in 2003 with continued low-level transmission in 2004 and 2005. Chart abstractions were completed for 42 of the 47 cases; 57 percent of which were diagnosed with meningitis and/or encephalitis, and 43 percent met the case definition for Dengue Fever. Two of the 47 cases were fatal, including one with illness compatible with Dengue Shock Syndrome. The co-authors conclude that their results support local transmission of DENV during the study period, and heighten the need for dengue surveillance in the southern United States.
“One of the reasons we established the National School of Tropical Medicine in Houston was to be at ‘ground zero’ where neglected tropical diseases are present because of the confluence and warm climate in the southern United States,” says Dr. Peter Hotez, Houston-based social activist physician and researcher Dr. Peter J. Hotez MD PhD, who is recognized as America’s leading advocate for and internationally recognized expert on tropical diseases and vaccine development. Dr. Hotez is President of the Sabin Vaccine Institute (Sabin), founding Dean of the National School of Tropical Medicine at Baylor College of Medicine, Professor of Pediatrics and Molecular Virology & Microbiology and Chief of the Section of Pediatric Tropical Medicine at BCM, Endowed Chair of Tropical Pediatrics at Texas Children’s Hospital, heads the Children’s Hospital Center for Vaccine Development, and was recently named the Fellow in Disease and Poverty at Baker Institute for Public Policy at the Rice University. In a paper published in PLOS in 2008, Dr. Hotez identified a group of neglected tropical diseases (NTDs) now afflicting at least five million Americans living in poverty, mostly in the American South, including Dengue Fever In Texas And Florida.
“Dr. Murray’s important work confirms our assumptions and preliminary studies that neglected tropical diseases such as dengue are likely widespread in Texas and the Gulf Coast,” says Dr. Hotez in the BCM release.
Dr. Kristy Murray is now working with the local health department to test for dengue as a part of routine diagnostics. She also worked with local health authorities to create a Dengue Working Group, which has regular meetings to talk about strategies to enhance surveillance for these types of diseases.
“This is another reminder to be cautious of mosquitoes, no matter what time of day it is, and to protect from getting mosquito bites, especially in children and the elderly,” advises Dr. Murray.
The WHO advises that at present, the only method to control or prevent the transmission of Dengue virus is to combat vector mosquitoes through:
• Preventing mosquitoes from accessing egg-laying habitats by environmental management and modification;
• Disposing of solid waste properly and removing artificial man-made habitats;
• Covering, emptying and cleaning of domestic water storage containers on a weekly basis;
• Applying appropriate insecticides to water storage outdoor containers;
• Using of personal household protection such as window screens, long-sleeved clothes, insecticide treated materials, coils and vaporizers;
• Improving community participation and mobilization for sustained vector control;
• Applying insecticides as space spraying during outbreaks as one of the emergency vector control measures;
• Active monitoring and surveillance of vectors should be carried out to determine effectiveness of control interventions.
The Texas Department of State Health Services has a Dengue Fever Web page containing descriptive, avoidance, and reporting information. Several Texas laws require specific information regarding notifiable conditions be provided to the Texas Department of State Health Services (DSHS). Health care providers, hospitals, laboratories, schools, and others are required to report patients who are suspected of having a notifiable condition within one week.
When reporting cases of Dengue, Dengue Hemorrhagic Fever, or Dengue Shock Syndrome, local and/or regional health agencies must complete a “Mosquito-borne Disease Case Investigation Form which you can download here:
http://www.dshs.state.tx.us/idcu/health/zoonosis/forms/human/MosquitoBorne.pdf
About Dr. Kristy Murray
According to her Baylor College of Medicine biography page, prior to joining the faculty at Baylor, Dr. Murray was an Associate Professor of Epidemiology for the Center for Infectious Diseases at the University of Texas Health Science Center at Houston, School of Public Health (2002-2012). She received a Doctorate in Veterinary Medicine from Texas A&M University in College Station in 1998 and a Ph.D. in Preventive Medicine and Community Health in Clinical Investigations from the University of Texas Medical Branch in Galveston.
Dr. Murray spent the first five years of her career at the Centers for Disease Control and Prevention (CDC). At CDC, she served two years as an Epidemic Intelligence Service Officer conducting outbreak investigations, including the initial outbreak of West Nile virus in New York City in 1999, bubonic plague in Wyoming, and unexplained illness and deaths in injection drug users in Ireland. She also had the opportunity to work on the polio eradication campaign in Bangladesh and research lyssaviruses in the Philippines. She received several awards at CDC including the Secretary’s Award for Distinguished Service for her work on the West Nile virus Encephalitis Investigation Team and for the Anthrax Investigation Emergency Response Team.
In 2002, Dr. Murray returned to Texas and joined the faculty at the University of Texas Health Science Center at Houston. Her research over the past 10 years has been focused on vector-borne and zoonotic diseases, including West Nile virus, dengue, St. Louis encephalitis, eastern equine encephalitis virus, Rocky Mountain Spotted Fever, Chagas, and rabies. She has made numerous discoveries regarding health outcomes related to West Nile virus infection, including identifying persistent infection of the kidneys in patients years past their initial infection, which has never before been reported. She teaches graduate-level courses on epidemiology and infectious diseases, and advises master’s and PhD-level students. Dr. Murray has received several awards for her work in academia, including the Innovation in Health Science Education Award from the UT Academy of Health Science Education, Dean’s Award for Teaching Excellence, the UT Health Science Center Young Investigator Award, and the Texas A&M College of Veterinary Medicine’s Distinguished Alumni Award. Dr. Murray serves on the editorial board of the journal Epidemiology and Infection and has authored more than 40 scientific and technical papers.
Sources:
Baylor College of Medicine
Dr. Peter Hotez
World Health Organization Dengue Fever Factsheet
Texas Department Of State Health Services
PLOS Neglected Tropical Diseases Journal
Committee to Advise on Tropical Medicine and Travel
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