Operational vector-borne disease surveillance and control: closing the capabilities gap through research at overseas military laboratories.
Subject: Dengue (Military aspects)
Malaria (Military aspects)
Laboratories (Military aspects)
Medical research (Military aspects)
Medicine, Experimental (Military aspects)
Authors: Evans, Brian P.
Clark, Jeffrey W.
Barbara, Kathryn A.
Mundal, Kirk D.
Furman, Barry D.
McAvin, James C.
Richardson, Jason H.
Pub Date: 07/01/2009
Publication: Name: U.S. Army Medical Department Journal Publisher: U.S. Army Medical Department Center & School Audience: Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 U.S. Army Medical Department Center & School ISSN: 1524-0436
Issue: Date: July-Sept, 2009
Product: Product Code: 8516000 R&D Facilities; 8000200 Medical Research; 9105220 Health Research Programs; 8000240 Epilepsy & Muscle Disease R&D NAICS Code: 5417 Scientific Research and Development Services; 54171 Research and Development in the Physical, Engineering, and Life Sciences; 92312 Administration of Public Health Programs
Accession Number: 242963584
Full Text: Introduction

Since its inception, the US military has consistently been called upon to wage battles and to conduct peacekeeping and humanitarian relief operations in locations of the world where the most formidable enemy is often a tiny, 6- or 8-legged creature. Indeed, in every war fought by the United States up through the Vietnam conflict, the number of casualties caused by arthropod-borne diseases has significantly exceeded the number of battlefield casualties. (1) It was the pioneering efforts of Walter Reed, William Gorgas, and others that helped to decipher the link between microbes, human disease, and mosquito vectors. (2) Their discoveries led the way in the fight against typhoid fever, yellow fever, malaria, and other diseases that had plagued military and civilian populations for millennia.

In spite of these discoveries, malaria continued to take its toll on US forces. During World War I, almost 17,000 troops acquired malaria. (1) Over 24,000,000 person days were lost during World War II to malaria and other arthropod-borne diseases such as scrub typhus and dengue fever. (1) In 1943, Allied forces averaged 208 new cases of malaria per 1,000 Soldiers stationed in the south Pacific. (3) In the Vietnam conflict, annual case rates of malaria reached as high as 600 per 1,000 troops. (1) In the 1940s, entomologists from the US Department of Agriculture developed methods and equipment to use DDT * to control mosquitoes, lice, and other vectors. In collaboration with military entomologists, they developed insecticide dispersal equipment and implemented malaria eradication programs which together reduced the number of malaria cases in the south Pacific to 5 per 1000 Soldiers by 1945. (3)

Despite these early successes, there has been a dramatic resurgence of mosquito-borne diseases during the post-DDT era, and today's military continues to face a significant threat from arthropod vectors. While significant strides have been made in the implementation of personal protective measures, including malaria chemoprophylaxis, bed nets, repellents, and permethrin-treated uniforms, the battle against arthropod-borne disease is far from won. Compliance with such measures remains a problem, as evidenced from a survey of Soldiers returning from Afghanistan. (4) In general, though, the advances in science and medicine have been outpaced by the adaptability of vectors and the evolution of pathogens. Novel more efficient strategies to reduce transmission of vector-borne diseases are required if the military is to effectively combat this threat.

The required tools would allow deployed PM personnel to accurately evaluate the risk of disease transmission through vector/pathogen surveillance, and subsequently implement control measures to break the cycle of transmission. However, there currently exists a gap between what preventive medicine assets have at their disposal for surveillance and control and what they require to more effectively minimize the potential for arthropod-borne disease transmission. Effective control measures are only achievable through the use of real-time, accurate surveillance tools along with a sufficient understanding of the biology and behavior of problem vectors.

US Army, Navy, and Air Force entomologists stationed in 5 overseas laboratories are focused on developing and evaluating tools and methods that would fill this capabilities gap:

* Thailand--the Armed Forces Research Institute of Medical Sciences (AFRIMS)

* Kenya--the US Army Medical Research Unit Kenya (USAMRU-K)

* Indonesia--the US Naval Medical Research Unit

No. 2 (NAMRU-2)

* Egypt--the US Naval Medical Research Unit

No. 3 (NAMRU-3)

* Peru--the US Naval Medical Research Center Detachment (NMRCD)

This group of researchers is on the front lines working to address the military's vector/pathogen surveillance and control shortfalls. What follows is a summary of the team's efforts associated with 5 priority arthropod-borne disease threats (malaria, dengue fever, chikungunya virus, visceral leishmaniasis, and cutaneous leishmaniasis). (5)

Disease Overview

Malaria

Annually, 300 to 500 million people are infected with malaria, with 1.5 to 2.7 million fatalities (mostly children). (6) Several hundred cases of malaria, transmitted by night-feeding Anopheles mosquitoes, continue to infect military personnel deployed in locations throughout southwest Asia, sub-Saharan Africa, and the Korean peninsula. A total of 425 cases of malaria were diagnosed in US military personnel between the years 2000 and 2005.7 Most notable was the occurrence of 38 cases of vivax malaria in a 725-man US Army Ranger task force that deployed to Afghanistan between June and September 2002.4 Another significant malaria outbreak occurred during the deployment of 225 Marines to Liberia in which 80 Marines contracted falciparum malaria. (8) Since the early 1990s, US troops deployed in South Korea have consistently been at risk of exposure to vivax malaria. (9) Although there are significant efforts underway from Department of Defense (DoD) researchers, the Gates Foundation, and private industry to develop antimalarial drugs and malaria vaccines, a licensed vaccine is likely a decade or more away, and drug resistant parasites are continually appearing. (10) In the interim, improved methods to reduce the risk of infection through mosquito control or personal protection are critical.

Dengue Fever

We are currently witnessing a worldwide resurgence (and in some cases emergence) of arthropod-borne viral (arboviral) diseases, and dengue fever leads the list as a public health threat. (11) The 4 dengue virus (DENV) strains are maintained in cycles involving humans and the container-breeding Aedes aegypti mosquito, a vector that typically feeds on humans during the daylight hours. The lack of treatment, the explosive nature of this disease, and the potential for acquiring dengue hemorrhagic fever (a deadly form of the disease) are causes for concern among DoD planners. While DoD researchers are working towards a vaccine that is protective against all 4 DENV serotypes, mosquito surveillance and control remain central to prevention and control of dengue fever outbreaks.

Chikungunya

Chikungunya virus (CHIKV) is an alphavirus transmitted to humans by container-breeding Aedes mosquitoes. The virus is endemic to Africa and various parts of Asia, including Indonesia and the Philippines. (12) This disease is currently showing a pattern of reemergence. In the last 5 years, explosive outbreaks have occurred in Kenya, the Seychelles, Comoros, Mayotte, Mauritius, Madagascar, India, and Italy. (13) A specific example of the alarming attack rates occurred on the island of La Reunion where almost 40% of the island's total population of 785,000 fell ill in 2005-2006. (14) Recent outbreaks have also been reported in Singapore, Malaysia, and Thailand. Symptoms include fever, incapacitating joint pain, and rash which generally disappear after a few days. While CHIKV is rarely fatal, joint pain can persist for months or even years. Given the lack of a vaccine or treatment and the history of large epidemics, prevention of infection through vector control is paramount.

Leishmaniasis

Leishmaniasis presents itself in 2 main forms: cutaneous leishmaniasis, which often results in skin lesions or attacks mucous membranes; and visceral leishmaniasis, which can lead to liver and other organ damage, and sometimes even death. Leishmaniasis is a parasitic infection caused by a variety of Leishmania species. Phlebotomine sand flies are involved in the transmission of Leishmania, from rodents and canids to humans. Sand flies are elusive, pinhead-sized insects of which little is understood about their biology and behavior. Consequently, control of these disease vectors continues to be a significant challenge for military entomologists. (15) No prophylactic drugs or vaccines are currently available, and emphasis is placed on preventive measures to break the cycle of transmission. (16)

Defining the Gap

Effective vector-borne disease prevention relies on answering a core set of questions. Once these questions are answered, decision makers can design strategies based on evidence and tailored to the unique dynamics of their specific situation (in space and time). The fewer questions we can answer, and the more assumptions we make, the more likely we are to implement ineffective, one-size-fits-all solutions. At a minimum, the following questions must be answered. (16)

1. Is there disease transmission in the area?

2. Which arthropod species are present and which ones are vectors of disease?

3. Which ones feed on humans?

4. Where does human-vector contact occur?

5. Where do the vector species breed and rest?

6. When and where should a vector control strategy be implemented?

7. What proportion of the vector population is susceptible or resistant to insecticides?

8. What vector control options will likely reduce disease transmission?

Malaria can be used as an example to highlight the importance of addressing the previous questions. Approximately 430 Anopheles species are found worldwide of which only 30 to 40 species transmit malaria in nature. (17) Of these, some feed indoors and others feed outdoors. If mosquito control programs are designed without determining when and where personnel are being exposed, they will likely fail to reduce the threat. However, with answers to the questions above, preventive medicine personnel may advise the use of insecticides inside sleeping areas to control a mosquito species which prefers to feed indoors at night. Although it is paramount that most, if not all, of the questions above be addressed prior to the implementation of a program, the current reality is that we do not yet have the capability to answer all of them. Seven of the major gaps are presented below, along with the measures that are being undertaken by military entomologists working overseas to overcome the recognized deficiencies.

Defining and Closing the Capabilities Gaps

Task: Conduct Vector Surveillance

Gap: Adult mosquito and sand fly collection devices are minimally effective

Problem. Numerous devices have been developed over the years to survey for Aedes (dengue/ chikungunya vectors) and Anopheles mosquitoes (malaria vectors).18 Sticky traps, visual traps, light traps and backpack aspirators are the most widely used tools for conducting mosquito surveillance, (19-21) with Centers for Disease Control and Prevention (CDC) light traps (Figure 1) often considered the industry standard for mosquito surveillance. However, all of these trap types have drawbacks. (18) For example: sticky traps can damage sampled mosquitoes, the degree of success with backpack aspirators is highly dependent on the collector/inspector, visual traps are generally of lower efficiency, and CDC light traps lack an olfactory-based attractant and contain a light source that has the unintended effect of repelling some mosquito species.

[FIGURE 1 OMITTED]

Ideally, human landing counts (HLCs) can be used to evaluate the efficacy of vector control. This technique involves collecting host-seeking arthropod females that land on an individual human's exposed legs. Data collected using this technique generally correlates well with local vector population densities. The HLCs can also be used to help determine entomological inoculation rates, which are true estimates of the disease risk posed to humans. While surveillance using HLCs is the most effective approach for determining mosquito densities, the ethical issue of placing humans at risk for contracting disease from pathogens originating from mosquito vectors makes this approach less appealing in today's environment. Currently, PM assets depend on the CDC light trap (or a related version) to conduct most adult mosquito surveillance. The main attractant is a 4- to 6-watt incandescent light bulb. As the mosquito approaches the light source, it is drawn downward into a collection bag by a fan mounted just below the light bulb. This surveillance tool has significant limitations with regard to collecting disease vectors:

* The trap is only effective for some mosquito species that feed at night (ie, Anopheles). The CDC light trap is an inadequate surveillance tool for mosquitoes which feed during the day, such as DENV and CHIKV vectors.

* Not all night-feeding adult mosquitoes are attracted to the light source of a CDC trap. Mosquitoes only see in the visible light spectra of blue, green, and red. Incandescent light sources emit light most strongly in the infrared spectra and weakly in the visible light spectra of blue, green, and red. (22) Therefore, even though Anopheles feed during the night, potentially important vectors are often "repelled" by the light source.

* The trap should be augmented with a carbon dioxide source to enhance trap effectiveness. The carbon dioxide source might come in the form of dry ice, granular C[O.sub.2]-sachets, or a canister of C[O.sub.2.] Blood-feeding mosquitoes use a combination of olfactory cues in addition to visual cues to find a suitable host. Carbon dioxide is considered to be a principal olfactory attractant.

* The efficiency of converting electrical current to light using incandescent light bulbs is exceptionally low (approximately 6%). The remainder (94%) is often dispersed as heat or infrared radiation. (22) As a consequence, this device consumes a great deal of energy.

* The effectiveness of these traps for collecting sand flies has not been systematically evaluated.

Solutions

BG-Sentinel Trap (BGS) (Biogents AG, Regensburg, Germany). The BGS (Figure 2) has shown significant promise as a tool for collecting Ae aegypti, (23-26) and Ae albopictus. (27) To our knowledge, this device has not been evaluated for malaria vectors in Asia. The BGS uses a blend of mosquito attractants consisting of lactic acid, ammonia, and caproic acid, substances all found on human skin. The blend is released in a fixed ratio from a dispenser known as the BG Lure. (23) The efficacy of the BGS (with and without carbon dioxide) relative to other surveillance devices for collecting DENV and malaria vectors is being evaluated in Thailand.

Bed Net Traps. An alternative to HLCs is needed, particularly in areas of high disease transmission. The performance of a self-supporting bed net trap is undergoing evaluation by Navy entomologists at NAMRU-2. Preliminary results show that a lightweight (2 kg), easy-to-assemble bed net trap collected significantly greater numbers of Anopheles spp and Culex spp (vectors of Japanese encephalitis virus and filariasis) than a CDC trap. The trap, shown in Figure 3, is designed to protect the person (the attractant) in the bed net while simultaneously trapping (in an outer tent structure) vectors that can be identified and tested for human pathogens. In areas where disease transmission is very high or drug resistant pathogens occur, collections of mosquitoes could be made while minimizing the risk to the collector. (28,29)

[FIGURE 2 OMITTED]

Mass Trapping Techniques for Surveillance/Control.

Traps that generate C[O.sub.2] by catalyzing propane have demonstrated a reduction in nuisance mosquito or biting midge populations. (30-33) Little is known regarding the effectiveness of these traps on reducing disease vector species in isolated, tropical environments. (33) Manufacturers of commercially available traps claim the ability to control mosquito populations over an area as large as one acre. * Future evaluations of this technology at overseas field sites will determine the efficacy of a commercial mosquito trap in reducing prevalence of mosquito populations in a specific area.

Sand Fly Attractants. Modified CDC light traps were recently tested in southern Egypt by NAMRU-3 researchers. The light traps were modified to accommodate light emitting diodes, and proved to be very effective for sand fly surveillance. (34) At present, field studies are being conducted to determine the efficacy of a wide range of semiochemicals, either repellents or attractants, on the activity of sand flies. Pheromones from Lutzomyia longipalpis (leishmaniasis vector) males have shown significant promise. (35) Like many sand flies, L longipalpis is a lekking species, one in which males gather for the purposes of a competitive mating display. Females are attracted to displays of male wing-fanning behavior and pheromones released by the male. It is therefore likely that traps baited with male pheromones will attract female sand flies in the field (their potential has already been shown in the laboratory). Efforts are underway in Colombia where scientists from the NMRCD, in collaboration with Rothamsted Research (Harpenden, Hertfordshire, UK) (20) are evaluating the efficacy of these pheromones as baits in a variety of commercial traps placed in jungle encampments in the Colombian Amazon.

[FIGURE 3 OMITTED]

Figure 3. The bed net trap.

Task: identify Vector species

Gap: Limited availability of country-specific taxonomic keys and limited knowledge of species' bionomics, relative vector status, and distribution

Problem. The Walter Reed Biosystematics Unit has made significant strides in designing user-friendly, regional keys for the identification of mosquitoes and sand flies worldwide. These keys have proven their utility, most especially in southwest Asia. However, regionally relevant identification keys along with descriptions related to the feeding, breeding, and resting behavior, relative vector status, and distribution of species are still lacking for much of the tropics. Without these references, PM planners are not able to answer the relevant questions which drive implementation of sound control programs.

Solutions

Sand Fly Biology and Taxonomic Research. The NAMRU-3 has been conducting extensive sand fly research and surveillance in countries throughout Africa and the Middle East for over 50 years. During that time, the NAMRU-3 Vector Biology Research Program (VBRP) has determined the vector status of numerous Phlebotomus species found throughout the Middle East and African region, (36-38) and has developed a better understanding of sand fly ecology in various countries within the aforementioned region, including extensive bionomics studies of sand flies in the Sinai (36,39) and in southern Egypt, where sand fly daytime resting sites were recently discovered for the first time. (40) Sand fly species distributions have been determined in Djibouti, (41) and NAMRU-3 is completing compilations for Egypt and parts of Ghana. Further, wide-scale species distribution projects are currently underway in Afghanistan and Libya. Collectively, NAMRU-3 has produced taxonomic keys for the sand flies of Afghanistan, Egypt, Ghana, Sudan (B.D.F., unpublished data, 2009), and Djibouti. (41) To supplement the morphological identification of sand flies, VBRP has a rapidly expanding polymerase chain reaction component which allows for the molecular identification of sand flies.

Mosquito Keys. World-renowned mosquito taxonomist Dr Rampa Rattanarithikul has spent decades at AFRIMS dissecting, classifying, and analyzing mosquitoes. (42) With the assistance of illustrator Prachong Panthusiri, they are on the verge of completing the last volume of a 6-volume publication entitled Illustrated Keys to the Mosquitoes of Thailand. (43-47) This tool will be exceptionally valuable for preventive medicine assets deploying to southeast Asia, especially for those associated with the annual Cobra Gold exercises in Thailand and current operations in the Republic of the Philippines.

Task: Conduct pathogen surveillance

Gap: Rapid pathogen surveillance devices are lacking

Problem. While a disease vector may be present in a particular area, the broad application of control measures may not necessarily be warranted. Pathogen surveillance tools allow for the effective local targeting of control measures, thereby enhancing the possibility of managing the disease, while reaping the benefits of reduced costs and avoidance of the potential environmental and human health risks often associated with insecticide application. For example, the malaria dipstick assay is a rapid, one-step procedure that uses a test strip capable of detecting and then differentiating between infections of P falciparum and P vivax in adult mosquito collections within minutes. (48) This particular hand-held device is of lower cost and is very user-friendly relative to polymerase chain reaction methods, and can potentially identify areas where the risk of contracting malaria is high. Such a tool can help to prioritize control efforts and has significant impact when requesting support or the assistance of the command. This type of rapid screening tool is not available for most vector-borne pathogens.

Solutions. The overseas laboratories are actively involved in the field evaluation of hand-held dipstick assays for the detection of leishmaniasis, DENV, Japanese encephalitis virus, and Rift Valley fever virus. In addition, in collaboration with both the US Army Research Institute for Infectious Diseases and the US Air Force 59th Clinical Research Division, entomologists at AFRIMS, NAMRU-3, and USAMRU -K are conducting field evaluations of real-time polymerase chain reaction assays to detect vector-borne pathogens. Many of these assays are designed for the Joint Biological Agent Identification and Diagnostic System using the Ruggedized Advanced Pathogen Identification Device (Idaho Technology Incorporated, Salt Lake City, Utah) as the platform. (49,50)

Task: provide personal protective Measures

Gap: The military has yet to field bed nets, tents, or other materials which have been treated with long lasting insecticides

Problem. The use of insecticide-treated nets (ITNs) and insecticide-treated tents is regarded as one of the most promising measures available to reduce vector-borne disease transmission. (51) However, treatment of ITNs with insecticide is performed in the field (not at the factory) which presents an added burden for PM assets. Application of insecticide to bed nets and tents is labor-intensive and not often a command priority.

Solutions

Long-lasting Insecticidal Net (LLIN) Evaluations. Manufacturers have developed LLINs such as Perma-Net[R] (Vestergaard Frandsen, Lausanne, Switzerland) which are ready-to-use, factory pretreated nets. Many of these nets are designed to release insecticide slowly so that the nets retain their efficacy after repeated washings. Some LLINs are said to require no further treatment during their physical lifespan of 4 to 5 years. (51) Currently, AFRIMS is evaluating the long-term efficacy of LLINs on vector densities in villages located in western Thailand. If shown to be effective, LLINs may be a valuable alternative to the field-application of insecticide to bed nets.

Insecticide-impregnated Tent Evaluations. US Army Deployable Rapid Assembly Shelter (DRASH) tents are woven from a noncanvas XYTEX[R] (DHS Technologies LLC, Orangeburg, New York) fabric, which is polyester-coated with polyvinyl chloride. Studies are underway in southeastern Thailand to determine whether insecticide-impregnated tents are indeed a viable approach for protecting Soldiers from vector-borne disease over the long-term. If this is found to be the case, further studies will then evaluate the utility of insecticide-impregnated DRASH tents (assuming that the technology is developed) in affording protection for Soldiers.

Task: Conduct Vector Control

Gap: Lack of effective and sustainable control methods for Aedes mosquitoes (CHIKV and DENV vectors)

Problem. Given adequate personnel, community involvement, money, and time, Ae aegypti population control can be achieved through sanitation and the elimination of mosquito breeding sites. This option is often not viable for military pest controllers during deployments. Effective source reduction is difficult when the military has no control of areas surrounding encampments occupied by US personnel. Chemical control using DoD-registered larvicides (larval stage insecticides) such as methoprene, temephos, and Bacillus thuringiensis israelensis (Bti) and various adulticides (adult stage insecticides) has proven effective in managing both larval and adult populations respectively of Ae aegypti (52) However, these options have obvious limitations when it comes to deployments and protecting the Warfighter. Indoor adulticide application can effectively reduce Ae aegypti populations but must be applied inside occupied structures on a regular basis. This can be difficult to justify as a preventive measure and is often unachievable. In general, the military is more likely to practice indoor adulticide application in response to disease transmission rather than as a preventive measure. Traditional larval control is logistically daunting and is minimally effective if surrounding areas are left untreated, or if coverage in the target area is low. What is lacking is an expedient, low risk, efficient, and sustainable approach to achieving epidemiologically-relevant levels of Ae aegypti population suppression.

Solutions

Resting/oviposition Lures Treated with Pyriproxyfen. Pyriproxyfen is classified as an insect growth regulator and a potent inhibitor of embryogenesis, metamorphosis, and adult formation in insects. (53) In addition, it has been shown to decrease the fertility and fecundity of Ae aegypti adults that develop from sublethally exposed larvae. (54) Evidence also suggests that adult mosquitoes not killed by contact with pyriproxyfen that is applied to breeding containers can actually carry the chemical to uncontaminated environments. The tiny doses of pyriproxyfen that are moved can then negatively affect the development of susceptible larvae. (55) Pyriproxyfen has long residual efficacy yet has an excellent mammalian toxicity profile. The most promising scenario involves females resting on surfaces treated with pyriproxyfen, picking up tiny doses of chemical that sterilize the females which then transports the pesticide to other breeding sites. Work conducted by the NMRCD, Rothamsted Research, and the Peruvian health authorities suggests that this approach has considerable potential. The NMRCD is designing a variety of simple resting and oviposition lures which will attract Ae aegypti and which can be treated with pyriproxyfen. The efficacies of these treated lures on fecundity and on the horizontal transfer of pyriproxyfen will be evaluated under seminatural conditions with future plans for field evaluations to establish the optimal distribution of such treated lures.

Pyriproxyfen-treated Ovitrap/resting Station Device Design/evaluation. Researchers at AFRIMS are designing and evaluating a visually attractive, pyriproxyfen-treated ovitrap (egg trap)/resting station device. It is clear that Ae aegypti females tend to spread their eggs among many sites. This behavior should improve the natural transfer of pyriproxyfen. Ae aegypti tend to remain relatively close to their larval habitat, with maximum dispersal distances around 100 to 200 m,56 therefore significant control (or local eradication) via this approach is within reason. This is particularly relevant in the context of a military camp where sanitation is high and larval habitat can be minimized. Initial lab evaluation of prototypes is underway using field cages/tunnels. Field trials are scheduled to assess the impact of the final product, spatially arranged as a barrier-like treatment, on Ae aegypti densities in a simulated military camp within a dengue-endemic village.

ProVector[TM] Trap Evaluations. A possible tool for the control of adult Ae aegypti populations currently being evaluated at USAMRU-K is the ProVector[TM] trap (MIT Holding Inc, Savannah, Georgia). This low cost trap mimics visual and chemical cues used by mosquitoes in search of a sugar meal. The trap is designed in such a way that only mosquitoes can feed on it, thus reducing the possibility of exposure to nontarget organisms and accidental environmental contamination. These traps, designed at the Biodefense and Infectious Disease Laboratory at Georgia Southern University, use a formulation of Bacillus thuringiensis israeliensis bioinsecticide as the active ingredient. This trap will be evaluated not only for its efficacy as a method for DENV and malaria vector control tool, but also as a tool for increasing the efficacy of Ae aegypti surveillance.

Push-pull System. Research is underway at NMRCD to develop a novel insecticide treated material (ITM) push-pull system to reduce Ae aegypti inside homes where they are most likely to feed on humans and transmit DENV. The system is comprised of ITMs designed to repel Ae aegypti from inside homes and an attractive, lethal trap positioned outside the home to pull the mosquitoes from the peridomestic environment. Following proof-of-concept, long-term goals include defining the public health impact of the system through epidemiological studies for operational refinement.

Gap: No effective replacement for the insecticide DDT

Problem. The successful eradication of malaria from the developed world and large portions of tropical Asia and Latin America was due largely to the widespread use of DDT.57 The effectiveness of DDT is primarily a result of its long lasting persistence. Ironically, this quality also led to the cancellation of its registration by the Environmental Protection Agency. (58) Modern alternatives to DDT are relatively unstable in the environment and therefore have shorter windows of efficacy. Effective vector control operations thus require more frequent spraying with obvious repercussions on sustainability. A DDT alternative with similar durability and effectiveness is desperately needed.

Solution. Pyrethroids have replaced many older insecticides because of their effectiveness and relative safety for the applicator. (58) The chemical structure of pyrethroids resembles a component of the natural botanical insecticide known as pyrethrum. Pyrethroids are highly toxic to most insects at very low rates of application. While pyrethroids do not measure up to DDT in terms of stability, there is evidence that the pyrethroid bifenthrin may be efficacious against mosquitoes for a considerable length of time postapplication (6 weeks) when applied to vegetation relative to other insecticides. (59) [TalStarOne.sub.TM] (FMC Corp, Philadelphia, Pennsylvania) (bifenthrin 7.9%) is EPA-registered and endorsed by the Armed Forces Pest Management Board for use on military installations and during deployments. Recent work at USAMRU-K, in partnership with the US Department of Agriculture Center for Medical and Veterinary Entomology, have shown that bifenthrin-treated camouflage nets provide an effective protective barrier against mosquitoes and sand flies, significantly reducing total trap numbers for over 6 weeks. Additionally, mortality rates were significantly higher for those vectors that made it through the nets, suggesting that treated nets provide protection beyond the initial barrier effect for which they were tested. Evaluations are also being performed in Thailand to determine the extent to which this insecticide is effective for the long-term control of malaria vectors when applied to vegetation along the perimeter of a village (Figure 4).

Gap: No effective sand fly control strategies

Problem. Unlike mosquito control, sand flies pose numerous problems that prevent the coherent development of an effective control strategy. Sand fly breeding habitats are much more cryptic and often impossible to identify, thus preventing the development of any effective larviciding strategy. Sand fly populations are extremely focal, with significant geographical and seasonal variations. Sand fly surveillance is a challenge and without the surveillance data, it is difficult to make sound decisions for targeted sand fly control operations. In the absence of better alternatives, deployed personnel currently revert to mosquito control methods. Sustainable and evidence-based strategies for targeting sand flies are clearly needed.

Solution. Rodent Pass-through System. The effectiveness of a rodent pass-through system to control sand fly populations is being evaluated at USAMRU-K. Laboratory studies have shown that diflubenzuron can prevent synthesis of chitin (the material composing the outer skeleton of arthropods). Diflubenzuron is nontoxic to rodents and remains active after passage through the rodent digestive tract. (60) Since the larvae of many sand fly species feed on rodent feces, (61) this may provide the first truly effective technique for targeting larval sand flies. Once baits are formulated for the targeted rodent fauna, diflubenzuron will be incorporated and the baits offered on a monthly basis. It is important to note that this would target native rodent populations in areas where troops are deployed, not pest rodent populations that are normally targeted with anticoagulant baits. Also, preliminary work is underway to evaluate the efficacy of using a sugar solution spray as bait for targeting adult male and female sand flies in search of sugar meals.

[FIGURE 4 OMITTED]

Conclusion

There is a well recognized gap between the resources required and those available to manage the risks to the Warfighter posed by malaria, dengue fever, chikungunya virus, leishmaniasis, and myriad other vector-borne disease threats. Vector control experts are expected to accurately evaluate the vector-borne disease threat and then make sound decisions to reduce that threat. Following the models of the pioneering work of Reed, Gorgas, and others, US Army, Navy, and Air Force researchers working overseas are helping to close this gap. Their efforts are enhancing the combatant commander's ability to identify and mitigate the threat posed by these vector-borne diseases.

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Authors

MAJ Evans is Deputy Chief, Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

CPT Clark is Chief, Department of Entomology & Vector Borne Diseases, US Army Medical Research Unit-Kenya.

LT Barbara is Head, Medical Entomology Department, US Naval Medical Research Unit No. 2, Jakarta, Indonesia.

LT Mundal is Director, Entomology Research Program, US Naval Medical Research Center Detachment, Lima Peru.

LT Furman is Head, Vector Biology Research Program, US Naval Medical Research No. 3, Cairo, Egypt.

James McAvin is a visiting scientist at the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

MAJ Richardson is Chief, Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

MAJ Brian P. Evans, MS, USA

CPT Jeffrey W. Clark, MS, USA

LT Kathryn A. Barbara, MSC, USN

LT Kirk D. Mundal, MSC, USN

LT Barry D. Furman, MSC, USN

James C. McAvin,

MAJ Jason H. Richardson, MS, USA

* Dichlorodiphenyltrichloroethane

* Example: Mosquito Magnet[R], Woodstream Corp, Lititz, PA Information available at http://www.mosquitomagnet.com
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