Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases The Short-Term and Long-Term Outcomes: Workshop Report (2011) / Chapter Skim
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8 Prevention
8 Prevention
Pages 155-176
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From page 155... ...
But a wider array of simple and effective prevention modalities would be very beneficial and would, it is hoped, change the current trajectory of TBD incidence. Prevention measures can be divided into two categories: Pharmacologic preventive measures such as antibiotic prophylaxis or vaccines, and non-pharmacologic interventions such as behavior change or tick-targeted strategies (e.g., tick checks or tick reduction)
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From page 156... ...
To develop such vaccines, however, some basic research on these emerging infectious diseases needs to be done, including: • Defining immunoprotective pathogen proteins; • Understanding and defining pathogen antigenic variation; • Understanding variations in pathogenicity; • Understanding protective immune mechanisms;
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From page 157... ...
Initial efforts have focused on immunoreactive proteins, surface-exposed proteins, and effector proteins that either play a role in arthropod infection and transmission, induce both cell-mediated and humoral immunity, or are recognized by the acute-stage immune response. Initial experiments to molecularly characterize potential effector proteins have shown they contain tandem repeats (TRPs)
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From page 158... ...
Further, one tandem repeat protein -- TRP120 -- is expressed in both the tick and the mammalian host. Two outer membrane proteins are also expressed -- one that is expressed in the mammalian and tick hosts -- and one, outer membrane protein 1B expressed only in the tick host, which could be considered for a tick-specific vaccine for E
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From page 159... ...
A live attenuated vaccine based on that knockout that mimics natural infection would seem promising. Other efforts have focused on vector proteins that impair tick feeding while also modulating immune responses and coagulation in a mammalian host.
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From page 160... ...
Knowledge Gaps and Research Opportunities McBride noted there are a number of avenues for future work on vaccines against tick-borne diseases: • For Rickettsia, live attenuated vaccine mimics the natural infection; thus Rickettsia that are genetically attenuated by gene knockouts are promising for future development of vaccines for rickettsial diseases. • Vector proteins are attractive vaccine candidates.
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From page 161... ...
As research leads to understanding of the molecular characteristics and the cellular pathways involved in pathogenesis, a number of targets have been identified for developing potential vaccines. These include • Outer membrane or surface proteins produced during the host stage to prevent infection.
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From page 162... ...
For example, it is possible that the antigens tested thus far are not the ones that can induce protection, that multiple antigens need to be included in a vaccine, or that the association of proteins within the outer membrane confers ability to induce protective immunity through linked recognition of T cell and B cell epitopes. Individual outer membrane proteins that stimulate antibodies after infection or immunization have been typically targeted for vaccine development because it is easier to perform than screening antigens to find those that increase production of CD4 T cells.
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From page 163... ...
To begin to understand their role, there is a need to understand how subdominant, conserved antigens associate with other proteins in the outer membrane and how this interaction might affect the generation of immune responses through the linked recognition of T cell and B cell epitopes. In preliminary studies, proteins were selected based on immunoblots from A
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From page 164... ...
• Develop metrics to measure protective immune responses in these species.
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From page 165... ...
Familiar personal protective measures include frequent tick checks to remove crawling or attached ticks; use of protective clothing such as long-sleeved shirts, long pants, and light-colored clothes; tucking pants into socks; using repellent; and avoiding tick habitat. These strategies have yielded mixed results in analytic studies.
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From page 166... ...
However, about 77 percent of both patients and controls reported checking for ticks. A second study conducted in Connecticut a few years later examined a wide variety of personal protective behaviors and home landscaping practices among approximately 360 patients with Lyme disease and a similar number of matched controls.
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From page 167... ...
Despite these complexities, personal protective measures are relatively benign even if not always very effective, and there is little downside to encouraging people to use them. Assuming personal protective measures are effective, questions remain as to whether a sufficient number of individuals can be encouraged to practice these behaviors regularly.
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From page 168... ...
More than 50 percent of respondents also thought it was very likely or somewhat likely that someone in their household would contract Lyme disease in the next year. Approximately 5 percent of participants reported a previous diagnosis of Lyme disease.
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From page 169... ...
Third, educational campaigns should target behaviors that have some evidence of benefit, such as bathing, and not those that do not, such as tucking pants into socks. Finally, it is important to recognize that the personal protective measures are unlikely to have a major public health benefit for tick-borne diseases.
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From page 170... ...
Vertebrate hosts are needed to sustain the tick population, so targeting mammalian hosts is another prevention strategy. Tick larvae feed mainly on Peromyscus leucopus, the white-footed mouse, while adult ticks attach mostly to deer.
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From page 171... ...
The site of a tick bite is in an immunosuppressed state as tick saliva contains proteins that will block the activation of histamine, ATP, serotonin, bradykinin, and leukotriene B4, which trigger pain and itching in the hosts, thus the attached tick can go unnoticed unless that person happens to develop an allergy to one or more of its salivary proteins. In brief, tick saliva has antihemostatic, anti-inflammatory, and immunosuppressive properties.
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From page 172... ...
Another participant noted that often the last diagnosis a doctor will consider is Lyme disease, when it should be one of the first. Another participant noted that everyone needs to be a part of the education process because the entire community needs to consider tick-borne diseases as a serious health concern before protective measures will be effectively
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From page 173... ...
Mead noted that the CDC recognizes that Lyme disease is a growing problem and is among the top seven reportable disease in the country. In Northeastern United States, it is among the top two or three.
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From page 174... ...
These include better defining immunological responses to infection, understanding mechanisms of immune-based protection, developing the ability to measure protection, and creating animal models to study potential vaccine candidates. A significant challenge for vaccine development is the sheer diversity of human tick-borne pathogens, along with their antigenic variation.
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From page 175... ...
Mead explored multiple non-pharmaceutical interventions. The best studied are personal protective measures that involve behavioral change, such as the use of tick checks, long-sleeved clothing, and insecticides, but the results have been variable.
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From page 176... ...
Public health officials should consider similar campaigns -- even in lower incidence locations, or targeted to schoolchildren, people in high-risk occupations, and outdoor enthusiasts -- as they may improve adherence to prevention measures and reduce the incidence of disease.
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