Travel medicine interventions and neurological disease

It is estimated that worldwide international arrivals by any form of transport have been around 763 million in 2004. Such increased mobility involves all kind of travellers (tourists, workers, businessmen) and all age groups. As a consequence, people with underlying medical conditions set out on a journey more often than in the past, raising issues on the risks related to the underlying disease and on recommended immunizations, antimalarial chemoprophylaxis and drug/drug interactions.

Among pre-existing medical conditions, some neurological diseases, i.e. multiple sclerosis (MS) and other demyelinating diseases, Guillain–Barre syndrome (GBS) and myasthenia gravis often create management problems to travel medicine practitioners: there is some concern that these conditions could be worsened either by naturally acquired infections or by some travel medicine interventions. Moreover, medications to treat the underlying disease could interact with some antimalarials and vaccines.

The first step is a careful risk assessment based on the actual knowledge of host factors, travel characteristics and environmental factors. Contrary to what usually happens with healthy travellers, risk assessment may lead travel medicine practitioners to advise against the travel, e.g. when a primary travel medicine intervention is absolutely contraindicated and the patient is at high risk of infection or when the clinical condition of the patient may worsen because of the travel. When travel is not contraindicated, we have to consider the possibility to avoid some interventions when risk assessment shows a low risk.

The impact of some immunizations on the underlying disease represents an area of concern, since both infections and vaccinations may trigger (or have been suspected to) neurological autoimmune diseases like MS and GBS. The events leading to autoimmune activation after an infection (or an immunization) are unknown, but three mechanisms might be involved. The first is antigen-specific and it is called molecular mimicry: since some viral and bacterial proteins are similar to human proteins (e.g. myelin), the immune response may also be directed to self antigens. The second mechanism is called bystander activation and occurs when an infection, through the death of host cells, may release previously sequestered self-antigens and subsequently allow the activation of self-reactive T and B cells that are normally quiescent. This activation may be mediated by the release of cytokines. The third mechanism is non-specific: protein of viral and bacterial origin may activate T or B cells in ways that are independent from the antigen specificity of the responding lymphocyte; this process can activate autoreactive lymphocytes. The development of autoantibodies is frequently observed in virus-infected animal models and in patients with viral infections.8 Nevertheless, only a minority of patients develops clinically important autoimmune manifestations, presumably reflecting an individual susceptibility due to genetic factors.4 Since infection may cause an autoimmune disease, it is theoretically possible that (under particular circumstances) immunization also might trigger a demyelinating disease: some vaccines could contain proteins similar to myelin (molecular mimicry) or produce a cytokine cascade resulting in activation of autoreactive T and B cells leading to an immune-mediate inflammatory demyelination.4,9 Furthermore, adjuvants are added to several vaccines to improve the immunogenicity, and someone could raise doubts about a possible role of such substances in the development of autoimmunity. Fortunately, at present only aluminum salts are widely used in vaccines, with more than a 75 year record of safety all over the world. A recent systematic review on adverse events after exposure to aluminum-containing vaccines against diphtheria, tetanus, and pertussis found no evidence that aluminum salts cause any serious or longlasting adverse events. On the contrary, on the basis of experimental models, it has hypothesized that recently developed oil adjuvants like squalene may induce autoantibodies: their capacity to enhance production of proinflammatory cytokines could stimulate antibody responses to foreign antigens and, under particular conditions, selfantigens also. Further investigation is needed on this type of adjuvant and on its possible role in promoting autoimmunity. At present, a squalene-containig adjuvant (i.e. MF59) is utilized in an influenza vaccine marketed in Europe only.



Franco Giovanetti. Travel Medicine and Infectious Disease (2007) 5, 7–17