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The World Rabies Day

Anger: red in the high-risk areas, and in orange those at intermediate risk (Source: WHO, 2009)

size of the problem

The anger in the world kills one person every ten minutes, more than 50,000 deaths annually, mostly concentrated in Africa and Asia. In India alone about 30,000 deaths a year. To raise awareness populations and governments towards this silent massacre, for some years was established World Rabies Day: This year the event is September 28. E 'need for a broad international effort to achieve the elimination of animal rabies and, therefore, than that of humans. It is therefore a demanding action on public health and veterinary health.

Risk in the traveler

As operators of Travel Medicine, we must focus our attention on the risk of rabies in the individual traveler. It is estimated that each month from 2 to 4 travelers to endemic areas in 1000 receive a bite of mammals: in most cases they are at risk of exposure to rabies, almost invariably fatal.

The risk of rabies for a traveler in an endemic area is higher if the stay is prolonged (greater than or equal to 30 days), if you engage in certain activities (cycling, hiking, exploring caves), if you visit rural areas or areas inhabited by stray dogs, if the accommodation is insecure (eg. sleeping in tents or on mats placed in open space) or if there is an exhibition of professional (veterinarians, zoologists). The exposed person may underestimate the risk, as is the case in relation injuries from the bite of a bat, typically mild.

Children are particularly at risk: they tend to spontaneously get close to animals and also when they are small they can not detail the circumstances of the assault. In addition to animal bite injuries in children are usually more severe.

What happens if the traveler is not exposed vaccinated?

The unvaccinated traveler, as you know, in case of animal bite or other exposure to rabies risk and should receive the rabies immunoglobulin (RIG, Rabies Immune Globulins) is a series of 4 doses of vaccine at regular intervals. If the traveler has previously received a series of 3 doses of vaccine (pre-exposure prophylaxis) will only receive two additional doses of vaccine without RIG. The problem is that in developing countries access to a full and proper post-exposure prophylaxis is not always guaranteed, in particular, the RIG are often not available, so the hypothesis that the traveler remains exposed without treatment does not appear remote.

Vaccination against rabies in Italy

Modern rabies vaccines produced from cell cultures are very effective and extremely sure, but my impression is that in Italy are under-used. Travelers at risk are informed about the availability of the vaccine and the risk of failure to pre-exposure prophylaxis? Not necessarily, because of this issue, speaks very little during the training. In contrast, compared with foreign colleagues, especially northern Europeans and Americans, I noticed the attention they devote to the anger in the counseling of the traveler.

probably weigh negatively on the rabies vaccination reminder of the adverse reactions that occurred in the past following the administration of rabies vaccines derived from brain tissue mice and that were closely related to that particular medium. But such an attitude today is no longer a scientific basis, being merely a prejudice.

Main few references:

Wunner WH, Briggs DJ. Rabies in the 21 st Century. PLoS Neglected Tropical Diseases 2010 4 (3): e591. doi: 10.1371/journal.pntd.0000591

The full text of Article PLoS Neglected Tropical Diseases

Gautret P, Schwartz E, Shaw M et al. Animal-Associated Among related diseases and injuries returned travelers: a review of the GeoSentinel Surveillance Network. Vaccine 2007, 25:2656-63 doi: 10.1016/j.vaccine.2006.12.034

The site of the World Rabies Day: http://www.worldrabiesday.org

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TUESDAY 'September 28 17:00
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Japanese Encephalitis: how to identify travelers at risk?

Geographic Japanese encephalitis: the risk areas are marked by darker shades of color. Click on the map if you want to enlarge it.

Image taken from Fischer M et al. MMWR 2010 Vol.59/RR-1

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5901a1.htm

The recent marketing of new vaccine ' Japanese encephalitis from Vero cells (Vero Cell Culture-Derived JE Vaccine, JE-VC, strain SA14-14-2) I brought to mind a case report described three years ago by Peter Caramel and his group.

May 2007: a traveler just returned from Vietnam 49 years was admitted to the Hospital Amedeo di Savoia in Turin with a clinical picture characterized by high fever (39.5 ° C), disorientation, meningitis and other neurological signs. The EEG was pathological and magnetic resonance imaging documents the presence of lesions of the lentiform nucleus, right and left portion of the thalamus. Serology confirms an active infection by Japanese encephalitis virus (JEV, Japanese encephalitis virus). After treatment with intravenous immunoglobulin symptoms regressed and the patient was discharged, one month after discharge the patient appeared in good condition, except for a slight deficit of short-term memory.

What areas of Vietnam had been visited by the patient and for how long?

The patient between April 25 and May 16 had made a tour that included Ho Chi Minh, Hanoi, Halong Bay, Haipong, Mai Son, Dien Bien Phu, Sapa. Included a part of the rural areas and natural parks in the north. The arrangement had always been at the hotel. The patient had not received insect bites.

The patient had not been vaccinated: time the only vaccine against Japanese encephalitis was inactivated type, obtained from brain tissue of mice. However, the vaccine was not available in Italy, except in an ASL of Rome, and elsewhere in Europe was little used. Allergic reactions, mainly urticaria and angioedema, but sometimes severe reactions were reported with some frequency (a total of 180 to 640 casi/100.000 doses) and are 12-72 hours after administration, but sometimes after a few days. In addition, although very rarely, had been reported to ADEM (acute disseminated encephalomyelitis) temporally associated with the vaccine, it is a vaccine made from brain tissue, a possible causal relationship is biologically plausible ADEM, although the residual content of myelin in the final product was very low (\u0026lt;2 ng / ml).

It was therefore a vaccine with a safety profile is not optimal and that put limits to its acceptability among both health professionals and the public.

If a patient with the same itinerary of the case described by Pietro Caramello is today a center of Travel Medicine, health professionals should make it informed of the opportunity to get vaccinated?

I would say so. The vaccine is recommended for travelers to rural areas of endemic areas, particularly if they are permitted activities that include a prolonged outdoor exposure. The vaccine is also recommended for long stays (> 1 month) in endemic areas, irrespective of the route.

What is the risk of Japanese encephalitis in the traveler? What are the possible consequences of the disease?

The risk estimates found in literature are not uniform, either because they were drawn from heterogeneous populations and because the degree of risk varies according to region and, in some areas, even the season.

As for all the travelers who go to Asia, the risk appears very low (1 case / 1 million) are very different estimates for those who go to rural areas during the transmission period, I found estimates 1/5000/mese and even 1 / 5000 passengers per week. A recent review (GD Burchard et al. J Travel Med 2009, 16:204-216) reported on the basis of the interpolation attack rates observed during some epidemics, an estimate of 1/10.000/mese.

Danger areas are characterized by the simultaneous presence of the vector (Culex mosquitoes) and reservoir animals (pigs, water birds): mosquitoes, especially in many environments, you naturally want the intervention of ' man (growing rice), the abundance of water, keep circulating the virus in the animal reservoir, and occasionally can infect the human population.

The carrier stings usually outdoors (but it is also documented its activities in indoor environments) from the late afternoon and from dusk until dawn anyway. The rate of Culex mosquitoes infected with the virus is low (not more than 3%) and human cases with symptoms and signs of encephalitis are \u0026lt;1% of JEV infection.

Although this is an uncommon disease in traveler, give cause for concern is the high case fatality (20-30% of symptomatic cases) and the possibility of sequelae: 30-50% of patients have CNS sequelae even after years of illness.

what time of year is the transmission of the virus?

depends on latitude. In temperate areas of Asia the activity of JEV has a peak between May and December. In some tropical areas the transmission increases at the monsoon or rainy season, which have a distinctive pattern for each zone: for example, in South India the monsoon comes in different periods in the east coast and in the west, so also the same latitude as the period of risk of transmission of JEV is different. It follows that the health professional should know about, at least in broad terms, the climatic situation of each country to assess the risk depending on the itinerary of the traveler.

The new inactivated vaccine derived from Vero cells is effective and safe?

Effectiveness: the vaccine has been registered on the basis of serological correlate of protection as defined by WHO as the title neutralizing Ac > = 1:10. In clinical studies, seroconversion was observed in 96% of subjects at a distance of 56 days after the first dose. The cycle is two doses separated by an interval of 28 days. A booster dose is recommended at a distance of 12-24 months after the primary, before the potential new exposure to the virus.

Once you know the serological correlate of protection against a particular pathogen, the registration of a new vaccine can be demonstrated when, following vaccination, antibody response at or above the level considered protective. Of course, it is now necessary studies to know the effectiveness of the vaccine in the field (under field conditions).

Security: in clinical trials before registration of the vaccine have been reported headache (20%), myalgia (13%) and, more rarely, other systemic reactions (including asthenia and flu-like symptoms) or local (pain, edema, erythema) usually mild. These studies, of course, have been conducted on a restricted population, it requires careful post-marketing surveillance to detect rare and severe reactions.

When the vaccine is not is recommended in children and adolescents because they are not yet available data on safety and effectiveness in these age groups.

to write this post I used the following sources:

Caramello P, Canta F, Balbo R, F Lipani, Ariaudo S, De Agostini M, Calleri G, L Bogle, A. Di Caro A Case of Imported JE Acquired During Short Travel in Vietnam. Are Current Recommendations About Vaccination Broader? Journal of Travel Medicine 2007, 14:346-348

DOI: 10.1111/j.1708-8305.2007.00140.x

GD Burchard et al. Expert opinion on vaccination of travellers against Japanese Encephalitis. Journal of Travel Medicine 2009;16:204-216

DOI: 10.1111/j.1708-8305.2009.00330.x

M Fischer et al. Japanese Encephalitis Vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2010 Vol.59/RR-1 

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5901a1.htm

Ixiaro. Riassunto delle product characteristics. http://www.ema.europa.eu/docs/it_IT/document_library/EPAR_-_Product_Information/human/000963/WC500037287.pdf

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Kenya and Tanzania: Yellow fever vaccination is required for the traveler?

Until 2001 it was believed that the vaccine against yellow fever (FG) was extremely safe. This belief was changed by the discovery of a severe complication observed, albeit rarely, in some people vaccinated for the first time.

viscerotropic disease is associated with yellow fever vaccine (YEL-AVD, Yellow Fever Vaccine-Associated Disease Viscerotropic), similar to the disease caused from wild-type virus and burdened by a fatality of 60%. This complication is determined by the 17D vaccine virus, which is affected in subjects devoid of mutations able to determine their virulence, so that the research is directed towards any risk factors present in vaccinated individuals.

two have been identified: the presence of a disease that involves the thymus (eg. Myasthenia gravis, or a previous thymectomy) and age over 60 years (probably due to involution of the thymus that manifests itself in old age). The incidence of the disease viscerotropic is estimated at 1 in 200,000 to 400,000 vaccinated, but if we consider only the sixties, this rises to 1 in 50,000.

These data would suggest caution in recommending a particular vaccination FG, since only the real people at risk should be vaccinated. In my previous post I explained the situation of yellow fever in Africa, pointing to a different epidemiological situation in eastern Africa than the western portion of the continent. In particular, the two nations, half of an intense flow of Western tourists, they can create problems in the counseling prevaccinale long as there have been no cases of yellow fever, although classified as risk areas: the Kenya and Tanzania.

The International Health Regulations considers Kenya and Tanzania, countries at risk of virus transmission FG, as the primary vector and host (non-human primates) are present. The WHO and CDC recommend vaccination FG to all visitors on the grounds that the transmission of the virus may occur, so all travelers should be protected. As a result of that position, many Western travelers are vaccinated against FG.

Ron Behrens An article published in 2008 in the Journal of Travel Medicine about his Kenya, the title is very explicit: "Yellow fever recommendations for tourists to Kenya: a flawed risk assessment? "or" anti-yellow fever vaccination for travelers in Kenya: a distortion in the risk assessment? ".

Author considerations can be summarized as follows:

- before 1992 and since 1997 have not been reports of FG in Kenya. An outbreak occurred near Baringo between 1992 and 1993 produced a total of 72 cases;

- strengthening of the surveillance in 2004 did not identify the presence of virus circulation. Although the current surveillance of arbovirus infections has proved effective in identifying outbreaks like that which occurred recently, Rift Valley Fever and therefore should also immediately identify any cases of FG;

- although Kenya has introduced universal vaccination against FG in children after the epidemic of 1992, it is difficult Vaccine coverage has exceeded 50%. Therefore, the absence of cases is not the result of high vaccination coverage so as to prevent the circulation of the virus in the population;

- recommendations for travelers should be balanced taking into account the recent reports of serious adverse events associated with vaccination, especially in elderly patients (> 60 years) vaccinated for the first time;

- Kenya is visited each year by 1.54 million people, out of 3 Britons who travel to Kenya, one is aged over 55 years. Based on these data, the current vaccination policy of the GF is capable of producing 10 to 13 serious adverse events or fatalities each year. This incidence was much higher than the risk of disease is calculated on a historical basis, is the potential risk of a possible epidemic in Kenya will involve a traveler.

In response to the article by Ron Behrens, the Journal of Travel Medicine has published a letter from Thomas Monath and others, in which some facts are emphasized:

- Kenya is bordered by Uganda, Sudan and Ethiopia, where the FG is endemic, with recurrent outbreaks;

- Rift Valley Fever virus causes disease in cattle, where monitoring is easier, while the animal reservoir of yellow fever (non-human primates) is not subject to surveillance in Kenya

- the monitoring of FG in the human population in Kenya is passive, so that the less severe forms or sporadic cases could not be detected;

- the ecological situation in which FG is the transmission of the virus has not changed over time.

For these reasons Monath et al. believe that the traveler in Kenya is to be considered at risk, especially if prolonged outdoor activities (resulting in exposure to vector Aedes) in the northern and western part of Kenya.

In its reply to the letter of Monath et al., Behrens considers that the present position of the WHO does not seem to take into account the peculiarities of the individual traveler and urges (or, shall I say, challenge) its partners to produce an estimate on where (and when) the risk of yellow fever in Kenya exceeds the risk of serious adverse events post-vaccination.

In my view, similar considerations for or against a particularly prudent approach towards vaccination, could be made in Tanzania, where there are no reported human cases for decades.

What is the risk of yellow fever in unvaccinated travelers?

We must consider two situations: the epidemic and the ongoing inter-epidemic period (silent, with no notification of cases of disease but with possible viral circulation).

The estimated risk for a stay of two weeks in an area with epidemic act is 1 in 267 (1 death on 1333).

A two-week stay in an area with possible transmission of the virus but without ongoing epidemic poses a risk of 1 in 1000 travelers per month (1 death per month in 5000).

So, for a typical stay of two weeks, the figure is 1 in 2000 travelers (1 death in 10000). You can compare these data with the incidence of disease in vaccinated viscerotropic.

Behrens are right or they are right Monath and colleagues?

Wanting groped to answer this question, first we must not forget that the traveler is able to reduce the risk of yellow fever simply by applying, with due care, the measures antivettoriali. We therefore need to spend some 'time For information on these instructions on how to be applied and which products to use. But it's worth it, because - in addition to being essential to combat malaria - such precautions are necessary to guard against diseases such as dengue fever, to which there are currently no other means of prevention.

Second, we must carefully assess the risk based on the itinerary, length of stay in endemic areas considered and the type of activities that increase the risk (eg. Prolonged stay outdoors, especially in forest areas, or villages that are located on the edge of the jungle).

Last but not least, the age and health of the traveler assume paramount importance in our evaluation.

The decision is taken with the traveler, informing them on risks of the vaccine and the risks of non-immunization. In situations where vaccination FG is required under the International Health Regulations there is no choice and a possible exemption for medical reasons can only be true if there is a contraindication to vaccination.

A budget risks and benefits is very simple (and it is clearly in favor of vaccination) when the destination of the trip is an area where the virus circulation is ongoing, as large areas of South America or Africa, while it may be problematic for countries such as Kenya and Tanzania, for the reasons set out just now. And here comes our ability to provide effective counseling in order to reach a joint decision and a conscious choice by the patient.

Personally (just my opinion but it is an operator on the field) I feel more in tune with the position of Ron Behrens.

to write this post, I used the following literature sources:


Ron Behrens. Yellow fever recommendations for tourists to Kenya: a flawed risk assessment? Journal of Travel Medicine 2008;5:285-286.
DOI: 10.1111/j.1708-8305.2008.00225.x

Thomas P. Monath, Mark Gershman, David R. Hill, Nina Marano, J. Erin Staples, Annelies Wilder-Smith. Yellow Fever Recommendations for Tourists to Kenya: A Flawed Risk Assessment. Journal of Travel Medicine 2009;16:146.
DOI: 10.1111/j.1708-8305.2008.00295_1.x

Ron Behrens. Reply. Journal of Travel Medicine 2009;16:146-147.
DOI: 10.1111/j.1708-8305.2008.00295_2.x

TP Monath, MS Cetro, DE Teuwen. Yellow fever vaccine. In: S. Plotkin, W. Orenstein, P. Offit. Vaccines. Fifth Edition. Saunders Elsevier 2008
ISBN 978-1-4160-3611-1.

Monath TP. Dengue and Yellow Fever-Challenges for the Development and Use of Vaccines. NEJM 2007, 357:2222-25.
DOI: 10.1056/NEJMp0707161