A ProMED-mail post
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International Society for Infectious Diseases

Date: Fri 6 Dec 2019
From: Paola De Benedictis <pdebenedictis@izsvenezie.it> [edited]

A 44-year-old man was admitted to a public hospital (ICU Bisceglie, Barletta-Andria-Trani province, Apulia region, Italy) on 8 Oct 2019 with a suspected rabies infection. At the time of admission, he presented acute respiratory distress. Due to his deteriorating clinical conditions, he was transferred to the ICU of a tertiary hospital (ICU Policlinico, Bari, Italy), where he died of rabies on 19 Nov 2019, after a hospital stay of 42 days. Antemortem laboratory diagnostic tests for rabies performed at the National and FAO Reference Centre for Rabies, IZSVe (Padova, Italy) confirmed the initial suspicion based on the patient's clinical history.

 44歳の男性が狂犬病感染を疑われ、2019年10月8日に公営の病院(ICU Bisceglie, Barletta-Andria-Trani province, Apulia region, Italy)に入院した。入院時、彼は急性の呼吸器障害だった。容体が悪化したため、tertiary hospital(ICU Policlinico, Bari, Italy)に転院したが、42日間の入院の後、2019年11月19日に狂犬病で死亡した。National and FAOReference Centre for Rabies(Padova, Italy)における死亡後の狂犬病診断では、患者の臨床歴から最初の疑いが浮上した。

The man had been bitten on his right hand by an aggressive dog on 8 Sep 2019 on the Island of Zanzibar (Tanzania). He immediately underwent post-exposure prophylaxis, which consisted of wound washing with an antiseptic solution (Betadine and hydrogen peroxide) and rabies vaccination in absence of rabies immunoglobulin administration.



However, the patient was immunocompromised due to a corticosteroid therapy prescribed to treat an autoimmune disease and, unfortunately, such an important anamnesis went unnoticed until the onset of the symptoms.


Despite the internationally coordinated efforts to achieve a global goal of zero human dog-mediated rabies deaths by 2030, rabies still reaps human victims. In most cases, appropriate post-exposure prophylaxis [PEP] can safely prevent the infection in humans. However, shortages in rabies immunoglobulin (RIG) still represent the main constraint for human death prevention. Pre-exposure prophylaxis (PrEP) makes administration of RIG unnecessary after a bite. In this particular case, PrEP and antibody titration of the victim before his travel might have saved his life. Of note, recent WHO recommendations reshape the PrEP protocol from 3 to 2 shots administered within one week (0-7). Moreover, we believe that enhanced awareness and information should be envisaged at different levels, and disseminated by travel health advisors, travel agents, and resorts or through official public health guidelines, similarly to those recommended by the United States Centers for Disease Control (CDC-ATL,<https://wwwnc.cdc.gov/travel/destinations/traveler/none/Tanzania>, paragraph "Keep away from animals" under "Stay Healthy and Safe").



Lidia Dalfino, MD, Bari hospital Sergio Carbonara, MD, Bisceglie hospital Paola De Benedictis, DVM, PhD, FAO RC, IZSVe

[Zanzibar island is a popular tourist destination in a semi-autonomous region of Tanzania, located off the eastern coast of Africa. Its government has undertaken, with the support of NGOs, great efforts to control and eradicate canine rabies since the earlier decade of the century. This was done mainly by annual rabies vaccinations, leading to a significant decline in the number of clinically confirmed canine rabies cases.




In 2015, the Zanzibar government felt close to officially declaring the island free from canine rabies but this goal was eventually not achieved. In October 2017, the Global Alliance for Rabies Control (GARC) informed that The local authorities were "working hard towards ensuring a 70% vaccination coverage across the entire island within next 2 months" and that Zanzibar "is very closeto being declared the 1st region in Africa to be free from rabies." (<https://rabiesalliance.org/news/towards-freedom-canine-mediated-rabies-zanzibar-island-wide-strategic-dog-vaccination>). This end, unfortunately, has not yet been reached, as tragicallydemonstrated by the case described above.

 2015年、ザンジバル自治政府は島内のイヌ狂犬病根絶の公式発表まであと1歩のところまで来ていると感じていたが、実際にはこの目標は達成されなかった。2017年10月、Global Alliance for Rabies Control (GARC)は、現地事務所が「2か月以内に、島全体におけるワクチン接種率70%達成を成し遂げるため全力を尽くす」とし、ザンジバル島が「アフリカにおいて最初の狂犬病清浄地域と宣言するまでもう少しである」という情報を発信した(上記URL参照)。結果としては、残念ながら前述した悲劇で示された通り、これはまだ達成されていない。

According to media reports, the victim, a businessman from the city of Andria in southern Italy, was visiting Kiwengwa beach, a resort area in the northeast of the island. "The family had arrived only a day earlier in Zanzibar and was on an excursion in the area when the animal attacked him. The animal was reportedly suffering from rabies and the wound was treated by local medics, which included it being disinfected at the local hospital."

 メディアの報道によると、この犠牲者はイタリア南部の都市アンドリアのビジネスマンであり、この島の北東部にあるリゾート地のKiwengwa beachを訪れていた。「家族は1日早くザンジバル島に到着しており、彼が襲われている時にはこの地域を周遊していた。この犬は狂犬病にかかっており、消毒を含む傷の治療は地域の診療所で行われていたようだ」

According to the report above, for which the authors, Drs De Benedictis, Dalfino, and Carbonara are gratefully acknowledged, PEP was applied in Zanzibar but did not include rabies immunoglobulin. The victim continued with his holiday before returning to Italy. "He showed no signs of ill health for 2 weeks after returning, but then towards the end of September (2019), he started to feel unwell.

 上記の報道では、(前述の記事の著者であるDe Benedictis、Dalfino、Carbonara医師らに敬意を表する)ザンジバル島でのPEPではRIGは投与されなかったとしている。犠牲者は残りの休暇を過ごしてイタリアへ帰った。「戻ってからも2週間は彼に病気の兆候は見られなかったが、(2019年の)9月末頃から不調を感じ始めていた。」


Speaking to a friend before he died, he said the symptoms had included high blood pressure and spasms." The friend told local media: "The rabies [pre-exposure] vaccination was not something he had because it was only recommended, and was not listed as compulsory. An absurdity. [He] was very unlucky." (<https://ananova.news/tourist-bitten-by-rabid-stray-dog-in-zanzibar-dies>.)


The US CDC website provides pre-travel vaccination advice to "all travelers", "most travelers", and "some travelers". Rabies is one of the 5 vaccines which "some travelers" to Tanzania should be vaccinated with "after consulting their doctors." It is recommended for the following groups:

- Travelers involved in outdoor and other activities (such as camping, hiking, biking, adventure travel, and caving) that put them at risk for animal bites;
- people who will be working with or around animals (such as veterinarians, wildlife professionals, and researchers);
- people who are taking long trips or moving to Tanzania;
- children, because they tend to play with animals, might not report bites, and are more likely to have animal bites on their head and neck. (<https://wwwnc.cdc.gov/travel/destinations/traveler/none/tanzania#vaccines-and-medicines>).







WHO's advice concerning pre-travel vaccination, for all destinations, fall in broad line with CDC's, while adding the following:


"Pre-exposure vaccination is also recommended for individuals travelling to isolated areas, or to areas where immediate access toappropriate medical care is limited, or to countries where modern rabies vaccines are in short supply and locally available rabiesvaccines might be unsafe and/or ineffective." (<https://www.who.int/ith/vaccines/rabies/en/>).


Should immunocompromised travelers apply PrEP? The availability of RIG at destination may influence such a decision. The advice of one's GP and/or travel medicine expert deserves to be sought in a timely fashion.


A report of previous cases of inadequate antibody response to rabies vaccine in an immunocompromised patient and a literature search revealing 15 additional immunocompromised patients, of whom 7 did not exhibit the minimum acceptable level of antibodies after a complete postexposure prophylaxis regimen, are available in ref 1 below.


1. Kopel E, Oren G, Sidi Y, David D. Inadequate antibody response to
rabies vaccine in immunocompromised patient. Emerg Infect Dis. 2012;
18(9): 1493-5;
- Mod.AS

HealthMap/ProMED-mail maps:
Apulia, Italy: <http://healthmap.org/promed/p/5918>
Kiwengwa Beach, Zanzibar North, Tanzania:

[See Also:
Rabies - Indonesia: (BA) monkey, human exp, susp
Rabies - Americas (11): USA, Canada, multiple animals, human exp
http://promedmail.org/post/20160528.4250423 [see item 2]
Rabies, equine, human exposure - USA (02): (TX), clarification
Rabies, post exposure prophylaxis (3)