Fatal rabies despite post-exposure prophylaxis

Deshmukh, Durgesh G.; Damle, Ajit; Jk, Bajaj; Bhakre, JB; Patil, N. K. Biradar

doi:10.4103/0255-0857.81786

Cited by 17 publications

(11 citation statements)

References 3 publications

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“…However, investigation into these cases shows that for the majority of patients there was an omission of at least one of the essential steps of PEP (wound treatment, administration of RIG and complete course of vaccine) [85][86][87][88][89]. Physicians should be advised that immediate and correct PEP management without delay according to official recommendations is essential for patient survival.…”

Section: Rabies Pep Failurementioning

confidence: 99%

30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience

Giesen

Gniel

Malerczyk

2015

Expert Review of Vaccines

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Section: Rabies Pep Failurementioning

confidence: 99%

30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience

Giesen

Gniel

Malerczyk

2015

Expert Review of Vaccines

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“…[In fact, this estimate is likely very low, because many human rabies cases occur in areas where incidence is underreported by up to 100-fold (2).] Because vaccine efficacy for postexposure prophylaxis is strictly time limited, millions more are at risk, even in areas with adequate health care resources (3). Upon onset of symptoms, the disease has a nearly 100% case fatality rate (4), making it arguably the most deadly viral disease of humans, and no effective small-molecule therapeutic has been found previously.…”

mentioning

confidence: 99%

Host–rabies virus protein–protein interactions as druggable antiviral targets

Lingappa¹,

Macieik³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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We present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. First, we conceptualized viral capsid assembly as occurring via a hostcatalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. This suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. Second, we hypothesized these host proteins to be components of heterogeneous, labile, and dynamic multi-subunit assembly machines, not easily isolated by specific target protein-focused methods. This suggested the need to identify active compounds before knowing the precise protein target. A cell-free translation-based small molecule screen was established to recreate the hypothesized interactions involving newly synthesized capsid proteins as host assembly machine substrates. Hits from the screen were validated by efficacy against infectious rabies virus in mammalian cell culture. Used as affinity ligands, advanced analogs were shown to bind a set of proteins that effectively reconstituted drug sensitivity in the cell-free screen and included a small but discrete subfraction of cellular ATP-binding cassette family E1 (ABCE1), a host protein previously found essential for HIV capsid formation. Taken together, these studies advance an alternate view of capsid formation (as a host-catalyzed biochemical pathway), a different paradigm for drug discovery (whole pathway screening without knowledge of the target), and suggest the existence of labile assembly machines that can be rendered accessible as next-generation drug targets by the means described.assembly intermediate | viral-host interaction | whole pathway screen | drug discovery paradigm | protein heterogeneity

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“…Patient 1 and 2 received no HRIG as part of their PEP. This is concerning, as rabies has been documented where HRIG has not been infiltrated into the wounds of exposed patients [24], [25]. Failure to access HRIG whilst overseas, particularly in developing countries, appears to be a common problem, even following severe hand or facial injuries [2], [26], [27].…”

Section: Discussionmentioning

confidence: 99%

Using Serology to Assist with Complicated Post-Exposure Prophylaxis for Rabies and Australian Bat Lyssavirus

et al. 2013

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BackgroundAustralia uses a protocol combining human rabies immunoglobulin (HRIG) and rabies vaccine for post-exposure prophylaxis (PEP) of rabies and Australian bat lyssavirus (ABLV), with the aim of achieving an antibody titre of ≥0.5 IU/ml, as per World Health Organization (WHO) guidelines, as soon as possible.Methodology/Principal FindingsWe present the course of PEP administration and serological testing for four men with complex requirements. Following dog bites in Thailand, two men (62 years old, 25 years old) received no HRIG and had delayed vaccine courses: 23 days between dose two and three, and 18 days between dose one and two, respectively. Both seroconverted following dose four. Another 62-year-old male, who was HIV-positive (normal CD4 count), also suffered a dog bite and had delayed care receiving IM rabies vaccine on days six and nine in Thailand. Back in Australia, he received three single and one double dose IM vaccines followed by another double dose of vaccine, delivered intradermally and subcutaneously, before seroconverting. A 23-year-old male with a history of allergies received simultaneous HRIG and vaccine following potential ABLV exposure, and developed rash, facial oedema and throat tingling, which was treated with a parenteral antihistamine and tapering dose of steroids. Serology showed he seroconverted following dose four.Conclusions/SignificanceThese cases show that PEP can be complicated by exposures in tourist settings where reliable prophylaxis may not be available, where treatment is delayed or deviates from World Health Organization recommendations. Due to the potentially short incubation time of rabies/ABLV, timely prophylaxis after a potential exposure is needed to ensure a prompt and adequate immune response, particularly in patients who are immune-suppressed or who have not received HRIG. Serology should be used to confirm an adequate response to PEP when treatment is delayed or where a concurrent immunosuppressing medical condition or therapy exists.

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Fatal rabies despite post-exposure prophylaxis

Cited by 17 publications

References 3 publications

30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience

30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience

Host–rabies virus protein–protein interactions as druggable antiviral targets

Using Serology to Assist with Complicated Post-Exposure Prophylaxis for Rabies and Australian Bat Lyssavirus

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