Saturday, September 16, 2017

Allograft-Transmissible Infections

Diseases can be passed from person to person via transplants. How do we prevent this? Read on...

Transmissibility of infectious agents

For a pathogen to be transmitted via allograft, it must give rise to asymptomatic infection in the donor (symptomatic donors are generally excluded from the get-go), be present in the allograft, and survive storage and processing of the allograft. Bacteria (e.g. T. pallidum and M. tuberculosis), viruses (e.g. Hep B and HIV), protozoa (e.g. malaria and toxoplasma), and prions (e.g. Creutzfeldt-Jakob Disease) can be transmitted via allografts.

Allograft contamination

Allografts can be contaminated when in situ or during processing. An example of in situ contamination is Clostridium sordelli sepsis. During the dying process, gut microorganisms can pass through the intestinal wall. Hypoxic cadaveric tissue "selects" for anaerobes (such as C. sordelli), which sporulate as nutrient levels decrease. Spores are very hardy, so they may survive allograft processing. Thankfully, in situ contamination is quite rare and has not been reported in Australia. Exogenous contamination occurs when an allograft is contaminated during processing. The most common organisms in exogenous contamination are Staphylococcus species.

Preventing transmission

There are several ways in which we can try and prevent transmission of an allograft-transmissible infection. For starters, we can implement stringent donor selection criteria. If someone has been exposed to an infectious disease (e.g. by going to a country where an outbreak has occurred), they may be deferred for the length of the incubation period. Certain high-risk behaviours may also require a deferral or exclude the donor entirely. The grafts themselves may also be screened for certain diseases, such as syphilis and Hep B. There is a small chance that such screening may come up with false negatives, due to a testing "window period" (the time between infection and first detection of the pathogen), but this is a very low chance. Nucleic acid testing (NAT) reduces the length of the window period and thus reduces the risk of false negatives, but it is quite expensive and may not be worth it in some cases. (Also, waiting for a NAT result may compromise the viability of the organ.)

Using aseptic technique is also important. Processing of grafts is done in a "cleanroom," as mentioned here. Processed grafts can also be sent off for microbiological culturing for screening purposes. In the case of living donors, milled bone can be washed in saline before being sent for microbiological culturing. For cadaveric donors, the allograft is washed in sterile water (and the water is sent off for culturing), and membrane filtration is applied. Also, with cadaveric donors, time is important: the body must have been refrigerated within 12 hours after death, and tissue retrieval must occur within 24 hours after death.

Monitoring for post-transplant infections is critical not just for the infected patient, but also for the purposes of keeping our graft supply safe. Emerging infections, such as the Zika virus, need to be assessed for the possibility of transmission via allograft.

This is kind of unrelated, but there were two slides on Zika virus, so I guess I'll expand on it here. Zika was originally discovered in a rhesus monkey in Zika forest in Uganda. It is transmitted by certain mosquitoes, but can also be transmitted via sex or transfusions. During the 2007 outbreak in Micronesia, it was generally mild, with short-lived symptoms. However, during the more recent 2015 Brazil outbreak, the virus was associated with microcephaly and Guillain-Barré Syndrome. The RNA of Zika virus is detectable in urine, blood and semen.

Risk of infection

One way to quantitate the risk of a certain infection is to multiply the incidence rate (rate of newly acquired infections) by the duration of the window period. Risk can be communicated to patients by using the Calman scale, which compares numbers like "1 in 100 000" to something that might be more easily understood, such as "probability of death from a train accident."

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