Infections and solid organ transplant rejection a cause effect relationship

Invasive Mold Infections in Solid Organ Transplant Recipients

infections and solid organ transplant rejection a cause effect relationship

Infections and solid organ transplant rejection: a cause-and-effect relationship? reactivation with CMV-related disease in kidney and liver transplant recipients. de Sevilla, Seville, Spain. Infectious diseases after solid organ transplantation . In the European Liver. Transplant Registry, chronic rejection was the cause of. Infections and solid organ transplant rejection: a cause-and-effect .. of the relation between a virus infection and the occurrence of rejection;.

Organ procurement In most countries there is a shortage of suitable organs for transplantation. Countries often have formal systems in place to manage the process of determining who is an organ donor and in what order organ recipients receive available organs. UNOS does not handle donor cornea tissue; corneal donor tissue is usually handled by various eye banks.

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Individual regional organ procurement organizations OPOsall members of the OPTN, are responsible for the identification of suitable donors and collection of the donated organs.

UNOS then allocates organs based on the method considered most fair by the scientific leadership in the field. The allocation methodology varies somewhat by organ, and changes periodically. For example, liver allocation is based partially on MELD score Model of End-Stage Liver Diseasean empirical score based on lab values indicative of the sickness of the person from liver disease.

The Scientific Registry of Transplant Recipients was also established to conduct ongoing studies into the evaluation and clinical status of organ transplants. An example of "line jumping" occurred in at Duke University as doctors attempt to recover from a clear mistake.

An American teenager received a heart-lung donation with the wrong blood type for her.

Infections and solid organ transplant rejection: a cause-and-effect relationship?

She then received a second transplant even though she was then in such poor physical shape that she normally would not be considered a good candidate for a transplant. He stated, "Conventionally we would say if people's life expectancy was a year or less we would consider them a candidate for a heart transplant. But we also have to manage expectations. If we know that in an average year we will do 30 heart transplants, there is no point putting 60 people on our waiting list, because we know half of them will die and it's not right to give them false hope.

If medically suitable, the allocation system is subverted, and the organ is given to that person. In the United States, there are various lengths of waiting times due to the different availabilities of organs in different UNOS regions. In other countries such as the UK, only medical factors and the position on the waiting list can affect who receives the organ. One of the more publicized cases of this type was the Chester and Patti Szuber transplant. This was the first time that a parent had received a heart donated by one of their own children.

Although the decision to accept the heart from his recently killed child was not an easy decision, the Szuber family agreed that giving Patti's heart to her father would have been something that she would have wanted. Reasons for donation and ethical issues[ edit ] Living related donors[ edit ] Living related donors donate to family members or friends in whom they have an emotional investment. The risk of surgery is offset by the psychological benefit of not losing someone related to them, or not seeing them suffer the ill effects of waiting on a list.

Paired exchange[ edit ] Diagram of an exchange between otherwise incompatible pairs A "paired-exchange" is a technique of matching willing living donors to compatible recipients using serotyping. For example, a spouse may be willing to donate a kidney to their partner but cannot since there is not a biological match.

infections and solid organ transplant rejection a cause effect relationship

The willing spouse's kidney is donated to a matching recipient who also has an incompatible but willing spouse. The second donor must match the first recipient to complete the pair exchange. Typically the surgeries are scheduled simultaneously in case one of the donors decides to back out and the couples are kept anonymous from each other until after the transplant. Paired exchange programs were popularized in the New England Journal of Medicine article "Ethics of a paired-kidney-exchange program" in by L.

Rapport [35] in as part of his initial proposals for live-donor transplants "The case for a living emotionally related international kidney donor exchange registry" in Transplant Proceedings. Good Samaritan[ edit ] Good Samaritan or "altruistic" donation is giving a donation to someone not well-known to the donor.

Some people choose to do this out of a need to donate. Some donate to the next person on the list; others use some method of choosing a recipient based on criteria important to them. Web sites are being developed that facilitate such donation. It has been featured in recent television journalism that over half of the members of the Jesus Christiansan Australian religious group, have donated kidneys in such a fashion.

infections and solid organ transplant rejection a cause effect relationship

Organ theft and Organ trade Now monetary compensation for organ donors is being legalized in Australia, and strictly only in the case of kidney transplant in the case of Singapore minimal reimbursement is offered in the case of other forms of organ harvesting by Singapore. Transplantation Outcomes Prior totreatment for HIV infection largely failed to extend life expectancy, and very few centers attempted solid-organ transplantation in HIV-infected individuals.

Data from the early years of the epidemic are limited to case reports and small case series, but in general, mortality was high, particularly in those with unrecognized HIV infection at the time of transplantation, and HIV-infected patients experienced significantly higher 5-year mortality and rates of graft loss relative to HIV-uninfected individuals.

Data from larger studies document acceptable patient and graft survival rates for liver transplants and survival rates for kidney transplants that approximate those seen in HIV-negative recipients Table 1.

Studies to date do not suggest that transplant-associated immunosuppression results in increased incidence of or mortality from HIV-associated OIs. Coinfection with hepatitis C virus HCV has been associated with poorer survival in liver transplant recipients, compared with HCV-monoinfected recipients.

infections and solid organ transplant rejection a cause effect relationship

Kidney graft survival was Initial use of thymoglobulin to induce immunosuppression, HCV coinfection, and older age decreased survival in kidney recipients.

Among liver transplant recipients in the HIVTR study, 3-year survival was lower than among kidney transplant recipients at Receiving a dual-organ transplant, lower pretransplant body mass index BMIolder age, and HCV coinfection were associated with decreased survival.

Kidney transplantation, on the other hand, did not confer a survival benefit. Infectious Complications The infectious complications of posttransplantation immunosuppression overlap broadly with the array of OIs seen in advanced HIV disease. In the HIVTR cohort, there were only 4 cases of cutaneous Kaposi sarcoma, 2 cases of Pneumocystis jiroveci pneumonia PCP1 case of cryptosporidiosis, and 6 esophageal or bronchial Candida infections, and a history of OIs was not associated with recurrence or survival differences after transplantation.

Serious infections were more common in liver and kidney recipients with HCV coinfection, in kidney recipients who received thymoglobulin, and in liver recipients of Caucasian ethnicity. Nadir CD4 was predictive of infection risk in kidney recipients, and higher current CD4 was protective in liver recipients.

Risk of Cancer after Transplantation Experience to date suggests that the incidence of malignancy after solid-organ transplantation in the HIV-infected population may not be significantly different than that seen in HIV-uninfected patients.

There were 3 cancer-related deaths in the kidney transplantation group. Twelve of the patients undergoing liver transplantation developed 14 malignancies at a median follow-up of 2. All de novo Kaposi sarcoma lesions in the HIVTR study were cutaneous, and all were treated successfully with the addition of rapamycin to the immunosuppressive regimen.

Rapamycin has well-documented therapeutic effects on Kaposi sarcoma. In 89 patients followed prospectively with anal cytology, there was increased risk of developing high-grade squamous intraepithelial lesions HSILs after transplantation, which was not influenced by the type of transplanted organ kidney vs liver or by the use of T-cell-depleting agents.

Similarly, Vibert et al reported on 16 HIV-infected patients undergoing liver transplantation for HCC and found no significant difference in overall survival or recurrence-free survival compared with 58 HIV-uninfected patients with HCC from the same time period.

HCC recurrence has been seen in 2 patients at a median follow-up of 34 months. The majority of these patients were maintained on calcineurin inhibitor-based immunosuppressive regimens; the possible significance of this is under study. European centers generally have adopted similar criteria. The CD4 percentage may be a better indicator of immune function than the absolute CD4 cell count in patients who are undergoing interferon-based treatment for HCV infection, as well as in those with portal hypertension.

Inability to achieve complete viral suppression prior to liver transplantation has been associated with elevated mortality. In patients who maintain undetectable viral load in the absence of ART "elite suppressors"the safety of undertaking organ transplantation and subsequent immunosuppression in the absence of ART is not known.

There is evidence from cohort studies that chronic immune activation and inflammation persists in these individuals despite undetectable viremia, and they should not be considered immunologically equivalent to persons without HIV infection, or to those who are immunosuppressed on ART. At this time, the most prudent approach with these "elite suppressors" is to initiate fully suppressive ART before transplantation. Patients with a history of opportunistic diseases or neoplasms for which current treatments are suboptimal eg, progressive multifocal leukoencephalopathy, chronic cryptosporidiosis, and primary central nervous system lymphoma usually are excluded from transplantation.

Individuals with a history of resolved cutaneous Kaposi sarcoma can be offered transplantation.

Infections and solid organ transplant rejection: a cause-and-effect relationship? - Dimensions

Pretransplant Vaccinations Prior to transplantation, all nonimmune individuals should be immunized against hepatitis A and B viruses. Pneumococcal vaccine should be administered to any individual who has not been vaccinated in the prior 5 years, and inactivated influenza vaccine should be administered as seasonally appropriate. Careful attention should be given to assessment of tuberculosis risk, which should include history of possible exposure eg, imprisonment, residence in homeless shelters, institutionalization, country of origin, and travel destinations as well as chest radiograph and either skin testing or interferon-gamma release assay.

Exposed patients should be treated appropriately. Another retrospective review of renal transplant candidates identified factors associated with failure to be listed for transplant.

The most common reasons for not listing the HIV-infected candidates were lack of CD4 or viral load data at evaluation, CD4 and HIV viral load levels not meeting eligibility criteria, and illicit drug use. At this time, the use of organs from HIV-infected donors for HIV-infected recipients is not being considered outside resource-limited settings in which the prevalence of HIV in the general population is high enough to effectively limit the donor pool and access to organ transplantation for HIV-infected patients is restricted.

Organ transplantation

Limited data suggest this approach may be successful. A recent analysis utilizing 2 national databases in the United States estimated that deceased HIV-infected patients constitute potential donors per year for HIV-infected transplant candidates. Concerns have been raised about the risk of transmission of a second strain of HIV or drug-resistant HIV from donor to recipient with this strategy, but the actual risk is unknown. Transplantation of organs from HIV-infected donors should be carried out only in a research setting.

Perioperative Management HIV infection is associated with an increased risk of venous thromboembolism that is associated with increased rates of protein C and S deficiency, the presence of anticardiolipin antibodies, low nadir CD4, CMV viremia, elevated D-dimers pre-thrombosis, and several markers of immune activation.

infections and solid organ transplant rejection a cause effect relationship

Posttransplant Management Antiretroviral Therapy After transplant, continuous treatment with both antiretroviral and immunosuppressive medications is required to control HIV infection and to prevent graft rejection.

Posttransplant management is complicated by multiple and reciprocal drug interactions between antiretroviral and immunosuppressive medications.

Changes of antiretroviral medications or interruption of ART can alter serum levels of immunosuppressants significantly and can precipitate organ rejection.

For more on interactions between antiretroviral and immunosuppressive medications, see Choice of Immunosuppressive Regimenbelow.

Coadministration of antiretroviral and immunosuppressive agents also may cause increased or overlapping treatment toxicities. Other agents commonly used after transplantation may require adjustments in ART. Examples of special considerations are shown in Table 3.