ABSTRACT.
Pretransplant recommendations advise risk-based screening for strongyloidiasis, schistosomiasis, and Chagas disease. We evaluated the implementation of a chronic parasite screening protocol at a health system in a nonendemic region serving a large foreign-born population. Candidates listed for kidney transplant at Hennepin Healthcare (Minneapolis, MN) between 2010 and 2020 were included. Country of birth and serologic screening for strongyloidiasis, schistosomiasis, and Chagas disease were retrospectively obtained from electronic medical records. Parasite screening frequency and seropositivity was assessed before and after implementation of a geographic risk factor–based screening protocol in 2014. Cost-efficiency of presumptive treatment was modeled. Of 907 kidney transplant candidates, 312 (34%) were born in the United States and 232 (26%) outside the United States, with the remainder missing country of birth information. The 447 (49%) candidates evaluated after implementation of the screening protocol had fewer unidentified countries of birth (53%–27%, P < 0.001) and were more frequently screened for strongyloidiasis, schistosomiasis, and Chagas disease (14%–44%, 8%–22%, and 1–14%, respectively, all Ps < 0.001). The number of identified seropositive candidates increased after protocol implementation from two to 14 for strongyloidiasis and from one to 11 for schistosomiasis, with none seropositive for Chagas disease. The cost-efficiency model favored presumptive ivermectin when strongyloidiasis prevalence reaches 30% of those screened. Implementing a geographic risk screening protocol before kidney transplant increases attention to infectious disease risk associated with country of birth and identification of chronic parasitic infections. In populations with higher strongyloidiasis prevalence or lower ivermectin costs, presumptive treatment may be cost-efficient.
INTRODUCTION
Parasitic infections in kidney transplant recipients cause significant morbidity and mortality.1 In the United States, where travel and migration facilitate exposure to nonendemic parasites, there is increasing awareness of the need to consider parasitic infections during the transplant process.2 Importantly, there are three parasitic diseases—strongyloidiasis, schistosomiasis, and Chagas disease—that cause chronic and frequently asymptomatic infections and may reactivate in the setting of transplant-related immunosuppression.
Of these, morbidity and mortality associated with severe strongyloidiasis is most widely recognized, with reported 30-day mortality in kidney transplant recipients approaching 30%.3 Strongyloidiasis, which is a caused by the nematode Strongyloides stercoralis, is endemic in tropical areas, with a global prevalence that reaches 100 million.4 Of particular concern after kidney transplantation is risk for severe disease—hyperinfection syndrome and disseminated strongyloidiasis—which can occur when exposure to steroids or other immunosuppressants triggers increased reproduction and nematode migration throughout the body of an individual with chronic strongyloidiasis. This results in life-threatening respiratory and gastrointestinal disease that can be complicated by bacteremia and septic shock.2
Schistosomiasis, another chronic parasitic infection, is caused by five species of the trematode Schistosoma that are also endemic in tropical areas. The clinical impact of posttransplant schistosomiasis is less clear, with limited studies suggesting a possible association with urologic complications but not death, rejection, or graft loss.5–7 Finally, Chagas disease, caused by the protozoa Trypanosoma cruzi and endemic in Latin America, with rare reports of autochthonous transmission in the United States,8 has implications for transplant candidates. Reactivation of Chagas disease is estimated to be 8% to 22% after kidney transplantation and can involve the skin, heart, or central nervous system.9 Although there is a greater understanding of the role for Chagas disease screening and monitoring in heart transplant recipients due to a higher risk of reactivation, there is increasing evidence for similar approaches in other solid organ transplants as well.9,10
In the United States, endemic parasitic infections are uncommon, although Strongyloides is present in the southeastern United States and evidence suggests strongyloidiasis-related deaths may be more common in the United States than previously approximated.11 In single-center experiences, the prevalence of Strongyloides seropositivity in solid organ transplant candidates ranged from 4% in Louisiana and Florida to nearly 10% in Houston, Texas,12–15 without a clear association to certain demographic characteristics or risk factors.15,16 There is minimal published information about imported schistosomiasis or Chagas disease prevalence among U.S. kidney transplant candidates. Current guidelines recommend using epidemiologic risk factors to guide screening for strongyloidiasis, schistosomiasis, and Chagas disease before transplant.2,9,17
In Hennepin County, Minnesota, nearly 14% of 1.3 million residents are foreign-born,18 often having migrated to Minnesota from Asia, Africa, and Latin America.19 Given this, the Kidney Transplant Program at Hennepin Healthcare, the county safety-net hospital, is well poised to assess the use of geographic screening for parasitic infections in a nonendemic state. We retrospectively reviewed renal transplant evaluations over 10 years to assess strongyloidiasis, schistosomiasis, and Chagas disease screening frequency and seropositivity before and after implementation of a targeted screening protocol at a healthcare system that serves a large proportion of foreign-born patients.
METHODS
This retrospective cohort study included renal transplant candidates who were listed for transplant at Hennepin Healthcare (Minneapolis, MN) between January 1, 2010, and October 15, 2020. Hennepin Healthcare is a large safety-net health system that serves the greater Minneapolis area in Minnesota and includes a 484-bed academic medical center and large network of downtown and suburban clinics.20 The primary objective was to describe screening and subsequent seropositivity for strongyloidiasis, schistosomiasis, and Chagas disease after implementation of a geographic screening protocol. Secondary objectives were to identify demographic and clinical risk factors associated with seropositivity for parasitic infections, whether seropositivity was associated with graft failure or death, and whether presumptive treatment of candidates at risk for strongyloidiasis or schistosomiasis may be cost-efficient compared with a screen-and-treat approach. This study was reviewed and determined exempt by the Hennepin Healthcare Institutional Review Board.
Data collection.
Candidates were retrospectively identified through the Kidney Transplant Program’s Claris FileMaker Pro database (version 19.4.2.204, Cupertino, CA). From the FileMaker database the following variables were obtained: age; sex; country of origin; year of entry to the United States; reason for transplant (underlying kidney disease); diabetes; dates of transplant information session, transplant listing, and transplant; donor type; donor and recipient Epstein–Barr virus (EBV), cytomegalovirus (CMV), and toxoplasmosis serology results; degree of maintenance immune suppression and whether adjusted; and outcomes of rejection, graft failure, or death. Review of electronic medical records (EMR) was subsequently performed to confirm country of birth and adjustments to immune suppression and to collect the following variables: absolute eosinophil count at the time of transplant evaluation; strongyloidiasis, schistosomiasis, and Chagas disease serology results; tuberculosis and HIV screening results; stool ova and parasite results; and parasite treatment regimens. Medical records were also reviewed, as needed, to obtain any missing information from variables in the FileMaker database. Data collection was facilitated by REDCap electronic data capture tools hosted by Hennepin Healthcare Research Institute.21,22
For cost-efficiency modeling, we obtained the prices for Strongyloides IgG and Schistosoma IgG testing charged by Hennepin Healthcare to third-party payors (and self-pay), which was $72 for Strongyloides IgG and $97 for Schistosoma IgG as of March 2022. We did not include costs associated with phlebotomy because this would also occur for other laboratory testing, aside from parasite screening, obtained at the initial transplant evaluation visit. We searched GoodRx.com in March 2022 to obtain the average retail price for antiparasitic treatment with ivermectin and praziquantel for strongyloidiasis and schistosomiasis, respectively. Average retail price on GoodRx.com was used rather than another measure, such as average wholesale price, because we felt it more closely approximated the payor’s cost. The average retail price to treat an 80-kg person with four doses of ivermectin for strongyloidiasis was $102.54 (22, 3-mg tablets).23 Four doses was chosen based on the most recent American Society of Transplantation Infectious Diseases Community of Practice recommendations for strongyloidiasis treatment with 200 mcg/kg daily for two doses, repeated after 2 weeks.2 Likewise, to treat schistosomiasis with a divided dose of 40 mg/kg in an 80-kg person,2 the average retail price for praziquantel was $515.66 (six 600-mg tablets).24
Pretransplant infectious diseases screening.
In July 2014, our institution expanded pretransplant infectious diseases screening to include asking candidates about geographic risk factors; if these were present, serologic testing for chronic parasitic infections was obtained. At the time, standard pretransplant infectious diseases screening included CMV, EBV, syphilis, hepatitis B and C, varicella, measles, HIV, and tuberculosis. Screening for infectious diseases was broadened to include strongyloidiasis, schistosomiasis, and/or Chagas disease if a candidate was from or had extensive high-risk travel (> 3 months) to endemic areas (Supplemental Table 1). Tuberculosis screening included tuberculin skin testing at a hemodialysis unit (not captured by our EMR) or interferon gamma release assay (IGRA). Candidates from strongyloidiasis-endemic areas, including the southeastern United States, or who had unexplained eosinophilia received testing for Strongyloides IgG (ARUP Laboratories). Those from schistosomiasis-endemic areas were likewise tested for Schistosoma IgG (ARUP Laboratories). Finally, those from Latin America underwent testing for T. cruzi antibodies (ELISA to Quest Diagnostics, with reflex serology testing sent to Mayo Clinic Laboratories).
Implementation of the chronic parasite screening protocol was facilitated through multiple modalities. First, educational trainings provided information about chronic parasitic diseases and recommendations for screening, then introduced the protocol. Second, nurse pretransplant coordinators were asked to collect country of birth information and then order and collect indicated screening tests at the initial transplant evaluation visit. Third, screening tests were included in the EMR pretransplant evaluation order set to prompt and facilitate screening. Fourth, transplant ID review was required for all candidates before listing for transplant.
Posttransplant immunosuppression.
Kidney transplant recipients were stratified into high, standard, or low immune risk profiles based on race, age, previous transplant, donor type, panel reactive antibody > 20%, complete human leukocyte antigen mismatch, and presence of preformed donor-specific antibodies deemed clinically relevant. Patients deemed high risk received induction with antithymocyte globulin, and standard and low-risk patients received induction with basiliximab. Both groups were maintained on a calcineurin inhibitor, mycophenolate, and a corticosteroid that was tapered to prednisone 5 mg daily over 3 months after transplant. Cyclosporine was the preferred calcineurin inhibitor before January 2013, after which the preferred agent was tacrolimus.
Data categorization and analysis.
For screening findings, equivocal strongyloidiasis and schistosomiasis serology results were grouped with positive results because, clinically, treatment was offered for equivocal results for either parasite. One candidate with discordant Chagas disease screening results (initial positive screen but repeated screen negative) was considered seronegative based on diagnostic guidelines and after further medical record review revealed the infectious diseases clinician (author M. S.) felt there was a low risk for Chagas disease. Per EMR review, the clinical determination for low risk was based on social history (previous residence in a low-risk area) and absence of signs or symptoms consistent with chronic Chagas disease. Eosinophilia was defined as an absolute eosinophil count > 500 cells/mL. Underlying kidney disease was categorized into 10 groups, which included the eight most frequently reported etiologies, unknown etiology, and a miscellaneous grouping for all other etiologies. Countries of birth were grouped by World Bank regions25 with Hmong immigrants grouped with the East Asia/Pacific region if country of birth was not available in the EMR. A composite outcome of graft failure defined as death or dialysis requirement was used in the survival analysis with all dates censored after October 31, 2020.
Statistical analyses were performed with R software version 4.1.3.26 Univariate analyses used Fisher’s exact test to compare categorical variables and a two-sample t test to compare continuous variables. Survival was compared across seropositivity groups using Kaplan–Meir curves and Cox proportional hazards models. A cost-efficiency analysis assuming treatment of an 80-kg person (SD = 7 kg) with the minimum number of whole tablets needed based on dosing guidelines was performed to estimate the population prevalence for which presumptive treatment of strongyloidiasis or schistosomiasis would cost less than serologic testing followed by treatment of positive results.
RESULTS
Nine hundred and seven renal transplant candidates were identified, of which 383 (42%) ultimately underwent transplantation. Of the transplant candidates, the majority (550, 61%) were male, and 351 (39%) had diabetes. The average age was 49 years (SD = 12.7) at the time of transplant evaluation. Kidney disease from diabetes, hypertension, or a combination of those (346, 38%) was the most frequent reason for transplant listing. Country of birth information was available for the majority of candidates with 312 (34%) born in the United States and 232 (26%) born outside the United States, with 363 (40%) having an unidentified country of birth (Table 1).
Table 1.
Baseline characteristics and infectious diseases screening by place of birth
| All N = 907 | Foreign born N = 232 | U.S. born N = 312 | Unidentified N = 363 | |
|---|---|---|---|---|
| Cohort characteristics, n (%) | ||||
| Age, mean ± SD | 49.5 ± 12.7 | 46.8 ± 12.3 | 49.3 ± 13.0 | 51.3 ± 12.5 |
| Male sex | 550 (61) | 132 (57) | 196 (63) | 222 (61) |
| Comorbid diabetes | 351 (39) | 80 (34.5) | 128 (41) | 143 (39) |
| Reason listed for transplant | ||||
| Diabetes | 218 (24) | 58 (25) | 69 (22) | 91 (25) |
| Hypertension | 98 (11) | 25 (11) | 31 (10) | 42 (12) |
| Diabetes and hypertension | 30 (3) | 3 (1) | 12 (4) | 15 (4) |
| Retransplant/graft failure | 101 (11) | 19 (8) | 45 (14) | 37 (10) |
| Polycystic kidney disease | 73 (8) | 8 (3) | 25 (8) | 40 (11) |
| IgA nephropathy | 57 (6) | 23 (10) | 17 (5) | 17 (5) |
| Focal segmental glomerulosclerosis | 44 (5) | 12 (5) | 13 (4) | 19 (5) |
| Systemic lupus erythematosus | 25 (3) | 9 (4) | 7 (2) | 9 (3) |
| Other | 177 (20) | 36 (16) | 62 (20) | 79 (22) |
| Unknown | 84 (9) | 39 (17) | 31 (10) | 14 (4) |
| Transplant received | 383 (42) | 75 (32) | 150 (48) | 158 (44) |
| Pretransplant eosinophilia | 52 (6) | 24 (10) | 13 (4) | 15 (4) |
| Infectious diseases screening (no. positive/no. screened) | ||||
| HIV | 8/900 | 6/232 | 1/307 | 1/361 |
| Tuberculosis* | 48/541 | 39/182 | 7/197 | 2/162 |
| Strongyloidiasis | 16/260 | 12/175 | 4/57 | 0/28 |
| Schistosomiasis | 12/133 | 9/101 | 3/17 | 0/15 |
| Chagas disease | 0/66 | 0/43 | 0/12 | 0/11 |
By interferon-gamma assay only (does not include tuberculin skin testing).
There were 460 transplant candidates before implementation of the geographic screening protocol and 447 candidates after implementation. A reduction in candidates with unidentified country of birth was noted after protocol implementation (244 [53%] to 119 [27%], P < 0.001). Protocol implementation was associated with increased screening among all candidates for strongyloidiasis (64 [14%] to 196 [44%]), schistosomiasis (35 [8%] to 98 [22%]), and Chagas disease (5 [1%] to 61 [14%]) (P < 0.001 for all) (Table 2). Increased screening for tuberculosis with IGRA testing (as opposed to tuberculin skin testing) was also observed after protocol implementation (146 [32%] to 395 [88%]; P < 0.001). For strongyloidiasis, protocol-defined screening occurred in 19 (68%) candidates with eosinophilia, 41 (84%) candidates born in Latin America or the Caribbean, 38 (100%) born in sub-Saharan Africa, 46 (96%) born in East Asia or the Pacific, and 1 (100%) born in South Asia. For schistosomiasis, protocol-defined screening occurred for 38 (100%) candidates born in sub-Saharan Africa. For Chagas disease, protocol-defined screening occurred for 38 (78%) candidates born in Latin America or the Caribbean.
Table 2.
Infectious diseases screening before and after implementation of geographic screening protocol
| Before protocol (N = 460) | After protocol (N = 447) | P value | |
|---|---|---|---|
| Region of birth, n (% total) | < 0.001 | ||
| North America | 128 (27.8) | 190 (42.5) | |
| Latin America and Caribbean | 12 (2.6) | 49 (11.0) | |
| East Asia and Pacific | 45 (9.8) | 48 (10.7) | |
| Sub-Saharan Africa | 23 (5.0) | 38 (8.5) | |
| Europe and Central Asia | 4 (0.9) | 2 (0.4) | |
| South Asia | 4 (0.9) | 1 (0.2) | |
| Unidentified | 244 (53.0) | 119 (26.6) | |
| Eosinophilia | |||
| Screened, n (% total) | 458 (99.6) | 440 (98.4) | 0.103 |
| Positive, n (% screened) | 24 (5.2) | 28 (6.4) | |
| HIV | |||
| Screened, n (% total) | 458 (99.6) | 442 (98.9) | 0.281 |
| Positive, n (% screened) | 3 (0.7) | 5 (1.1) | |
| Tuberculosis | |||
| Screened, n (% total) | 146 (31.7) | 395 (88.4) | < 0.001 |
| Positive, n (% screened) | 13 (8.9) | 35 (8.9) | |
| Strongyloidiasis | |||
| Screened, n (% total) | 64 (13.9) | 196 (43.8) | < 0.001 |
| Positive, n (% screened) | 2 (3.1) | 14 (7.1) | |
| Schistosomiasis | |||
| Screened, n (% total) | 35 (7.6) | 98 (21.9) | < 0.001 |
| Positive, n (% screened) | 1 (2.9) | 11 (11.2) | |
| Chagas disease | |||
| Screened, n (% total) | 5 (1.1) | 61 (13.6) | < 0.001 |
| Positive, n (% screened) | 0 (0) | 0 (0) | |
After protocol implementation, 14 (7% of screened) candidates were seropositive for strongyloidiasis versus two (3%) before implementation, and 11 (11%) seropositive for schistosomiasis versus one (3%) prior. Chagas disease was not identified in any screened candidates. Positive screening for a parasitic infection was not associated with age, sex, region of birth, eosinophilia, HIV, or positive tuberculosis screen (Supplemental Table 2). All seropositive strongyloidiasis candidates were treated with ivermectin. All seropositive schistosomiasis candidates were treated with praziquantel, except for one case that was deemed a false positive by an infectious disease clinician (author M. S.). No severe disease or disease reactivation after transplant was observed for either strongyloidiasis or schistosomiasis.
Of 383 candidates who underwent kidney transplantation, 40 (10%) experienced graft failure. Of those with graft failure, 21 (53%) died and 19 (48%) required dialysis. Among 95 transplanted candidates screened for strongyloidiasis, there were no observed episodes of graft failure among seropositive candidates (N = 3) and two observed episodes of graft failure among seronegative candidates (N = 92). Among 47 transplanted candidates screened for schistosomiasis, there was one observed episode of graft failure among seropositive candidates (N = 7) and no episodes of graft failure among seronegative candidates (N = 40). Among candidates screened for parasitic infection, seropositivity was not significantly associated with time to graft failure (hazard ratio [HR] = 12.52, 95% CI: 0.78–201) (Supplemental Figure 1). Diabetes and biopsy-confirmed rejection of the transplanted kidney were associated with shorter time to graft failure (HR = 1.90, 95% CI: 1.01–3.55 and HR = 2.62, 95% CI: 1.14–5.99, respectively) (Table 3).
Table 3.
Regression analysis for graft failure (N = 383)
| Hazard ratio* | 95% CI | P value | |
|---|---|---|---|
| Age (mean = 48.6, SD = 13.0) | 1.02 | 0.99–1.04 | 0.172 |
| Male sex (N = 223) | 1.89 | 0.96–3.72 | 0.066 |
| Diabetes (N = 117) | 1.90 | 1.01–3.55 | 0.046 |
| Country of birth | 0.108 | ||
| Foreign-born (N = 75) | Ref | Ref | |
| U.S.-born (N = 150) | 2.73 | 0.61–12.3 | 0.191 |
| Unidentified (N = 158) | 4.16 | 0.98–17.7 | 0.053 |
| Rejection (biopsy-confirmed) (N = 18) | 2.62 | 1.14–5.99 | 0.023 |
| Immune risk | 0.143 | ||
| High (N = 191) | Ref | Ref | |
| Standard (N = 157) | 1.38 | 0.42–4.58 | 0.598 |
| Low (N = 35) | 0.63 | 0.17–2.34 | 0.494 |
| Maintenance immunosuppression decreased (N = 12) | 0.46 | 0.06–3.37 | 0.446 |
| Positive parasite screen† (N = 10) | 12.52 | 0.78–201 | 0.074 |
| Positive tuberculosis screen‡ (N = 17) | 0 | N/A | 0.998 |
| Living with HIV§ (N = 4) | 0 | N/A | 0.997 |
| High risk EBV (donor+/recipient–) (N = 18) | 0 | N/A | 0.997 |
| High risk CMV (donor+/recipient–) (N = 62) | 1.75 | 0.85–3.57 | 0.127 |
| High risk toxoplasmosis (donor+/recipient–)ǁ (N = 6) | 6.58 | 0.84–51.70 | 0.073 |
CI = confidence interval; CMV = cytomegalovirus; EBV = Epstein–Barr virus; N/A = not applicable; Ref = reference.
Bold indicates a significant P value.
There were no events of graft failure among transplant recipients with positive tuberculosis screening, living with HIV, or at high risk for EBV, and thus a hazard ratio could not be calculated for these variables.
Includes 100 transplant recipients with strongyloidiasis (N = 95) and/or schistosomiasis (N = 47) screening results. Due to the small number of graft failure events among these transplant recipients, individual hazard ratios for strongyloidiasis and schistosomiasis screening could not be calculated.
Includes 216 transplant recipients with interferon gamma release assay tuberculosis screening results.
Includes 378 transplant recipients with known HIV status.
Includes 304 transplant recipients with known toxoplasmosis status.
The estimated cost of serologic testing with reflexive treatment of positive findings was $78.31 and $142.53 per person in our cohort screened for strongyloidiasis or schistosomiasis, respectively. Using a presumptive treatment model with the retail price for strongyloidiasis or schistosomiasis treatment courses ($102.54 and $515.66 for an 80-kg person, respectively), strongyloidiasis seroprevalence of 30% and schistosomiasis seroprevalence of almost 80% in the population at risk were necessary for presumptive treatment to be cost-efficient compared with screening followed by treatment as needed (Supplemental Figure 2).
DISCUSSION
Our findings demonstrate that implementing a pretransplant protocol that uses geographic risk factors to screen for chronic parasitic infections results in improved screening practices for both the targeted parasitic infections and more consistent and/or documented screening via IGRA for tuberculosis, another infectious disease characterized by geographic risk factors. This was evidenced by the approximately 3-fold increase in screening for tuberculosis via IGRA, strongyloidiasis, schistosomiasis, and Chagas disease after the protocol was developed. Given that testing was occurring, to a lesser extent, before protocol implementation, we suspect that clinicians were aware of the importance of chronic parasitic infections but may not have regularly assessed a candidate’s risk. This is further supported by the drastic decrease in transplant candidates without country-of-birth information in the EMR following the protocol’s implementation.
It is extremely important to collect demographic information that includes country of birth because relying on routinely collected information such as race or ethnicity can limit the accuracy of risk assessments. Here, we describe how collecting that information is essential for transplant programs to adhere with guidelines recommending screening of transplant candidates at risk for strongyloidiasis, schistosomiasis, and Chagas disease.2,9,17 The importance of country of birth in epidemiologic risk also extends beyond the pretransplant evaluation and infections that are not endemic in the United States. For example, others have demonstrated the added value of incorporating country-of-birth information in addition to race/ethnicity and socioeconomic status for HIV, hepatitis B, and tuberculosis epidemiologic risk assessments in nontransplant U.S. populations.27–29
The prevalence of strongyloidiasis among transplant candidates screened at our institution (7%) is similar to the range of 4% to 10% identified among universally screened transplant candidates in the Gulf Coast region.12–14,16 Although it is reassuring that our findings among transplant candidates with geographic risk factors for strongyloidiasis are similar to those in the southeastern United States where the parasite is endemic,11,30 it is important to recognize that the prevalence of strongyloidiasis in the United States, and globally, is largely unknown.31,32 Further efforts are needed to better characterize geographic endemicity in the United States and assess whether geographic-based screening is sufficient. For example, universal strongyloidiasis screening in nonendemic regions may offer added benefit as suggested by one transplant center’s detection of seropositive individuals without geographic risk factors.15
There was a higher prevalence of schistosomiasis (11%) among protocol-screened kidney transplant candidates than strongyloidiasis (7%). Given the limited published information regarding schistosomiasis screening before transplant in the United States, this suggests an underappreciation of the burden of schistosomiasis in transplant candidates and highlights the need for additional descriptions of screening practices, results, and outcomes at other locations. Our lack of identifying serologic evidence of Chagas disease is consistent with other institutional experiences in nonendemic areas.33,34 Given that risk for Chagas disease may be more nuanced based on factors such as exposure to thatched housing, this may illustrate a lack of specificity with using only country of birth or travel to determine risk for Chagas disease.
Because presumptive treatment (without first testing) for strongyloidiasis with ivermectin and schistosomiasis with praziquantel may be cost-efficient in foreign-born populations where the prevalence is greater than 2%,35,36 we explored whether a similar approach may be cost-efficient in the pretransplant evaluation. Although our findings suggest that the current average retail price of praziquantel is cost-prohibitive for this approach, the price of ivermectin may be conducive to a presumptive treatment approach for strongyloidiasis. In considering this, it is important to acknowledge the profound impact of commercial factors behind U.S. drug costs and alternative ivermectin dosing options. For example, using the average retail price of ivermectin and a four-dose treatment course, we calculated a threshold prevalence of 30%—more than 3 times the prevalence in our cohort—at which it would cost less to treat presumptively with ivermectin. However, with available coupons, the price of ivermectin is about half the cost of the laboratory screening test ($35 versus $72),23 and in this setting, it costs much less to presumptively treat anyone with geographic risk factors. It may also be possible to treat transplant candidates who are not on immunosuppressing medications with a single dose of ivermectin,37 at which the average retail price would also be less than screening ($30 versus $72).23 Because of this variation in cost, clinicians may find that for certain patients, presumptive treatment may be economically advantageous.
The interpretation of our findings is limited by the significant number of kidney transplant candidates who still did not have a documented country of birth in the EMR following implementation of the screening protocol. Because our data were collected retrospectively, it is unknown whether this reflects a lack of asking candidates about country of birth or a lack of documentation in the EMR. Similarly, we were unable to assess the impact of travel on screening practices, or account for screening performed outside the institution because this information was not reliably available in the EMR or FileMaker database. We were also unable to assess which patients arrived in the United States as refugees and therefore had already received presumptive predeparture antiparasitic treatment of strongyloidiasis and schistosomiasis,38 potentially decreasing the importance of pretransplant screening and/or treatment. Furthermore, our estimates of cost-efficiency are limited in the use of institutional pricing data for laboratory tests and an approximation of drug cost, both of which vary by institution and over time, making it difficult to generalize these findings.
Implementation of a geographic screening protocol was successful at incorporating current recommendations for screening of chronic parasitic infections at an institution in a nonendemic region. By more routinely inquiring about country of birth, screening practices for strongyloidiasis, schistosomiasis, and Chagas disease improved and resulted in more seropositive kidney transplant candidates being appropriately treated before transplant. It is feasible for other institutions likewise to incorporate routine screening for geographic risk factors and improve infectious disease detection before kidney transplant. The most cost-effective approach to screening and treating foreign-born patients for chronic parasitic diseases before transplant deserves further study.
Supplemental files
ACKNOWLEDGMENTS
We thank Anne Spenningsby and John Silkensen for their assistance.
Note: Supplemental materials appear at www.ajtmh.org.
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