Environmental Factors as Key Determinants for Visceral Leishmaniasis in Solid Organ Transplant Recipients, Madrid, Spain

During a visceral leishmaniasis outbreak in an area of Madrid, Spain, the incidence of disease among solid organ transplant recipients was 10.3% (7/68). Being a black person from sub-Saharan Africa, undergoing transplantation during the outbreak, and residing <1,000 m from the epidemic focus were risk factors for posttransplant visceral leishmaniasis.

( Table 2). The mean interval between transplant and diagnosis was 1.34 ± 0.89 years. No patients had visited highly VL-endemic countries.
Black sub-Saharan African SOT recipients were more likely than other recipients to become affected by VL (relative risk 6.40, 95% CI 1.76-23.29, p = 0.049) ( Table 1). All 7 episodes of VL occurred in patients who underwent transplantation during the outbreak period ( Figure 1).
The median distance between the place of residence and the park was significantly shorter for recipients with VL (399 m) than for those without (1,370 m; p = 0.001) ( Figure  2; online Technical Appendix Figure 2). We explored the predictive accuracy of this variable by establishing the optimal cutoff value with the area under the receiving operating characteristic curve analysis. Recipients living <1,000 m from the park (26.1%, 6/23) had a higher incidence of VL than recipients living >1,000 m away (2.2%, 1/45; relative risk, 11.74, 95% CI 1.50-91.78; p = 0.005). At 4 years, a lower percentage of the SOT recipients living <1,000 m from the park were free from VL than those living >1,000 m away (61.0% vs 98%; p = 0.001 by log-rank test) (online Technical Appendix Figure 3).
Our study suggests that the incidence of VL in SOT recipients is notably higher than that in the general population (11). Acquisition of the parasite most likely occurred posttransplant because all but 1 recipient affected with VL (from whom serum samples could be recovered) were seronegative for Leishmania spp. before transplantation.
Our findings suggest that environmental factors might be crucial in modulating the incidence of VL in immunocompromised hosts, such as SOT recipients; the distance from the patient's residence to the focus of the outbreak (6,7) emerged as a key risk factor. The median distance between the park and the homes of recipients with posttransplant VL was <500 m; the maximum flight distance of female sand flies is 600 m (12,13). Therefore, persons living within this radius had a higher chance of being bitten by the VL vector. A similar association was described for the general population during this outbreak (6). 1156 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017 Undergoing transplantation during the outbreak period was another risk factor for VL. This finding suggests that, in the case of an outbreak in a country with low baseline incidence, pretransplant screening of patients listed for SOT for VL-specific antibodies should be considered and repeated during the posttransplant period for the prompt detection of de novo infection. Recipients should also receive specific counseling to reduce the risk of being bitten by sand flies. In addition, treating physicians must maintain a low threshold of suspicion for VL for persons on immunosuppressive therapy during a VL outbreak.
We found that 28% of posttransplant VL cases occurred in black recipients born in sub-Saharan Africa, even though this subgroup only represented 2.4% of the overall population in the affected area (14). An association between sub-Saharan African ethnicity and VL has also been reported in the general population (4). No apparent relationship was found between the race of the patient and the frequency of parkland visits. Both black recipients in question came from Equatorial Guinea, a country not considered endemic for leishmaniasis by the World Health Organization (15). Therefore, the potential association between genetic susceptibility and posttransplant VL warrants further investigation.
Limitations of this study include the small sample size and that interviewers were not blinded to the diagnosis of VL. However, the objective nature of the questionnaire minimized the potential risk for bias. When assessing degree of exposure to sand flies, we used only indirect variables (i.e., distance between the patient's residence and park, habit of visiting the park) as surrogate measures. Regarding the distance from the park, only linear distances were assessed without considering the potential presence of physical obstacles in the sand fly flight trajectory. Because of these limitations, our findings must be interpreted with caution.

Conclusions
Our study indicates several risk factors (being black and from sub-Saharan Africa, having an SOT during the outbreak, and living <1,000 m from the outbreak focus) useful for helping physicians treat SOT recipients during a VL outbreak. Doctors should select the patients with these risk factors for counseling to minimize their exposure to vectors and active monitoring for prompt diagnosis. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017