Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Disease Reservoirs* ; Disease Transmission, Infectious*; Leishmania infantum/*isolation & purification ; Leishmaniasis, Visceral/*epidemiology ; Leishmaniasis, Visceral/*transmission; Adult ; Animals ; Antibodies, Protozoan/blood ; Asymptomatic Diseases/epidemiology ; DNA, Protozoan/blood ; Female ; Humans ; Leukocytes, Mononuclear/immunology ; Male ; Middle Aged ; Psychodidae/parasitology ; Spain/epidemiology

Background: In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain.
Methodology and Main Findings: Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient with multiple myeloma and symptomatic active VL, and 2 immunocompetent patients with untreated active VL. All blood donors were negative for both xenodiagnosis and conventional PCR.
Conclusions / Significance: There is no consensus amongst authors on the definition of an 'asymptomatic case' nor on the tools for screening; we, therefore, have adopted one for the sake of clarity. Immunocompetent subjects, both infected asymptomatics and those treated for VL, are limited in number and appear to have no epidemiological relevance. The impact is limited for immunocompetent patients with untreated active VL, whilst immunosuppressed individuals undergoing immunosuppressive therapy and immunosuppressed individuals HIV / L. infantum coinfected were the most infectious towards sand flies. It is noteworthy that the HIV / L. infantum coinfected patient with asymptomatic leishmaniasis was easily infectious to sand flies for a long time, despite being under continuous prophylaxis for leishmaniasis. Accordingly, screening for latent Leishmania infection in HIV-infected patients is recommended in scenarios where transmission occurs. In addition, screening for VL in HIV-infected patients who have spent time in VL-endemic areas should also be implemented in non-endemic areas. More research is needed to better understand if some asymptomatic coinfected individuals contribute to transmission as 'super-spreaders'.
Competing Interests: The authors have declared that no competing interests exist.

PLoS Pathog. 2017 Oct 19;13(10):e1006571. (PMID: 29049371)
Parasitol Res. 2018 Apr;117(4):1237-1244. (PMID: 29478175)
Rev Soc Bras Med Trop. 2020 Feb 21;53:e20190446. (PMID: 32130324)
Clin Infect Dis. 2014 Aug 15;59(4):552-5. (PMID: 24814660)
Trans R Soc Trop Med Hyg. 2002 Mar-Apr;96(2):129-32. (PMID: 12055798)
Clin Infect Dis. 2019 Jul 2;69(2):251-258. (PMID: 30357373)
J Clin Microbiol. 1999 Jun;37(6):1953-7. (PMID: 10325353)
Vet Parasitol. 2014 May 28;202(3-4):296-300. (PMID: 24774435)
Euro Surveill. 2019 May;24(22):. (PMID: 31164191)
Am J Trop Med Hyg. 1999 Jan;60(1):51-3. (PMID: 9988321)
Parasit Vectors. 2013 Apr 26;6:122. (PMID: 23622683)
Clin Microbiol Infect. 2016 Aug;22(8):739.e1-4. (PMID: 27265372)
Infection. 2019 Oct;47(5):739-747. (PMID: 30888587)
PLoS One. 2018 Jun 14;13(6):e0198199. (PMID: 29902188)
HIV Med. 2010 Nov;11(10):670-3. (PMID: 20500233)
Acta Trop. 2011 Aug;119(2-3):69-75. (PMID: 21679680)
Acta Trop. 2015 Jun;146:127-34. (PMID: 25800329)
Clin Infect Dis. 2014 May;58(10):1424-9. (PMID: 24585564)
Clin Infect Dis. 2017 Jul 1;65(1):150-153. (PMID: 28520851)
BMC Infect Dis. 2009 Dec 10;9:199. (PMID: 20003257)
Trans R Soc Trop Med Hyg. 2004 Feb;98(2):102-10. (PMID: 14964810)
Am J Trop Med Hyg. 2018 Jan;98(1):126-133. (PMID: 29141704)
Lancet Glob Health. 2014 Dec;2(12):e683-4. (PMID: 25433617)
Rev Inst Med Trop Sao Paulo. 1962 May-Jun;4:198-212. (PMID: 13884626)
Parasitology. 2009 Dec;136(14):1915-34. (PMID: 19835643)
AIDS. 1994 Feb;8(2):277-9. (PMID: 8043238)
J Infect Dis. 2000 Sep;182(3):997-1000. (PMID: 10950806)
Trends Parasitol. 2017 Oct;33(10):748-750. (PMID: 28867329)
Trans R Soc Trop Med Hyg. 2002 Apr;96 Suppl 1:S185-9. (PMID: 12055836)
Parasit Vectors. 2017 Apr 26;10(1):209. (PMID: 28446214)
Ann Trop Med Parasitol. 2009 Dec;103(8):659-70. (PMID: 20030990)
PLoS Negl Trop Dis. 2019 Jun 3;13(6):e0007461. (PMID: 31158223)
Vet Parasitol. 2012 Nov 23;190(1-2):268-71. (PMID: 22677135)
AIDS. 1994 Jun;8(6):854. (PMID: 8086149)

0 (Antibodies, Protozoan)
0 (DNA, Protozoan)

Date Created: 20200424 Date Completed: 20200630 Latest Revision: 20200630

20240105

PMC7200008

10.1371/journal.pntd.0008253

32324738