Download Determinants of the Outcomes of Leishmania Chagasi

Poster # 7
DETERMINANTS OF THE OUTCOMES OF LEISHMANIA CHAGASI INFECTION
IN RIO GRANDE DO NORTE, BRAZIL
Selma M. B. Jeronimo1, Priya Duggal2, Gloria R. Monteiro1, Bruna L. Maciel1, Eliana T. Nascimento1,
Angela P. Cabral1, Núbia N. Pontes1, Hênio G. Lacerda1, Paula V. Queiroz1, Carlos G. Maia1,
Richard D. Pearson3, Jenefer M. Blackwell4, Terri H. Beaty5, Stephen E. McGowan6,
Edgar M. Carvalho7, Mary E. Wilson6
1
Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; 2National Human Genome Research
Institute, Baltimore, MD; 3University of Virginia School of Medicine Charlottesville, VA; 4University of
Cambridge School of Clinical Medicine, Cambridge, UK; 5Johns Hopkins Bloomberg School of Public
Health, 6 University of Iowa, IA, USA, 7Universidade Federal da Bahia, Salvador , Brazil.
The outcome of Leishmania chagasi infection ranges from self-resolving infection to progressive
visceral leishmaniasis (VL), a disease that is fatal if left untreated. The risk factors that determine the
development of disease are not totally understood, but include environmental and host genetic factors. In
Brazil, there has been urbanization of VL during the last 20 years with the majority of the cases occurring
in perimetropolitan areas of major cities. Studies conducted in endemic VL areas in Brazil, including our
own, have shown that only approximately 10% of individuals infected with the L. chagasi develop
clinical disease. The rest develop protective cell-mediated immunity that can be measured as a positive
delayed-type hypersensitivity (DTH) skin-test response to Leishmania antigen. They are resistant to
developing disease provided that they remain imunocompetent. We have studied the determinants
(including environmental and host genetics factors) of the outcomes of L. chagasi infection in Natal,
Brazil, an area recent endemic for Leishmania.
A family study was performed. Subjects who lived in the endemic area for at least 2 years were
assessed for VL or asymptomatic infection, defined as a positive delayed type hypersensitivity (DTH)
skin test response to Leishmania antigen and absence of clinical symptoms. A genome scan of 405
microsatellite markers in 1254 subjects was analyzed for regions of linkage. The results indicated loci of
potential linkage to DTH response on chromosomes 15 and 19, and a novel region of potential interest for
VL on chromosome 9. In addition, we assessed nutritional status to determine whether it was associated
with the outcome of Leishmania infection comparing children who had VL with relatives who had either
self-resolving Leishmania infection or were apparently uninfected. We observed a decrease in body mass
index (p < 0.0005) and mid-upper arm circumference for age (p = 0.022) among children with VL.
Vitamin A was lower in children with VL measured by serum retinol (p = 0.035) and the modifiedrelative-dose-response test (p = 0.009). Higher birth weight (B < -0.001 ± 0.00; OR = 0.84; 95% CI 0.73
– 0.99; p = 0.047) and albumin concentrations (B = -2.31 ± 1.13; OR = 0.09; 95% CI 0.01 - 0.90 p =
0.040) associated with protection against disease. Older age (B = 0.64 ± 0.31; OR = 1.90; 95% CI 1.03 3.52; p = 0.041), and increased breastfeeding time (B = 0.15 ± 0.07; OR = 1.16; 95% CI 1.01 - 1.33; p =
0.036) were associated with asymptomatic infection. The results indicate that modifiable nutritional
factors are associated with the outcome of Leishmania infection. Teasing out the distinct components
influencing whether an individual will develop symptomatic or asymptomatic infection with L. chagasi
may reveal essential factors which lead to immune protection against this parasitic disease. The ultimate
goal of such studies is to discover rational strategies for prevention of symptomatic disease.
41