Human Leptospirosis: Seroreactivity and Genetic Susceptibility in the Population of São Miguel Island (Azores, Portugal)

Abstract

BackgroundLeptospirosis is a worldwide zoonotic and recognized neglected infectious disease. It has been observed that only a proportion of individuals exposed to pathogenic species of Leptospira become infected and develop clinically evident disease. Moreover, little information is available in subsequent reinfections. In the present study, we determine if a first infection with leptospirosis protects against subsequent reinfection, and investigate which of the host genetic factors are involved in the susceptibility and resistance to leptospirosis.Methodology and FindingsWe conducted, in 2011, a retrospective hospital-based case-control study in the São Miguel Island population (Azores archipelago). In order to determine the seropositivity against pathogenic Leptospira after the first episode of leptospirosis, we performed a serological evaluation in 97 unrelated participants diagnosed with leptospirosis between 1992 and 2011. The results revealed that 46.4% of the 97 participants have circulating anti-Leptospira antibodies, and from these participants 35.6% maintained the seroprevalence for the same serogroup. Moreover, three of them were reinfected with unrelated Leptospira serovars. The genetic study was carried out by adding a control group composed of 470 unrelated healthy blood donors, also from São Miguel Island. Twenty five SNPs among twelve innate immune genes – IL1α, IL1β, IL6, IL10, IL12RB1, TLR2, TLR4, TLR9, CD14, CISH, LTA and TNF – were genotyped, as well as HLA class I (–A and –B) genes. Association analysis indicates that genotypes -511GG (OR = 1.6, 95%CI 1.01-2.56, p = 0.04) in IL1β, +1196CG (OR = 2.0, 95%CI 1.26-3.27, p = 0.003) in IL12RB1, -292TA (OR = 1.8, 95% CI 1.06–2.1, p = 0.03) and +3415CG (OR = 1.8, 95% CI 1.08–3.08, p = 0.02), both in CISH confer susceptibility to pathogenic Leptospira.ConclusionThe present study suggests some degree of long-term protection against leptospires with an attenuation of symptoms in case of reinfection. Moreover, our data supports the genetic influence of IL1β, IL12RB1 and CISH genes and the susceptibility to leptospirosis infection.

Molecular diagnosis of infectious diseases in São Miguel Island (Azores, Portugal): A hospital-based descriptive study

“…The data showed that males and farmers were the most affected by this pathogen. These results are in accordance with the study developed by Vieira et al [5] and Esteves et al [6], where a significant link to professional activities and/or contact with rodents and domestic animals (natural reservoirs for leptospires) was observed.…”

“…These spirochetes are responsible for severe human disease leading to a systemic infection, characterized by clinical manifestations that vary greatly from flu-like symptoms to multiple organ failure and death [6]. Leptospirosis is known for its endemicity, and is considered a public health problem due to its high annual incidence rate in semi-tropical climates, such as the Azores Islands (Portugal) [5,6]. Transmission of leptospirosis can occur through direct contact with an infected animal or its urine, placental fluids, or milk.…”

IL12Rβ1: The cytokine receptor that we used to know

“…( C ) Corresponding to each of the polymorphisms indicated in (A) are reports of its association with disease susceptibility or outcome; listed below each polymorphism is whether this is an infectious disease (ID), cancer (CA), pediatric asthma (PA) or dermatological disease (DD). The literature references supporting these assignments are described in the article text and reproduced here: rs393548 (116), rs436857 (116), rs2305742 (146), rs429774 (135, 158), rs11575934 (130, 145), rs375947 (130, 144, 158), rs401502 (130, 137), rs372889 (139, 140), rs383483 (135). Given that rs11575934, rs375947, and rs401502 are frequently linked, they are often referred to in the literature as the “RTR haplotype” (129) ( D ) Depicted are the thirteen alternative splice variants expressed in human PBMCs and lung tissue.…”

“…liver dysfunction, myocarditis). Among individuals living on the Azores archipelago (Portugal), Esteves et al (137) reported that the rs401502 allele conferred susceptibility to pathogenic leptospira. Finally, unlike TB, malaria or leptospirosis, measles is of viral origin (a paramyxovirus of the genus Morbillivirus) and is vaccine-preventable.…”

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis

“…However, our patients represent primarily individuals of mixed Caucasian and African descent and it will be important to identify whether the pathways we identified are generalizable to global populations, given that several studies have shown association of specific alleles with increased susceptibility to leptospirosis [15, 16, 58, 59]. Further, it will be important to compare our findings on whole blood transcriptional profile with samples from the lungs in patients that develop LPHS.…”