PLoS Neglected Tropical Diseases: New Articles

An “In-Depth” Description of the Small Non-coding RNA Population of Schistosoma japonicum Schistosomulum

2010-02-09T08:00:00Z

Author Summary

Schistosomiasis is one of the most prevalent and serious parasitic diseases in tropical and subtropical regions. Schistosomes are pathogens that have a unique repertoire of genes expressed at different life cycle stages. Small regulatory RNAs play an important role in the control of gene expression at the post-transcriptional level. In a previous study, we identified five conserved miRNAs in adult S. japonicum worms through traditional sequencing methods. In this work, we discovered more microRNAs, including 16 new schistosome-specific miRNA families in addition to 20 conserved miRNA families. We identified two miRNA gene clusters using the data obtained from high-throughput sequencing. We demonstrated, for the first time, the presence of endogenous small interfering RNAs in schistosomes. Identification of these small regulatory RNAs should provide a foundation for future studies aimed at understanding functions of small RNAs and ultimately of small RNA regulatory networks in this important pathogen.

Schistosoma mansoni Stomatin Like Protein-2 Is Located in the Tegument and Induces Partial Protection against Challenge Infection

2010-02-09T08:00:00Z

Author Summary

Schistosomiasis is a parasitic disease causing serious chronic morbidity in tropical countries. Together with the publication of the transcriptome database, a series of new vaccine candidates were proposed based on their functional classification. However, the prediction of vaccine candidates from sequence information or even by proteomics or microarrays data is somewhat speculative and there remains the considerable task of functional analysis of each new gene/protein. In this study, we present the characterization of one of these molecules, a stomatin like protein 2 (SmStoLP-2). Sequence analysis predicts signals that could contribute to protein membrane association and mitochondrial targeting, which was confirmed by differential extractions of schistosome tegument membranes and mitochondria. Additionally, confocal microscope analysis showed SmStoLP-2 present in the tegument of 7-day-old schistosomula and adult worms. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1, IgG2, IgG3 and IgA anti-SmStoLP-2 antibodies in individuals resistant to reinfection. Recombinant SmStoLP-2 protein, when used as vaccine, induced significant levels of protection in mice. This reduction in worm burden was associated with a typical Th1-type immune response. These results indicate that SmStoLP-2 could be useful in association with other antigens for the composition of a vaccine against schistosomiasis.

Temporal Expression of Chemokines Dictates the Hepatic Inflammatory Infiltrate in a Murine Model of Schistosomiasis

2010-02-09T08:00:00Z

Author Summary

Schistosomiasis, a disease caused by parasitic worms, is a significant cause of illness and death in the developing world. Furthermore, recent reports suggest that the global burden of disease due to schistosomiasis has been significantly underestimated. Schistosomiasis of the liver arises due to inflammation and the deposition of scar tissue around parasite eggs trapped in this organ. In the current study we analysed the gene-expression profile of the mouse liver at several time points following infection with a virulent strain of Schistosoma japonicum to better understand the mechanisms that regulate this process. Progression of disease was associated with increased expression of different groups of genes with distinct biological functions. Specifically, we identified several genes encoding chemical signalling molecules that contribute to different phases of the response by recruiting key cell types to the site of inflammation. This study represents the most comprehensive report to date of the gene expression profile in the liver during schistosomiasis. These results provide further insight into the mechanisms that regulate the development of schistosome-induced inflammation and scarring and will aid in the development of novel treatments to alleviate the burden of disease caused by this parasite.

Of Cattle, Sand Flies and Men: A Systematic Review of Risk Factor Analyses for South Asian Visceral Leishmaniasis and Implications for Elimination

2010-02-09T08:00:00Z

Author Summary

Visceral leishmaniasis (VL) is a potentially deadly parasitic disease that affects 200,000 to 300,000 people per year in the Indian subcontinent, where an effort is currently underway to eliminate the disease. Studies have identified fairly consistent patterns of risk factors for VL. This information can help to inform the elimination effort. Because humans form the sole source of infection, clustering of VL cases is a prominent feature, both at the household level and on a larger scale. Mud walls, dampness in houses, and peri-domestic vegetation increase infection risk by promoting the survival of the insect vector. Bed nets, sleeping on a cot and indoor residual spraying decrease risk. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting a complex effect on vector abundance and vector infection rates. Poverty is a major underlying factor increasing risk of VL infection and disease. A well-designed demonstration project is needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid return of disease when interventions are scaled back.

Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes

2010-02-09T08:00:00Z

Author Summary

Schistosome blood flukes cause more mortality and morbidity than any other human worm infection, but current control methods primarily rely on a single drug. There is a desperate need for new approaches to control this parasite, including vaccines. People become infected when the free-swimming larva, the cercaria, enters through the skin and becomes the schistosomulum. Schistosomula are susceptible to immune responses during their first few days in the host before they become adult parasites. We characterised the genes that these newly transformed parasites switch on when they enter the host to identify molecules that are critical for survival in the human host. Some of these highly up-regulated genes can be targeted for future development of new vaccines and drugs.

Reductions in the Prevalence and Incidence of Geohelminth Infections following a City-wide Sanitation Program in a Brazilian Urban Centre

2010-02-02T08:00:00Z

Author Summary

In the city of Salvador, a large urban centre in Northeast Brazil, a city-wide sanitation intervention started in 1997, aiming to improve the sewerage coverage of households from 26% to 80%. Our aim was to study the impact of the intervention on the prevalence and incidence of geohelminths in the school-aged population. The longitudinal study comprised two cohorts: from the beginning of 1997 to 1998, where data was collected before the intervention, and at the end of 2003 to 2004, after the intervention. Copro-parasitological examinations were carried out on every individual from both cohorts, at the start and nine months later. Demographic, socio-economic, and environmental data were collected using semi-structured questionnaires. The variables utilized to demonstrate the effects of intervention, when utilized together in a multivariate model, accounted for a 100% observed reduction in the prevalence ratio (PR) and incidence ratio (IR). As well as proving that the variables associated with the effect of the program intervention were mediators in this reduction, the reduction in the PR and IR between these periods demonstrated that modifications to the urban environment, particularly those associated with sanitary sewage systems, affected the health of the population, significantly reducing the prevalence of geohelminths.

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reservoir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection

2010-02-02T08:00:00Z

Author Summary

For Leishmania, one genus among several genera belonging to the parasitic Trypanosomatidae family, many nonhuman mammals are known to be hosts in addition to humans. Most studies that describe Leishmania wild reservoirs are based on isolated descriptions of infection that can lead to misinterpretation of information. The definition of the epidemiological importance of a putative reservoir host depends on adequate data on the dynamics and peculiarities inherent to the host-parasite interactions and their involvement in the transmission cycle of these parasites. Our objectives were to sort out the features displayed by nonhuman mammal populations (the caviomorph rodent Thrichomys laurentius) which, with an insect host, perpetuate Leishmania transmission cycles. This rodent species had the ability to act as maintenance and/or amplifier host of both tested Leishmania species. The similar pattern of infection displayed by T. laurentius infected by these two Leishmania species shows that the definition of dermotropic or viscerotropic based on the clinical features observed in humans should not be applied to natural hosts, and it emphasizes that the search for Leishmania reservoirs should consider all possibilities of the infection course, independent of current knowledge in other mammal hosts.

Prevalence, Clinical Staging and Risk for Blood-Borne Transmission of Chagas Disease among Latin American Migrants in Geneva, Switzerland

2010-02-02T08:00:00Z

Author Summary

Chagas disease, a parasitic disease caused by Trypanosoma cruzi, is a leading cause of cardiac and digestive tract disorders in Mexico, Central and South America. An increasing number of cases have recently been reported in North America and Europe due to international human migration, but data outside Latin America remains scarce. This study showed that Chagas disease is an emerging health problem in Switzerland, affecting a substantial proportion of Latin American migrants (13%). Persons at increased risk of infection were Bolivian, older than 35 years or had a mother infected with T. cruzi. Early signs of cardiac or digestive tract disease were found in one out of six infected patients. The risk of local transmission by blood transfusion or organ transplant was illustrated by the frequent willingness expressed by patients to donate blood or organs in Switzerland. The authors recommend the screening of persons at risk of infection and the diffusion of appropriate information to the medical community to increase awareness of this emerging health problem. Considering that affected persons frequently lack health insurance in Switzerland, a facilitated access to medical care is an important step towards better recognition and management of Chagas disease.

Electroporation Facilitates Introduction of Reporter Transgenes and Virions into Schistosome Eggs

2010-02-02T08:00:00Z

Author Summary

The genome sequences of two of the three major species of schistosomes are now available. Molecular tools are needed to determine the importance of these new genes. With this in mind, we investigated introduction of reporter transgenes into schistosome eggs, with the longer-term aim of manipulation of schistosome genes and gene functions. The egg is a desirable developmental stage for genome manipulation, not least because it contains apparently accessible germ cells. Introduction of transgenes into the germ cells of schistosome eggs might result in transgenic schistosomes. However, the egg is surrounded by a thick shell which might block access to entry of transgenes. We cultured eggs in the presence of three types of reporter transgenes of increasing molecular size, and in addition we tried to produce transient holes in the eggs by electroporation to investigate whether the transgenes would more easily enter the eggs. Electroporation of eggs appeared to allow entry of two larger types of transgenes into cultured schistosome eggs, messenger RNA encoding firefly luciferase, and retroviral virions. We anticipate that this approach, electroporation of transgenes into schistosome eggs, will facilitate genetic manipulation of schistosomes for investigating the importance of schistosome genes and gene products as new intervention targets.

Prevalence and Risk Factors of Porcine Cysticercosis in Angónia District, Mozambique

2010-02-02T08:00:00Z

Author Summary

Porcine cysticercosis is an infection of pigs caused by the larval stage of Taenia solium, a tapeworm that causes taeniosis in humans. The disease is very common in pigs from many developing countries around the world and poses a serious public health risk and causes significant economic losses in pig production. In Mozambique there is scanty information regarding the occurrence of this disease. Our work conducted in Angónia district, northwestern Mozambique, allowed us to collect important information to evaluate the magnitude and identify the risk factors associated with porcine cysticercosis. This study found that cysticercosis is highly prevalent in pigs and that the free-range husbandry system was by far the main risk factor for the transmission of the disease in the district. These findings should help in the design of control strategies to prevent continuous transmission of this disease in Angónia and in Mozambique.

PLoS Neglected Tropical Diseases Issue Image | Vol. 4(1) January 2010

2010-01-26T08:00:00Z

A new approach to unravel the origin of syphilis.

The origin of numerous infectious diseases is still a mystery. Syphilis and the other treponematoses are among them. Integrating information on treponematosis from ancient human remains across time and space with modern phylogenetic data on the treponemes holds the potential to enable calculations of the evolutionary rate of treponemes. This in turn allows the origin of syphilis to be disentangled. Such a combination of tools could also be used to shed light on the origin of other infectious diseases that are still a burden to humankind (see article by de Melo et al., doi:10.1371/journal.pntd.0000575).

Artwork: Eduardo Gameiro. Original photographs: "Syphilis of Skull," Otis Historical Archives National Museum of Health and Medicine; "Electron micrograph of Treponema pallidum on cultures of cotton-tail rabbit epithelium cells (Sf1Ep)," Centers for Disease Control and Prevention's Public Health Image Library (CDC/Dr. David Cox).

Considerations for the Design and Conduct of a Pharmacovigilance Study Involving Mass Drug Administration in a Resource-Constrained Setting

2010-01-26T08:00:00Z

Quantifying the Lack of Scientific Interest in Neglected Tropical Diseases

2010-01-26T08:00:00Z

Characterization of a Subunit of the Outer Dynein Arm Docking Complex Necessary for Correct Flagellar Assembly in Leishmania donovani

2010-01-26T08:00:00Z

Author Summary

Leishmania parasites are responsible for the disease leishmaniasis. They are spread through sandflies. The primary hosts are mammals, including humans. They occur in two different morphological forms. The flagellated promastigotes live in the gut of the sandfly vector. After transmission to the mammalian host they get phagocytized by macrophages and convert into the amastigote form, which is able to survive within the phagolysosome. The molecular mechanisms underlying this transformation process from promastigote to amastigote are poorly understood so far. A striking difference of the life cycle stages is a long flagellum in the promastigote compared to only a rudimentary flagellum in the mammalian stage amastigote. During an earlier study of the stage differentiation of Leishmania donovani we identified a flagellar protein, a subunit of the outer dynein arm docking complex (ODA-DC2). This protein is part of a flagellar structure called the axoneme. Here we have further characterized the protein regarding its role within the life cycle of the parasite. Mutant promastigotes lacking DC2 protein show reduced flagellar length and a more amastigote-like appearance overall. In addition, the motility is heavily retrenched and transmission electron microscopy indicated that the flagellar ultrastructure is affected. Furthermore, the mutants express amastigote-specific genes and show increased in vitro infectiousness towards macrophages. Therefore, we conclude that the correct assembly of the flagellum is vital for maintenance of the promastigote stage of the parasite.

Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial

2010-01-26T08:00:00Z

Author Summary

Visceral leishmaniasis (VL) is a vector-borne disease causing at least 60,000 deaths each year amongst an estimated half million cases, and until recently there have been no significant initiatives to reduce this burden. However, in 2005, the governments of India, Bangladesh and Nepal signed a memorandum of understanding at the World Health Assembly in Geneva for the elimination of the disease by 2015. In the absence of an effective vaccine, the program will rely on the active detection and prompt treatment of cases throughout the endemic region, combined with a recurrent indoor residual spraying (IRS) of all villages at risk. Vector control programs based on IRS are notorious for failing to maintain comprehensive spray coverage over time owing to logistical problems and lack of compliance by householders. Long-lasting insecticidal nets (LNs) have been postulated as an alternative or complement to IRS. Here we describe how comprehensive coverage of LN in trial communities reduced the indoor density of sand flies by 25% compared to communities without LNs. This provides an indication that LNs could be usefully deployed as a component of the VL control program in the Indian subcontinent.

A CATT Negative Result after Treatment for Human African Trypanosomiasis Is No Indication for Cure

2010-01-26T08:00:00Z

Author Summary

The 2 year follow-up period required after treatment of human African trypanosomiasis (HAT) patients is a major challenge for patients and control programmes alike. The patient should return every 6 months for lumbar puncture and cerebrospinal fluid examination since, so far, no markers for cure have been identified in blood. The Card Agglutination Test for Trypanosomiasis (CATT) is a simple, rapid test for trypanosome-specific antibody detection in blood that is extensively used in endemic areas to screen for HAT. We examined the value of a normalising CATT as a marker for treatment outcome. We observed that CATT titres decreased after treatment both in patients who experienced treatment failure as well as in cured patients. We conclude that CATT, though a good screening test, is unreliable for monitoring treatment outcome. We also showed that the sensitivity of CATT in relapse cases was as low as 78%, and as a consequence some relapse cases might be missed in screening programs if they have no clinical signs yet.

Snake Bite in South Asia: A Review

2010-01-26T08:00:00Z

Snake bite is one of the most neglected public health issues in poor rural communities living in the tropics. Because of serious misreporting, the true worldwide burden of snake bite is not known. South Asia is the world's most heavily affected region, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of functional snake bite control programs. Despite increasing knowledge of snake venoms' composition and mode of action, good understanding of clinical features of envenoming and sufficient production of antivenom by Indian manufacturers, snake bite management remains unsatisfactory in this region. Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. Care-givers need better training and supervision, and national guidelines should be fed by evidence-based data generated by well-designed research studies. Poorly informed rural populations often apply inappropriate first-aid measures and vital time is lost before the victim is transported to a treatment centre, where cost of treatment can constitute an additional hurdle. The deficiency of snake bite management in South Asia is multi-causal and requires joint collaborative efforts from researchers, antivenom manufacturers, policy makers, public health authorities and international funders.

Neglected Infections of Poverty among the Indigenous Peoples of the Arctic

2010-01-26T08:00:00Z

Prevalence and Spatial Distribution of Entamoeba histolytica/dispar and Giardia lamblia among Schoolchildren in Agboville Area (Côte d'Ivoire)

2010-01-19T08:00:00Z

Author Summary

According to WHO, intestinal amoebiasis caused by Entamoeba histolytica is the third principal parasitic disease responsible for mortality in the world. This protozoal parasite infects approximately 180 million individuals throughout the world, among whom 40 to 110 thousand die from it each year. Giardiasis, caused by another protozoan parasite, Giardia lamblia, infects approximately 200 million individuals throughout the world, is a frequent cause of diarrhea in children, and can have negative impact on growth and development. Unfortunately, these intestinal protozoa are taken into account in few epidemiologic studies. The investigation we carried out to determine prevalence and spatial distribution of these infections shows the importance of these parasites in the Agboville department in southeast Cote d'Ivoire. Determination of spatial distribution of these parasites will help to focus delivery of chemotherapy in this area. In addition, our description of the relation of sources of drinking water with these parasitic infections will contribute to the development of an integrated treatment program for these parasites in this area of Côte d'Ivoire. This work will help make the population and political powers aware of the importance of these parasites and the need for safe drinking water in all localities of this area.

Active Trachoma among Children in Mali: Clustering and Environmental Risk Factors

2010-01-19T08:00:00Z

Author Summary

Active trachoma is not uniformly distributed in endemic areas, and local environmental factors influencing its prevalence are not yet adequately understood. Determining whether clustering is a consistent phenomenon may help predict likely modes of transmission and help to determine the appropriate level at which to target control interventions. In this work, we estimated the magnitude of clustering at different levels and investigated the influence of socio-economic factors and environmental features on active trachoma prevalence among children in Mali (1996–1997 nationwide survey). Clustering revealed significant results at the child, caretaker, household, and village levels. Moreover, beyond some well-established individual risk factors (age between 3 and 5, dirty face, and flies on the face), we found that temperature, sunshine fraction, and presence of rainy days were negatively associated with active trachoma prevalence. This study clearly indicates the importance of directing control efforts both at children with active trachoma as well as those with close contact, and at communities. These results support facial cleanliness and environmental improvements as population-health initiatives to combat blinding trachoma.

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

2010-01-19T08:00:00Z

Author Summary

Visceral leishmaniasis is a vector-borne disease characterized by fever, spleen and liver enlargement, and low blood cell counts. In the Americas VL is zoonotic, with domestic dogs as main animal reservoirs, and is caused by the intracellular parasite Leishmania infantum (syn. Leishmania chagasi). Humans acquire the infection through the bite of an infected sand fly. The disease is potentially lethal if untreated. VL is reported from Mexico to Argentina, with recent trends showing a rapid spread in Brazil. Control measures directed against the canine reservoir and insect vectors have been unsuccessful, and early detection and treatment of human cases remains as the most important strategy to reduce case fatality. Well-designed studies evaluating diagnosis, treatment, and prevention/control interventions are scarce. The available scientific evidence reasonably supports the use of rapid diagnostic tests for the diagnosis of human disease. Properly designed randomized controlled trials following good clinical practices are needed to inform drug policy. Routine control strategies against the canine reservoirs and insect vectors are based on weak and conflicting evidence, and vector control strategies and vaccine development should constitute research priorities.

Climate Change and Risk of Leishmaniasis in North America: Predictions from Ecological Niche Models of Vector and Reservoir Species

2010-01-19T08:00:00Z

Author Summary

We explored the consequences of climate change for the spread of leishmaniasis in North America. We modeled the distribution of two sand fly vector and four rodent reservoir species found in northern México and the southern United States. Models were based on occurrence data and environmental and topographic layers. Successful models were projected to 2020, 2050, and 2080 using an extreme (A2) and a conservative (B2) future climate scenario. We predicted potential range shifts of vector and reservoir species varying assumptions about dispersal ability and capacity to persist in habitats with different degrees of ecological suitability. Even with the most conservative assumptions the distributions of both vector and reservoir species expand northwards, potentially reaching as far as southern Canada in the east. Assuming that at least one vector and one reservoir species must be present for a parasite cycle, the extent of this shift is predicted to be controlled by the availability of suitable habitat for sand fly vector species. Finally, we computed the human population potentially exposed to leishmaniasis because of these range shifts. Even in the most optimistic scenario we found that twice as many individuals could be exposed to leishmaniasis in North America in 2080 compared to today.

Increasing Trends of Leptospirosis in Northern India: A Clinico-Epidemiological Study

2010-01-12T08:00:00Z

Author Summary

Leptospirosis is often not suspected by physicians in patients with acute febrile illnesses reporting from supposedly “non-endemic areas,” including north India. Clinical manifestations are protean, and complications can affect most organ systems, including liver, kidneys, lungs, and the central nervous system. Timely diagnosis and specific therapy can reduce severity of illness and, in turn, mortality. In this study conducted at a tertiary care center in north India, we find how a much-neglected disease entity has emerged as a major cause of acute febrile illness in a so called “non-endemic area.” Incidence is increasing yearly. The majority of patients were from a rural background, and were farmers or farm labourers. Poor hygiene, contact with animals, rat infestation of houses, and contact with stagnant dirty water are the major determinants of disease. Apart from the usual symptoms of intermittent fever with chill and rigor, hepatosplenomegaly, renal decompensation, muscle pain and tenderness, and conjunctival suffusion, signs and symptoms indicating involvement of the respiratory and central nervous systems were also commonly observed. Severe complications resulting in mortality do occur and is especially due to late suspicion among primary level physicians, and the resulting inappropriate therapy.

Leishmania major Glycosylation Mutants Require Phosphoglycans (lpg2−) but Not Lipophosphoglycan (lpg1−) for Survival in Permissive Sand Fly Vectors

2010-01-12T08:00:00Z

Author Summary

Phlebotomine sand flies are small blood-feeding insects, medically important as vectors of protozoan parasites of the genus Leishmania. Sand flies species can be divided roughly into two groups, termed specific or permissive, depending on their ability to support development of one or a few strains vs. a broad spectrum of these parasites. In this study, we explored the ability of two Leishmania major glycocalyx mutants to survive within these different types of vectors. The lpg1⁻ mutant, which specifically lacks lipophosphoglycan (LPG), was able to survive normally in two permissive species, Phlebotomus argentipes and P. perniciosus, but was only able to survive within the specific species P. duboscqi for a limited time prior to dissolution of the peritrophic matrix. Consistent with its classification as a specific sand fly vector, P. duboscqi was not able to support development of L. infantum. The lpg2⁻ L. major mutant, which is a broader mutant and lacks all phosphoglycans including LPG and proteophosphoglycans, was unable to survive in all the three vector species tested. This study extends the knowledge on the role of Leishmania major surface glycoconjugates to development in three important vector species and gives supporting evidence for the existence of an LPG-independent mechanism for survival in sand flies, as well as the importance of LPG2-dependent glycoconjugates in parasite survival.

Detection and Identification of Old World Leishmania by High Resolution Melt Analysis

2010-01-12T08:00:00Z

Author Summary

Protozoal parasites of the genus Leishmania are transmitted by sand fly bites to humans and animals. Three major forms of disease are caused by these parasites: cutaneous leishmaniasis, responsible for disfiguring skin wounds; mucocutaneous leishmaniasis, causing non-healing ulceration around the mouth and nose; and the potentially fatal visceral leishmaniasis, involving internal organs such as the spleen and liver. More than 2 million new human infections are caused annually by leishmaniasis globally, it is endemic in more than 88 countries and prevalent also as an imported disease in non-endemic regions due to travel and tourism. Most species of Leishmania that infect humans are zoonotic and transmitted from animal reservoir hosts. As various leishmanial parasites cause disease with similar symptoms, but require different therapeutic regimens and have dissimilar prognoses, reliable, sensitive and rapid diagnostic assays are needed. This study focuses on the five main species that cause leishmaniasis in the Old World. It presents a new assay for rapid detection, species identification and quantification of leishmanial parasites in clinical samples, reservoir hosts and sand flies. This technique could be especially valuable in regions where several leishmanial species exist, in non-endemic regions where infected patients require a rapid diagnosis, and for epidemiological host and vector studies leading to prevention programs.

Differential Cytokine Gene Expression According to Outcome in a Hamster Model of Leptospirosis

2010-01-12T08:00:00Z

Author Summary

Leptospirosis is a widespread bacterial infection that is transmitted by soil or water contaminated by the urine of infected animals, or directly from these animals. It has highly diverse clinical presentations, making its differential diagnosis difficult. Though most cases are minor and self-resolving, there are also severe forms that include a sepsis pattern and multiple organ failure, and have possible fatal outcomes. Predictors of disease evolution and outcome are scarce, yet they would be very valuable to clinicians as well as to better decipher disease pathogenesis. In this study, we used a hamster model of leptospirosis to evaluate if immune genes were differentially expressed between individuals and if their expression levels could help forecast the outcome of the disease. We found that hamsters that later died from leptospirosis had significantly higher expression levels of both pro- and anti-inflammatory mediators compared to survivors. These results suggest that expression levels of these immune effectors might be helpful predictors of outcome in leptospirosis and that septic shock contributes to fatal leptospirosis.