Situacion y nuevos conceptos de la Leptospirosis en el Mundo

Situacion y nuevos conceptos de la Leptospirosis en el Mundo

Situación actual y nuevos conceptos
de la Leptospirosis en el Mundo
Joseph Vinetz, MD, FACP, FIDSA,
FASTMH, C-TropMed
University of California, San Diego
Universidad Peruana Cayetano Heredia
The Leptospirosis Aphorism
Wherever leptospires and leptospirosis are
searched for, they are invariably discovered
–Torten and Marshall, Handbook of
Zoonoses, 1994, CRC Press
Patterns of Leptospirosis Transmission
• Sporadic
– Recreational exposure
– Adventure travel
– Military training
– Industrialized countries
• Endemic
– All humid tropical regions
– Disease manifestations may depend on acquired
immunity, genetics
• Epidemic
– Brazil, Korea, India,, more
– Different patterns of immunity and severe disease
Epidemiology of Highly Endemic Leptospirosis
• Related to daily activities of living
– Frequent, ubiquitous exposure
• Zoonotic Reservoirs
– Differ between urban and rural settings
– Is biodiversity in rural area vs. urban areas related to
transmission?
• Serovars/strains/species regionally distributed
– Copenhageni in Salvador, Brazil dominant
– Multiple serovars/species co-exist in Iquitos, Peru
• New species/serovars being discovered
– L. fainei serovar Hurstbridge
– Serovar Sehgali in Andaman Islands
– L. licerasi serovar Varillal, dominant
species/serovar in Iquitos, Peru
Estimated annual morbidity of
leptospirosis by country or territory
Estimated 1,000,000 cases per year, 5-20% mortality
Annual disease incidence represented as white (0-3), yellow (7-10),
orange (20-25), red (over 100), in cases per 100,000 population.
Unpublished
Aqui en la selva
• Mujer de 24 años, llevó a sus 2 niñas (2, 4 de edad) a la postea
de Los Delfines
• Las dos niñas con fiebre
• La mama asymptomática
• Sangre y orina
Will Bruno, MS1
Jessica Ricaldi MD, PhD
Michael Matthias PhD
Julian Torres, BS, Lic
Joseph Vinetz, MD
Madre y niñas qPCR positive for Lepto
• Mother’s initial
serum LipL32 qPCR
positive; urine
negative
• 16 days later, serum
LipL32 qPCR
negative, urine
positive
• The first time a
patient has been
identified as acutely
bacteremic yet
asymptomatic
• Both daughters' urine
lipL32 qPCR positive
(2 weeks later)
qPCR+
Urine
qPCR-
First sample
collection
Second sample
collection
Serum
Third sample
collection
Potential mechanisms for Leptospiral
Infection
• Point source family outbreak?
• Rats seen in home
• Swimming in local creek
(quebrada)
Implications for assessing
burden of disease
Environmental risk
factors confirmed
• Lepto detected
(qPCR) in quebrada
frequented by the
patient/family
• MLST, 16S
sequencing,
metagenomic
analysis of urine,
water underway, to
identify pathogenic
Leptospira present
Julian
Dot blot hybridization confirming leptospiral
DNA in patient urine samples
Ganoza CA, Matthias MA, Saito M, Cespedes M, et al. (2010) Asymptomatic Renal Colonization of Humans in the Peruvian Amazon
by Leptospira. PLoS Negl Trop Dis 4(2): e612. doi:10.1371/journal.pntd.0000612
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0000612
Phylogenetic
relatedness of
leptospiral 16s
rRNA gene
sequences using a
Bayesian
approach
Ganoza CA, Matthias MA, Saito M, Cespedes M, et al. (2010) Asymptomatic Renal Colonization of Humans in the Peruvian Amazon
by Leptospira. PLoS Negl Trop Dis 4(2): e612. doi:10.1371/journal.pntd.0000612
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0000612
Characteristics of Leptospira dot blot-positive
subjects (N = 13)(3.5% point prevalence)
Ganoza CA, Matthias MA, Saito M, Cespedes M, et al. (2010) Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by
Leptospira. PLoS Negl Trop Dis 4(2): e612. doi:10.1371/journal.pntd.0000612
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0000612
Agampodi, Matthias
Am J Trop Med Hyg 2013 vol. 88 no. 1 184-185
Perspectives About Control of
Zoonotic Diseases
• Identify animal source of human infection
• Cull (kill) individuals, groups, or herds
– Impossible for leptospirosis because diverse reservoirs
• Vaccinate animals
– Brucellosis: goats, cattle (live attenuated bacterium)
– Cysticercosis: pigs (protein subunit vaccine)
– Rabies: dogs, wild animals (oral rabies vaccine)
• Foxes, raccoons, skunks, coyotes
– Leptospirosis
• Limited, need new technologies
Human Leptospirosis Vaccine
• Who to vaccinate?
– Geographic diversity of risk groups
– Disease uncommon, not transmitted human-tohuman
– Public health vs. individual health importance
• What to vaccinate with?
– Leptospiral diversity
• How often to vaccinate?
– Effectiveness of vaccine
Perspectives on addressing
leptospirosis
• Quantify burden of disease
– Unknown
– WHO Leptospirosis Epidemiology Reference Group (LERG)
formally constituted
• www.who.int/entity/zoonoses/diseases/lerg/en/index.html
• Develop new diagnostic tools
– Genomic analysis, cross-species, cross-serovar
• Determine conserved molecular targets of protective immunity
• Determine ways to deliver oral vaccine against diverse Leptospira to
infected animal populations
• Determine novel ways to interrupt leptospiral persistence in
environment
Thanks to …
• UCSD
– Michael Matthias, Kathleen Pestal, Mark Swancutt
• Universidad Peruana Cayetano Heredia, Lima, Peru and
Iquitos, Peru
– Jessica Ricaldi, Julian Torres, Freddy Alava, Silvia Rengifo,
Eduardo Gotuzzo, Christian Ganoza, Humberto Guerra,
Kalina Campos, Eddy Segura, Monica Diaz, Sonia Torres,
nursing and technical staff
• MINSA, Hospital de Apoyo Iquitos
– Hermann Silva, Moises Sihuincha, Renzo Lopez, Carlos
Vidal Ore, Hugo Rodriguez
• WHO/FAO/OIE Collaborating Centre for Reference &
Research on Leptospirosis, Western Pacific Region
– Lee Smythe and colleagues
• NIH/NIAID DMID, NIH/Fogarty International Center