Leptospirosis in Puerto Rico - A One Health View - Final

Jonathan M. Chapman, DVM, MPH (c)Work-Study Student Intern

CDC Dengue Branch – Special SeminarApril 14, 2015

Leptospirosis in Puerto Rico: A One Health View

Division of Vector-Borne Diseases – Dengue Branch National Center for Emerging and Zoonotic Infectious Diseases

Presentation Outline An introduction to One Health The importance veterinarians and human physicians

to each other in medical practice An introduction to leptospirosis Leptospirosis in human and veterinary medicine The history and current status of leptospirosis in

Puerto Rico The plan to study leptospirosis on the island Summary and recommendations

What is One Health?

“One Health is the integrative effort of multiple disciplines working locally, nationally, and globally to attain optimal health for people, animals, and the environment.”1 – The American Veterinary Medical Association

1American Veterinary Medical Association. " One Health - It's All Connected."

One Health in the past Hippocrates (c. 460 BC – c. 375 BC)1

A Greek Physician known as the “Father of Western Medicine”. Described the relationship between human health and environment (such as weather, water

quality, living environment) in his work entitled “Airs, Waters, and Places” (c. 400 BC).2

Louis Pasteur (1822 – 1895)3

Studied and helped us to understand rabies, anthrax, chicken cholera, and silkworm diseases. Discovered the principles of pasteurization and vaccination. Developed the first rabies vaccine.

Calvin Schwab (1927 – 2006)4

Known as the “Father of Veterinary Epidemiology”. Contributed to a wide range of topics, including epidemiology, zoonotic diseases (diseases

transmitted between animals and humans), interactions of veterinary and human medicine, parasitic zoonoses, tropical health, and public health practice.

Author of Veterinary Medicine and Human Health (1984) where the term “One Medicine” was first mentioned.5

1Goldberg, Herbert S. “Hippocrates: Father of Medicine.”2Hippocrates. “On Airs, Waters, and Places.” Trans. Francis Adams. Daniel C. Stevenson3Rhee, Seung Yon. "Louis Pasteur (1822-1895).“4Kass, Philip H., Richard H. McCapes, and William R. Pritchard, Chair. "Calvin W. Schwabe." 5American Veterinary Medical Association. " One Health - It's All Connected.”

One Health today The One Health Initiative1

Informs the general public about the mission and vision of the One Health Initiative.

Provides publications and scholarly materials relating to various One Health topics from wide range of sources.

Links to the AVMA One Health Initiative Task Force. The AVMA One Health Initiative Task Force2

Defines One Health and describes the commission. Outlines information about what the AVMA is doing to

contribute to One Health and how people can be involved. Provides links to additional resources for further information

about various organizations, subjects, and publications.

1Khan, Laura H., MD, MPH, MPP, et al. One Health Initiative.2American Veterinary Medical Association. " One Health - It's All Connected."

Current world facts highlighting the importance of One Health1

World population exceeded 7 billion people in 2011.

Contact between human and wild animal habitats continues to increase.

Human-animal bond continues to grow throughout societies.

At least 75% of emerging and re-emerging diseases are either zoonotic or vector-borne.

Contamination by personal care products and pharmaceuticals has been detected in our waters.

1American Veterinary Medical Association. " One Health - It's All Connected."

Steps to achieving One Health1

Joint efforts between human and veterinary practitioners are needed for:

1. Educational efforts between all schools of medicine.2. Communication efforts in publications and

conferences.3. More effective and consistent clinical care across species. 4. Cross-species disease surveillance and control efforts in

public health. 5. Effective comparative medicine and environmental

research. 6. Development and evaluation of diagnostics, medicines,

and vaccines.7. Properly informing and educating political leaders and

the general public.1Khan, Laura H., MD, MPH, MPP, et al. One Health Initiative.

Why are veterinarians important to human health?1

Many emerging diseases are zoonotic. Examples of emerging zoonotic diseases: Ebola, avian influenza, Bovine Spongiform

Encephalitis (BSE) Examples of other zoonotic diseases: Rabies, brucellosis, leptospirosis, and many parasitic

diseases. Veterinarians bridge the gap between agriculture, the

environment, and human medicine. Over 14 diseases have been eliminated from equine, poultry, and livestock populations in the

United States.• Examples: Rinderpest, Foot and Mouth Disease

Decreases the risk of food-bourne disease transmission as well as zoonotic disease infection. Allows public access to a safer and more affordable food supply. Food animal and wildlife populations are inextricably linked to some environmental problems.

• Example: Waste and other potential run-offs into streams, rivers, lakes, and oceans. Much of the research into human health involves animal research. Many domestic animals are considered part of the family. Many potential bioterrorism agents are zoonotic diseases.

Examples: Variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague).

1King, Lonnie J., DVM. "Veterinary Medicine and Public Health at CDC."

Why are human physicians important to animal health?1

Human physicians help keep veterinarians healthy.

Zoonotic diseases transmit from humans to animals too.

Much of the human health research involves animals.

1King, Lonnie J., DVM. "Veterinary Medicine and Public Health at CDC."

What is leptospirosis?1

Leptospirosis is a bacterial disease of worldwide significance that infects both animals and humans. The disease is a problem in dogs, people, and livestock. Cats can be infected, but hey rarely show signs of disease.

Signs and symptoms of disease include: Fever, anorexia, vomiting, dehydration, increased thirst, shivering, muscle

or kidney pain, and icterus (yellowing of the skin, eyes, and mucous membranes).

Infection may result in chronic renal (kidney) failure and may also be fatal. Chronically infected hosts may show no outward signs or symptoms, but

may intermittently shed bacteria in the urine for months or years.

1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis.“Image: Jansen, Andreas and Schneider, Thomas. “Weil’s disease in a rat owner”.

Transmission1

There are over 200 different strains (serovars). There are eight that are of importance for domestic animals. Different strains produce different levels and types of disease depending on the animals they

infect. Leptospirosis is transmitted between animals through contact with the

following: Infected urine Venereal and placental transfer Bite wounds Ingestion of infected tissue

Crowding can increase the spread of infection. Example: Kennels

Contaminated water sources, food, and animal bedding serves as an indirect risk for exposure.

Stagnant or slow moving water provides a suitable habitat for leptospira. Disease outbreaks often increase during periods of flooding. In dry areas, infections are more common around water sources.

Infections are more common in summer and fall and in areas of temperate climate.

Freezing greatly reduces the survival of the organism in the environment. 1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis."

Infection with leptospirosis1

Bacteria penetrate mucous membranes or abraded skin, multiply rapidly in the blood system, and have an effect on several organs. Kidneys, liver, spleen, nervous system, eyes and genital

tract. The organism is cleared from most organs.

May persist in the kidneys and be shed for weeks or months in the urine.

After 7 or 8 days of infection, the host will begin to recover, if the damage to the kidneys or liver is not too severe.

1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis."

Maintenance hosts & associated serovars1

Mammal species Serogroup, serovar

Rats icterohemorrhagiae, ballumMice ballumDairy cattle hardjo, pomona, grippotyphosaPigs pomona, tarrassovi, bratislavaSheep hardjo, pomonaDogs canicola

1Puerto Rico Department of Health, San Juan, PR.

Diagnosis1

Positive diagnosis can be made through serology using a blood agglutination test. Tests for individual serovars and the level of antibody (titer) against these

strains. Titers may be negative in the first 10 days after initial infection. Additional samples may need to be drawn and tested to get a positive diagnosis. 4-fold rise in antibody titer is often observed in paired serum samples 7–10 days

apart. Previous animal vaccination can give an elevated titer and must

be taken into consideration when interpreting the titers. It is possible to culture a urine sample and get a positive

diagnosis. Acutely and chronically infected animals will most likely be shedding leptospires

in urine. Urine culture is not as reliable because of intermittent shedding and bacterial

contamination. Other diagnostic tools include immunofluorescence, PCR, and

blood culture, but are not considered as well validated yet.1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis."

Treatment1

Treatment consists of the following: Antibiotics

• Penicillin or fluoroquinoloes such as Doxycylcine Intravenous fluids Anti-emetics Other supportive medications for renal and liver function


Prevention1

Limit animal and human contact with potential sources of infection. Contaminated water sources Wildlife reservoirs Domestic animals that are infected or chronic carriers.

Since leptospirosis is a zoonotic disease, any potentially infected animal should be handled very carefully to avoid human exposure. Wear protective clothing Clean possible contaminated areas thoroughly


Vaccination1

There are currently many different vaccines available for dogs for a wide variety of serovars.

These vaccines are chemically inactivated (killed) whole culture vaccine.

Leptospiral vaccines for dogs offer about 6 to 8 months of protection. Dogs that are at a higher risk of contracting Leptospiral infections should be

vaccinated twice a year. Until 2000, leptospiral vaccines in dogs only protected against L.

canicola and L. icterohaemorrhagiae. Protection against serovars L. grippotyphosa and L. pomona have since

been added. Many veterinarians have begun to recommend leptospiral

vaccinations only for those dogs at higher risk. Lack of cross protection between strains The high incidence of reactions The need for frequent vaccination 1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis.”

Leptospirosis human medicine vs veterinary medicine

In general, leptospirosis is diagnosed, treated, and prevented in similar ways across medical practices.

The main differences between human and veterinary medical practice in regards to leptospirosis include: Types of diseases that may be confused with

leptospirosis The time between presentation and diagnosis Surveillance and reporting

Confusing leptospirosis with other diseases

The differential diagnosis for a patient presenting with signs and symptoms consistent with leptospirosis can be rather daunting.

Other diseases confused with in human medicine1

Dengue, influenza, rickettsial infections (typhus, scrub typhus), meliodosis, enterovirus, meningococcemia, bacterial sepsis, West Nile virus, HIV seroconversion.

Other diseases confused with in veterinary medicine Ehrlichiosis, autoimmune hemolytic anemia, infectious canine hepatitis

virus, canine brucellosis, canine herpesvirus infection, canine distemper, hepatitis, piroplasmosis

These discrepancies have led to increased time between presentation and diagnosis, especially in human cases.1Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR.

Surveillance and reporting leptospirosis

Surveillance and reporting for leptospirosis is not consistent between human and veterinary medicine.

Surveillance and reporting for leptospirosis in human medicine1

Leptospirosis in humans is a nationally reportable disease in the United States.

Surveillance for leptospirosis is generally through passive surveillance.

Surveillance and reporting for leptospirosis in veterinary medicine

Leptospirosis in animals is not a nationally reportable disease Some state and local laws may vary in reporting requirements for

leptospirosis. Surveillance for leptospirosis is generally through active surveillance.

There is currently no combined surveillance or reporting system for animals and humans.

1Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR.

What can human physicians and veterinarians learn from each other

about leptospirosis? Veterinarians and human physicians can

work together to better understand leptospirosis. Serovar prevalence Incidence rates Cross-species medical practices for optimal care

Collaboration between veterinarians and human physicians is necessary!

History of leptospirosis in Puerto Rico Leptospirosis is endemic to Puerto Rico.1

Historical information about leptospirosis in Puerto Rico is not widely available. The disease was first documented on the island in 1942. Under-reporting of the disease over the years is suspected.

Concurrent leptospirosis and Dengue outbreaks are common due to heavy rainfall.2

Periods of heavy flooding in Puerto Rico occurred in 1996 and 2010 due to factors such as hurricanes.

In 1996, serum specimens of 4 patients with suspected dengue tested negative for the disease, but tested positive leptospirosis.

In 2010, 68 non-fatal cases and 25 fatal cases of leptospirosis were found.3

Out of 93 total cases in 2010, 59 cases were reported to the Puerto Rico Department of Health.

1Koppisch, ER, et al. "Weil's Disease in Puerto Rico: Report of Five Cases, One of Them with Post-mortem Findings.” 2Sanders, EJ, et al. "Increase of Leptospirosis in Dengue-negative Patients after a Hurricane in Puerto Rico in 1996.”3Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR.

Leptospirosis in Puerto Rico today1

Human physicians report suspected and confirmed leptospirosis cases to the Puerto Rico Department of Health. A diagnostic test is required.

• There is fee of $150 per test.• The test is sent off-island and results are received in 5-7 days.

A high rate of under-reporting is suspected. There are 15-100 cases of leptospirosis reported to the

Puerto Rico Department of Health each year. Reported cases began to increase in the early 2000’s. In 2007, a peak occurred when nearly 100 cases were reported. In 2010, cases began to rise again with 59 reported cases. It is unclear if these figures are representative of the true incidence of

Leptospirosis in Puerto Rico due to the high rate of under-reporting that is suspected.

The Vital Registry of Puerto Rico reports fatal cases to the Puerto Rico Department of Health.

1Puerto Rico Department of Health, San Juan, PR.

Leptospirosis cases reported to the Puerto Rico Department of Health,

1990-20131

*The data for 2013 is current to June 30, 2013.

1Epidemiology & Research Office, Puerto Rico Department of Health, San Juan, PR.

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

0

20

40

60

80

100

120

Year

Case

s re

port

ed

N=710

*

Incidence of leptospirosis by municipality in the Ponce area, 2006-

20101

1Epidemiology & Research Office, Puerto Rico Department of Health, San Juan, PR.

Adjunta

s

Coamo

Guanic

a

Guayam

a

Guayan

illaJay

uya

Juana

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elas

Ponce

Salina

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Yauco

0

20

40

60

80

Municipality

Rate

per

100

,000

res

iden

ts

N = 58

Epi-Aid in Puerto Rico Epi-Aids are requests to the CDC for epidemiological

assistance within the United States and throughout the world.1

In 2011, an Epi-Aid was conducted in Puerto Rico.2

21 confirmed and 5 suspected deaths due to leptospirosis were identified from 2010 in total.

18 deaths due to leptospirosis were identified through enhanced Acute Febrile Illness (AFI) surveillance.

4 confirmed and 4 suspected death cases due to leptospirosis were identified through the Vital Registry of Puerto Rico.

Only 18 deaths due to leptospirosis were reported to the Puerto Rico Department of Health.

1Centers for Disease Control and Prevention. "Epi-Aid Investigations.” 2Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR.

Epidemic curve for cases of leptospirosis, 20101


Ja Fe M AMay Jul

y A Se Oc No De0

5

10

15

20

25

30

35

40Non-fa...

Month, 2010

Case

s

(n = 147)(n = 26)

Interviews with human physicians1

Interviews were conducted with physicians from two reference hospitals. Ponce (N = 11) San Juan (N = 8)

Physicians volunteered to be interviewed. Interviews were done using a standardized

questionnaire. Administered by staff of the Centers for Disease Control

and Prevention and the Puerto Rico Department of Health






Interviews with veterinarians1

Interviews with veterinarians were conducted Aug 19 -20, 2011 during the XXV Annual Convention. August 19 (N = 27) August 20 (N = 12)

Veterinarians volunteered to be interviewed.

Interviews were done using a standardized questionnaire. Administered by staff of the Centers for Disease Control

and Prevention and the Puerto Rico Department of Health






What does this all mean?

Many facts about leptospirosis in Puerto Rico remain unknown. How many people are affected? What behaviors are causing people to get infected? What animals are shedding leptospires in their urine?

A comprehensive investigation of leptospirosis in Puerto Rico is needed!

The plan to study leptospirosis in Puerto Rico1

It would be the first comprehensive investigation of leptospirosis in Puerto Rico and one of the first in the Caribbean.

Examples from the Caribbean:• Martinique, April 2011• Jamaica, September 2010

Results of an investigation in Puerto Rico are expected to educate the public as well as clinicians. Risk stratification, behavioral, or other interventions to reduce human exposure

to leptospires. Culture-specific approaches for source reduction and use of barrier methods.

2 areas in Puerto Rico have been selected for a leptospirosis study based on a high incidence of Leptospirosis infection. Urban: Caño Martín Peña, a neighborhood in San Juan Rural: Jayuya, a municipality in the Ponce area

The study is tentatively set to begin in June 2015 pending approval.

1Puerto Rico Department of Health, San Juan, PR. Collaborators: Centers for Disease Control and Prevention, Ponce School of Medicine and Health Sciences, University of Florida College of Medicine, Yale University School of Public Health.

Who will be performing the study?1

Primary Investigator Puerto Rico Department of Health

Collaborating Investigators Centers for Disease Control and Prevention Ponce School of Medicine and Health Sciences University of Florida College of Medicine Yale University School of Public Health


The aims of the study1

1. Determine the prevalence of anti-Leptospira antibodies among residents of these two communities to estimate the prevalence of past infection with leptospires.

2. Inform approaches to develop educational interventions for the prevention and control of leptospirosis.

3. Investigate peri-domestic small mammals that may serve as enzootic animal reservoirs for leptospires.

4. Detect leptospires in water and soil through molecular detection assays.

5. Look for risk factors using the data collected with seropositivity as the outcome.


How can you help? Everyone can get involved in some way!

One Health Increase awareness about One Health through discussion. Refer to resources.

• The One Health Initiative: http://onehealthinitiative.com• The AVMA One Health Task Force: http://www.avma.org/onehealth

Leptospirosis in Puerto Rico Protect yourself and your animals and pets against disease.

• Cover any open wounds and wear proactive footwear and eyewear when walking or swimming in water.

• When working with soil, wear gloves in addition to the precautions listed for water.• Avoid contact with animal urine or bodily fluids, especially if you have cuts or abrasions

on your skin.• Consult with a veterinarian about vaccinating your dog(s) against leptospirosis.

Report any suspected cases of leptospirosis to a physician, veterinarian, or the Puerto Rico Department of Health.

The proposed study Phlebotomists are needed for the study.

• Compensation will be provided.• If you or someone you know can volunteer or help find volunteers, please contact Dr.

Tyler Sharp at [email protected].

Summary and recommendations One Health is vital to humans, animals, and

the environment. Integration of surveillance systems between humans

and animals. Increase consistency between human and veterinary

medicine. Human physicians, veterinarians, and the

general public need further education. Increased awareness about One Health and

Leptospirosis. Education for prevention, especially in high risk groups.

Surveillance for leptospirosis in Puerto Rico needs to be improved. The proposed study for 2015 should only be the

beginning.

AcknowledgementsCDC Dengue Branch, San Juan, PR Tyler Sharp, PhD Janice Pérez-Padilla, RN, MPH Aidsa Rivera, MS Kay Tomashek, MPH, MD Harold Margolis, MD Marrielle Mayshack, BS Nicole M. Pérez Rodríguez, MPH

CDC Bacterial Special Pathogens Branch, Atlanta, GA William Bower, MD Marta Guerra, DVM, PhD Dianna Blau, DVM Renee Galloway, MPH Sean Shadomy, DVM Sherif Zaki, MD Rita Traxler, MPH

CDC Epidemiology and Laboratory Capacity Grant, Atlanta, GA Alvin Shultz, MBA Wayne Brathwaite, PHA Angelica O’Connor, PHA

Puerto Rico Department of Health, San Juan, PR Brenda Rivera-García, DVM, MPH Johnny Rullán, MD, FACPM Shirley Morales Estrada, MPH Kyle R. Ryff, MPH

Yale University School of Public Health, New Haven, CT Emily Briskin Elsio Wunder, DVM, PhD Vimla Bisht, PhD Albert Ko, MD

University of Florida College of Medicine, Gainesville, FL Anthony P. Cannella, MD, MSc Jason S. Lehmann, PhD

Ponce School of Medicine and Health Sciences, Ponce, PR Jesús Hernández Burgos, DrPH (c)

Hospital Episcopal San Lucas, Ponce, PR Julio Bracero, MD

Also, a special thanks to the entire staff at the CDC Dengue Branch for being so supportive!

For more information please contact Centers for Disease Control and Prevention1600 Clifton Road NE, Atlanta, GA 30333Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: [email protected] Web: www.cdc.gov

Any questions?

National Center for Emerging and Zoonotic Infectious DiseasesDivision of Vector-Borne Diseases – Dengue Branch

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Maintenance Hosts and Associated Serovars1

Leptospira

Serovars

Primary Host

Dog Cat Human Other Domestic Animals

Wild Animals

Bratislava Rat, pig, horse

+ _ + Cow, horse Mouse, raccoon, opossum, vole, fox, skunk

Autumnalis

Mouse + _ + Cow Rat, raccoon, opossum

Ictero-haemorrhagiae

Rat + + + Cow, horse, pig

Mouse, raccoon, opossum, hedgehog, fox, woodchuck, ape, muskrat, skunk, civet

Pomona Cow, pig, skunk, opossum

+ + + Horse, sheep, goat, rabbit

Mouse, raccoon, hedgehog, wolf, fox, woodchuck, deer

1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis." The Merck Veterinary Manual. Whitehouse Station, NJ: Merck, 2010. Print.

Maintenance Hosts and Associated Serovars1

Leptospira Serovars

Primary Host

Dog Cat Human Other Domestic Animals

Wild Animals

Canicola Dog + + + Cow, horse, pig

Rat, raccoon, hedgehog, armadillo, mongoose, skunk

Bataviae Dog, rat, mouse

+ + + Cow Hedgehog, armadillo, vole, shrew,

Hardjo Cow + - + Pig, horse, sheep

Wild bovidae

Grippotyphosa

Vole, raccoon, skunk, opossum

+ + + Cow, pig, sheep, goat, rabbit, gerbil

Mouse, rat, fox, squirrel, bobcat, shrew, hedgehog, muskrat, weasel

1Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis." The Merck Veterinary Manual. Whitehouse Station, NJ: Merck, 2010. Print.

Characteristics of Fatal Leptospirosis Cases, 20101


ReferencesAmerican Veterinary Medical Association. " One Health - It's All Connected." AVMA, Schuamburg, IL, 2015. Web. 08 Apr. 2015. <http://www.avma.org/onehealth>.

Centers for Disease Control and Prevention. "Epi-Aid Investigations." Centers for Disease Control and Prevention, Atlanta, GA, 26 Nov. 2014. Web. 09 Apr. 2015. <http://www.cdc.gov/nceh/eis/epi_aid.html>.

Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR. Charts, graphs, and information. 2011.

Goldberg, Herbert S. “Hippocrates: Father of Medicine.” Bloomington, IN: Iuniverse, 2006. Print.

Hippocrates. “On Airs, Waters, and Places.” Trans. Francis Adams. Daniel C. Stevenson, Web Atomics, and Massachusetts Institute of Technology, 2009. Web. 08 Apr. 2015. <http://classics.mit.edu/Hippocrates/airwatpl.html>.

Kass, Philip H., Richard H. McCapes, and William R. Pritchard, Chair. "Calvin W. Schwabe." The University of California, Davis, CA, 2006. Web. 08 Apr. 2015. <http://senate.universityofcalifornia.edu/inmemoriam/calvinwschwabe.htm>.

Kahn, Cynthia M., and Scott Line. "Overview of Leptospirosis." The Merck Veterinary Manual. Whitehouse Station, NJ: Merck, 2010. Print.

Khan, Laura H., MD, MPH, MPP, et al. One Health Initiative. Bruce Kaplan, DVM, Sarasota, FL, 2012. Web. 08 Apr. 2015. <http://onehealthinitiative.com/>.

King, Lonnie J., DVM. "Veterinary Medicine and Public Health at CDC." Centers for Disease Control and Prevention, 22 Dec. 2006. Web. 08 Apr. 2015. <http://www.cdc.gov/mmwr/preview/mmwrhtml/su5502a4.htm>.

Koppisch, ER, et al. "Weil's Disease in Puerto Rico: Report of Five Cases, One of Them with Post-mortem Findings." Puerto Rico Journal of Public Health and Tropical Medicine (1942): 305-31. Print.

Puerto Rico Department of Health, San Juan, PR. Charts, graphs, and information. 2011.

Puerto Rico Department of Health, San Juan, PR. Collaborators: Centers for Disease Control and Prevention, Ponce School of Medicine and Health Sciences, University of Florida College of Medicine, Yale University School of Public Health. 2015.

Rhee, Seung Yon. "Louis Pasteur (1822-1895).“ Access Excellence at the National Health Museum, Silver Spring, MD, 2009. Web. 07 Apr. 2015. <http://www.accessexcellence.org/RC/AB/BC/Louis_Pasteur.php>.

Sanders, EJ, et al. "Increase of Leptospirosis in Dengue-negative Patients after a Hurricane in Puerto Rico in 1996." The American Journal of Tropical Medicine and Hygiene 61.3 (1999): 399-404. Print.

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Leptospirosis in Puerto Rico - A One Health View - Final