AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Leptospirosis is a worldwide zoonosis caused by pathogenic species of the genus Leptospira. In 90% of cases, leptospirosis manifests as an acute febrile illness with a biphasic course and an excellent prognosis. Nonspecific signs and symptoms of leptospirosis (eg, fever, headache, nausea, vomiting) are often confused with viral illness.

In 10% of cases, the presentation is more dramatic, and the infection has a mortality rate of 10%. Known as Weil disease or icteric leptospirosis, the classic definition of this form of leptospirosis includes fever, jaundice, renal failure, and hemorrhage. Other organ systems (ie, pulmonary system, cardiac system, CNS) are also frequently involved.

Weil is credited with first describing leptospirosis as a unique disease process in 1886, 30 years before Inada and colleagues identified the causal organism.¹

The genus Leptospira belongs to the Leptospiraceae family of the order Spirochaetales. The nomenclature system used to organize leptospires has been revised, making review of the literature often confusing. The traditional system divided the genus into 2 species: the pathogenic Leptospira interrogans and the nonpathogenic Leptospira biflexa. These species were divided further into serogroups, serovars, and strains based on shared antigens. L interrogans included more than 250 serovars.

The current classification system is based on DNA homology and recognizes the heterogeneity of the classic leptospires, dividing L interrogans and L biflexa into 12 named species, 4 unnamed species, and 2 additional genera.²

• Leptospira interrogans
• Leptospira weilii
• Leptospira santarosai
• Leptospira noguchi
• Leptospira borgpetersenii
• Leptospira kirschner
• Leptospira alexanderi
• Leptospira inadai (pathogenicity unclear)
• Leptospira fainei (pathogenicity unclear)
• Leptospira meyeri (pathogenicity unclear)
• L biflexa (saprophytes)
• Leptospira wolbachi (saprophytes)
• Unnamed Genomospecies 1 (pathogenicity unclear), 3 (saprophytes), 4, and 5 (saprophytes)
• Turneria parva (formerly Leptospira parva, saprophytes)
• Leptonema illini (saprophytes)

Within these species, leptospires are further grouped by serogroups, serovars, and strains on the basis of microscopic agglutination testing (MAT). Serologic grouping may, however, cross DNA based species boundaries. Although certain species (eg, L interrogans) have a classic association with Weil disease, knowledge of the species type does not necessarily help predict disease severity.

Leptospires infect many types of mammals including rats, dogs, cats, cattle, pigs, squirrels, raccoons, mongooses, and bandicoots.^{3, 4} Leptospiral species' and serogroups' host animals vary from region to region. Individual animals may carry several serovars.

Leptospirosis in animals is often subclinical. An infected animal may appear healthy even as it sheds leptospires in its urine. Leptospirosis has also been reported in immunized dogs, a finding possibly explained by either partial immunity or vaccines that did not cover the serovars responsible for the infection. Humans are dead-end hosts for the leptospire. Although both nosocomial and congenital leptospirosis have been described, both are rare.^{5, 6}

Leptospires are transmitted via infected urine. Leptospires infect humans by invasion across mucosal surfaces or nonintact skin. Infection may occur via direct contact with urine or through contact with contaminated water and soil. In favorable conditions, leptospires can survive in freshwater for as many as 16 days and in soil for as many as 24 days.⁷

Many published case series focus on seasonal outbreaks and leptospirosis acquired occupationally or recreationally. Seasonal outbreaks associated with changes in local water levels have been described: flood conditions increase risk of exposure to the population at large, and drought causes leptospire concentrations to peak in isolated pools.^{8, 9} Animal handlers, farmers, and people active in freshwater sports are well-known high-risk groups for leptospirosis.^{10, 11}

Pathophysiology

Leptospire invasion across the epithelium is followed by proliferation and widespread dissemination. Every major organ system may be affected, and leptospire antigens can be detected in affected tissues. Leptospire-mediated injury characterizes the initial phase of the disease. A host-immune response marks onset of the second phase of symptoms.

Although direct invasion of tissue may cause some pathologic effects, researchers note that the marked degree of multiorgan tissue injury appears inconsistent with the number of leptospires found on microscopic examination of tissue. Other mediators induced by the leptospire are the suspected causes of the disease's various manifestations. Research has suggested endotoxin, hemolysin, and lipase as possible sources of pathogenicity. However, the true mechanism of host tissue injury remains unclear and likely involves a complex set of interactions.

The most consistent pathologic finding in leptospirosis is vasculitis of capillaries manifested by endothelial edema, necrosis, and lymphocytic infiltration. Capillary vasculitis is found in every affected organ system. The resulting loss of RBCs and fluid through enlarged junctions and fenestrae, which cause secondary tissue injury, probably accounts for many of the clinical findings.

Capillary vasculitis and leakage cause petechiae, intraparenchymal bleeding, and bleeding along serosa and mucosa. Thrombocytopenia sometimes is observed but is not a consistent finding in patients with bleeding. No disseminated intravascular coagulation (DIC) occurs. Prothrombin time (PT) sometimes increases in patients with leptospirosis, but vitamin K administration and concomitant correction of the PT do not alter the course of bleeding.

Direct hepatic injury appears to cause jaundice, although jaundice resulting from hemolysis and biliary obstruction has been suggested. Vascular congestion and disorganization of the liver cell plates are hallmarks of liver tissue injury in patients with leptospirosis. Hemolytic anemia is not associated consistently with jaundice.

Pulmonary findings are caused by alveolar capillary injury, either focal or diffuse. Interstitial and intra-alveolar edema and bleeding occur in areas affected by vasculitis and, in severe cases, may progress to frank hemorrhage. Regions without infiltrate also are free of vasculitis.

Renal findings include tubular necrosis and, later in the disease course, interstitial nephritis. Capillary vasculitis is readily identified. Although the glomeruli are spared, the progression from normal renal function to decreased glomerular filtration rate (GFR) to renal failure requiring dialysis can be rapid.

Cardiac lesions have been identified in postmortem examinations. In a series of 20 fatal cases, epicardial and endocardial petechiae were present in 70% of the patients, myocardial interstitial edema was present in 90%, lymphocyte/plasma cell infiltrate (consistent with myocarditis) was present in 50%, and coronary arteritis was present in 70%.

Hemorrhage, focal necrosis, and inflammatory infiltration have been documented within the adrenal gland. Although these complications do not appear clinically, some researchers speculate that adrenal insufficiency may mediate, in part, the final vascular collapse associated with fatal leptospirosis.

Frequency

United States

Leptospirosis, as a clinical entity, is underdiagnosed and underreported. The reported annual incidence ranged from 0.02-0.04 cases per 100,000 persons in 1985-1994. In 1994, 38 leptospirosis cases were reported nationwide,¹² and the Council of State and Territorial Epidemiologists recommended removing leptospirosis from the list of notifiable diseases. Hawaii, which reports the highest annual occurrence rate, had 22 of those 38 confirmed cases. Between June 1998 and February 1999, Hawaii reported 405 suspected cases of leptospirosis; 61 of those cases were confirmed.¹³ Case numbers widely varied from island to island within the state. Incidence rates ranged from 2.3-40.2 cases per 100,000 persons, with the highest numbers of cases on Kauai and Hawaii. Serologic MAT of healthy blood donors among the military population in Hawaii showed a seroprevalence of 1.4%.¹⁴

These reported cases starkly contrast with the prevalence rates found under active surveillance.¹⁵ Using active surveillance measures, Hawaiian researchers projected the state's true local incidence at approximately 128 cases per 100,000 persons. Major risk factors identified in Hawaii include the use of water catchment systems, wild pig hunting, and the presence of skin wounds.

Although less dramatic and often unrecognized, people with no obvious risk factor have significantly higher background infection rates than reports often indicate. Approximately 30% of children in urban Detroit¹⁶ and 16% of adults in Baltimore¹⁷ demonstrated serologic evidence of past infection. This pattern has been reproduced elsewhere; rural and suburban seropositivity rates reportedly lag behind urban rates. The Detroit study also showed correlation between degree of rat infestation and seropositivity rates. This finding suggests rats are major, if not the most important, vectors for human leptospirosis in the mainland United States. In Hawaii, the state with the highest reported incidence of leptospirosis, feral pigs are also important vectors.¹⁵

International

Leptospirosis has been documented worldwide, but formal reporting systems widely vary. Reported incidence rates often are comparable to those in the United States and suffer from the same pitfalls. High-risk areas include the Caribbean islands, Central and South America, Southeast Asia, and the Pacific islands. Frequently, the disease gains public attention when outbreaks occur in association with natural disasters, such as flooding in Nicaragua in 1995 or among foreign travelers, as with extreme athletes competing in tropical rainforests.

Mortality/Morbidity

In 10% of cases, leptospirosis has severe manifestations including renal failure, hepatitis, pulmonary hemorrhage, reaching mortality rates of 10%.

Sex

Leptospirosis is most common among adult males, probably resulting from occupational and recreational exposures. In the converse, the difference in rates may be caused by practitioners who are more likely to look for and, hence, diagnose the disease in patients who have obvious risk factors. When population groups other than adult males are actively surveyed, prevalence rates are higher than those previously reported.

Age

Although most case series and reviews of leptospirosis indicate men as the key risk group, outbreaks have been reported in which more than 40% of patients were younger than 15 years, a reversal of traditional prevalence rates. Potential explanations in such cases include childhood predilections to play with suspected vectors (eg, dogs) or indiscriminate contact with water. Active surveillance measures have detected leptospire antibodies in as many as 30% of children in some urban American populations.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

Patients with leptospirosis may present with a wide range of complaints and physical findings. Leptospirosis has historically been called a protean disease in reference to various signs and symptoms that may occur throughout its biphasic clinical course.

Symptom onset often occurs abruptly after the 2-day to 20-day incubation period. Direct tissue injury from leptospire invasion and toxins, which have been theorized yet never clearly elucidated, characterize the acute phase. Symptoms then abate with cessation of the systemic proliferation of leptospires.

The second or immune phase is characterized by increasing antibody titers and inflammatory infiltration of affected organ systems. Aseptic meningitis and renal dysfunction are hallmarks of the immune phase. Symptoms may persist for 6 days to more than 4 weeks, with a mean duration of 14 days.

• Approximately 10% of patients diagnosed with leptospirosis develop signs of Weil disease. The classic definition of Weil disease is severe leptospirosis presenting with jaundice, renal failure, and pulmonary hemorrhage. Mortality rates among these patients is 10%, despite care in an ICU, and even higher in regions with less sophisticated care. Severe, fatal cases of leptospirosis may occur without associated jaundice.
• In both children and adults, leptospirosis commonly presents with fever, myalgia, and headache. Lethargy, emesis, abdominal pain, photophobia, arthralgia, cough, diarrhea, or constipation also may occur. The differential diagnosis for these symptoms is confoundingly broad and ranges from benign viral syndromes of childhood to meningitis and sepsis.
• Despite reports of fever as a cardinal symptom, research by the Hawaii Department of Health found the presence of fever varied.^{15, 18} In serologically confirmed cases, 5% of patients gave no history of fever, and 55% were afebrile at the time of presentation. Myalgias and headache were universally reported at the time of presentation and were the chief complaint in 25% of patients.
• Leptospirosis occurring during pregnancy is particularly ominous. In a review of 16 cases, spontaneous abortion was likely during the first 2 trimesters.⁶ A third of pregnancies ended in abortion or perinatal death when disease occurred in the third trimester. Successful treatment of congenital leptospirosis has been described. Leptospirosis may cause fetal deaths, even from infections that were subclinical in the mother.

Physical

Physical examination at the time of presentation may reveal conjunctival hyperemia, exquisite myositis, and abdominal tenderness. Jaundice or scleral icterus occurs but is not a universal finding, even in severe cases.⁸ Examination of the lower extremities often reveals abrasions or other breaks in the skin which may serve as a portal of entry for the organism.

The term suffusion, referring to a reddening of the eye surface, has historically been linked to findings of leptospirosis. Formal ophthalmologic evaluation of the eye during the acute phase of leptospirosis may reveal dilation of the conjunctival vasculature, subconjunctival hemorrhage, and retinal vasculitis. During the immune phase, iridocyclitis is the predominant ocular finding. The anterior chamber most is frequently involved, but uveitis of the posterior chamber has also been documented.

Lymphadenopathy of the cervical, axillary, and mediastinal regions may occur at presentation or develop over the course of disease progression.

GI manifestations of leptospirosis include jaundice, hepatitis, acalculous cholecystitis, pancreatitis, and GI bleeding. Bilirubin levels in patients with Weil disease can exceed 30 mg/dL. Brief elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are relatively mild. These levels may be normal, even in children with jaundice. Leptospire induced acalculous cholecystitis is well described in pediatric literature and frequently results in surgical intervention.

Although uncommonly reported, clinicians at Tripler Army Medical Center in Hawaii published a case series of 10 patients (8 of whom were pediatric patients) with leptospiral pancreatitis.^{19, 20} Amylase levels ranged from 112-663 U/L and lipase peaked at a range of 377-2887 U/L. Pancreatic enzyme levels peaked on days 8-10 of illness. Patients experienced 3-11 days of abdominal pain and recovered without pancreatic sequelae, although some patients required total parenteral nutrition (TPN). Common complaints of abdominal pain, nausea, and vomiting associated with leptospirosis warrant evaluation of pancreatic function. GI bleeding related to systemic vasculitis may develop throughout the GI tract and varies in severity.

Pulmonary manifestations include cough, hemoptysis, and pneumonia. Chest radiography may reveal unilateral, bilateral, or multifocal infiltrates, as well as pleural effusions. Anatomic and histologic studies show these infiltrates are areas of interstitial and intra-alveolar hemorrhage surrounded by focal capillary injury. Respiratory symptoms may become severe and progress to acute respiratory distress syndrome (ARDS), requiring intubation and mechanical ventilation.

Meningitis has classic association with the immune phase of disease. Headache is often a presenting symptom. Leptospires may be cultured from the cerebrospinal fluid (CSF) during the leptospiremic phase of the disease. A lymphocyte-predominant pleocytosis as high as 580 cells per high power field (hpf) occurs as early as day 4 of disease. Cell counts peak between days 5-10. Although CSF evidence of meningitis is present in more than 80% of patients in some series, only half of those patients may have signs and symptoms of meningeal irritation.

Renal pathology appears to vary during the course of the disease. Urinalysis may reveal sterile pyuria, hematuria, proteinuria, and granular casts. Acute tubular necrosis (ATN) and interstitial nephritis are the 2 classic renal lesions associated with leptospirosis. Direct leptospire injury may cause ATN, whereas interstitial nephritis occurs later and is probably related to antigen-antibody complexes of the immune phase. Patients may rapidly progress from normal renal function to renal failure requiring dialysis.

Hypokalemia secondary to tubular wasting may occur. Hyperkalemia associated with metabolic acidosis and hyponatremia have been reported with leptospirosis. Acute renal failure marked by oliguria or polyuria may appear 4-10 days after the onset of symptoms. Ranges of BUN of 55-185 mg/dL with average peak creatinine levels of 10.6 mg/dL have been described in a series of 16 pediatric patients with leptospiral acute renal failure.²¹ Average BUN-to-creatinine ratios were 10:1, which suggests dehydration was not a factor in the cause of renal failure, as previously believed by some investigators. Of the 16 patients, 10 (63%) required dialysis.

Rash may present as a macular or maculopapular eruption with erythematous, urticarial, petechial, or desquamative lesions.

Myositis often begins during the first week of symptoms and may last into the third and fourth weeks. Hemorrhage into muscle beds, particularly those of the abdominal wall and lower extremities, causes exquisite pain and is believed responsible for some acute abdomen presentations.

Bleeding may occur in as many as 39% of patients. Findings range from epistaxis and gingival oozing to hematuria, hemoptysis, and pulmonary hemorrhage. Disseminated intravascular coagulation (DIC) has not been described in cases of leptospirosis. Thrombocytopenia and elevations in prothrombin time (PT) may occur but do not appear causally related. Anemia may occur in the context of a bleeding diathesis. CBC analysis may reveal white cell counts within the normal range, with a left shift to as high as 4 X 10³/µL and a neutrophilic predominance. Erythrocyte sedimentation rate typically is elevated.

Leptospire vasculitis also presents with third spacing of fluids that may progress to hypovolemic shock and vascular collapse. Vigorous fluid resuscitation may be required, but clinicians should consider renal failure among the possible comorbidities of severe leptospirosis.

Cardiac complications are well described in patients with severe-to-fatal disease.^{22, 23} Myocarditis and coronary arteritis may occur. Friction rubs may be noted in some patients. In one series, ECG abnormalities were found in 48% of patients older than 14 years with severe disease. First-degree atrioventricular (AV) block is most common (ie, 30% of patients), presents early in the disease course, and resolves in patients who survive. T-wave inversions occurred in 18% of patients, ST-segment elevation in 15%, and dysrhythmias in 11%, but the latter were not associated with progression to shock or congestive heart failure.

Causes

See Pathophysiology.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Influenza
Malaria
Brucellosis
Rickettsiosis
Hantavirus
Other hemorrhagic fevers

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• In leptospirosis, because of long culture times and low recovery rates, low sensitivity of acute serology alone, and the time required to obtain paired acute and/or convalescent serologic results, these tests should not be the basis on which treatment is initiated. In a patient with compatible symptoms and a plausible exposure history, empiric therapy should be started.
• Leptospires may be identified directly from infected tissues by using dark-field microscopy or direct fluorescent-antibody assay. Cultures of blood, cerebrospinal fluid (CSF), urine, and affected organs (eg, kidney) may yield positive results. Coordinate sample collection in consultation with the local microbiology laboratory because processing requires specialized techniques.
• • Leptospires may be cultured on selective media (eg, Fletcher, Stuart, Ellinghausen), combined with neomycin or 5-fluorouracil.
  • To improve the sensitivity, multiple inoculates are incubated for as many as 4 months before dark-field microscopy results are confirmed.
  • During the first 7-10 days of symptoms, blood and CSF may produce positive cultures. After that, the urine, which may contain leptospires for weeks to months, should be cultured. Urine cultures should be plated in 2 hours or less to ensure viability of the leptospire.
  • Consultation with the local microbiology laboratory is essential.
• Serologic identification of leptospires may be more useful clinically if performed rapidly; however, the traditional gold standard, the microscopic agglutination testing (MAT) is available only at reference laboratories, such as the Centers for Disease Control and Prevention (CDC).
• • In the United States, 3 additional serologic tests available are available: the Indirect hemaglutination assay (Focus Technologies, Cyprus, CA), the leptospirosis immunoglobulin (IgM) Dip-S-Tick test (PanBio Integrated Diagnostics; Baltimore MD), and the Leptospira immunoglobulin G (IgG) enzyme-linked immunosorbent assay (PanBio Integrated Diagnostics; Baltimore MD).
  • An indirect fluorescent antibody test, the microcapsule agglutination test, the dried latex agglutination test, and several dipstick tests are available internationally.
• MAT uses a battery of antigens taken from common (frequently locally endemic) leptospire serovars. Positive results are defined as a 4-fold rise in titer between acute and convalescent specimens.
• • A single titer exceeding 1:200 or serial titers exceeding 1:100 suggest leptospirosis; however, neither is diagnostic.
  • Reported sensitivity and specificity of the MAT are as high as 92% and 95%, respectively. Positive predictive values of 95% and negative predictive values of 100% also have been documented.
  • False-negative MAT findings may result from testing a single specimen obtained before the immune phase of disease. Test accuracy is also affected by appropriate selection of antigens for the battery, necessitating discussion with the laboratory about which serovars are suspected or predominate in the region where the case originated. MAT false-positive results may occur with cases of Legionella, Lyme disease, and syphilis.
  • MAT is further limited by its time-consuming nature and the need for a reference laboratory (eg, CDC in Atlanta, GA; World Health Organization [WHO]/Food and Agriculture Organization [FAO] Collaborating Centers in Amsterdam, the Netherlands, and in Brisbane, Australia).
• Indirect hemaglutination assay is a rapid and easily performed method of diagnosis that is based on genus-specific antibodies.
• • Serum from patients is mixed with either antigen-coated or uncoated control cells in a microtiter tray. The tray is incubated for 1 hour, and results are read on a scale ranging from 0 to ++++.
  • Initial testing has demonstrated a sensitivity of 92-100% (with matched acute and convalescent sera) and a specificity of 94-95%. Obtaining samples as early as day 6.8 (study mean) lowered sensitivity to 81%; follow-up testing on day 8 (study mean) increased sensitivity to 100%. These levels of accuracy contrast with results obtained by researchers at the Hawaii Department of Health and the CDC who found only 15% sensitivity before the 14th day of illness. Convalescent testing after day 14 improved sensitivity to 68%. A possible explanation for this variation is differences in regional strains.
• The dipstick test IgM dot-enzyme-linked immunosorbent assay kit is simple enough for basic laboratories to perform and can yield results in approximately 1 hour using serum, plasma, heparinized whole blood, or finger-stick capillary blood samples.
• • As many as 4 dots appear during positive reactions. A finding of 2 or more well-defined dots is considered positive. An observation of one or no dots is considered negative.
  • The test uses L biflexa serovar Patoc 1 strain antigens to bind antibodies.
  • The test has excellent sensitivity (95.5%) and specificity (98.8%) when paired acute and convalescent sera are evaluated. Single acute-phase sera sensitivity is 52%.
  • The CDC recommends referring positive results for confirmatory testing.
• Additional diagnostic tests for leptospirosis, particularly the polymerase chain reaction (PCR), are undergoing testing and presently have no widespread clinical use.
• Detailed discussion of the diagnostic techniques and culture methods is available in Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control.²

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

Empiric antimicrobial therapy in leptospirosis must be comprehensive and should cover all likely pathogens in the context of the clinical setting. No controlled studies have been performed to evaluate the efficacy of antibiotics for leptospirosis specifically in children, nor have specific doses been used consistently in reported case series. The following dosage guidelines are extrapolated from research on adult patients.

Besides the antibiotics described below, many case series report other antimicrobials that have been used to successfully treat leptospirosis. A randomized, controlled study comparing azithromycin to doxycycline suggested efficacy.²⁴ Broth microdilution testing has shown sensitivity to macrolides, fluoroquinolones, cephalosporins, and carbapenems.²⁵

Antibiotic therapy should be initiated as soon as the diagnosis is considered and should be continued for a full course despite initial serologic results because most patients are diagnosed only through acute and convalescent testing. Early treatment has been shown to offer the best clinical outcomes; results from controlled studies of treatment during the immune phase have yielded mixed results.^{26, 27}

According to some reports, patients with leptospiral renal failure, hypothesized to be immune complex mediated, have been successfully treated without dialysis by administering high-dose pulsed steroids (methylprednisolone 30 mg/kg/d, not to exceed 1500 mg). These authors also discuss the role of high-dose pulsed steroids in areas with limited resources where dialysis treatment is unavailable and would involve lengthy medical transport. The use of renal dose dopamine in conjunction with steroids or diuretics has also been described.¹³ Pulse-dose steroids may also play a role in the management of severe pulmonary disease.^{28, 29} Ophthalmic drops of mydriatics and corticosteroids have been used for relief of ocular symptoms.³⁰

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Treatment for leptospirosis consists of empiric antibiotic therapy. If renal failure ensues, corticosteroids may be considered. Additional supportive care may include inotropic agents, diuretics, or ophthalmic drops.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Transfer

• Leptospirosis has a regional epidemiology with high incidence of cases in remote regions that offer limited medical care.
• Although transporting patients with severe disease to appropriate medical centers is preferred, military physicians who have treated patients from Western Pacific islands averted the need for transoceanic transport for dialysis by administering high-dose steroids.^{20, 19}

Deterrence/Prevention

• Oral doxycycline (200 mg every week) has been 95% effective in preventing leptospirosis among high-risk adults.³¹ The role of prophylaxis in children has not been adequately studied.
• Public awareness campaigns and warning signs are common in some endemic areas but have uncertain efficacy. Protective garments and environmental controls have little proven benefit for at-risk groups.
• Despite current research in some countries, human vaccines may offer little benefit because of the vast number of different pathogenic serotypes. Although animal vaccines have prevented symptomatic disease from covered serotypes, infection, organism shedding, and transmission may still occur.

Prognosis

• The mortality rate for patients with severe leptospirosis is approximately 10%. Patients without access to ICU-equivalent care have higher death rates. Most deaths occur from renal failure, massive hemorrhage, or acute respiratory distress syndrome (ARDS).
• In general, survivors of leptospirosis experience little long-term morbidity, regardless of disease severity.
• Hepatic and renal functions return to normal, despite severe dysfunction during acute illness, even among patients who required dialysis.
• Approximately a third of patients with documented aseptic meningitis may continue to complain of periodic headaches of varying severities.
• Some patients with histories of leptospiral uveitis have persistent visual acuity loss (caused by lens pigmentation following anterior uveitis) and blurry vision (associated with keratic precipitates in the anterior chamber).

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• The major medicolegal risk is incorrect diagnosis.
• Misdiagnosis is a substantial risk because leptospirosis symptoms are often discounted as viral. Although this may have little clinical significance in the 90% of cases that are mild, delayed treatment for the 10% of cases that are severe may negatively affect patient outcome.
• A possible key to correct diagnosis is a thorough history focusing on the patient's travel history, activities, and exposure to animals.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Denise Demers, MD, to the development and writing of this article.

The opinions or assertions contained herein are the private views of the authors and do not reflect the views of Walter Reed Army Medical Center, The Uniformed Services University of Health Sciences, the Department of the Army, or the Department of Defense.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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8. Trevejo RT, Rigau-Perez JG, Ashford DA, et al. Epidemic leptospirosis associated with pulmonary hemorrhage-Nicaragua, 1995. J Infect Dis. Nov 1998;178(5):1457-63. [Medline].
9. Jackson LA, Kaufmann AF, Adams WG, et al. Outbreak of leptospirosis associated with swimming. Pediatr Infect Dis J. Jan 1993;12(1):48-54. [Medline].
10. Everard CO, Bennett S, Edwards CN, et al. An investigation of some risk factors for severe leptospirosis on Barbados. - Carrington DG. Feb 1992;95(1):13-22. [Medline].
11. Katz AR, Manea SJ, Sasaki DM. Leptospirosis on Kauai: investigation of a common source waterborne outbreak. Am J Public Health. Oct 1991;81(10):1310-2. [Medline].
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Article Last Updated: Oct 8, 2008