Brucelosis y Leptospirosis: Zoonosis Bacterianas
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Similar a Brucelosis y Leptospirosis: Zoonosis Bacterianas
Similar a Brucelosis y Leptospirosis: Zoonosis Bacterianas (20)
Más de Sandru Acevedo MD
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Brucelosis y Leptospirosis: Zoonosis Bacterianas
- 1. Brucellosis y Leptospirosis Sandra Milena Acevedo Rueda MD Residente 2do año, Medicina Interna UNAB Octubre de 2012
- 2. Brucellosis • Zoonosis • USA – 200 casos año • Bioterrorismo • Evaluación epidemiológica MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 3. Brucellosis Militares británicos Isla de Malta Martson, 1861 Brucella melitensis “Leche cruda de cabra” Bruce, 1904 MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 4. Brucellosis Coco bacilo gram negativo, no encapsulado No productor de esporas Relación filogenética con Bartonella MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 5. Brucellosis Infecta al Especies Huésped natural hombre Mellitensis Cabra, oveja SI Abortus Vaca SI Suis Cerdo, roedores SI Canis Perro SI Ovis Oveja NO Neotomae Roedores NO MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 6. Brucellosis Transmisión • Directa • Inhalatoria • Ingestión de productos no pasteurizados Carnes (raro) • Sexual • Transfusiones, TMO, Transplacentaria MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 7. Brucellosis Según la OMS en América latina los países que Según la OMS en América latina los países que demuestran tener mayor incidencia de la demuestran tener mayor incidencia de la enfermedad son Argentina, México y Perú, enfermedad son Argentina, México y Perú, seguidos de Colombia, Chile y Ecuador seguidos de Colombia, Chile y Ecuador
- 8. Brucellosis La OMS reporta cada año 500.000 nuevos casos de brucelosis humana que solo representan el 4% de los casos que realmente ocurren
- 9. La especie más patógena e invasora para el hombre es B. mellitensis sin embargo aún no se han reportado casos en el país
- 10. Brucellosis Patogénesis Estado nutricional, inmunológico e inóculo pH gástrico bajo Inhibición función bactericida fagocitos Genes de virulencia: VirB operon MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 12. Brucellosis Inmunidad del hospedero Gen Nramp1 (proteína de resistencia natural asociada a macrófago tipo 1) – Slc11a1 Efecto pleiotrópico Estabilización de RNAm citokinas Primera semana Ig M Segunda semana Ig G MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 13. Brucellosis Manifestaciones clínicas • Fiebre, malestar, osteomialgias, anorexia, lumbago • 2 a 4 semanas inoculación • Ondulante • Sudoración y sabor en la boca típicos • Hepato – esplenomegalia 10-30% • Recaídas 3 a 6 meses • Cronicidad: otros focos
- 14. Brucellosis Complicaciones GIT Anorexia Diarrea Hiperemia mucosa intestinal Pancreatitis Vómito MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 15. Brucellosis Sistema hepatobiliar Transaminasas normales o levemente aum. Espectro variable B. abortus: granuloma B. Melitensis: necrosis – inflamación NE B.Suis : abscesos hepatoesplenicos Otros: peritonitis, colecistitis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 16. Brucellosis Sistema óseo • Sacroiliitis, espondilitis • Osteomielitis vertebral • Espondiloartritis, tenosinovitis, bursitis • Artritis grandes articulaciones MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 17. Brucellosis Sistema nervioso central 5% de los casos Encefalitis, meningitis, absceso cerebral, mielitis, radiculoneuritis, granuloma, sindromes meningovasculares Pérdida auditiva Secuelas neurológicas MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 18. Brucellosis Sistema cardiovascular Endocarditis 2% Válvula aórtica más comúnmente afectada Pericarditis, glomerulonefritis, aneurismas micóticos MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 19. Brucellosis Sistema respiratorio Raro Rinofaringitis, bronquitis, derrame pleural, adenopatías, absceso, empiema MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 20. Brucellosis Tracto genitourinario Raro Nefritis intersticial, pielonefritis, glomeruloneftitis, nefropatía IgA Epididimo-orquitis 20% MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 21. Brucellosis Otras manifestaciones • Cutáneas • Hematológicas • Embarazo • Oculares
- 22. Brucellosis Diagnóstico • Clínica • Diagnóstico serológico 10-90% • Muestras (sangre, médula ósea) • Hemograma, VSG • Error en identificación con: – Moraxella phenylpyruvica y Ochrobactrum anthropi MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 23. Brucellosis Diagnóstico • Rosa de Bengala • PCR • ELISA • Títulos de 1:160 • Ac contra lipopolisacáridos ó contra proteínas intracitoplasmáticas
- 24. Brucellosis
- 25. Brucellosis 6 SEMANAS 6 SEMANAS Tratamiento Suceptibilidad in vitro Tetraciclinas Tetraciclina y Estreptomcina Doxiciclina y Gentamicina Doxiciclina y Rifampicina Trimetropin Sulfametoxazol
- 26. Brucellosis MESES MESES Tratamiento Meningitis , endocarditis TMP SX, gentamicina, rifampicina Neurobrucellosis Corticoides? MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 27. Leptospirosis Zoonosis Infección renal crónica del huésped natural Espectro amplio de la enfermedad MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 28. Leptospirosis Historia Weil 1886 Japón, Alemania Fiebre amarilla MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 29. Leptospirosis Espiroqueta Lipopolisacárido O Griego leptos , Latin spira Campo oscuro L. Interrogans y L. biflexa 250 variantes (serogrupos) MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 30. Leptospirosis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 31. Leptospirosis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 32. Hasta la semana epidemiológica 28 de 2012 se han notificado 1417 casos, de los cuales 1007 (71,2 %) permanecen como sospechosos
- 33. Leptospirosis
- 34. Leptospirosis • Temporada de lluvias • Hawaii 128 casos / 100.000 • Roedores y mamíferos pequeños • Exposición ocupacional MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 35. Leptospirosis • Abrasiones, mucosas, conjuntivas, aerosoles • Mucosa oral • Ingesta de agua lagos • SNC, humor acuoso • Diseminación hematógena y penetración a tejidos MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 36. Leptospirosis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 37. Leptospirosis • LipL32 • Toxinas • Adhesinas • Proteínas de superficie • Susceptibilidad individual • HLA DQ6 • Anticardiolipinas, Ac antiplaquetarios, complejos inmunes circulantes MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 38. Leptospirosis Manifestaciones clínicas • Espectro amplio de síntomas – Fiebre, calofrio, mialgias, e. conjuntival, cefalea. – Al exámen físico hepato-espleno, adenopatias • Falla renal, falla hepática, neumonitis, diátesis hemorrágicas – Meningitis aséptica • Período de incubación: 10 días • Mortalidad 5 – 40% MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 39. Leptospirosis
- 40. Leptospirosis
- 41. Leptospirosis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 42. Leptospirosis Laboratorio Detección directa Tinción de plata (sensibilidad y especificidad ) Inmunofluorescencia Inmunoperoxidasa PCR Inmunohistoquímica MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 43. Leptospirosis MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 44. Leptospirosis Laboratorio Aislamiento Orina Sangre 10 días LCR Liq. peritoneal MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 45. Leptospirosis Laboratorio Detección indirecta MAT 1:4 (1:800 aguda) Reacción cruzada con otros Ac MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 46. Leptospirosis Tratamiento • Enfermedad leve – grave • Doxiciclina y PNC • Reacción de Jarisch-Herxheimer MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 47. Leptospirosis Azitromicina MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES. Seventh Edition. Copyright © 2010,
- 48. Gracias !
Notas del editor
- Brucellosis is a disease of animals (zoonosis) that under certain circumstances can be transmitted to humans.1 Although it occurs worldwide, brucellosis is more common in countries that do not have effective public health and animal health programs.2,3 In the United States and other developed countries, brucellosis in domestic animals has been largely controlled or eliminated. Consequently, the incidence of human brucellosis is low, with fewer than 200 cases reported annually to the Centers for Disease Control and Prevention. As one of the first bacteria to be weaponized, Brucella remains a potential bioterrorism agent,4,5 and all confirmed cases should have epidemiologic evaluation.
- Brucellosis has likely been present since man first domesticated animals; however, the early history of the disease is linked to the British military and their presence on the island of Malta.7 It was there in 1861 that Marston first differentiated brucellosis from other clinical fevers and where 25 years later Bruce first isolated Brucella melitensis from victims of Malta fever.8 From 1904 to 1907, the Mediterranean Fever Commission studied the disease on Malta, concluding that native goats were the reservoir and raw goat’s milk was the vehicle of transmission from animal to human.9 In Denmark in 1895, Bang identified Brucella abortus as a cause of contagious abortion in cattle, and in the United States in 1914, Traum isolated Brucella suis from aborted swine. However, it was not until the 1920s, from the work of Alice Evans and others, that the relatedness of these apparently disparate microorganisms was recognized and the genus was named to honor Bruce.10 In the 1950s, Brucella ovis from sheep and Brucella neotomae from desert wood rats were added to the genus, but they have not been shown to cause disease in humans. In 1966, Brucella canis was isolated from kennel-bred dogs, but it is an infrequent human infection.11 Since 1994, novel members of the genus have been isolated from a variety of marine mammals. The names Brucella pinnipediae and Brucella ceteceae have been proposed for the seal and cetacean (whales and dolphins) isolates, respectively. The role of these organisms as a source of human infection remains to be determined.12
- Brucellae are small, gram-negative, unencapsulated, nonsporulating coccobacilli. They grow aerobically, although some require supplemental CO2 for primary isolation. All strains are catalase positive, but oxidase and urease activities and the production of H2S are variable. The major nomen species and their biovars are differentiated based on metabolic tests, growth on media containing dyes, and lysis by specific bacteriaphages.13
- Brucellae are small, gram-negative, unencapsulated, nonsporulating coccobacilli. They grow aerobically, although some require supplemental CO2 for primary isolation. All strains are catalase positive, but oxidase and urease activities and the production of H2S are variable. The major nomen species and their biovars are differentiated based on metabolic tests, growth on media containing dyes, and lysis by specific bacteriaphages.13
- Routes of transmission from animal to human include (1) direct contact with infected animals or their secretions through cuts or abrasions in the skin or conjunctival sac, (2) inhalation of contaminated aerosols, and (3) ingestion of unpasteurized dairy products. Consequently, brucellosis is an occupational risk for ranchers, veterinarians, abattoir workers, and laboratory personnel.28 Meat products are rarely the source of infection because they are not usually consumed raw and the numbers of organisms in muscle tissue are low. In areas where drinking animal blood or ingesting raw liver are traditions, foodborne infection from other than dairy products is possible.29 Person-to-person transmission of brucellosis is unusual; however, rare cases in which sexual transmission was suspected have been reported.30 In addition, blood transfusions and bone marrow transplants31 have been sources of brucellosis, emphasizing the need for Brucella antibody screening, especially in endemic areas. Although persons with HIV are at risk of a number of zoonotic agents, very few cases of brucellosis are reported.32 Brucellosis is not uncommon in children, especially in areas where B. melitensis is endemic and animals and children share a common living space.33,34 It is not unusual to find more than one case of brucellosis in a household;
- Routes of transmission from animal to human include (1) direct contact with infected animals or their secretions through cuts or abrasions in the skin or conjunctival sac, (2) inhalation of contaminated aerosols, and (3) ingestion of unpasteurized dairy products. Consequently, brucellosis is an occupational risk for ranchers, veterinarians, abattoir workers, and laboratory personnel.28 Meat products are rarely the source of infection because they are not usually consumed raw and the numbers of organisms in muscle tissue are low. In areas where drinking animal blood or ingesting raw liver are traditions, foodborne infection from other than dairy products is possible.29 Person-to-person transmission of brucellosis is unusual; however, rare cases in which sexual transmission was suspected have been reported.30 In addition, blood transfusions and bone marrow transplants31 have been sources of brucellosis, emphasizing the need for Brucella antibody screening, especially in endemic areas. Although persons with HIV are at risk of a number of zoonotic agents, very few cases of brucellosis are reported.32 Brucellosis is not uncommon in children, especially in areas where B. melitensis is endemic and animals and children share a common living space.33,34 It is not unusual to find more than one case of brucellosis in a household;
- Routes of transmission from animal to human include (1) direct contact with infected animals or their secretions through cuts or abrasions in the skin or conjunctival sac, (2) inhalation of contaminated aerosols, and (3) ingestion of unpasteurized dairy products. Consequently, brucellosis is an occupational risk for ranchers, veterinarians, abattoir workers, and laboratory personnel.28 Meat products are rarely the source of infection because they are not usually consumed raw and the numbers of organisms in muscle tissue are low. In areas where drinking animal blood or ingesting raw liver are traditions, foodborne infection from other than dairy products is possible.29 Person-to-person transmission of brucellosis is unusual; however, rare cases in which sexual transmission was suspected have been reported.30 In addition, blood transfusions and bone marrow transplants31 have been sources of brucellosis, emphasizing the need for Brucella antibody screening, especially in endemic areas. Although persons with HIV are at risk of a number of zoonotic agents, very few cases of brucellosis are reported.32 Brucellosis is not uncommon in children, especially in areas where B. melitensis is endemic and animals and children share a common living space.33,34 It is not unusual to find more than one case of brucellosis in a household;
- Infection with any Brucella nomen species, including naturally rough species and attenuated vaccine strains, can result in serious human illness. The nutritional and immune status of the host as well as the size of the infectious inoculum and possibly the route of transmission can be determinants of disease. For example, the low pH of gastric juice appears to be more effective in preventing oral infection with B. abortus than B. melitensis,38 and antacids have been implicated as playing a role in foodborne infections.39 The brucellae are facultative intracellular pathogens that can survive and multiply within phagocytic cells of the host. The mechanisms by which brucellae evade intracellular killing by professional phagocytes are not completely understood, but appear to involve inhibition of bactericidal functions, including phagolysosomal fusion, neutrophil degranulation, and the oxidative burst.40 Brucellae within macrophages and monocytes become localized in organs of the reticuloendothelial system, such as the lymph nodes, liver, spleen, and bone marrow. Their adaptation to the intracellular milieu requires virulence genes, notably the virB operon, that encode a type IV secretion system.41 This system is necessary for brucellae within membrane-bound vacuoles to obtain nutrients with which to replicate in organelles derived from the endoplasmic reticulum.42 The eventual elimination of virulent brucellae depends on the activation of macrophages with the development of Th1-type cell–mediated immunity. The principal cytokines involved in anti- Brucella activity of macrophages include tumor necrosis factor- α, tumor necrosis factor- γ, interleukin-1, and interleukin-12.43
- Alimentary tract symptoms such as anorexia, nausea, vomiting, pain, diarrhea, and constipation are elicited in as many as 70% of patients with brucellosis. Pathologic lesions include hyperemia of the intestinal mucosa with inflammation of Peyer’s patches. Acute ileitis has been documented radiographically and histologically in patients infected with B. melitensis.55 Rare cases of acute pancreatitis have been reported.56
- Hepatic involvement is common in brucellosis; however, transaminase levels can be normal or only mildly elevated. The histologic findings are often subtle and can be overlooked entirely. The spectrum of hepatic pathology is quite variable depending in part on the etiologic agent. Infection with B. abortus is characterized by granuloma indistinguishable from sarcoidosis.57 In contrast, infection with B. melitensis yields lesions ranging from small, almost insignificant aggregates of mononuclear cells surrounding foci of necrosis, to a diffuse nonspecific inflammation resembling viral hepatitis.58 In other cases, epithelioid granulomas have been reported.59 Infection with B. suis (and occasionally other brucellae) often results in hepatosplenic abscesses.
- Osteoarticular complications are the most common focal forms of the disease and have been reported in 10% to 80% of cases depending on the series, the ages of the patients, and the infecting Brucella spp.49 The axial skeleton is the most common site with sacroiliitis occurring in younger patients63 and spondylitis occurring in older persons, usually in the lumbar spine.64 Vertebral osteomyelitis is a particularly serious complication, with associated paravertebral, epidural, or psoas abscesses occurring in almost one half of case s.65 Such cases require prolonged (at least 3 months) antimicrobial therapy and may also need surgical intervention. Peripheral Brucella arthritis usually involves large weight-bearing joints (hips and knees); however, any joint, including sternoclavicular, can be involved.66 Synovial fluid contains a preponderance of lymphocytes, and recovery of brucellae is improved by the use of techniques that lyse leukocytes67 (see Chapter 17 for the lysis-centrifugation method). Although rare, prosthetic joint infection caused by Brucella spp. has been reported and excisional arthroplasty may be necessary for cure.68 Postinfectious spondyloarthritis, bursitis, and tenosynovitis have also been reported associated with brucellosis.69
- Neurologic syndromes in brucellosis include meningitis, encephalitis, myelitis-radiculoneuronitis, brain abscess, epidural abscess, granuloma, and demyelinating and meningovascular syndromes. Acute or chronic meningitis is the most frequent nervous system complication.70-72 Sensorineural hearing loss has been reported as a complication of Brucella meningitis.73 Vasculitis associated with brucellosis, which may be immune mediated, can involve blood vessels throughout the body including the brain.74,75 Analysis of cerebrospinal fluid in Brucella meningitis reveals a lymphocytic pleocytosis, elevated protein, and normal or low glucose concentrations. Gram stains and cultures of cerebrospinal fluid are often negative; therefore, the diagnosis depends on the presence of specific antibodies or real-time po� lymerase chain reaction.76 The prognosis of treated neurobrucellosis is generally favorable; however, cases of severe neurologic sequelae have been reported.77
- Endocarditis occurs in less than 2% of cases, but it accounts for the majority of brucellosis-related deaths.78 Before effective therapy, including valve replacement surgery, Brucella endocarditis was nearly always fatal.79 The aortic valve is most often involved, and both native and prosthetic valve infections, as well as infections of other vascular prostheses, have been reported.80 Pericarditis, glomerulonephritis, and mycotic aneurysms involving the brain, aorta, and other blood vessels are secondary complications. Automated blood culture techniques and echocardiography have improved the ability to make an early diagnosis.
- GENITOURINARY TRACT Although brucellae can be recovered from urine, renal complications of brucellosis are rare. Interstitial nephritis, pyelonephritis, glomerulonephritis, and immunoglobulin A nephropathy have been reported.85 Epididymoorchitis occurs in as many as 20% of men with brucellosis. It is usually unilateral with normal urine sediment and can mimic tuberculosis or tumor.86
- Cutaneas, hematologicas, embarazo y oculares The principal manifestation of brucellosis in animals is spontaneous abortion, and erythritol in the tissues of susceptible animals is thought to enhance the growth of brucellae in the genital tract. Brucellosis can also cause abortion in humans; however, it is not clear whether it is any more common than with other bacteremic infections. Reports from areas where B. melitensis is endemic suggest that the incidence of abortion among pregnant women is high and that prompt therapy can be lifesaving for the fetus.87 Hematologic manifestations of brucellosis include anemia, leukopenia, thrombocytopenia, and clotting disorders. Such abnormalities are generally mild and resolve with therapy.88 Granulomas are found in the bone marrow in as many as 75% of cases. Rarely, severe thrombocytopenia with cutaneous purpura and/or bleeding from mucosal sites can occur. The etiology may include hypersplenism, reactive hemophagocytosis, or immune destruction of platelets.89 Skin lesions occur in approximately 5% of patients with brucellosis. Many nonspecific, often transient lesions have been reported, including rashes, papules, ulcers, abscess, erythema nodosum, petechiae, purpura, and vasculitis.90 Contact dermatitis was once a common finding among veterinarians exposed to infected animals.91
- A regimen of tetracycline (500mg every 6 hours PO for 6 weeks) plus streptomycin (1g/day IM for 2 to 3 weeks) had long been the treatment of choice. Subsequently, doxycycline was substituted for tetracycline and gentamicin for streptomycin. Currently, the combination of doxycycline (200mg/day PO for 6 weeks) plus gentamicin (5mg/kg/day IM for 7 days) provides excellent results.23,104,105 The combination of doxycycline (200mg/day PO for 6 weeks) plus rifampin (600 to 900mg/day PO for 6 weeks) offers the advantage of an all-oral regimen, but it is not advised in cases with complications, such as spondylitis Although there was initial enthusiasm for trimethoprimsulfamethoxazole (cotrimoxazole) for the treatment of human brucellosis, some studies showed an unacceptably high relapse rate. Nevertheless, when used in combination with other drugs, such as rifampin, a quinolone, or an aminoglycoside, trimethoprimsulfamethoxazole is useful for treating children younger than 8 years of age, in whom tetracycline is contraindicated owing to the potential for staining teeth. Both trimethoprim-sulfamethoxazole and rifampin appear to be safe drugs for treating brucellosis during pregnancy. The quinolones vary widely in activity against brucellae, but their concentration within phagocytic cells would appear to make them ideal for treating brucellosis. However, monotherapy with quinolones has been disappointing, and their use should always be in combination with other drugs.
- A regimen of tetracycline (500mg every 6 hours PO for 6 weeks) plus streptomycin (1g/day IM for 2 to 3 weeks) had long been the treatment of choice. Subsequently, doxycycline was substituted for tetracycline and gentamicin for streptomycin. Currently, the combination of doxycycline (200mg/day PO for 6 weeks) plus gentamicin (5mg/kg/day IM for 7 days) provides excellent results.23,104,105 The combination of doxycycline (200mg/day PO for 6 weeks) plus rifampin (600 to 900mg/day PO for 6 weeks) offers the advantage of an all-oral regimen, but it is not advised in cases with complications, such as spondylitis Although there was initial enthusiasm for trimethoprimsulfamethoxazole (cotrimoxazole) for the treatment of human brucellosis, some studies showed an unacceptably high relapse rate. Nevertheless, when used in combination with other drugs, such as rifampin, a quinolone, or an aminoglycoside, trimethoprimsulfamethoxazole is useful for treating children younger than 8 years of age, in whom tetracycline is contraindicated owing to the potential for staining teeth. Both trimethoprim-sulfamethoxazole and rifampin appear to be safe drugs for treating brucellosis during pregnancy. The quinolones vary widely in activity against brucellae, but their concentration within phagocytic cells would appear to make them ideal for treating brucellosis. However, monotherapy with quinolones has been disappointing, and their use should always be in combination with other drugs.
- Leptospirosis is a zoonosis of global distribution, caused by infection with pathogenic spirochetes of the genus Leptospira. The disease is greatly underreported, particularly in tropical regions, but attempts at surveillance suggest that it may be the most common zoonosis.1 The disease is maintained in nature by chronic renal infection of carrier animals, which excrete the organism in their urine, contaminating the environment. Human infection occurs by direct contact with infected urine or tissues or, more commonly by indirect exposure to the organisms in damp soil or water. Most human infections are probably asymptomatic; the spectrum of illness is extremely wide, ranging from undifferentiated febrile illness to severe multisystem disease with high mortality rates. The extreme variation in clinical presentation is partly responsible for the significant degree of underdiagnosis.
- A syndrome of severe multisystem disease, presenting with profound jaundice and renal function impairment, was described by Weil in Heidelberg in 1886. Other descriptions of disease that probably represent leptospirosis were made earlier, but the cause could not be definitively ascribed to leptospiral infection.2 Leptospires were first visualized in autopsy specimens from a patient thought to have had yellow fever,3 but were not isolated until several years later, almost simultaneously, in Germany and Japan.4 Diagnostic confusion between severe icteric leptospirosis and yellow fever continued, with prominent researchers such as Stokes and Noguchi dying in their attempts to discover the causative agent.4 Several authoritative reviews have been published.2,4-7
- “ Leptospira” derives from the Greek leptos (thin) and Latin spira (coiled). Aptly named, the leptospires are a mere 0.1€μm in diameter by 6 to 20€μm in length. The cells have pointed ends, one or both of which is usually bent into a characteristic hook (Fig. 240-1). Motility is conferred by the rotation of two axial flagella underlying the membrane sheath, which are inserted at opposite ends of the cell and extend toward the central region.8 Because of their small diameter, leptospires are best visualized by darkfield microscopy, appearing as actively motile spirochetes (Fig. 240-2). Leptospires are readily cultured in polysorbate-albumin medium Historically, the genus Leptospira was classified into two species, L. interrogans and L. biflexa, comprised of pathogenic and nonpathogenic strains, respectively. Within each species, large numbers of serovars were differentiated using agglutinating antibodies. Serovar specificity is conferred by lipopolysaccharide (LPS) O antigens.10 More than 250 serovars of pathogenic leptospires have been described; because of the large number of serovars, antigenically related serovars were grouped into serogroups for convenience in serologic testing
- The great majority of cases are acquired by this route in the tropics, either through occupational exposure to water, as in rice or taro farming, flooding after heavy rains, or exposure to damp soil and water during avocational activities.
- Leptospires enter the body through cuts and abrasions, mucous membranes or conjunctivae, or aerosol inhalation of microscopic droplets. Swallowing contaminated lake water was the only behavioral risk factor identified in a case-control study of a large leptospirosis outbreak at the 1998 Springfield Triathlon.21 However, the oral mucosae are probably a more important route of entry after ingestion than the intestinal tract. On entering the body, there is widespread hematogenous dissemination and penetration of tissue barriers, including invasion of the central nervous system and aqueous humor of the eye. Transendothelial migration of spirochetes is facilitated by a systemic vasculitis, accounting for a broad spectrum of clinical illness. Severe vascular injury can ensue, leading to pulmonary hemorrhage, ischemia of the renal cortex and tubular-epithelial cell necrosis, and destruction of the hepatic architecture, resulting in jaundice and liver cell injury, with or without necrosis.
- The mechanisms whereby leptospires cause disease are not clearly understood. Potential virulence factors include immune mechanisms, toxin production, adhesins, and other surface proteins. Human susceptibility to leptospirosis may be related to poor recognition of leptospiral LPS by the innate immune system.27,28 Human toll-like receptor (TLR) 4, which responds to extremely low concentrations of gram-negative LPS (endotoxin), appears to be unable to bind leptospiral LPS,28,29 perhaps because of the unique methylated phosphate residue of its lipid A.30 Direct tissue damage may also be caused by production of hemolytic toxins, which may act as sphingomyelinases, phospholipases, or pore-forming proteins. Immune-mediated mechanisms have been postulated as one factor influencing the severity of symptoms.32 Investigation of the triathlon outbreak mentioned earlier identified the human leukocyte antigen (HLA) DQ6 as an independent risk factor for leptospirosis.33 The structural location of HLA-DQ6 polymorphisms associated with disease suggested that leptospires produce a superantigen that can cause nonspecific T-cell activation in susceptible individuals.
- The mean incubation period is 10 days (range, 5 to 14 days); determination of precise exposures may be difficult, leading to significant imprecision in estimated incubation times. The acute septicemic phase of illness begins abruptly with a high remittent fever (38° to 40°â•›C) and headache, chills, rigors, and myalgias; conjunctival suffusion without purulent discharge; abdominal pain; anorexia, nausea, and vomiting; diarrhea; and cough and pharyngitis; a pretibial maculopapular cutaneous eruption occurs rarely (Table 240-2). Conjunctival suffusion (redness without exudate) and muscle tenderness, most notable in the calf and lumbar areas, are the most characteristic physical findings, but may occur in a minority of cases (see Table 240-2). Other less common signs include lymphadenopathy, splenomegaly, and hepatomegaly. The acute phase lasts from 5 to 7 days. Routine laboratory tests are nonspecific but indicative of a bacterial infection. Leptospires can be recovered from blood and cerebrospinal fluid (CSF) during the acute phase of illness, but meningeal signs are not prominent in this phase. Leptospires may also be recovered from urine, beginning about 5 to 7 days after the onset of symptoms (Fig. 240-4). Urinalysis reveals mild proteinuria and pyuria, with or without hematuria, and hyaline or granular casts. Death is rare in the acute phase of illness.
- Other poor prognostic signs include acute renal failure (oliguria, hyperkalemia, serum creatinine >3.0€mg/dL), respiratory insufficiency (dyspnea, pulmonary rales, chest x-ray infiltrates), hypotension, and arrhythmias. 49 Conjugated serum bilirubin levels may rise to 80€mg/dL, accompanied by more modest elevations of serum transaminases, alanine aminotransferase, and aspartate aminotransferase, which rarely exceed 200€U/L.56 This is in marked contrast to viral hepatitis. Jaundice is slow to resolve, but death caused by liver failure almost never occurs in the absence of renal failure. At autopsy, degenerative changes are seen in hepatocytes, Kupffer cells may be hypertrophied, cholestasis is evident, and erythrophagocytosis and mononuclear
- Other poor prognostic signs include acute renal failure (oliguria, hyperkalemia, serum creatinine >3.0€mg/dL), respiratory insufficiency (dyspnea, pulmonary rales, chest x-ray infiltrates), hypotension, and arrhythmias. 49
- MAT Test de aglutinacion microscopica
- Human immunization is not widely practiced. A vaccine containing serovar Icterohaemorrhagiae is available in France for workers in highrisk occupations, and a vaccine has been developed for human use in Cuba.105 Immunization has been more widely used in Asia to prevent large-scale epidemics in agricultural laborers.