Wednesday, April 13, 2011

Leptospirosis Infections in Humans

Incubation Period The incubation period in humans is usually 7 to 12 days, with a range of 2 to 29 days.

Clinical Signs Human infections vary from asymptomatic to severe. Many cases are mild or asymptomatic, and go unrecognized. Some serovars tend to be associated more often with some syndromes (e.g., severe disease is often associated with serovar icterohaemorrhagiae).However, any serovar can cause any syndrome. In humans, leptospirosis is usually a biphasic illness. The first phase, called the acute or septicemic phase, usually begins abruptly and lasts approximately a week. This phase is characterized by nonspecific signs including fever, chills, headache and conjunctival suffusion. Myalgia, which typically affects the back, thighs or calves, is often severe. Occasionally, a transient skin rash occurs. Other symptoms may include weakness, photophobia, lymphadenopathy, abdominal pain, nausea, vomiting, a sore throat, cough, chest pain and hemoptysis. Mental confusion, neck stiffness and other signs of aseptic meningitis have been reported in this phase. Jaundice can be seen in more severe infections. These symptoms last for approximately 4 to 9 days, then are typically followed by a 1 to 3 day period during which the temperature drops and the symptoms abate or disappear. The second phase of leptospirosis, called the immune phase, is characterized by the development of anti-Leptospira antibodies, and the excretion of the organisms in the urine. This phase can last up to 30 days or more, but does not develop in all patients. During the immune phase, the patient becomes ill again. Nonspecific symptoms seen in the first stage, such as fever and myalgia, recur but may be less severe than in the first stage of disease. Two forms of disease, icteric and anicteric, are seen. Most infections are of the anicteric form. The most important symptoms in this form are associated with aseptic meningitis. A severe headache, stiff neck and other meningeal symptoms occur in approximately half of all patients, and usually last a few days. Occasionally, these signs may be present for up to two weeks. Less common symptoms include cranial nerve palsies, encephalitis, confusion and changes in consciousness. Deaths are rare in the typical anicteric form; however, a syndrome of fatal pulmonary hemorrhage, without jaundice, has recently been reported. The icteric form is more severe. It occurs in 5-10% of all patients, is often rapidly progressive, and may be associated with multiorgan failure. The most commonly involved organ systems are the liver, kidneys and central nervous system (CNS). In the icteric form, there may be no period of improvement between the septicemic and immune phases. Jaundice can be severe and may give the skin an orange tone, but it is not usually associated with severe hepatic necrosis. Acute renal failure occurs in 16-40% of cases. Some patients also have pulmonary symptoms, with clinical signs ranging from cough, dyspnea, chest pain, and mild to severe hemoptysis, to adult respiratory distress syndrome. Cardiac involvement can result in congestive heart failure, myocarditis and pericarditis. Hemorrhages may also be seen; epistaxis, petechiae, purpura and ecchymoses are the most common signs, but severe gastrointestinal bleeding, adrenal or subarachnoid hemorrhage, and pulmonary hemorrhages can occur. Rare complications include stroke, rhabdomyolysis, thrombotic thrombocytopenic purpura, acute acalculous cholecystitis, erythema nodosum, aortic stenosis, Kawasaki syndrome, reactive arthritis, epididymitis, nerve palsy, male hypogonadism, Guillain-Barre´ syndrome and cerebral arteritis. Deaths can occur from kidney failure, cardiac involvement. pulmonary hemorrhage or other serious organ dysfunction. Convalescence from the icteric form may take 1-2 months. Although jaundice can persist for weeks, liver function returns to normal after recovery, and hepatic disease is rarely the cause of death. Most patients also recover kidney function Anterior uveitis occurs up to a year after recovery in 2-10% of cases. Most of these patients recover full vision. Iridocyclitis and chorioretinitis can also be complications, and may persist for years. Abortions, fetal death, and rare congenital infections in newborns have been reported. Abortions can occur at any time, including the convalescent period.

Communicability Direct person-to-person transmission is rare but possible. Leptospira organisms are found in the urine during the second (immune) phase of the disease. Most people excrete these bacteria for 60 days or less, but shedding for months or years has been documented. Other routes of transmission are also possible: one infant was infected during breast feeding, and a case of transmission during sexual intercourse was reported.

Diagnostic Tests Leptospirosis can be diagnosed by culture, detection of antigens or nucleic acids, or serology. Serum chemistry values and analysis of the CSF may support the diagnosis. In humans, Leptospira can be isolated from the blood, cerebrospinal fluid or urine. Culture can be difficult and may require up to 13 to 26 weeks. Identification to the species, serogroup and serovar level is done by reference laboratories, using genetic and immunologic techniques. Leptospira spp. can also be identified in clinical samples by immunofluorescnce and immunhistochemical staining, as well as DNA probes and polymerase chain reaction (PCR) techniques. Darkfield microscopy can be used but is not specific. Most human cases of leptospirosis are diagnosed by serology. The most commonly used serologic tests are the microscopic agglutination test (MAT, previously known as the agglutination-lysis test) or ELISAs. The MAT test is serogroup but not serovar specific, and can be complicated by cross-reactions. Less commonly used tests include complement fixation,radioimmunoassay,immunofluorescence,counter immunoelectrophoresis and thin layer immunoassay. The macroscopic slide agglutination test may be used for a presumptive diagnosis, but is not specific. A high titer with consistent symptoms is suggestive of an acute case, but a rising titer is necessary for a definitive diagnosis. Few serovarspecific assays are available in human medicine.

Treatment Severe leptospirosis is treated with antibiotics. The use of antibiotics for the mild form of disease is controversial, and the research is still inconclusive. Antibiotics used in humans include doxycycline, ampicillin, amoxicillin, penicillin and erythromycin. Supportive treatment and management of complications such as renal failure, hepatic complications, hemorrhages and CNS disease may also be necessary.

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