Dr.Mustafa Nema/Baghdad College of Medicine 2014 Leptospirosis Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Objectives Identify the causative agent of leptospirosis. Determine the ways of disease transmission. Describe how can patients with this disease present. Clarify management and prevention plan. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Case scenario A 29 year’s old male presented to the hospital with fever, headache, marked muscle and joint pain. 3 days later, he deteriorated and developed skin rash, red conjuctivae, yellowish discoloration of sclera and low urine output. His urine looks dark. Then he develped severe dyspnea and his consciousness decreased . He work as a farmer, with many animals around. How can you approach the diagnosis? Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Introduction Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Introduction Adolf Weil's desribe in 1886 a disease with fever and jaundice. Rats as a carrier (reservoir host) were then identified. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Causative agent Leptospirosis is one of the most common zoonotic diseases, favoured by a tropical climate and flooding, but occurring worldwide. More than 200 subtypes present. Leptospira interrogans is pathogenic for humans. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 The etiologic agent, which can be as a motile spirochete. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Leptospirosis present in wildlife and in many domestic animals. The organisms persist indefinitely in the convoluted tubules of the kidney of the animal host and are shed into the urine in massive numbers, but infection is asymptomatic in the host. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 The bacteria that cause leptospirosis are spread through the urine of infected animals, which can get into water or soil and can survive there for weeks to months. Many different kinds of wild and domestic animals carry the bacterium. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 The most frequent hosts are rodents, especially the common rat. Other animals can include, but are not limited to:   Cattle Horses Dogs Wild animals Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Who is at risk? Farmers Mine workers Sewer workers Slaughterhouse workers Veterinarians and animal caretakers Fish workers Dairy farmers Military personnel Dr.Mustafa Nema/Baghdad College of Medicine 2014

What are the ways of transmission? Leptospires can enter their human through intact skin or mucous membranes, but entry is facilitated by cuts and abrasions. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Prolonged immersion in contaminated water will also favour invasion, as the spirochaete can survive in water for months. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Drinking contaminated water can also cause infection. Outbreaks of leptospirosis are usually caused by exposure to contaminated water, such as floodwaters. Person to person transmission is rare. Dr.Mustafa Nema/Baghdad College of Medicine 2014

How can a patient with leptospirosis presents? Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Clinical features The incubation period averages 1–2 weeks. After a relatively brief bacteraemia, invading organisms are distributed throughout the body, mainly in kidneys, liver, meninges and brain. . Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Signs and Symptoms In humans, Leptospirosis can cause a wide range of symptoms, including: High fever Headache Chills Muscle aches Vomiting Jaundice Red eyes Abdominal Pain Diarrhea Rash Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Four main clinical syndromes can be discerned and clinical features can involve multiple organ systems. 1. Bacteraemic leptospirosis 2. Aseptic meningitis 3. Icteric leptospirosis (Weil’s disease) 4. Pulmonary syndrome Dr.Mustafa Nema/Baghdad College of Medicine 2014

1. Bacteraemic leptospirosis Bacteraemia can produce a nonspecific illness with high fever, weakness, muscle pain and tenderness (especially of the calf and back), intense headache, photophobia, and sometimes diarrhoea and vomiting. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Conjunctival congestion is the only notable physical sign. The illness comes to an end after about 1 week, or else merges into one of the other forms of infection. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 2. Aseptic meningitis This illness is very difficult to distinguish from viral meningitis. The conjunctivae may be congested but there are no other differentiating signs. Laboratory clues include a neutrophil leucocytosis and abnormal liver function tests. Dr.Mustafa Nema/Baghdad College of Medicine 2014

3. Icteric leptospirosis (Weil’s disease) Fewer than 10% of symptomatic infections result in severe icteric illness. Weil’s disease is a dramatic life-threatening event, characterised by fever, haemorrhages, jaundice and renal impairment. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Conjunctival hyperaemia is a frequent feature. Conjunctival suffusion in a patient with Weil’s disease. Conjunctival suffusion, a characteristic sign of leptospirosis Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 The patient may have a transient macular erythematous rash, but the characteristic skin changes are purpura and large areas of bruising. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Jaundice is deep and the liver is enlarged. Renal failure, primarily caused by impaired renal perfusion and acute tubular necrosis, manifests as oliguria or anuria. In severe cases there may be epistaxis, haematemesis and melaena. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Weil’s disease may also be associated with myocarditis and encephalitis Uveitis and iritis may appear months after apparent clinical recovery. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 4. Pulmonary syndrome This syndrome is characterised by haemoptysis, patchy lung infiltrates on chest X-ray, and respiratory failure. Total bilateral lung consolidation and acute respiratory distress syndrom (ARDS) with a high mortality (over 50%). Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Clinical syndromes of leptospirosis Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 In assessing a patient the most important factor to apply is their recollection of the risk event (patient occupation, animal or contaminated water contact), as this is often the only clue to the potential cause. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Investigations needed for diagnosis Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Diagnosis Blood count: A polymorphonuclear leucocytosis is accompanied in severe infection by thrombocytopenia and elevated blood levels of creatine kinase (CK enzyme) . In jaundiced patients, there is hepatitis and the prothrombin time (PT) may be prolonged. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Acute renal failure is common with elevated blood urea and serum creatinine. The cerebrospinal fluid (CSF) in leptospiral meningitis shows a variable cellular response, a moderately elevated protein level and normal glucose content. Dr.Mustafa Nema/Baghdad College of Medicine 2014

differential diagnoses Important differential diagnoses. Malaria Typhoid fever Acute viral hepatitis Acute viral meningitis Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Blood cultures: are most likely to be positive if taken before the tenth day of illness. Urine culture: Leptospires appear in the urine during the second week of illness, and in untreated patients may be recovered on culture for several months. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Serology: Serological tests are diagnostic if seroconversion or a fourfold increase in titre is demonstrated. The microscopic agglutination test (MAT) is the test of choice. E LISA and immunofluorescent (IF) techniques also useful. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 PCR: Detection of leptospiral DNA by PCR is possible in blood in early symptomatic disease, and later on in urine and for many months thereafter. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Treatment plan Dr.Mustafa Nema/Baghdad College of Medicine 2014

Management and prevention The general care of the patient is critically important. Blood transfusion for haemorrhage and careful attention to renal failure, the usual cause of death, are especially important. Renal failure is potentially reversible with adequate support, such as dialysis. The optimal antimicrobial regimen has not been established. Most infections are self-limiting. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Therapy with either oral doxycycline (100 mg twice daily for 1 week) or intravenous penicillin (900 mg 4 times daily for 1 week) is effective but may not prevent the development of renal failure. Parenteral ceftriaxone (1 g daily) is as effective as penicillin. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Uveitis is treated with a combination of systemic antibiotics and local corticosteroids. There is no role for the routine use of corticosteroids in the management of leptospirosis. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Prevention The risk of acquiring leptospirosis can be greatly reduced by not swimming or wading in water that might be contaminated with animal urine, or eliminating contact with potentially infected animals. Protective clothing or footwear should be worn by those exposed to contaminated water or soil because of their job or recreational activities. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Trials in military personnel have shown that infection with L. interrogans can be prevented by taking prophylactic doxycycline 200 mg weekly. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Summary Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Infection with Leptospira spirochetes occurs during contact with animal reservoirs or an environment contaminated with their urine. The clinical course of leptospirosis ranges from a mild acute febrile illness to life-threatening manifestations such as Weil’s disease, which consists of the triad of jaundice, acute renal failure, and bleeding. Leptospirosis has also been recognized as an important cause of pulmonary hemorrhage syndrome worldwide. Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Further readings Davidson clinical and practice of medicine 22th ed. 2014. Goldman’s Cecil Medicine 24th ed 2012. www.cdc.gov/leptospirosis/ Dr.Mustafa Nema/Baghdad College of Medicine 2014

Dr.Mustafa Nema/Baghdad College of Medicine 2014 Thank you Dr.Mustafa Nema/Baghdad College of Medicine 2014