Dr.T.V.Rao MD TRYPANOSOMA CRUZI TRYPANOSOMA CRUZI CHAGAS’ DISEASE DR.T.V.RAO MD 1

Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. The organism T cruzi and infection in humans were first described in 1909 by the Brazilian physician Carlos R. J. Chagas CHAGAS DISEASE DR.T.V.RAO MD 2

WHY CHAGAS DISEASE IS IMPORTANT An estimated 10 million people are infected with Trypanosoma cruzi (the parasite that causes Chagas disease) worldwide, mostly in Latin America. Chagas disease was once entirely confined to the Region of the Americas – principally Latin America – but it has now spread to other continents. Chagas disease is curable if treatment is initiated soon after infection. DR.T.V.RAO MD 3

WHY CHAGAS DISEASE IS IMPORTANT Up to 30% of chronically infected people develop cardiac alterations and up to 10% develop digestive, neurological or mixed alterations, for which specific treatment may become necessary. Vector control is the most useful method to prevent Chagas disease in Latin America. Blood screening is vital to prevent infection through transfusion and organ transplantation. DR.T.V.RAO MD 4

TRYPANOSOMA CRUZI AND CHAGAS’ DISEASE The etiological agent of Chagas’ disease is the intracellular protozoan parasite Trypanosoma cruzi (T. cruzi), which is transmitted by the insect vector Triatoma infestans (reduviid bug) Reduviid bugs live in mud filled walls of huts in rural areas The bug bites human hosts and transmits the parasite Triatoma infestans (Reduviid bug) Trypanosoma cruzi with human erythrocytes DR.T.V.RAO MD 5

Triatomines, which transmit T cruzi, belong to the family Reduviidae in the order Hemiptera. Reduviidae has 22 subfamilies, including the Triatominae REDUVIIDAE TRANSMIT THE INFECTION DR.T.V.RAO MD 6

WHERE IS CHAGAS DISEASE FOUND? Primarily found in Latin America (16-18 million infected) Increased infections are being detected in the United States DR.T.V.RAO MD 7

TRANSMISSION In Latin America, T. cruzi parasites are mainly transmitted by the infected faeces of blood-sucking triatomine bugs. These bugs typically live in the cracks of poorly-constructed homes in rural or suburban areas. Normally they hide during the day and become active at night when they feed on human blood. They usually bite an exposed area of skin such as the face, and the bug defecates close to the bite. The parasites enter the body when the person instinctively smears the bug faeces into the bite, the eyes, the mouth, or into any skin break. DR.T.V.RAO MD 8

Food contaminated with T. cruzi through for example the contact with triatomine bug faeces blood transfusions using blood from infected donors passage from an infected mother to her new-born during pregnancy or childbirth organ transplants using organs from infected donors laboratory accidents.. CRUZI CAN ALSO BE TRANSMITTED BY: DR.T.V.RAO MD 9

THE LIFE CYCLE OF T. CRUZI DR.T.V.RAO MD 10 The life cycle of T. cruzi: The vector, reduviid bug, bites and defecates on host. Parasites, in the form of trypomastigotes, are able to enter the blood via mucous membranes or a cut. During cell invasion, the trypomastigotes transform into amastigotes and undergo multiplication. Parasites are then released into the blood stream as Trypomastigotes where they either spread to other tissues or are taken up by the vector to perpetuate the life cycle

DR.T.V.RAO MD 11

CLINICAL PRESENTATIONS Acute Chagas disease occurs immediately after infection, may last up to a few weeks or months, and parasites may be found in the circulating blood. Infection may be mild or asymptomatic. There may be fever or swelling around the site of inoculation (where the parasite entered into the skin or mucous membrane). Rarely, acute infection may result in severe inflammation of the heart muscle or the brain and lining around the brain. DR.T.V.RAO MD 12

HUMAN AMERICAN TRYPANOSOMIASIS DR.T.V.RAO MD 13 Human American trypanosomiasis, or Chagas disease, has two forms, a trypomastigote found in human blood and an Amastigote found in tissues. The acute form usually goes unnoticed and may present as a localized swelling at the site of entry. The chronic form may develop 10 to 20 years after infection. This form affects internal organs (e.g., the heart, the oesophagus, the colon, and the peripheral nervous system). Affected people may die from heart failure.

CHAGAS DISEASE Acute stage : Immediate reaction to infection Only occurs in about 1% of people infected Swelling of the eye, tiredness, fever, rash, loss of appetite Can be fatal for infants, young children and immunocompromised recipients Intermediate : 8 to 10 weeks after infection No symptoms Chronic : 10 to 20 years after infection Enlarged heart and digestive tract Can result in heart failure Little effective therapy (toxic drugs/low cure rates)

BASIS OF CLINICAL ILLNESS The clinical manifestations of Chagas disease are due to cell death in the target tissues that occurs during the infective cycle, by sequentially inducing an inflammatory response, cellular lesions, and fibrosis. For example, intracellular amastigotes destroy the intramural neurons of the autonomic nervous system in the intestine and heart, leading to mega intestine and heart aneurysms, respectively. If left untreated, Chagas disease can be fatal, in most cases due to heart muscle damage. DR.T.V.RAO MD 15

Many people may remain asymptomatic for life and never develop Chagas- related symptoms. However, an estimated % of infected people will develop debilitating and sometimes life-threatening medical problems over the course of their lives. PROGRESS OF THE DISEASE DR.T.V.RAO MD 16

Romaña's sign, the swelling of the child's eyelid, is a marker of acute Chagas disease. The swelling is due to bug feces being accidentally rubbed into the eye, or because the bite wound was on the same side of the child's face as the swelling. Photo courtesy of WHO/TDR. ROMAÑA'S SIGN DR.T.V.RAO MD 17

Complications of chronic Chagas disease may include heart rhythm abnormalities that can cause sudden death; a dilated heart that doesn’t pump blood well ; a dilated esophagus or colon, leading to difficulties with eating or passing stool. COMPLICATIONS DR.T.V.RAO MD 18

In people who have suppressed immune systems (for example, due to AIDS or chemotherapy), Chagas disease can reactivate with parasites found in the circulating blood. This occurrence can potentially cause severe disease. CHAGAS DISEASE IN AIDS PATIENTS DR.T.V.RAO MD 19

The diagnosis of Chagas disease can be made by observation of the parasite in a blood smear by microscopic examination. A thick and thin blood smear are made and stained for visualization of parasites. DIAGNOSIS DR.T.V.RAO MD 20

CURRENT DIAGNOSTIC METHODS DR.T.V.RAO MD 21 Serologic methods, which check for the presence of Haemoflagellates, in general, may also be used Indirect immunofluorescence assay (IFA), the Machado- Guerreiro test (a test for antibodies to the parasite which uses an antigen from T. cruzi), radioimmunoassay (RIA), and polymerase chain reaction (PCR) diagnostic tests are also effective diagnostic techniques. PCR, though highly sensitive and specific, is not yet used commercially. Parasites may also be revealed in the Amastigote stage via biopsy of enlarged lymph nodes.

TREATING OF CHAGAS DISEASE The etiological treatment is urgently indicated in the acute phase and reactivation (immunosuppression). At that moment parasitological cure rates are almost 100% and they decrease with longer duration of the infection/disease. At younger age the prevalence of side-effects is also lower. The etiological treatment is indicated, as well, in congenital infection and early chronic phase DR.T.V.RAO MD 22

TREATING CHAGAS DISEASE DR.T.V.RAO MD 23 Chagas disease is treatable and curable with benznidazole and nifurtimox chemotherapy. Early detection and speedy treatment are the key to an effective remedy. However, early detection is difficult because the individual may initially be asymptomatic and parasitological screening tests have a high rate of false negatives with respect to T. cruzi. With the onset of chronic stage Chagas disease, a cure is no longer possible and medical professionals will focus on managing and minimalizing the symptoms.

GENERAL PREVENTIVE MEASURES In endemic areas of Mexico, Central America, and South America improved housing and spraying insecticide inside housing to eliminate triatomine bugs has significantly decreased the spread of Chagas disease.. Early detection and treatment of new cases, including mother-to- baby (congenital) cases, will also help reduce the burden of disease. DR.T.V.RAO MD 24

There is no vaccine for Chagas disease. Vector control is the most effective method of preventing Chagas disease in Latin America. Blood screening is necessary to prevent infection through transfusion and organ transplantation. BLOOD SCREENING BEFORE TRANSPLANTATION OR TRANSFUSION DR.T.V.RAO MD 25

PUBLIC HEALTH TO CONTROL CHAGAS DISEASE Insecticide spraying of houses and surrounding areas; house improvements to prevent vector infestation; personal preventive measures such as bed nets; good hygiene practices in food preparation, transportation, storage and consumption; screening of blood donors; testing of organ, tissue or cell donors and receivers; and screening of new-borns from infected mothers, and siblings of infected children to provide early diagnosis and treatment. DR.T.V.RAO MD 26

UPDATE ON INFECTIONS Chagas disease occurs exclusively in the Americas. As of 2008, million people from 18 countries are infected, particularly in poor, rural areas of Mexico, Central America, South America, and, very rarely, in the Southern United States. About 20,000 people are killed annually [Carlier 2003], and about 100 million (close to one in four Latin American people) or more are at risk of exposure to infection DR.T.V.RAO MD 27

DR.T.V.RAO MD 28 Programme Created by Dr.T.V.Rao MD for Medical and Health Workers in the Developing World