Chagas Disease
American Trypanosomiasis.
PKGhatak,MD.
Chagas disease is named after Dr. Carlos Chagas of Brazil. Trypanosoma cruzi causes Chagas disease in South America, and Trypanosoma gambiese causes Sleeping Sickness in Africa. Several species of Leishmania are pathogenic to humans, and both Trypanosoma and Leishmania belong to one family.
In 1909, Dr. Chagas investigated an unknown illness that was common in the rural areas of Brazil. He found a blood sucking insect feeding on humans and leaving behind feces and urine near the wound. The excreta of the kissing bug were loaded with the infective form of the parasite. The victims, while sleeping, rubbed the feces and contaminated the wound and the parasite also entered the body through the conjunctiva of the eyes.
Trypanosoma cruzi can infect in other ways - Contaminated food and drink by vectors' feces and urine often cause local endemics, contaminated blood transmission and organ transplantation are less common. Mother to child transmission during pregnancy is a major concern, and the children in subsequent pregnancies are also infected.
The victims developed illness in two phases – 1. The initial or the first stage. 2. The chronic stage.
The initial stage.
The initial illness is a mild local inflammation and the regional lymph adenitis and in a few instances only mild systemic symptoms. Occasionally, a furuncle, called Chagoma, develops at the wound site. The illness is self limited. About 50 % of new infections may remain symptom free.
In the 2nd or Chronic phase.
Years may pass without any signs of illness, and then patients present with symptoms of serious heart, gastrointestinal and neurological diseases.
The parasite Dr. Chagas discovered was a flagellated Protozoa in the blood of the victims. He conclusively proved the pathogenicity of the protozoa by recovering the same organism is susceptible animals. Dr Chagas named the parasite Trypanosoma cruzi to honor his mentor Dr. Cruz.
The Life Cycle of the Protozoa Parasite:
The organism is a motile, unicellular organism having one flagellum. The protozoa have 5 stages of development and two methods of propagation - one by binary fission and the other by sexual union. The different stages of life of the protozoa are named according to the point of attachment of the flagellum to its body or the absence of the flagella. The Greek word for the flagella is mastigot. The infective form that circulates in the blood of the victims is called Trypomastigotes.
Inside the bug.
In the midgut of the insect, the trypomastigotes transform into Epimastigotes, having the flagellum attached to the end of the body. Here epimastogotes multiply, and the epimastogotes enter the hind gut and transform back to Trypanostigotes, And infect humans when the bug takes a bloody meal.
In the victim.
The Trypomastigotes transform into a round, small unicellular organism inside the victims' cells. The parasite has no visible flagella and is called Amastigotes. Amastigotes multiply by binary fission. Amastigotes transform into trypomastigotes and burst open the victim's cells. The released Trypomastigotes infect more tissue, and also enter the bloodstream and lymphatics and are widely distributed in the body. Some of the Trypomastigotes switch back to Amastigotes, divide again and keep on multiplying by binary division. And the cycle repeats again and again.
Besides humans, small animals like monkeys, armadillos and dogs are also infected.
The insect vector.
The bug that transmits Chagas disease is a Triatomine bug, a variety of Reduviid bug, locally known as the Kissing bug, as they find it on the faces of victims.
There are several species of the Triatomine bug, one species is active in a certain locality or another. The bug is active at night. They come out of cracks of the wall, fall from the ceiling or just crawl on the bed from outside. The bugs bite on the faces of humans (part not covered during cold nights). A recent report says oral route of infection, in recent days, has been the dominant path of infection of Chagas disease.
Chagas Disease:
The incubation period is short.
The initial illness is mild and self limited, and often remains asymptomatic.
The chronic phase of Chagas disease is a protracted severe symptomatic disease of the cardiovascular, gastrointestinal and Neurovascular systems. The mortality rate is high and the disability is severe.
Pathophysiology:
The amastigotes invade muscle cells of the heart and the smooth muscles of the esophagus, and colon, and also invade the brain. The inflammatory reactions are mediated by acute phase Cytokines. The initial myocarditis is followed by necrosis of muscles are replaced by fibrous tissues. The cardiac and smooth muscles of the GI tract become weak and flabby. The heart is the most common organ affected by Chagas disease. Cardiac impulse propagation along the His bundle due to fibrosis manifests as heart block, branch block, cardiac arrhythmia and systemic embolism. Massive dilated cardiomegaly and heart failure are the prominent features of this disease. Megaesophagus leads to difficulty in swallowing solid food, and megacolon leads to chronic constipation and abdominal distention and discomfort.
The CNS infection results in strokes and many other neurological manifestations.
Diagnosis:
The mainstay of diagnosis of Chagas disease is the demonstration of moving Trypomastigotes under the coverslip of a thick smear of blood. Under the trained eyes, the movement of the transparent parasite around stationary red cells is not difficult. It is a cost-effective test and practical in the rural communities.
Other confirmatory tests and PCR antigen detection and indirect ELISA antibody detection.
Medical treatment:
Two oral medications, Benznidazole and Nifurtimox are effective in killing the parasite but the drugs must be given early in the acute phase of the disease in children 2 to 18 years of age. The older adults develop toxic side effects more frequently, and drug therapy is not recommended in adults. Women of reproductive age are tested and treated with drugs to prevent congenital Chagas disease.
Benznidazole is an imidazole derivate, actives against intracellular parasites. In Chagas disease, the drug is prescribed for 60 consecutive days. The drug inactivates parasitic enzymes and damages DNA and large protein molecules by generating cation radicals. Common side effects of this drug are various GI symptoms, skin rashes peripheral neuritis, thrombocytopenia and leukopenia, and anemia. It is potentially carcinogenic.
Nifurtimox is a nitrofuran drug. The mode of action of Nifurtimox against the parasite is similar to Benznidazole and it generates radicals through its action of nitrogenous enzymes. The adverse reactions are also like Benznidazole. But when prolonged treatment is necessary, Nitrofurans is not suitable because of its adverse effects, which are more intense than Benznidazole. Both drugs are contraindicated in pregnancy.
Surgery:
In the past various types of cardiac surgery were tried to improve function of the failing frail and flabby heart muscles. In the long run, none of those procedures proved to be beneficial and subsequently abandoned. Heart block is effectively treated with cardiac pacemakers. Only cardiac transplantation is a solution is severe heart failure.
Megaesophagus.
Laparoscopic myomectomy, esophageal mucosectomy are less involved procedures. Heller-Pinotti procedure is a more involved operation and is done in early swallowing difficulties. It is a modified Fundoplication operation.
In advanced cases, Thal-Hatakufu operation is done. In this operation, Esophgogastroplasty is performed. The success of the Thal-Hatakufu operation is moderate.
Megacolon.
A Total Colectomy operation is required with anastomosis with -(a) ileorectal, or, (b) ileoanal, or, simply a colostomy.
Prognosis of Chagas disease depends on the stage of the disease. In the early actives phase, the drug treatment is curative.
The survival in the chronic phase is poor.
Incidence and prevention of Chagas disease.
18 million people in 21 countries of Central and South America are infected with Trypanosoma cruzi and 100 million people are at risk of infection.
Insecticide is used to control the insect vector. Better housing and public education have been successful in bringing down the spread of Chagas disease.
***************************************************
No comments:
Post a Comment