Skip to main content

A REVIEW ON CHAGAS DISEASE

 

Clinical courses

About Author:
B. Krishna
Vasavi Institute of Pharmaceutical Sciences,
Kadapa, JNTUA
krishna5432.b@gmail.com

Abstract:
Chagas' disease is caused by the protozoan parasite Trypanosomacruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents like skunks and coyotes are also infected with T. cruzi.. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century.

REFERENCE ID: PHARMATUTOR-ART-1679

INTRODUCTION
Chagasdisease is a tropicalparasitic disease caused by the flagellateprotozoanTrypanosomacruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking "kissing bugs" of the subfamily Triatominae (family Reduviidae) most commonly species belonging to the Triatoma, Rhodnius.


Trypanosomacruzi
The impact of Chagas disease is not limited to the rural areas in Latin America in which vectorborne transmission occurs. Large-scale population movements from rural to urban areas of Latin America and to other regions of the world have increased the geographic distribution and changed the epidemiology of Chagas disease. In the United States and in other regions where Chagas disease is now found but is not endemic, control strategies should focus on preventing transmission from blood transfusion, organ transplantation, and mother-to-baby (congenital transmission.


HISTORY

Chagas disease was named after Carlos Chagas, who first described the parasite Trypanosomacruzi in infected humans in 1909 while working for the Oswaldo Cruz Institute in Brazil.

Chagas discovered that the parasites are transmitted to humans by entering breaks in the skin after they are deposited on the skin in insect feces.

Chagas was the first scientist to discover all aspects of a new infectious disease; its pathogen (T. cruzi), main insect vector (Triatominae or kissing bugs), hosts (humans, mammals), clinical manifestations, and epidemiology.


The parasite species was named cruzi to honor his employer and scientific mentor, OswaldoCruzi

ETIOLOGY
In Chagas-endemic areas, the main mode of transmission is through an insect vector called a triatomine bug.

A triatomine becomes infected with T. cruzi by feeding on the blood of an infected person or animal. During the day, triatomines hide in crevices in the walls and roofs.

The bugs emerge at night, when the inhabitants are sleeping. Because they tend to feed on people’s faces, triatomine bugs are also known as "kissing bugs". After they bite and ingest blood, they defecate on the person.

Triatomines pass T. cruzi parasites (called trypomastigotes) in feces left near the site of the bite wound.

Scratching the site of the bite causes the trypomastigotes to enter the host through the wound, or through intact mucous membranes, such as the conjunctiva.

Once inside the host, the trypomastigotes invade cells, where they differentiate into intracellular amastigotes. The amastigotes multiply by binary fission and differentiate into trypomastigotes, which are then released into the bloodstream.

This cycle is repeated in each newly infected cell. Replication resumes only when the parasites enter another cell or are ingested by another vector. (See: Life cycle and transmission of T. cruzi)

Dense vegetation and urban habitats are not ideal for the establishment of the human transmission cycle.

However, in regions where the sylvatic habitat and its fauna are thinned by economic exploitation and human habitation, such as in newly deforested areas, piassava palm culture areas, and some parts of the Amazon region, a human transmission cycle may develop as the insects search for new food sources.

Infection can also occur from:
1. mother-to-baby (congenital),
2. contaminated blood products (transfusions),
3. an organ transplanted from an infected donor,
4. laboratory accident, or
5. contaminated food or drink (rare)

T. cruzican also be transmitted through blood transfusions. With the exception of blood derivatives (such as fractionated antibodies), all blood components are infective.

The parasite remains viable at 4°C for at least 18 days or up to 250 days when kept at room temperature. It is unclear whether T. cruzi can be transmitted through frozen-thawed blood components.

Other modes of transmission include organ transplantation, through breast milk, and by accidental laboratory exposure. Chagas disease can also be spread congenitally (from a pregnant woman to her baby) through the placenta, and accounts for approximately 13% of stillborn deaths in parts of Brazil.

EPIDEMOLOGY & RISK FACTORS

Chagas Disease in Latin America (Endemic zones)

Chagas disease affects eight to 10 million people living in endemic Latin American countries, with an additional 300,000–400,000 living in nonendemic countries, including Spain and the United States.

An estimated 41,200 new cases occur annually in endemic countries, and 14,400 infants are born with congenital Chagas disease annually. About 20,000 deaths are attributed to it each year.

The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina.

In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces, and major progress toward this goal has also been made in both Paraguay and Bolivia.

Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries.

Risk factors :
1. Living in an area where the vectors (kissing bugs) that spread the disease are plentiful is a major risk factor for Chagas disease.

2. Such areas are impoverished areas in Mexico and Central and South America.

3. Any residence that is infested with these vectors is a high-risk area; eliminating the areas where the vectors reside reduces the risk.

4. Another risk factor is obtaining a blood transfusion, especially in an endemic region, if the blood donors are not screened for Chagas disease.

5. This risk also occurs for recipients of donated organs. Immunocompromised patients have a higher risk for development of the disease, and some infected women with chronic Chagas (as many as 10%) may transmit the parasites to their newborns.

SIGNS & SYMPTOMS
The symptoms of Chagas disease can be quite variable and range from no symptoms at all to severe and distressing symptoms. The first symptoms, when present in the acute phase, may include some of the following:

1. Swelling and/or redness at the skin infection site (termed chagoma)
2. Rash
3. Swollen lymph nodes
4. Fever
5. Head and body aches
6. Fatigue
7. Nausea, vomiting, and/or diarrhea
8. Liver and/or spleen enlargement
9. Romaña sign (unilateral painless edema [swelling] of tissues around the eye)

Most individuals who get the above acute-phase symptoms have them resolve spontaneously in about three to eight weeks. Occasionally, acute infections show chronic symptoms (listed below) if the patient's immune function is weakened.

Most investigators suggest that the intermediate or indeterminate phase has no symptoms. This stage may last throughout the person's life and the individuals may never know they have Chagas disease, especially if they had mild or no symptoms in the acute phase.

However, this stage may only last about 10-20 years in some patients before the chronic symptoms develop in about 10%-30% of those infected. Some researchers compare the chronic phase of Chagas disease to HIV/AIDS. Whereas HIV/AIDS slowly attacks the immune system, Chagas disease slowly attacks the heart and the tissues of the gastrointestinal tract.

Symptoms of chronic Chagas disease vary according to the organs most affected; in most cases, the heart or the gastrointestinal tract (or both) show the most serious symptoms. Chronic Chagas disease symptoms may include the following:

1. Irregular heartbeats

2. Palpitations

3. Fainting (syncope)

4. Cardiomyopathy (chronic disease of the heart muscle)

5. Congestive heart failure

6. Shortness of breath (dyspnea)

7. Emphysema

8. Stroke

9. Sudden death

10. Chronic abdominal pain

These symptoms are due to organ damage caused by the persistent presence of the parasites within the tissues of these organs.Chronic inflammation develops as the body reacts to the parasites; it affects the nerve cells or neurons in these tissues, causing electrical conduction changes in the heart (arrhythmias) and poor muscle tone in the intestines.

DIAGNOSIS
Unless the person lives in an area where the chagomas associated with Chagas disease are well recognized, the acute phase is not often diagnosed.

The majority of acute-phase infections are not diagnosed because many people develop nonspecific symptoms, and the people who get the infection usually are very poor, have primitive living conditions, and no access to medical care.

Unfortunately, if Chagas disease is not diagnosed and treated in the early phase, those infections that progress to chronic phase are then are diagnosed in this later stage when they are not easily treated because the damage to the body organs is usually irreversible.

There are multiple types of blood tests available to test for Chagas disease.

Most are based on the host (human) production of antibodies directed against the infecting parasites, although direct microscopic examination of blood smears may visualize the parasites.

However, microscopic visualization of the parasites usually requires confirmation by immunological studies because visually, the parasites may be confused with those seen in people with malaria, leishmaniasis, babesiosis, giardiasis, or African sleeping sickness.

Microscopic preparation and examination should be performed by experienced lab technicians or experts in parasitology.

Giemsa-stained microscopic picture of Trypanosomacruzi in a blood smear; SOURCE: CDC/Dr. Mae Melvin

In the U.S., the FDA approved an immunologic test (enzyme-linked immunosorbent assay or ELISA test) for Chagas disease by Ortho-Clinical Diagnostics in 2006.

It detects antibodies formed against T. cruzi with high sensitivity and specificity and currently is the only FDA-approved test. Since 2007, about 800 blood-donor samples have been detected as Chagas-positive across the U.S. (see map, reference five).

Other tests used in other countries (indirect immunofluoresence, hemagglutination) are less sensitive and specific but are still used.

A ChagasRadioimmune Precipitation assay (Chagas RIPA) is used in research and with FDA permission in some clinical testing but is not widely available.

Most cases of Chagas disease are diagnosed when individuals donate blood; most people are not aware they have been infected with T. cruzi.

However, since blood and organ donation can pass the disease to other people, most labs now test donated blood and organs for Chagas disease with the approved ELISA assay. If the donors are positive, they are notified (diagnosed).

The prevalence of Chagas-positive blood donors is estimated by various studies to widely range between about one positive case per 2,000-29,000 donors.

Chronic-phase Chagas disease is diagnosed also with the above-mentioned blood tests, but these patients also often have physical findings that indicate the patient has chronic disease.

Physical findings may include swelling of the extremities (peripheral edema), ascites, pulmonary congestion, and arrhythmias in patients with heart involvement.

Patients with mainly chronic gastrointestinal involvement may have weight loss, severe gastroesophageal reflux, esophageal erosions, inability to swallow normally, or an enlarged colon (megacolon) with an enlarged abdomen.

Many different diseases can cause these physical findings so it is important to know that the patient has a positive blood test for T. cruzi before concluding the person has Chagas disease.

Conversely, if such physical findings and history of possible contact with Chagas vectors is present, then the blood tests could be done to either prove or rule out the diagnosis of Chagas disease in chronic phase.

PATHOPHYSIOLOGY:
The parasite is typically transmitted by an infected triatomine bug. Triatomines hide in the nests or resting places of wild animals.

They feed on blood while the animal is sleeping (sylvatic cycle). Some of these insect species have adapted to human dwellings, where they hide in crevices, emerging at night for their blood meal (domestic cycle). Within the vector's intestine, T cruzi undergoes several successive developmental stages, the last of which is a flagellated form living in the vector's rectum.

Ingestion of the blood meal causes the vector to defecate and deposit faeces containing infectious metacyclictrypomastigotes onto the victim's skin, close to the bite wound. Upon awakening, the victim commonly rubs the itching bite area, pushing the trypanosome-laden faeces into the bite wound or onto the conjunctiva.

Metacyclictrypomastigotes enter the victim's bloodstream through the bite wound, or penetrate mucous membranes such as the conjunctiva (leading to Romaña sign). This initiates the acute stage of disease.

This infective form of the parasite invades macrophage cells, and transforms into intracellular amastigotes. The amastigotes multiply by binary fission, and are released as trypomastigotes into the bloodstream and tissues.

Life-cycle of Trypanosomacruzi, the causative parasite of Chagas disease

Trypomastigotes infect new cells of various tissues (e.g., reticuloendothelial system, myocardium, muscles, nervous system) and transform into intracellular amastigotes. After infection, inflammatory responses, cellular lesions, and fibrosis occur sequentially (mainly in the heart, oesophagus, and colon).

In the acute phase, multiple cycles of intracellular parasite multiplication occur. This leads to high parasitaemia, which further amplifies inflammation and cell lesions.

This process is less intense during chronic Chagas disease.

Myocytes and the nervous cells (causing autonomic denervation) are typically affected. Direct destruction occurs by intracellular parasitism, necrosis related to inflammation, and other cytotoxic mechanisms.

Fibrosis is more intense than the fibrosis associated with any other cardiological disease.

The cardiac form in the chronic phase is due to destruction of the conduction system, myocytes, and parasympathetic cardiac nerves.

In association with the appearance of arrhythmogenic electric foci in the inflammatory areas, it gives rise to arrhythmic syndrome.

The hypertrophy of myocytes, and the intense fibrosis replacing the destroyed cells, predispose to cardiac dilatation and failure.

The left ventricular wall becomes thinner, typically allowing for the formation of an apical aneurysm. Thrombi are often present in such aneurysms, easily explaining the common occurrence of systemic (CNS) and pulmonary thromboembolism.

Parasympathetic intramural denervation is irregularly found within the gastrointestinal system, and mainly affects the oesophagus and the colon (most frequently the sigmoid colon).

The affected intestine may have a normal macroscopic appearance with functional peristaltic disturbance, but may also dilate, leading to megaoesophagus or megacolon.

Volvulus of the sigmoid colon is a rare complication appearing in advanced cases, and is associated with a high risk of intestinal necrosis.

The factors that predispose a patient in the indeterminate phase of T cruzi infection to develop symptomatic disease are not defined.

Many factors may contribute. These include parasite strain; interaction with other mammal reservoirs; human immunogenetics; nutrition profile; age at first infection; and comorbidities (important in the pathogenesis of chronic symptomatic/determinate Chagas disease).

TREATMENT
Treatment for Chagas disease often depends on the phase of the disease and the age of the patient.

Acute-phase treatment centers on killing the T. cruzi parasites with antiparasitic drugs. The prescription medications.

1. Benznidazole (Rochagan, Ragonil),
2. Nifurtimox (Lampit) may eliminate or reduce the number of parasites in the body.
3. Melarsoprol

Some investigators suggest that drug-resistant parasites occur and others suggest these drugs of choice never eliminate all of the parasites.

These two drugs currently available for Chagas treatment are Benznidazole and Nifurtimox.

Interestingly, neither drug is on the list of essential medicines for most Latin American countries, indicating the general lack of funding, advocacy, and awareness of Chagas disease worldwide (see below for more details). Both drugs have shown up to 80% cure rates of acute Chagas, while documented cure in chronic patients is harder to achieve.

The downside of these drugs is their side effect profile, which leads to non-compliance in a large number of patients, particularly adults.

The treatment course also lasts for 6 weeks and requires weekly clinical monitoring for side-effects. Clinical trial dropout rates with both of these drugs have approached 20-30%.

Accordingly, more effective Chagas drugs with fewer side effects are urgently needed, and research on that front has been slow and underfunded.

However, the CDC recommends drug treatment for "all people diagnosed with an acute (Chagas) infection, congenital infection, and for those with suppressed immune systems, and for all children with chronic infection.

Adults with chronic infection may also benefit from treatment." The CDC advises caution about treating adults over 50 years of age and recommends that treatment plans for older adults be individualized.

Both of these antiparasitic drugs are available in Central and South America. In the United States, however, the drugs can be obtained only through the CDC (Centers for Disease Control and Prevention).

During the intermediate or indeterminate phase, the vast majority of adult patients obtain no antiparasitic treatments; however, children in this stage of disease should continue drug therapy.

The situation with adults may change as new investigations with antiparasitic drug treatments are being done in South America.

As quoted above, the CDC says adults with chronic infection may benefit from drug treatment, but most experts suggest there is no benefit to adults with chronic phase Chagas disease.

However, treatment of the symptoms of chronic Chagas disease is often necessary and can be life prolonging or lifesaving. For example, pacemaker placement or even cardiac transplantation can be lifesaving to some patients who develop arrhythmias or cardiomyopathy.

Surgical resection of the gastrointestinal tract may help alleviate some gastrointestinal problems.

In addition, there are many medications available to treat specific arrhythmias and other bowel problems that may be seen in chronic Chagas disease; cardiac and gastrointestinal consultants often can help manage chronic-phase Chagas disease.

Benznidazole :
Benznidazole is used as an alternative agent in the treatment of American trypanosomiasisChagas' disease) caused by Trypanosomacruzi.

However, nifurtimox is considered the primary agent in the treatment of American trypanosomiasis.

It is a imidazole derivative.

Structure of Benznidazole

Mechanism of action/Effect:
Trypanocidal  although the mode of action has not been studied in detail, benznidazole appears to inhibit protein and ribonucleic acid (RNA) synthesis in the trypanosome

Pharmacokinetics:

Absorption:
Rapidly absorbed from the gastrointestinal tract of healthy volunteers following a single oral 100-mg dose.
Distribution:
Rapidly and evenly distributed between the plasma and the red blood cells in humans.
Relative volume of distribution—Average 0.56 L per kg (L/kg).
Protein binding:
About 44%.
Half-life:  12 hours
Elimination: Approximately 10.5 to 13.6 hours with an average of 12 hours.
Time to peak concentration:
About 3 to 4 hours in healthy volunteers following a single oral 100-mg dose.
Peak plasma concentration:
About 2.2 to 2.8 mcg per mL (mcg/mL) with an average of 2.54 mcg/mL in healthy volunteers following a single oral 100-mg dose.

Elimination:
Renal—60 to 67% of the medication was eliminated in the urine within 4 days in healthy volunteers given a dose of 14 mg per kg of body weight (mg/kg) of 14C-tagged benznidazole.

Fecal—About 22 to 28%.

Pregnancy/Reproduction;
Pregnany Studies have not been done in humans.The World Health Organization (WHO) prescribing information does not recommend the use of benznidazole during the first trimester of pregnancy.
Studies done in female rats given benznidazole in oral doses of 25 to 75 mg/kg a day from the seventh to the sixteenth day of pregnancy and in rabbits given oral doses of 25 mg/kg a day from the seventh to the nineteenth day of pregnancy, have not shown benznidazole to be embryotoxic or teratogenic.

Benznidazole may decrease the concentration of leukocytes and platelets on rare occasion

Side/Adverse Effects:
1. Peripheral neuropathy,
2. progressive purpuric dermatitis(reddish spots on skin or reddish discoloration of skin)
3. Blood dyscrasias, specifically leukopenia(fever or chills; sore throat), and thrombocytopenia (pinpoint red spots on skin; unusual bleeding or bruising
4. Gastrointestinal disturbances(abdominal or stomach pain; diarrhea; nausea; vomiting)
5. Fatigue(unusual tiredness or weakness
6. psychic disturbances such as (disorientationconfusion), insomnia (trouble in sleeping), inability to concentrate,restlessness.

Nifurtimox:
Category: Antiprotozoal  (systemic)

Chemical group:Synthetic nitrofuran compound.

Nifurtimox is used as a primary agent in the treatment of American trypanosomiasis (Chagas disease) caused by Trypanosomacruzi , especially in the acute, early stage of the disease.

In the chronic stage, the therapeutic benefit of this agent is less certain.The efficacy of nifurtimox in the treatment of chronic Chagas disease varies from one country to another, possibly due to variation in the sensitivity of different strains of the organism

Mechanism of action/Effect:
Trypanocidal. Two hypotheses may explain the mechanism of action of nifurtimox.

One involves the ability of this agent to form a nitro-anion radical metabolite, which reacts with the nucleic acids of the parasite, causing a significant breakage in the deoxyribonucleic acid (DNA).

This mechanism is similar to that proposed for the antibacterial action of other nitrofuran agents.

The other involves the production of superoxide anions, and hence, hydrogen peroxide (both of which are very toxic to the parasite) and inhibition of trypanothionereductase, which is a parasite-specific antioxidant defense enzyme.

Another enzyme, ascorbate-linked peroxidase, is also present but at relatively low levels in the organism.

Lack of these enzymes leads to the accumulation of hydrogen peroxide to cytotoxic levels, resulting in death of the parasite.

Pharmacokinetics:

Absorption:
Rapidly absorbed from the gastrointestinal tract.
Distribution:
Low concentrations of the unchanged substance appear in the serum and plasma following oral administration of nifurtimox in healthy volunteers.
Biotransformation:
Rapidly and extensively metabolized  in the liver where it undergoes nitroreduction involving cytochrome P-450 and P-450 reductase.

Interindividual variability was noted suggesting that metabolism of nifurtimox may be under genetic control.

Half-life:
Elimination half-life—2.95±1.19 hours in healthy volunteers following a single oral dose of 15 mg/kg.
Time to peak concentration:
About 2 hours.

Elimination:
Renal Very little nifurtimox (less than 1%)  is excreted in the urine, with an apparent clearance of 193.4±93.2 L per hour in healthy volunteers following a single oral dose of 15 mg/kg.

Patients with renal failure were found to have a 50% lower clearance.

This may be due to a reduction in the metabolic clearance of nifurtimox due to altered hepatic enzyme reactions caused by the chronic renal disease itself.

Drug interactions :
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate) not necessarily inclusive (» = major clinical significance):

Side/Adverse Effects:
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate) not necessarily inclusive:

Those indicating need for medical attentionIncidence less frequent:
1.      Skin rash  about 5%
2.      CNS toxicity including disorientation(confusion}), disturbances of equilibrium such as ataxia (clumsiness or unsteadiness), and nystagmus (uncontrolled back-and-forth and/or rolling eye movements), excitation.
3.      forgetfulness,
4.      insomnia(trouble in sleeping), irritability, psychosis (mood or mental changes),  seizures (convulsions) and tremors.
5.      eosinophilia(fever)
6.      impotence(decreased sexual drive or ability)
7.      leukopenia(fever; chills or sore throat) occurs with excessively high doses but disappears spontaneously after withdrawal of the medication

Proper use of this medication:
1.      Taking with meals to minimize gastrointestinal irritation

  1. Compliance with full course of therapy
  2. When treating infants, crushing the tablets and mixing with food at beginning of meal
  3. Proper dose
  4. Proper storage

Melarsoprol:

Systematic (IUPAC) name:

(2-(4-(4,6-diamino-1,3,5-triazin-2-ylamino)phenyl)- 1,3,2-dithiarsolan-4-yl)methanol

Melarsoprolis a medicinal drug used in the treatment of human African trypanosomiasis such as chagas disease and African sleeping sickness.

It is also sold under the trade names “Mel B” and “Melarsen Oxide-BAL.”

Mechanism of action/Effect:
Trypanocidal; melarsoprol is believed to work by disruption of energy generation in the trypanosome parasite due to the high affinity of melarsoprol for sulfhydryl groups. These groups form the active sites of many enzymes (especially the kinases), and are involved in the maintenance of the secondary and tertiary structures of proteins. Once inside the trypanosome, melarsoprol inactivates the enzyme, pyruvate kinase, which is present in the cytoplasm. This causes inhibition of the synthesis of adenosine triphosphate (ATP), which is the energy required for the survival of the parasite. The trypanosome eventually dies as a result of diminished energy production.

Selectivity of melarsoprol is thought to be related to 3 factors, namely: efficient binding of melarsoprol to the trypanosome rather than the mammalian host enzyme, some concentration of the medication in the trypanosome, and total dependence of the trypanosome on glycolysis for energy (ATP) generation.

Pharmacokinetics:

Absorption:
Fairly well absorbed after oral administration but is not normally given by this route; usually given parenterally.
Distribution:
Crosses the blood-brain barrier; cerebrospinal fluid (CSF) concentration is about 50-fold lower than that in the serum; significant variability has been shown when CSF concentration was measured 24 hours after the last injection of each therapeutic course and 120 hours after the very last injection; maximum CSF concentration is about 260 ng per mL (ng/mL) and the minimum CSF concentration is below the limit of detection; mean CSF concentration is about 30 ng/mL.
Volume of distribution (VolD) >100 L per kg.

Half-life:
Mean terminal elimination half-life About 35 hours.
Peak serum concentration:
Most serum concentrations are between 2 and 4 mcg per mL (mcg/mL) 24 hours after initial administration and are still ³ 0.1 mcg/mL after 120 hours;.
Elimination:
Renal Rapidly excreted in the urine  within days of administration; total clearance is about 50 mL per minute.

Side/Adverse Effects:

1. Jarisch-Herxheimer-like reaction(chills; fever; general feeling of illness or discomfort; headache; rigidity; sweating)

2. local swelling at injection site

3. peripheral neuropathy(numbness, tingling, pain, or weakness of hands or feet)

4. phlebitis(pain at injection site)

5. reactive arsenical encephalopathy(confusion; convulsions; fever; headache; loss of consciousness; restlessness; slurring of speech; tremors

6. Incidence less frequent

7. Cutaneous reactions, such as exfoliative dermatitis(red, thickened, or scaly skin), or urticaria (skin rash or itching)

8. hepatic dysfunction(fever with or without chills; yellow eyes or skin)

9. hypertension(increased blood pressure)

10. myocardial toxicity(irregular heartbeat)

11. Incidence less frequent.

12. Gastrointestinal disturbances.

PREVENTION & CONTROL
Awareness and prevention campaign poster in Cayenne, French Guiana, 2008.

There is currently no vaccine against Chagas disease and prevention is generally focused on fighting the vector Triatoma by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in rural areas.

For urban dwellers, spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous; a mosquito net is recommended. Some measures of vector control include:
1. A yeast trap can be used for monitoring infestations of certain species of triatomine bugs (Triatomasordida, Triatomabrasiliensis, Triatomapseudomaculata, and Panstrongylusmegistus).

2. Promising results were gained with the treatment of vector habitats with the fungus Beauveriabassiana.

3. Targeting the symbionts of Triatominae through paratransgenesis can be done.

A number of potential vaccines are currently being tested. Vaccination with Trypanosomarangeli has produced positive results in animal models.

More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas disease is being tested by several research groups.

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease, but the development and implementation of blood bank screening tests has dramatically reduced this risk in the last decade.

Blood donations in all endemic Latin American countries undergo Chagas screening, and testing is expanding in countries, such as France, Spain and the United States, that have significant or growing populations of immigrants from endemic areas.

The US FDA has approved two Chagas tests, including one approved in April 2010, and has published guidelines that recommend testing of all donated blood and tissue products.

While these tests are not required in U.S., an estimated 75–90% of the blood supply is currently tested for Chagas, including all units collected by the American Red Cross, which accounts for 40% of the U.S. blood supply. The ChagasBiovigilance Network reports current incidents of Chagas-positive blood products in the United States, as reported by labs using the screening test approved by the FDA in 2007.

Research:
Several experimental treatments have shown promise in animal models.

These include inhibitors of oxidosqualenecyclase and squalene synthase, cysteine protease inhibitors, dermaseptins collected from frogs in the genus(PhyllomedusaP. oreades and P. distincta), the sesquiterpene lactone dehydroleucodine (DhL), which affects the growth of cultured epimastigote–phase Trypanosomacruzi, inhibitors of purine uptake, and inhibitors of enzymes involved in trypanothione metabolism.

Hopefully, new drug targets may be revealed following the sequencing of the T. cruzi genome. A 2004 in vitro study suggests components of green tea (catechins) may be effective against T. cruzi.

REFERENCES
1.    Marr JJ, Docampo R. Chemotherapy for Chagas disease: a perspective of current therapy and considerations for future research. Rev Infect Dis 1986; 8(6): 884-903.
2.    Cerisola JA. Chemotherapy of Chagas infection in man. In: Proceedings of an international symposium held in conjunction with the fifth international congress on protozoology; 1977 June 27; New York (NY): 35-47. (PAHO Scientific Publication No. 347).
3.    Polak A, Richle R. Mode of action of the 2-nitroimidazole derivative benznidazole. Ann Trop Med Parasitol 1978; 72(1): 45-54.
4.    Raaflaub J, Ziegler WH. Single-dose pharmacokinetics of the trypanosomidebenznidazole in man. Arzneimittelforschung 1979; 29: 1611-4.
5.  Raaflaub J. Multiple-dose kinetics of the trypanosomidebenznidazole in man. Arzneimittelforschung 1980; 30(12): 2192-4.
6.    Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 79.
7.    Abramowicz M, editor. Drugs for parasitic infections. Med Lett Drugs Ther 1992; 34(865): 17-26.
8.    Markell EK, Voge M, John DT. Medical parasitology. 7th ed. Philadelphia: W.B. Saunders Company, 1992: 147.
9.    Goldsmith RS. Antiprotozoal drugs. In: Katzung BG, editor. Basic and clinical pharmacology. Norwalk: Appleton and Lange, 1992: 723-47.
10.    Van Voorhis WC. Therapy and prophylaxis of systemic protozoan infections. Drugs 1990; 40(20): 176-202.
11.    Gorla NB, Ledesma OS, Barbieri GP, Larripa IB. Assessment of cytogenetic damage in Chagasic children treated with benznidazole. Mutat Res 1988: 206, 217.
12.    Andrade SG, Rassi A, Magalhaes JB, Filho FF, Luquetti AO. Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains. Trans R Soc Trop Med Hyg 1992; 86: 624-6.
13.    Gallerano RH, Marr JJ, Sosa RR. Therapeutic efficacy of allopurinol in patients with chronic Chagas disease. Am J Trop Med Hyg 1990; 43(2): 159-66.
14.    Apt W, Arribada A, Arab F, Ugarte JM, Luksic I, Sole C. Clinical trial of benznidazole and an immunopotentiator against Chagas disease in Chile. Trans R Soc Trop Med Hyg 1986; 80: 1010.
15.    WHO Model Prescribing Information: Drugs used in parasitic diseases. Geneva: World Health Organization, 1990: 71-4.
16.    Rochagan product monograph (Roche—Brazil), Rec 2/94.
17.    Rochagan package insert (Roche—Brazil), Rec 2/94.
18.    Dukes MNG, editor. Meyler's side effects of drugs. An encyclopedia of adverse reactions and interactions. 10th ed. Amsterdam: Elsevier, 1994: 706.
19.    Payan DG. Nonsteroidal anti-inflammatory drugs; nonopioid analgesics; drugs used in gout. In: Katzung BG, editor. Basic and clinical pharmacology. Norwalk: Appleton and Lange, 1992: 491-512.
20.    Viotti R, Vigliano C, Armenti H, et al. Treatment of chronic Chagas' disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 1994; 127(1): 151-62.
21.    Reynolds JEF, editor. Martindale, the extra pharmacopeia. 29th ed. London: The Pharmaceutical Press, 1989: 515.
22.    Gutteridge WE. Existing chemotherapy and its limitations. Br Med Bull 1985; 41(2): 162-8.
23.    Abramowicz M, editor. Drugs for parasitic infections. Med Lett Drugs Ther 1993; 35(911): 111-22.
24.    Van Voorhis WC. Therapy and prophylaxis of systemic protozoan infections. Drugs 1990; 40(20): 176-202.
25.    Pepin J, Guerin C, Ethier L, et al. Trial of prednisolone for the prevention of melarsoprol-induced encephalopathy in gambiense sleeping sickness. Lancet 1989: 1246-50.
26.    Fleeger CA, editor. USAN 1995. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 410.
27.    Burri C, Baltz T, Giroud C, et al. Pharmacokinetic properties of the trypanocidal drug melarsoprol. Chemotherapy 1993; 39: 225-34.
28.    WHO Model Prescribing Information: Drugs used in parasitic diseases. Geneva: World Health Organization, 1990: 68-70.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE