Chagas Disease — Know It All!

Editorial

All you need to know about American Trypanosomiasis.

Know your ailment well, so you can manage it better!!

Here we come with Chagas Disease today!

What is Chagas Disease?

Chagas Disease is also known as American Trypanosomiasis.

Chagas disease is a highly life-threatening disease caused by the protozoan parasite Trypanosoma cruzi, also known as American trypanosomiasis (T. cruzi).

It is estimated that about 6 million to 7 million people worldwide are afflicted with the parasite that causes Chagas disease, Trypanosoma cruzi. Chagas disease is primarily present in endemic areas of 21 continental Latin American countries,1 where triatomine bugs (vector-borne) known as ‘kissing bugs’ have been mostly transmitted to humans through contact with faeces or urine, among many other common names, depending on the geographical region.

Chagas disease is named for a Brazilian physician and scholar who discovered the disease in 1909, Carlos Ribeiro Justiniano Chagas. The World Day of Chagas Disease was developed in May 2019, following the resolution of the 72nd World Health Assembly, to be celebrated on 14 April (the date of the year 1909 when Carlos Chagas diagnosed the first human case of the disease, a two-year old girl called Berenice).

What are the causes of Chagas Disease?

A protozoan parasite called Trypanosoma cruzi causes Chagas disease. Human infection occurs when faeces carrying parasites are released on human skin by an insect vector (primarily Triatominae or kissing bugs, a subfamily of the Reduviidae family and sometimes referred to as reduviid bugs). Via the bug bite, or cracks in the skin or conjunctiva, the parasites then enter the mammalian (human) host. Occasionally, when swallowed or inhaled, the parasites penetrate by mucosal cells in the mouth or airway. The bugs frequently bite and/or deposit faeces near the eyes and lips; swelling and redness (called a chagoma) often occur as the parasites reach the skin. The idea of kissing bugs derives from the presence of these signs that mimic skin modifications that occur with repeated kissing (hickies). The parasites eventually go into the bloodstream in certain individuals and lodge in different organs, especially the organs’ muscular structure. The parasites reproduce and ultimately induce recurrent symptoms that may include life-threatening heart failure, arrhythmias, weak gastrointestinal motility, meningoencephalitis or mortality due to the main organ or organs concerned.

In the regular life cycle of insect vectors (bees) and their typical hosts (over 100 species of animals), humans who live in weak or primitive living environments that border or threaten the habitats of Triatominae bugs create a split called the sylvatic loop. Then the bugs enter the human world and its domesticated animals (cats, dogs) and transmit T. To them, cruzi. Uh, when T. Cruzi is passed on from bugs to humans or human pets and the life cycle is referred to as the home cycle back to the bugs. The cycle of life of T. Cruzi is complex; both the insect vector (Triatominae bugs, also referred to as triatomine bugs) and the mammalian (human and animal) hosts have several developmental stages. The CDC figure below shows the stages of growth that exist in both the sylvatic and domiciliary periods.

What are the symptoms of Chagas Disease?

The symptoms and signs of Chagas disease vary from no symptoms at all to extreme and distressing symptoms and can be very variable. When present in the acute period, the first symptoms and signs can include any of the following:

  • Swelling and/or redness at the location of the skin infection (termed chagoma)
  • Rash of skin
  • Swollen lymph ganglions
  • A fever
  • Body aches and pains
  • Tiredness
  • Vomiting, nausea, and/or diarrhoea
  • Discomfort or pain in the abdomen
  • Enlargement of Liver and/or Spleen
  • Sign Romaña (unilateral painless edoema [swelling] of tissues around the eye)
  • There may be EKG variations that indicate myocarditis and/or arrhythmias.
  • Aching muscles

In around three to eight weeks, most people who experience the above acute-phase symptoms relieve them spontaneously. Occasionally, if the immune system of the patient is compromised, acute infections show chronic symptoms (listed below).

Many researchers say that there are no signs at the intermediate or indeterminate stage (symptom-free people). This stage can continue throughout the life of the individual, and people may never know they have Chagas disease, particularly if in the acute period they have mild to no symptoms. However, in some patients, this symptom-free stage may last only about 10–20 years before persistent symptoms occur in about 10 percent-30 percent of those affected. The recurrent phase of Chagas disease is related by some researchers to HIV/AIDS. Although HIV/AIDS slowly assaults the immune system, the heart and tissues of the gastrointestinal tract are slowly targeted by Chagas disease. Such a reference is regarded by some investigators as unjustified advertising or hype to spotlight Chagas disease.

The signs of chronic Chagas disease differ according to the most damaged organs; the most severe symptoms appear in most cases in the heart or gastrointestinal tract (or both). The signs of Chagas Chronic Disease can include:

  • Heartbeats that are abnormal
  • Palpitations Of (abnormal heartbeat sensations)
  • Fainting Over (syncope)
  • Via cardiomyopathy (chronic disease of the heart muscle)
  • Congestive cardiac insufficiency (dilated heart)
  • Shortness of Respiration (dyspnea)
  • Emphysema, Emphysema
  • Stroke stroke
  • Death abruptly
  • Chronic pain in the abdomen
  • Constipation and chronic
  • Esophagus and/or colon dilated
  • Swallowing Trouble

These signs are caused by organ damage caused by the presence of parasites in the tissues of these organs that remain. If the body responds to the parasites, chronic inflammation develops; it damages nerve cells or nerves in these tissues, causing changes in electrical conduction in the heart (arrhythmias) and weak muscle tone in the intestines.

What are the risk factors of Chagas Disease?

A big risk factor of Chagas disease is living in an environment where the vectors (kissing bugs) that transmit the disease are abundant. These regions in Mexico and Central and South America are deprived areas. A high-risk environment is any household that is infested with these vectors; removing the areas where the vectors live decreases the risk. Blood transfusion is another risk factor, especially in an endemic area, if blood donors are not tested for Chagas disease. For beneficiaries of donated organs, this possibility often happens. Immunocompromised patients are at greater risk of contracting the disease, and some women with chronic Chagas infection (up to 10%) may spread the parasites to their newborns (congenital Chagas disease). Eating unwashed foods polluted with faeces from the infected bugs may also cause Chagas disease (food-borne disease).

What are the complications of Chagas Disease?

Significant cardiac or digestive complications can occur if Chagas disease progresses to the long-lasting (chronic) process. This may include:

  • Heart insufficiency. When the heart gets so sluggish or rigid that it does not pump enough blood to satisfy the needs of the body, heart failure happens.
  • Oesophagus enlargement (megaesophagus). The irregular stretching (dilation) of your oesophagus triggers this unusual disorder. This can result in swallowing and digestive difficulties.
  • Colon Enlargement (megacolon). When the colon gets abnormally dilated, Megacolon happens, causing stomach pain, swelling and extreme constipation.

How is Chagas Disease diagnosed?

A physical examination will be performed by the doctor asking about your signs and any conditions that place you at risk for Chagas disease.

Blood testing will prove the identity of the parasite or the proteins that your immune system produces (antibodies) to combat the parasite in your blood if you have the signs and symptoms of Chagas disease.

You’ll definitely get more checks if you’re afflicted with Chagas disease. To assess if the condition has reached the chronic process and has caused cardiac or intestinal problems, these tests can be performed.

Tests involve following investigations::

  • Electrocardiogram, a test which records the electrical activity of your heart
  • Chest X-ray, an imaging procedure that helps the doctor to see if you have an enlarged heart
  • A procedure that uses sound waves to take moving pictures of the heart, enabling the doctor to see any changes in your heart or its operation.
  • Abdominal X-ray, a procedure that captures pictures of the liver, intestines and colon using radiation
  • Upper endoscopy, a procedure in which a thin, lighted tube (endoscope) is swallowed and images of the oesophagus are sent to a screen

 What is the treatment for Chagas Disease?

Medical care:

In people with Trypanosoma cruzi infection, the purposes of treatment are to remove parasites with specific drug therapy and to treat the signs and symptoms arising from the often permanent lesions associated with the disease. In 2017, for the treatment of Chagas disease caused by T cruzi in children aged 2–12 years, benznidazole was approved by the FDA. In 2020, Nifurtimox received accelerated FDA clearance for the treatment of Chagas disease (American Trypanosomiasis) caused by T cruzi in paediatric patients (born to patients younger than 18 years who weigh at least 2.5 kg). The approval for nifurtimox was based on the number of patients treated who were IgG antibody negative or who displayed an optical density decrease of at least 20% on 2 separate IgG antibody T cruzi antigen studies.

For the most part, both benznidazole and nifurtimox, especially in chronically infected patients, are limited in their capacity to affect parasitological cure. Moreover, in appropriately planned trials, it has not been proven that treatment of chronically contaminated patients with either benznidazole or nifurtimox improves results. Therefore, the use of these medications appears to be problematic in those patients.

The safety and effectiveness of benznidazole in children aged 6–12 years was confirmed in 2 placebo-controlled clinical trials. In the tests, antibody test findings in approximately 55 percent -60 percent of children administered with benznidazole modified from positive to negative, compared with approximately 5 percent -14 percent who got placebo. A supplemental protection and pharmacokinetics review of benznidazole offered information on guidelines for dosing of children as young as 2 years of age.

For all forms of acute (i.e., congenital) or reactivated Chagas illness, except for chronic T cruzi in children up to the age of 18 years, the CDC suggests antiparasitic therapy. The CDC also highly advised treatment for people with a chronic infection aged 50 years or younger who do not already have advanced Chagas cardiomyopathy.

Chagas’ Acute Illness

Both patients with acute Chagas disease should be treated with either benznidazole or nifurtimox, including children with congenital infection and individuals with reactivation of chronic immunosuppression infections.

In general, the younger the recipient, the greater the likelihood of parasitological cure, and the closer to the acquisition of the infection. The best risk of treatment is for babies with congenital Chagas disease. Data from Argentina reveals that if care is offered during the first year of existence, the cure rate reaches 90%. Some reports have indicated that the average incidence of parasitological cure for individuals with acute Chagas disease is 70%, but the author is unaware of concrete evidence confirming this prediction.

The efficacy of corticosteroids or interferon-γ has not been identified in patients with acute meningoencephalitis or Chagasic myocarditis.

Indeterminate-phase illness of Chagas

The current evidence-based opinion on the management of chronic T cruzi infection is that only benznidazole or nifurtimox should be prescribed for chronically compromised children and teenagers aged 18 years or younger. Convincing evidence from experiments in Argentina and Brazil show that a large percentage of these patients are cured from parasites.

In comparison, in adults with long-standing T cruzi infection, including individuals in the indeterminate period, the likelihood of parasitological cure with a full course of either treatment, as well as those with manifest chagasic signs, most of whom were likely infected when very young, is less than 10 percent.

In addition, it is difficult to decide which patients treated are cured, as therapy suppresses parasitemia, as expressed in decreased positivity rates in post-treatment PCR assays, as well as in xenodiagnosis and hemoculture, and anti-T cruzi antibodies can remain positive for years.

Until recently, there has been a shortage of evidence from adequately organised randomised clinical trials (RCTs) assessing the effects of particular medical outcomes in chronically contaminated adults. The findings from the Benznidazole Assessment for Interrupting Trypanosomiasis (BENEFIT) trial have recently filled a segment of this gap. A total of 2,854 T cruzi-infected patients with minor heart failure were tracked for an average of 5.4 years in this blind, placebo-controlled benznidazole vs placebo study conducted in Brazil, Argentina, and Colombia. Parasite identification, as seen in the PCR assay, was suppressed as predicted, but benznidazole did not dramatically reduce clinical cardiac deterioration. Relevant care of adults with long-standing T cruzi infection and demonstrable heart dysfunction cannot be recommended in light of these findings.

Importantly, no patients were involved in the Gain study in the indeterminate phase of chronic T cruzi infection, so there is also a shortage of evidence from sufficient comparative research addressing the effectiveness of treating individuals in this community. In 2006, a two-day conference organised by the CDC of a panel of experts from many endemic countries and the United States, in which the author of this article was a member, took place to address this topic in depth. In the publication arising from that meeting, the panel recommended that medication should be provided to chronically infected individuals (the BENEFIT statistics were not available at the time) and that treatment choices should be made by patients and providers after discussion of the dangers and potential benefits. This suggestion was based on evidence from many non-randomized controlled experiments that showed that care could be effective for chronically infected individuals and on the premise that parasitemia suppression was a proxy for improved health outcomes. The findings of BENEFIT explicitly suggest that this is not the case, as such inhibition has been clearly reported in patients in the benznidazole arm, but no therapeutic benefit has been identified. Thus, as a justification for treating chronically infected patients, the presumption about the suppression of parasitisms can no longer be left out.

Present CDC guidelines notes that treatment for adults 50 years of age or younger with chronic infection who do not already have advanced Chagas cardiomyopathy is highly recommended. he latest recommendations made by the Ministries of Health in Brazil and Argentina are in accordance with those reported at the 2006 CDC conference. However, the author of this article does not advocate the treatment of benznidazole or nifurtimox in adults with chronic T cruzi infection, irrespective of their health condition, provided that these guidelines are not evidence-based, the findings of the Gain trial and the appearance of alarming side effects in a large proportion of treated patients. It should be remembered that, after the findings of the Gain trial were released, the CDC guidelines and the recommendations of the Ministries of Health in Brazil and Argentina have not been revised.

Few research has been published which sheds light on the issue of whether prophylactically treating women of childbearing age with either nifurtimox or benznidazole before they become pregnant will reduce the rate of congenital transmission. In one of the inquiries related to this question, only a limited number of women were treated as adults in the sample group. The study did not provide any details on parasitemia suppression or parasitological cure. In the research, none of the babies born to women had congenital Chagas disease, meaning that pre-pregnancy care of women with chronic T cruzi infection could be effective in minimising congenital transmission. In a broader analysis, this issue needs to be answered.

There is no evidence available on the basis of recommendations for prophylactic management of chronic infection in persons undergoing immunosuppression (e.g. pretransplantation) or in persons already undergoing immunosuppression (eg, those with HIV infection).

Chronic symptomatic disorder of Chagas

Antiparasitic care should not be given to people who have already experienced cardiac or gastrointestinal symptoms.

Treatment for general medical:

Surgical Care:

Cardiopathy Disorder

Pacemaker positioning may be needed for atrial and ventricular rhythm disruptions. In certain patients with Chagas disease, ablation procedures have been used for tachyarrhythmias as well as implanted defibrillators.

The effectiveness of implantable cardioverter systems is controversial in patients with progressive heart disease caused by Chagas.

The efficacy of left ventricular apical aneurysm resections that occur in some Chagas cardiomyopathy patients has not been identified.

For certain patients with end stage Chagas heart disease, cardiac transplantation is an alternative, and hundreds of patients in Argentina, Brazil, and the United States have undergone this treatment. It is important to note that the survival rate for patients with Chagas disease who have undergone heart transplantation is higher than in the general community of patients who have undergone heart transplantation for other causes, presumably because, as is the case with diabetes mellitus, the pathogenic mechanism resulting in cardiomyopathy in Chagas disease is not systemic. When the first such transplantations were conducted in Brazil in the late 1980s, reactivation of the underlying T cruzi infection was a significant issue; however, this is now less of a problem with decreased immunosuppressive dosing.

Megaesophagus

Large esophagus cardiac myectomy of the anterior gastroesophageal junction, combined with valvuloplasty to alleviate reflux, is frequently done in patients with chagasic megaesophagus in whom esophageal dilation is insufficient. For the treatment of extreme megaesophagus, laparoscopic myotomy is gradually being used. In extreme cases, incomplete esophageal resection with replacement with esophagogastroplasty has been used.

Megacolon

Usually used in the treatment of idiopathic congenital megacolon, patients with extreme chagasic megacolon can benefit from the Duhamel-Haddad procedure.

In certain cases, patients with sigmoid volvulus who were awaiting the Duhamel-Haddad operation underwent anterior sigmoidostomy with potential necrosis segment resection.

References:

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https://www.mayoclinic.org/diseases-conditions/chagas-disease/diagnosis-treatment/drc-20356218

Chagas Disease Symptoms, Treatment & Diagnosis

https://emedicine.medscape.com/article/214581-treatment#d6

https://medlineplus.gov/chagasdisease.html