Chagas Disease: A Review of the Disease and Its Interaction with COVID-19

Abstract

Chagas disease is a chronic and silent disease caused by Trypanosoma cruzi. It is endemic to Latin America, but it has spread to non-endemic countries worldwide. It is primarily a vector-borne disease that is transmitted by triatomines. It has a broad clinical spectrum and infected individuals can develop life-threatening complications if left undiagnosed and remain untreated. COVID-19 is a complex and evolving disease caused by SARS-CoV-2. It has caused a catastrophic global effect, infecting about 768 million people, of which almost 200 million live in America, where both diseases overlap. The resources that have been assigned to fight back its burden have disrupted essential health services that are needed to advance towards the control, elimination, and eradication of Chagas disease. This chapter includes an overview of the disease, discusses its interaction with COVID-19, and highlights the crucial priorities for healthcare professionals and policymakers to leave no one behind.

1. Introduction

Chagas disease is a chronic and silent disease caused by Trypanosoma cruzi, an intracellular protozoan that is mainly transmitted by the bite of infected triatomines. It is endemic to Latin America, but cases have been increasing significantly in non-endemic countries, making it a global health issue [1]. When acquired, the disease develops in stages. During the acute stage, most people remain asymptomatic, meanwhile, during the chronic stage, some people develop cardiovascular and gastrointestinal complications. Delayed diagnosis and inadequate treatment decrease their life quality and increase their risk of death. Up to date, awareness is the best option for prevention. There is no preventive or therapeutic vaccine available [1, 2]. Although it has been historically neglected, the Coronavirus Disease 19 (COVID-19) pandemic has worsened the situation, especially for Neglected Tropical Diseases (NTDs), which mainly affect impoverished and marginalized populations. Awareness and advocacy campaigns were discontinued, access and quality of healthcare were limited or inconsistent, control and surveillance programs were disrupted, and research and development were paused or slowed down [3, 4].

2. Epidemiology

2.1 Background

Chagas disease is one of twenty NTDs that have been recognized by the World Health Organization. They are common in tropical and subtropical regions, where adequate climate conditions enable their transmission. NTDs are intimately linked to communities in which disparities and inequities prevail. When acquired, they cause disabilities and suffering, but they also lead to discrimination and stigmatization, excluding people from their role in their societies. In this context, Chagas disease is the most common NTD in Latin America, but it is increasingly raising worldwide [2, 3].

2.2 Endemic countries

Chagas disease is endemic to Latin America (Central and South America), where it is estimated that there are about 6 million infected people, but almost 65 million are at risk of becoming infected. Endemic countries include Argentina, Belize, Bolivarian Republic of Venezuela, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Guiana, French Guiana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Plurinational State of Bolivia, Surinam, and Uruguay. Each year approximately 30,000 new cases and around 12,000 deaths are reported. Besides, its annual burden is estimated in 6.2 billion dollars for endemic countries [5, 6].

2.3 Non-endemic countries

Chagas disease has become a global health issue, as it has spread to non-endemic countries, where it is estimated that there are around 400,000 infected people, but at least 32 million immigrants from endemic countries should be screened. It has been reported in North America (Canada and the United States of America), Asia (Japan), Europe (Austria, Belgium, Croatia, Denmark, France, Luxembourg, Italy, Netherlands, Norway, Portugal, Romania, Sweden, Spain, Switzerland, and the United Kingdom), and Oceania (Australia and New Zealand). Climate change and migration are the main reasons for its spread. Furthermore, its annual burden is estimated in 1 billion dollars for non-endemic countries [6, 7].

3. Etiology and transmission

3.1 Taxonomy

Chagas disease is caused by a parasite that belongs to the class Kinetoplastea, order Trypanosomatida, family Trypanosomatidae, genus Trypanosoma, and species cruzi [8].

3.2 Lineages

T. cruzi is an intracellular obligate parasite with genetic heterogeneity. It has been classified into six discrete typing units (DTUs) or lineages (TcI to TcVI). Each of them has its distribution, ecology, and pathogenicity [9].

3.3 Vector-borne transmission

It is primarily a vector-borne disease. When an infected triatomine has a blood meal from a non-infected host, it defecates and releases metacyclic trypomastigotes. Metacyclic trypomastigotes enter through the bite site to reach phagocytic and non-phagocytic cells in the subcutaneous tissues, where they bind to a parasitophorous vacuole, differentiate into amastigotes, escape the parasitophorous vacuole, and replicate in the cytoplasm by binary fission. Then, amastigotes differentiate into bloodstream trypomastigotes, induce lysis of the cell membrane, and travel through the blood vessels to infect new cells. When a non-infected triatomine has a blood meal from an infected host, it ingests blood trypomastigotes. Blood trypomastigotes migrate through the gastrointestinal tract to reach the stomach and midgut, where they differentiate into epimastigotes and replicate by binary fission. Then, epimastigotes migrate towards the hindgut, attach to peri microvillar membranes, differentiate into metacyclic trypomastigotes, travel to the rectum, and adhere to the epithelium to be ready to infect new non-infected hosts (Figure 1) [10, 11]. Other morphological forms have been described elsewhere [11].

Figure 1.

Trypanosoma cruzi life cycle. Created with BioRender.com.

3.4 Non-vector-borne transmission

Chagas disease can also be acquired by blood transfusion or organ transplantation from an infected donor to a non-infected receptor, during pregnancy or childbirth from an infected mother to a non-infected fetus or newborn (congenital or vertical transmission), by consuming beverages or food contaminated with the feces of an infected triatomine (oral transmission), or by having contact with contaminated blood or tissue samples at the laboratory or hospital (accidental or occupational transmission) [1, 12].

4. Risk factors

Lack of awareness, living or visiting endemic countries, being exposed to triatomines and their reservoirs, and poor-quality housing are the main risks for acquiring the disease [2, 13].

5. Clinical manifestations

5.1 Incubation

Chagas disease has an incubation period that ranges from 7 to 14 days if the infection was acquired by vector-borne transmission and from 3 to 120 days if it was acquired by non-vector-borne transmission (3 to 22 days for oral transmission and 90 to 120 days for blood transfusion and organ transplantation). Then, the disease develops into stages: [14, 15].

5.2 Acute stage

95% of the infected individuals remain without clinical manifestations. The other 5% can develop fever, fatigue, weakness, myalgia, arthralgia, headache, nausea, vomiting, abdominal pain, hepatomegaly, and splenomegaly. Seldomly, a painful mobile nodule can arise at the inoculation site when the parasite load is high (chagoma), and a unilateral painless palpebral swelling can be seen when the parasite enters through the mucous membrane of the eye (Romaña’s sign). Rarely, meningoencephalitis, myocarditis, or pericardial effusion can develop, especially if there is immunosuppression or when the infection was acquired by oral transmission. The duration of the acute stage ranges from 120 to 240 days [14, 15].

5.3 Chronic stage

70 to 90% of the infected individuals establish in the chronic indeterminate stage, in which they have a positive serology for T. cruzi, but remain without clinical manifestations. The other 10 to 30% can develop the chronic determinate stage, in which they have a positive serology for T. cruzi and experience the clinical manifestations of the cardiac and digestive forms: [14, 15].

5.3.1 Cardiac form

It causes damage to the cardiac conduction system and generates a classical dilated cardiomyopathy that leads to arrhythmias, heart failure, and pulmonary thromboembolism. Infected individuals with arrythmias can experience anxiety, dizziness, syncope, dyspnea, bradycardia, tachycardia, palpitations, and chest pain. Infected individuals with heart failure can experience anxiety, fatigue, weakness, hyporexia, anorexia, nausea, vomiting, dyspnea, paroxysmal nocturnal dyspnea, orthopnea, bendopnea, chronic and persistent cough, bradycardia, tachycardia, palpitations, chest pain, and edema. Infected individuals with pulmonary thromboembolism can experience anxiety, confusion, dizziness, syncope, dyspnea, tachypnea, hemoptysis, and chest pain that worsens when breathing or coughing. Cardiac sudden death occurs in 50 to 60% of the cases [14, 15].

5.3.2 Digestive form

It causes damage to the enteric nervous system and generates dilatation and dysfunction of the smooth muscle that leads to megaesophagus and megacolon. Infected individuals with megaesophagus can experience weight loss, hyporexia, anorexia, nausea, vomiting, odynophagia, dysphagia, achalasia, pyrosis, regurgitation, bronchoaspiration, and chronic and persistent cough. Infected individuals with megacolon can experience weight loss, hyporexia, anorexia, nausea, vomiting, abdominal pain, abdominal distention, constipation, fecaloma, volvulus, and bowel ischemia [14, 15].

5.3.3 Reactivation

It occurs when infected individuals that are at the chronic stage become immunocompromised due to immunodepression or immunosuppression, allowing the parasite’s reactivation and replication. It can cause life-threatening meningoencephalitis, myocarditis, or panniculitis [14, 15].

6. Diagnosis

6.1 Background

Chagas disease must be suspected when people that live or visit endemic countries experience the above-mentioned clinical manifestations, but it should be confirmed with laboratory tests, which depend upon the stage of the disease: [16].

6.2 Acute stage

Direct examination of the blood trypomastigotes in a fresh or stained blood smear with conventional microscopy is the gold standard for diagnosis. Concentration techniques can be employed if the level of parasitemia is low, and multiple samples should be obtained to improve the chances of detection. It is a cheap and simple test that can be performed in adequately equipped laboratories with highly trained technicians. Other tests that can be employed for parasitological observation are hemoculture, in which a blood sample is collected, cultured, and incubated, and xenodiagnoses, in which a blood sample is collected and given to a non-infected triatomine. Both allow the exponential growth of the parasites and have an improved sensitivity, but consume plenty of time. Hence, they have been displaced and disused. Detection of the genetic material of T. cruzi in a blood sample can be done with a Polymerase Chain Reaction (PCR), in which the DNA is extracted, amplified, and detected. It can be employed if the level of parasitemia is low. Its results are highly sensitive and specific and can be performed in adequately equipped laboratories with highly skilled technicians. However, it is expensive. Therefore, although it is a desired laboratory study, it is not available in remote settings that lack resources [16, 17].

6.3 Chronic stage

Detection of the antibodies against T. cruzi in a blood sample with an Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Hemagglutination Assay (IHA), Indirect Immunofluorescence Assay (IFA), or Western Blot (WB) is the gold standard for diagnosis. However, as they are moderately sensitive, the Pan American Health Organization (PAHO) and the WHO have established that at least two different serological tests with different principles must be employed to obtain reliable results. If both are positive, then it is a conclusive diagnosis, but if one of them is negative and the other is positive, then a third serological test should be used. All require adequately equipped laboratories with highly trained technicians, but ELISA is the most cost-effective and easy to perform. IFA is more sensitive and specific than IHA, and WB is mainly used for research [16, 17].

6.4 Complimentary examination

Cabinet and imaging studies must be employed to assess cardiac and digestive involvement: [14].

6.4.1 Cardiovascular tests

Chest X-rays, electrocardiography, and echocardiography should be performed, according to the available resources and the index of suspicion if the infected individual experiences cardiac clinical manifestations. Cardiomegaly and pulmonary congestion can be detected in chest X-rays. Conduction disorders (first, second, or third atrioventricular block, complete and incomplete right bundle branch block plus left anterior fascicular block, and isolated left anterior fascicular block), bradyarrhythmia’s (sinus bradycardia), and tachyarrhythmias (atrial fibrillation, frequent and isolated polymorphic premature ventricular contractions, and non-sustained ventricular tachycardia) can be identified in the electrocardiogram. Abnormalities in the cardiac valves (mitral and tricuspid regurgitation), in the motion of the segmental wall (hypokinesia, dyskinesia, or akinesia in the apical and inferolateral walls), in the function of the ventricles (left and right ventricular dilation with systolic and diastolic dysfunction), apical aneurysms and mural thrombosis can be observed in the echocardiogram [14, 15].

6.4.2 Gastrointestinal tests

Barium esophagram, upper endoscopy, barium cologram, and lower endoscopy should be performed, according to the available resources and the index of suspicion if the infected individual experiences digestive clinical manifestations. Megaesophagus (dilation of the esophagus, impaired peristalsis, and esophageal stasis) can be seen in the barium esophagram and the upper endoscopy. Megacolon (dilation of the colon, impaired peristalsis, fecaloma, and volvulus) can be spotted in the barium enema and lower endoscopy [14, 18].

7. Treatment

7.1 Trypanocides

Chagas disease can be treated with benznidazole or nifurtimox. Both have activity against T. cruzi, but their efficacy depends upon the stage of the disease. Therefore, the PAHO and the WHO encourage their use for infected individuals who are at the acute stage or at the chronic indeterminate stage, in which the benefits of giving them outweigh the risks of prescribing them, and discourage their use for infected individuals who are at the chronic determinate stage, in which specific organ damage has already developed. Both have their contraindications, dosage regimen, and adverse effects: [17, 19].

7.1.1 Benznidazole

It is absolutely contraindicated during pregnancy and in case of severe hepatic failure. It is relatively contraindicated during breastfeeding and in case of severe kidney failure. Its dosage regimen for children is 5 to 10 milligrams per kilogram per day, administered orally, and divided into 2 doses for 60 days. Its dosage regimen for adults is 5 milligrams per kilogram per day, administered orally, and divided into 2 doses for 60 days. It can cause allergic dermatitis, weight loss, anorexia, nausea, vomiting, abdominal discomfort, dose-dependent peripheral neuropathy, and leukopenia. The latter are enough reasons to stop treatment. Other adverse effects have been reported [19, 20].

7.1.2 Nifurtimox

It is absolutely contraindicated during pregnancy and in case of severe hepatic failure. It is relatively contraindicated during breastfeeding and in case of severe mental or psychiatric disorders, seizures, or kidney failure. Its dosage regimen for children is 10 to 15 milligrams per kilogram per day, administered orally, and divided into 3 doses for 60 days. Its dosage regimen for adults is 8 to 10 milligrams per kilogram per day, administered orally, and divided into 3 doses for 60 days. It can cause confusion, disorientation, insomnia, dizziness, headache, weight loss, anorexia, nausea, vomiting, abdominal discomfort, dose-dependent peripheral neuropathy or polyneuropathy, and leukopenia. The latter are enough reasons to stop treatment. Other adverse effects have been reported [19, 20].

Alternative dosage regimens can be consulted elsewhere, but their prescription should be aligned with country guidelines and policies. Biweekly reassessment of the complete blood count and hepatic and kidney tests is recommended [21, 22].

7.1.3 Emerging therapies

Antiarrhythmics (amiodarone/dronedarone), ergosterol inhibitors (albaconazole, fosravuconazole/ravuconazole, itraconazole, posaconazole, and voriconazole), nitroimidazoles (fexinidazole), purine synthesis inhibitors (allopurinol), and supplements (selenium) are being studied as emerging therapies [23].

7.2 Complimentary management

Once the cardiac and digestive forms have developed, they must be managed and treated: [14, 23].

7.2.1 Cardiovascular treatment

Infected individuals with the cardiac form of the disease must be encouraged to modify their diet and lifestyle. Pharmacological treatment (anticoagulants, antiarrhythmics, antihypertensives, β-blockers, cardiac glycosides, diuretics, and hypolipemiants) should be prescribed to decrease the cardiovascular risk, and surgical procedures (pacemaker implantation, implantable cardiac defibrillators insertion, cardiac bridging, and heart transplantation) may be required to control or prevent complications [23, 24].

7.2.2 Gastrointestinal treatment

Infected individuals with the digestive form of the disease must be encouraged to modify their diet and lifestyle. Non-pharmacological treatment (pneumatic dilatation for megaesophagus and colon enemas for megacolon) and pharmacological treatment (botulinum toxin and sphincter relaxants for megaesophagus, and laxatives for megacolon) should be prescribed to decrease the duration and intensity of the clinical manifestations, and surgical procedures (cardiomyotomy and esophagectomy for megaesophagus, and anterior rectosigmoidoscopy, hemicolectomy, or total colectomy for megacolon) may be required to control or prevent complications [23, 25].

8. Prevention

8.1 Vector-borne transmission

Improving housing conditions, installing bed nets, and spraying insecticides indoors and outdoors can reduce the risk of acquiring Chagas disease through vector-borne transmission [5, 26].

8.2 Non-vector-borne transmission

Screening blood and organ donors and receptors can reduce the risk of acquiring Chagas disease through blood transfusions and organ transplantations. Screening women of childbearing age or who are pregnant can reduce the risk of acquiring it through congenital or vertical transmission. Strengthening hygienic measures while preparing and consuming beverages and food can reduce the risk of acquiring Chagas disease through oral transmission. Using standard precautions while handling and manipulating biological specimens can reduce the risk of acquiring it through accidental or occupational transmission [5, 26].

8.3 Prophylactic and therapeutic vaccines

Stopping Chagas disease transmission or progression can be done through vaccination. Primary prevention could be done with prophylactic vaccines, meanwhile, secondary prevention could be done with therapeutic vaccines. However, although several formulations and platforms have been tested in pre-clinical stages with encouraging and promising results, none is currently in clinical stages. The diversity of the parasite and the immunogenicity of the host are among the challenges that need to tackled. Investment is required to keep moving forward [27, 28].

9. Chagas disease and COVID-19

9.1 COVID-19

On December 31st, 2019, the WHO collected a media statement from the Wuhan Municipal Health Commission, in which they reported a cluster of atypical pneumonia cases in Wuhan, People’s Republic of China. On January 9th, 2020, Chinese investigators determined that the cluster of atypical pneumonia cases was caused by a novel coronavirus. On January 13th, 2020, the Ministry of Public Health of Thailand reported the first case outside of the People’s Republic of China and on January 21st, 2020, the United States of America reported the first case in the American continent. The disease had quickly spread. On January 30th, 2020, the WHO declared that the novel coronavirus outbreak was a “Public Health Emergency of International Concern”. On February 11th, 2020, the International Committee for Taxonomy of Virus named the virus “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2), and the WHO named the disease “Coronavirus Disease 2019” (COVID-19). On March 11th, 2020, the WHO declared that COVID-19 could be characterized as a “pandemic” [29].

9.2 COVID-19 and NTDs

The COVID-19 pandemic has had a great impact on the economic and social spheres, disrupting essential health services and specific health programs worldwide. According to the WHO, 48 countries experienced disruptions in their NTDs programs, especially in low-and-middle-income countries in the African, American, Eastern Mediterranean, and South-Eastern Asian regions. Disruptions affected the community-based interventions (active case finding, awareness and education, hygiene and sanitation, mass treatment and preventive chemotherapy, psychosocial and rehabilitation services, vector control, and veterinary health), delayed health facility-based services (diagnosis and treatment, morbidity management, and disability prevention), interrupted the evaluation and monitorization of health programs (population surveys and routine surveillance), paused or slowed down the development, shipment, and transportation of consumables and medicines, and needed the reallocation of economic and human resources to support the COVID-19 response [30]. These increased the burden of most NTDs and jeopardized the fulfillment of the global targets for 2030 [31].

9.3 COVID-19 and Chagas disease

COVID-19 is a viral disease caused by the SARS-CoV-2 that has had a catastrophic global effect, [30] meanwhile Chagas disease is a parasitic disease caused by T. cruzi that has had a great impact in Latin America and that has become a global health issue [6]. Both are challenging and complex diseases with differences and similarities, which will be discussed from a practical perspective in this section of the book chapter:

9.3.1 Epidemiology

COVID-19 has been confirmed in about 768 million people worldwide, from which almost 200 million live in America, [32] where at least 6 million people have Chagas disease, and from which close to 1 million have developed the chronic determinate stage in its cardiac form. COVID-19 had a greater impact on this population, especially when essential health services were disrupted, and health systems were overloaded [33].

9.3.2 Etiology and transmission

COVID-19 is caused by a virus that belongs to the class Pisoniviricetes, order Nidovirales, family Coronaviridae, genus Betacoronavirus, and species Severe acute respiratory syndrome-related coronavirus [8]. SARS-CoV-2 is a positive-stranded RNA virus that has been classified into clades, lineages, and variants, depending on the classification system. Each of them has their distribution and pathogenicity [34]. SARS-CoV-2 is primarily transmitted through aerosols and droplets exhaled by an infected individual, but contact transmission has also been reported [35]. COVID-19 and Chagas disease do not have common features in etiology and transmission, but SARS-CoV-2 has demonstrated that it evolves quickly and that it can be highly transmissive. This has been quite challenging for maintaining community-based interventions and health facility-based services that require face-to-face interactions during the pandemic. Chagas disease interventions and services were displaced [33].

9.3.3 Risk factors

Lack of awareness, living or visiting crowded or urban areas, being exposed to an infected individual, and having chronic diseases are the main risk factors for acquiring COVID-19 [36]. Besides the lack of awareness, COVID-19 and Chagas disease do not have common risk factors for acquiring them, but advanced age, cancer, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, heart disease, and smoking are the main risk factors for developing severe COVID-19. Coinfected individuals do have a higher risk of developing severe COVID-19 because of aging and heart disease. On the other hand, the cytokine storm caused by COVID-19 can accelerate the progression of the chronic determinate stage, and immunodepression or immunosuppression are the main risk factors for having a reactivation of the disease. Coinfected individuals do have higher morbidity and mortality and have a higher risk of having a reactivation of the disease because of the overactivation of the immune system caused by COVID-19 and the administration of immunomodulators and steroids for its control [37].

9.3.4 Clinical manifestations

SARS-CoV-2 has an incubation period that ranges from 2 to 14 days. Infected individuals with COVID-19 can remain without clinical manifestations or can develop fever, anxiety, confusion, fatigue, weakness, dizziness, myalgia, arthralgia, headache, anosmia, dysosmia, rhinorrhea, dyspnea, cough, hemoptysis palpitations, chest pain, hyporexia, anorexia, nausea, vomiting, ageusia, dysgeusia, odynophagia, abdominal pain, diarrhea, and dermatosis [38]. T. cruzi has an incubation period that ranges from 7 to 14 days. Infected individuals with Chagas disease can remain without clinical manifestations or can develop fever, fatigue, weakness, myalgia, arthralgia, headache, nausea, vomiting, and abdominal pain during the acute stage of the disease; and, anxiety, confusion, fatigue, weakness, dizziness, dyspnea, cough, hemoptysis, palpitations, and chest pain, during the chronic stage of the disease in its cardiac form, or hyporexia, anorexia, nausea, vomiting, odynophagia, abdominal pain, and diarrhea during the chronic stage of the disease in its digestive form [14, 15]. COVID-19 and Chagas disease have a broad clinical spectrum that can overlap in some instances or stages. Coinfected individuals do develop arrhythmias, heart failure, and pulmonary thromboembolism with an increased frequency and severity. The background and clinical context are essential for intervening on time [33, 37].

9.3.5 Diagnosis

COVID-19 must be suspected when people that have been exposed to an infected individual experience the above-mentioned clinical manifestations, but it should be confirmed with laboratory tests. Detection of the antigens or the genetic material of SARS-CoV-2 in a nasal or nasopharyngeal swab can be done with an antigen test or with a PCR, respectively. Antigen tests are cheaper and quicker than PCR, but also are less sensitive and need to be repeated several times. Therefore, PCR is the gold standard for diagnosis. Detection of antibodies against SARS-CoV-2 in a blood sample can be done with serologic tests, but they are only useful for surveillance. In a couple of years, about 1000 brands of COVID-19 diagnostic tests became available for commercial use to test inside and outside hospital settings. Exposed individuals could go almost anywhere for testing [39]. In contrast, screening and testing for Chagas disease and other parasitic and tropical diseases were paused or slowed down, even in countries with plenty of resources. Exposed individuals had limited testing locations, and many did not go because they feared COVID-19 transmission. This situation has evidentiated the need for a better diagnosis framework and an expanded infrastructure to improve access and opportunity [40]. Furthermore, a complimentary examination is required for infected individuals who develop cardiac or digestive manifestations, but hospitals were overcrowded, and many patients were lost during their follow-up [37].

9.3.6 Treatment

COVID-19 can be treated with anti-inflammatories, antivirals, corticosteroids, interleukin-6 receptor blockers, and Janus kinase inhibitors, depending upon the severity of the disease [41]. Chagas disease can be treated with benznidazole or nifurtimox during the acute and chronic indeterminate stage [19, 20], and with anticoagulants, antiarrhythmics, antihypertensives, β-blockers, cardiac glycosides, diuretics, and hypolipemiants during the chronic determinate stage in its cardiac form [23, 24], or with botulinum toxin, sphincter relaxants, and laxatives during the chronic determinate stage in its digestive form [23, 25]. Coinfected individuals do need to treat both diseases, but doing it simultaneously can cause drug interactions and may increase the frequency and severity of adverse effects. Coinfected individuals must receive treatment for COVID-19 and Chagas disease during the acute stage or when there is reactivation, but should be delayed or postponed during the chronic indeterminate stage until COVID-19 is resolved. Drugs for the chronic determinate stage in its cardiac form should be screened and switched for controlling the disease and reducing the risk of complications, especially when azithromycin, chloroquine, hydroxychloroquine, and ivermectin have been administered for COVID-19 [33, 41], despite of the current evidence and recommendations [42].

9.3.7 Prevention

Avoiding crowds, keeping physical space, using face masks, and vaccinating can reduce the risk of acquiring COVID-19 through aerosols and droplets. Washing hands with soap and water can reduce the risk of acquiring COVID-19 through contact transmission. COVID-19 and Chagas disease do not have common features in prevention, but COVID-19 has demonstrated that adequate ventilation can reduce the risk of acquiring it, meanwhile, Chagas disease has demonstrated that adequate housing can reduce the risk of acquiring it. Infrastructure is a common ground for both. Still, an effective and safe vaccine for Chagas disease is needed [41, 42].

10. Conclusions

Chagas disease has been historically neglected, but the efforts that have been made during the last decades have decreased its incidence in Latin America and have alerted the rest of the world about the mechanisms of its spread. However, the emergence of COVID-19 required the implementation of radical and unprecedented measures, including the reallocation of economic and human resources to control and mitigate the effects of an evolving and highly transmissible virus. Chagas disease became even more neglected. Exposed individuals could not be diagnosed and infected individuals could not be followed-up. Furthermore, coinfected individuals appeared in the scope. Chagas disease increases the risk of developing severe COVID-19, and COVID-19 enhances the progression or reactivation of Chagas disease. Up to date, we do not know much about its impact and pathophysiology. Research is required to better understand the consequences of its interaction.

The COVID-19 pandemic is far from over, but as we advance into the next stage of transition, we must acknowledge that what has been done during the last years should be applied to control, eliminate, and eradicate Chagas disease and other NTDs. Health professionals and policymakers must play their role and raise their voices to leave no one behind, especially those who are placed at the economic and social margins. We must develop a better framework to increase our infrastructure and overcome the challenges of our century in an improved and sustainable way.