Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 116 | 2021

Emerging and reemerging forms of Trypanosoma cruzi transmission

Maria Aparecida Shikanai Yasuda1,2,3/+

1Universidade de São Paulo, Faculdade de Medicina, Departamento de Moléstias Infecciosas e Parasitárias, São Paulo, SP, Brasil
2Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina, Laboratório de Imunologia, São Paulo, SP, Brasil
3WHO Technical Group IVb on Prevention and Control of Transmission and Case Management of Trypanosoma cruzi Infections, WHO, Geneva, Switzerland

DOI: 10.1590/0074-02760210033
840 views 369 downloads

This review aims to update and discuss the main challenges in controlling emergent and reemergent forms of Trypanosoma cruzi transmission through organ transplantation, blood products and vertical transmission in endemic and non-endemic areas as well as emergent forms of transmission in endemic countries through contaminated food, currently representing the major cause of acute illness in several countries. As a neglected tropical disease potentially controllable with a major impact on morbimortality and socioeconomic aspects, Chagas disease (CD) was approved at the WHO global plan to interrupt four transmission routes by 2030 (vector/blood transfusion/organ transplant/congenital). Implementation of universal or target screening for CD are highly recommended in blood banks of non-endemic regions; in organ transplants donors in endemic/non-endemic areas as well as in women at risk from endemic areas (reproductive age women/pregnant women-respective babies). Moreover, main challenges for surveillance are the application of molecular methods for identification of infected babies, donor transmitted infection and of live parasites in the food. In addition, the systematic recording of acute/non-acute cases and transmission sources is crucial to establish databases for control and surveillance purposes. Remarkably, antiparasitic treatment of infected reproductive age women and infected babies is essential for the elimination of congenital CD by 2030.

Chagas disease (CD) is an active disease in urban centres of endemic and non-endemic areas in several continents due to immigration of infected population to the urban centres of endemic regions and non-endemic areas (Europe and Asia, Australia, US and Canada, Japan, Australia,(1) affecting according to estimates in 2006, around 6-7 million persons in Mexico and Central and South America and causing 12,500 deaths per year and 41,200 new cases annually.(2)

Although vector and blood transmitted disease have been reported under control in almost all endemic areas, the globalisation of the disease in urban centres of all continents made possible the reemergence of blood and/or organs transplant and maternofetal transmission in the US,(3, 4, 5, 6) Europe, Australia, Asia,(1, 7, 8, 9, 10) the latter two still as challenges in endemic regions.(11, 12) Additionally, regarding vector control, autochthonous chronic CD cases have been reported in previously non registered endemic areas such as part of Amazonia and non-endemic regions US.(6, 13, 14)

Trypanosoma cruzi infection prevalence in immigrants was variable from 1-26%, depending on the country and nationality.(1, 7) Approximately 300,000 individuals are estimated to be infected with T. cruzi in the US(15, 16) and around 97,556 in Europe.(17) Different initiatives have been implemented in several countries of non-endemicity aiming to control blood transfusion and organs transplant transmission. However, other factors, as the physician unawareness of vertical transmission and congenital CD (cCD) reactivation are unfavorable for their control and prevention.(18, 19)

Of note, acute CD (ACD) emerged in unpredictable circumstances in the Brazilian Amazon region and other Latin American areas, where the domiciliary triatomine cycle has been under control, transmitted by contaminated food as a result of serious disturbances in the wild cycle of vectors and reservoirs of T. cruzi.(20, 21)

As one of the neglected tropical disease potentially controllable with a major impact on morbimortality and socioeconomic aspects, CD has been included in the World Health Organization (WHO) global plan to interrupt four transmission routes by 2030 (vectorial, blood transfusion, organ transplant and maternofetal).(22) The implementation of the World Chagas Day during the 72nd World Health Assembly (Geneva/Switzerland, 2019) provides not only more visibility but also contributes to establish comprehensive integral health care with diagnosis, treatment and quality of life for millions of infected patients.(23)

The aim of this work is to discuss the main challenges in the control of emerging and reemerging transmission routes through blood transfusion, organ transplantation, maternofetal and contaminated food.


Transmission by blood or blood products


Tables I(24, 25) and II(8, 17, 26, 27) show the number of infected people as well as prevalence estimates of vectorial and congenital transmission and of blood bank candidates in endemic and non-endemic countries.

In endemic countries, universal screening should be implemented in every blood bank candidate by applying a reliable and reproducible high performance serological test with about 99-100%, followed by confirmatory test with at least 95% of specificity.(28)

It is possible to observe that in some regions of non-endemicity, the prevalence is similar or higher than those of endemic areas, perhaps by concentration of immigrants (Table II).(8, 17, 26) Additionally, high underdiagnosis indexes between 89% and 99% of expected cases are estimated in Europe(26) and risk of blood transfusion transmission has been recognised in several countries (US, Spain, Canada, Belgium),(8, 9, 29) leading to the implementation of different policies in some regions of non-endemicity, as observed in Table III.







In the US blood banks, screening is universal and in Canada, screening targets people at risk for CD. Seven countries in Europe, France, Italy, Portugal, Spain, Sweden, Switzerland, and the United Kingdom, where the majority of Latin American immigrants live currently, have implemented or are recently changing their recommendation for screening at blood donor with risk factors for T. cruzi infection.(30) Target screening does not cover donors born to mothers, who lived in endemic areas or donors that lived less than five years in endemic areas,(31) neither donors that travelled during three months to vector transmission area, as registered in infected people in the US.(31)

In parallel, the deferral of donation for six months after travelling to endemic regions, applicable for some diseases is not useful for CD, since chronic disease occurs after the infection without symptoms in the majority of cases, so the disease could be not easily suspected in blood/organ donors’ candidates. Moreover, even with recommendation for screening people at risk guided by European guidelines, it is not known whether these measures have been implemented in some countries.(30)

In addition, countries in the Western Pacific region do not apply any health policy to systematically identify individuals at risk for T. cruzi infection. In Japan, deferral of at risk donor and in China no policies have been described. In Australia, screening is carried out using a questionnaire to identify at-risk donors through clinical and epidemiological data and exclusion of those affected.(27)




Comments - Considering the current situation in regions of endemicity and non-endemicity it is strongly recommended: (a) universal screening in regions of endemicity or non-endemicity with a high concentration of infected immigrants through a highly sensitivity serological method in blood banks followed by confirmation by a high specific method, according to the criteria recommended by Pan American Health Organization (PAHO);(28) (b) in regions of non-endemicity, with a low prevalence of infected immigrants, screening target at risk people, including old or recent infection, followed by laboratorial confirmation (vectorial infection during the life or during travel to endemic areas, blood/blood products/organ transplant, congenital disease); (c) blood products from these donors should not be used except after exclusion of T. cruzi infection. Epidemiological data should consider the region where the donor lived, the presence of the vector in the house or in the neighborhood and/or relatives and mother with CD,(32) even in the absence of signals and symptoms, characteristics of the chronic indeterminate or early cardiac phase of CD.


Solid organ transplantation (SOT) and allogeneic haematopoietic stem cells transplantation (Allo-SCT) transmission


As a route of CD transmission known in endemic regions since the 80s,(33) SOT emerged in urban centres of endemic and non-endemic regions with high impact due to immunodepressed receptor evolving with serious illness.(4) Increasing number of solid transplants have been reported due to improved immunosuppressive management as well physician’s awareness and knowledge since the first publications.(33) Although less frequently, Allo-SCT has also been described in endemic areas.(34)

In contrast to retrospective studies of donor derived infections where the infected recipients were suspected lately, when clinical symptoms appear and the prognosis is worse, active monitoring by parasitological and molecular methods allows the detection of asymptomatic infections, introduction of early treatment and better prognosis.(11, 35) The risk of potentially fatal outcomes in immunosuppressed recipients, specially from heart and kidney-pancreas transplants under aggressive therapy for graft rejection, requires prevention strategies starting with donor screening.

Universal screening is highly recommended in endemic areas and/or non-endemic regions with Latin America immigrants’ prevalence (Table III).(30) In the US, only 19% of organ procurement organisation performed universal or targeted donor screening for T. cruzi infection by 2009.(36) Target screening has been recommended when the potential donor or recipient has been in risk areas for acquiring of T. cruzi infection during at least three months(29) or was born in endemic areas (Table I).

Guidelines for organs transplant for prevention and management of CD were recorded in Argentina,(37) Europe (including South American experts)(38) and US(39) guiding for serological screening but not always recommending high (99-100%) sensitivity tests.(28) Usually, one screening test is employed according to the choice of responsible institution, followed by one confirmatory test for CD diagnosis. In Brazil, although regulated by National Transplant Agency, the main challenge is to consider the use of highly sensitive and specific test as mandatory regardless of the competitive cost at each centre. In fact, a few cases have been reported of suspected donor derived infection in a liver and in a renal transplant recipient associated with a single negative serological test in the donor.(40, 41) Moreover, considering the safety and effectiveness of screening in this first phase, we recommend the employment of two highly sensitive tests as strategy for donor screening, followed by a high specific confirmatory test, as recommended by PAHO, 2019.(28)

Donor status concerning T. cruzi infection should be known before the transplant. In case of confirmed infection, the next step is to decide whether the donor should be treated before the procedure (Figure). In this situation, 60 days and, at least 30 days is the minimum period recommended instead of a shorter period. In case of emergency or retrospective knowledge of the donor’s infection, CD monitoring and /or prophylaxis of non-immune recipient is recommended.




Regardless of any decision, careful monitoring of recipient parasitaemia is mandatory, starting before the transplant and considering the patient’s immune status after the procedure.

It is essential in the follow-up:

A - To search for ACD during immunosuppression (and/or reactivation) in the initial months post-transplant and/or under aggressive immunosuppressive therapy for graft rejection or under signs and symptoms of suspected ACD or reactivation:

(i) Methods? Direct parasitological tests in peripheral blood or other secretions, preferably through microscopy concentration methods (microhematocrit, Strout, buffy coat) more sensitive than stained slides or fresh blood are recommended. Qualitative polymerase chain reaction (PCR) is highly sensitive and recommended for diagnosis of the primary infection since the initial days post-transplant up to 12 months, although not advisable to distinguish CD from reactivation, for which quantitative PCR is indicated. Indirect parasitological methods complement CD diagnosis but they are time consuming and less safe than PCR.

(ii) When? Day 0 to 12 months after the transplant, according to the method:

Direct microscopy - After the transplant: once a week during three months and twice a week any time under symptoms/signs under suspicion of reactivation or during aggressive immunosuppressive therapy for graft during the follow up period. Once a week from 4-9 months, when the majority of acute cases where diagnosed.

PCR - 0, once a week in the first month, twice a month int he 2nd and third month and once a month from 4-12 months.

Other indirect enrichment parasitological methods (blood culture, xenodiagnosis): Day 0, 15 days, one month after the transplant up to 6-12 months. Repeat each 3 months: 3, 6, 9 and 12 months after the transplant.

Serology - 0, 3 weeks, 1,3,6, 9, 12 months. This method is less sensitive in transplanted patients than in immunocompetent patients, since T dependent antibodies production is impaired as seen by negative seroconversion in 43.4% of infected renal recipients in Argentina.(11)

(iii) How to interpretate immediate positive and negative results post-treatment? Persistent parasite identification by microscope examination raises the possibility of therapeutic failure, recommending the change of the antiparasitic drug. On the other hand, negative results should be carefully interpretated since these drugs temporarily inhibit the parasite and parasitaemia could return later in the follow-up. After 3-6 months of treatment, PCR and other parasitological methods are more reliable for parasitaemia monitoring than direct microscopy, excluding recurrence episodes.

B - To search also for chronic Chagas disease, asymptomatic or symptomatic, acquired by transplant in the late post-transplant phase, from 6 months post-transplant:

(i) Methods? PCR and serology are recommended. The latter is less sensitive in immunosuppressed patients as cited before(11) and should be repeated many times if negative and never employed as unique method. If possible, parasitological enrichment methods (blood culture, xenodiagnosis) are useful for the identification of phenotypic and genotypic characteristics of the parasite.

(ii) When? Preferably, collect samples before the transplant. In the absence of antiparasitic treatment: repeat 6, 9, 12, 18, 24 and 36 months after the transplant. During antiparasitic treatment and even a few periods later, negative results for indirect parasitology/serology/PCR do not represent therapeutic success, as cited before and this negative result should remain for a long period to indicate such effect.

In conclusion for diagnosis of ACD, direct concentration parasitological methods (Strout, buffy coat, microhematocrit) together PCR are recommended for the entire period of immunosuppression, mainly in the first 9-12 months after the transplant. In case of chronic CD, this follow-up should continue at least 36 months by PCR and serology preferably, and, if accessible, by parasitological enrichment method (haemoculture). After antiparasitic treatment, follow-up up to 12-36 months after the end of therapy.

Table IV depicts case reports and transmission rates from donors to receptors associated with prophylaxis (0%) with no accurate cure control and without prophylaxis (15.5%) in Kidney transplant.(11, 33, 35, 42, 43, 44, 45, 46, 47, 48) In liver transplantation, 25.9% and 14.3%, respectively with or without prophylaxis,(35, 47, 49, 50, 51, 52, 53, 54) again accurate methods for cure control are sometimes incompletely employed. As indicated in Table IV, no accurate control means that serology is not sufficient as the unique method for therapeutic control in immunosuppressed recipients. Additionally, indirect parasitological/molecular methods are complementary for chronic CD in the late and/or short follow-up period. The same table depicts transmission rates in a few cases of heart, lung transplant, stem cell and kidney-pancreas transplantation with or without prophylaxis.(35, 36, 48)

Table IV shows only two deaths by CD(35) in highly immunosuppressed heart and kidney recipients with delayed ACD diagnosis by unknown donor infection. An additional question, is the use of infected donors advocated by some authors in liver and kidney(48, 50, 53) and even stem cell transplants since antiparasitic donor treatment is ensured, followed by recipient’s prophylaxis and careful parasitaemia control. As discussed, risk of chronic CD is not always excluded. This circumstance represents an exception, reserved only for individual emergency situation and/or joint decision of health committees of professionals and patients’ communities waiting for transplants where the lack of organs and long queues are associated with significant mortality.




Comments - Universal or target screening for organs transplant donor should be mandatory, and at least two high performance serological tests are recommended. Serological, molecular and parasitological methods should be employed repeatedly, according to different stages of the transplant, and the recipient’s immunological “status”. Monitoring with quantitative PCR (qPCR) should be implemented to support an adequate parasitaemia control with or without recipient prophylaxis and/or donor treatment. Evidences of the benefit of prophylaxis need to be confirmed in larger samples carefully monitored for longer periods through adequate methods for ACD and chronic CD diagnoses.


Congenital Chagas disease (cCD)


Maternofetal represents the main route of T. cruzi transmission in free vector regions within and outside Latin America over blood products and organ transplants transmissions. Its interruption around 2030 has been decided as a goal for WHO in 2018,(55) after demonstration of its prevention in several reports.(56, 57, 58, 59, 60)

A systematic review including 13 case reports/series and 51 observational studies(61) estimated the pooled congenital transmission rate as 4.7% [95% confidence interval (CI): 3.9-5.6%], higher in endemic than in non-endemic areas (5.0% vs. 2.7%). Congenital infection rates depend on design and period of study, methods for diagnosis, patients´ age, region and presence of the vector transmission as well as patients’ age. Most reports are from Latin American, Southern Cone and Bolivia; rates are less known in Mexico and Central America. It is estimated in 6.1% in Argentina,(62, 63) 5.0-6.0% in Bolivia,(64) 0.8-6.3% in Mexico,(63, 64, 65) 3-10% in Paraguay,(66) 1.8% in Chile,(67) 1.7% in Brazil(68) and 0% in Honduras.(63) The estimated numbers of infected pregnant women and newborns are 40,000 and 2,000 newborns in Canada, Mexico and the United States.(62) cCD was reported in several continents and the estimated annual numbers of children congenitally infected are represented in Tables I-II.(5, 10, 69, 70)


Determinants of congenital transmission


cCD and temporal evolution - The spectrum of cCD is variable from abortions and stillbirths, hydrops foetalis congenital megaesophagusprematurity and low birth weight in the early stage of pregnancy to severe cases similar to sepsis in late intrauterine or perinatal infection.(71, 72, 73, 74) The last group is described as TORCH: toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus, hepatitis and human immunodeficiency virus, parvovirus B19, and enteroviruses(75) with hepato-splenomegaly and/or anaemia and/or thrombocytopenia and, less frequently, meningoencephalitis and/or myocarditis, pneumonitis.(76, 77) Other have mild symptoms and signs (hepatomegaly, hepatosplenomegaly) or are asymptomatic. The majority of infected pregnant women, asymptomatic, may be at increased risk of cCD transmission.

Rates between 35.0-68.4% of symptomatic cases have been reported in different countries and/or periods.(64, 76, 77) In a Bolivian cohort, such rate decreased from 50% to 18% and mortality from 20% to 4%, in 1992-1994 and 1999-2001, respectively.(64) Asymptomatic infection seems to be more frequent than severe cases, recently,(78) possibly due to the vector control and to better prenatal/neonatal care. In parallel, rates of infected women decreased from 28% to 17% but transmission rate of cCD was similar (5-6%) in both periods.


Maternal parasitaemia - Higher morbidity and mortality of cCD was associated with higher parasitaemia in mothers living in high vector density areas compared to those living in vector free areas.(78, 79) Of note, influence of high maternal parasitaemia on the transmission rates over 50% have been shown in T. cruzi/HIV infected mothers without highly active antiretroviral therapy (HAART) control.(18, 76, 80, 81, 82, 83) Other factors influence the outcome of cCD: period of pregnancy,(74, 84, 85) previous transmission and higher transmission rate,(86) geographical origin of the mother or parasite strain,(84, 87) virulence of infecting isolate, genetic regulation of immune response of infant and mother, malnutrition, poverty and cesarean delivery avoiding gut colonisation.


Parasite diversity - In cohorts of infected mother from Chile, Southern Brazil, and Paraguay and Argentina registered TcI, TcII, TcIII, and TcVI lineages were usually related to the predominant regional lineage and TcV in Bolivia was associated with high cCD transmission rate.(88, 89, 90) In Argentina, Honduras and Mexico, non TcI predominates in the maternal samples analysed(63) while in Peru and Mexico, TcI like genotype was observed in a few samples.(91, 92) In Argentina identity between most TcIId lineages predominates in the mother/neonate pairs,(88) however, minor variants suggest the presence of different TcIId variants or selection at placental level and/or neonates immune response.(88, 89, 93, 94)


T cruzi virulence factors - T cruzi strains present different abilities to cause placental infection.(87) The sequence of the protease TcGP63, considered as a virulence factor, was analysed in parasite clones from mother/infant pairs.(94) No congenital murine infection was observed both with T. cruzi K98 clone and an isolate from congenital case VD/TcVI. However, the latter induced upregulation of genes of innate immune response and IFNγ(95) secretion in placenta. Comparing isolates, VC/TcVI was more infective in human trophoblast than Y strain/TcII.(96) Moreover, the human isolate VC/TcVI has a higher survival rate in placenta than Tulahuén strain but both parasites are virulent in placental explantswhen a high inoculum is employed.(97)


Host parasite interaction in cCD


Immune response in mother/foetus - IFNγ has been reported as a key mediator to control T. cruzi infection,(98) in synergism with TNF Fα by killing the parasite through nitrite oxide secretion.(99) Impaired immune response to control the parasite was shown in infected children ´s maternal cells compared to mothers of uninfected children. In the first group, lower levels of both TNFα and TGFβ,(100, 101) increased IL10 levels,(102) lower IFNγ and TNFα secretion under antigen stimulation and low activation of T cell phenotype were reported.(103) Moreover, the mother of uninfected children with parasitaemia have shown increased levels of IFNγ and TNFα in placental, peripheral and cord blood compared to infected mother without parasitaemia.(104)

On the other hand, upregulation of infected maternal cells and their respective uninfected neonates is represented by proinflammatory and anti-inflammatory cytokines (IFNγ, IL-2, and IL-4) under mitogens and/or parasite stimulation.(105)

In contrast, in infected infant, lower levels of IFNγ, decreased activity of cord blood natural killer and cord blood CD8+T cells, higher spontaneous T cell apoptosis(106) were reported compared to uninfected newborn from uninfected mother.(107) Moreover, infected infants show a Th1 immune response to vaccinal antigens.(108) Finally, before the diagnosis of cCD, in the absence of IFNγ, IL17 seems to represent neonate immune response to control T. cruzi parasitaemia, before the diagnosis of cCD.(106)

These data suggest that a high parasitaemia plus a strong inflammatory cytokine response is associated with absence of congenital transmission. Moreover, babies from infected mother are protected from cCD by upregulation of mother immune response through innate and adaptive immunity, decreasing the chance of CD transmission.


Approach, prevention and elimination


Although no studies have been analysed during pregnancy, antiparasitic treatment is not recommended since teratogenic risks of benznidazole and nifurtimox have been reported in peripheral blood lymphocytes of patients exposed to the drugs,(109, 110) although no studies have been reported during pregnancy.

The elimination of cCD is the goal established by WHO after reports of more than two hundred pregnant women treated before pregnancy in Argentina and Bolivia(56, 57, 58, 59, 60) without cCD transmission. Along with this evidence, 100% of cure was registered in infected newborn treated in the first year of life(60) and over 95% of cure have been reported in 10 days-19 years old children (median 6.9 years), using PCR as therapeutic control at 1 and 3 years.(58) A randomised study in Brazil enrolled older children (7-19 years) and, applying serology as therapeutic control, showed 64.7-84.7%, respectively, by intention-to treat and by per protocol analysis.(111) In addition, in regions where other T cruzi lineages occur and failure rates have been reported in children, future studies with larger number of women are needed to know the incidence of cCD in treated women.(112)

Considering these findings, the treatment of 15-44-year-old women in reproductive age is strongly recommended. Table I depicts their estimated number in countries of endemicity and Table II shows the estimates of pregnant women in countries of non-endemicity who should be screened before the pregnancy to receive antiparasitic treatment.

In Brazil, the recent approval of the compulsory notification of the chronic CD in Portaria No. 264 of February 17, 2020, will contribute for the control of code. In parallel, a PAHO initiative represents an excellent strategy in endemic regions to eliminate maternal and child infection caused by HIV, syphilis, hepatitis B, and Chagas’ disease.(113)

Although no country of non-endemicity has a national policy for screening to control congenital transmission, some regions in Spain, Italy and Switzerland implemented CD screening during antenatal care and newborns follow up for diagnosis and treatment of cCD. In Australia and New Zealand, interventions have been considered to identify pregnant women at risk of transmission.

Moreover, cost savings analyses showed that this strategy in areas of non-endemicity represents the best strategy for cCD control.(114, 115, 116)


Comments - In conclusion, cCD elimination depends on surveillance for diagnosis of infected women in reproductive age, pregnant infected women and infected babies. A new tool not accessible in the routine diagnosis worldwide is qualitative PCR, necessary for early diagnosis of cCD associated to reliable serological tests. Finally, cCD elimination around 2030, as proposed by WHO, requests joining government and Community efforts, to support a strong primary health and antenatal care to guarantee antiparasitic treatment of infected children and infected reproductive age women to achieve this goal.


Oral transmission


In the context of major prevalence of millions of chronic cases of CD in Latin America, acute orally transmitted cases emerged as outbreaks in Amazon extending to South American Andean and coast mountain areas in Brazil, Venezuela, Colombia, Bolivia and French Guiana.(117, 118, 119, 120, 121, 122, 123, 124)Interestingly, these outbreaks were registered in non- endemic areas in Brazil, where intradomicile and peri domestic triatomine were under vector control.(20, 24)

During 1965-2009, 138 outbreaks were reported, predominantly in Brazilian Amazon while only 7-8 occurred in areas outside Amazonia. Between 2000-2009, 855 cases represent an increased number of ACD.(125) Approximately 3.060 ACD cases were reported in Brazil, between 2007-2019, predominantly in North region (94.4%) and Pará (74.54%), the majority attributed to the ingestion of contaminated food.(126) Temporal comparison shows a trend towards an increasing incidence coefficient of oral transmission in the last 4 years, when a total > 300 cases /year were recorded.(126) In addition, in Venezuela from 2011-2015, 11 outbreaks involved 249 people, predominantly children,(122) and in Colombia from 1999-2017, 18 outbreaks affected 576 people.(118, 123)


Risks factor for oral transmission of CD


Changes in sylvatic cycles - Deforestation introduces changes in wildlife biodiversity and in sylvatic cycles of vectors and animals.(127) Human activities exploring açaí as a source of food and economic survival closer to the sylvatic cycle and forest have been suggested as a risk factor for oral transmission of CD.

On the other hand, in Amazon and some Andean regions, several palm trees distributed throughout Colombia, Ecuador, Guatemala, Mexico, Panama, Peru, Venezuela and Brazil have been reported as ecotopes for a broad range of triatomine vectors. High vector infection rates make possible the contamination of homemade food or beverages.(17, 122, 123, 124) Other source of infection is represented by sylvatic hosts, especially Didelphis, found in deforested areas near the outbreaks with infectant parasite forms in 12-100% of their anal glands secretion.(123, 128, 129)


Lack of good practices in food preparation - Table V represents the outbreaks with the possible source of contaminated food (açaí or bacaba fruit), water or soup, juices, water or soup, guava, orange, tangerine juices, mayo fruit juice or “viño de palma”, shared by the people involved in the outbreaks,(118,119,120,121,124,129-140) contaminated with infected triatomine or their feces; or with anal glands secretions of infected marsupials.




Clinical symptoms


Oral transmission of CD is considered when > 1 acute case of febrile disease without other causes is linked to a suspected food and should be confirmed by the presence of the parasite in the patients´ blood or biological fluid sample and/or suspicious food by direct microscopic examination.

Incubation period is 3-22 days for oral transmission 38-39ºC and the involvement of phagocytic mononuclear system with splenomegaly, hepatomegaly, adenomegaly(20, 119, 129, 132, 133, 134, 135, 138) and peri palpebral oedema. However, some peculiarities need to be emphasised. No signs of parasite entry like Romaña signal are present, but facial oedema particularly peri palpebral oedema is very frequent, exanthema (maculopapular, petechial or erythema nodosum) and cardiac manifestations (pericardial effusion, pleural effusion, and icterus), are more commonly seen in oral rather than vector-borne disease. Gastric haemorrhage possibly represents entry through the digestive mucosa, which shows amastigotes in an intense inflammatory infiltrate.(141)


Definition of ACD orally transmitted - Laboratorial definition of ACD by oral transmission in oligosymptomatic patients represents a challenge when direct microscopy was not positive due to late suspicion or lack of application of concentration methods. In these cases, patients with unrecognised chronic CD and febrile disease are at risk of ACD diagnosis if only indirect enrichment parasitological methods, qualitative PCR, and even serology (without increasing titers) or false positive IgM(142) are considered. As such parasitological and molecular tests are positive in chronic CD,(143) they are useful only in previously non infected patients with acute symptoms and epidemiological link. Quantitative PCR could be useful if high DNA parasite counts not present in chronic cases were observed.(144) In addition, live parasites found in the suspect food for the first time, confirmed the proved disease by oral contamination.(140) Therefore, the new advances in molecular qualitative and quantitative methods are challenges to be included in the classic concepts of confirmed, probable and suspected cases (PAHO),(145) as shown in the Table VI.






Pathogenesis and parasite strain - Analyses of Tc lineage in patients, reservoir and vectors possibly involved in ACD outbreaks are useful to identify possible sources of contamination.(146) In addition, several lineages showed differential virulence regarding the route of infection in experimental infection. So, Peruvian strain (TcII) is less virulent by gastric than intraperitoneal inoculation whereas Colombian strain (TcI, sylvatic cycle), infects by gastric as well as by intraperitoneal route.(147) Metacyclic forms of gp82-expressing Y82 strain (related to TcVI human outbreaks) have been reported as better adapted to invade gastric mucosa and to cause oral infection than Y30 strain (TcII).(148) Moreover, TcIV orally infected mice (with both reference and isolated strains from human oral outbreak) showed higher parasitaemia and tissular parasitical load than those intraperitonially infected.(149, 150) In addition, TcI was less infective by oral route than TcIV which is less infective than TcVI. As TcIV express less pepsin-resistant gp-90 (which downregulated cell invasion) than TcI, their invasion capacity in gastric epithelium is higher than TcI.(151) In summary, the severity of the infection depends on parasite factors (load, glycoprotein resistant to gastric juice), and host factors (gastric secretions, regulation of invasion process and hosts immune response). At oral level, Th2 immune response protects the host, however a Th1 immune response is necessary to protect the host against systemic infection.(152)


Inactivation of the parasite in the food - Considered since 1921 as the natural route of vectors and animals contaminations and a mechanism for parasite dispersion among animals,(153) orally transmitted human infection was first documented in 1936.(154) In addition, sylvatic and domestic animals have been experimentally infected by food contaminated with triatomines or their feces.(155, 156) Parasites survival in contaminated fruits and vegetables experimentally contaminated with T. cruzi was reported from 6 to 72 h,(157) in sugar cane up to 12 h by direct methods and up to 24 h by experimental inoculation(158) and are extremely sensitive to dryness, although resistant to extremes of pH and temperature. In mice virulence has been demonstrated after frozen at -20ºC for up to 26 h.(159) Inactivation of Tc in açaí pulp has been shown by heating above 45ºC and pasteurisation.(160) Heating fruits (70 ± 1ºC for 10 s) or pasteurising juice (82.5 ºC for 1 min) inactivates the parasite. In addition, T. cruzi I and T. cruzi III have been reported to be more resistant to chemical products like sodium hypochlorite and heat temperature compared to Y strain.(161)


Molecular methods to search for parasites in the food - Improvement of methods to detect parasites were reported with detection of DNA copies in 10% of commercialised açaí derived products with mixtures of Tc I-TcII and more rarely TcIV and TcVI.(162) In addition, quantitative PCR(163, 164) proved to be sensitive to search parasite in the food. Recently, possible detection of live parasites in food by mRNA-base reverse transcriptase PCR could represent a new strategy to ensure a better-quality food and to improve handmade and manufactured food.(161)


Comments - The dramatic increase in the outbreaks of orally transmitted CD seen in the last 12 years and mainly in the latter years is likely to be attributed to the lack of good handling practices in food processing, and changes in sylvatic cycles, and to the better recognition of this disease. Although the Brazilian Health Minister and Programa Estadual da Qualidade do Açaí, Pará government have recommended good handling practices to control food contamination,(165, 166, 167) unfortunately, evidences of lack of good quality of food were shown even with general impurity, microbes and parasite DNA presence in commercially available açaí products.(168, 169, 170)

Since açaí is employed as food and as source of subsistence by Amazon population, policies for good practices in food preparation should be monitored by rigorous health surveillance, including food heating above 45ºC and/or pasteurisation,(160, 167) associated to the application of new tools for detection of parasite DNA or mRNA for food quality control.(161, 162, 163, 164)

On the other hand, as access for early diagnosis and treatment is not easy in Brazilian Amazon, active surveillance on ACD cases should be implemented by improvement of the structure for diagnosis as well as for health attention to severe cases of ACD, including the search of ACD in Febrile Syndrome Surveillance and training of health professionals for diagnosis and management of orally transmitted CD.




To Carlos José Quinteiro and Eliane Araújo for their support in the search for old references.

01. Schmuñis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop. 2010; 115: 14-21.
02. Moncayo A, Silveira AC. Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy. Mem Inst Oswaldo Cruz. 2009; 104(Suppl. 1): 17-30.
03. CDC - Centers for Disease Control and Prevention. Chagas disease after organ transplantation - United States, 2001. MMWR Morb Mortal Wkly Rep. 2002; 15; 51(10): 210-2.
04. CDC - Centers for Disease Control and Prevention. Chagas disease after organ transplantation - Los Angeles, California, 2006. MMWR Morb Mortal Wkly Rep. 2006; 5: 798-800.
05. CDC - Centers for Disease Control and Prevention. Congenital transmission of Chagas disease - Virginia, 2010. MMWR Morb Mortal Wkly Rep. 2012; 61(26): 477-9.
06. Garcia MN, Woc-Colburn L, Aguilar D, Hotez PJ, Murray KO. Historical perspectives on the epidemiology of human Chagas disease in Texas and recommendations for enhanced understanding of clinical Chagas disease in the Southern United States. PLoS Negl Trop Dis. 2015; 9(11): e0003981.
07. Jackson Y, Gétaz L, Wolff H, Holst M, Mauris A, Tardin A, et al. Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland. PLoS Negl Trop Dis. 2010; 4(2): e592.
08. Angheben A, Boix L, Buonfrate D, Gobbi F, Bisoffi Z, Pupella S, et al. Chagas disease and transfusion medicine: a perspective from non-endemic countries. Blood Transfus. 2015; 13(4): 540-50.
09. Blumental S, Lambermont M, Heijmans C, Rodenbach MP, El Kenz H, Sondag D, et al. First documented transmission of Trypanosoma cruzi infection through blood transfusion in a child with sickle-cell disease in Belgium. PLoS Negl Trop Dis. 2015; 9(10): e0003986.
10. Imai K, Maeda T, Sayama Y, Osa M, Mikita K, Kurane I, et al. Chronic Chagas disease with advanced cardiac complications in Japan: case report and literature review. Parasitol Int. 2015; 64(5): 240-2.
11. Riarte A, Luna C, Sabatiello R, Sinagra A, Schiavelli R, De Rissio A, et al. Chagas’ disease in patients with kidney transplants: 7 years of experience 1989-1996. Clin Infect Dis. 1999; 29: 561-7.
12. Torrico F, Alonso-Vega C, Suárez E, Rodríguez P, Torrico MC, Dramaix M, et al. Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. Am J Trop Med Hyg. 2004; 70: 201-9.
13. Coura JR, Junqueira ACV, Ferreira JMBB. Surveillance of seroepidemiology and morbidity of Chagas disease in the Negro River, Brazilian Amazon. Mem Inst Oswaldo Cruz. 2018; 113(1): 17-23.
14. Cantey PT, Stramer SL, Townsend RL, Kamel H, Ofafa K, Todd CW, et al. The United States Trypanosoma cruzi infection study: evidence for vector-borne transmission of the parasite that causes Chagas disease among United States blood donors. Transfusion. 2012; 52(9): 1922-30.
15. Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis. 2009; 49: e52-4.
16. Manne-Goehle J, Umeh CA, Montgomery SP, Wirtz VJ. Estimating the burden of Chagas disease in the United States. PLoS Negl Trop Dis. 2016; 10(11): e0005033.
17. Strasen J, Williams T, Ertl G, Zoller T, Stich A, Ritter O. Epidemiology of Chagas disease in Europe: many calculations, little knowledge. Clin Res Cardiol. 2014; 103(1): 1-10.
18. Sartori AM, Ibrahim KY, Westphalen EVN, Braz LMA, Oliveira Jr OC, Gakiya E, et al. Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/ AIDS. Ann Trop Med Parasitol. 2007; 101: 31-50.
19. Stimpert KK, Montgomery SP. Physician awareness of Chagas disease, USA. Emerg Infect Dis. 2010; 16: 871-2.
20. Shikanai-Yasuda MA, Carvalho NB. Oral transmission of Chagas disease. Clin Infect Dis. 2012; 54(6): 845-52.
21. Alarcón de Noya BA, Díaz-Bello Z, Colmenares C, Ruiz-Guevara R, Mauriello L, Muñoz-Calderón A, et al. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches. Mem Inst Oswaldo Cruz. 2015: 10(3): 377-86.
22. WHO - World Health Organization. Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021-2030. Geneva: World Health Organization; 2020. Available from:
23. WHO - World Health Organization. World Chagas disease day: raising awareness of neglected tropical diseases. 2019. Available from: https://www. diseases/news/world-Chagasday-approved/en/.
24. No authors listed. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec. 2015; 90(6): 33-44.
25. Luna EJA, Furucho CR, Silva RA, Wanderley DM, Carvalho NB, Satolo CG, et al. Prevalence of Trypanosoma cruzi infection among Bolivian immigrants in the city of São Paulo, Brazil. Mem Inst Oswaldo Cruz. 2017; 112(1): 70-4.
26. Basile L, Jansà JM, Carlier Y, Salamanca DD, Angheben A, Bartoloni A, et al. Chagas disease in European countries: the challenge of a surveillance system. Euro Surveill. 2011; 16(37): pii=19968.
27. Jackson Y, Pinto A, Pett S. Chagas disease in Australia and New Zealand: risks and needs for public health interventions. Trop Med Int Health. 2014; 19: 212-8.
28. PAHO - Pan American Health Organization. Guidelines for the diagnosis and treatment of Chagas disease. Risk of exposure to Chagas’ disease among seroreactive Brazilian blood donors. Washington, D.C.: PAHO; 2019. ISBN: 978-92-75-12043-9. Available from: Guidelines for the Diagnosis and Treatment of Chagas Diseases (
29. Benjamin RJ, Stramer SL, Leiby DA, Dodd RY, Fearon M, Castro E. Trypanosoma cruzi infection in North America and Spain: evidence in support of transfusion transmission (CME). Transfusion. 2012; 52(9): 1913-21.
30. Requena-Méndez A, Albajar-Viñas P, Angheben A, Chiodini P, Gascón J, Muñoz J, et al. Health policies to control Chagas disease transmission in European countries. PLoS Negl Trop Dis. 2014; 8(10): e3245.
31. Custer B, Agapova M, Bruhn R, Cusick R, Kamel H, Tomasulo P, et al. Epidemiologic and laboratory findings from 3 years of testing United States blood donors for Trypanosoma cruzi. Transfusion. 2012; 52: 1901-11.
32. Salles NA, Sabino EC, Cliquet MG, Eluf-Neto J, Mayer A, Almeida Neto C, et al. Risk of exposure to Chagas’ disease among seroreactive Brazilian blood donors. Transfusion. 1996; 36: 969-73.
33. Chocair PR, Sabbaga E, Amato Neto V, Shiroma M, de Goes GM. Kidney transplantation: a new way of transmitting chagas disease. Rev Inst Med Trop São Paulo. 1981; 23(6): 280-2.
34. Altclas J, Sinagra A, Dictar M, Luna C, Veron MT, De Risio AM, et al. Chagas disease in bone marrow transplantation: an approach to preemptive therapy. Bone Marrow Transplant. 2005; 36(2): 123-9.
35. Huprikar S, Bosserman E, Patel G, Moore A, Pinney S, Anyanwu A, et al. Donor-derived Trypanosoma cruzi infection in solid organ recipients in the United States, 2001-2011. Am J Transplant. 2013; 13(9): 2418-25.
36. Schwartz BS, Mawhorterb SD, AST Infectious Diseases Community of Practice. Parasitic infections in solid organ transplantation. Am J Transplant. 2013; 13(Suppl. 4): 280-303.
37. Chagas’ Disease Argentine Collaborative Transplant Consortium, Casadei D. Chagas’ disease and solid organ transplantation. Transplant Proc. 2010; 42(9): 3354-9.
38. Pinazo MJ, Miranda B, Rodriguez-Villar C, Altclas J, Brunet Serra M, Garcia-Otero EC, et al. Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas. Transplant Rev (Orlando). 2011; 25(3): 91-101.
39. Chin-Hong PV, Schwartz BS, Bern C, Montgomery SP, Kontak S, Kubak B, et al. Screening and treatment of Chagas cisease in organ transplant recipients in the United States: recommendations from the Chagas in Transplant Working Group. Am J Transplant. 2011; 11(4): 672-80.
40. Carvalho MF, de Franco MF, Soares VA. Amastigotes forms of Trypanosoma cruzi detected in a renal allograft. Rev Inst Med Trop São Paulo. 1997; 39(4): 223-6.
41. Souza FF, Castro-E-Silva O, Marin Neto JA, Sankarankutty AK, Teixeira AC, Martinelli ALC, et al. Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: a case report. Transplant Proc. 2008; 40(3): 875-8.
42. Figueiredo JF, Martinez R, da Costa JC, Moyses Neto M, Suaid HJ, Ferraz AS. Transmission of Chagas disease through renal transplantation: report of a case. Trans R Soc Trop Med Hyg. 1990; 84(1): 61-2.
43. Cantarovich F, Vazquez M, Garcia WD, Abbud Filho M, Herrera C, Villegas Hernandez A. Special infections in organ transplantation in South America. Transplant Proc. 1992; 24(5): 1902-8.
44. De Arteaga J, Massari PU, Galli B, Garzon ME, Zlocowsky JC. Renal transplantation and Chagas’ disease. Transplant Proc. 1992; 24(5): 1900-1.
45. Vázquez MC, Riarte A, Pattin M, Lauricella M. Chagas’ disease can be transmitted through kidney transplantation. Transplant Proc. 1993; 25(6): 3259-60.
46. Sousa AA, Lobo MC, Barbosa RA, Bello V. Chagas seropositive donors in kidney transplantation. Transplant Proc. 2004; 36(4): 868-9.
47. Cura CI, Lattes R, Nagel C. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors. Am J Transplant. 2013; 13: 3253-61.
48. Cicora F, Paz M, Mos FA, Petroni J, Roberti JE. Belatacept-based immunosuppression in a chagasic adult recipient of en bloc pediatric kidneys. Transplantation. 2014; 98(4): e34-35.
49. D’Albuquerque LA, González AM, Filho HLVN, Copsteina JLM, Larrea FIS, Mansero JMP, et al. Liver transplantation from deceased donors serologically positive for Chagas disease. Am J Transplant. 2007; 7: 680-4.
50. Salvador F, Len O, Molina I, Sulleiro E, Sauleda S, Bilbao I, et al. Safety of liver transplantation with Chagas disease - Seropositive donors for seronegative recipients. Liver Transpl. 2011; 17(11): 1304-8.
51. Goldaracena N, Wolf MM, Quinonez E, Anders M, Mastai R, McCormack L. Is it safe to use a liver graft from a Chagas disease - Seropositive donor in a human immunodeficiency virus - Positive recipient? A case report addressing a novel challenge in liver transplantation. Liver Transpl. 2012; 18: 979-83.
52. McCormack L, Quinonez E, Goldaracena N, Anders M, Rodríguez V, Orozco Ganem, et al. Liver transplantation using Chagas - infected donors in uninfected recipients: a single-center experience without prophylactic therapy. Am J Transplant. 2012; 12(10): 2832-7.
53. Rodríguez-Guardado A, González ML, Rodríguez M, Flores-Chávez M, Boga JA, Gascon J. Trypanosoma cruzi infecton in a Spanish liver transplant recipient. Clin Microbiol Infect. 2015; 21: 687.e1-687.e3.
54. Balderramo D, Bonisconti F, Alcaraz A, Giordano E, Sánchez A, Barrabino M, et al. Chagas disease and liver transplantation: experience in Argentina using real-time quantitative PCR for early detection and treatment. Transpl Infect Dis. 2017; 19(6).
55. Carlier Y, Altcheh J, Angheben A, Freilij H, Luquetti AO, Schijman AG, et al. Congenital Chagas disease: updated recommendations for prevention, diagnosis, treatment, and follow-up of newborns and siblings, girls, women of childbearing age, and pregnant women. PLoS Negl Trop Dis. 2019; 13(10): e0007694.
56. Sosa-Estani S, Cura E, Velázquez E, Yampotis C, Segura EL. Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission. Rev Soc Bras Med Trop. 2009; 42(5): 484-7.
57. Fabbro DL, Danesi E, Olivera V, Codebo MO, Denner S, Heredia C, et al. Trypanocide treatment of women infected with Trypanosoma cruzi and its effect on preventing congenital Chagas. PLoS Negl Trop Dis. 2014; 8: e3312.
58. Moscatelli G, Moroni S, Garcıa-Bournissen F, Ballering G, Bisio M, Freilij H, et al. Prevention of congenital Chagas through treatment of girls and women of childbearing age. Mem Inst Oswaldo Cruz. 2015; 110(4): 507-9.
59. Alvarez MG, Vigliano C, Lococo B, Bertocchi G, Viotti R. Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study. Acta Trop. 2017; 174: 149-52.
60. Murcia L, Simón M, Carrilero B, Roig M, Segovia M. Treatment of infected women of childbearing age prevents congenital Trypanosoma cruzi infection by eliminating the parasitemia detected by PCR. J Infect Dis. 2017; 215: 1452-8.
61. Howard EJ, Xiong X, Carlier Y, Sosa-Estani S, Buekens P. Frequency of the Congenital transmission of Trypanosoma cruzi: a systematic review and meta-analysis. Brit J Obst Gynecol. 2014; 121(1): 22-33.
62. De Rissio AM, Riarte AR, Garcıa MM, Esteva MI, Ruiz AM, Quaglino M, et al. Congenital Trypanosoma cruzi infection. Efficacy of its monitoring in an urban reference health center in a non-endemic area of Argentina. Amer J Trop Med Hyg. 2010: 82: 838-45.
63. Buekens P, Cafferata ML, Alger J, Althabe F, Belizán JM, Bustamante N, et al. Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: an observational prospective study. Am J Trop Med Hyg. 2018; 98(2): 478-85.
64. Torrico F, Alonso-Vega C, Suarez E, Rodriguez P, Torrico MC, Dramaix M, et al. Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. Amer J Trop Med Hyg. 2004; 70(2): 201-9.
65. Montes-Rincón LM, Silva LG, González-Bravo FE, Molina-Garza ZJ. Trypanosoma cruzi seroprevalence in pregnant women and screening by PCR and microhaematocrit in newborns from Guanajuato, Mexico. Acta Trop. 2016; 164: 100-6.
66. Russomando G, de Tomassone MM, de Guillen I, Acosta N, Vera N, Almirón M, et al. Treatment of congenital Chagas’ disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg. 1998; 59: 487-91.
67. Tello P, Fernández P, Sandoval L, Ampuero G, Pizarro T, Schenone H. Incidencia de la infección por Trypanosoma cruzi en madres e hijos de un sector del Area Norte de Santiago. Bol Chil Parasitol. 1982; 37(1-2): 23-24.
68. Martins-Melo FR, Lima MS, Ramos Jr AN, Alencar CH, Heukelbach J. Systematic review prevalence of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in Brazil: a systematic review and meta-analysis. Trop Med Int Health. 2014: 19: 943-57.
69. Pehrson PO, Wahlgren M, Bengtsson E. Asymptomatic congenital Chagas’ disease in a five-year-old child. Scand J Infect Dis. 1981; 13: 307-8.
70. Riera C, Guarro A, El-Kassab H, Jorba JM, Castro M, Angril R. Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report. Am J Trop Med Hyg. 2006; 75: 1078-81.
71. Bern C, Martin DL, Gilman RH. Acute and congenital Chagas disease. Adv Parasitol. 2011; 75: 19-47.
72. Bittencourt AL, Mota E, Ribeiro Filho R, Fernandes LG, Cerqueira de Almeida PR, Sherlock I, et al. Incidence of congenital Chagas’ disease in Bahia, Brazil. J Trop Ped. 1985, 31:242-8.
73. Bittencourt AL. Doença de Chagas congênita na Bahia. Rev Baiana Saúde Pub. 1984; 11: 159-209.
74. Azogue E, La Fuente C, Darras C. Congenital Chagas’ disease in Bolivia: epidemiological aspects and pathological findings. Trans R Soc Trop Med Hyg. 1985; 79(2): 176-80.
75. Neu N, Duchon J, Zachariah P. TORCH infections. Clin Perinatol. 2015; 42(1): 77-103.
76. Freilij H, Altcheh J. Congenital Chagas’ disease: diagnostic and clinical aspects. Clin Infect Dis. 1995; 21(3): 551-5.
77. Azogue E, Darras C. Prospective study of Chagas disease in newborn children with placental infection caused by Trypanosoma cruzi (Santa Cruz-Bolivia)]. Rev Soc Bras Med Trop. 1991; 24(2): 105-9.
78. Torrico F, Vega CA, Suarez E, Tellez T, Brutus L, Rodriguez P, et al. Are maternal reinfections with Trypanosoma cruzi associated with higher morbidity and mortality of congenital Chagas disease? Trop Med Int Health. 2006; 11(5): 628-35.
79. Brutus L, Schneider D, Postigo J, Romero M, Santalla J, Chippaux JP. Congenital Chagas disease: diagnostic and clinical aspects in an area without vectorial transmission, Bermejo, Bolivia. Acta Trop. 2008; 106(3): 195-9.
80. Freilij H, Altcheh J, Muchinik G. Perinatal human immunodeficiency virus infection and congenital Chagas’ disease. Ped Inf Dis. 1995; 14(2): 161-2.
81. Nisida IV, Amato Neto V, Braz LM, Duarte MI, Umezawa ES. A survey of congenital Chagas’ disease, carried out at three health institutions in São Paulo city, Brazil. Rev Inst Med Trop São Paulo. 1999; 41: 305-11.
82. Scapellato PG, Bottaro EG, Rodríguez-Brieschke MT. Mother-child transmission of Chagas disease: could coinfection with human immunodeficiency virus increase the risk? Rev Soc Bras Med Trop. 2009; 42(2): 107-9.
83. Agosti MR, Ercole P, Dolcini G, Andreani G, Peralta LM, Ayala SG. Two cases of mother-to-child transmission of HIV and Trypanosoma cruzi in Argentina. Braz J Infect Dis. 2012; 16(4): 398-9.
84. Bittencourt A. Possible risk factors for vertical transmission of Chagas’ disease. Rev Inst Med Trop São Paulo. 1992; 34(5): 403-8.
85. Moretti E, Basso B, Castro I, Carrizo Paez M, Chaul M, Barbieri G, et al. Chagas’ disease: study of congenital transmission in cases of acute maternal infection. Rev Soc Bras Med Trop. 2005; 38(1): 53-5.
86. Negrette OS, Mora MC, Basombrío MA. High prevalence of congenital Trypanosoma cruzi infection and family clustering in Salta, Argentina. Pediatrics. 2005; 115(6): e668-72.
87. Andrade SG. The influence of the strain of Trypanosoma cruzi in placental infections in mice. Trans R Soc Trop Med Hyg. 1982; 76(1): 123-8.
88. Virreira M, Truyens C, Alonso-Vega C, Brutus L, Jijena J, Torrico F. Comparison of Trypanosoma cruzi lineages and levels of parasitic DNA in infected mothers and their newborns. Am J Trop Med Hyg. 2007; 77: 102-6.
89. Burgos JM, Altcheh J, Bisio M, Duffy T, Valadares HM, Seidenstein ME, et al. Direct molecular profiling of minicircle signatures and lineages of Trypanosoma cruzi bloodstream populations causing congenital Chagas disease. Int J Parasitol. 2007; 37(12): 1319-27.
90. Corrales RM, Mora MC, Negrette OS, Diosque P, Lacunza D, Virreira M, et al. Congenital Chagas disease involves Trypanosoma cruzi sub-lineage IId in the northwestern province of Salta, Argentina. Infect Genet Evol. 2009; 9: 278-82.
91. Mendoza Ticona CA, Benzaquen EC, Juárez JA, Díaz JS, Choque AT, Talavera RV, et al. The prevalence of Chagas’ disease in puerperal women and congenital transmission in an endemic area of Peru. Rev Panam Salud Publica. 2005; 17(3): 147-53.
92. Olivera MA, Ortega FG, Vidal SC, Hernández-Becerril N, Galdamez EP, Concepcion GC, et al. Serological and parasitological screening of Trypanosoma cruzi 32 infection in mothers and newborns living in two Chagasic areas of Mexico. Arch Med Res. 2006; 37(6): 774-7.
93. Ortiz S, Zulantay I, Solari A, Bisio M, Schijman A, Carlier Y, et al. Presence of Trypanosoma cruzi in pregnant women and typing of lineages in congenital cases. Acta Trop. 2012; 124: 243-6.
94. Llewellyn MS, Messenger LA, Luquetti AO, Garcia L, Torrico F, Tavares SBN, et al. Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. PLoS Negl Trop Dis. 2015; 9(4): e0003458.
95. Juiz NA, Solana ME, Acevedo GR, Benatar AF, Ramirez JC, da Costa PA, et al. Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection. PLoS Negl Trop Dis. 2017: 11: 1-19.
96. Medina L, Castillo C, Liempi A, Herbach M, Cabrera G, Valenzuela L, et al. Differential infectivity of two Trypanosoma cruzi strains in placental cells and tissue. Acta Trop. 2018; 186: 35-40.
97. Triquell MF, Díaz-Luján C, Freilij H, Paglini P, Fretes RE. Placental infection by two subpopulations of Trypanosoma cruzi is conditioned by differential survival of the parasite in a deleterious placental medium and not by tissue reproduction. Trans R Soc Trop Med Hyg. 2009; 103(10): 1011-8.
98. Hoft DF, Schnapp AR, Eickhoff CS, Roodman ST. Involvement of CD41 Th1 cells in systemic immunity protective against primary and secondary challenges with Trypanosoma cruzi. Inf Immun. 2000; 68(1): 197-204.
99. Carlier Y, Truyens C. Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses. Acta Trop. 2015; 151: 103-15.
100. Cardoni RL, Garcia MM, De Rissio AM. Proinflammatory and anti-inflammatory cytokines in pregnant women chronically infected with Trypanosoma cruzi. Acta Trop. 2003; 90: 65-72.
101. Garcia MM, De Rissio AM, Villalonga X, Mengoni E, Cardoni RL. Soluble tumor necrosis factor (TNF) receptors (sTNF-R1 and -R2) in pregnant women chronically infected with Trypanosoma cruzi and their children. Am J Trop Med Hyg. 2008; 78(3): 499-503.
102. Alonso-Vega C, Hermann E, Truyens C, Rodríguez P, Torrico MC, Torrico F, et al. Immunological status of mothers infected with Trypanosoma cruzi. Rev Soc Bras Med Trop. 2005; 38(Suppl. 2): 101-4.
103. Hermann E, Truyens C, Alonso-Vega C, Rodríguez P, Berthe A, Torrico F, et al. Congenital transmission of Trypanosoma cruzi is associated with maternal enhanced parasitemia and decreased production of interferon - gamma in response to parasite antigens. J Infect Dis. 2004; 189(7): 1274-81.
104. Cuna WR, Choque AGH, Passera R, Rodriguez C. Pro-inflammatory cytokine Production in chagasic mothers and their uninfected newborns. J Parasitol. 2009; 95(4): 891-4.
105. Vekemans J, Truyens C, Torrico F, Solano M, Torrico M, Rodriguez P, et al. Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate cells to produce pro- and anti-inflammatory cytokines. Infect Immun. 2000; 68: 5430-4.
106. Hermann E, Alonso-Vega C, Berthe A, Truyens C, Flores A, Cordova M, et al. Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells. Pediatr Res. 2006; 60: 38-43.
107. Volta BJ, Bustos PL, Cardoni RL, De Rissio AM, Laucella SA, Bua J. Serum cytokines as biomarkers of early Trypanosoma cruzi infection by congenital exposure. J Immunol. 2016; 196: 4596-602.
108. Dauby N, Alonso-Vega C, Suarez E, Flores A, Hermann E, Cordova M, et al. Maternal infection with Trypanosoma cruzi and congenital Chagas disease induce a trend to a type 1 polarization of infant immune responses to vaccines. PLoS Negl Trop Dis. 2009; 3(12): e571.
109. Gorla NB, Ledesma OS, Barbieri GP, Larripa IGB. Assessment of cytogenetic damage in chagasic children treated with benznidazole. Mut Res Genet Toxicol. 1988; 206: 217-20.
110. Gorla NB, Ledesma OS, Barbieri GP, Larripa IGB. Thirteenfold increase of chromosomal aberrations non-randomly distributed in chagasic children treated with nifurtimox. Mut Res. 1989; 224: 263-7.
111. Andrade ALSS, Martelli CMT, Oliveira RM, Silva SA, Aires AIS, Soussumi LMT, et al. Am J Trop Med Hyg. 2004; 71: 594-7.
112. Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières. PLoS Negl Trop Dis. 2009; 3(7): e488.
113. PAHO - Pan American Health Organization. EMTCT Plus. Framework for elimination of mother-to-child transmission of HIV, syphilis, hepatitis B and Chagas. PAHO/CHA/17-009, 2017. [cited 2019 Oct 9]. Available from:
114. Sicuri E, Muñoz J, Pinazo MJ, Posada E, Sanchez J, Alonso PL, et al. Economic evaluation of Chagas disease screening of pregnant Latin American women and of their infants in a non-endemic area. Acta Trop. 2011; 118: 110-7.
115. Stillwaggon E, Perez-Zetune V, Bialek SR, Montgomery SP. Congenital Chagas disease in the United States: cost savings through maternal screening. Am J Trop Med Hyg. 2018; 98: 1733-42.
116. Crudo F, Piorno P, Krupitzki H, Guilera A, López-Albizu C, Danesi E, et al. How to implement the framework for the elimination of mother-to-child transmission of HIV, syphilis, hepatitis B and Chagas (EMTCT Plus) in a disperse rural population from the Gran Chaco region: a tailor-made program focused on pregnant women. PLoS Negl Trop Dis. 2020; 14(5): e0008078.
117. Valente SA, Valente VC, das Neves Pinto AY, César MJB, Santos MP, Miranda COS, et al. Analysis of an acute Chagas disease outbreak in the Brazilian Amazon: human cases, triatomines, reservoir mammals and parasites. Trans R Soc Trop Med Hyg. 2009; 103: 291-7.
118. Hernández LM, Ramírez AN, Cucunubá ZM, Zambrano P. Brote de Chagas agudo en Lebrija, Santander 2008. Rev Observ Salud Pública (Santander). 2009; 1: 28-36. Available from:
119. Alarcón de Noya B, Díaz-Bello Z, Colmenares C, Ruiz-Guevara R, Mauriello L, Zavala-Jaspe R, et al. Large urban outbreak of orally acquired acute Chagas disease at a school in Caracas, Venezuela. J Infect Dis. 2010; 201(9): 1308-15.
120. Santalla J, Oporto P, Espinoza E, Rios T, Brutus L. Primer brote reportado de la enfermedad de Chagas en la Amazonia Boliviana: reporte de 14 casos agudos por transmisión oral de Trypanosoma cruzi en Guayaramerín, Beni-Bolivia. Biofarbo. 2011; 19(1): 52-58.
121. Blanchet D, Frédérique Brenière SF, Schijman AG, Bisio M, Simon S, Véron V, et al. First report of a family outbreak of Chagas disease in French Guiana and posttreatment follow-up. Infect Genet Evol. 2014; 28: 245-50.
122. Alarcón de Noya B, Díaz-Bello Z, Colmenares C, Ruiz-Guevara R, Mauriello L, Muñoz-Calderón A, et al. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches. Mem Inst Oswaldo Cruz. 2015; 110(3): 377-86.
123. Rendón LM, Guhl F, Cordovez JM, Erazo D. New scenarios of Trypanosoma cruzi transmission in the Orinoco region of Colombia. Mem Inst Oswaldo Cruz. 2015; 110(3): 283-8.
124. MS/SVS - Ministério da Saúde/Secretaria de Vigilância em Saúde. Nota Técnica - 4/4/05. Doença de Chagas aguda relacionada à ingestão de caldo de cana em Santa Catarina. Brasil, 2005. Available from:
125. MS/SVS - Ministério da Saúde/Secretaria de Vigilância em Saúde. Boletim epidemiológico 46, N° 21 - 2015. Doença de Chagas aguda no Brasil, série histórica de 2000 a 2013. Available from:
126. MS/SVS - Ministério da Saúde/Secretaria de Vigilância em Saúde. Boletim Epidemiológico 51 - Doença de Chagas: 14 de abril - Dia Mundial. 2020. Available from:
127. Roque AL, Xavier SC, Rocha MG, Duarte AC, D’Andrea PS, Jansen AM. Trypanosoma cruzi transmission cycle among wild and domestic mammals in three areas of orally transmitted Chagas disease outbreaks. Am J Trop Med Hyg. 2008; 79: 742-9.
128. Urdaneta-Morales S, Nironi I. Trypanosoma cruzi in the anal glands of urban opossums. I- Isolation and experimental infections. Mem Inst Oswaldo Cruz. 1996; 91(4): 309-403.
129. Shikanai-Yasuda MA, Marcondes CB, Guedes LA, Siqueira GS, Barone AA, Dias JC, et al. Possible oral transmission of acute Chagas’ disease in Brazil. Rev Inst Med Trop São Paulo. 1991; 33(5): 351-7.
130. Silva NN, Clausel DT, Nolibus H, Mello AL, Ossanai J, Rapone T, et al. Surto epidêmico de Doença de Chagas com provável contaminação oral. Rev Inst Med Trop São Paulo. 1968; 10: 265-76.
131. Shaw J, Lainson R, Fraiha H. Considerações sobre a epidemiologia dos primeiros casos autóctones de doença de Chagas registrados em Belém, Pará, Brasil. Rev Saude Publica. 1969; 3: 153-7.
132. Pinto AYN, Harada GS, Valente VC, Abud JEA, Gomes FS, de Souza GCR, et al. Acometimento cardíaco em pacientes com doença de Chagas aguda em microepidemia familiar, em Abaetetuba, na Amazônia brasileira. Rev Soc Bras Med Trop. 2001; 34(5): 413-9.
133. Pinto AYN, Valente AS, Valente VC, Ferreira Jr AG, Coura JR. Acute phase of Chagas disease in the Brazilian Amazon Region. Study of 233 cases from Pará, Amapá and Maranhão observed between 1988 and 2005. Rev Soc Bras Med Trop. 2008; 41: 602-14.
134. Beltrão HB, Cerroni MP, Freitas DR, Freitas DRC, Pinto AYN, Valente VC, et al. Investigation of two outbreaks of suspected oral transmission of acute Chagas disease in the Amazon Region, Pará, State, Brazil, in 2007. Trop Doct. 2009; 39(4): 231-2.
135. Dias JP, Bastos C, Araújo E, Mascarenhas AV, Martins Netto E, Grassi F, et al. Acute Chagas disease outbreak associated with oral transmission. Rev Soc Bras Med Trop. 2008; 41(3): 296-300.
136. Nóbrega AA, Garcia MH, Tatto E, Obara MT, Costa E, Sobel J, et al. Oral transmission of Chagas disease by consumption of açai palm fruit, Brazil. Emerg Infect Dis. 2009; 15: 653-5.
137. Cavalcanti LPG, Rolim DB, Pires Neto RDJ, Vilar DCLF, Nogueira UOL, Pompeu MMDL, et al. Microepidemics of acute Chagas’ disease by oral transmission in Ceará. Cad Saude Colet. 2009; 17(4): 911-21.
138. Bastos CJ, Aras R, Mota G, Reis F, Dias JP, Jesus RS, et al. Clinical outcomes of thirteen patients with acute Chagas disease acquired through oral transmission from two urban outbreaks in northeastern Brazil. PLoS Negl Trop Dis. 2010; 4: e711.
139. Vargas A, Malta JMAS, Costa VM, Cláudio LG, Alves RV, Cordeiro GS, et al. Investigação de surto de doença de Chagas aguda na região extra-amazônica, Rio Grande do Norte, Brasil, 2016. Cad Saude Publica. 2018: 34(1): e00006517.
140. Santana RAG, Guerra MGVB, Sousa DR, Couceiro K, Ortiz JV, Oliveira M, et al. Oral transmission of Trypanosoma cruzi, Brazilian Amazon. Emerg Infect Dis. 2019; 25(1): 132-5.
141. de Almeida-Ribeiro R, Lourenço Jr DM, Dias JC, Shikanai-Yasuda MA, Chapadeiro E, Lopes ER. Intracardial autonomous nervous system in a fatal case of acute Chagas disease. Rev Soc Bras Med Trop. 1993; 26: 35-8.
142. Camargo M, Amato Neto V. Anti-Trypanosoma cruzi IgM antibodies as serological evidence of recent infection. Rev Inst Med Trop São Paulo. 1974; 16: 200-2.
143. Portela-Lindoso A, Shikanai-Yasuda MA. Chronic Chagas’ disease: from xenodiagnosis and hemoculture to polymerase chain reaction. Rev Saude Publica. 2003; 37: 107-15.
144. Besuschio SA, Picado A, Muñoz-Calderón A, Wehrendt DP, Fernández M, Benatar A, et al. Trypanosoma cruzi loop-mediated isothermal amplification (Trypanosoma cruzi Loopamp) kit for detection of congenital, acute and Chagas disease reactivation. PLoS Negl Trop Dis. 2020; 14(8): e0008402.
145. OPAS - Organização Panamericana da Saúde. Guia para vigilância, prevenção, controle e manejo clínico da doença de Chagas aguda transmitida por alimentos. Rio de Janeiro: PANAFTOSA-VP/OPAS/OMS; 2009. 92 pp.
146. Andrade SG, Campos RF, Steindel M, Guerreiro ML, Magalhães JB, Almeida MC, et al. Biological, biochemical and molecular features of Trypanosoma cruzi strains isolated from patients infected through oral transmission during a 2005 outbreak in the state of Santa Catarina, Brazil: its correspondence with the new T. cruzi Taxonomy Consensus (2009). Mem Inst Oswaldo Cruz. 2011; 106(8): 948-56.
147. Camandaroba EL, Lima CMP, Andrade SG. Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection. Rev Inst Med Trop São Paulo. 2002; 44: 97-103.
148. Cortez C, Martins RM, Alves RM, Silva RC, Bilches LC, Macedo S, et al. Differential infectivity by the oral route of Trypanosoma cruzi lineages derived from Y strain. PLoS Negl Trop Dis. 2012; 6: e-1804.
149. Silva-dos-Santos D, Barreto-de-Albuquerque J, Guerra B, Moreira OC, Berbert LR, Ramos MT, et al. Unraveling Chagas disease transmission through the oral route: gateways to Trypanosoma cruzi infection and target tissues. PLoS Negl Trop Dis. 11(4): e0005507.
150. Teston APM, Abreu AP, Abegg CP, Gomes ML, Toledo MJO. Outcome of oral infection in mice inoculated with Trypanosoma cruzi IV of the Western Brazilian Amazon. Acta Trop. 2017; 166: 212-7.
151. Maeda FY, Clemente FM, Macedo S, Cortez C, Yoshida N. Host cell invasion and oral infection by Trypanosoma cruzi strains of genetic groups TcI and TcIV from chagasic patients. Parasit Vectors. 2016; 9: 189-212.
152. Hoft DF, Eickhoff CS. Type 1 immunity provides optimal protection against both mucosal and systemic Trypanosoma cruzi challenges. Infect Imun. 2002; 70: 6715-25.
153. Nattan-Larrier L. Infections à Trypanosomes et voies de penetrations des virus. Bull Soc Pathol Ex. 1921; 14: 537-42.
154. Mazza S, Montana A, Benitez C, Janzi E. Transmisson del Schizotripanum cruzi al niño por leche de la madre con enfermedad de Chagas. MEPRA. 1936; 28: 41-6.
155. Mayer HF. Infección experimental con Trypanosoma cruzi por via digestiva. An Inst Med Reg. 1961; 5: 43-8.
156. Dias JC. Notas sobre o Trypanosoma cruzi e suas características bioecológicas, como agente de enfermidades transmitidas por alimentos. Rev Soc Bras Med Trop. 2006; 39: 370-5.
157. Añez N, Crisante G. Survival of culture forms of Trypanosoma cruzi in experimentally contaminated food [in Spanish]. Bol Malariol Salud Ambient. 2008; 48: 91-9.
158. Cardoso AV, Lescano SA, Amato Neto V, Gakiya E, Santos SV. Survival Trypanosoma cruzi in sugar cane used to prepare juice. Rev Inst Med Trop São Paulo. 2006; 48: 287-9.
159. Barbosa-Labello R. Transmissão oral do Trypanosoma cruzi pela polpa de açaí em camundongos [PhD Thesis]. Campinas: Universidade Estadual de Campinas; 2021. Available from:
160. Barbosa RL, Pereira KS, Dias VL, Schmidt FL, Alves DP, Guaraldo AMA, et al. Virulence of Trypanosoma cruzi in açai (Euterpe oleraceae martius) pulp following mild heat treatment. J Food Prot. 2016; 79(10): 1807-12.
161. Oliveira AC, Soccol VT, Rogeza H. Prevention methods of foodborne Chagas disease: disinfection, heat treatment and quality control by RT-PCR. Int J Food Microbiol. 2019; 301: 34-40.
162. Ferreira RTB, Cabral ML, Martins RS, Araujo PF, Silva SA, Britto C, et al. Detection and genotyping of Trypanosoma cruzi from açai products commercialized in Rio de Janeiro and Pará, Brazil. Parasit Vectors. 2018; 11(1): 233.
163. Mattos EC, Meira-Strejevitch CDS, Marciano MAM, Faccini CC, Lourenço AM, Pereira-Chioccola VL. Molecular detection of Trypanosoma cruzi in açaí pulp and sugarcane juice. Acta Trop. 2017; 176: 311-5.
164. Godoi PAS, Piechnik CA, de Oliveira AC, Sfeir MZ, de Souza EM, Rogez H, et al. qPCR for the detection of foodborne Trypanosoma cruzi. Parasitol Int. 2017; 66(5): 563-6.
165. ANVISA - Agência Nacional de Vigilância Sanitária. Regulamento técnico de avaliação de matérias macroscópicas e microscópicas prejudiciais à saúde humana em alimentos embalados (RDC 175, 08 Jul 2003). Available from: http://www. Accessed 22 Jan 2018.
166. ANVISA - Agência Nacional de Vigilância Sanitária. Regulamento técnico de procedimento higiênico sanitários para manipulação de alimentos e bebidas preparados com vegetais (RDC 218, 29 Jul 2005). Available from: http://portalanvisagovbr/ documents/33916/388704/RDC_218pdf Acessed 22 Jan 2018.
167. DOEPA - Diário Oficial do Estado do Pará. [homepage on the Internet]. 2018 [updated cited 2012 Sep 20]. Decreto no. 326 de 20/01/2012. Available from:
168. Fregonesi BM, Yokosawa CE, Okada IA, Massafera G, Braga Costa TM, Prado SPT. Polpa de açaí congelada: características nutricionais, físico-químicas, microscópicas e avaliação da rotulagem. Rev Inst Adolfo Lutz. 2010; 69(3): 387-95.
169. Pereira JMATK, Oliveira KAM, Soares NFF, Gonçalves MPJC, Pinto CLO, Fontes EAF. Avaliação da qualidade físico-química, microbiológica e microscópica de polpas de frutas congeladas comercializadas na cidade de Viçosa - MG. Alim Nutr Araraquara. 2006; 17(4): 437-42.
170. Freitas B, Bento FS, Santos FQ, Figueiredo M, América P, Marçal P. Características físico-químicas, bromatológicas, microbiológicas e microscópicas de polpa de açaí (Euterpe oleraceae) congeladas do tipo B. J Appl Pharm Sci. 2015; 2(2): 2-13.

Financial support: FAPESP (2012/50273-0).
+ Corresponding author:
Received 02 February 2021
Accepted 08 February 2021

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program


fiocruz governo
faperj cnpq capes