5 Reasons Why Your Business Needs Chagas Rapid Test？

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2. Standard methods and protocols for CD diagnosis

CD is marked by an acute and chronic phase, each with specific aspects that reflect the diagnostic methods of choice. Given that the onset of infection is characterized by a high parasitemia, the techniques related to direct parasite detection on peripheral blood by light microscopy comprise the gold standard for diagnosis during the acute stage, including in cases of congenital infection [18, 19]. Thus, the methods mainly applied are thin, thick, or fresh blood films. Alternatively, concentration methods, such as Strout and microhematocrit, may be employed [18, 19]. These protocols are especially indicated for the diagnosis of congenital infection and can be performed with either umbilical cord or venous blood from neonates and infants [20]. Polymerase chain reaction (PCR) can also be used, however, it should preferably be carried out within the first and third months of life [20]. In addition, serological follow-up is indicated for infected infants as well as for those with negative direct parasite detection with an infected mother. This analysis should be performed from the eighth month of life, when maternal IgG is no longer detected [20, 21].

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In contrast, the chronic phase features a subpatent parasite load. In this sense, indirect detection methods that rely on parasite amplification, such as hemoculture, xenodiagnosis, and PCR, may be performed [19]. However, these tests show low sensitivity at this stage, so that a negative result has poor conclusive value to discard infection [19]. As the end of the acute phase is accompanied by seroconversion, the chronic stage is characterized by a continuous production of IgG. Ergo, diagnosis of suspected cases of long-lasting infections is predominantly based on immunoassays. Nevertheless, there is no gold standard or reference test since none of the kits commercially available exhibit ideal performance regarding both sensitivity and specificity [19]. Consequently, at least two tests must be performed, so that infection is either confirmed or ruled out only if both assays present the same profile of reactivity (positive or negative, respectively) [18]. Hence, when inconclusive results are obtained, another test must be carried out [18]. The immunoassays applied must necessarily differ in terms of either detection principles or antigenic set and present complementary sensitivity and specificity [18]. Furthermore, in the absence of a biomarker for cure, conversion to non-reactive profile in subsequent tests in an interval of time has been considered a parameter to confirm the parasite elimination by trypanocidal treatment [22].

Although indirect hemagglutination (IHA) and indirect immunofluorescence (IIF) are frequently used, enzyme-linked immunosorbent assay (ELISA) is the most employed method, once (i) it is better suited for large-scale analysis and (ii) presents a considerable variety in terms of antigenic preparations [23]. In addition, chemiluminescent microparticle immunoassay (CMIA) and western are also recommended, the latter mainly employed as a confirmatory assay and/or discriminatory test in inconclusive cases [18, 19].

ELISA kits are produced with either (i) whole parasite extract, (ii) semi-purified fractions, (iii) recombinant proteins (full-length or chimeras), or (iv) synthetic peptides—the latter two being commonly used as multiplexed formulations. Alternatively, combining purified homogenate with recombinant proteins is employed as well [23]. This flexibility is a major advantage given that test reactivity may vary according to sample origin due to host genetic background and/or differences among parasite strains. As a matter of fact, T. cruzi presents a wide genetic variability, so that populations are classified into six groups named discrete typing units (DTU) TcI-VI and Tcbat [24], which exhibit different geographical prevalence [25, 26]. Moreover, the diversity of ELISA kits also covers the necessary arrangement of sensitivity and specificity complementation. In this regard, the implementation of recombinant proteins and synthetic peptide have shown to improve test accuracy by reducing cross-reactivity with other diseases, especially leishmaniasis [19].

Noteworthily, the protocol for the screening process in blood banks and prenatal care—as a health policy measure to reduce T. cruzi infection dissemination—rely on the application of a single immunoassay, which must present a high sensitivity. In this context, ELISA and CMIA are the main recommended methods [18]. Nonetheless, in case of a positive result, another test must be carried out to confirm the diagnosis.

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3. Applicability of rapids tests and its perspectives in CD context

Considering that those most affected by CD are from either remote areas or small towns with low resource in developing countries, the main immunoassays used for diagnosis and screening purposes do not meet the reality of local points of care, which commonly lack the needed infrastructure and the specialized personnel [27]. Furthermore, field studies are also hampered, as these tests are usually performed with plasma or serum obtained from venous blood extraction [28]. Thus, even if the assay is not carried out locally, transport of materials and equipment for sample adequate handling and storage are still required, as well as a trained team, which often translates in logistic complexity and, ultimately, in higher cost. More importantly, depending on the notification system applied, patient acknowledgment regarding their results is not safely guaranteed when the tests are performed latter on. Consequently, there is a patent demand for rapid tests [29], which have as basic concept a cheap and fast assay, with an easy development that ideally eliminates the necessity of specialized technicians, equipment, including in terms of sample manipulation, and cold storage, enabling their use on-site [30].

The World Health Organization and the Pan American Health Organization’s guidelines consider rapid tests as an alternative screening method for ELISA only in the context of seroepidemiological studies [18]. Their use is not recommended for clinical diagnosis or screening in hemotherapy services based on (i) the detection variation, (ii) the increased false negative rate (2–7 per ) in comparison to the association of two conventional serological methods for diagnosis of chronic patients and (iii) the cost-effectiveness, especially when there is a high demand, such as in blood banks [18].

Nonetheless, in , the Chagas National Program of Bolivia incorporated the use of a specific rapid test (Chagas Stat-Pak, Chembio Inc.) as the frontline method in both clinical practice and seroepidemiological surveys [31]. Notably, Chagas Stat-Pak (CSP) has shown sensitivity and specificity ranging from 93.4 to 100.0% and from 97.3 to 99.3%, respectively, among Bolivian municipalities [28, 31, 32, 33]. However, to follow the recommended diagnosis algorithm, positive cases still must be confirmed by a conventional immunoassay [31]. In this sense, studies have shown promising results regarding the synchronous combination of two rapid tests with different antigen composition as an alternative strategy for definitive diagnosis in low-resources settings in Bolivia, Argentina, and Colombia [28, 31, 34, 35, 36, 37]. The association of two rapid tests displayed ≥93.3% of diagnostic efficiency when using results obtained by at least two conventional immunoassays as reference [28, 31, 35, 36]. This alternative protocol has a great advantage in speeding up the process of patient continued medical assistance, especially regarding the offer of trypanocidal drugs and, eventually, other necessary treatments. In line with that, the combination of rapid testing with electrocardiogram (ECG) performed by a mobile device was also evaluated in Bolivia [38]. Interestingly, out of the 25 people with ECG abnormalities compatible with chagasic chronic cardiomyopathy, 22 (88%) presented a positive profile on the rapid test. As per the current protocol, the diagnosis of these patients was later confirmed by ELISA. ECG was carried out in a device connected to a smartphone and processed by a medically certified app; the exams were performed by non-physicians in a remote area, however, within 24 h the data were analyzed, and results were reported by cardiologists located overseas [38]. Taking into account the lack of clinical tools for patient’s progression monitoring toward symptomatic stage [22, 39, 40, 41], the incorporation of already known potential protein markers for such questions, especially those for early cardiac impairment [42, 43], in rapid test is an appealing and strategical approach to improve the assistance of individuals infected and should be addressed in the near future.

In view of congenital transmission, rapid testing has also been evaluated in Latin American pregnant women, mainly at the time of delivery [44, 45, 46, 47, 48]. This practice has a great impact on disease control when the mother was not tested during prenatal care, once trypanocidal efficacy is high and well tolerated by infants [20, 48]. Surprisingly, reported data indicates that a rapid test outperformed ELISA assays [45, 46]. Furthermore, aiming to investigate the recovery time of newborns infected congenitally and submitted to trypanocidal treatment 1 day after birth, Chippaux et al. [21] monitored periodically the level of specific anti-T. cruzi antibodies by ELISA; newborns without infection, but with an infected mother were included as control. From the eighth month, the authors carried out rapid testing in parallel to the conventional assay. At the ninth month, none of the patients showed immunoreactivity in the rapid test, while 12% remained testing positive by ELISA. Within the following 7 months, all of these patients presented antibodies titres below the ELISA cut-off [21]. This delayed seronegativity may be related to the extended set of antigens and/or the different epitopes components of the ELISA kit in comparison to the rapid test used. Moreover, anti-T. cruzi IgG originally from the mother was not detected in the mentioned control group since the fifth month despite the continued breastfeeding [21]. Conversely to the observed in infants, Jackson et al. [49] still detected reactivity in 2 ELISA assays and in the same rapid test when applying sera from adults of endemic regions after 3 years of treatment with nifurtimox.

Up on the released data reporting rapid tests performance on endemic population, a health center in Geneva, Switzerland, sought to study its feasibility regarding the screening of Latin American immigrants [50]. The majority of infected individuals was from Bolivia, and as a result of the rapid testing agreement with the conventional immunoassays and reproducibility, it was incorporated at the hospital as a point-of-care test in both the primary care center and the maternity ward (testing at delivery) [50]. In Italy, a different test has shown high specificity and was used as a third assay for evaluation of samples with discordant results [51], while in Spain, a rapid test was applied to screen co-infection in Latin Americans immigrants diagnosed with HIV [52].

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4. Performance of immunochromatographic rapid tests commercially available

As previously mentioned, parasite and/or host genetic background may be related to reactivity discrepancy. Thereby, it is strongly suggested that the rapid test is field validated in the area of interest before officially incorporating its use [31, 35]. This process should ideally be carried out at a national level by encompassing different sites [31], once circulating strains may vary from one region to another within the endemic countries [24, 25]. Thus, this topic is focused on the main marketed rapid tests with reported performance studies (Table 1).

Rapid testAntigenSampleVol. (μL)RT (min)SS (%)SP (%)Sample originRef.Chagas
Stat-Pak
(Chembio)B13, 1F8 and H49/JL7S or P
WB5
.4 to 100.097.3 to 99.3Bolivia[28, 31, 32, 33]100..0Colombia[35]97.1 to 100.094.8 to 99.9LATAM1[53, 54]87.2 to 96.093.2 to 99.9LATAM2[34, 50, 56]Trypanosoma
Detect
(InBios)ITC8.2S or P
WB10
.897.9LATAM1[62]89.6 to 92.994.0 to 100.0LATAM2[56, 64]Chagas Detect
Plus
(InBios)ITC8.2S or P
WB10
.2 to 100.087.1 to 99.3Bolivia[28, 31, 60]100.099.1Colombia[35]Simple Stick
Chagas
(Operon)Pep2, TcD, TcE and SAPAS.4 to 100.091.6 to 92.4LATAM2[67, 68]Simple Chagas
WB
(Operon)Pep2, TcD, TcE and SAPAS or P
WB10
NS.9 to 92.570.7 to 96.8LATAM2[56, 67, 70]SD Bioline Chagas Ab
(Standard Diognostics)1F8 and H49S, P or WB.6 to 100.093.8 to 97.7Argentina[36, 37]90.794LATAM2[56]WL Check
Chagas
(Wiener Lab)NSS, P or WB–.3 to 93.498.8 to 100Argentina[36, 37, 74]88.797LATAM2[56]OnSite Chagas
Ab Combo
(CTK Biotech)NSS or P
WB20
40–.1 to 95.591.0 to 96.9LATAM2[56, 68]Chagas Instantest
(Silanes)NSS or P–.679.0LATAM2[56]TR Chaga*
(Bio-Manguinhos)IBMP-8.1
IBMP-8.4S..0Brazil[75]

These assays are based on the detection of anti-T. cruzi antibodies circulating in the bloodstream upon recognition of recombinant proteins (Figure 1). In the absence of a gold standard immunoassay, conventional serology methods have been used as reference to evaluate rapid test performance (Table 2). Generally, the tests can be carried out with small volumes (5 to 100 μL) of either plasma, serum, or whole blood (Table 1). However, the latter comprises the best working sample type as it does not require further processing and, in the case of immediate testing, it may be obtained from fingertip puncture, perfect for the context of the field research. Moreover, the results are obtained within 10–35 min (Table 1).

Conventional immunoassayPrincipleAntigenRapid testRef.Bioelisa Chagas (Biokit)ELISATcD, TcE, Pep 2 and TcLo1.2CSP, SSC, OnSite, SCWB, SD Bioline[50, 57, 68, 69, 70, 73]Certest (BiosChile)ELISALysate (Tulahuén and Mn strains)SSC, OnSite[68]Chagas III (BiosChile)ELISAParasite lysateCSP, CDP, TD, TR Chagas[35, 62, 75]Chagas IgG + IgM I (Vircell)ELISAFRA, B13 and MACHaCSP, CDP, TD[35, 64]Chagas HAI-Immunoserum (TIIC)IHANSCSP[53]Chagas Polychaco (Lemos Lab.)IHANSCSP, CDP, TD, WL Check Chagas, SD Bioline[31, 32, 36, 60, 63, 65, 74]Chagatest v.2.0 (Wiener)ELISAParasite lysateCSP, TD, CDP[28, 31, 32, 33, 34, 60, 63]Chagatest v.3.0 (Wiener)ELISAPep 1, 2, 13, 30, 36, and SAPACSP, CDP, TD, SD Bioline[28, 31, 32, 33, 34, 44, 45, 46, 54, 60, 65, 66, 73]Chagatest (Wiener)IHAPep 1, 2, 13, 30, 36, and SAPASD Bioline[73]Chagatek (Lemos Lab.)ELISAPurified antigensCSP, CDP[28]Elecsys Chagas (Roche Diagnostics)E-CLIARecombinant proteinsTD[64]ELISA cruzi (bioMérieux)ELISAParasite lysateCSP, TD, SSC, OnSite[50, 62, 68]Gold ELISA Chagas (Rem Diag.)ELISARecombinant proteins and purified lysateTR Chagas[75]Hemagen Chagas (Hemagen Lab.)ELISAPurified antigensCSP, CDP, TD[34, 44, 66]IFI Chagas (Bio-Manguinhos)IFIStrain not specifiedTR Chagas[75]ID-PaGIA2 (DiaMed)GAAg2 and TcESSC, OnSite[68]ID-PaGIA3 (DiaMed)GAAg2, TcE and TcDSSC, OnSite[68]Ortho Trypanosoma cruzi (Ortho-Clinical Diag.)ELISAParasite lysateCDP, SSC, OnSite, SCWB[66, 68, 69]T. cruzi IgG (BLK Diag.)ELISAParasite lysateSSC, OnSite[68]—IIFParasite Tulahuén strainWL Check Chagas, SD Bioline[36]In-housebELISAParasite lysate (Y strain)CSP[53]ELISAParasite lysate (Peru strain)CSP[54]ELISAParasite lysate (H1 strain)CSP[46]ELISAParasite lysate (Tulahuén strain)TD, WL Check Chagas, SD Bioline[37, 62]ELISAParasite lysate (PM strain)TD[62]ELISAParasite lysate (Mc, T and Dm28 strains)SSC, OnSite, SCWB[67, 68]ELISAParasite lysateSCWB[69, 70]ELISAParasite lysate (MHOM/CO/06/338)SD Bioline[73]IIFParasite Y strainCSP[53]IIFParasite Colombian strainCSP, CDP[35]IIFNSCDP[60]IIFParasite
Tulahuén strainTD, WL Check Chagas, SD Bioline[62, 37, 74]IIFParasite
Mc, T and Dm28 strainSSC, OnSite, SCBW[67, 68]IHANS
(Tulahuén strain)TD[62]IHANS
(PM strain)TD[62]IHANSWL Check Chagas, SD Bioline[37]TESA-blotSecreted/excreted proteins (Y strain)CSP, CDP[34]Western blotParasite lysate (H1 strain)CSP[46]

CSP detection capability relies on the recognition of the recombinant antigens B13, 1F8, and H49/JL7 [53]. Notably, it has been trending as the most evaluated rapid test in both field and clinical seroprevalence studies, including in non-endemic countries. By using serum as testing sample, CSP has shown sensitivity ranging from 97.1 to 100.0%, and specificity from 94.8 to 99.9% among populations from South and Central Americas [53, 54]. Surprisingly, reactivity of samples from Midwest and Northeast regions of Brazil resulted in 98.5 and 94.8% of sensibility and specificity, respectively [53], even though the epitope B13 is derived from a 140 kDa protein detected in the surface of Y strain trypomastigotes [55], which belongs to one of the predominant DTUs in the respective area [24, 25]. Furthermore, sera from El-Salvador displayed the lowest sensitivity (97.1%) [53]. In a multicenter study carried out by Sánchez-Camargo et al. [56] with sera tested in national reference laboratories for Chagas disease diagnosis located in Brazil, Argentina, Colombia, Costa Rica, Mexico, United States of America, France, Spain, and Japan, the CSP exhibited 87.2 and 93.2% of sensibility and specificity, respectively [56]. On average, 50 samples (ca. of 25 positive and 25 negative) per region were analyzed, however, neither the origin of the donors sorted by each facility in non-endemic areas nor the correspondent data per country was discriminated. The reduced performance was accounted to sera selection, which comprised samples stored for averagely 2 years and with moderate to low reactivity profiling. The later aspect is of major importance, once one cannot rule out that methods used for sample reactivity classification could vary among the laboratories enrolled [56]. Curiously, this study also reported a lower sensitivity when using plasma in comparison to serum, while two other studies have demonstrated high level of agreement (99.7–100.0%) among different sample types (sera stored with or without 50% glycerol, plasma, whole blood and/or eluates from filter paper containing dried whole blood) [50, 53]. In this regard, CSP exhibited outstanding results (100.0% for both sensitivity and specificity) in whole blood testing in Colombia [35].

Interestingly, analysis of CSP in surveys of Latin Americans living in non-endemic countries showed a predominant seroprevalence in Bolivian immigrants [34, 50, 57]; sera testing presented low performance [34], while whole blood accused a sensibility and specificity of 95.2 and 99.9%, respectively, being 97.2% of the positive results from Bolivian origin [50]. By the time the CSP was implemented as a diagnostic tool by the Bolivian Ministry of Health, only one of the studies conducted so far had included samples from such region (n = 21) [53]. Therefore, since then, studies have been done to evaluate and field validate CSP performance in different Bolivian sites. Most of these works used whole blood for the CSP testing and either serum or plasma for conventional serological assays taken as reference. As previously mentioned, detection performance varied among municipalities, with sensibility and specificity ranging from 93.4 to 100.0% and from 97.3 to 99.3%, respectively [28, 31, 32, 33]. Noteworthily, lower sensitivities were obtained by Roddy et al. and Chippaux et al. when working with age groups ranging from 9 months to 17.9 years old (93.4%) and from 11 to 20 years old (89.2%), respectively [32, 33]. More worrisome, up to 7.6% of discrepancy between CSP and ELISA results was observed in women pregnant either at the moment or in the preceding 3 years at the time of the respective study [33]. Nevertheless, the same Chagatest v.3.0 (Wiener) failed to detect infection in 29.5% of women PCR-positive at delivery, while the overall CSP rate of false negative was 9.6% [45]. This research enrolled women from Argentina, Honduras, and Mexico, which displayed 97.3, 96.1, and 67.3% of CSP reactivity, respectively [45]. Although the detection in Mexican women was expressively reduced, CSP still outperformed the ELISA assay applied by 39.4% [45]. In a lower-prevalence scenario in Mexico, by taking western blot as confirmatory test, Gamboa-Léon et al. [46] demonstrated similar results between CSP and Chagatest v.3.0 (Wiener), especially in samples collected from umbilical cord.

Both the Trypanosoma Detect (TD) and Chagas Detect Plus (CDP) are based on the multiepitope recombinant protein ITC8.2 [58]. Produced by InBios, their main differences reside in product format and clearance by the U.S. Food and Drugs Administration agency. While TD is presented as a dipstick with application restricted to research [59], the CDP consists of an improved version [60], designed in cassette format—with the gold conjugate maintained in liquid solution—and is marketed for diagnostic use in the USA [60, 61].

TD evaluation in sera samples from Argentina, Ecuador, Mexico, and Venezuela resulted in 82.5, 84.3, 77.5, and 95.0% sensitivity, respectively. On the other hand, specificity was high, with the lower result detected in Ecuador (95.6%) and the greater in both Mexico and Venezuela (100.0%) [62]. In the work by Sánchez-Camargo et al. [56] previously mentioned, it presented an overall sensitivity and specificity of 92.9 and 94.0%, respectively. Similar sensitivity was observed in Bolivian women at delivery (92.7%), however, a higher specificity was shown (99.0%) [63]. In addition, regarding the same study performed with PCR-confirmed infected women with whole blood also collected at delivery in Argentina, Honduras and Mexico, TD testing resulted in more cases of seroreactivity in comparison to ELISA Wiener (v. 3.0) in samples from the latter two countries, while no difference was observed for those from Argentina [45]. Given that the ELISA kit used and the TD share 4 epitopes (peptides 1, 30, 36 and SAPA) between their sets of antigens [58], the TcF and Kmp-11 peptides included in the latter test may be related to the differential detection observed. Nonetheless, CSP still outperformed TD in both Honduras and Argentina [45]. In a survey of immigrants from endemic countries living in Spain that included an electrochemiluminescence immunoassay as reference, a lower sensitivity was obtained (89.6%) with whole blood, while excellent specificity was maintained (100.0%) [64]. Notably, such reference test (Elecsys Chagas, Roche Diagnostics) does not share any antigen with TD.

Aiming to increase sensitivity, the TD was modified, resulting in the CDP assay [60]. Its first performance evaluation was carried out with paired sets of whole blood and sera samples from Bolivian populations encompassing adults (with or without heart disease), pregnant women at delivery and children up to 17 years old. Tests results obtained with each type of sample displayed 90.3% of agreement, with whole blood showing a reduced sensitivity (96.2 vs. 99.3%) and higher specificity (98.8 vs. 96.9%) [60]. Following studies testing whole blood from individuals in different regions of Bolivia reported sensitivity of 92.1–100.0% and specificity of 87.1–99.3%, being the best results obtained in a high seroprevalence area [28, 31, 65]. In Colombia, CDP showed an outstanding performance with whole blood testing as CSP (≥ 99.1% for both parameters) [35]. Interestingly, reported data of Latin American CDP testing in the USA points to difference of performance between plasma and serum, with greater relevance for those from Mexico and Central America (mostly represented by El-Salvador) [34, 66]. More importantly, CDP showed superior sensitivity to samples from these same regions in comparison to three others conventional serological assays (two ELISAs and one IHA), whereas a lower specificity (87.5–92.3%) was observed in the overall analysis [66].

Simple Stick Chagas (SSC) and Simple Chagas WB (SCWB) also comprise rapid tests elaborated in two different formats that are based on the same antigen, a chimeric recombinant protein that englobes the peptide 2, TcD, TcE and SAPA epitopes [67] (Table 1). The former has a dipstick design and can be used with serum, while the latter is displayed as a cassette and can be carried out with either whole blood, plasma, or serum [67]. Studies that include these tests were mainly centered in evaluating their applicability as screening tool of Latin American immigrants and others with epidemiological background of risk living in Spain [67, 68, 69, 70]. Sera testing with SSC showed 92.4–100.0% of sensitivity and 97.9% of specificity, which is reduced to 91.6–92.4% when considering cross-reactivity [67, 68]. As for whole blood testing with SCWB, peripheral samples exhibited a 92.1 and 93.6% of sensitivity and specificity, respectively [67]. Interestingly, capillary samples obtained by finger prick displayed a performance of 86.4 and 95% for the respective parameters [67, 71]. In these works, the onsite results were confirmed latter on by conventional immunoassays carried out with samples collected and stored on filter paper [67, 71]. On the other hand, a 92.5% of sensitivity was observed by Chejade et al. [70] when working with capillary blood and confirmatory assays done with samples frozen until use. Poorer performance was observed by Sánchez-Camargo et al. [56] when testing sera with SCWB, which displayed an overall of sensitivity and specificity of 84.9% and 70.7%, respectively, and a variable response in the quality control evaluation among the laboratories. Authors also called attention to misguiding instructions in the manufacture datasheet, which reflected in the outcome. However, such errors were already corrected [72]. Finally, little to no cross-reactivity was observed for leishmania with SSC and SCWB, however, both assays showed relevant number of false-positives with samples from individuals infected with malaria [67, 68].

The SD Bioline Chagas Ab rapid test relies on the recognition of recombinant antigens H49 and 1F8 (Table 1). Although Sánchez-Camargo et al. [56] reported 90.4 and 94.0% of sensitivity and specificity, respectively, in Colombia, this assay presented a great potential value for diagnosis confirmation when using sera (100.0% specificity), but not as a screening tool [73]. Nonetheless, in Argentinean adult population, sera and whole blood testing presented satisfactory sensitivity (97.6–100%), whereas better specificity was achieved with the latter type of sample (93.8 vs. 97.7%) [36, 37]. WL Check Chagas (WLC) was used in parallel in both studies, which reported similar results [36, 37]. Adding up to other works, WLC is more suitable as a confirmatory test regardless of the type of sample used, especially in Argentina (≥ 98.8% of specificity) [36, 37, 56, 74].

Contact us to discuss your requirements of Chagas Rapid Test. Our experienced sales team can help you identify the options that best suit your needs.

Performance data of Chagas Instantest, OnSite Chagas Ab Combo, and TR Chagas is scarce, beginning with the antigenic formulations (Table 1). Except for the last one, all rapid tests were analyzed by Sánchez-Camargo et al. [56], which—for the best of our knowledge—consists of the only independent source of information for Chagas Instantest. This assay showed sensitivity of 76.6% along with a specificity of 79.0% [56]. A moderate agreement was detected between the obtained and expected results, besides a bad profile and reproducibility on the quality control evaluation [56]. Moreover, authors reported a high frequency of invalid tests and a strong background color, making a clearer interpretation difficult [56]. As for the OnSite Chagas Ab Combo, sera testing presented 90.1–95.5% of sensitivity and 91.0–96.9% of specificity and displayed cross-reactivity with samples from individuals with either leishmaniasis or malaria [56, 68]. At last, a prototype version of TR Chagas was evaluated in a small sampling group formed by sera from Brazilians (n = 32). In this context, densitometry analysis of bands signaling reactivity toward the chimeric recombinant proteins IBMP-8.1 and/or − 8.4 led to excellent results (100.0% for both parameters) [75]. Apart from the small quantity of samples tested, the study also portraits an analysis assessment opposite to reality in point-of-care settings and field study. In addition, there are no surveys done with the final formulation. Finally, we emphasize that TR Chagas is currently only at disposal of Brazilian Ministry of Health.

The T. cruzi parasites are mainly transmitted by the infected feces of blood-sucking triatomine bugs. These bugs typically found in the Americas, live in the cracks of poorly constructed homes in rural or suburban areas. Normally they hide during the day and become active at night when they feed on blood, including human blood. They usually bite an exposed area of skin or mucosa membranes (lips, conjunctiva, etc.), and the bug defecates close to the bite. The parasites enter the body when the person instinctively smears the bug feces into the bite, and contaminate the eyes, the mouth, or any lesion in the skin. 

Although less common T. cruzi can also be transmitted through blood transfusions (20% if the cases) or organ transplant, vertically from an infected mother to child during pregnancy or childbirth (1% of the cases), and by the accidental ingestion of food contaminated with T. cruzi.

Chagas disease has two clinical forms or phases: an acute phase and a chronic phase.  Many people (70- 80% of the infected) are asymptomatic all of their lives, while a 20-30% of the ones infected evolve into the chronic phase, which includes symptoms that indicate damages to the tissue of the heart, digestive system and/ or nerves system.

The acute phase, when it is symptomatic, lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood.

Signs and Symptoms for acute Chagas disease can be absent or mild and include the following:

• Signs of entry of the parasite
• Rash and inflammatory nodules (Chagoma)
• Swelling of periorbital soft tissue (Romaña's sign)
• Fever
• Headache
• Nausea, diarrhea or vomiting
• Enlarged lymph glands
• Difficulty breathing
• Muscle, abdominal or chest pain

Although not typical, a first visible sign can be a skin chancre, called 'chagoma', or a purplish swelling of the lids of one eye. If the infection is left untreated, it can advance into the chronic phase.

A first visible signal can be a skin lesion, called "inoculation chagoma" a regional subcutaneous nodule with adenitis at the site of the bite; and in cases of ocular inoculation, very typical but rare (2% o f acute symptomatic cases) is possible to identify the "sign of Romagna" bipalpebral edema, with retroauricular adenitis. If the infection is not treated, it can progress to the chronic phase.

Over several years or even decades, Chagas disease affects the central nervous system and the enteric nervous system, the digestion system and the heart.  Specific medical treatments and surgery may be necessary.

Signs and symptoms for chronic Chagas disease can include the following:

• About 30% of people will develop cardiac damage:
  • Cardiomyopathy
  • Heart rhythm abnormalities
  • Apical aneurysm.  
  • Sudden death or heart failure caused by progressive destruction of the heart muscle.
• Less than 10% of patients will experience enlargement of the gastrointestinal tract and organs, and gastrointestinal motor disorders.
• Enlargement of the esophagus.
• Enlargement of the colon.
• Disturbances of gastric emptying.
• Colon and gallbladder motor disorders.

Chagas disease may be etiologically treated in order to eliminate the infection T. cruzi with benznidazole or nifurtimox. If treatment was initiated during the acute phase, both drugs are effective in killing the parasite. 
Every infected child should be treated.

Nevertheless, the efficacy of both drugs diminishes the longer a person has been infected, although all patients including chronic cases benefit from improved clinicopathologic changes if treated.   Benznidazole and nifurtimox should not be taken by pregnant women.

The potential benefits of medication in chronic cases preventing or delaying the development of Chagas disease should be weighed against the long duration of treatment (up to 2 months), possible adverse reactions (occurring in up to 40% of treated patients), age, comorbidities, and other important characteristics of each patient.

The patients correctly diagnosed patients should receive further medical or surgical, pathophysiological or symptomatic, treatment, specific to each case.

Chagas disease is associated with multiple social and environmental factors that expose millions of people to infection.  Among the main risk factors for Chagas disease are living in poorly constructed housing - particularly in rural and suburban areas - having limited resources, residing in areas of poverty that are socially or economically unstable or have high rates of migration, and belonging to groups linked to seasonal farm work and crop harvests. This disease contributes and perpetuates the cycle of poverty, reduces learning capacity, productivity, and the ability to generate income.

In the early 's, the countries affected by Chagas disease, especially those where the disease was endemic, were organized to combat this public health threat. Along with the Pan American Health Organization/ World Health Organization, country representatives generated a successful scheme for horizontal technical cooperation between countries, called the Sub-regional Initiatives for Prevention and Control of Chagas Disease. These initiatives have been developed in the Southern Cone (), Central America (), Andean countries (), Amazonian Countries (), and Mexico (). These countries have contributed in creating substantial improvements in the situation through the interruption of vector transmission in all or part of the territory of the affected countries, the elimination of exotic species of vectors, the introduction of universal screening of blood donors, the detection of congenital cases, the reduction of prevalence in children, reduction in morbidity, expansion of access to diagnosis and treatment, and improvement of the quality of diagnosis, clinical care, and treatment of infected and ill persons.

The initiatives in the Americas have helped achieve significant reductions in the number of acute cases of disease and the presence of domiciliary triatomine vectors in endemic areas. The estimated number of people infected with T. cruzi worldwide dropped from 30 million in to 6 to 8 million in . In those 20 years, the annual incidence decreased from 700,000 to 28,000 new cases of infection and the burden of Chagas disease decreased from 2.8 million in  - to disability-adjusted life years lost to less than half a million years.

While substantial progress has been made, not all countries have managed to achieve the goals that have been proposed. New challenges have emerged such as the spread of disease due to the migration of people living in endemic countries to non-endemic countries, the need to ensure the sustainability of programs, confronting the emergence or re-emergence of cases of Chagas disease, recovering from natural disasters, expanding coverage of diagnosis and treatment, and achieving universal access to treatment.

Geographical distribution of Chagas disease in the Americas according to the status of transmission by the main vector in each area. Year: .

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