Predictors of <i>Trypanosoma cruzi</i> PCR positivity in patients with chronic Chagas disease

de Lima, Ana Carolina Bastos; Mendes, Veronica Gonçalves; Ferreira, Roberto Rodrigues; Nisimura, Lindice Mitie; Horita, Samuel Iwao Maia; Veloso, Henrique H; Costa, Andréa R; da Silva, Gilberto Marcelo S; Sangenis, Luiz Henrique C; Holanda, Marcelo T; Rimolo, Lorena; Cunha, Ademir B; Garzoni, Luciana Ribeiro; Hasslocher-Moreno, Alejandro Marcel; Mediano, Mauro Felippe F; Moreira, Otacílio da Cruz; Britto, Constança; Saraiva, Roberto M

doi:10.1590/0074-02760230115

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RESEARCH ARTICLE • Mem. Inst. Oswaldo Cruz 118 • 2023 • https://doi.org/10.1590/0074-02760230115 copy

Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease

Authorship SCIMAGO INSTITUTIONS RANKINGS

BACKGROUND

A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD).

OBJECTIVES

To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD.

METHODS

This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant.

FINDINGS

Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR.

MAIN CONCLUSIONS

Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Key words:
Chagas disease; Trypanosoma cruzi; clinical forms; biomarkers

Instituto Oswaldo Cruz, Ministério da Saúde Av. Brasil, 4365 - Pavilhão Mourisco, Manguinhos, 21040-900 Rio de Janeiro RJ Brazil, Tel.: (55 21) 2562-1222, Fax: (55 21) 2562 1220 - Rio de Janeiro - RJ - Brazil
E-mail: memorias@fiocruz.br

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[1] + Corresponding author: roberto.saraiva@ini.fiocruz.br

Variable
Chagas disease clinical forms
Indeterminate	92 (27.6)
Digestive	11 (3.3)
Cardiac	185 (55.5)
Stage A	71 (21.3)
Stage B	70 (21.0)
Stage C	38 (11.4)
Stage D	6 (1.8)
Cardiodigestive	45 (13.5)
Stage A	19 (5.7)
Stage B	19 (5.7)
Stage C	6 (1.8)
Stage D	1 (0.3)
Age, years	61.7 ± 10.4
Sex, men	188 (56.4)
Body mass index, kg/m²	27.3 ± 5.1
Arterial hypertension	228 (68.5)
Diabetes mellitus	76 (22.8)
Previous trypanocidal treatment	39 (11.7)
Self-reported skin colour
White	79 (23.7)
Black	45 (13.5)
Indigenous	10 (3.0)
Mixed-race	199 (59.8)
Electrocardiogram
RBBB	116 (34.8)
LBBB	14 (4.2)
LAHB	100 (30.0)
Primary T wave changes	102 (30.6)
Electric inactive areas	29 (8.7)
Low voltage	24 (7.2)
Cardiac device	44 (13.2)
2D echocardiogram
LA volume, ml/m²	34.0 ± 14.8
LVd, cm	5.5 ± 0.8
LVs, cm	3.6 ± 1.2
LV ejection fraction, %	58.4 ± 13.7
E/E’ ratio	10.4 ± 4.9
LV aneurysm	50 (13.8)
LV systolic function
Normal	248 (74.5)
Mild dysfunction	47 (14.1)
Moderate dysfunction	23 (6.9)
Severe dysfunction	15 (4.5)
LV diastolic dysfunction
Normal	98 (29.4)
Grade I	156 (46.8)
Grade II	46 (13.8)
Grade III	17 (5.1)
Non-classifiable	16 (4.8)
Medications
Carvedilol	87 (26.1)
ACE inhibitors	143 (42.9)
ARB	105 (31.5)
Digoxin	20 (6.0)
Spironolactone	42 (12.6)
Furosemide	49 (14.7)
Warfarin	43 (12.9)
Amiodarone	38 (11.4)
Metformin	66 (19.8)

Variable	OR	95% CI	p value	AUC (95% CI)
Cardiac form	1.37	0.85-2.22	0.19	0.53 (0.48-0.59)
Age, years	1.00	0.98-1.02	0.85	0.51 (0.45-0.56)
Sex, men	0.70	0.45-1.09	0.11	0.54 (0.49-0.60)
Body mass index, kg/m²	0.96	0.92-1.00	0.06	0.58 (0.52-0.63)
Hypertension	1.35	0.84-2.18	0.21	0.53 (0.48-0.59)
Diabetes mellitus	0.63	0.37-1.09	0.10	0.54 (0.48-0.59)
Previous trypanocidal treatment	0.14	0.05-0.40	<0.0001	0.57 (0.52-0.63)
Electrocardiogram
RBBB	1.65	1.05-2.61	0.03	0.56 (0.50-0.61)
LBBB	1.08	0.36-3.17	0.89	0.50 (0.45-0.56)
LAHB	1.11	0.69-1.79	0.65	0.51 (0.46-0.57)
Primary T wave changes	0.89	0.55-1.43	0.63	0.51 (0.46-0.57)
Electric inactive areas	1.60	0.74-3.43	0.23	0.51 (0.46-0.57)
Low voltage	1.23	0.53-2.83	0.63	0.51 (0.45-0.56)
Cardiac device	1.10	0.58-2.09	0.77	0.51 (0.45-0.56)
2D echocardiogram
LA volume, ml/m²	1.00	0.99-1.01	0.95	0.51 (0.45-0.56)
LVd, cm	0.89	0.68-1.18	0.43	0.52 (0.47-0.58)
LVs, cm	1.00	0.83-1.21	0.98	0.51 (0.45-0.56)
LV ejection fraction, %	1.00	0.98-1.01	0.81	0.53 (0.47-0.58)
E/E’ ratio	1.01	0.97-1.06	0.65	0.50 (0.45-0.56)
LV aneurysm	0.63	0.33-1.19	0.15	0.53 (0.47-0.58)
Biomarkers
BNP, ng/mL	1.00	0.99-1.00	0.62	0.50 (0.44-0.56)
Troponin I, ng/mL	0.16	0.01-9.58	0.17	0.54 (0.48-0.59)
TGF-β1, ng/mL	1.00	0.99-1.02	0.54	0.52 (0.46-0.58)
TNF, pg/mL	1.02	0.96-1.08	0.53	0.54 (0.48-0.60)
IL-6, pg/mL	1.02	0.98-1.07	0.30	0.50 (0.44-0.57)
IL-10, pg/mL	1.00	0.99-1.01	0.85	0.55 (0.49-0.61)
IL-17, pg/mL	1.01	0.98-1.05	0.51	0.53 (0.45-0.60)
MMP-2, ng/mL	1.00	0.95-1.05	0.96	0.51 (0.46-0.57)
MMP-9, ng/mL	1.05	0.99-1.11	0.12	0.55 (0.49-0.60)
MMP-2/MMP-9 ratio	1.01	0.98-1.03	0.58	0.55 (0.50-0.61)
TIMP-1, ng/mL	1.00	0.99-1.00	0.92	0.52 (0.44-0.60)
TIMP-4, ng/mL	1.00	0.99-1.00	0.67	0.51 (0.42-0.59)
Medications
Carvedilol	1.15	0.70-1.89	0.58	0.51 (0.46-0.57)
ACE inhibitors/ARB	1.49	0.89-2.49	0.12	0.54 (0.48-0.59)
Digoxin	0.95	0.38-2.39	0.91	0.50 (0.45-0.56)
Spironolactone	1.35	0.71-2.59	0.36	0.52 (0.46-0.57)
Furosemide	1.09	0.59-2.01	0.79	0.50 (0.45-0.56)
Warfarin	1.59	0.84-3.03	0.15	0.52 (0.47-0.58)
Amiodarone	1.89	0.96-3.75	0.065	0.53 (0.48-0.59)
Metformin	0.77	0.44-1.35	0.37	0.52 (0.46-0.57)

Variable	R²	p value
Age, years	0.00	0.79
Body mass index, kg/m²	0.00	0.80
2D echocardiogram
LA volume, ml/m²	0.00	0.78
LVd, cm	0.00	0.72
LVs, cm	0.00	0.51
LV ejection fraction, %	0.01	0.31
E/E’ ratio	0.01	0.22
Biomarkers
BNP, ng/mL	0.02	0.13
Troponin I, ng/mL	0.01	0.22
TGF-β1, ng/mL	0.00	0.96
TNF, pg/mL	0.01	0.31
IL-6, pg/mL	0.02	0.15
IL-10, pg/mL	0.02	0.15
IL-17, pg/mL	0.01	0.35
MMP-2, ng/mL	0.00	0.97
MMP-9, ng/mL	0.00	0.76
MMP-2/MMP-9 ratio	0.00	0.42
TIMP-1, ng/mL	0.01	0.32
TIMP-4, ng/mL	0.03	0.18

		Cardiac form
Variable	Indeterminate form n = 92	Stages A/B n = 179	Stages C/D n = 51
IL-6, pg/mL	2.5 (0.8-4.0)	3.2 (1.8-4.5)	3.6 (2.0-4.7)
IL-10, pg/mL	20.1 (16.2-23.1)	19.5 (9.4-23.0)	20.2 (18.3-22.8)
IL-17, pg/mL	5.0 (3.6-6.5)	5.7 (4.4-8.0)*	6.4 ± 3.0*
TIMP-1, ng/mL	0.39 ± 0.18	0.37 ± 0.16	0.41 ± 0.22
TIMP-4, ng/mL	0.62 ± 0.39	0.81 ± 0.47*	0.82 ± 0.64

Variable	OR	95% CI	p values
Diabetes mellitus	0.53	0.30-0.93	0.028
History of trypanocidal treatment	0.13	0.04-0.38	0.0002
RBBB	1.78	1.10-2.89	0.019