Diagnosis of tuberculosis in non-human primates through intradermal
testing in wildlife centers in the city of Guayaquil, Ecuador
Published Instituto
Superior Tecnológico Edwards Deming. Quito - Ecuador Periodicity January - March Vol. 1, Num. 24, 2025 pp. 27-41 http://centrosuragraria.com/index.php/revista Dates of receipt Received: July 22, 2024 Approved: November 10, 2024 Correspondence author jose.echeverria05@cu.ucsg.edu.ec
Creative Commons License Creative Commons License, Attribution-NonCommercial-ShareAlike
4.0 International.https://creativecommons.org/licenses/by-nc-sa/4.0/deed.es
José Alberto Echeverría Alcívar1
Thara Carolina Cango Rivadeneira2
Melissa Joseth Carvajal Capa3
Fabiola Lissette Jiménez Valenzuela4
Irina Trejo Cedeño5
1 Ingeniero en Medicina Veterinaria, Universidad Católica
Santiago de Guayaquil, jose.echeverria05@cu.ucsg.edu.ec, https://orcid.org/0009-0007-8319-5091 2 Ingeniera en Medicina Veterinaria, thara_carol@hotmail.com,
https://orcid.org/0000-0002-6814-0822 3 Ingeniera
en Medicina Veterinaria, Universidad Católica Santiago de Guayaquil, melissa.carvajal01@cu.ucsg.edu.ec, https://orcid.org/0009-0001-5343-9506 4 Ingeniera
en Medicina Veterinaria, Universidad Católica Santiago de Guayaquil, Fabiola.jimenez01@cu.ucsg.edu.ec, https://orcid.org/0009-0004-1521-7437 5 Ingeniera en Medicina Veterinaria, Universidad Católica
Santiago de Guayaquil, Irina.trejo@cu.ucsg.edu.ec, https://orcid.org/0000-0003-0295-4273
Keywords: Tuberculosis,
non-human primates, Diagnosis, Intradermal Tests, Wildlife.
Resumen: La tuberculosis es una enfermedad zoonótica de
peligro para la salud pública. Los primates no humanos son un grupo
susceptible, siendo el objetivo de la presente investigación el determinar
casos positivos a tuberculosis y correlacionar los factores de riesgo con los
grados de reacción presentados. La tuberculina intradérmica fue la prueba a
elección en el presente estudio, orientado bajo una intención experimental, de
enfoque cuantitativo, de tipo aplicado. Se examinó la población total de
primates no humanos en condiciones de cautiverio en dos Centros de Rescate de
Animales Silvestres en la Ciudad de Guayaquil, inoculando a 13 especímenes con
0.1 ml de Tuberculina PPD Bovina intradérmica en el párpado derecho.
Posteriormente, se evaluó los grados de reacción postinoculación, bajo un
criterio de 0 a 5 durante las 24, 48 y 72 horas. Resultando 0 % de casos
positivos detectados, con reacción grado 1 en dos primates, atribuyendo la
reacción según el historial clínico, al estrecho contacto humano- animal como
posible factor de riesgo. Concluyendo así que no hay diferencia entre los
factores de riesgo respecto a las reacciones que presentaron los primates, sin
embargo, si hay diferencia en la cantidad de reacciones en relación con los
primates registrados.
Palabras
clave: Tuberculosis, primates no
humanos, Diagnóstico, Pruebas Intradérmicas, Fauna Silvestre
Introduction
Tuberculosis is a zoonotic disease with a high epidemiological risk
because it is one of the infections with the highest mortality rate in the world.
In the year 2022, it is estimated that 1.3 million people died from
tuberculosis worldwide (WHO, 2023). A member of the Mycobacterium group is the
cause of this disease that affects humans and a wide variety of animals, both
domestic and wild, and it is this human-animal relationship that increases the
risk of spreading tuberculosis.
In Ecuador, 6 094 cases of susceptible tuberculosis were registered in 2018,
with an incidence rate of 34.53 per 100 000 inhabitants. The province of Guayas
experienced the highest concurrence, with 3 354 cases, representing 55.03 % of
the total (Ministry of Public Health, 2018). To this is added, poor management
in treatment and drug resistance, which do not allow the success of
tuberculosis control programs (Trivedi et al., 2012, Howie et al., 2021).
In the group of wild animals, non-human primates have been a point of interest
in studies of zoonotic diseases, because they are intermediate hosts and
reservoirs of a variety of infectious agents. The risk of infection of non-human
primates with tuberculosis increases when in contact with humans and domestic
animals, since the habitat of this primate species is located in countries with
the highest rates of this disease in the world. However, cases have been
reported in captive species, with zoos being a point of exposure between wild
species and humans (Namasivayam et al., 2019).
Currently, accurate diagnosis of tuberculosis in non-human primate colonies
remains a challenge. The tuberculin skin test is known as the standard screening
tool for the diagnosis of tuberculosis infection (Bonovska et al., 2005; Gong
et al., 2017). Despite the questioning in its results due to false positives or
false negatives, it is still a very good diagnostic validity tool (Bonovska et
al., 2005; Gong et al., 2017). Of the 21 existing species of primates in the
country (Ministry of Environment, 2019), there were no data on the evaluation
of the presence of tuberculosis in these animals, under this lack of
information the results presented in this article, fulfills the function of
keeping a record of control of cases of the disease in this species.
Tuberculinization method in non-human primates
The tuberculin test in primates is based on the use of bovine PPD. This is
produced from PPD (Purified Protein Derivative), made from filtered protein
extracts of Mycobacterium bovis. A dose of 0.1 ml is administered by
intradermal injection in the eyelid of the animal, with a concentration of
20,000 IU/ml of bovine PPD (Proaño-Pérez et al., 2006).
To perform the test, it is recommended to depilate the area of 5 to 6 cm2 and
preferably that the same professional who performed the tests is the one who
maintains an adequate follow-up of the symptoms through touch, observation and
measurement of the induration in the following 24, 48 and 72 hours (Cely et
al., 2011).
To consider whether the animal is positive to the tuberculin test, the size of
the protrusion formed must be equal or greater than 5 mm. If the animal is
positive, it should be isolated and the result confirmed, since the test
performed is only considered as a recognition test (Albornoz Villacrés, 2012).
Metodología
The present methodology was oriented by an experimental intention, of
applied type, whose objectives are descriptive and using experimental
variables, in a diachronic exercise considering that the species are under
observation, so the environment is controlled in a laboratory of the wildlife
center of Guayaquil, Ecuador, taking as reference what the author Von Pirquet
proposes, on the diagnosis of tuberculosis, thus our scopes in this research
were quantitative as we sought to identify the relevance of the test and in
this way the method that was followed maintained an inductive logic. In the
last reviews of non-human primates, it was empirically observed through the
recording of their behaviors that these species have greater possibilities of
contracting tuberculosis derived from these behaviors, so the detection of
tuberculosis is fundamental to ensure their health within the Fauna Centers in
question. Based on the above, the methodological approach is to test the
recommendations made by Nagar et al (2006) on the correct way to diagnose the
pathology and thus prevent contagion. In this sense, the approach followed was
oriented by methodological inputs that allowed assuring a rigorous traceability
route on the environmental conditions that promote non-human primates to
contract Tuberculosis and the way in which the intradermal test is effective
for its detection.
The research was developed with the total population of non-human primates in
captivity conditions in two Wild Animal Rescue Centers in the city of Guayaquil,
Fundación Proyecto Sasha and Narayana, inoculating each specimen with 0.1 ml of
Bovine PPD Tuberculin intradermally in the right eyelid. Subsequently, the
local palpebral reaction was evaluated at 24, 48 and 72 hours, according to the
assessment criteria in Table 1.
Table 1. Intradermal
tuberculin: palpebral assessment
|
Grado |
Reaction |
|
0 |
No reaction (SR) |
|
1 |
Hematoma-extravasation
of blood in the eyelid (H) |
|
2 |
Varying
degrees of palpebral erythema (E) |
|
3 |
Moderate
swelling with or without erythema (TM) |
|
4 |
Evident
eyelid swelling with drooping and with or without erythema (TM) |
|
5 |
Palpebral
necrosis, variable degrees of swelling and partial or complete closure of the
eyelid (NP). |
Fuente: WOAH (2022)
Based on the above criteria, the interpretation determines that grades 1
and 2 are considered as negative, grade 3 as inconclusive and grades 4 and 5
are interpreted as positive.
Resultados
The results obtained through the inoculation of Intradermal Bovine PPD Tuberculin
in this study showed that of the 13 non-human primates evaluated, 100% were
negative to the test. In Table 2, it can be observed that, between the months
of November to December of 2023 and January of 2023, the results were negative.
December 2023 and January 2024, a total population of 13 non-human
primates were studied, of which 7 belonged to the Sacha Project Foundation and
6 to Narayana. According to their species, they were grouped into: Saguinus
fuscicollis (8 % 1/13), Cebus aequatorialis (46 % 6/13), Sapajus apella (15 %
2/13), Saimiri cassiquiarensis (8 % 1/13), Alouatta palliata (15 % 2/13) and
Ateles geoffroyi (8 % 1/13).
Table 2 Distribution of
non-human primates according to species, sex and age in relation to the
wildlife center
|
|
|
Fundación Proyecto Sacha |
Narayana |
TOTAL |
FR |
|
Especies |
Saguinus fuscicollis |
1 |
0 |
1 |
8% |
|
Cebus aequatorialis |
2 |
4 |
6 |
46% |
|
|
Sapajus apella |
1 |
1 |
2 |
15% |
|
|
Saimiri cassiquiarensis |
1 |
0 |
1 |
8% |
|
|
Alouatta palliata |
2 |
0 |
2 |
15% |
|
|
Ateles geoffroyi |
0 |
1 |
1 |
8% |
|
|
Especímenes |
7 |
6 |
13 |
100% |
|
|
Sexo |
Hembras |
3 |
1 |
4 |
31% |
|
Machos |
4 |
5 |
9 |
69% |
|
|
Edad |
Juvenil |
5 |
1 |
6 |
46% |
|
Adulto |
2 |
4 |
6 |
46% |
|
|
Geronte |
0 |
1 |
1 |
8% |
The
postinoculation evaluations carried out at the first 24, 48 and 72 hours,
determined 100% of the population as negative, presenting 2 individuals with
grade 1 reaction corresponding to the presentation of hematoma or blood
extravasation in the eyelid, which is detailed in Table 3. Likewise,
information corresponding to each wildlife center regarding the origin, habitat
and health plan of each of the non-human primates evaluated, in order to
identify the possible risk factors that could influence or not the diagnosis of
tuberculosis.
Table 3 Results of
tuberculinization during 24, 48 and 72h in relation to risk factors.
|
|
|
R24H+ |
R24H- |
R48H+ |
R48H- |
R72H+ |
R72H- |
TOTAL R+ |
|
Centro |
Proyecto Sacha |
2 |
5 |
1 |
6 |
0 |
7 |
3 |
|
Narayana |
0 |
6 |
0 |
6 |
0 |
6 |
0 |
|
|
Lugar de origen |
Naranjal |
0 |
2 |
0 |
2 |
0 |
2 |
0 |
|
Milagro |
1 |
2 |
1 |
2 |
0 |
3 |
2 |
|
|
Bucay |
0 |
1 |
0 |
1 |
0 |
1 |
0 |
|
|
Cañar |
1 |
0 |
0 |
1 |
0 |
1 |
1 |
|
|
Sin registro |
0 |
5 |
0 |
5 |
0 |
5 |
0 |
|
|
Nacido en el centro |
0 |
1 |
0 |
1 |
0 |
1 |
0 |
|
|
Comparte jaula |
Si |
2 |
6 |
1 |
7 |
0 |
8 |
3 |
|
No |
0 |
5 |
0 |
5 |
0 |
5 |
0 |
|
|
Contacto con Humanos |
Si |
2 |
11 |
1 |
12 |
0 |
13 |
3 |
|
No |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Contacto con otras especies |
Si |
2 |
11 |
1 |
12 |
0 |
13 |
3 |
|
No |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Cuarentena |
Si |
2 |
11 |
1 |
12 |
0 |
13 |
3 |
|
No |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Vacuna |
Si |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
No |
2 |
11 |
1 |
12 |
0 |
13 |
3 |
R(n)H+: If it presented reaction at n (24, 48 or 72) hours.
R(n)H-: No reaction at n (24, 48 or 72) hours.
According to the records in the table, in relation to the place of origin,
there were 3 grade 1 reactions, 2/3 (67%) correspond to a primate from the
Milagro canton during the first 24 and 48 hours respectively and 1/3 (33%)
reactions during the first 24 hours in a primate from the province of Cañar.
When relating the grades with the presence or absence of cage companions, it
was obtained that the 3 (100 %) reactions registered during the first 24h and
48h after tuberculinization in 2/13 primates were living in cages shared with
primates of the same species.
To evaluate the habitat from the shared cage variable, 8 shared (62 %) cages
with the same species, while 5 (38 %) did not. Relating this data with the
degree of reaction, it was determined that the 3 (100 %) reactions registered
during the first 24h and 48h later, in 2/13 primates were living in cages
shared with primates of the same species.
Regarding the people who come in direct contact with the primates
studied, either for feeding, cleaning, medical attention or cage maintenance.
It was obtained as a result that the first group of primates 5/13 (38 %)
registered approximately a number of 10 people who had direct contact with
them, the second group 2/13 (15 %) had direct contact with approximately 5
people daily and the third group that were 6/13 (46 %) had contact with 3
people. When establishing a relationship between the degrees of reaction
presented, it is established that 3/3 registered reactions (100%) were
reflected in primates that were in daily contact with more than 10 persons per
day.
When analyzing whether the primates studied were close to other species
in relation to their cages, 6/13 (46%) were close to birds and goats, 2/13
(15%) were close to birds, felines and canines, and 5/13 (38%) were close to
birds, reptiles and canines, i.e. 100% were close to other species.
Regarding sanitary management, all individuals (100 %) registered having
been subjected to quarantine during the first days prior to their introduction
in each center; however, no primate (0 %) was vaccinated as a prevention method
for tuberculosis.
Table 4 shows the analysis of variance to establish the correlation
between the degrees of reaction and the risk factors, obtaining the following
results.
Table 4 Summary of mean and variance between risk factors and reactions to the
intradermal tuberculin test.
|
RESUMEN |
Cuenta |
Suma |
Promedio |
Varianza |
|
Contacto con humanos |
2 |
13 |
6,5 |
40,5 |
|
Comparte jaula |
2 |
13 |
6,5 |
40,5 |
|
Vacuna |
2 |
13 |
6,5 |
84,5 |
|
Cuarentena |
2 |
13 |
6,5 |
40,5 |
|
Reaccionó |
4 |
6 |
1,5 |
1 |
|
No reaccionó |
4 |
46 |
11,5 |
1 |
Table 5 Analysis of variance
between risk factors and intradermal tuberculin test reactions.
|
ANÁLISIS DE VARIANZA |
||||||
|
Origen de las variaciones |
Suma de cuadrados |
Grados de libertad |
Promedio de los cuadrados |
F |
Probabilidad |
Valor crítico para F |
|
Filas |
0 |
3 |
0 |
0 |
1 |
9,27662815 |
|
Columnas |
200 |
1 |
200 |
100 |
0,0021284 |
10,1279645 |
|
Error |
6 |
3 |
2 |
|
||
|
|
|
|||||
|
Total |
206 |
7 |
|
|
|
|
A p value of 1 (> 0.05) was obtained, so the null hypothesis is
accepted, that is, there is no difference between the risk factors with respect
to the reactions presented by the primates, however, a second p value of 0.002
(< 0.05) was obtained, so it is deduced that there is a difference in the
number of reactions in relation to the registered primates (Table 5).
At present, there are not enough studies in Ecuador to evaluate the situation
of tuberculosis in wildlife and therefore in non-human primates. The data
obtained in the present investigation generate new information regarding the
disease, obtaining 0 % of positive cases for tuberculosis in the primates under
study. However, in the research of Albornoz (2012), he detected the presence in
2 out of 25 primates, carried out in the Guayabamba Zoo in Quito, reflecting 12
% of positivity for tuberculosis by means of the tuberculin test. There are
studies in Colombia, carried out by Estrada (2011) where the same technique was
used, under the same parameters, obtaining the same results, 0 % of positive
cases. It is important to note that each data is added to give a reference of
the status of the primates and the current condition regarding the presence of
tuberculosis. In a study conducted by Obaldía, et al. (2018) reported an
outbreak of tuberculosis in a colony of Aotus primates in Panama, using
antibody release tests and gamma interferon for diagnosis. In their
epidemiological analysis, they confirmed that the outbreak was the result of
exposure to the disease, ensuring that humans were the most likely source of
transmission, a conclusion that supports the results of the present study that
identified direct human-nonhuman primate contact as the main risk factor in the
wildlife centers evaluated.
Currently, accurate diagnosis of tuberculosis in nonhuman primates
remains a challenge and infection can often go undetected. The Intradermal
Tuberculin test is considered the standard tool for the diagnosis of
tuberculosis. However, it is often questioned due to false positive or negative
results (Bonovska et al., 2005; Gong et al., 2017). The possible alteration in
the response to the Tuberculin test as a result of mishandling has been ruled
out in this research because the reagent used, has already been tested in
cattle. However, in this study it is suggested to reevaluate the cases of
primates that registered reactions using serological, radiographic,
pathological, microbiological and cytological tests, due to the high risk of
transmission of the disease, which could easily spread in relation to the
origin of these animals, management of their habitat, feeding and proximity to
humans and other species within the wildlife centers.
Conclusiones
In the present study, 0% of positive cases of tuberculosis were detected
in the population of non-human primates in captivity in the two wildlife
centers of the city of Guayaquil, of the species Saguinus fuscicollis, Cebus
aequatorialis, Sapajus apella, Saimiri cassiquiarensis, Alouatta Palliata and
Ateles geoffroyi, by intradermal test with inoculation of Bovine PPD
Tuberculin. However, there was a grade 1 postinoculation reaction in two
primates of the study during the first 24 and 48 hours, considering this
reaction as negative to tuberculosis, attributing the reaction to contact with
infected humans or animals, basing this criterion on the results obtained. In
addition, a p value of 1 (> 0.05) was obtained, so it is concluded that
there is no difference between species with respect to the degree of reaction,
however, there is a difference in the number of reactions with the primates in
the study. The exposed results contribute significantly to the monitoring of
wildlife animals, visualizing a current panorama of non-human primates in the
country and mainly contribute significantly to the control of tuberculosis, a
threatening disease for humans and animal species.
Referencias
Aranaz Martín,
Alicia., Domínguez Rodríguez, L., Mateos García, A., Suárez Fernández, G.,
& animal), U. C. de M. F. de V. D. P. A. I. (Sanidad. (2002). Aplicación
de la técnica de PCR (Reacción en cadena de la polimerasa) en el diagnóstico y
epidemiología de la tuberculosis en animales. Universidad Complutense de
Madrid, Servicio de Publicaciones. http://hdl.handle.net/20.500.14352/63036
Azé, J., Sola,
C., Zhang, J., Lafosse-Marin, F., Yasmin, M., Siddiqui, R., Kremer, K., van
Soolingen, D., & Refrégier, G. (2015). Genomics and Machine Learning for Taxonomy
Consensus: The Mycobacterium tuberculosis Complex Paradigm. PLOS ONE, 10(7),
e0130912. https://doi.org/10.1371/journal.pone.0130912
Bonovska, M.,
Tzvetkov, Y., Najdenski, H., & Bachvarova, Y. (2005). PCR for Detection of
Mycobacterium tuberculosis in Experimentally Infected Dogs. Journal of
Veterinary Medicine, Series B, 52(4), 165–170. https://doi.org/10.1111/j.1439-0450.2005.00839.x
Bucsan, A. N., Mehra,
S., Khader, S. A., & Kaushal, D. (2019). The current state of animal
models and genomic approaches towards identifying and validating molecular
determinants of Mycobacterium tuberculosis infection and tuberculosis disease.
Pathogens and Disease, 77(4). https://doi.org/10.1093/femspd/ftz037
Capuano, S. V.,
Croix, D. A., Pawar, S., Zinovik, A., Myers, A., Lin, P. L., Bissel, S.,
Fuhrman, C., Klein, E., & Flynn, J. L. (2003). Experimental Mycobacterium
tuberculosis Infection of Cynomolgus Macaques Closely Resembles the Various
Manifestations of Human M. tuberculosis Infection. Infection and Immunity,
71(10), 5831–5844. https://doi.org/10.1128/IAI.71.10.5831-5844.2003
Cardona, P. J.
(2018). Pathogenesis of tuberculosis and other mycobacteriosis. Enfermedades Infecciosas y
Microbiologia Clinica, 36(1), 38–46. https://doi.org/10.1016/j.eimc.2017.10.015
Cely, G. E. E.,
Valencia-Aguirre, S., & Lugo, W. O. V. (2011). Prevalencia de tuberculosis
en primates en cautiverio. CES Medicina Veterinaria y Zootecnia, 6(2), 62–72. https://revistas.ces.edu.co/index.php/mvz/article/view/2057
Churchyard, G., Kim,
P., Shah, N. S., Rustomjee, R., Gandhi, N., Mathema, B., Dowdy, D., Kasmar,
A., & Cardenas, V. (2017). What We Know About Tuberculosis Transmission:
An Overview. The Journal of Infectious Diseases, 216(suppl_6), S629–S635. https://doi.org/10.1093/infdis/jix362
De la Torre, S.
(2010). Los primates ecuatorianos, estudios y perspectivas. ACI Avances En
Ciencias e Ingenierías, 2(2). https://doi.org/10.18272/aci.v2i2.30
De Waard, J. H.
(2005). Tuberculosis bovina. Manual de Ganaderia Doble Propósito.
Gonzalez-Stagnaro E. Soto-Belloso (Eds.). Maracaibo Venezuela: Ediciones Astro
Data SA.
Foreman, T. W.,
Mehra, S., Lackner, A. A., & Kaushal, D. (2018). Translational Research in
the Nonhuman Primate Model of Tuberculosis. ILAR Journal, 58(2), 151–159. https://doi.org/10.1093/ilar/ilx015
Gong, W. P., Yang, Y.
R., Luo, Y., Li, N., Bai, X. J., Liu, Y. P., Zhang, J. X., Chen, M., Zhang, C.
L., & Wu, X. Q. (2017). Alerta por infección por Mycobacterium tuberculosis de macacos rhesus
en un zoológico salvaje de China. Experimental Animals , 66(4), 357–365.
https://doi:
10.1538/expanim.16-0095.
Howie, S. R. C.,
Ebruke, B. E., McLellan, J. L., Deloria Knoll, M., Dione, M. M., Feikin, D.
R., Haddix, M., Hammitt, L. L., Machuka, E. M., Murdoch, D. R., O’Brien, K.
L., Ofordile, O., Olutunde, O. E., Parker, D., Prosperi, C., Salaudeen, R. A.,
Shamsul, A., Mackenzie, G., Antonio, M., & Zaman, S. M. A. (2021). The Etiology of Childhood Pneumonia
in The Gambia. Pediatric Infectious Disease Journal, 40(9S), S7–S17. https://doi.org/10.1097/INF.0000000000002766
Ministerio del
Ambiente. (2019). Protocolo para el censo y monitoreo de
primates y guacamayo verde de la Costa ecuatoriana https://www.ambiente.gob.ec/wp-content/uploads/downloads/2019/02/protocolo-Primates-y-guacamayos-09-08-18.pdf-
Ministerio de
Salud Pública. (2018). Boletín Anual Tuberculosis. https://www.salud.gob.ec/wp-content/uploads/2019/03/informe_anual_TB_2018UV.pdf
Nagar, R., Pande,
S., & Khopkar, U. (2006). Intradermal tests in dermatology-I: Tests for infectious diseases.
Indian Journal of Dermatology, Venereology and Leprology, 72(6), 461. https://doi.org/10.4103/0378-6323.29351
Namasivayam, S.,
Kauffman, K. D., McCulloch, J. A., Yuan, W., Thovarai, V., Mittereder, L. R.,
Trinchieri, G., Barber, D. L., & Sher, A. (2019). Correlation between
Disease Severity and the Intestinal Microbiome in Mycobacterium
tuberculosis-Infected Rhesus Macaques. MBio, 10(3). https://doi.org/10.1128/mBio.01018-19
Obaldía N, Nuñez
M, Montilla S, Otero W, Marin C. (2018). Tuberculosis (TB) outbreak in a closed Aotus
monkey breeding colony: Epidemiology, diagnosis and TB screening using
antibody and interferon-gamma release testing, Comparative Immunology,
Microbiology and Infectious Diseases https://doi.org/10.1016/j.cimid.2018.06.007
OMS. (2023,
November 23). Tuberculosis. Organización Mundial de La Salud. https://www.who.int/es/news-room/fact-sheets/detail/tuberculosis
Proaño-Pérez, F.,
Rigouts, L., Brandt, J., Dorny, P., Ron, J., Chavez, M.-A., Rodriguez, R.,
Fissette, K., Van Aerde, A., & Portaels, F. (2006). Preliminary observations on
Mycobacterium spp. in dairy cattle in Ecuador. The American Journal of
Tropical Medicine and Hygiene, 75(2), 318–323. https://doi.org/10.4269/ajtmh.2006.75.318
Trivedi, A., Singh,
N., Bhat, S. A., Gupta, P., & Kumar, A. (2012). Chapter 4 - Redox
Biology of
Tuberculosis Pathogenesis. In R. K. Poole (Ed.), Advances in Microbial
Physiology (Vol. 60, pp. 263–324). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-398264-3.00004-8
World Organisation
for Animal Health (WOAH). (2022). Manual Terrestre de la OIE 2022. Tuberculosis de los
Mamíferos (Infección por el Complejo Mycobacterium Tuberculosis) Capítulo 3
.1. 1 3. Obtenido de https://www.woah.org/fileadmin/Home/esp/Health_standards/tahm/3.01.13_Mammalian_tuberculosis.pdf