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Microorganisms causing vulvovaginitis: analysis of 1,688 cervicovaginal cytology

The vaginal microbiota is formed by several aerobic, anaerobic and facultative bacteria, being considered one of the most important defense mechanisms of the reproductive function, as it prevents the growth of pathogenic microorganisms (Resende et al., 2019RESENDE, A.F., SANTOS, R.W.F., GASPAR, L.M.A.C. and ALMEIDA, P.O.S., 2019. Prevalência de vaginoses bacterianas em pacientes que executaram bacterioscopia de força vaginal.Revista de Ciências Médicas e Biológicas, vol. 18, n. 2, pp. 190-193.http://dx.doi.org/10.9771/cmbio.v18i2.29698.
http://dx.doi.org/10.9771/cmbio.v18i2.29...
). The bacterial microbiota in the vagina of a healthy woman of reproductive age is dominated by lactobacilli (Wójkowska-Mach et al., 2021WÓJKOWSKA-MACH, J., POMORSKA-WESOLOWSKA, M., ROMANIK, M. and ROMANISZYN, D., 2021. Prevalence and antimicrobial susceptibility profiles of microorganisms associated with lower reproductive tract infections in women from Southern Poland: retrospective laboratory-based study. International Journal of Environmental Research and Public Health, vol. 18, no. 1, pp. 335. http://dx.doi.org/10.3390/ijerph18010335. PMid:33466345.
http://dx.doi.org/10.3390/ijerph18010335...
). Lactobacilli produce lactic acid as a result of the fermentation of carbohydrates, mainly glycogen, present in the vaginal epithelium of women at menarche. This acidic environment provides protection against infectious diseases by preventing the vaginal colonization of potential pathogens (Kalia et al., 2020KALIA, N., SINGH, J. and KAUR, M., 2020. Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review. Annals of Clinical Microbiology and Antimicrobials, vol. 19, no. 1, pp. 5. http://dx.doi.org/10.1186/s12941-020-0347-4. PMid:31992328.
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).

Among reproductive tract infections, vulvovaginitis and vaginosis stand out, processes in which the vaginal microbiota is altered, thus allowing the proliferation of other microorganisms and may be associated with an inflammatory process (vaginitis) or without any evidence of inflammation (vaginosis) (Linhares et al., 2018LINHARES, I.M., AMARAL, R.L., ROBIAL, R. and ELEUTÉRIO JUNIOR, J., 2018.Vaginites e vaginoses. São Paulo: FEBRASGO. Protocolo FEBRASGO - Ginecologia, no. 24. Comissão Nacional Especializada em Doenças Infectocontagiosas.). The entry of microorganisms into the female genital tract is influenced by several physical, behavior and physiological factors. Among the physical factors, we commonly have: sexual activity, number of sexual partners, phase of the menstrual cycle, immunity, age and the anatomical location of the female genital tract (Oliveira and Carneiro, 2020OLIVEIRA, J.A.G. and CARNEIRO, C.M., 2020. Fatores associados a alterações da microbiota no trato genital feminino inferior. Pensar Acadêmico, vol. 18, no. 2, pp. 289-299. http://dx.doi.org/10.21576/pa.2020v18i2.1707.
http://dx.doi.org/10.21576/pa.2020v18i2....
).

Vulvovaginitis or vaginosis are the most common causes of pathological vaginal discharge, and consequently are the most frequent causes of gynecological complaints. The most common pathogens are Gardnerella vaginalis, Candida sp. and Trichomonas vaginalis, the last two being the main etiological agents of vaginal candidiasis and trichomoniasis, respectively (Rodrigues et al., 2022RODRIGUES, H.J.C., SILVA, H.F.M., PEREIRA, L.S., CASTRO, G.J.B., SILVA, S.A.M., ARAÚJO, E.A., LOPES, D.A. and PINHO, J.D., 2022. Prevalence of vulvovaginite in women rural.Research, Social Development, vol. 11, no. 3, pp. e2611326192. http://dx.doi.org/10.33448/rsd-v11i3.26192.
http://dx.doi.org/10.33448/rsd-v11i3.261...
).

G. vaginalis is an anaerobic and immobile Gram-variable pleomorphic bacillus. It is a vaginal commensal commonly isolated in women of reproductive age, being the main organism responsible for bacterial vaginosis (Wong et al., 2022WONG, Y.P., CHEAH, F.C., WONG, K.K., SHAH, S.A., PHON, S.E., NG, B.K., LIM, P.S., KHONG, T.Y. and TAN, G.C., 2022. Gardnerella vaginalis infection in pregnancy: effects on placental development and neonatal outcomes. Placenta, vol. 120, pp. 79-87. http://dx.doi.org/10.1016/j.placenta.2022.02.018. PMid:35231793.
http://dx.doi.org/10.1016/j.placenta.202...
). It is currently present in 95-100% of cases of bacterial vaginosis, being the main cause of vaginal discharge complaints among women of reproductive age (Jesus et al., 2021JESUS, J.D.P., SANTOS, D.C., BASTOS, L.P., SOARES, A.N.G., BITTENCOURT, R.S. and FERREIRA, J.B., 2021. Gardnerella vaginalis infection: main age groups and inflammatory response mechanisms. Brazilian Journal of Health Review, vol. 4, no. 5, pp. 23162-23175. http://dx.doi.org/10.34119/bjhrv4n5-391.
http://dx.doi.org/10.34119/bjhrv4n5-391...
). It may be asymptomatic or present clinical symptoms such as grayish-white vaginal discharge with an unpleasant odor (Cruz et al., 2020CRUZ, G.S., BRITO, E.H.S., FREITAS, L.V. and MONTEIRO, F.P.M., 2020. Candidíase vulvovaginal na Atenção Primária à Saúde: diagnóstico e tratamento. Revista Enfermagem Atual In Derme, vol. 94, no. 32, pp. e-020074. http://dx.doi.org/10.31011/reaid-2020-v.94-n.32-art.735.
http://dx.doi.org/10.31011/reaid-2020-v....
). In the Pap smear test, G. vaginalis appears in the form of leucorrhea and cellular alterations of great diagnostic value called “guide cells” (Lopes et al., 2020LOPES, J.R., EICKSTAEDT, A.S., DIEFETHALER, V., ZANELLA, J.F.P., COSES, J. and FELIPPIN, T., 2020. Prevalência de Gardnerella vaginalis em esfregaços citopatológicos analisados no laboratório Escola de citopatologia da Unicruz. In: Anais do Seminário Interinstitucional de Ensino, Pesquisa e Extensão, 2020, Rio Grande do Sul, Brazil. Cruz Alta, Brazil: UNICRUZ, pp. 1-4.). Vulvovaginal candidiasis is an infection, in which about 70% of the female population will have at least one episode of the disease during their reproductive life, and is therefore considered the second leading cause of vaginitis (Cruz et al., 2020CRUZ, G.S., BRITO, E.H.S., FREITAS, L.V. and MONTEIRO, F.P.M., 2020. Candidíase vulvovaginal na Atenção Primária à Saúde: diagnóstico e tratamento. Revista Enfermagem Atual In Derme, vol. 94, no. 32, pp. e-020074. http://dx.doi.org/10.31011/reaid-2020-v.94-n.32-art.735.
http://dx.doi.org/10.31011/reaid-2020-v....
). Vaginal candidiasis is caused by the opportunistic yeast Candida sp., an agent that makes up the normal human microbiota, and which, depending on predisposing factors, grows excessively, causing imbalance in the vaginal microbiota. Candidiasis can be asymptomatic, but it usually causes redness, itching, pain, whitish and thick vaginal discharge and a burning sensation (Dutra et al., 2023DUTRA, A.M.G., CHIUCHETTA, G.I.R. and ECKER, A.B.S., 2023. Comparativo da incidência de Candida sp. E Gardnerella Mobiluncus em um laboratório privado de uma cidade da região noroeste do Paraná. Brazilian Journal of Development, vol. 9, no. 1, pp. 5649-5659. http://dx.doi.org/10.34117/bjdv9n1-385.
http://dx.doi.org/10.34117/bjdv9n1-385...
). In clinical practice, women diagnosed with candidiasis are those whose identification of Candida sp. Are an occasional finding in the routine examination (Pap smear test), or women who went to the office presenting the first symptoms and those who have a history of recurrent episodes of candidiasis (Cruz et al., 2020CRUZ, G.S., BRITO, E.H.S., FREITAS, L.V. and MONTEIRO, F.P.M., 2020. Candidíase vulvovaginal na Atenção Primária à Saúde: diagnóstico e tratamento. Revista Enfermagem Atual In Derme, vol. 94, no. 32, pp. e-020074. http://dx.doi.org/10.31011/reaid-2020-v.94-n.32-art.735.
http://dx.doi.org/10.31011/reaid-2020-v....
).

T. vaginalis is a flagellate protozoan, being the etiological agent of trichomoniasis, whose reservoir in women is the uterine cervix, vagina and urethra. T. vaginalis infection is a sexually transmitted infection (STI), with a non-viral characteristic, which is the most prevalent in the world (França et al., 2022FRANÇA, M.E.R., OLIVEIRA, M.L.G.L.S., FRANÇA, E.G.V.M., TAVARES, L.M., LUCENA, R.M., SOUZA, M.G.N., COSTA, A.B.L. and SLAUTA, M., 2022. Ações educativas de enfermagem: uma estratégia para promoção à saúde e prevenção de Trichomonas vaginalis. Brazilian Journal of Health Review, vol. 5, no. 5, pp. 21134-21145. http://dx.doi.org/10.34119/bjhrv5n5-265.
http://dx.doi.org/10.34119/bjhrv5n5-265...
). Trichomoniasis appears as an asymptomatic infection in 10-50% of cases. The most common symptoms are vaginal discharge with a foul odor and greenish-yellow colors, itching, dysuria and abdominal discomfort (Freitas et al., 2020FREITAS, L.F.Q., MAIA, L.R.S., DEUS, M.R.A.R., OLIVEIRA, S.R. and PERES, A.L., 2020. Prevalência de microrganismos em secreção vaginal de gestantes de alto risco de uma maternidade em Caruaru, Pernambuco, Brasil. Jornal Brasileiro de Patologia e Medicina Laboratorial, vol. 56. http://dx.doi.org/10.5935/1676-2444.20200048.
http://dx.doi.org/10.5935/1676-2444.2020...
). The most used method for diagnosis is fresh microscopy, in which the parasite is observed with pendulum movements (sensitivity of 51% to 65%). Microscopy with Gram staining also allows the identification of T. vaginalis, in this case, immobile (Linhares et al., 2018LINHARES, I.M., AMARAL, R.L., ROBIAL, R. and ELEUTÉRIO JUNIOR, J., 2018.Vaginites e vaginoses. São Paulo: FEBRASGO. Protocolo FEBRASGO - Ginecologia, no. 24. Comissão Nacional Especializada em Doenças Infectocontagiosas.).

Due to the high prevalence of these vaginal agents, and how important their complications are when undiagnosed, knowledge about the subject and awareness of the importance of performing routine cytological examinations is of great importance. The analysis was carried out through a descriptive retrospective, cross-sectional study with a quantitative approach in 1,688 cervicovaginal cytology exams in a Clinical Pathology Laboratory in the city of Maceió-AL from September/2018 to September/2019. All results of cytological tests were filed in the Laboratory’s operating system. Patients who underwent cytological examination outside the research period were not included in the research, thus being an exclusion criteria. The results regarding the presence of microbiological agents (G. vaginalis, Candida sp. and T. vaginalis), were distributed by age group. The following ranges were analyzed: 14 to 34 years old, 35 to 49 years old and 50 to 75 years old.

During the studied period, 1.688 Pap smear exams of women aged between 14 and 88 years were registered by the operating system of the Adolf Lutz Clinical Pathology Laboratory. The age range of positive cases were divided into 4 groups, 14 - 34 years old (Group 1), 35 - 49 years old (Group 2), 50 - 70 years old (Group 3) and 71 - 88 years old (Group 4).

A total of 1.688 cytological exams were analyzed, with 23.45% (396 out of 1688) being the total percentage of positive cases for G. vaginalis, Candida sp. T. vaginalis and association of cocci and/or bacilli with Candida sp. Table 1 shows the number of positive cases according to age group, where women aged 14 - 34 years old had the highest number of positivity, followed by women aged 35 - 49 years old and patients aged between 50 - 70 years old. For women over 71 years old, it was possible to observe a decrease in positive cases which according to Nascimento et al. (2022)NASCIMENTO, C.G.S., BORGES, J.S., FIORIO, M.S., MEZZOMO, L.C., MEZZARI, A. and CALIL, L.N., 2022. Frequência de alterações citológicas e agentes microbiológicos em pacientes atendidas em um projeto de extensão universitária na cidade de Porto Alegre - RS. Revista Eletrônica de Extensão, vol. 19, no. 41, pp. 16-31. http://dx.doi.org/10.5007/1807-0221.2022.e82485.
http://dx.doi.org/10.5007/1807-0221.2022...
there is a lower demand for cytological examination, in the age group between 66 and 84 years.

Table 1
Prevalence of vulvovaginitis and vaginosis in patients, according to age group, who underwent cytological examination in a laboratory in Maceió-AL, from September/2018 to September/2019.

The higher prevalence of infections in young women may be related to high hormone levels, which would be associated with the etiopathogenesis of infections. Another explanation would be the existence of risk factors, such as the early onset of sexual activity, the use of the IUD and the use of oral contraceptives, as well as the large number of sexual partners (Resende et al., 2019RESENDE, A.F., SANTOS, R.W.F., GASPAR, L.M.A.C. and ALMEIDA, P.O.S., 2019. Prevalência de vaginoses bacterianas em pacientes que executaram bacterioscopia de força vaginal.Revista de Ciências Médicas e Biológicas, vol. 18, n. 2, pp. 190-193.http://dx.doi.org/10.9771/cmbio.v18i2.29698.
http://dx.doi.org/10.9771/cmbio.v18i2.29...
).

In many gynecological services, vaginal discharge is the main complaint of women assisted, followed by itching and vaginal odor, these symptoms generally indicative of vulvovaginitis and can interfere with their sexual intercourse and their quality of life. Given these considerations, the prevention and early identification of vulvovaginitis can be identified as one of the gynecological priorities in women’s health care, in order to offer adequate treatment for each scenario (Carvalho et al., 2022CARVALHO, F.S., PORTO, N.K.A., AZEVEDO, P.V.M., MAGALHÃES, P.K.A., ARAÚJO, P.T., CORREIA, M.S., SILVA, K.M., PAVÃO, J.M.S.J., FERREIRA, J.R.S., MAIOR, L.P.S., CAVALCANTI, M.G.S., FERREIRA-JÚNIOR, G.C. and MATOS-ROCHA, T.J., 2022. Agentes causadores de infecções genitais em exames citológicos de rotina: frequência e características do Papanicolau. Brazilian Journal of Biology = Revista Brasileira de Biologia, vol. 82, pp. e238180. http://dx.doi.org/10.1590/1519-6984.238180.
http://dx.doi.org/10.1590/1519-6984.2381...
).

In all 396 positive cases, it can be observed that 55.30% (219/396) of the cases were positive for G. vaginalis, 40.40% (160/396) positive cases for Candida sp. Associated with cocci and/or bacilli, 16.28% (13/396) positive cases only for Candida sp. and 1.01% (4/396) cases for T. vaginalis, not being observed only candidiasis or trichomoniasis in women over 50 years old. In the study carried out by Rodrigues et al. (2022)RODRIGUES, H.J.C., SILVA, H.F.M., PEREIRA, L.S., CASTRO, G.J.B., SILVA, S.A.M., ARAÚJO, E.A., LOPES, D.A. and PINHO, J.D., 2022. Prevalence of vulvovaginite in women rural.Research, Social Development, vol. 11, no. 3, pp. e2611326192. http://dx.doi.org/10.33448/rsd-v11i3.26192.
http://dx.doi.org/10.33448/rsd-v11i3.261...
and Silveira et al. (2022)SILVEIRA, D.C.M., FERNANDES, R.L., MENDONÇA, A.P.A.S., LEITE, A.P.N., GOMES, M.T.B.P., PAZ, B.K.B. and ALIANÇA, A.S.S., 2022. Prevalência de microrganismos patogênicos em mulheres em um ambulatório particular de ginecologia de São Luís, Maranhão.Revista Ibero-Americana de Humanidades, Ciência & Educação (Bauru), vol. 8, no. 9, pp. 152-163. http://dx.doi.org/10.51891/rease.v8i9.6829.
http://dx.doi.org/10.51891/rease.v8i9.68...
the most prevalent microorganisms were similar to those observed in the present study.

In Graph 1, the prevalence of positive cases for the different infectious agents according to the age group can be observed, also observing that there were cases of association of cocci and/or bacilli and Candida sp.

Graph 1
Prevalence of etiological agents that causes vulvovaginitis and vaginosis in patients, related to age group, who underwent cytological examination in a laboratory in Maceió-AL, from September/2018 to September/2019.

In Brazil, bacterial vaginosis, mainly represented by G. vaginalis, is very frequent, affecting approximately 45% of women with a complaint of vaginal discharge, and may also be present even in asymptomatic women, affecting approximately 10% to 30% of pregnant women and 10% of women assisted in primary care (Alves et al., 2021ALVES, G.B., ALVIM, M.C.T., ODORIZZI, V.F., BORGES, A.K.P. and BAPTISTA, A.B., 2021. Perfil etiológico e epidemiológico das vulvovaginites que acometem mulheres em uma cidade do estado de Tocantins. Revista Eletrônica Acervo Saúde, vol. 13, no. 2, pp. e5383. http://dx.doi.org/10.25248/reas.e5383.2021.
http://dx.doi.org/10.25248/reas.e5383.20...
). According to Silveira et al. (2022)SILVEIRA, D.C.M., FERNANDES, R.L., MENDONÇA, A.P.A.S., LEITE, A.P.N., GOMES, M.T.B.P., PAZ, B.K.B. and ALIANÇA, A.S.S., 2022. Prevalência de microrganismos patogênicos em mulheres em um ambulatório particular de ginecologia de São Luís, Maranhão.Revista Ibero-Americana de Humanidades, Ciência & Educação (Bauru), vol. 8, no. 9, pp. 152-163. http://dx.doi.org/10.51891/rease.v8i9.6829.
http://dx.doi.org/10.51891/rease.v8i9.68...
G. vaginalis is one of the reasons that most lead women to the gynecologist. In the study carried out by Rodrigues et al. (2022)RODRIGUES, H.J.C., SILVA, H.F.M., PEREIRA, L.S., CASTRO, G.J.B., SILVA, S.A.M., ARAÚJO, E.A., LOPES, D.A. and PINHO, J.D., 2022. Prevalence of vulvovaginite in women rural.Research, Social Development, vol. 11, no. 3, pp. e2611326192. http://dx.doi.org/10.33448/rsd-v11i3.26192.
http://dx.doi.org/10.33448/rsd-v11i3.261...
there was also a prevalence of G. vaginalis infections, representing 14.2% of the analyzed cases of women who sought care at a Basic Health Unit (BHU).

In this study, a total of 43.68% (173/396) positive reports for Candida sp. With and without association with cocci and/or bacilli were identified, being a proportionally higher result when compared to the study by Carvalho et al. (2022)CARVALHO, F.S., PORTO, N.K.A., AZEVEDO, P.V.M., MAGALHÃES, P.K.A., ARAÚJO, P.T., CORREIA, M.S., SILVA, K.M., PAVÃO, J.M.S.J., FERREIRA, J.R.S., MAIOR, L.P.S., CAVALCANTI, M.G.S., FERREIRA-JÚNIOR, G.C. and MATOS-ROCHA, T.J., 2022. Agentes causadores de infecções genitais em exames citológicos de rotina: frequência e características do Papanicolau. Brazilian Journal of Biology = Revista Brasileira de Biologia, vol. 82, pp. e238180. http://dx.doi.org/10.1590/1519-6984.238180.
http://dx.doi.org/10.1590/1519-6984.2381...
, which showed the presence of this pathogen in 5.01% of 18,645 reports analyzed. However, even with the relatively lower prevalence of this microorganism, the study by Carvalho et al. (2022)CARVALHO, F.S., PORTO, N.K.A., AZEVEDO, P.V.M., MAGALHÃES, P.K.A., ARAÚJO, P.T., CORREIA, M.S., SILVA, K.M., PAVÃO, J.M.S.J., FERREIRA, J.R.S., MAIOR, L.P.S., CAVALCANTI, M.G.S., FERREIRA-JÚNIOR, G.C. and MATOS-ROCHA, T.J., 2022. Agentes causadores de infecções genitais em exames citológicos de rotina: frequência e características do Papanicolau. Brazilian Journal of Biology = Revista Brasileira de Biologia, vol. 82, pp. e238180. http://dx.doi.org/10.1590/1519-6984.238180.
http://dx.doi.org/10.1590/1519-6984.2381...
concluded that Candida sp. Was the second most found agent, as well as this study. In addition, about 75% of adult women have at least one case of fungal vulvovaginitis in their lives, where 40 to 50% of them will have new outbreaks, and if symptoms are present, fungal vulvovaginitis can be confirmed through tests that identify the etiological agent, such as a cytological examination.

Another infectious agent diagnosed by the Pap smear test is T. vaginalis, a flagellate protozoan, commonly found in the lower level of the genitals of women. Although Nascimento et al. (2022)NASCIMENTO, C.G.S., BORGES, J.S., FIORIO, M.S., MEZZOMO, L.C., MEZZARI, A. and CALIL, L.N., 2022. Frequência de alterações citológicas e agentes microbiológicos em pacientes atendidas em um projeto de extensão universitária na cidade de Porto Alegre - RS. Revista Eletrônica de Extensão, vol. 19, no. 41, pp. 16-31. http://dx.doi.org/10.5007/1807-0221.2022.e82485.
http://dx.doi.org/10.5007/1807-0221.2022...
demonstrated a prevalence of 13.76% of cases for trichomoniasis, in a sample of 129 cytologies, in this study a much lower rate was observed, with only 1.01%, similar to the work by Alves et al. (2021)ALVES, G.B., ALVIM, M.C.T., ODORIZZI, V.F., BORGES, A.K.P. and BAPTISTA, A.B., 2021. Perfil etiológico e epidemiológico das vulvovaginites que acometem mulheres em uma cidade do estado de Tocantins. Revista Eletrônica Acervo Saúde, vol. 13, no. 2, pp. e5383. http://dx.doi.org/10.25248/reas.e5383.2021.
http://dx.doi.org/10.25248/reas.e5383.20...
, who noted a 2% prevalence of this pathogen in 1,095 reports analyzed. One of the reasons for the low prevalence of this pathogen may be that according to Carvalho et al. (2022)CARVALHO, F.S., PORTO, N.K.A., AZEVEDO, P.V.M., MAGALHÃES, P.K.A., ARAÚJO, P.T., CORREIA, M.S., SILVA, K.M., PAVÃO, J.M.S.J., FERREIRA, J.R.S., MAIOR, L.P.S., CAVALCANTI, M.G.S., FERREIRA-JÚNIOR, G.C. and MATOS-ROCHA, T.J., 2022. Agentes causadores de infecções genitais em exames citológicos de rotina: frequência e características do Papanicolau. Brazilian Journal of Biology = Revista Brasileira de Biologia, vol. 82, pp. e238180. http://dx.doi.org/10.1590/1519-6984.238180.
http://dx.doi.org/10.1590/1519-6984.2381...
, this infection is transmitted almost exclusively during sexual intercourse.

Most affected women were young with an active sex life, aged between 14-34 years old. The highest prevalence was for G. vaginalis, followed by Candida sp. and T. vaginalis. Regarding the method applied for the study, the Pap smear test, a test primarily used to screen precursor lesions of cervical cancer, is effective for detecting infectious agents, representing a valuable instrument for the diagnosis of these infections.

Vaginal discharge is a very common symptom in women and may or may not be associated with sexually transmitted infections. It is important to know the cause and perform the appropriate treatment to reduce the risk of possible transmission and dissemination of the causative agent. The high rate of positivity for vaginal infections caused by G. vaginalis, Candida sp and T. vaginalis points to the need for greater monitoring and guidance regarding the prevention of these infections. The periodicity of the exams directly influences the reduction of cases of vaginitis.

References

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    » http://dx.doi.org/10.25248/reas.e5383.2021
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    » http://dx.doi.org/10.1590/1519-6984.238180
  • CRUZ, G.S., BRITO, E.H.S., FREITAS, L.V. and MONTEIRO, F.P.M., 2020. Candidíase vulvovaginal na Atenção Primária à Saúde: diagnóstico e tratamento. Revista Enfermagem Atual In Derme, vol. 94, no. 32, pp. e-020074. http://dx.doi.org/10.31011/reaid-2020-v.94-n.32-art.735
    » http://dx.doi.org/10.31011/reaid-2020-v.94-n.32-art.735
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Publication Dates

  • Publication in this collection
    26 Feb 2024
  • Date of issue
    2023

History

  • Received
    26 May 2023
  • Accepted
    22 Aug 2023
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