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Autovaccination Therapy in Recurrent Vulvovaginal Candidiasis

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Autovaccination Therapy in Recurrent Vulvovaginal Candidiasis Microbiology and virology Autovaccination therapy in recurrent vulvovaginal candidiasis Summary 20-30% of women affected by vulvo-vaginal Candidiasis frequently develops recurrences. Therapy and phar- macology prophylaxis have shown a high percentage of insuccess. Objective of the study was the evaluation of immunotherapy to prevent the recurrences of candida vaginitis. 74 women between 20-50 years old unde- rwent treatment with an autogenous vaccine. Treated women had been suffering, from at least, four vaginitis episodes/year for at least 2 years and therapy and long-term pharmacological prophylaxis had any result during the year after the suspension. Sintomatology disappeared in 62 of the patients and 6 reported a rele- vant improvement. Laboratory follow-up showed absence of Candida in the vaginal secretion of 64 of 68 women who reported recovery or improvement. The approach with autovaccination may be an excellent alter- native in recurrent vulvovaginal candidiasis. The results achieved are encouraging for the prosecution of the study based on the immunological approach to therapy and prophylaxis in fungal infections. Lanzafame P. Autovaccination therapy in recurrent vulvovaginal candidiasis. Trends Med 2011; 11(2):81-84. ©2011 Pharma Project Group srl. ISSN: 1594-2848 Key words: Introduction immunoprophylaxis Immunocompetent T cells are therapy Vaginal mycotic infection repre- crucial in host defenses against autogenous vaccine sent more than 50% of all vagi- many pathogenic fungi including candida nitis. 20-30% of women affected Candida albicans. CD4+ T cells vulvo-vaginal candidiasis by vulvo-vaginal candidiasis fre- are essential for host defenses quently develops recurrent epi- and the principal mechanism by sodes and sometimes even chro- which they influence host resi- nicization. Therapy and long- stance is by production of cytoki- term pharmacology prophylaxis nes. CD4+ T cells are separated have shown a high percentage into two functional categories: T (20 % ca.) of insuccess. Recur- helper 1 (Th1) and T helper 2 rent vulvo-vaginal candidiasis is (Th2). The former produce IFN- defined as four or more episo- gamma and IL-2 and are the pri- des of infection per year, in only mary mediators of host defenses a minority the pathogenesis, in- associated with activation of pha- cluding uncontrolled diabetes gocytes. Th2 cells release IL-4, IL- and immunosoppressive the- 5, IL-10 and IL-13 that are invol- rapy, is apparent15. ved in antibodies production1,3,5. Cell-mediated immunity and Another important effector nonspecific cellular immunity mechanism is cytotoxic activity. are generally believed to provide CD8+ T cells can damage the main defenses against fun- C.albicans hyphae and kill Crip- Paolo Lanzafame tococcus neoformans directly. Department of Microbiology, S.Chiara gi. The importance of cellular Hospital defense mechanism is suppor- Another primary contribution of L.go Medaglie d’Oro , 9 - 38100 ted by the clinical observation T cells is the production of anti- Trento - Italy bodies5. Business phone +39.0461.903270 that most invasive fungal infec- Fax +39.0461.903615 tions occur in individuals with Also the role of natural antibody e-mail: [email protected] defective cellular immunity3. immunity in mucosal defense is April 2011 Volume 11 Number 2 Trends in Medicine 81 P. Lanzafame uncertain. IgA deficiency is not Before the approach to fungal Saboraud and the colonies of usually associated with C. albi- vaccines it is important to deter- Candida present in the plate cul- cans infections, nonspecific IgA mine what are the expectations ture were isolated and identified enhanced adherence of C. albi- for an effective fungal vaccine. and the fungi subcultured in cans to epithelial cells, levels of The first goal that must be met Trypticase Soy Agar. After 48 vaginal IgA and IgG to C. albicans is to create a vaccine that can hours at 37 °C the surface of are similar in women with and limit the ability of the fungus to medium were very gently scra- without vaginal candidiasis and establish a latent state. The hu- ped by a calibrated plastic loop the presence of specific IgA in man host is most often succes- and the spherules were washed vaginal secretions did not pro- sful in limiting the spread of fun- three times with saline solution tects against recurrent infec- gal infections, but a fraction of and resuspended in saline solu- tions2,3,7. However, several stu- the infection may survive for ye- tion with an opacity of 1 Mc Far- dies have shown that secretory ars. These niduses of infection land. The solution so obtained IgA reduced adherence of may serve as resorvoirs for re- were heated at 70°C in a water C.albicans to epithelial cells and activation if the host immune bath for an hour for three days some antibodies can mediate system becomes impaired. Thus and tested for sterility. The sphe- protection in rat vaginal candi- any vaccine against fungi must rules so killed were separated in diasis3,8,14. Vaginal vaccination prevent the establishment of a four vials of 2 millilitre at the with a monoclonal antibody spe- dormant state in the host and same concentration of fungi: The cific for yeast killer toxin elicited consequently protect against re- vials were injected in the deltoid a secretory IgA anti-idiotypic re- activation3. of the patients9-11,13,18. sponse which protected rats In recurrent vulvo-vaginal candi- Selection of patients: 74 women from challenge with C. albicans; diasis, similarly in invasive fun- 20-50 years old underwent the passive protection was demon- gal infections, there is frequen- immunoprophylaxis treatment strated with vaginal fluid contai- tly a dormant state of fungi in the with the autogenous vaccine ning antibodies to mannan con- host and a local vaginal immu- obtained from their Candida. 64 stituents and the aspartyl prote- ne mechanism may be respon- were affected from C. albicans inase of C. albicans5,12,16. sible for the frequent relapses6. infection, 3 from C. parapsilosis, In the medical history many vac- Until some years ago the auto- 2 from C. glabrata, 3 from C. kru- cines have been licensed for vi- genous vaccine held pride of pla- sei and 2 from C. tropicalis. The ral or bacterial diseases of hu- ce in the treatment of chronic patients were women who had mans but none have been licen- infections. They was made use been suffering from at least four sed for medically important fun- of chronic bacterial infections as Candida vaginitis episodes per gi. The largest clinical trial of a recurrent urinary tract infections year for at least two years not vaccine for a mycosis was per- or staphylococcal boils. Killed suffering of diabetes or unde- formed by The Valley Fever Vac- bacteria isolated from the pa- rwent immunosoppressive the- cine Study Group about fifteen tient’s discharges were injected rapy. All of them had already years ago. Nearly 3000 subjects in the hope that they would sti- been placed on therapy to myco- who were skin test negative for mulate the formation of specific tic infections several times as coccidioidomycosis were rando- immunity which would overcome well as on long-term pharmaco- mized blindly to receive either the infection. The value of auto- logical prophylaxis. Clinical and whole spherules killed with for- genous vaccine therapy or microbiological follow-up were maldheyde or saline. During five prophylaxis has never been sati- extended for three years after years of observation the differen- sfactorily investigated and may the end on the vaccination pro- ces in the groups, the vaccine yet be proved, in the meantime tocol. General clinical laboratory recipients and the placebo con- it is used as a last resort when and specific immunological tests trols, was statistically insignifi- antibiotics and other forms of were preventively carried out cant and less than 30% of vac- treatment have failed6. periodically at the end of the tre- cinated subjects manifested evi- atment and every two and six dence of a response to the sphe- months. Materials and methods rule preparation, thus it is possi- ble that in almost 70% of su- Methods of preparation of au- Results bjects the vaccine was not im- togenous vaccine: Vaginal di- munogenic3,7,16. scharge were cultured in agar At the end of the treatment with 82 Trends in Medicine April 2011 Volume 11 Number 2 Autovaccination therapy in recurrent vulvovaginal candidiasis the autogenous vaccine sinto- cells, of the seric IgG, IgA, IgM, not vary, also in those with Can- matology disappeared in 62 of C3 and C4 components of Com- dida in the vaginal secretions. In the patients. 6 patients reported plement, of vaginal nonspecific the remaining six patients a relevant improvement, althou- IgA and of seric and vaginal spe- without good results Candida gh they still presented a modest cific total Igs. A significant incre- vaginitis was detectable for all vaginal discharge and a slight ase of the reaction at the skin three years of observation. vulvar itching. The remaining six test with 0,4 ml of the same so- Collateral effects did not showed patients reported only a modest lution of the autogenous vacci- during and after the treatment reduction in the intensity of ne was showed in 66 patients. except a muscular pain in the symptoms. They showed no skin reaction sites of injections for two or three Laboratory follow-up in this pha- before the vaccine treatment days after. se showed absence of Candida and a large reaction (1-2,5 cm in the vaginal secretion of 64 of of diameter) 15 days after the Conclusions 68 women who reported recove- end of treatment. This represent ry or improvement; persistence the only evidence of a cell me- Autogenous vaccines has a long of the mycetes was checked in diated immunitary response to medical history, they are used the six patients with only modest the stimulation by the autoge- for threating chronic or recur- improvement and in four su- nous vaccine.
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