The microbiological aetiology of vaginal discharge was studied in 208 women attending various outpatient clinics at King Edward VIII Hospital. Specimens from the lower genital tract were collected for microscopy and culture. Vaginal wet smear examination, amine liberation test and vaginal pH estimation were performed and assessed for their reliability for the rapid diagnosis of vaginal infections. Vaginal and endo-cervical infections were present in 163 (78,4%) women. G. vaginalis (65,4%), T. vaginalis (37,9%), genital yeasts (37,0%), M. hominis (59,6%), g. urealyticum (48,1%), anaerobic bacteria (32,6%), N. gonorrhoeae (11,1%), f. trachomatis (22,1%) and Herpes simplex virus (0,9%) were detected. Of the 104 women in • whom vaginal infections were detected, bacterial vaginosis was present as the sole infection in 32 (22,2%), I. vaginalis in 35 (24,3%) and C. albicans in 23 (15,9%). Bacterial vaginosis occurred concurrently with T. vaginalis and f. albicans in 24 (16,5%) and 11 (7,5%) women respectively; whilstT. vaginalis and f. albicans occurred concurrently in 14 (9,7%) women. In 6 (4,1%) women all three infections were present. No vaginal or endo-cervical pathogens were detected in 45 (21,6%) women. Women with bacterial vaginosis were found to be significantly colonised with G. vaginalis, M, hominis, anaerobic bacteria and curved Gram-negative bacilli (p < 0,05). Vaginal wet smear microscopy detected T.. vaginalis in 29% and "clue" cells in 41,3% of smears. The presence of "clue" cells (91,8%) and a positive amine test (76,7%) was significantly associated with bacterial vaginosis. Although a raised vaginal pH was also significantly associated with bacterial vaginosis, this test was less specific (65,2%) than "clue" cells (85,9%) and the amine test (95,5%). The vaginal Gram stain, as performed in this study, was found to be unreliable for the detection of "clue" cells. G. vaginalis biotypes 1 and 5 were significantly associated with bacterial vaginosis, however the serotyping scheme did not distinguish between strains isolated from women with and without bacterial vaginosis. The antimicrobial susceptibility pattern of 93 strains of G. vaginalis was not typical of either Gram-positive or Gram-negative bacteria. Serological tests revealed reactive syphilis serology in 47 (22,6%) and the presence of hepatitis B surface antigen in 16 (7,7%) women. Antibody to human immunodeficiency virus was detected in 4 (1,9%) women attending the colposcopy clinic. This study clearly demonstrates the high prevalence of vaginal and/or endo-cervical infections in women locally, the majority of whom were asymptomatic. The high frequency of concurrent infections is of concern and there is a need for the recognition, and appropriate management of such infections. / Thesis (M. Med. Sci.)- University of Natal, Department of Microbiology. 1990

The microbiological aetiology of vaginal discharge was studied in 208 women attending various outpatient clinics at King Edward VIII Hospital. Specimens from the lower genital tract were collected for microscopy and culture. Vaginal wet smear examination, amine liberation test and vaginal pH estimation were performed and assessed for their reliability for the rapid diagnosis of vaginal infections. Vaginal and endo-cervical infections were present in 163 (78,4%) women. Q. vaginalis (65,4%), I. vaginalis (37,9%), genital yeasts (37,0%), ~. hominis (59,6%), g. urealyticum (48,1%), anaerobic bacteria (32,6%), ~. gonorrhoeae (11,1%), f. trachomatis (22,1%) and Herpes simplex virus (0,9%) were detected. Of the 104 women in • whom vaginal infections were detected, bacterial vaginosis was present as the sole infection in 32 (22,2%), I. vaginalis in 35 (24,3%) and C. albicans in 23 (15,9%). Bacterial vaginosis occurred concurrently with I. vaginalis and f. albicans in 24 (16,5%) and 11 (7,5%) women respectively; whilst I. vaginalis and f. albicans occurred concurrently in 14 (9,7%) women. In 6 (4,1%) women all three infections were present. No vaginal or endo-cervical pathogens were detected in 45 (21,6%) women. Women with bacterial vaginosis were found to be significantly colonised with G. vaginalis, M, hominis, anaerobic bacteria and curved Gram-negative bacilli (p < 0,05). Vaginal wet smear microscopy detected T. vaginalis in 29% and "clue" cells in 41,3% of smears. The presence of "clue" cells (91,8%) and a positive amine test (76,7%) was significantly associated with bacterial vaginosis. Although a raised vaginal pH was also significantly associated with bacterial vaginosis, this test was less specific (65,2%) than "clue" cells (85,9%) and the amine test (95,5%). The vaginal Gram stain, as performed in this study, was found to be unreliable for the detection of "clue" cells. G. vaginalis biotypes 1 and 5 were significantly associated with bacterial vaginosis, however the serotyping scheme did not distinguish between strains isolated from women with and without bacterial vaginosis. The antimicrobial susceptibility pattern of 93 strains of G. vaginalis was not typical of either Gram-positive or Gram-negative bacteria. Serological tests revealed reactive syphilis serology in 47 (22,6%) and the presence of hepatitis B surface antigen in 16 (7,7%) women. Antibody to human immunodeficiency virus was detected in 4 (1,9%) women attending the colposcopy clinic. This study clearly demonstrates the high prevalence of vaginal and/or endo-cervical infections in women locally, the majority of whom were asymptomatic. The high frequency of concurrent infections is of concern and there is a need for the recognition, and appropriate management of such infections. / Thesis (M. Med. Sci.)- University of Natal, Department of Microbiology. 1990

Thesis (doctoral)--Munich, 1934. / Includes bibliographical references (p. [18].

Thesis (doctoral)--Munich, 1934. / Includes bibliographical references (p. [18].

Mucosal surfaces are prominent in the gastrointestinal, urogenital, and respiratory tracts and provide portals of entry for pathogens. The mucosal immune system consists of molecules, cells, and organised lymphoid structures intended to provide immunity to pathogens that impinge upon mucosal surfaces. The aim of this study was to assess humoral immunity in the vaginal mucosa and compare this immune response to a systemic response. The use of commercially available tampons provided a self-administered, pain free method for the collection of vaginal secretions. To standardise specimens, a total protein determination was performed on vaginal secretions and on sera. All subjects were screened for sexually transmitted infections (STIs) using conventional and deoxyribonucleic acid (DNA) amplification tests. Immunoglobulin levels in vaginal secretions and in sera were quantitated using a quantitative sandwich enzyme- linked- immunosorbent assay (ELISA). The immunoglobulin levels quantitated were analysed on the basis of pregnancy status and the presence or absence of an STI. Immunoglobulin results for serum showed a significant increase in IgG and IgA in women with an STI regardless of pregnancy (p< 0.001). This study showed a decrease in vaginal IgG and IgA in women with an STI. Non-pregnant women with an STI had significantly lower levels of IgG and IgA in the cervico-vaginal secretions as compared to the controls (p=0.002 and p=0.0002 respectively). This was also observed in pregnant women (p= 0.03 and p< 0.001 respectively). IgM levels were mostly too low to be detectable but showed a tendency to increase in vaginal secretions of women with an STI. Pregnancy did not have an effect on immunoglobulin levels except for IgA. The effects observed were due to the presence of an STI. All the STI pathogens studied displayed a similar effect on immunoglobulin levels. Bacterial vaginosis, however, appears to exert an effect specifically on lowering IgG (p=0.008) in vaginal fluid and increasing IgG levels (p=0.008) in serum. Once a more complete understanding of the mechanisms associated with the host defence of the vaginal mucosa is obtained, specific immunotherapeutic strategies can be developed. A greater knowledge of host defence factors specific to the vagina will provide insights into understanding susceptibility to opportunistic infections and STIs. / Thesis (M.Med.Sc.)-University of Natal, 2003.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Pathology / Master / Master of Medical Sciences

Preterm birth is a leading cause of both maternal and neonatal morbidity and mortality. It occurs in roughly one in every ten pregnancies, and at an even higher rate among Black Americans and residents of underdeveloped nations. Preterm birth can be initiated in response to a maternal or neonatal indication, or can occur spontaneously. Though indications for the former may vary, the most frequent indication for indicated preterm birth is preeclampsia, a disorder of pregnancy marked by high blood pressure and systemic organ damage. While spontaneous preterm birth and preeclampsia account for a substantial fraction of the burden of prematurity, our understanding of the triggers for and pathogenesis of both diseases are lacking. As a result, we are not able to accurately identify women early in pregnancy who are at high risk of having a spontaneous preterm birth or of developing preeclampsia. There is mounting evidence that local and systemic inflammation, infection, and environmental exposures impact the vaginal ecosystem and may be triggers of spontaneous preterm birth and preeclampsia. In this thesis, I explore the role of vaginal microbes, metabolites, and immune factors in spontaneous preterm birth and preeclampsia. After reviewing what is known about the vaginal ecosystem in spontaneous preterm birth and preeclampsia, I present a paired study of the vaginal microbiome and metabolome in a cohort of 232 women, 80 of whom delivered spontaneously preterm, and whose vaginal ecosystems were profiled during the second trimester of pregnancy. In this study I identify several metabolites strongly associated with spontaneous preterm birth, and suggest that many of these may be exogenous in origin. I also use metabolic models to investigate tyramine, a metabolite found to be associated with lower risk of spontaneous preterm birth. Finally, using predictive models I show that vaginal metabolite levels can be used to identify women at risk of spontaneous preterm birth months in advance. I then present a second study of the vaginal microbiome and immune factors in a cohort of 124 women, 62 of whom developed severe preeclampsia, and whose vaginal ecosystems were profiled at the end of the first trimester. In this study, I demonstrate for the first time that the levels of vaginal microbes early in pregnancy as well as genomic variation in the vaginal microbiome are associated with the risk of developing preeclampsia. I also identify that many vaginal immune factors are significantly depleted in the vaginal ecosystem of women who develop severe preeclampsia. I then use predictive models to show that the levels of vaginal microbes are modestly predictive of preeclampsia risk, and that features from the vaginal ecosystem can be used to improve current methods for the identification of women at risk for severe preeclampsia. Finally, I show that the microbiome signature associated with severe preeclampsia replicates in an independent cohort, suggesting that the early pregnancy vaginal microbiome is robustly associated with the diagnosis of preeclampsia months later in pregnancy. Overall, the microbial and molecular signatures that I identify in these studies contribute novel insight to our understanding of the signs and pathogenesis of both spontaneous preterm birth and preeclampsia, and in doing so, suggest novel approaches to intervention and diagnosis.