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- Hadad, Ronza, 1984-
(författare)
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Implementation of strategies for management and prevention of sexually transmitted infections with focus on Neisseria gonorrhoeae and Chlamydia trachomatis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sexually transmitted infections (STIs) are a public health issue of great importance worldwide, with effects on fertility and reproduction. Chlamydia trachomatis and Neisseria gonorrhoeae, causative agents of chlamydia and gonorrhoea, respectively, are the most common bacterial STIs with an estimated 127 million new global cases of chlamydia and 87 million new gonorrhoea cases. The continued emergence of antimicrobial resistance (AMR) in N. gonorrhoeae may in the future lead to an untreatable infection. Prevention of these infections and controlling the development of AMR rely on several strategies developed by the World Health Organization (WHO). This thesis aimed to implement several of these strategies, including supporting vaccine development for C. trachomatis and N. gonorrhoeae, evaluating molecular methods for detecting N. gonorrhoeae, predicting AMR and supporting surveillance of the spread and prevalence of AMR in N. gonorrhoeae. The present studies on a C. trachomatis recombinant vaccine antigen and the investigation of similarities of N. gonorrhoeae antigen amino acid sequences to the antigens included in the meningococcal vaccine 4CMenB contributed to the field of vaccine development for STIs. The assay SpeeDx ResistancePlus® GC performed well in detecting N. gonorrhoeae and predicting ciprofloxacin resistance and could be used in AMR surveillance and individualised treatment. In 2016, the first national genomic surveillance of all N. gonorrhoeae isolates in Sweden was performed. This national surveillance study included whole-genome sequencing combined with phenotypic AMR and epidemiological data, which provides valuable information on circulating strains, epidemiology and phylogeny. Greater knowledge of gonorrhoea and gonococcal AMR epidemiology could inform decisions on guidelines and prevention. It is essential to continue to implement WHO strategies at the national and global levels to prevent and control chlamydia and gonorrhoea infections.
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| 2. |
- Unemo, Magnus, 1970-
(författare)
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Genotypic and phenotypic characterisation of Neisseria gonorrhoeae
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The bacterium Neisseria gonorrhoeae (the gonococcus) is the aetiological agent of gonorrhoea, which remains a major sexually transmitted infection/disease (STI/STD) worldwide. The incidence of gonorrhoea was previously high in many countries, Sweden included. The incidence in Sweden culminated in 1970 with 487 cases per 100,000 inhabitants. After that, the incidence declined almost every year until an all-time low of 2.4 was observed in 1996. ln 1997 the incidence of gonorrhoea began to significantly increase in Sweden, due mainly to a larger number of domestic cases of young heterosexuals of both sexes and homosexual men. This observation, in combination with the widespread use of suboptimal methods for characterisation and, in some countries, for diagnosis of the bacterium, as well as the rapid increase of resistance to several antibiotics, has intensified the research in the field of N. gonorrhoeae.In the present thesis (paper 1), a high prevalence of decreased susceptibility or resistance to several of the traditionally used gonorrhoea antibiotics was identified and correlated to the geographic area of exposure, especially Asia. Nevertheless, effective antibiotics for treating gonorrhoea are at hand. A substantial genetic heterogeneity within identical serological variants (serovars), i.e. intraserovar, as well as interserovar of N. gonorrhoeae strains circulating within the community was revealed, emphasising the importance of using highly discriminative (DNA-based) epidemiological characterisation methods for the bacteria (papers II-V). Effective DNA-based characterisation methods, i.e. pulsed-field gel electrophmesis (PFGE) of genomic DNA digested with rarely cutting restriction endonucleases and porB gene sequencing, were adapted, optimised and evaluated against conventional phenotypic methods, as epidemiological tools on Swedish N. gonorrhoeae isolates. These molecular techniques showed a significantly higher discriminatory ability, reproducibility, and objectivity than the serovar determinations using the Genetic Systems (OS) or the Pharmacia panel (Ph) ofmonoclonal antibodies (MAbs) (papers II & III). According to a comparison of serologic and genetic parB-based typing of N. gonorrhoeae, the precise amino acid residues of porB, critical for the reactivity of several of the GS MAbs, were difficult to identity (paper IV). In papers IV & V, a determination of genetic group (genogroup) and genetic variant (genovar) was developed based on real-time PCR of the entire porB gene with subsequent sequence analysis in real-time by synthesis, i.e. pyrosequencing technology, of short, highly polymorphic porB gene segments. This method provides a rapid, high-throughput, objective, highly discriminative, typeable, portable for interlaboratory comparisons, and reproducible molecular characterisation for N. gonorrhoeae. Genogroup and genovar determination can complement or even replace the internationally established serovar determination in routine use for following the transmission of individual strains in the community and confirming presumed epidemiological connections or discriminating isolates of suspected clusters of gonorrhoea cases.
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