The impact of a single round of community mass treatment with azithromycin on disease severity and ocular Chlamydia trachomatis load in treatment-naïve trachoma-endemic island communities in West Africa

Burr, Sarah E.; Harding-Esch, Emma; Cassama, Eunice; Nabicassa, Meno; Mabey, David; Holland, Martin J.; Bailey, Robin L.

doi:10.1186/s13071-017-2566-x

Cited by 15 publications

(23 citation statements)

References 33 publications

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“…In in vitro experiments, antibiotic treatment with penicillin, rifampin, or azithromycin results in development of a persistent, nonreplicative aberrant form of the organism that can recover on removal of the antibiotic (16, 17). This may be one explanation for the recent decrease in the clinical efficacy of azithromycin (18–20).…”

Section: Introductionmentioning

confidence: 99%

Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon

Somboonna

Ziklo

Suh

et al. 2019

mBio

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Clinical persistence of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) is a major public health concern. In vitro persistence is known to develop through interferon gamma (IFN-γ) induction of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, an essential amino acid for Ct replication. The organism can recover from persistence by synthesizing tryptophan from indole, a substrate for the enzyme tryptophan synthase. The majority of Ct strains, except for reference strain B/TW-5/OT, contain an operon comprised of α and β subunits that encode TrpA and TrpB, respectively, and form a functional αββα tetramer. However, trpA mutations in ocular Ct strains, which are responsible for the blinding eye disease known as trachoma, abrogate tryptophan synthesis from indole. We examined serial urogenital samples from a woman who had recurrent Ct infections over 4 years despite antibiotic treatment. The Ct isolates from each infection episode were genome sequenced and analyzed for phenotypic, structural, and functional characteristics. All isolates contained identical mutations in trpA and developed aberrant bodies within intracellular inclusions, visualized by transmission electron microscopy, even when supplemented with indole following IFN-γ treatment. Each isolate displayed an altered αββα structure, could not synthesize tryptophan from indole, and had significantly lower trpBA expression but higher intracellular tryptophan levels compared with those of reference Ct strain F/IC-Cal3. Our data indicate that emergent mutations in the tryptophan operon, which were previously thought to be restricted only to ocular Ct strains, likely resulted in in vivo persistence in the described patient and represents a novel host-pathogen adaptive strategy for survival. IMPORTANCE Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium with more than 131 million cases occurring annually worldwide. Ct infections are often asymptomatic, persisting for many years despite treatment. In vitro recovery from persistence occurs when indole is utilized by the organism’s tryptophan synthase to synthesize tryptophan, an essential amino acid for replication. Ocular but not urogenital Ct strains contain mutations in the synthase that abrogate tryptophan synthesis. Here, we discovered that the genomes of serial isolates from a woman with recurrent, treated Ct STIs over many years were identical with a novel synthase mutation. This likely allowed long-term in vivo persistence where active infection resumed only when tryptophan became available. Our findings indicate an emerging adaptive host-pathogen evolutionary strategy for survival in the urogenital tract that will prompt the field to further explore chlamydial persistence, evaluate the genetics of mutant Ct strains and fitness within the host, and their implications for disease pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon

Somboonna

Ziklo

Suh

et al. 2019

mBio

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“…One year prior to our study, azithromycin, an antibiotic that has activity against Ct, Ng, Mg and Tp , had been distributed to the population as part of an MDA programme for trachoma elimination. 16 In the Solomon Islands, a similar MDA campaign resulted in a 40% reduction in age-adjusted urogenital Ct prevalence. 20 It is possible that STIs in our population have been similarly affected but unfortunately no data on STI prevalence prior to MDA is available for Bubaque.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the Bijagos Islands have been a site for mass drug administration (MDA) with azithromycin for trachoma control. 16 Azithromycin is an antibiotic that is effective against a number of STI 17 ; however, the impact of MDA on STI prevalence is not known in this setting.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of and risk factors for curable sexually transmitted infections on Bubaque Island, Guinea Bissau

Cowley

Milne

Silva³

et al. 2020

Sex Transm Infect

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ObjectivesComplications from sexually transmitted infections (STIs) can result in severe morbidity and mortality. To date, no STI population studies have been conducted on the Bijagos Islands, Guinea Bissau. Our objective was to estimate the prevalence of and identify risk factors for Chlamydia trachomatis (Ct), Neisseria gonorrhoea (Ng), Mycoplasma genitalium (Mg), Trichomonas vaginalis (Tv) and Treponema pallidum (Tp) on Bubaque, the most populated island.MethodsA cross-sectional survey was conducted on the island of Bubaque among people aged 16–49 years. Participants were asked to answer a questionnaire on STI risk factors, to provide urine samples (men and women) and vaginal swabs (women) for PCR testing for Ct, Ng, Mg and Tv, and to provide dry blood spots for Tp particle agglutination assays. Data were analysed to estimate the prevalence of STIs and logistic regression was used to identify risk factors.ResultsIn total, 14.9% of participants were found to have a curable STI, with the highest prevalence being observed for Tv (5.9%) followed by Ct (3.8%), Ng (3.8%), Mg (1.9%) and Tp (0.8%). Significant risk factors for having any STI included being female, younger age and concurrent partnership. Having had a previous STI that was optimally treated was a protective factor.ConclusionsThis study demonstrates that there is a considerable burden of STI on the Bijagos Islands, stressing the need for diagnostic testing to facilitate early detection and treatment of these pathogens to stop ongoing transmission. Moreover, these results indicate the need to conduct further research into the STI burden on the Bijagos Islands to help inform and develop a national STI control strategy.

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“…Anticipating patterns of mobility can enable programmes and policies to be more effective, such as delivering MDA during seasons where populations are relatively more sedentary (DIAL et al, 2014), extending the duration of campaigns, or running campaigns in occasionally inhabited areas. These strategies could be particularly effective on the Bijagós Islands, where most interventions are community based and coverage remains a challenge (Last et al, 2017). Without knowledge of local movements and disparate risk environments, population mobility can threaten disease elimination efforts (Burkot and Ichimori, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The islands are co-endemic for malaria and Neglected Tropical Diseases (NTDs) such as lymphatic filariasis, scabies and soil transmitted helminths (Thompson et al, 2015; Marsden et al, 2013, Last et al, 2014). Trachoma is close to elimination from the islands and is currently under surveillance (Last et al, 2017). Whilst the Guinea-Bissau Ministry of Health has prioritised NTD elimination, there is a lack of good quality, recent epidemiological, social and behavioural data on the burden of these diseases and their local transmission patterns.…”

Section: Introductionmentioning

confidence: 99%

“Moving like birds”: A qualitative study of population mobility and health implications in the Bijagós Islands, Guinea Bissau

Durrans

Boiro

Gonçalves

et al. 2019

Social Science & Medicine

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Population movement is a major driver for infectious disease transmission and can impact the success of disease control and elimination strategies. The relationship between disease transmission and permanent migration is well documented, but fewer studies have considered how different types of population mobility affects disease transmission and control programmes. This qualitative study was conducted on two islands of the Bijagós archipelago, Guinea Bissau to understand spatial and temporal population movement, and reasons for these movements, within, between and away from the Bijagós islands. Data were collected on two islands using key informant interviews (n = 8), daily activity-location interviews (n = 30) and focus group discussions (n = 6). Data were analysed thematically using an adapted typology of mobility. Findings revealed that movement within and between islands, and from islands to the mainland, was a common feature of island life for men and women alike. It was usual for trips away from home to last for several months at a time. Five key reasons for travel were identified: subsistence activities; family events; income generating activities; cultural festivities and healthcare. These movements often occurred erratically all year round, with the exception of seasonal travel within and between islands for agricultural purposes. Our study characterised detailed patterns of human mobility in the Bijagós islands as a first step towards understanding the potential impact of different types of mobility on disease exposure, transmission and public health programmes. Short-term mobility may have a significant impact on the spread of infectious diseases with short incubation periods. Predictable movements, such as travel for seasonal agricultural work, should be taken into account for tailoring and increasing the reach of public health interventions. Further research is needed to understand the role of human behaviour and mobility in disease transmission and control across the archipelago.

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The impact of a single round of community mass treatment with azithromycin on disease severity and ocular Chlamydia trachomatis load in treatment-naïve trachoma-endemic island communities in West Africa

Cited by 15 publications

References 33 publications

Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon

Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon

Prevalence of and risk factors for curable sexually transmitted infections on Bubaque Island, Guinea Bissau

“Moving like birds”: A qualitative study of population mobility and health implications in the Bijagós Islands, Guinea Bissau

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