Introduction
Sexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of ...untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point‐of‐care tests (POCTs), including those in the pipeline, to diagnose STIs in resource‐constrained settings.
Methods
We prioritized updating the systematic review and meta‐analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer‐reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.
Results and discussions
The diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low‐cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near‐patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource‐constrained settings. This is driving the development of lower cost solutions.
Conclusions
The WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource‐constrained settings to support the uptake of aetiological diagnosis and treatment.
Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone ...in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality.
To systematically review, critically appraise ...and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use.
Systematic review and meta-analysis.
We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis.
We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias.
Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs.
The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis.
PROSPERO 2016:CRD42016049168.
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious public health problem, compromising the management and control of gonorrhoea globally. Resistance in N. gonorrhoeae to ...ceftriaxone, the last option for first-line empirical monotherapy of gonorrhoea, has been reported from many countries globally, and sporadic failures to cure especially pharyngeal gonorrhoea with ceftriaxone monotherapy and dual antimicrobial therapies (ceftriaxone plus azithromycin or doxycycline) have been confirmed in several countries. In 2018, the first gonococcal isolates with ceftriaxone resistance plus high-level azithromycin resistance were identified in England and Australia. The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Program (GASP) is essential to monitor AMR trends, identify emerging AMR and provide evidence for refinements of treatment guidelines and public health policy globally. Herein we describe the WHO GASP data from 67 countries in 2015-16, confirmed gonorrhoea treatment failures with ceftriaxone with or without azithromycin or doxycycline, and international collaborative actions and research efforts essential for the effective management and control of gonorrhoea. In most countries, resistance to ciprofloxacin is exceedingly high, azithromycin resistance is present and decreased susceptibility or resistance to ceftriaxone has emerged. Enhanced global collaborative actions are crucial for the control of gonorrhoea, including improved prevention, early diagnosis, treatment of index patient and partner (including test-of-cure), improved and expanded AMR surveillance (including surveillance of antimicrobial use and treatment failures), increased knowledge of correct antimicrobial use and the pharmacokinetics and pharmacodynamics of antimicrobials and effective drug regulations and prescription policies (including antimicrobial stewardship). Ultimately, rapid, accurate and affordable point-of-care diagnostic tests (ideally also predicting AMR and/or susceptibility), new therapeutic antimicrobials and, the only sustainable solution, gonococcal vaccine(s) are imperative.
In 2016 the World Health Assembly adopted the global strategy on Sexually Transmitted Infections (STI) 2016-2021 aiming to reduce curable STIs by 90% by 2030. We costed scaling-up priority ...interventions to coverage targets.
Strategy-targeted declines in Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis were applied to WHO-estimated regional burdens at 2012. Syndromic case management was costed for these curable STIs, symptomatic Herpes Simplex Virus 2 (HSV-2), and non-STI vaginal syndromes, with incrementally expanding etiologic diagnosis. Service unit costs were multiplied with clinic attendances and people targeted for screening or prevention, by income tier. Human papilloma virus (HPV) vaccination and screening were costed for coverage increasing to 60% of 10-year-old girls for vaccination, and 60% of women 30-49 years for twice-lifetime screening (including clinical follow-up for positive screens), by 2021.
Strategy implementation will cost an estimated US$ 18.1 billion over 2016-2021 in 117 low- and middle-income countries. Cost drivers are HPV vaccination ($3.26 billion) and screening ($3.69 billion), adolescent chlamydia screening ($2.54 billion), and antenatal syphilis screening ($1.4 billion). Clinical management-of 18 million genital ulcers, 29-39 million urethral discharges and 42-53 million vaginal discharges annually-will cost $3.0 billion, including $818 million for service delivery and $1.4 billion for gonorrhea and chlamydia testing. Global costs increase from $2.6 billion to $ 4.0 billion over 2016-2021, driven by HPV services scale-up, despite vaccine price reduction. Sub-Saharan Africa, bearing 40% of curable STI burdens, covers 44% of global service needs and 30% of cost, the Western Pacific 15% of burden/need and 26% of cost, South-East Asia 20% of burden/need and 18% of cost.
Costs of global STI control depend on price trends for HPV vaccines and chlamydia tests. Middle-income and especially low-income countries need increased investment, innovative financing, and synergizing with other health programs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a substantial global public health problem. Gonococcal infections acquired in or from Asia represent most verified ceftriaxone treatment ...failures, and several ceftriaxone-resistant strains have emerged in Asia and subsequently spread globally. Additionally, in Thailand the gonorrhoea incidence remains high. Herein, we investigate the genomic diversity, AMR and AMR determinants in gonococcal isolates cultured in 2018 in Bangkok, Thailand.
Gonococcal isolates from males (n = 37) and females (n = 62) were examined by Etest and WGS. AMR determinants and molecular epidemiological STs were characterized. For phylogenomic comparison, raw sequence data were included from China (432 isolates), Japan (n = 270), Vietnam (n = 229), Thailand (n = 3), a global dataset (n = 12 440) and the 2016 WHO reference strains plus WHO Q (n = 15).
In total, 88, 66 and 41 different NG-MAST, NG-STAR and MLST STs, respectively, and 31 different NG-STAR clonal complexes were found. A remarkably high frequency (88%) of β-lactamase TEM genes was detected and two novel TEM alleles were found. The phylogenomic analysis divided the isolates into the previously described lineages A and B, with a large proportion of Thai isolates belonging to the novel sublineage A3.
We describe the first molecular epidemiological study using WGS on gonococcal isolates from Thailand. The high prevalence of AMR and AMR determinants for ciprofloxacin, tetracycline and benzylpenicillin, and some strains belonging to clones/clades especially in sublineage A2 that are prone to develop resistance to extended-spectrum cephalosporins (ESCs) and azithromycin, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Thailand.
BoxWHO National and Global Sexually Transmitted Infection Surveillance Priorities for Action Priority actions for countries Strengthen and integrate sexually transmitted infection surveillance into ...the national health information system as a part of health system strengthening, using standardized indicators and methodologies as guided by WHO; ensure that data collection methods yield high‐quality information, meet ethical standards, and do not pose risks for communities or the health care workers involved. Identify specific populations who are most at risk for sexually transmitted infections and places where most of the transmission is occurring; establish mechanisms to promote the participation of affected communities; conduct routine case reporting and periodic prevalence assessments of core sexually transmitted infections to assess the magnitude of the sexually transmitted infection problem in target populations, including by disaggregating the data; describe the sexually transmitted infection epidemics and measure the impact in terms of sequelae and cost. Priority actions for WHO Provide global leadership and assistance to countries in strengthening sexually transmitted infection surveillance and in using standard methodologies for such surveillance and estimation of the burden and impact; support the development of strategic information systems and sexually transmitted infection epidemics and response mapping, including the analysis of disaggregated data for monitoring inequities; support countries in strengthening case reporting, prevalence assessment, aetiologic assessment and antimicrobial resistance monitoring; strengthen global systems for collecting and sharing national surveillance data on sexually transmitted infections, including disaggregated data and analysis for monitoring equity. Funding The project was funded by the World Health Organization, Department of Reproductive Health and Research, STI programme and furthermore supported by a cooperative agreement from the U.S. Centers for Disease Control and Prevention in support of strengthening STI surveillance.
BACKGROUNDTo assess the potential market for 2 hypothetical diagnostic tests, one for Neisseria gonorrhoeae/Chlamydia trachomatis (NG/CT) detection and one for NG antimicrobial resistance (AMR) ...marker identification.
METHODSThis is a qualitative interview-based study. Semistructured interviews with global- and country-level experts were performed. Interviewees were provided with simplified versions of Foundation for Innovative New Diagnostics/World Health Organization–developed target product profiles for each test. Interviewees were asked to comment on use cases, test characteristics, and factors that may influence test adoption.
RESULTSTwenty-one experts were interviewed, including 15 country-level experts (from South Africa, India, Zimbabwe, Ghana, China, Peru, Kenya, and Cambodia). Interviewees welcomed an NG/CT point-of-care test, with near-universal preference for a test that could detect symptomatic and asymptomatic infections. Interviewees also saw value in a test that could be used to screen high-risk populations. Factors that may drive adoption of the NG/CT test identified by interviewees included price, cost-effectiveness, evidence of public health benefit, and World Health Organization guidance. Interviewees felt that AMR test use would likely be limited to patients failing first-line treatment.
CONCLUSIONSAlthough the potential target population for an NG/CT diagnostic test in low- and middle-income countries is sizeable, there are areas of uncertainty relating to the price of the test and its intended use, warranting further research to determine the most effective positioning. An NG AMR test would likely be used very selectively.
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