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Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proporti

BACKGROUND: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. METHODS: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. FINDINGS: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. INTERPRETATION: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. FUNDING: This work was supported by an Australian

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study particip

BACKGROUND: WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea. METHODS: HPV-STAT was a large-scale, prospective, single-arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702. FINDINGS: Between June 5, 2018, and Jan 6, 2020, we recruited 4285 women, 3638 (84·9%) of whom tested negative for HPV and 647 (15·1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect

BACKGROUND: Sexually transmissible infections (STIs), such as gonorrhoea and chlamydia, are highly prevalent, particularly in remote Aboriginal and Torres Strait Islander communities in Australia. In these settings, due to distance to centralised laboratories, the return of laboratory test results can take a week or longer, and many young people do not receive treatment, or it is considerably delayed. Point-of-care testing (POCT) provides an opportunity for same day diagnosis and treatment. Molecular POC testing for STIs was available at 31 regional or remote primary health care clinic sites through the Test-Treat-And-GO (TANGO2) program. This qualitative study sought to identify barriers and facilitators to further scaling up STI POCT in remote Aboriginal communities within Australia. METHODS: A total of 15 healthcare workers (including nurses and Aboriginal health practitioners) and five managers (including clinic coordinators and practice managers) were recruited from remote health services involved in the TTANGO2 program to participate in semi-structured in-depth interviews. Health services' clinics were purposively selected to include those with high or low STI POCT uptake. Personnel participants were selected via a hybrid approach including nomination by clinic managers and purposive sampling to include those in roles relevant to STI testing and treatment and those who had received TTANGO2 training for POCT technology. Milat's scaling up guide informed the coding framework and analysis. RESULTS: Acceptability of STI POCT technology among healthcare workers and managers was predominantly influenced by self-efficacy and perceived effectiveness of POCT technology as well as perceptions of additional workload burden associated with POCT. Barriers to integration of STI POCT included retention of trained staff to conduct POCT. Patient reach (including strategies for patient engagement) was broadly considered an enabler for STI testing scale up using POCT technology.

BACKGROUND: Timely diagnosis and early initiation of life-saving antiretroviral therapy are critical factors in preventing mortality among HIV-infected infants. However, resource-limited settings experience numerous challenges associated with centralised laboratory-based testing, including low rates of testing, complex sample referral pathways and unacceptably long turnaround times for results. Point-of-care (POC) HIV testing for HIV-exposed infants can enable same-day communication of results and early treatment initiation for HIV-infected infants. However, complex operational issues and service integration can limit utility and must be well understood prior to implementation. We explored and documented the challenges and enabling factors in implementing the POC Xpert® HIV-1 Qual test (Cepheid, Sunnyvale, CA, USA) for early infant diagnosis (EID) as part of routine services in four public hospitals in Myanmar. METHODS: This sub-study was part of a randomised controlled stepped-wedge trial (Australian and New Zealand Clinical Trials Registry, number 12616000734460) designed to investigate the impact of POC testing for EID in Myanmar and Papua New Guinea. Infants recruited during the intervention phase underwent POC testing at the participating hospitals as part of routine care. Semi-structured interviews with 23 caregivers, 12 healthcare providers and 10 key informants were used to explore experiences of POC-EID testing. The research team and hospital staff documented and discussed implementation challenges throughout the study. RESULTS: Overall, caregivers and healthcare workers were satisfied with the short turnaround time of the POC test. Occasional delays in POC testing were mostly attributable to late receipt of samples by laboratory technicians and communication constraints among healthcare staff. Hospital staff valued technical assistance from the research group and the National Health Laboratory. Despite staff shortages and infrastructure challenges such as

Much about the range of pathogens, frequency of coinfection, and clinical effects of reproductive tract infections (RTIs) among pregnant women remains unknown. We report on RTIs (Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum subspecies pallidum, bacterial vaginosis, and vulvovaginal candidiasis) and other reproductive health indicators in 699 pregnant women in Papua New Guinea during 2015-2017. We found M. genitalium, an emerging pathogen in Papua New Guinea, in 12.5% of participants. These infections showed no evidence of macrolide resistance. In total, 74.1% of pregnant women had >1 RTI; most of these infections were treatable. We detected sexually transmitted infections (excluding syphilis) in 37.7% of women. Our findings showed that syndromic management of infections is greatly inadequate. In total, 98.4% of women had never used barrier contraception. These findings will inform efforts to improve reproductive healthcare in Papua New Guinea.

Critical to facilitating SARS-CoV-2 point-of-care (POC) testing is assurance that viruses present in specimens are inactivated onsite prior to processing. Here, we conducted experiments to determine the virucidal activity of commercially available Viral Transport Mediums (VTMs) to inactivate SARS-CoV-2. Independent testing methods for viral inactivation testing were applied, including a previously described World Health Organization (WHO) protocol, in addition to a buffer exchange method where the virus is physically separated from the VTM post exposure. The latter method enables sensitive detection of viral viability at higher viral titre when incubated with VTM. We demonstrate that VTM formulations, Primestore® Molecular Transport Medium (MTM) and COPAN eNAT™ completely inactivate high-titre SARS-CoV-2 virus (>1 × 107 copies/mL) and are compatible with POC processing. Furthermore, full viral inactivation was rapidly achieved in as little as 2 min of VTM exposure. We conclude that adding certain VTM formulations as a first step post specimen collection will render SARS-CoV-2 non-infectious for transport, or for further in-field POC molecular testing using rapid turnaround GeneXpert platforms or equivalent.

Background: In this paper, factors associated with HIV and syphilis infection in three cities in Papua New Guinea are explored. Methods: Respondent-driven sampling surveys among FSW in Port Moresby, Lae, and Mt. Hagen (2016-17) were conducted. FSW who were aged ≥12 years, who were born female, who spoke English or Tok Pisin and who had sold or exchanged vaginal sex in the past 6 months were eligible to participate. Participants were interviewed face-to-face and offered rapid HIV and syphilis testing. Survey logistic procedures were used to identify factors associated with HIV and syphilis infection, including modern contraception use, physical violence and having a casual male partner. Weighted data analysis was conducted. Results: Overall, 2901 FSW (Port Moresby, 673; Lae, 709; and Mt. Hagen, 709) were enrolled in the study. HIV prevalence was 15.2% in Port Moresby, 11.9% in Lae and 19.6% in Mt. Hagen. Factors associated with HIV varied by city; for example, use of modern contraception in Port Moresby, experiences of physical violence in Lae and ever having tested for HIV in Mt. Hagen. No one variable was associated with HIV in all cities. Prevalence of syphilis infection was 7.1%, 7.0%, and 3.0% in Port Moresby, Lae, and Mt. Hagen, respectively. Factors associated with syphilis infection also varied by city and were only significant in Lae. Conclusion: The different factors associated with HIV and syphilis infection in each city highlight the complex HIV and syphilis epidemics among FSW and the importance of conducting surveys in multiple locations and developing local interventions.

Background: The aim of this study was to compare the performance of pooled self-collected urogenital, pharyngeal and anorectal specimens to that of individual specimen results for the molecular detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) near the point of care (POC) for diagnostic sensitivity. Methods: Clients (mostly men who have sex with men) attending an urban community testing service and three sex-on-premises venues in Brisbane, Australia, were offered CT and NG testing by trained lay providers. Participants provided three self-collected specimens (urine, pharyngeal and rectal) for testing by GeneXpert (Cepheid, Sunnyvale, CA, USA). If any of the individual specimens from a participant were positive, all three specimens were pooled and retested. Results: Of the 388 participants who provided three individual anatomical specimens, 76 (19.6%) were found to be positive for CT and/or NG at one or more sites. The pooling approach failed to detect five CT rectal and four NG pharyngeal infections. The overall performance (sensitivity) of the pooling approach compared with individual specimen testing and Cohen's κ were 90.0% and 0.86 respectively for CT and 89.7% and 0.89 respectively for NG. Conclusions: Reduced sensitivity was observed when using pooled specimens for the detection of CT and NG using GeneXpert near the POC, similar to results reported in laboratory-based CT and NG pooling studies. These data suggest specimen pooling is feasible near to the POC, potentially saving time and costs when screening at-risk populations for CT and NG. Our data also suggest a reduction in pooled urine could improve overall test sensitivity.

Background: Biobehavioral data about men who have sex with men (MSM) and transgender women (TGW) in Papua New Guinea (PNG) are limited to those who sell sex. Information about those MSM and TGW who do not sell sex is necessary to guide HIV prevention and treatment efforts. Methods: We conducted respondent-driven sampling (RDS) surveys among MSM and TGW in Port Moresby, Lae, and Mt. Hagen, PNG from in 2016 and 2017. Eligibility criteria was: aged > 12 years, born male, could speak English or Tok Pisin and had oral or anal sex with another person born male in the past 6 months. Participants were interviewed face-to-face and offered rapid HIV testing. Weighted data analysis was conducted using RDS-Analyst (v. 0.62). Results: We enrolled 400 participants in Port Moresby, 352 in Lae, and 111 in Mt. Hagen. In the last six months, 73.2% of MSM/TGW in Port Moresby, 77.9% in Lae, and 75.9% in Mt. Hagen, had a concurrent sexual partnership. Upwards of 70% of MSM/TGW in all three cities had sex with a woman in the same period. Less than half of MSM/TGW had ever tested for HIV. HIV prevalence among MSM/TGW was 8.5% in Port Moresby and 6.9% in Lae. Among participants in Mt. Hagen it was 1.3%. HIV was associated with not having sex with a woman in the last six months and sexually transmitted disease symptoms in the last 12 months in Port Moresby and Lae. In Port Moresby, it was also associated with an uncut foreskin, and in Lae with earning income in the formal sector and being unable to rely on other MSM or TGW to accompany them to healthcare services. Conclusions: The large proportion of MSM and TGW with concurrent sexual partnerships, combined with the low testing coverage, indicates strong potential for the spread of HIV. The different correlates of HIV in Port Moresby and Lae highlight the importance of conducting surveys in multiple locations and using data to develop locally appropriate interventions even within a country.

Background: Papua New Guinea (PNG) has a high prevalence of sexually transmitted infections (STIs). There is increasing evidence that anorectal STIs are important in terms of the dual epidemics of HIV and STIs in this setting. At the time of this study, anorectal STI testing was not possible, and there was no mechanism for self-collection of anorectal specimen among at risk 'key populations'. This paper documents the development of a culturally appropriate tool that has been used to facilitate self-collection of anorectal specimens with key populations in PNG. Methods: This qualitative study involved four focus groups conducted with a purposive sample of 35 participants, including female sex workers, men who have sex with men and transgender women in Port Moresby and Goroka in 2015. During focus groups, participants reviewed and provided critical feedback for the adaption of a previously piloted and published pictorial anorectal specimen collection tool for use with key populations in PNG. Results: The final instruction tools are presented in English language and Tok Pisin. To develop these, participants feedback resulted in six key areas of the existing instruction document being modified to ensure it was appropriate for use in PNG. These included translating complex words for sexual health issues (i.e. 'STIs', 'anorectal STIs', 'anus', 'anal sex'), biomedical instruments (i.e. 'specimen bottle', 'specimen packet' and 'swab'), and aspects of the clinical procedure (i.e. inserting the swab 3-4 cm into the anus to collect a specimen). The visual identity of the graphics was redesigned to localise the images for use in PNG. Conclusions: This paper describes the development of a culturally and linguistically appropriate tool for a biomedical and clinical intervention with key populations in PNG based around self-collection of anorectal specimens for molecular STI testing. The final tools have been used to facilitate the self-collection of anorectal specimens following

Objectives: Papua New Guinea has among the highest prevalences of sexually transmissible infections (STIs) globally with no services able to accurately test for anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections. Here we prospectively evaluated the diagnostic performance of a molecular CT/NG assay used at the point-of-care (POC) with the aim of enhancing anorectal STI screening and same-day treatment. Methods: Men who have sex with men, transgender women and female sex workers taking part in Papua New Guinea's first large-scale biobehavioural study were enrolled and asked to provide a self-collected anorectal swab for POC GeneXpert CT/NG testing. Same-day treatment was offered if positive. A convenience sample of 396 unique and randomly selected samples were transported to Australia for comparison using the Cobas 4800 CT/NG test (Roche Molecular Diagnostics, Pleasanton, CA, USA). Results: A total of 326 samples provided valid results by Cobas whereas 70 samples provided invalid results suggesting inhibition. The positive, negative and overall percentage agreements of GeneXpert CT/NG for the detection of C. trachomatis were 96.7% (95% CI 92.3%–98.9%), 95.5% (95% CI 91.3%–98.0%) and 96.0% (95% CI 93.3%–97.8%), and for N. gonorrhoeae were 93.0% (95% CI 86.1%–97.1%), 100.0% (95% CI 98.3%–100.0%) and 97.8% (95% CI 95.6%–99.1%), respectively. Conclusions: The overall rate of agreement between the GeneXpert and Cobas CT/NG assays was high with 96.0% for C. trachomatis and 97.8% for N. gonorrhoeae. Results from this study data suggest that the GeneXpert CT/NG assay is suitable for testing self-collected anorectal specimens at the POC and that same-day treatment was feasible.

Background: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low- and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods: The Women and Newborn Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI 'syndromic' management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their newborns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access t

Background: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low-and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods: The Women and New born Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI ‘syndromic’ management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their new borns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access

Objectives A new molecular test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) (GeneXpert CT/NG) has been demonstrated to be as accurate as conventional nucleic acid amplification tests (NAAT), but performance has not been evaluated in routine primary care, performed at the point of care by clinicians. We aimed to examine its diagnostic performance when used by clinicians in remote community health services in Australia with high prevalences of CT and NG infection. The trial was registered with the Australian and New Zealand Clinical Trials Registry (#12613000808741) Methods At 12 health services, training was provided to 99 clinicians in the use of the GeneXpert CT/NG assay who tested specimens from all patients undergoing STI screening. Specimens were also sent in parallel for conventional laboratory-based NAATs and the concordance of results was evaluated. Results Clinicians conducted 2486 tests: CT concordance was 99.4% (95% CI 99.1 to 99.7) with a positive concordance of 98.6% (95% CI 95.9 to 99.7) and negative concordance of 99.5% (95% CI 99.1 to 99.8); NG concordance was 99.9% (95% CI 99.7 to 100.0) with a positive concordance of 100.0% (95% CI 97.5 to 100.0) and negative concordance of 99.9% (95% CI 99.7 to 100.0). Conclusions In this first study reporting routine point-of-care use of GeneXpert CT/NG by primary care clinicians, we found excellent concordance with conventional NAATs. The use of the GeneXpert CT/NG at the point of care could potentially transform management and control of these infections in many endemic settings, including low/middle-income countries.

The performance of different clinical screening algorithms comprising point-of-care HPV-DNA testing using self-collected vaginal (‘V’) specimens, and visual inspection of the cervix with acetic acid (VIA) was evaluated in Papua New Guinea. Women aged 30–59 years provided V specimens that were tested at point-of-care using the Xpert HPV Test (Cepheid, Sunnyvale, CA). A clinician-collected cervical (‘C’) specimen was then collected for point-of-care Xpert testing, and liquid-based cytology (LBC). Following this, VIA examination was conducted, blind to HPV test results, and ablative cervical cryotherapy provided if indicated. Detection of high-grade squamous intraepithelial lesion (HSIL) by LBC was the reference standard used to evaluate clinical screening algorithms. Of 1005 women, 36 had HSIL+. Xpert HPV Test performance using V specimens (sensitivity 91.7%, specificity 87.0%, PPV 34.0%, NPV 99.3%) was superior to VIA examination alone (51.5%, 81.4%, 17.5%, 95.6% respectively) in predicting underlying HSIL+. A screening algorithm comprising V specimen HPV testing followed by VIA examination had low sensitivity (45.5%) but comparable specificity, PPV and NPV to HPV testing alone (96.3%, 45.5%, 96.3% respectively). A ‘test-and-treat’ screening algorithm based on point-of-care HPV testing of V specimens had superior performance compared with either VIA examination alone, or a combined screening algorithm comprising HPV testing plus VIA.

Objectives Global concerns regarding the prevalence, asymptomatic nature and burden of disease associated with Trichomonas vaginalis (TV) continue. The lack of a portable molecular point-of-care assay to detect this infectious disease has meant that many remote or low-resource settings still need to rely on delayed results from central laboratories and/or syndromic management as treatment strategies. We evaluated the new GeneXpert (Gx) TV nucleic acid amplification test (NAAT) compared with an in-house laboratory NAAT to determine whether it would be suitable for use at the point of care. Methods In a state-based laboratory and using their in-house NAAT, we selected the first 60 urine samples that were positive and the first 60 that were negative (n=120) in the study period for Gx TV testing in order to reduce collection delays and avoid the freezing of samples. Results Positive percentage agreement between the Gx TV and NAAT was 95.0% (95% CI 86.1% to 99.0%), negative percentage agreement was 100.0% (95% CI 93.5% to 100.0%) and overall percentage agreement was 97.4% (95% CI 92.5% to 99.5%). Three discordant results were detected with each being close to the cycle threshold of detection using the in-house NAAT assay. Conclusions Findings suggest the Gx TV assay is easy to use and has suitable overall agreement for sexually transmissible infection (STI) testing at the point of care. It may be used in combination with the Gx CT/NG assay to test for all three STIs simultaneously using this portable and modular-based NAAT platform.

© 2016 The Author(s).Sexually transmitted and genital infections in pregnancy are associated with an increased risk of adverse maternal and neonatal health outcomes. High prevalences of sexually transmitted infections have been identified among antenatal attenders in Papua New Guinea. Papua New Guinea has amongst the highest neonatal mortality rates worldwide, with preterm birth and low birth weight major contributors to neonatal mortality. The overall aim of our study was to determine if a novel point-of-care testing and treatment strategy for the sexually transmitted and genital infections Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Bacterial vaginosis (BV) in pregnancy is feasible in the high-burden, low-income setting of Papua New Guinea. Methods: Women attending their first antenatal clinic visit were invited to participate. CT/NG and TV were tested using the GeneXpert platform (Cepheid, USA), and BV tested using BVBlue (Gryphus Diagnostics, USA). Participants received same-day test results and antibiotic treatment as indicated. Routine antenatal care including HIV and syphilis screening were provided. Results: Point-of-care testing was provided to 125/222 (56 %) of women attending routine antenatal care during the three-month study period. Among the 125 women enrolled, the prevalence of CT was 20.0 %; NG, 11.2 %; TV, 37.6 %; and BV, 17.6 %. Over half (67/125, 53.6 %) of women had one or more of these infections. Most women were asymptomatic (71.6 %; 47/67). Women aged 24 years and under were more likely to have one or more STI compared with older women (odds ratio 2.38; 95 % CI: 1.09, 5.21). Most women with an STI received treatment on the same day (83.6 %; 56/67). HIV prevalence was 1.6 % and active syphilis 4.0 %. Conclusion: Point-of-care STI testing and treatment using a combination of novel, newly-available assays was feasible during routine antenatal care in this setting. This strategy has not previously been ev

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.

© 2015 CSIRO. Background Point-of-care (POC) tests could be important public health tools in settings with treatment delays and high rates of sexually transmissible infections (STIs). Use is limited due to suboptimal performance. The performance and ease-of-use of a new molecular-based POC test for simultaneous detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was assessed, alongside two single-organism immunochromatographic tests (ICT). Methods: The evaluation occurred between May 2012 and March 2013 during community STI screens in two remote Aboriginal health services. Urine was tested with the GeneXpert®CT/NG and if sufficient volume, also with Diaquick CT and Gonorrhoea Card. The gold standard comparison was laboratory nucleic acid amplification testing (NAAT). Operational characteristics were also assessed. Results: Among 198 samples, GeneXpert CT sensitivity and specificity was 100% [95% confidence intervals (CI): 75.9-100] and 99.5% (95% CI: 96.5-100), and NG was 100% (95% CI: 96.5-100) and 100% (95% CI: 97.5-100), respectively. Among a sample subset, Diaquick CT (n≤104) sensitivity and specificity was 27.3% (95% CI: 7.3-60.7) and 66.7% (95% CI: 12.5-98.2), and Gonorrhoea Card (n≤29), was 66.7% (95% CI: 12.5-98.2) and 76.9% (95% CI: 56.0-90.2), respectively. GeneXpert required 1mL of urine, four steps, 1min specimen preparation and 90min to result. ICTs required 15mL of urine, eight steps, 18min preparation and 10-15min to result. Conclusion: The accuracy and operational benefits of GeneXpert CT/NG make it very suitable in these settings where delays to treatment are encountered.

Background Point-of-care tests for chlamydia (CT) and gonorrhoea (NG) could increase the uptake and timeliness of testing and treatment, contribute to improved disease control and reduce reproductive morbidity. The GeneXpert (Xpert CT/NG assay), suited to use at the pointof- care, is being used in the TTANGO randomised controlled trial (RCT) in 12 remote Australian health services with a high burden of sexually transmissible infections (STIs). This represents the first ever routine use of a molecular point-of-care diagnostic for STIs in primary care. The purpose of this study was to explore the acceptability of the GeneXpert to primary care staff in remote Australia. Methods In-depth qualitative interviews were conducted with 16 staff (registered or enrolled nurses and Aboriginal Health Workers/Practitioners) trained and experienced with GeneXpert testing. Interviews were digitally-recorded and transcribed verbatim prior to content analysis. Results Most participants displayed positive attitudes, indicating the test was both easy to use and useful in their clinical context. Participants indicated that point-of-care testing had improved management of STIs, resulting in more timely and targeted treatment, earlier commencement of partner notification, and reduced follow up efforts associated with client recall. Staff expressed confidence in point-of-care test results and treating patients on this basis, and reported greater job satisfaction. While point-of-care testing did not negatively impact on client flow, several found the manual documentation processes time consuming, suggesting that improved electronic connectivity and test result transfer between the GeneXpert and patient management systems could overcome this. Managing positive test results in a shorter time frame was challenging for some but most found it satisfying to complete episodes of care more quickly. Conclusions In the context of a RCT, health professionals working in remote primary care in Australia

OBJECTIVES: With accurate molecular tests now available for diagnosis of chlamydia and gonorrhoea (Chlamydia trachomatis (CT)/Neisseria gonorrhoeae (NG)) at the point-of-care (POC), we aimed to explore the public health implications (benefits and barriers) of their integration into remote primary care in Australia.

BACKGROUND: Point-of-care tests for chlamydia (CT) and gonorrhoea (NG) could increase the uptake and timeliness of testing and treatment, contribute to improved disease control and reduce reproductive morbidity. The GeneXpert (Xpert CT/NG assay), suited to use at the point-of-care, is being used in the TTANGO randomised controlled trial (RCT) in 12 remote Australian health services with a high burden of sexually transmissible infections (STIs). This represents the first ever routine use of a molecular point-of-care diagnostic for STIs in primary care. The purpose of this study was to explore the acceptability of the GeneXpert to primary care staff in remote Australia. METHODS: In-depth qualitative interviews were conducted with 16 staff (registered or enrolled nurses and Aboriginal Health Workers/Practitioners) trained and experienced with GeneXpert testing. Interviews were digitally-recorded and transcribed verbatim prior to content analysis. RESULTS: Most participants displayed positive attitudes, indicating the test was both easy to use and useful in their clinical context. Participants indicated that point-of-care testing had improved management of STIs, resulting in more timely and targeted treatment, earlier commencement of partner notification, and reduced follow up efforts associated with client recall. Staff expressed confidence in point-of-care test results and treating patients on this basis, and reported greater job satisfaction. While point-of-care testing did not negatively impact on client flow, several found the manual documentation processes time consuming, suggesting that improved electronic connectivity and test result transfer between the GeneXpert and patient management systems could overcome this. Managing positive test results in a shorter time frame was challenging for some but most found it satisfying to complete episodes of care more quickly. CONCLUSIONS: In the context of a RCT, health professionals working in remote primary care in Austra

Objectives: Point-of-care (POC) testing for chlamydia (CT) and gonorrhoea (NG) offers a new approach to the diagnosis and management of these sexually transmitted infections (STIs) in remote Australian communities and other similar settings. Diagnosis of STIs in remote communities is typically symptom driven, and for those who are asymptomatic, treatment is generally delayed until specimens can be transported to the reference laboratory, results returned and the patient recalled. The objective of this study was to explore the clinical implications of using CT/NG POC tests in routine clinical care in remote settings. Methods: In-depth qualitative interviews were conducted with a purposively selected group of 18 key informants with a range of sexual health and laboratory expertise. Results: Participants highlighted the potential impact POC testing would have on different stages of the current STI management pathway in remote Aboriginal communities and how the pathway would change. They identified implications for offering a POC test, specimen collection, conducting the POC test, syndromic management of STIs, pelvic inflammatory disease diagnosis and management, interpretation and delivery of POC results, provision of treatment, contact tracing, management of client flow and wait time, and re-testing at 3 months after infection. Conclusions: The introduction of POC testing to improve STI service delivery requires careful consideration of both its advantages and limitations. The findings of this study will inform protocols for the implementation of CT/NG POC testing, and also STI testing and management guidelines. © 2014 Natoli et al.

OBJECTIVES: Point-of-care (POC) testing for chlamydia (CT) and gonorrhoea (NG) offers a new approach to the diagnosis and management of these sexually transmitted infections (STIs) in remote Australian communities and other similar settings. Diagnosis of STIs in remote communities is typically symptom driven, and for those who are asymptomatic, treatment is generally delayed until specimens can be transported to the reference laboratory, results returned and the patient recalled. The objective of this study was to explore the clinical implications of using CT/NG POC tests in routine clinical care in remote settings. METHODS: In-depth qualitative interviews were conducted with a purposively selected group of 18 key informants with a range of sexual health and laboratory expertise. RESULTS: Participants highlighted the potential impact POC testing would have on different stages of the current STI management pathway in remote Aboriginal communities and how the pathway would change. They identified implications for offering a POC test, specimen collection, conducting the POC test, syndromic management of STIs, pelvic inflammatory disease diagnosis and management, interpretation and delivery of POC results, provision of treatment, contact tracing, management of client flow and wait time, and re-testing at 3 months after infection. CONCLUSIONS: The introduction of POC testing to improve STI service delivery requires careful consideration of both its advantages and limitations. The findings of this study will inform protocols for the implementation of CT/NG POC testing, and also STI testing and management guidelines.