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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: As of mid-2021, Australia's only nationwide coronavirus disease 2019 (COVID-19) epidemic occurred in the first 6 months of the pandemic. Subsequently, there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroprevalence generated during this time, we undertook Australia's largest national SARS-CoV-2 serosurvey. METHODS: Between June 19 and August 6, 2020, residual specimens were sampled from people undergoing general pathology testing (all ages), women attending antenatal screening (20-39 years), and blood donors (20-69 years) based on the Australian population's age and geographic distributions. Specimens were tested by Wantai total SARS-CoV-2-antibody assay. Seroprevalence estimates adjusted for test performance were produced. The SARS-CoV-2 antibody-positive specimens were characterized with microneutralization assays. RESULTS: Of 11 317 specimens (5132 general pathology; 2972 antenatal; 3213 blood-donors), 71 were positive for SARS-CoV-2-specific antibodies. Seroprevalence estimates were 0.47% (95% credible interval [CrI], 0.04%-0.89%), 0.25% (CrI, 0.03%-0.54%), and 0.23% (CrI, 0.04%-0.54%), respectively. No seropositive specimens had neutralizing antibodies. CONCLUSIONS: Australia's seroprevalence was extremely low (<0.5%) after the only national COVID-19 wave thus far. These data and the subsequent limited community transmission highlight the population's naivety to SARS-CoV-2 and the urgency of increasing vaccine-derived protection.

BACKGROUND: Scabies causes intense itching and skin lesions. A small number of studies have shown that scabies impacts health-related quality of life (HRQoL), but no studies have been conducted in the Pacific region. We assessed the impact of scabies on HRQoL in a high-prevalence setting using the Children's Dermatology Life Quality Index (CDLQI) and Dermatology Life Quality Index (DLQI). We also assessed the validity of these tools in a Pacific Island population. METHODS: The study was conducted in the Solomon Islands. Participants with and without skin disease were randomly selected. HRQoL indices were scored on a scale of 0-30. RESULTS: We surveyed 1051 adults (91 with scabies) and 604 children (103 with scabies). Scabies had a small impact on HRQoL, with a median DLQI score of 2 (interquartile range [IQR] 0-6) and a CDLQI score of 2 (IQR 0-4). Scores increased linearly with severity. The greatest impact on QoL was due to itch, sleep disturbance and impacts on education and employment. CONCLUSIONS: Scabies has a small but measurable impact on HRQoL. The DLQI and CDLQI scores were discriminated between the skin-related QoL of patients with scabies and the control group, indicating that these tools are appropriate to measure skin-related QoL in the Solomon Islands.

OBJECTIVE: Recent surveys identified trachomatous inflammation - follicular (TF) at endemic levels in the Torres Strait Islands; however, local health staff do not report trachomatous trichiasis (TT) in adults. We undertook a cross-sectional survey involving eye examination and microbiological testing to better understand this disconnect. METHODS: We examined 169 of 207 (82%) residents and collected ocular swabs for polymerase chain reaction (PCR) testing for Chlamydia trachomatis. Other viral PCR tests and bacterial culture were also performed. RESULTS: TF prevalence in children aged 5-9 years was 23% (7/30). No ocular C. trachomatis was identified by PCR. For the 72 participants (43%) with follicles, bacterial culture was positive for 11 (15%) individuals. No individual had trachomatous trichiasis. CONCLUSIONS: Follicular conjunctivitis consistent with TF was prevalent but ocular C. trachomatis and cicatricial trachoma were absent. Non-chlamydial infections or environmental causes of follicular conjunctivitis may be causing TF in this community. IMPLICATIONS FOR PUBLIC HEALTH: In similar settings, reliance on simplified clinical assessment alone may lead to an overestimation of the public health problem posed by trachoma. Consideration should be given to incorporating C. trachomatis PCR, and in certain settings, a detailed clinical exam could be performed by an experienced ophthalmologist during prevalence surveys.

BACKGROUND: Scabies is a neglected tropical disease of the skin that can lead to impetigo, serious secondary bacterial infections and immune-mediated diseases. Mass drug administration (MDA) has been reported in several studies to reduce the prevalence of scabies and impetigo. We aimed to assess the efficacy of MDA for scabies on scabies and impetigo. METHODS: We conducted a systematic review and meta-analysis of reports on the impact of MDA on scabies and impetigo. We included randomized control trials and observational evaluations reported from January 1970 to April 2021 and involving human participants. We searched PubMed, Ovid Medline, Embase, and Cochrane. We considered MDA as treatment intended for the whole population, regardless of individual infection status or symptoms. The main outcome assessed was the change in scabies and impetigo prevalence following MDA. This review is registered with PROSPERO (CRD42020169839). RESULTS: We identified 1110 records, of which 11 met inclusion criteria for the review and 9 were deemed suitable for meta-analysis for scabies and 4 for impetigo. Most studies were in small populations. There was a high degree of heterogeneity between studies (I2 value 96.19%). The overall relative reduction of the impact of MDA on scabies prevalence was 79%. The effect size was comparable for MDA based on ivermectin and permethrin. MDA for scabies also led to a reduction in impetigo prevalence with a relative reduction of 66%. CONCLUSIONS: MDA for scabies is highly effective in reducing the prevalence of scabies and impetigo. Further research is needed to determine the durability of impact, and the effectiveness of MDA regimens in larger populations.

Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June and September 2020. The aim was to determine the extent of infection spread and whether seroprevalence varied demographically in proportion to reported cases of infection. The design involved stratified sampling of residual specimens from blood donors (aged 20-69 years) in three postcode groups defined by low (<3 cases/1,000 population), medium (3-7 cases/1,000 population) and high (>7 cases/1,000 population) COVID-19 incidence based on case notification data. All specimens were tested using the Wantai SARS-CoV-2 total antibody assay. Seroprevalence was estimated with adjustment for test sensitivity and specificity for the Melbourne metropolitan blood donor and residential populations, using multilevel regression and poststratification. Overall, 4,799 specimens were collected between 23 November and 17 December 2020. Seroprevalence for blood donors was 0.87% (90% credible interval: 0.25-1.49%). The highest estimates, of 1.13% (0.25-2.15%) and 1.11% (0.28-1.95%), respectively, were observed among donors living in the lowest socioeconomic areas (Quintiles 1 and 2) and lowest at 0.69% (0.14-1.39%) among donors living in the highest socioeconomic areas (Quintile 5). When extrapolated to the Melbourne residential population, overall seroprevalence was 0.90% (0.26-1.51%), with estimates by demography groups similar to those for the blood donors. The results suggest a lack of extensive community transmission and good COVID-19 case ascertainment based on routine testing during Victoria's second epidemic wave. Residual blood donor samples provide a practical epidemiological tool for estimating seroprevalence and information on popula

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

OBJECTIVES: To compare the usability and acceptability of oral fluid- and blood-based HIV self-test kits among men who have sex with men in Australia. DESIGN: Randomised crossover trial. SETTING, PARTICIPANTS: Gay, bisexual, and other men aged 18 years or older who have sex with men, who attended two metropolitan sexual health clinics in Sydney and Melbourne, 7 January - 10 December 2019. MAIN OUTCOME MEASURES: Ease of use of HIV self-test kits; preferred HIV self-test type; difficulties encountered during HIV self-testing. RESULTS: 170 men were recruited (median age, 34 years; interquartile range, 29-43 years); 144 identified as gay (85%), 96 were born outside Australia (57%). Participants were more likely to report the oral fluid HIV self-test was easy to use than the blood-based self-test (oral fluid, 99%; blood, 86%; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4-6.6). The oral fluid test was preferred by 98 participants (58%; 95% CI, 50-65%), the blood-based test by 69 (41%; 95% CI, 33-48%). Difficulties with the oral fluid test kit identified by observing nurses included problems placing the buffer solution into the stand (40 of 170 participants, 24%) and not swabbing both gums (23 of 169, 14%); difficulties with the blood-based test kit included problems filling the device test channel (69 of 170, 41%) and squeezing the finger firmly enough to generate a blood drop (42 of 170, 25%). No participant received an invalid result with the oral fluid self-test; two of 162 participants (1%) received invalid results with the blood self-test. After adjusting for age, education level, and ethnic background, characteristics associated with higher odds of using HIV self-testing in the future were overseas birth (adjusted OR, 3.07; 95% CI, 1.42-6.64), and self-evaluated ease of use and confidence in using the kits. CONCLUSION: It is important to provide options for obtaining both oral fluid- and blood-based HIV self-tests. The usability and acceptability of both k

Background: HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. Methods: We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. Results: Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit’s reliability, particularly when compared with highly reliable clinic-based testing. Conclusion: HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.

Background A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. Methods Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). Findings Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. Interpretation In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. Funding This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

BACKGROUND: Bancroftian filariasis remains endemic in Fiji despite >10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomized trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated. METHODS: This cluster randomized study compared the individual efficacy and community impact of IDA vs DA as MDA for lymphatic filariasis in 35 villages on 2 islands of Fiji. Participants were tested at enrollment for circulating filarial antigen and, if positive, for microfilariae. Weight-dosed treatment was offered according to village randomization. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma were retested at 24 months. RESULTS: A total of 3816 participants were enrolled and 3616 were treated. At 12 months, microfilariae clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA, 69.2% (95% confidence interval [CI], 57.2%-79.1%) vs IDA, 62.5% (95% CI, 43.6%-78.2%); risk difference, 11.3 % (95% CI, -10% to 32.7%); P = .30. There was no difference between treatment groups in community prevalence of microfilariae at 12 months or individual clearance at 24 months. CONCLUSIONS: We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected reinfection rates. Clinical Trials Registration: NCT03177993 and Australian New Zealand Clinical Trial Registry: N12617000738325.

BACKGROUND: Scabies causes considerable morbidity in disadvantaged populations. The International Alliance for the Control of Scabies (IACS) published consensus criteria in 2020 to standardize scabies diagnosis. However, these criteria are complex, and a WHO informal consultation proposed simplified criteria for mapping, to identify regions of high prevalence as targets for mass drug administration. We aimed to investigate the accuracy of simplified criteria in determining scabies prevalence, compared to the 2020 IACS criteria. METHODS: We obtained data relating to demographics, relevant history and skin lesions from all-age prevalence surveys from Fiji (n = 3365) and Solomon Islands (n = 5239), as well as school-aged children in Timor-Leste (n = 1043). We calculated prevalence using the 2020 IACS criteria and simplified criteria and compared these disease estimates. RESULTS: There was no significant difference in the pooled prevalence using the two methods (2020 IACS criteria: 16.6%; simplified criteria: 15.6%; difference = 0.9, [95% CI -0.1, 2.0]). In Timor-Leste, the prevalence using simplified criteria was lower (26.5% vs 33.8%). Simplified criteria had a sensitivity of 82.3% (95% CI 80.2, 84.2) and specificity of 97.6% (95% CI 97.2, 97.9) compared to the 2020 IACS criteria. CONCLUSIONS: The scabies prevalence estimation using simplified criteria was similar to using the 2020 IACS criteria in high prevalence, tropical countries. The prevalence estimation was lower in the school-based survey in Timor-Leste. Mapping using simplified criteria may be a feasible and effective public health tool to identify priority regions for scabies control. Further work assessing use of simplified criteria for mapping in a field setting should be conducted.

OBJECTIVES: To estimate SARS-CoV-2-specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID-19) in Sydney. SETTING, PARTICIPANTS: People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20-39 years who had received routine antenatal screening; and Australian Red Cross Lifeblood plasmapheresis donors aged 20-69 years. DESIGN: Cross-sectional study; testing of de-identified residual blood specimens collected during 20 April - 2 June 2020. MAIN OUTCOME MEASURE: Estimated proportions of people seropositive for anti-SARS-CoV-2-specific IgG, adjusted for test sensitivity and specificity. RESULTS: Thirty-eight of 5339 specimens were IgG-positive (general pathology, 19 of 3231; antenatal screening, 7 of 560; plasmapheresis donors, 12 of 1548); there were no clear patterns by age group, sex, or location of residence. Adjusted estimated seroprevalence among people who had had general pathology blood tests (all ages) was 0.15% (95% credible interval [CrI], 0.04-0.41%), and 0.29% (95% CrI, 0.04-0.75%) for plasmapheresis donors (20-69 years). Among 20-39-year-old people, the age group common to all three collection groups, adjusted estimated seroprevalence was 0.24% (95% CrI, 0.04-0.80%) for the general pathology group, 0.79% (95% CrI, 0.04-1.88%) for the antenatal screening group, and 0.69% (95% CrI, 0.04-1.59%) for plasmapheresis donors. CONCLUSIONS: Estimated SARS-CoV-2 seroprevalence was below 1%, indicating that community transmission was low during the first COVID-19 epidemic wave in Sydney. These findings suggest that early control of the spread of COVID-19 was successful, but efforts to reduce further transmission remain important.

Pacific Island countries have a high burden of scabies and impetigo. Understanding of the epidemiology of these diseases is needed to target public health interventions such as mass drug administration (MDA). The aim of this study is to determine the prevalence of scabies and impetigo in Solomon Islands as well as the relationship between them and their distribution. We conducted a prevalence study in 20 villages in Western Province in Solomon Islands. All residents of the village were eligible to participate. Nurses conducted clinical assessments including history features and skin examination. Diagnosis of scabies was made using the 2020 International Alliance for the Control of Scabies diagnostic criteria. Assessments were completed on 5239 participants across 20 villages. Overall scabies prevalence was 15.0% (95%CI 11.8-19.1). There was considerable variation by village with a range of 3.3% to 42.6%. There was a higher prevalence of scabies in males (16.7%) than females (13.5%, adjusted relative risk 1.2, 95%CI 1.1-1.4). Children aged under two years had the highest prevalence (27%). Overall impetigo prevalence was 5.6% (95%CI 4.2-7.3), ranging from 1.4% to 19% by village. The population attributable risk of impetigo associated with scabies was 16.1% (95% CI 9.8-22.4). The prevalence of scabies in our study is comparable to previous studies in Solomon Islands, highlighting a persistent high burden of disease in the country, and the need for public health strategies for disease control.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

BACKGROUND: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. METHODS: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). FINDINGS: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. INTERPRETATION: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. FUNDING: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

OBJECTIVE: To examine associations between Neisseria gonorrhoeae (NG) infection during pregnancy and the risk of preterm birth, spontaneous abortion, premature rupture of membranes, perinatal mortality, low birth weight and ophthalmia neonatorum. DATA SOURCES: We searched Medline, EMBASE, the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature for studies published between 1948 and 14 January 2020. METHODS: Studies were included if they reported testing for NG during pregnancy and compared pregnancy, perinatal and/or neonatal outcomes between women with and without NG. Two reviewers independently assessed papers for inclusion and extracted data. Risk of bias was assessed using established checklists for each study design. Summary ORs with 95% CIs were generated using random effects models for both crude and, where available, adjusted associations. RESULTS: We identified 2593 records and included 30 in meta-analyses. Women with NG were more likely to experience preterm birth (OR 1.55, 95% CI 1.21 to 1.99, n=18 studies); premature rupture of membranes (OR 1.41, 95% CI 1.02 to 1.92, n=9); perinatal mortality (OR 2.16, 95% CI 1.35 to 3.46, n=9); low birth weight (OR 1.66, 95% CI 1.12 to 2.48, n=8) and ophthalmia neonatorum (OR 4.21, 95% CI 1.36 to 13.04, n=6). Summary adjusted ORs were, for preterm birth 1.90 (95% CI 1.14 to 3.19, n=5) and for low birth weight 1.48 (95% CI 0.79 to 2.77, n=4). In studies with a multivariable analysis, age was the variable most commonly adjusted for. NG was more strongly associated with preterm birth in low-income and middle-income countries (OR 2.21, 95% CI 1.40 to 3.48, n=7) than in high-income countries (OR 1.38, 95% CI 1.04 to 1.83, n=11). CONCLUSIONS: NG is associated with a number of adverse pregnancy and newborn outcomes. Further research should be done to determine the role of NG in different perinatal mortality outcomes because interventions that reduce mortality will have the greatest impact on reducing

Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals.

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.

© 2020 Hardy et al. Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community pro-grams where preventative chemo

Background. Ivermectin-based mass drug administration has emerged as a promising strategy for the control of scabies and impetigo in settings where the diseases are endemic. Current follow-up data are limited to 12 months for the majority of studies. Longer-term data are vital to inform the sustainability of interventions. Methods. We conducted a prevalence survey for scabies and impetigo in 10 villages in Choiseul Province of the Solomon Islands 36 months after a single round of ivermectin and azithromycin mass drug coadministration. In the primary analysis, we compared the prevalence of scabies and impetigo at 36 months to the prevalence at baseline. Results. At 36 months, the prevalence of scabies was 4.7% (95% confidence interval [CI], 3.6-6.1), which was significantly lower than at baseline (18.7%; relative reduction, 74.9%; 95% CI, 61.5%-87.7%; P <.001). The prevalence of impetigo was 9.6% (95% CI, 8.1%-11.4%), significantly lower than at baseline (24.7%; relative reduction, 61.3%; 95% CI, 38.7%-100%; P <.001). The highest prevalence of scabies was among children aged <5 years (12.5%; adjusted odds ratio, 33.2; 95% CI, 6.6-603.2), and the highest prevalence of impetigo was among children aged 5-9 years (16.4%; adjusted odds ratio, 8.1; 95% CI, 3.6-21.8). Conclusions. There was a sustained impact of a single round of ivermectin and azithromycin mass drug coadministration on the prevalence of scabies and impetigo 3 years after the intervention. Our data provide further support to adopt this intervention as a central component of global scabies control efforts.

Objectives Key strategies to control chlamydia include testing, treatment, partner management and re-testing. We developed a diagnosis and care cascade for chlamydia to highlight gaps in control strategies nationally and to inform efforts to optimise control programmes. Methods The Australian Chlamydia Cascade was organised into four steps: (1) annual number of new chlamydia infections (including re-infections); (2) annual number of chlamydia diagnoses; (3) annual number of diagnoses treated; (4) annual number of diagnoses followed by a re-test for chlamydia within 42-180 days of diagnosis. For 2016, we estimated the number of infections among young men and women aged 15-29 years in each of these steps using a combination of mathematical modelling, national notification data, sentinel surveillance data and previous research studies. Results Among young people in Australia, there were an estimated 248 580 (range, 240 690-256 470) new chlamydia infections in 2016 (96 470 in women; 152 100 in men) of which 70 164 were diagnosed (28.2% overall: women 43.4%, men 18.6%). Of the chlamydia infections diagnosed, 65 490 (range, 59 640-70 160) were treated (93.3% across all populations), but only 11 330 (range, 7660-16 285) diagnoses were followed by a re-test within 42-180 days (17.3% overall: women 20.6%, men 12.5%) of diagnosis. Conclusions The greatest gaps in the Australian Chlamydia Cascade for young people were in the diagnosis and re-testing steps, with 72% of infections undiagnosed and 83% of those diagnosed not re-tested: both were especially low among men. Treatment rates were also lower than recommended by guidelines. Our cascade highlights the need for enhanced strategies to improve treatment and re-testing coverage such as short message service reminders, point-of-care and postal test kits.

BACKGROUND: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. METHODS: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. RESULTS: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. CONCLUSION: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.

Routine antenatal screening for chronic hepatitis B (HBV) in countries with high migrant populations provides an opportunity to monitor trends in HBV prevalence and can inform estimates locally and in countries with limited seroprevalence data. We linked perinatal birth register records with HBV notifications in the largest Australian state, over the period 2000-2016. Among women aged 15-44 years, we estimated age-standardized chronic HBV prevalence overall and by country of birth and also estimated trends in age-standardized HBV prevalence over time using regression modelling. Among 903 831 women, 8001 linked to a chronic HBV infection record (overall age-standardized prevalence 0.76%, 95% CI: 0.74-0.78). Prevalence varied by country of birth with the highest estimates among women born in Sierra Leone (11.13%, 95% CI: 8.29-13.96), Taiwan (8.08%, 95% CI: 6.74%-9.43%), Cambodia (7.47%, 95% CI: 6.50%-8.45%) and Vietnam (7.36%, 95% CI: 6.97%-7.75%); more moderate estimates among women from North Korea (2.76%, 95% CI: 1.99-3.53) and Samoa (2.64%, 95% CI: 1.99%-3.29%); prevalence was 0.18% (95% CI: 0.17-0.19) in Australian-born women. Over 17 years, there were significant reductions in HBV prevalence among all women (from 0.88% in 2000 to 0.57% in 2016; P < .0001). Among women from high prevalence countries, the greatest absolute reductions were observed among those from Taiwan (10.1%, P < .001) followed by Tonga (5.4%, P < .001), whereas no reductions were observed for women born in Vietnam (P = .08), South Korea (P = .41) and Sudan (P = .06). In conclusion, routine antenatal HBV testing can be used to inform HBV prevalence estimates and vaccine programme impact in countries with limited surveillance and high migration to Australia.

The prevalence of antibodies to Strongyloides stercoralis was measured in 0-12-year-olds using a bead-based immunoassay before and after ivermectin mass drug administration (MDA) for scabies in the Solomon Islands. Seroprevalence was 9.3% before and 5.1% after MDA (P = .019), demonstrating collateral benefits of ivermectin MDA in this setting.

Australia's new HPV-based cervical screening program is based on an algorithm that incorporates reflex cytology to guide decisions about further follow-up with colposcopy and, if indicated, biopsy. We reviewed results for 2300 women referred directly for colposcopy after their first positive HPV screening test, to determine the proportion that had underlying histological high-grade abnormality (HGA). Overall, HGA was detected in 24.3% of women. Among HPV16/18 positive women, 18.0% had HGA, increasing from 6.6% among women with negative cytology to 79.7% among women with high-grade squamous lesion or worse, or any glandular lesion on cytology (HSIL+; P-trend < .001). For this latter group, the proportion with HGA was higher among HPV16/18 positive women than among those positive for other oncogenic types (68.8%; P = .029). Among women with ASC-H cytology, 51.8% had HGA, with no difference between HPV groups (P = .314). In analyses by age-groups, detection of HGA was highest, at 36.4%, among women younger than 35 years, then decreased significantly to 5.9%, among women aged 65 to 74 years (P-trend < .001). The relationship of decreasing HGA detection with increasing age was strong for women with negative cytology, and those with ASC-H cytology (P-trend < .001 for each). For women with HSIL+ cytology, detection of HGA was high and stable, regardless of age (P-trend = .211). This report describes the first follow-up colposcopy findings in Australia's new HPV-based cervical screening program. The results demonstrate the additional value of reflex cytology in managing HPV positive women and suggest that further refinement of the risk-based algorithm to account for age may be warranted.

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for

Objectives: To estimate rates of HIV infection, chlamydia, gonorrhoea, and infectious syphilis in transgender men and women in Australia; to compare these rates with those for cisgender people. Design: Cross-sectional, comparative analysis of de-identified health data. Setting, participants: We analysed data for 1260 transgender people (404 men, 492 women, 364 unrecorded gender), 78 108 cisgender gay and bisexual men, and 309 740 cisgender heterosexual people who attended 46 sexual health clinics across Australia during 2010–2017. Main outcome measures: First-visit test positivity for sexually transmitted infections (STIs), stratified by patient group and year; demographic and behavioural factors associated with having STIs. Results: 14 of 233 transgender men (6.0%) and 34 of 326 transgender women (10%) tested during first clinic visits were chlamydia-positive; nine transgender men (4%) and 28 transgender women (8.6%) were gonorrhoea-positive. One of 210 tested transgender men (0.5%) and ten of 324 tested transgender women (3.1%) were diagnosed with infectious syphilis; 14 transgender men (3.5%) and 28 transgender women (5.7%) were HIV-positive at their first visit. The only significant change in prevalence of an STI among transgender patients during the study period was the increased rate of gonorrhoea among transgender women (from 3.1% to 9.8%). Compared with cisgender gay and bisexual men, transgender men were less likely (adjusted odds ratio [aOR], 0.46; 95% CI, 0.29–0.71; P = 0.001) and transgender women as likely (aOR, 0.98; 95% CI, 0.73–1.32; P = 0.92) to be diagnosed with a bacterial STI; compared with heterosexual patients, transgender men were as likely (aOR, 0.72; 95% CI, 0.46–1.13; P = 0.16) and transgender women more likely (aOR, 1.56; 95% CI, 1.16–2.10; P = 0.003) to receive a first-visit bacterial STI diagnosis. Conclusions: The epidemiology of STIs in transgender people attending Australian sexual health clinics differs from that of cisgender patient

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.

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

Gonorrhea and chlamydia are important causes of pelvic inflammatory disease. Chlamydia also causes long-term sequelae, but the role of gonorrhea is unclear. We followed 300 000 reproductive-aged women for 10 years for ectopic pregnancy and tubal infertility; our findings suggest both infections confer similar increases in risk of these outcomes.

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: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. Methods: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16–34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Ze

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

Background: In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. Methods: The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7–14 days apart using weight-based bands, or 5% permethrin cream 7–14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The tria

Background Scabies is a public health problem in many countries, with impetigo and its complications important consequences. Ivermectin based mass drug administration (MDA) reduces the prevalence of scabies and, to a lesser extent, impetigo. We studied the impact of co-administering azithromycin on the prevalence of impetigo and antimicrobial resistance. Methods Six communities were randomized to receive either ivermectin-based MDA or ivermectin-based MDA co-administered with azithromycin. We measured scabies and impetigo prevalence at baseline and 12 months. We collected impetigo lesions swabs at baseline, 3 and 12 months to detect antimicrobial resistance. Results At baseline, scabies and impetigo prevalences were 11.8% and 10.1% in the ivermectin-only arm and 9.2% and 12.1% in the combined treatment arm. At 12 months, the prevalences had fallen to 1.0% and 2.5% in the ivermectin-only arm and 0.7% and 3.3% in the combined treatment arm. The proportion of impetigo lesions containing Staphylococcus aureus detected did not change (80% at baseline vs 86% at 12 months; no significant difference between arms) but the proportion containing pyogenic streptococci fell significantly (63% vs 23%, P <.01). At 3 months, 53% (8/15) of S. aureus isolates were macrolide-resistant in the combined treatment arm, but no resistant strains (0/13) were detected at 12 months. Conclusions Co-administration of azithromycin with ivermectin led to similar decreases in scabies and impetigo prevalence compared to ivermectin alone. The proportion of impetigo lesions containing pyogenic streptococci declined following MDA. There was a transient increase in the proportion of macrolide-resistant S. aureus strains following azithromycin MDA. Clinical Trials Registration clinicaltrials.gov (NCT02775617).

BACKGROUND: Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children. METHODS: The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population 'bounce-back' if deworming is ceased due to low STH prevalence. DISCUSSION: The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs. TRIAL REGISTRATION: ACTRN12619000309189

BACKGROUND: Scabies, a parasitic disease of the skin, is a major public health problem, largely affecting children. Scabies is often complicated by impetigo which can result in serious complications including invasive infections and immune mediated diseases. Scabies and impetigo are reported to have high prevalence in tropical settings including the Solomon Islands. METHODS: We conducted a cross-sectional prevalence survey at Gizo Primary School in the Western Province of the Solomon Islands in August 2018. The diagnosis of scabies was based on criteria developed by the International Alliance for the Control of Scabies in 2018. Population attributable risk was calculated to determine the effect of scabies on the prevalence of impetigo, and both adjusted and unadjusted risk ratios were calculated to identify differences between sexes and age groups. RESULTS: A total of 324 students were assessed (47.5% of those enrolled at the school). The prevalence of scabies was 54.3% (95% confidence interval [CI] 48.7-59.8) and most disease was mild (68.8%). The prevalence was higher in males (63.5%; adjusted risk ratio [ARR] 1.4, 95% CI 1.1-1.7), and in those aged 10-12 years (61.4%; ARR 1.8, 95% CI 1.1-2.9 when compared to those aged 4-6 years). The prevalence of impetigo was 32.1%, with males more likely to be affected (41.7%, ARR 1.7, 95% CI 1.2-2.4) but with no significant differences between age groups. 63.5% of those with impetigo had scabies, corresponding to a population attributable risk of 11.8%. CONCLUSIONS: There is a very high burden of scabies and impetigo among primary school students in Gizo. There is a critical need for the development and implementation of control programs in areas where scabies is endemic.