Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

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 proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.

Water, Sanitation, and Hygiene (WASH) Factors Influencing the Effectiveness of Mass Drug Administration to Eliminate Trachoma as a Public Health Problem in Malawi.

PURPOSE: Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1-9 years following MDA. METHODS: A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1-9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. RESULTS: Among 16,142 children aged 1-9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p = .034, or more than 1 h away aOR: 0.31, p = .018) compared with water in the yard. CONCLUSION: The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma.

Community-wide versus school-based targeted deworming for soil-transmitted helminth control in school-aged children in Vietnam: the CoDe-STH cluster-randomised controlled trial.

Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC ("school arm") or community-wide MDA ("community arm"). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5-36.9) and the community arm (34.6%, 95% CI 19.9-49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9-72.1) compared to the school arm (3.4%, 95% CI -24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7-92.6) compared to the school arm (39.0%, 95% CI 13.7-64.2). Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. Funding: National Health and Medical Research Council, Australia (APP1139561).

Perceived risk of HIV transmission by blood transfusion among gay, bisexual, and other men who have sex with men (gbMSM) in Australia.

BACKGROUND: In Australia, men who have sex with men (MSM) are deferred from blood donation for 3 months from last sexual contact. Internationally, deferral policies for MSM are evolving in the direction of expanded inclusivity in response to community expectations. To inform future policy options, we assessed perceptions of the risk of HIV transmission from blood transfusion among Australian MSM. STUDY DESIGN AND METHODS: Flux is an online prospective cohort of Australian gay and bisexual men (cis or trans, regardless of their sexual history) and other men who have had sex with men (gbMSM). We included questions on blood donation rules, window period (WP) duration, infectivity of blood from people with HIV on treatment and attitudes to more detailed questioning of sexual practices in the regular survey of Flux participants and conducted a descriptive analysis of responses. RESULTS: Of 716 Flux participants in 2019, 703 responded to the blood donation questions. The mean age was 43.7 years (SD 13.6 years). Overall, 74% were willing to confidentially respond to specific sexual behavior questions, such as the last time they had sex and the type of sex they had, in order to be considered eligible to donate blood. The majority (92%) of participants correctly assessed the duration of the WP as less than 1 month. When asked whether transfusion of blood from a donor with HIV and an undetectable viral load could transmit HIV, just under half (48%) correctly said yes. CONCLUSION: Our study suggests Australian gbMSM are generally comfortable with answering more detailed questions regarding sexual activity during the assessment to donate, indicating they would do so honestly. gbMSM are knowledgeable about the WP duration, important for their ability to correctly self-assess their HIV risk. However, half of participants incorrectly assessed the transmissibility by blood transfusion from an HIV positive person with an undetectable viral load, suggesting the need for a targeted education campaign.

Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam.

BACKGROUND: Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. METHODS: During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. RESULTS: The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84, P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63, P < 0.01). CONCLUSIONS: This study is the largest reported prevalence survey of STH infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes.

Detection of dengue virus infection in children presenting with fever in Hawassa, southern Ethiopia.

Dengue fever is a mosquito-borne viral infection, with rising incidence globally. Eastern Ethiopia has had dengue fever outbreaks in recent years. However, the extent to which the infection contributes to hospital presentation among children with fever in southern Ethiopia is unknown. We examined 407 stored plasma samples collected to investigate the aetiology of fever in children aged at least 2 months and under 13 years presenting to the outpatient of the largest tertiary hospital in southern Ethiopia. We analyzed samples for dengue virus non-structural 1 antigen using enzyme-linked immunosorbent assay. The median (interquartile range) age of the 407 children examined was 20 (10-48) months, and 166 (40.8%) of the children were females. Of 407 samples analyzed, 9 (2.2%) were positive for dengue virus non-structural 1 antigen, of whom 2 were initially treated with antimalarial drugs despite having negative malaria microscopy, and 1 of the 8 patients had a persistent fever at the seventh day of follow-up time. The presence of active dengue virus infection in the study area highlights the need for studies at the community level as well as the integration of dengue diagnostics into fever-management strategies. Further research to characterize circulating strains is warranted.

One versus two doses of ivermectin-based mass drug administration for the control of scabies: A cluster randomised non-inferiority trial.

BACKGROUND: Mass drug administration (MDA) based on two doses of ivermectin, one week apart, substantially reduces prevalence of both scabies and impetigo. The Regimens of Ivermectin for Scabies Elimination (RISE) trial assessed whether one-dose ivermectin-based MDA would be as effective. METHODS: RISE was a cluster-randomised trial in Solomon Islands. We assigned 20 villages in a 1:1 ratio to one- or two-dose ivermectin-based MDA. We planned to test whether the impact of one dose on scabies prevalence at 12 and 24 months was non-inferior to two, at a 5% non-inferiority margin. RESULTS: We deferred endpoint assessment to 21 months due to COVID-19. We enrolled 5239 participants in 20 villages at baseline and 3369 at 21 months from an estimated population of 5500. At baseline scabies prevalence was similar in the two arms (one-dose 17·2%; two-dose 13·2%). At 21 months, there was no reduction in scabies prevalence (one-dose 18·7%; two-dose 13·4%), and the confidence interval around the difference included values substantially greater than 5%. There was however a reduction in prevalence among those who had been present at the baseline assessment (one-dose 15·9%; two-dose 10·8%). Additionally, we found a reduction in both scabies severity and impetigo prevalence in both arms, to a similar degree. CONCLUSIONS: There was no indication of an overall decline in scabies prevalence in either arm. The reduction in scabies prevalence in those present at baseline suggests that the unexpectedly high influx of people into the trial villages, likely related to the COVID-19 pandemic, may have compromised the effectiveness of the MDA. Despite the lack of effect there are important lessons to be learnt from this trial about conducting MDA for scabies in high prevalence settings. TRIAL REGISTRATION: Registered with Australian New Zealand Clinical Trials Registry ACTRN12618001086257.

Differences in diagnosis, management, and outcomes of acute febrile illness by health facility level in southern Ethiopia.

We assessed the diagnosis, management and outcomes of acute febrile illness in a cohort of febrile children aged under 5 years presenting at one urban and two rural health centres and one tertiary hospital between 11 August 2019 and 01 November 2019. Pneumonia was diagnosed in 104 (30.8%) of 338 children at health centres and 128 (65.0%) of 197 at the hospital (p < 0.001). Malaria was detected in 33 (24.3%) of 136 children at the urban health centre, and in 55 (55.6%) of 99 and 7 (7.4%) of 95 children at the rural health centres compared to 11 (11.6%) of 95 at the hospital. Antibacterials were prescribed to 20 (11.5%) of 174 children without guidelines-specified indications (overprescribing) at health centres and in 7 (33.3%) of 21 children at the hospital (p = 0.013). Antimalarials were overprescribed to 13 (7.0%) of 185 children with negative malaria microscopy at the hospital. The fever resolved by day 7 in 326 (99.7%) of 327 children at health centres compared to 177 (93.2%) of 190 at the hospital (p < 0.001). These results suggest that additional guidance to health workers is needed to optimise the use of antimicrobials across all levels of health facilities.

Sexual and reproductive health needs and practices of female sex workers in Papua New Guinea: findings from a biobehavioral survey Kauntim mi tu ('Count me too').

BACKGROUND: Little research has explored the sexual and reproductive health (SRH) experience of female sex workers (FSW), including girls aged < 18 years who are commercially sexually exploited (CSE), in Papua New Guinea (PNG). This paper describes the SRH history of FSW and CSE girls and factors associated with their use of moderately or highly effective contraceptive methods in three settings in PNG. METHODS: From 2016 to 2017, respondent-driven sampling (RDS) surveys were conducted among FSW and CSE girls in Port Moresby, Lae, and Mt. Hagen. FSW and CSE girls who were born female, aged ≥12 years, sold or exchanged vaginal sex in the past 6 months, spoke English or Tok Pisin, and had a valid RDS study coupon were eligible to participate. Interviews were conducted face-to-face and participants were offered rapid routine HIV and syphilis testing. Survey logistic regression procedures were used to identify factors associated with the use of moderately or highly effective contraceptive methods. Weighted data analysis was conducted. RESULTS: A total of 2901 FSW and CSE girls (Port Moresby, 673; Lae, 709; and Mt. Hagen, 709) were enrolled. The proportion using moderately or highly effective contraceptive methods was 37.7% in Port Moresby, 30.9% in Lae, and 26.5% in Mt. Hagen. After adjusting for covariates, factors significantly associated with the use of moderately or highly effective contraceptive methods in Port Moresby were being age 20-24, being married, being divorced or separated, having one or more dependent children, being away from home for more than 1 month in the last 6 months, and having tested HIV negative. No factors were significantly associated in Lae or Mt. Hagen. ANC attendance amongst FSW and CSE girls who gave birth in last 3 years was highest in Port Moresby at 91.2%. HIV testing was inconsistently and inadequately offered at ANC across the three cities. CONCLUSIONS: Kauntim mi tu provides much-needed insight into the SRH experiences of FSW and CSE girls in PNG, where their use of moderately or highly effective contraceptive methods is low. We hope to shed light on the complicated reality they face due to illegality of sex work and multitude of complex healthcare experiences.

Clinical signs of trachoma and laboratory evidence of ocular Chlamydia trachomatis infection in a remote Queensland community: a serial cross-sectional study.

OBJECTIVES: To compare the findings of standard clinical assessments and of complementary clinical and laboratory methods for determining whether community-wide treatment for trachoma is warranted in a remote Queensland community. DESIGN: Three cross-sectional screening surveys, 2019-2021, complemented by laboratory pathology testing. SETTING: Small community in northwest Queensland with geographic and cultural ties to Northern Territory communities where trachoma persists. PARTICIPANTS: Children aged 1-14 years; opportunistic screening of people aged 15 years or more. MAIN OUTCOME MEASURES: Prevalence of clinical signs of trachoma, Chlamydia trachomatis infection, ocular non-chlamydial infections, and seropositivity for antibodies to the C. trachomatis Pgp3 protein. RESULTS: During the three surveys, 73 examinations of 58 children aged 1-4 years, 309 of 171 aged 5-9 years, and 142 of 105 aged 10-14 years for trachoma were undertaken, as were 171 examinations of 164 people aged 15 years or more; 691 of 695 examinations were of Aboriginal or Torres Strait Islander people (99%), 337 were of girls or young women (48%). Clinical signs consistent with trachomatous inflammation-follicular were identified in 5-9-year-old children 23 times (7%), including in eleven with non-chlamydial infections and one with a C. trachomatis infection. One child (10-14 years) met the criteria for trachomatous scarring. Two of 272 conjunctival swab samples (all ages) were polymerase chain reaction-positive for C. trachomatis (0.7%). Two of 147 people aged 15 years or more examined in 2019 had trichiasis, both aged 40 years or more. Seven of 53 children aged 1-9 years in 2019 and seven of 103 in 2021 were seropositive for anti-Pgp3 antibodies. CONCLUSIONS: Despite the prevalence of clinical signs consistent with trachomatous inflammation-follicular among 5-9-year-old children exceeding the 5% threshold for community-wide treatment, laboratory testing indicated that childhood exposure to ocular C. trachomatis is rare in this community. Laboratory testing should be integrated into Australian trachoma guidelines.

Hepatitis B prevalence in women giving birth in the Northern Territory, Australia, 2005-2015.

Background: Hepatitis B virus (HBV) vaccination in the Northern Territory (NT) was funded for all Aboriginal and Torres Strait Islander newborns in 1988 and for all newborns in 1990. The prevalence of HBV in the Northern Territory was found to be higher in Aboriginal and Torres Strait Islander women than in non-Indigenous women across 2005-2010. We examined more recent data to assess whether the gap remains. Methods: We linked data from two routinely collected registries, the NT Perinatal Register and the NT Notifiable Diseases System, to investigate the prevalence of HBV infection, according to eligibility for infant HBV vaccination, in women giving birth during 2005-2015. Results: There were 22,781 women recorded as giving birth in public hospitals in the Northern Territory during 2005-2015. Hepatitis B virus prevalence was highest in Aboriginal and Torres Strait Islander (1.8%) and overseas-born women (1.8%). Among Aboriginal and Torres Strait Islander women, estimated hepatitis B virus prevalence was significantly higher in those born before the implementation of the vaccination program than in those born afterwards (2.4% versus 0.3%). Prevalence was highest amongst those living in very remote areas, both overall (2.2%) and within the birth cohort eligible for HBV vaccination. Conclusions: Hepatitis B virus prevalence in Northern Territory Aboriginal and Torres Strait Islander women appears to be declining as more individuals vaccinated as part of infant vaccination programs reach adulthood. Prevalence remains highest in remote areas, highlighting the importance of ongoing monitoring and of promoting vaccination in these regions.

Serological testing of blood donors to characterise the impact of COVID-19 in Melbourne, Australia, 2020.

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 population patterns of infection, against which the effectiveness of ongoing responses to the pandemic can be assessed.

The acceptability and usability of two HIV self-test kits among men who have sex with men: a randomised crossover trial.

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 kits were high, but the ease of use and perceived accuracy influenced test kit preference.

Point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation for the early detection and treatment of cervical pre-cancer in women in Papua New Guinea: a prospective, single-arm intervention trial (HPV-STAT).

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 HSIL or worse was 85·4% (95% CI 81·0-89·6), with specificity 89·6% (88·6-90·6), PPV 35·2% (31·6-39·0), and NPV 98·9% (98·6-99·2). Among HPV-positive women, 602 (93·0%) received same-day thermal ablation and 42 (6·5%) were referred for gynaecology review, 37 (88·1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15·5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events. INTERPRETATION: We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO. FUNDING: Australian National Health and Medical Research Council.

Timely health care seeking and first source of care for acute febrile illness in children in Hawassa, southern Ethiopia.

BACKGROUND: Timely health care seeking with access to quality health care are crucial to improve child survival. We conducted a study which aimed to identify factors influencing timely health care seeking and choice of first source of health care in Ethiopia. METHODS: A total of 535 caregivers who sought health care for febrile children aged under 5 years at a tertiary hospital, and one urban and two rural health centres in Hawassa, southern Ethiopia were recruited to participate in the study from August to November 2019. Caregivers were interviewed using pretested structured questionnaires on socio-demographic and clinical factors to identify associations with health care seeking practice and first source of care, and reasons for particular practices. Delayed care seeking was defined as seeking care from a health facility after 24 hours of onset of fever. RESULTS: Of 535 caregivers who participated, 271 (50.7%) had sought timely health care; 400 (74.8%) utilized a primary health care (PHC) facility as first source; and 282 (52.7%) bypassed the nearest PHC facility. Rural residents (adjusted odds ratio (AOR) 1.85; 95% CI 1.11-3.09), and those who reported cough (AOR 1.87; 95% CI 1.20-2.93) as a reason for consultation were more likely to delay seeking health care. While caregivers were less likely delayed for children aged 24-35 months (AOR 0.50; 95% CI 0.28-0.87) compared to infants. Utilizing higher-level hospitals as the first source of care was less frequent among rural residents (AOR 0.15; 95% CI 0.06-0.39) and in those with no formal education (AOR 0.03; 95% CI 0.01-0.27). Those having a longer travel time to the provider (AOR 2.11; 95% CI 1.09-4.08) more likely utilized higher hospitals. CONCLUSION: We identified a need to improve timely health seeking among rural residents, infants, and those presenting with respiratory symptoms. Improvements may be achieved by educating communities on the need of early care seeking, and ensuring the communities members' expectations of services at each level consistent with the services capacity.

Experiences of risk in Australian hotel quarantine: a qualitative study.

BACKGROUND: In response to the threat of COVID-19 infection, Australia mandated a 14 day quarantine period in a designated facility for all travellers returning from overseas from late March 2020. These facilities were usually hotels, or hotel-like serviced apartments, and also included a repurposed former mining village in the Northern Territory. This paper aimed to investigate the experiences of risk of people quarantined in designated supervised facilities in Australia, which has not been systematically explored before. METHODS: In this qualitative study semi-structured interviews were conducted with 58 participants quarantined between March 2020 and January 2021. Participants were returned Australian citizens and residents who were required to undergo mandatory supervised quarantine for COVID-19. Interviews were conducted using video teleconferencing (via Zoom), transcribed and coded, then analysed thematically. RESULTS: While participants generally supported the concept of quarantine to protect the Australian public, they were critical of elements of it where they felt exposed to risk (COVID-related or not). They also described instances where infection control within the system seemed inadequate. For some, particularly those quarantined with small children, they reported that the facilities were inadequate or inappropriate for health and wellbeing. Using thematic analysis, three major themes were identified that related to problems in the existing system: perception of being subjected to high risk through lax standards of COVID protection in the quarantine process; risks to the community identified in quarantine; and risk in non-hotel managed quarantine facilities. CONCLUSIONS: There are systemic issues with infection control in hotel quarantine, which can be further undermined by individual non-compliance. Risks to safety for those in quarantine can be reduced, both in terms of infection control within hotel quarantine and, in the case of the Northern Territory facility, timely in-person medical care as needed for non-COVID conditions. Systems of infection control need ongoing review to ensure that people entering quarantine are protected from known risks of infection at every stage. Medical services in quarantine facilities should be examined to ensure timely and appropriate non-COVID medical services are available.

Risk of variant Creutzfeldt-Jakob disease transmission by blood transfusion in Australia.

BACKGROUND AND OBJECTIVES: Most of the 233 worldwide cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion-transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980-1996. We have modified a previously published methodology to estimate the transfusion-transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed. MATERIALS AND METHODS: The prevalence of current pre-symptomatic vCJD infection in the United Kingdom by age at infection and genotype was estimated based on risk of exposure to the bovine spongiform encephalopathy agent for the period 1980-1996. These results were used to estimate the age-specific prevalence of undiagnosed, pre-symptomatic vCJD in the Australian population in the current year due to prior UK residency or travel. The primary model outputs were the 2020 vCJD risks/unit of vCJD contamination, transfusion-transmission (infections) and clinical cases. RESULTS: The overall (prior UK residency in and travel to United Kingdom, 1980-1996) mean risk of contamination per unit was 1 in 29,900,000. The risks of resulting vCJD transmission (infection) and clinical case were 1 in 389,000,000 and 1 in 1,450,000,000, respectively. CONCLUSION: Our modelling suggests that removing the Lifeblood donation deferral for travel to, or UK residence, would result in virtually no increased risk of vCJD transfusion-transmission and would be a safe and effective strategy for increasing the donor base.

Clinical management and outcomes of acute febrile illness in children attending a tertiary hospital in southern Ethiopia.

BACKGROUND: The management of febrile illnesses is challenging in settings where diagnostic laboratory facilities are limited, and there are few published longitudinal data on children presenting with fever in such settings. We have previously conducted the first comprehensive study of infectious aetiologies of febrile children presenting to a tertiary care facility in Ethiopia. We now report on clinicians' prescribing adherence with guidelines and outcomes of management in this cohort. METHODS: We consecutively enrolled febrile children aged 2 months and under 13 years, who were then managed by clinicians based on presentation and available laboratory and radiologic findings on day of enrolment. We prospectively collected outcome data on days 7 and 14, and retrospectively evaluated prescribing adherence with national clinical management guidelines. RESULTS: Of 433 children enrolled, the most common presenting syndromes were pneumonia and acute diarrhoea, diagnosed in 177 (40.9%) and 82 (18.9%), respectively. Antibacterial agents were prescribed to 360 (84.7%) of 425 children, including 36 (34.0%) of 106 children without an initial indication for antibacterials according to guidelines. Antimalarial drugs were prescribed to 47 (11.1%) of 425 children, including 30 (7.3%) of 411 children with negative malaria microscopy. Fever had resolved in 357 (89.7%) of 398 children assessed at day 7, and in-hospital death within 7 days occurred in 9 (5.9%) of 153 admitted patients. Among children with pneumonia, independent predictors of persisting fever or death by 7 days were young age and underweight for age. Antibacterial prescribing in the absence of a guideline-specified indication (overprescribing) was more likely among infants and those without tachypnea, while overprescribing antimalarials was associated with older age, anaemia, absence of cough, and higher fevers. CONCLUSION: Our study underscores the need for improving diagnostic support to properly guide management decisions and enhance adherence by clinicians to treatment guidelines.

Surveillance systems to monitor antimicrobial resistance in Neisseria gonorrhoeae: a global, systematic review, 1 January 2012 to 27 September 2020.

BackgroundEffective surveillance of antimicrobial resistance (AMR) in Neisseria gonorrhoeae is required for the early detection of resistant strains and to ensure that treatment guidelines are appropriate for the setting in which they are implemented. AMR in N. gonorrhoeae has been identified as a global health threat.AimWe performed a systematic review to identify and describe surveillance systems targeting AMR in N. gonorrhoeae.MethodsWe searched Medline, PubMed, Global Health, EMBASE, CINAHL, Web of Science and ProQuest databases and grey literature between 1 January 2012 and 27 September 2020. Surveillance systems were defined as the continuous, systematic collection, analysis and interpretation of N. gonorrhoeae resistance data. The key components of surveillance systems were extracted, categorised, described and summarised.ResultsWe found 40 publications reporting on N. gonorrhoeae AMR surveillance systems in 27 countries and 10 multi-country or global surveillance reports. The proportion of countries with surveillance systems in each of the WHO's six regions ranged from one of 22 countries in the Eastern Mediterranean and five of 54 in Africa, to three of 11 countries in South East Asia. Only four countries report systems which are both comprehensive and national. We found no evidence of a current surveillance system in at least 148 countries. Coverage, representativeness, volume, clinical specimen source, type and epidemiological information vary substantially and limit interpretability and comparability of surveillance data for public health action.ConclusionGlobally, surveillance for N. gonorrhoeae AMR is inadequate and leaves large populations vulnerable to a major public health threat.

A national survey integrating clinical, laboratory, and WASH data to determine the typology of trachoma in Nauru.

BACKGROUND: The epidemiology of trachoma in several Pacific Islands differs from other endemic settings, in that there is a high prevalence of clinical signs of trachoma, particularly trachomatous inflammation-follicular (TF), but few cases of trichiasis and limited evidence of ocular chlamydial infection. This so-called "Pacific enigma" has led to uncertainty regarding the appropriate public health response. In 2019 alongside Nauru's national trachoma population survey, we performed bacteriological and serological assessments of children to better understand the typology of trachoma and to determine whether there is a need for trachoma interventions. METHODS: We used two-stage cluster sampling, examining residents aged ≥1 year and collecting household-level water, sanitation, and hygiene (WASH) variables. Children aged 1-9 years provided conjunctival swabs and finger-prick dried blood spots to investigate the presence of Chlamydia trachomatis nucleic acid and anti-Pgp3 antibodies, respectively. PRINCIPAL FINDINGS: In 818 participants aged 1-9 years, the age-adjusted TF prevalence was 21.8% (95% CI 15.2-26.2%); ocular C. trachomatis prevalence was 34.5% (95% CI 30.6-38.9), and anti-Pgp3 antibody prevalence was 32.1% (95% CI 28.4%-36.3%). The age- and gender-adjusted prevalence of trichiasis in ≥15-year-olds was 0.3% (95% CI 0.00-0.85), but no individual with trichiasis had trachomatous scarring (TS). Multivariable analysis showed an association between age and both TF (OR per year of age 1.3 [95% CI 1.2-1.4]) and anti-Pgp3 positivity (OR 1.2 [95% CI 1.2-1.3]). There were high rates of access to water and sanitation and no WASH variable was associated with the presence of TF. CONCLUSIONS: TF, nucleic acid, and age-specific antibody prevalence collectively indicate that high levels of C. trachomatis transmission among children present a high risk of ocular damage due to trachoma. The absence of trichiasis with trachomatous scarring suggest a relatively recent increase in transmission intensity.