Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea) [version 1; peer review: 1 approved, 1 approved with reservations]

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 to these technologies and could improve maternal and neonatal health in high-burden settings worldwide. Registration: ISRCTN37134032

Point-of-care testing and treatment of sexually transmitted and genital infections during pregnancy in Papua New Guinea (WANTAIM trial): protocol for an economic evaluation alongside a cluster-randomised trial

INTRODUCTION: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG. METHODS AND ANALYSIS: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017-2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs. ETHICS AND DISSEMINATION: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs. TRIAL REGISTRATION NUMBER: ISRCTN37134032

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.

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. 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. 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. 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

The impact of tubal ectopic pregnancy in Papua New Guinea - a retrospective case review

BACKGROUND: Ectopic pregnancy (EP) is an important cause of morbidity and mortality amongst women of reproductive age. Tubal EP is well described in industrialised countries, but less is known about its impact in low-resource countries, in particular in the South Pacific Region. METHODS: We undertook a retrospective review of women with tubal EP treated at a provincial referral hospital in coastal Papua New Guinea over a period of 56 months. Demographic and clinical variables were obtained from patients’ medical records and analysed. The institutional rate of tubal EP was calculated, and diagnosis and management reviewed. Potential risk factors for tubal EP were identified, and delays contributing to increased morbidity described. RESULTS: A total of 73 women had tubal EP. The institutional rate of tubal EP over the study period was 6.3 per 1,000 deliveries. There were no maternal deaths due to EP. The mean age of women was 31.5+/−5.7 years, 85% were parous, 67% were rural dwellers and 62% had a history of sub-fertility. The most commonly used diagnostic aid was culdocentesis. One third of women had clinical evidence of shock on arrival. All women with tubal EP were managed by open salpingectomy. Tubal rupture was confirmed for 48% of patients and was more common amongst rural dwellers. Forty-three percent of women had macroscopic evidence of pelvic infection. Two-thirds of patients received blood transfusions, and post-operative recovery lasted six days on average. Late presentation, lack of clinical suspicion, and delays with receiving appropriate treatments were observed. CONCLUSIONS: Tubal EP is a common gynaecological emergency in a referral hospital in coastal PNG, and causes significant morbidity, in particular amongst women residing in rural areas. Sexually transmitted infections are likely to represent the most important risk factor for tubal EP in PNG. Interventions to reduce the morbidity due to tubal EP include the prevention, detection and treatment of sexually transmitted infections, identification and reduction of barriers to prompt presentation, increasing health workers’ awareness of ectopic pregnancy, providing pregnancy test kits to rural health centres, and strengthening hospital blood transfusion services, including facilities for autotransfusion

A case of ultrasound-guided prenatal diagnosis of prune belly syndrome in Papua New Guinea - implications for management

BACKGROUND: Prune belly syndrome is a rare congenital malformation of unknown aetiology and is characterised by abnormalities of the urinary tract, a deficiency of abdominal musculature and bilateral cryptorchidism in males. We report a case of prune belly syndrome from Papua New Guinea, which was suspected on pregnancy ultrasound scan and confirmed upon delivery. CASE PRESENTATION: A 26-year-old married woman, Gravida 3 Para 2, presented to antenatal clinic in Madang, Papua New Guinea, at 21(+5) weeks' gestation by dates. She was well with no past medical or family history of note. She gave consent to participate in a clinical trial on prevention of malaria in pregnancy and underwent repeated ultrasound examinations which revealed a live fetus with persistent megacystis and anhydramnios. Both mother and clinicians agreed on conservative management of the congenital abnormality. The mother spontaneously delivered a male fetus weighing 2010 grams at 34 weeks' gestation with grossly abnormal genitalia including cryptorchidism, penile aplasia and an absent urethral meatus, absent abdominal muscles and hypoplastic lungs. The infant passed away two hours after delivery. This report discusses the implications of prenatal detection of severe congenital abnormalities in PNG. CONCLUSION: This first, formally reported, case of prune belly syndrome from a resource-limited setting in the Oceania region highlights the importance of identifying and documenting congenital abnormalities. Women undergoing antenatal ultrasound examinations must be carefully counseled on the purpose and the limitations of the scan. The increasing use of obstetric ultrasound in PNG will inevitably result in a rise in prenatal detection of congenital abnormalities. This will need to be met with adequate training, referral mechanisms and better knowledge of women's attitudes and beliefs on birth defects and ultrasound. National medicolegal guidance regarding induced abortion and resuscitation of a fetus with severe congenital abnormalities may be required

Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the wantaim trial, papua new guinea) [version 2; peer review: 1 approved, 1 approved with reservations]

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 to these technologies and could improve maternal and neonatal health in high-burden settings worldwide