Stratification of malaria incidence in Papua New Guinea (2011-2019): contribution towards a sub-national control policy

Malaria risk in Papua New Guinea (PNG) is highly heterogeneous, between and within geographical regions, which is operationally challenging for control. To enhance targeting of malaria interventions in PNG, we investigated risk factors and stratified malaria incidence at the level of health facility catchment areas. Catchment areas and populations of 808 health facilities were delineated using a travel-time accessibility approach and linked to reported malaria cases (2011-2019). Zonal statistics tools were used to calculate average altitude and air temperature in catchment areas before they were spatially joined with incidence rates. In addition, empirical Bayesian kriging (EBK) was employed to interpolate incidence risk strata across PNG. Malaria annual incidence rates are, on average, 186.3 per 1000 population in catchment areas up to 600 m, dropped to 98.8 at (800-1400) m, and to 24.1 cases above 1400 m altitude. In areas above the two altitudinal thresholds 600m and 1400m, the average annual temperature drops below 22°C and 17°C, respectively. EBK models show very low- to low-risk strata ( 200 per 1000) strata are modelled mainly in Momase and Islands Regions. Besides, strata with moderate risk (100-200) predominate throughout the coastal areas. While 35.7% of the PNG population (estimated 3.33 million in 2019) lives in places at high or moderate risk of malaria, 52.2% (estimated 4.88 million) resides in very low-risk areas. In five provinces, relatively large proportions of populations (> 50%) inhabit high-risk areas: New Ireland, East and West New Britain, Sandaun and Milne Bay. Incidence maps show a contrast in malaria risk between coastal and inland areas influenced by altitude. However, the risk is highly variable in low-lying areas. Malaria interventions should be guided by sub-national risk levels in PNG

Levels of anti-pneumococcal antibodies in young children in Papua New Guinea

Anti-pneumococcal polysaccharide antibody (anti-PPS) levels were measured in 153 serum samples collected from children aged between 2 and 47 months living in the highlands of Papua New Guinea (PNG). Fifty-seven of the samples were collected during acute episodes of lower respiratory tract infection (ALRI). Total IgA and IgG increased steadily with age; however, no association was found between the levels of these antibodies and the health status of the child. Total IgM levels showed little relationship to the age of the child but under 12 months of age levels were somewhat higher on average in children with pneumonia. For most of eight pneumococcal serotypes tested, specific IgG levels were found to decline rapidly in the first 6-8 months, reaching a minimum at approximately 12 months of age. Serotype 3 was exceptional in having very low titres in the youngest children. A separate analysis of 24 cord sera suggested that antibodies to this serotype do not usually cross the placenta in PNG. Children with pneumonia tended to have lower levels of specific IgG than healthy controls of the same age. Specific anti-PPS IgA levels were found to increase steadily with age, but were not associated with health statu

A novel point-of-care testing strategy for sexually transmitted infections among pregnant women in high-burden settings: Results of a feasibility study in Papua New Guinea

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

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

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial

Background Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wucher-eria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-adminis-tered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbama-zine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. Methodology All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an addi-tional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. Principal findings Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treat-ment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treat-ment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/ 645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (rela-tive risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). Conclusion IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG

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