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

A qualitative study on the acceptability and preference of three types of long-lasting insecticide-treated bed nets in Solomon Islands: implications for malaria elimination

Background. In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation. Method. Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use. Results. Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands. Conclusion. Providing LLINs that are acceptable will be more important for improving compliance in areas of low or seasonal mosquito nuisance and malaria transmission. The implications of these findings on malaria elimination in Solomon Islands are discussed

Nebular spectra of 111 Type Ia supernovae disfavour single-degenerate progenitors

We place statistical constraints on Type Ia supernova (SN Ia) progenitors using 227 nebular-phase spectra of 111 SNe Ia. We find no evidence of stripped companion emission in any of the nebular-phase spectra. Upper limits are placed on the amount of mass that could go undetected in each spectrum using recent hydrodynamic simulations. With these null detections, we place an observational 3 sigma upper limit on the fraction of SNe Ia that are produced through the classical H-rich non-degenerate companion scenario of < 5.5 per cent. Additionally, we set a tentative 3 sigma upper limit otan He star progenitor scenarios of < 6.4 per cent, although further theoretical modelling is required. These limits refer to our most representative sample including normal, 91bg-like, 91T-like, and 'super-Chandrasekhar' SNe Ia but excluding SNe Iax and SNe Ia-CSM. As part of our analysis, we also derive a Nebular Phase Phillips Relation, which approximates the brightness of an SN Ia from 150 to 500 d after maximum using the peak magnitude and decline rate parameter Delta m(15)(B)

Individual, facility and policy level influences on national coverage estimates for intermittent preventive treatment of malaria in pregnancy in Tanzania

BACKGROUND: Delivery of two doses of intermittent preventive treatment of malaria during pregnancy (IPTp) is a key strategy to reduce the burden of malaria in pregnancy in sub-Saharan Africa. However, different settings have reported coverage levels well below the target 80%. Antenatal implementation guidelines in Tanzania recommend IPTp first dose to be given at the second antenatal visit, and second dose at the third visit. This investigation measured coverage of IPTp at national level in Tanzania and examined the role of individual, facility, and policy level influences on achieved coverage. METHODS: Three national household and linked reproductive and child health (RCH) facility surveys were conducted July-August 2005, 2006, and 2007 in 210 clusters sampled using two-stage cluster sampling from 21 randomly selected districts. Female residents who reported a livebirth in the previous year were asked questions about malaria prevention during that pregnancy and individual characteristics including education, pregnancy history, and marital status. The RCH facility serving each cluster was also surveyed, and information collected about drug stocks, health education delivery, and the timing of antenatal care delivery by clinic users. RESULTS: The national IPTp coverage had declined over the survey period being 71% for first dose in 2005 falling to 65% in 2007 (chi2 2.9, p = 0.05), and 38% for second dose in 2005 but 30% in 2007 (chi2 4.4, p = 0.01). There was no evidence of any individual factors being associated with second dose coverage beyond living in an urban area. Availability of sulphadoxine-pyrimethamine at RCH had decreased year on year from 85% of clinics in stock in 2005 to 60% in 2007 (chi2 20.6, p < 0.001). This reduction was evident in rural but not urban clinics. If safety recommendations and national antenatal care guidelines for IPTp delivery were followed, in 2007 only 76% of pregnant women could have received IPTp first dose and only 46% could have received second dose. CONCLUSION: There is scope to improve IPTp first and second dose coverage at national scale within existing systems by improving stock at RCH, and by revising the existing guidelines to recommend delivery of IPTp after quickening, rather than at a pre-defined antenatal visit

Direct evidence for shock-powered optical emission in a nova

Classical novae are thermonuclear explosions that occur on the surfaces of white dwarf stars in interacting binary systems1. It has long been thought that the luminosity of classical novae is powered by continued nuclear burning on the surface of the white dwarf after the initial runaway2. However, recent observations of gigaelectronvolt γ-rays from classical novae have hinted that shocks internal to the nova ejecta may dominate the nova emission. Shocks have also been suggested to power the luminosity of events as diverse as stellar mergers3, supernovae4 and tidal disruption events5, but observational confirmation has been lacking. Here we report simultaneous space-based optical and γ-ray observations of the 2018 nova V906 Carinae (ASASSN-18fv), revealing a remarkable series of distinct correlated flares in both bands. The optical and γ-ray flares occur simultaneously, implying a common origin in shocks. During the flares, the nova luminosity doubles, implying that the bulk of the luminosity is shock powered. Furthermore, we detect concurrent but weak X-ray emission from deeply embedded shocks, confirming that the shock power does not appear in the X-ray band and supporting its emergence at longer wavelengths. Our data, spanning the spectrum from radio to γ-ray, provide direct evidence that shocks can power substantial luminosity in classical novae and other optical transients

Baseline spatial distribution of malaria prior to an elimination programme in Vanuatu

BACKGROUND: The Ministry of Health in the Republic of Vanuatu has implemented a malaria elimination programme in Tafea Province, the most southern and eastern limit of malaria transmission in the South West Pacific. Tafea Province is comprised of five islands with malaria elimination achieved on one of these islands (Aneityum) in 1998. The current study aimed to establish the baseline distribution of malaria on the most malarious of the province's islands, Tanna Island, to guide the implementation of elimination activities. METHODS: A parasitological survey was conducted in Tafea Province in 2008. On Tanna Island there were 4,716 participants from 220 villages, geo-referenced using a global position system. Spatial autocorrelation in observed prevalence values was assessed using a semivariogram. Backwards step-wise regression analysis was conducted to determine the inclusion of environmental and climatic variables into a prediction model. The Bayesian geostatistical logistic regression model was used to predict malaria risk, and associated uncertainty across the island. RESULTS: Overall, prevalence on Tanna was 1.0% for Plasmodium falciparum (accounting for 32% of infections) and 2.2% for Plasmodium vivax (accounting for 68% of infections). Regression analysis showed significant association with elevation and distance to coastline for P. vivax and P. falciparum, but no significant association with NDVI or TIR. Colinearity was observed between elevation and distance to coastline with the later variable included in the final Bayesian geostatistical model for P. vivax and the former included in the final model for P. falciparum. Model validation statistics revealed that the final Bayesian geostatistical model had good predictive ability. CONCLUSION: Malaria in Tanna Island, Vanuatu, has a focal and predominantly coastal distribution. As Vanuatu refines its elimination strategy, malaria risk maps represent an invaluable resource in the strategic planning of all levels of malaria interventions for the island

Psychosocial, Behavioural and Health System Barriers to Delivery and Uptake of Intermittent Preventive Treatment of Malaria in Pregnancy in Tanzania - Viewpoints of Service Providers in Mkuranga and Mufindi Districts.

Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulphurdoxine-pyrimethamine (SP) is one of key malaria control strategies in Africa. Yet, IPTp coverage rates across Africa are still low due to several demand and supply constraints. Many countries implement the IPTp-SP strategy at antenatal care (ANC) clinics. This paper reports from a study on the knowledge and experience of health workers (HWs) at ANC clinics regarding psychosocial, behavioural and health system barriers to IPTp-SP delivery and uptake in Tanzania. Data were collected through questionnaire-based interviews with 78 HWs at 28 ANC clinics supplemented with informal discussions with current and recent ANC users in Mkuranga and Mufindi districts. Qualitative data were analysed using a qualitative content analysis approach. Quantitative data derived from interviews with HWs were analysed using non-parametric statistical analysis. The majority of interviewed HWs were aware of the IPTp-SP strategy's existence and of the recommended one month spacing of administration of SP doses. Some HWs were unsure of that it is not recommended to administer IPTp-SP and ferrous/folic acid concurrently. Others were administering three doses of SP per client following instruction from a non-governmental agency while believing that this was in conflict with national guidelines. About half of HWs did not find it appropriate for the government to recommend private ANC providers to provide IPTp-SP free of charge since doing so forces private providers to recover the costs elsewhere. HWs noted that pregnant women often register at clinics late and some do not comply with the regularity of appointments for revisits, hence miss IPTp and other ANC services. HWs also noted some amplified rumours among clients regarding health risks and treatment failures of SP used during pregnancy, and together with clients' disappointment with waiting times and the sharing of cups at ANC clinics for SP, limit the uptake of IPTp-doses. HWs still question SP's treatment advantages and are confused about policy ambiguity on the recommended number of IPTp-SP doses and other IPTp-SP related guidelines. IPTp-SP uptake is further constrained by pregnant women's perceived health risks of taking SP and of poor service quality

Impact of home-based management of malaria on health outcomes in Africa: a systematic review of the evidence

BACKGROUND: Home-based management of malaria (HMM) is promoted as a major strategy to improve prompt delivery of effective malaria treatment in Africa. HMM involves presumptively treating febrile children with pre-packaged antimalarial drugs distributed by members of the community. HMM has been implemented in several African countries, and artemisinin-based combination therapies (ACTs) will likely be introduced into these programmes on a wide scale. CASE PRESENTATIONS: The published literature was searched for studies that evaluated the health impact of community- and home-based treatment for malaria in Africa. Criteria for inclusion were: 1) the intervention consisted of antimalarial treatment administered presumptively for febrile illness; 2) the treatment was administered by local community members who had no formal education in health care; 3) measured outcomes included specific health indicators such as malaria morbidity (incidence, severity, parasite rates) and/or mortality; and 4) the study was conducted in Africa. Of 1,069 potentially relevant publications identified, only six studies, carried out over 18 years, were identified as meeting inclusion criteria. Heterogeneity of the evaluations, including variability in study design, precluded meta-analysis. DISCUSSION AND EVALUATION: All trials evaluated presumptive treatment with chloroquine and were conducted in rural areas, and most were done in settings with seasonal malaria transmission. Conclusions regarding the impact of HMM on morbidity and mortality endpoints were mixed. Two studies showed no health impact, while another showed a decrease in malaria prevalence and incidence, but no impact on mortality. One study in Burkina Faso suggested that HMM decreased the proportion of severe malaria cases, while another study from the same country showed a decrease in the risk of progression to severe malaria. Of the four studies with mortality endpoints only one from Ethiopia showed a positive impact, with a reduction in the under-5 mortality rate of 40.6% (95% CI 29.2 - 50.6). CONCLUSION: Currently the evidence base for HMM in Africa, particularly regarding use of ACTs, is narrow and priorities for further research are discussed. To optimize treatment and maximize health benefits, drug regimens and delivery strategies in HMM programmes may need to be tailored to local conditions. Additional research could help guide programme development, policy decision-making, and implementation