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Background: Compared to the general population, people who inject drugs have poor health and wellbeing. Longitudinal studies can provide insight into factors driving these worse health outcomes but are subject to methodological challenges, such as cohort attrition. The aim of this study was to assess and characterise attrition in a prospective cohort of people who inject drugs in Victoria, Australia., Methods: Using annually collected self-reported data from The Melbourne Injecting Drug User Cohort Study (SuperMIX) from September 2008 to January 2021, we estimated the incidence of participants being lost-to-follow-up (LTFU), with an episode of being LTFU defined as participants not undertaking a follow-up interview within two years of their last interview. We utilised a multiple event discrete-time survival analysis on participant period-observation data to estimate the associations between key factors and LTFU. Key areas of exposure measurement in analyses were sociodemographic, drug use and mental health., Results: A total of n = 1328 SuperMIX participants completed a baseline interview, with n = 489 (36.8%) LTFU, i.e. not completing a follow-up interview in the following two years. Increased attrition was observed among SuperMIX participants who were: born outside Australia, younger than 30 years, reporting having completed fewer years of education, not residing in stable accommodation, not in stable employment and not on opioid agonist therapy (OAT)., Conclusions: The attrition rate of the SuperMIX cohort has largely been stable throughout the duration of the study. Higher attrition rates among individuals at greater sociodemographic disadvantage and not on OAT suggest that additional efforts are required to retain these participants. Findings also suggest that SuperMIX might not be capturing data on adverse health and wellbeing outcomes among subpopulations at high risk of harm., (© 2024. The Author(s).)

Background: To enhance malaria elimination, Vietnam adopted a Reactive Surveillance and Response (RASR) Strategy in which malaria case notification and investigation must be completed within 2 days followed by a focus investigation within 7 days. The nationwide performance of Vietnam's RASR strategy has yet to be evaluated. This study aims to evaluate the performance and feasibility of RASR in Vietnam, thereby providing recommendations for improved RASR., Methods: To assess malaria RASR in Vietnam, a mixed-methods study of (1) secondary data analysis of nationwide malaria case-based dataset from 2017 to 2021; (2) a quantitative survey, and (3) qualitative in-depth interviews and focus group discussions administered to central, provincial and district level stakeholders/staff and to the commune and community level front line health services providers was conducted., Results: In Vietnam, there are guidelines and procedures for implementation of each step of RASR. The completeness of case notification on the reported monthly aggregated data was very high in both the paper-based (12,463/12,498, 99.7% in 2017-2020) and electronic reporting systems (467/467, 100% in 2021 when electronic reporting was introduced); however, there were delays in notification while using the paper-based system (timely notification-7,978/12,498, 63.8%). In 2021, the completeness (453/467, 97.0%) and timeliness (371/467, 79.4%) of case investigation were found to be high. Reactive case detection was the major focus investigation response, with fever screening achievement of 88.6% (11,481 / 12,965) and 88.5% (11,471 / 12,965) among index case and neighbouring household members, respectively., Conclusions: Overall, there was policy commitment for implementation of RASR in Vietnam. The completeness and timeliness of case notification and case investigation were high and improved after the introduction of the electronic reporting system. More evidence is required for reactive case detection in defining the screening area or population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Methamphetamine use impacts oral health, but little is known about its impacts on oral health related quality of life (OHRQoL). In this study we examined OHRQoL in a cohort of people who use methamphetamine and assessed associations with sociodemographic, behavioural, psychosocial and dental service utilisation correlates. A secondary aim was to examine the relationship between methamphetamine route of administration and OHRQoL, to test whether smoking the drug is associated with reduced OHRQoL., Methods: Cross-sectional analysis was performed, using data from VMAX, a cohort of people who use methamphetamine at least monthly in Victoria, Australia (n = 194). Utilising the oral health impact profile (OHIP-14), we assessed three OHRQoL outcomes: OHIP-14 prevalence, OHIP-14 extent and OHIP-14 severity. Regression analyses examined associations between independent variables and the three OHIP-14 outcome measures., Results: A significant segment of the cohort (35%) reported poor OHRQoL. Overall, no statistically significant association was detected between methamphetamine route of administration and the three OHIP-14 outcomes. Participants living in rural areas, with moderate-to-severe self-reported depression and with methamphetamine dependence had significantly worse OHRQoL levels, which persisted after adjusting for other covariates., Conclusion: Overall, VMAX cohort participants reported reduced OHRQoL levels. Our findings highlight the need for upstream interventions to improve the OHRQoL of people who use methamphetamine, with specific focus on those living in rural locations. Further research on the links between OHRQoL and mental health among people who use methamphetamine is required., (© 2023. The Author(s).)

Background: Despite recent reductions in Vietnam, malaria transmission persists in some areas in forests and farmlands where a high density of Anopheles mosquitoes relative to other environments occurs. To inform effective malaria control measures, it is important to understand vector bionomics and the malaria transmission role of Anopheles spp. in the highland regions of Vietnam. This study was conducted to quantify the abundance, composition and biting behaviour of the Anopheles mosquito population, and the proportion of Plasmodium spp. infected mosquitoes collected from forest and agricultural farm sites in Gia Lai province, Vietnam., Methods: Forest and agricultural farm sites in Gia Lai province were selected for mosquito collections (total eight sites). Mosquito collection was performed by Human-baited Double Net Trap (HDNT), animal-baited traps (ABT) using cattle, and CDC light traps. Captured mosquitoes were identified morphologically, and salivary glands of Anopheles mosquitoes were examined for sporozoites using microscopy. Plasmodium infection was determined by Polymerase Chain Reaction (PCR), and identification of blood meal type was determined by PCR and diffuse serum agglutination assay., Results: A total of 1815 Anopheles mosquitoes belonging to 19 species were collected by ABT (n = 1169), HDNT (n = 471) and CDC light trap (n = 175). Anopheles abundance and diversity varied by district and environment. Capture by HDNT of Anopheles of vectorial concern was observed between early evening and early morning. Plasmodium vivax infection was determined by PCR in two Anopheles dirus specimens captured by HDNT in forest sites. Blood from a range of hosts could, including human blood, could be detected in species considered primary and secondary vectors An. dirus, and Anopheles aconitus, and Anopheles maculatus, respectively., Conclusions: A low number of Anopheles spp. considered primary vectors of concern and very low numbers of Plasmodium spp. infected Anopheles mosquitoes were captured at the end of the rainy season in the Central Highlands of Vietnam. However, capture species of vectorial concern by HDNT throughout the early to late evening demonstrates that use of additional personal protective measures could supplement current preventative measures, such as bed nets to prevent exposure to vectors of concern in this region., (© 2023. The Author(s).)

Myanmar, a country in Greater Mekong Sub-region, aims to eliminate malaria by 2030. To achieve malaria elimination, Myanmar adopted a reactive surveillance and response strategy of malaria case notification within 1 day and case investigation, foci investigation and response activities within 7 days. A literature review was conducted to gain a better understanding of how the reactive surveillance and response strategies are being implemented in Myanmar including enablers and barriers to their implementation. Only two assessments of the completeness and timeliness of reactive surveillance and response strategy in Myanmar have been published to date. The proportion of positive cases notified within one day was 27.9% and the proportion of positive cases investigated within 7 days as recommended by the national guidelines varied from 32.5 to 91.8% under different settings in reported studies. Strong collaboration between the National Malaria Control Programme and implementing partners, and adequate human resource and financial support contributed to a successful and timely implementation of reactive surveillance and response strategy. Documented enablers for successful implementation of reactive surveillance and response strategy included frontline health workers having good knowledge of reactive surveillance and response activities and availability of Basic Health Staff for timely implementation of foci response activities. Barriers for implementation of reactive surveillance and response activities were also identified, including shortage of human resources especially in hard-to-reach settings, limited mobile phone network services and internet coverage leading to delays in timely notification of malaria cases, lengthy and complex case investigation forms and different reporting systems between Basic Health Staff and volunteers., (© 2023. The Author(s).)

Background: Countries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region., Methods: A personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package., Discussion: This study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy. Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021., (© 2022. The Author(s).)

Background: RTS,S is the first malaria vaccine recommended for implementation among young children at risk. However, vaccine efficacy is modest and short-lived. Antibodies play the major role in vaccine-induced immunity, but knowledge on the induction, decay, and determinants of antibody function is limited, especially among children. Antibodies that promote opsonic phagocytosis and other cellular functions appear to be important contributors to RTS,S immunity., Methods: We studied a phase IIb trial of RTS,S/AS02 conducted in young children in malaria-endemic regions of Mozambique. We evaluated the induction of antibodies targeting the circumsporozoite protein (CSP, vaccine antigen) that interact with Fcγ-receptors (FcRγs) and promote phagocytosis (neutrophils, monocytes, THP-1 cells), antibody-dependent respiratory burst (ADRB) by neutrophils, and natural killer (NK) cell activity, as well as the temporal kinetics of responses over 5 years of follow-up (ClinicalTrials.gov registry number NCT00197041)., Results: RTS,S vaccination induced CSP-specific IgG with FcγRIIa and FcγRIII binding activity and promoted phagocytosis by neutrophils, THP-1 monocytes, and primary human monocytes, neutrophil ADRB activity, and NK cell activation. Responses were highly heterogenous among children, and the magnitude of neutrophil phagocytosis by antibodies was relatively modest, which may reflect modest vaccine efficacy. Induction of functional antibodies was lower among children with higher malaria exposure. Functional antibody magnitude and the functional activity of antibodies largely declined within a year post-vaccination, and decay were highest in the first 6 months, consistent with the decline in vaccine efficacy over that time. Decay rates varied for different antibody parameters and decay was slower for neutrophil phagocytosis. Biostatistical modelling suggested IgG1 and IgG3 contribute in promoting FcγR binding and phagocytosis, and IgG targeting the NANP-repeat and C-terminal regions CSP were similarly important for functional activities., Conclusions: Results provide new insights to understand the modest and time-limited efficacy of RTS,S in children and the induction of antibody functional activities. Improving the induction and maintenance of antibodies that promote phagocytosis and cellular functions, and combating the negative effect of malaria exposure on vaccine responses are potential strategies for improving RTS,S efficacy and longevity., (© 2022. The Author(s).)

Background: Strengthening surveillance systems to collect near-real-time case-based data plays a fundamental role in achieving malaria elimination in the Greater Mekong Subregion (GMS). With the advanced and widespread use of digital technology, mHealth is increasingly taking a prominent role in malaria surveillance systems in GMS countries, including Myanmar. In Myanmar's malaria elimination program, an mHealth system called Malaria Case-based Reporting (MCBR) has been applied for case-based reporting of malaria data by integrated community malaria volunteers (ICMVs). However, the sustainability of such mHealth systems in the context of existing malaria elimination programs in Myanmar is unknown., Methods: Focus group discussions were conducted with ICMVs and semi-structured in-depth interviews were conducted with malaria program stakeholders from Myanmar's Ministry of Health and Sports and its malaria program implementing partners. Thematic (deductive followed by inductive) analysis was undertaken using a qualitative descriptive approach., Results: Technological and financial constraints such as inadequate internet access, software errors, and insufficient financial resources to support mobile phone-related costs have hampered users' access to MCBR. Poor system integrity, unpredictable reporting outcomes, inadequate human resources for system management, and inefficient user support undermined the perceived quality of the system and user satisfaction, and hence its sustainability. Furthermore, multiple parallel systems with functions overlapping those of MCBR were in use., Conclusions: Despite its effectiveness and efficiency in malaria surveillance, the sustainability of nationwide implementation of MCBR is uncertain. To make it sustainable, stakeholders should deploy a dedicated human workforce with the necessary technical and technological capacities; secure sustainable, long-term funding for implementation of MCBR; find an alternative cost-effective plan for ensuring sustainable system access by ICMVs, such as using volunteer-owned mobile phones for reporting rather than supporting new mobile phones to them; and find a solution to the burden of multiple parallel systems., Trial Registration: Not applicable., (© 2021. The Author(s).)

Background: In the Greater Mekong Subregion (GMS), current malaria surveillance strategies rely on a network of village health volunteers (VHVs) reporting the results of rapid diagnostic tests (RDTs), known to miss many asymptomatic infections. Integration of more sensitive diagnostic molecular and serological measures into the VHV network may improve surveillance of residual malaria transmission in hard-to-reach areas in the region and inform targeted interventions and elimination responses. However, data on residual malaria transmission that would be captured by these measures in the VHV-led testing and treatment surveillance network in the GMS is unknown., Methods: A total of 114 VHVs were trained to collect dried blood spots from villagers undergoing routine RDTs as part of VHV-led active and passive case detection from April 2015 to June 2016. Samples were subjected to molecular testing (quantitative polymerase chain reaction [qPCR]) to determine Plasmodium falciparum and P. vivax infection and serological testing (against P. falciparum and P. vivax antigens) to determine exposure to P. falciparum and P. vivax., Results: Over 15 months, 114 VHVs performed 32,194 RDTs and collected samples for molecular (n = 13,157) and serological (n = 14,128) testing. The prevalence of molecular-detectable P. falciparum and P. vivax infection was 3.2% compared to the 0.16% prevalence of Plasmodium spp. by RDT, highlighting the large burden of infections undetected by standard surveillance. Peaks in anti-P. falciparum, but not P. vivax, merozoite IgG seroprevalence coincided with seasonal P. falciparum transmission peaks, even in those with no molecularly detectable parasites. At the individual level, antibody seropositivity was associated with reduced odds of contemporaneous P. falciparum (OR for PfCSP 0.51 [95%CI 0.35, 0.76], p = 0.001, PfAMA1 0.70 [95%CI 0.52, 0.93], p = 0.01, and PfMSP2 0.81 [95%CI 0.61, 1.08], p = 0.15), but not P. vivax infection (OR PvAMA1 1.02 [95%CI 0.73, 1.43], p = 0.89) indicating a potential role of immunity in protection against molecular-detectable P. falciparum parasitaemia., Conclusions: We demonstrated that integration and implementation of sample collection for molecular and serological surveillance into networks of VHV servicing hard-to-reach populations in the GMS is feasible, can capture significant levels of ongoing undetected seasonal malaria transmission and has the potential to supplement current routine RDT testing. Improving malaria surveillance by advancing the integration of molecular and serological techniques, through centralised testing approaches or novel point-of-contact tests, will advance progress, and tracking, towards malaria elimination goals in the GMS.

Background: To achieve malaria elimination in the Greater Mekong Subregion, including Myanmar, it is necessary to ensure all malaria cases are detected, treated, and reported in a timely manner. Mobile phone-based applications for malaria reporting, case management, and surveillance implemented at a community-level may overcome reporting limitations associated with current paper-based reporting (PBR), but their effectiveness in this context is unknown., Methods: A mixed methods evaluation study was undertaken to determine the effectiveness of a national Malaria Case-Based Reporting (MCBR) mobile phone application in improving malaria case reporting compared to the existing PBR reporting system in Myanmar. Methods included secondary analysis of malaria case report data, questionnaires, focus group discussions and field observations of community volunteers, interviews and direct observations of malaria programme stakeholders, and cost analysis. Using a combination of these approaches the following areas were investigated: data quality and completeness, data access and usage, capacity for timely reporting, the acceptability, functionality, and ease of use of the application and facilitators and barriers to its use, and the relative cost of MCBR compared to the PBR system., Results: Compared to PBR, MCBR enabled more accurate and complete data to be reported in a much timelier manner, with 63% of MCBR users reporting they transmit rapid diagnostic test outcomes within 24 h, compared to 0% of PBR users. MCBR was favoured by integrated community malaria volunteers and their supervisors because of its efficiency. However, several technical and operational challenges associated with internet coverage, data transmission, and e-literacy were identified and stakeholders reported not being confident to rely solely on MCBR data for programmatic decision-making., Conclusions: Implementation of MCBR provided timely and accurate data for malaria surveillance. Findings from this evaluation study will enable the optimization of an application-based reporting system for malaria monitoring and surveillance in the Greater Mekong Subregion and advance systems to track progress towards, and certify, the achievement of malaria elimination targets.

Background: In endemic areas, pregnant women are highly susceptible to Plasmodium falciparum malaria characterized by the accumulation of parasitized red blood cells (pRBC) in the placenta. In subsequent pregnancies, women develop protective immunity to pregnancy-associated malaria and this has been hypothesized to be due to the acquisition of antibodies to the parasite variant surface antigen VAR2CSA. In this systematic review we provide the first synthesis of the association between antibodies to pregnancy-specific P. falciparum antigens and pregnancy and birth outcomes., Methods: We conducted a systematic review and meta-analysis of population-based studies (published up to 07 June 2019) of pregnant women living in P. falciparum endemic areas that examined antibody responses to pregnancy-specific P. falciparum antigens and outcomes including placental malaria, low birthweight, preterm birth, peripheral parasitaemia, maternal anaemia, and severe malaria., Results: We searched 6 databases and identified 33 studies (30 from Africa) that met predetermined inclusion and quality criteria: 16 studies contributed estimates in a format enabling inclusion in meta-analysis and 17 were included in narrative form only. Estimates were mostly from cross-sectional data (10 studies) and were heterogeneous in terms of magnitude and direction of effect. Included studies varied in terms of antigens tested, methodology used to measure antibody responses, and epidemiological setting. Antibody responses to pregnancy-specific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies)., Conclusions: Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations. Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.

Background: Community-delivered models have been widely used to reduce the burden of malaria. This review aimed to explore different community-delivered models and their relative effectiveness in terms of coverage and malaria-metric outcomes in order to inform the design and implementation of Community Health Worker (CHW) programmes for malaria control and elimination., Methods: A systematic review of studies investigating the impact of community-delivered models on coverage and malaria-metric (parasitaemia and hyperparasitaemia, malaria case and mortality, anaemia, and fever) outcomes compared to non- community-delivered models was undertaken by searching in five databases of published papers and grey literature databases. Data were extracted from studies meeting inclusion and quality criteria (assessed using relevant tools for the study design) by two independent authors. Meta-analyses were performed where there was sufficient homogeneity in effect and stratified by community-delivered models to assess the impact of each model on coverage and malaria-metric outcomes., Results: 28 studies were included from 7042 records identified. The majority of studies (25/28) were performed in high transmission settings in Africa and there was heterogeneity in the type of, and interventions delivered as part of the community-delivered models. Compared to non- community-delivered models, community-delivered models increased coverage of actual bed net usage (Relative Risk (RR) = 1.64 95% CI 1.39, 1.95), intermittent preventive treatment in pregnancy (RR = 1.36 95% CI 1.29, 1.44) and appropriate and timely treatment of febrile children, and improved malaria-metric outcomes such as malaria mortality (RR = 0.58 95% CI 0.52, 0.65). However, the considerable heterogeneity was found in the impact of community-delivered models in reducing, parasitaemia and hyperparasitaemia prevalence, anaemia incidence, fever prevalence and malaria caseload. Statistical comparisons of different community-delivered models were not undertaken due to the heterogeneity of the included studies in terms of method and interventions provided., Conclusion: Overall, the community-delivered model is effective in improving the coverage of malaria interventions and reducing malaria-associated mortality. The heterogeneity of the community-delivered models and their impact on malaria-metric indices suggests that evidence for context-specific solutions is required. In particular, community-delivered models for malaria elimination, integrated with services for other common primary health problems, are yet to be evaluated.

Background: Leading malaria vaccine, RTS,S, is based on the circumsporozoite protein (CSP) of sporozoites. RTS,S confers partial protection against malaria in children, but efficacy wanes relatively quickly after primary immunization. Vaccine efficacy has some association with anti-CSP IgG; however, it is unclear how these antibodies function, and how functional antibodies are induced and maintained over time. Recent studies identified antibody-complement interactions as a potentially important immune mechanism against sporozoites. Here, we investigated whether RTS,S vaccine-induced antibodies could function by interacting with complement., Methods: Serum samples were selected from children in a phase IIb trial of RTS,S/AS02 A conducted at two study sites of high and low malaria transmission intensity in Manhiça, Mozambique. Samples following primary immunization and 5-year post-immunization follow-up time points were included. Vaccine-induced antibodies were characterized by isotype, subclass, and epitope specificity, and tested for the ability to fix and activate complement. We additionally developed statistical methods to model the decay and determinants of functional antibodies after vaccination., Results: RTS,S vaccination induced anti-CSP antibodies that were mostly IgG1, with some IgG3, IgG2, and IgM. Complement-fixing antibodies were effectively induced by vaccination, and targeted the central repeat and C-terminal regions of CSP. Higher levels of complement-fixing antibodies were associated with IgG that equally recognized both the central repeat and C-terminal regions of CSP. Older age and higher malaria exposure were significantly associated with a poorer induction of functional antibodies. There was a marked decay in functional complement-fixing antibodies within months after vaccination, as well as decays in IgG subclasses and IgM. Statistical modeling suggested the decay in complement-fixing antibodies was mostly attributed to the waning of anti-CSP IgG1, and to a lesser extent IgG3., Conclusions: We demonstrate for the first time that RTS,S can induce complement-fixing antibodies in young malaria-exposed children. The short-lived nature of functional responses mirrors the declining vaccine efficacy of RTS,S over time. The negative influence of age and malaria exposure on functional antibodies has implications for understanding vaccine efficacy in different settings. These findings provide insights into the mechanisms and longevity of vaccine-induced immunity that will help inform the future development of highly efficacious and long-lasting malaria vaccines.

Background: To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria., Methods: The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide - 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites., Discussion: This study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS., Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12616001434482 ). Retrospectively registered 14th October 2016.

Background: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment., Methods: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy., Discussion: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV., Trial Registration: ClinicalTrials.gov , ID: NCT02555475 . Registered on 15 September 2015.

Objective: We sought to establish the extent of repeat participation in a large annual cross-sectional survey of people who inject drugs and assess its implications for analysis., Results: We used "porn star names" (the name of each participant's first pet followed by the name of the first street in which they lived) to identify repeat participation in three Australian Illicit Drug Reporting System surveys. Over 2013-2015, 2468 porn star names (96.2%) appeared only once, 88 (3.4%) twice, and nine (0.4%) in all 3 years. We measured design effects, based on the between-cluster variability for selected estimates, of 1.01-1.07 for seven key variables. These values indicate that the complex sample is (e.g.) 7% less efficient in estimating prevalence of heroin use (ever) than a simple random sample, and 1% less efficient in estimating number of heroin overdoses (ever). Porn star names are a useful means of tracking research participants longitudinally while maintaining their anonymity. Repeat participation in the Australian Illicit Drug Reporting System is low (less than 5% per annum), meaning point-prevalence and effect estimation without correction for the lack of independence in observations is unlikely to seriously affect population inference.

Background: Populations of low and middle-income countries are ageing rapidly; there is a need for policies that support an increase in the duration of old age lived in good health. There is growing evidence that social participation protects against morbidity and mortality, but few studies explore patterns of social participation. Analysis of baseline quantitative and qualitative data from a trial of the impact of Elders' Clubs on health and well-being in the hill country of Sri Lanka provided an opportunity to better understand the extent of, and influences on, social participation among elders., Methods: We analysed data from 1028 baseline survey respondents and from 12 focus group discussions. Participants were consenting elders, aged over 60 years, living in Tamil tea plantation communities or Sinhala villages in 40 randomly selected local government divisions. We assessed participation in organised social activities using self-reported attendance during the previous year. Multivariable regression analyses were used to explore associations with community and individual factors. The quantitative findings were complemented by thematic analysis of focus group discussion transcripts., Results: Social participation in these poor, geographically isolated communities was low: 63% reported 'no' or 'very low' engagement with organised activities. Plantation community elders reported significantly less participation than village elders. Attendance at religious activities was common and valued. Individual factors with significant positive association with social participation in multivariable analyses were being younger, male, Sinhala, married, employed, and satisfied with one's health. Domestic work and cultural constraints often prevented older women from attending organised activities., Conclusions: Elders likely to benefit most from greater social contact are those most likely to face barriers, including older women, the oldest old, those living alone and those in poor health. Understanding these barriers can inform strategies to overcome them. This might include opportunities for both informal and formal social contact close to elders' homes, consulting elders, providing childcare, improving physical access, advocating with elders' families and religious leaders, and encouraging mutual support and inter-generational activities. Influences on social participation are interrelated and vary with the history, culture and community environment. Further study is required in other low and middle-income country contexts.

Background: Point-of-care (POC) CD4 testing increases patient accessibility to assessment of antiretroviral therapy eligibility. This review evaluates field performance in low and middle-income countries (LMICs) of currently available POC CD4 technologies., Methods: Eight electronic databases were searched for field studies published between January 2005 and January 2015 of six POC CD4 platforms: PointCare NOW™, Alere Pima™ CD4, Daktari™ CD4 Counter, CyFlow® CD4 miniPOC, BD FACSPresto™, and MyT4™ CD4. Due to limited data availability, meta-analysis was conducted only for diagnostic performance of Pima at a threshold of 350 cells/μl, applying a bivariate multi-level random-effects modelling approach. A covariate extended model was also explored to test for difference in diagnostic performance between capillary and venous blood., Results: Twenty seven studies were included. Published field study results were found for three of the six POC CD4 tests, 24 of which used Pima. For Pima, test failure rates varied from 2 to 23 % across study settings. Pooled sensitivity and specificity were 0.92 (95 % CI = 0.88-0.95) and 0.87 (95 % CI = 0.85-0.88) respectively. Diagnostic performance by blood sample type (venous vs. capillary) revealed non-significant differences in sensitivity (0.94 vs 0.89) and specificity (0.86 vs 0.87), respectively in the extended model (Wald χ 2 (2) = 4.77, p = 0.09)., Conclusions: POC CD4 testing can provides reliable results for making treatment decision under field conditions in low-resource settings. The Pima test shows a good diagnostic performance at CD4 cut-off of 350 cells/μl. More data are required to evaluate performance of POC CD4 testing using venous versus capillary blood in LMICs which might otherwise influence clinical practice.

Background: CD4 testing is, and will remain an important part of HIV treatment and care in low and middle income countries (LMICs). We report the findings of a systematic review assessing acceptability and feasibility of POC CD4 testing in field settings., Methods: Electronic databases were searched for studies published in English between 2005 and 2015 that describe POC CD4 platforms. Studies conducted in LMICs and under field conditions outside a laboratory environment were eligible. Qualitative and descriptive data analysis was used to present the findings., Results: Twelve studies were included, 11 of which were conducted in sub-Saharan countries and used one POC CD4 test (The Alere Pima CD4). Patients reported positively regarding the implementation of POC CD4 testing at primary health care and community level with ≥90 % of patients accepting the test across various study settings. Health service providers expressed preference toward POC CD4 testing as it is easy-to-use, efficient and satisfied patients' needs to a greater extent as compared to conventional methods. However, operational challenges including preference toward venous blood rather than finger-prick sampling, frequent device failures and operator errors, quality of training for test operators and supervisors, and increased staff workload were also identified., Conclusions: POC CD4 testing seems acceptable and feasible in LIMCs under field conditions. Further studies using different POC CD4 tests available on the market are required to provide critical data to support countries in selection and implementation of appropriate POC CD4 technologies.

Background: There are few studies of mortality amongst people who inject drugs (PWID) in Australia. In this study, we estimate mortality in a cohort of PWID in Melbourne and examine predictors of mortality including health service use, demographic characteristics, drug use and personal wellbeing., Findings: We linked identifiers from the Melbourne injecting drug use cohort study (MIX; n = 655) to the National Death Index from 2008 to 2012 to estimate standardised mortality ratios (SMRs). Cox regression was used to examine the bivariate relationship between exposures determined at baseline and subsequent mortality. There were 24 (3.6%) deaths over the study period. The mortality rate in the cohort was 1.0 per 100 PY (95% CI 0.71-1.57), with an SMR of 17.3 (95 % CI 11.6-25.8). Baseline reports of four or more lifetime incarcerations (HR 3.65, 95 % CI 1.16-11.52), past month ambulance attendance (HR 4.43, 95 % CI 1.76-11.17), past month emergency department presentation (HR 3.44, 95 % CI 1.47-8.03) and past 6-month self-reported heroin overdose (HR 3.14, 95 % CI 1.24-7.96) were associated with increased mortality risk., Conclusions: Contact with emergency services, particularly for drug overdose, remains a lost opportunity to provide referrals for harm reduction and naloxone training programmes to PWID at greater risk of mortality.

Background: Evidence suggests that increasing male involvement in maternal and newborn health (MNH) may improve MNH outcomes. However, male involvement is difficult to measure, and further research is necessary to understand the barriers and enablers for men to engage in MNH, and to define target groups for interventions. Using data from a peri-urban township in Myanmar, this study aimed to construct appropriate indicators of male involvement in MNH, and assess sociodemographic, knowledge and attitude correlates of involvement., Methods: A cross-sectional study of married men with one or more children aged up to one year was conducted in 2012. Structured questionnaires measured participants' involvement in MNH, and their sociodemographic characteristics, knowledge and attitudes. An ordinal measure of male involvement was constructed describing the subject's participation across five areas of MNH, giving a score of 1-4. Proportional-odds regression models were developed to determine correlates of male involvement., Results: A total of 210 men participated in the survey, of which 203 provided complete data. Most men reported involvement level scores of either 2 or 3 (64 %), with 13 % reporting the highest level (score of 4). Involvement in MNH was positively associated with wives' level of education (AOR = 3.4; 95 % CI: 1.9-6.2; p < 0.001) and men's level of knowledge of MNH (AOR = 1.2; 95 % CI: 1.1-1.3; p < 0.001), and negatively correlated with number of children (AOR = 0.78; 95 % CI: 0.63-0.95; p = 0.016)., Conclusions: These findings can inform the design of programs aiming to increase male involvement, for example by targeting less educated couples and addressing their knowledge of MNH. The composite index proved a useful summary measure of involvement; however, it may have masked differential determinants of the summed indicators. There is a need for greater understanding of the influence of gender attitudes on male involvement in Myanmar and more robust indicators that capture these gender dynamics for use both in Myanmar and globally.

Background: Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations., Methods: We performed a systematic review with meta-analysis of population-based, cross-sectional, case-control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria., Results: The majority of studies were published in South America (all from Brazil) and the rest from geographically diverse areas in the Asia-Pacific region. Considerable heterogeneity in estimates was observed, but IgG responses to PvCSP, PvMSP-119, PvMSP-9RIRII, and PvAMA1 were associated with increased odds of P. vivax infection in geographically diverse populations. Potential sources of heterogeneity included study design, different transmission intensities and transmigrant populations. Protective associations were observed for antibodies to PvMSP-119, PvMSP-1NT, PvMSP-3α and PvMSP-9NT antigens, but only in single geographical locations., Conclusions: This systematic review revealed several antigen-specific antibodies that were associated with active infection and protective immunity, which may be useful biomarkers. However, more studies are needed on additional antigens, particularly cohort studies to increase the body of evidence for protective immunity. More studies representing diverse geographical regions encompassing varying P. vivax endemicities are needed to validate the generalizability of the findings and to provide a solid evidence base for the use of P. vivax antigens in vaccines and serosurveillance tools.