Effectiveness of an expanded role for community health workers on malaria blood examination rates in malaria elimination settings in Myanmar: an open stepped-wedge, cluster-randomised controlled trial.

Background: As Greater Mekong Subregion countries approach malaria elimination, the motivation and social role of community health workers (CHWs), and malaria blood examination rates, have declined in parallel with decreasing malaria burden. To address this issue, a health system model which expanded the role for CHWs was co-designed with communities and health stakeholders in the Mekong Subregion and field-tested in Myanmar. Methods: An open stepped-wedge cluster-randomised (at the village-level) controlled trial (ClinicalTrials.govNCT04695886) was conducted in 72 villages in Myanmar from Nov 1, 2021 to April 17, 2022 to evaluate the effectiveness and cost-effectiveness of the expanded CHW model. One-off and continuous implementation costs of the models were calculated. Findings: A total of 2886 malaria rapid diagnostic tests (RDTs) (control period: 1365; intervention period: 1521) were undertaken across 72 villages during the 24-week study period. Compared to the existing CHW model, the introduction of an expanded role for CHWs resulted in a 23% relative increase in village weekly malaria blood examination rates by RDT, the primary outcome, (adjusted incidence rate ratio (AIRR) = 1.23, 95% CI = 1.01, 1.50, p = 0.036), adjusting for time and season. A 3.3-fold relative increase in village weekly referral rate of dengue, tuberculosis, diarrhoea, or RDT-negative fever cases after the introduction of the expanded CHW model (AIRR = 3.17, 95% CI = 1.23, 8.18, p = 0.017), was also observed. The total cost per CHW per five-year period was US$14,794 for the expanded CHW model and $5816 for the existing CHW model. Interpretation: An expanded CHW model, co-designed with communities and health stakeholders, can increase malaria blood examination rates in malaria elimination settings and referral rates for other infectious diseases. Expanded CHW models will facilitate maintaining annual blood examination rates required for malaria elimination accreditation by the WHO. Funding: An International Multilateral Donor (QSE-M-UNOPS-BI-20864-007-40).

Mental Health Problems Among Indonesian Adolescents: Findings of a Cross-Sectional Study Utilising Validated Scales and Innovative Sampling Methods.

PURPOSE: This study aimed to estimate the prevalence of mental health problems and identify potential risk and protective exposures for adolescents in Indonesia. METHODS: An innovative sampling approach was applied to simultaneously recruit school- and community-based adolescents aged 16-18 years old from Jakarta (urban megacity) and South Sulawesi (remote province). We used multistage cluster sampling for in-school (N = 1,337) and respondent driven sampling for out-of-school (N = 824) adolescents. Mental health was measured using two validated scales: Kessler-10 and Center for Epidemiologic Studies Depression Scale-Revised . Psychiatric interviews were conducted in a subsample (N = 196) of students from Jakarta to validate the self-report scales. RESULTS: The estimated population prevalence of psychological distress and depression were 24.3% (95% CI = 21.5-27.2) and 12.6% (10.5-14.4) for in-school and 23.7% (20.7-26.7) and 23.5% (20.4-26.5) for out-of-school adolescents, respectively. In participants who completed a psychiatric interview, common psychiatric morbidities were social anxiety, depression, and suicidality. Compared to in-school females, male in-school adolescents reported a lower prevalence of psychological distress (16.9% (13.1-20.7) vs. 30.4% (26.4-34.4)) and depression (10.1% (7.2-13.1) vs. 14.6 (11.4-17.8)). By contrast, for out-of-school adolescents, males reported a higher prevalence of psychological distress (25.2% (21.6-28.9) vs. 20.2% (15.1-25.3)) and depression (26.3% (22.5-30.1) vs. 16.9% (11.8-21.9)). In-school adolescents who did not seek healthcare despite a perceived need were more likely to report psychological distress and depression. DISCUSSION: Adolescent mental health problems are highly prevalent in Indonesia, with substantial variation by gender, geography, and school enrolment. This study and its approach to sampling and measurement may serve as a model to improving mental health surveillance across other settings.

Characteristics of attrition within the SuperMIX cohort of people who inject drugs: a multiple event discrete-time survival analysis.

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.

Comprehensive evaluation of malaria reactive surveillance and response strategies in Lao People's Democratic Republic: a mixed-methods study.

OBJECTIVES: To achieve malaria elimination by 2030, the Lao People's Democratic Republic (PDR) adopted a reactive surveillance and response (RASR) strategy of malaria case notification within 1 day, case investigation and classification within 3 days and foci investigation and response within 7 days. It is important to evaluate the performance and feasibility of RASR implementation in Lao PDR so that the strategy may be optimised and better contribute towards the goal of malaria elimination. DESIGN: A mixed-methods study comprising of secondary data analysis of routinely collected malaria surveillance data, quantitative surveys and qualitative consultations was conducted in 2022. SETTING: Primary data collections for quantitative surveys and qualitative consultations were conducted in Huaphan, Khammouane, Luangprabang and Savannakhet Provinces of Lao PDR. PARTICIPANTS: Quantitative surveys were conducted among malaria programme stakeholders and service providers. Qualitative interviews were conducted with malaria programme stakeholders, and focus group discussions with malaria programme stakeholders, service providers and mobile and migrant populations (MMPs). OUTCOME MEASURES: Outcomes of interests were awareness and acceptability of current RASR activities by different group of participants, implementation, performance and feasibility of RASR activities including enablers and barriers. RESULTS: In Lao PDR, malaria programme stakeholders and service providers were aware of RASR; however, these activities were not well known in MMPs. Respectively, the timeliness of case notification and case investigation was 0.0% and 15.6% in 2018 but increased to 98.0% and 98.6% in 2022. Implementation of RASR was acceptable to the malaria programme stakeholders and service providers, and continued implementation was perceived as feasible. Nevertheless, issues such as low level of community awareness, high level of migration and limitations in health system capacity were identified. CONCLUSION: Overall, the timeliness of case notification and investigation in Lao PDR was high, and malaria programme stakeholders and service providers had positive opinions on RASR. However, some operational and health system-related barriers were identified, which need to be addressed to improve the performance of RASR in Lao PDR.

Geospatial joint modeling of vector and parasite serology to microstratify malaria transmission.

The World Health Organization identifies a strong surveillance system for malaria and its mosquito vector as an essential pillar of the malaria elimination agenda. Anopheles salivary antibodies are emerging biomarkers of exposure to mosquito bites that potentially overcome sensitivity and logistical constraints of traditional entomological surveys. Using samples collected by a village health volunteer network in 104 villages in Southeast Myanmar during routine surveillance, the present study employs a Bayesian geostatistical modeling framework, incorporating climatic and environmental variables together with Anopheles salivary antigen serology, to generate spatially continuous predictive maps of Anopheles biting exposure. Our maps quantify fine-scale spatial and temporal heterogeneity in Anopheles salivary antibody seroprevalence (ranging from 9 to 99%) that serves as a proxy of exposure to Anopheles bites and advances current static maps of only Anopheles occurrence. We also developed an innovative framework to perform surveillance of malaria transmission. By incorporating antibodies against the vector and the transmissible form of malaria (sporozoite) in a joint Bayesian geostatistical model, we predict several foci of ongoing transmission. In our study, we demonstrate that antibodies specific for Anopheles salivary and sporozoite antigens are a logistically feasible metric with which to quantify and characterize heterogeneity in exposure to vector bites and malaria transmission. These approaches could readily be scaled up into existing village health volunteer surveillance networks to identify foci of residual malaria transmission, which could be targeted with supplementary interventions to accelerate progress toward elimination.

Adaptive NK Cells Rapidly Expand during Acute HIV Infection and Persist Despite Early Initiation of Antiretroviral Therapy.

HIV is associated with NK cell dysfunction and expansion of adaptive-like NK cells that persist despite antiretroviral therapy (ART). We investigated the timing of NK cell perturbations during acute HIV infection and the impact of early ART initiation. PBMCs and plasma were obtained from people with HIV (PWH; all men who have sex with men; median age, 26.0 y) diagnosed during Fiebig stages I, II, III, or IV/V. Participants initiated ART a median of 3 d after diagnosis, and immunophenotyping was performed at diagnosis and longitudinally after ART. Anti-CMV Abs were assessed by ELISA. Samples from matched HIV-uninfected males were also analyzed. Proportions of adaptive NK cells (A-NKs; defined as Fcε-Receptor-1γ-) were expanded at HIV diagnosis at all Fiebig stages (pooled median 66% versus 25% for controls; p < 0.001) and were not altered by early ART initiation. Abs to CMV immediate early protein were elevated in PWH diagnosed in Fiebig stages III and IV/V (p < 0.03 for both). Proportions of A-NKs defined as either Fcε-Receptor-1γ- or NKG2C+/CD57+ were significantly associated with HIV DNA levels at diagnosis (p = 0.046 and 0.029, respectively) and trended toward an association after 48 wk of ART. Proportions of activated HLA-DR+/CD38+ NK cells remained elevated in PWH despite early ART initiation. NK cell activation and A-NK expansion occur very early after HIV transmission, before T cell activation, and are not altered by ART initiation during acute infection. A-NKs may contribute to HIV control and thus be useful for HIV cure.

Union and Complication Rates After Total Wrist Arthrodesis: A Systematic Review and Meta-Analysis.

PURPOSE: Total wrist arthrodesis (TWA) has been performed using various techniques. We aimed to provide pooled prevalence estimates of union and complications of TWA by technique. A secondary aim was to provide estimates of union and complication rates by treatment of the carpometacarpal joint (CMCJ) in TWA using plates. Given the widespread adoption of wrist arthrodesis plates (WAP), we hypothesized that these implants would result in higher union and lower complication rates. We also hypothesized that TWA with CMCJ arthrodesis would improve these outcomes. METHODS: Online databases including PubMed, Medline, Embase, and Cochrane were searched. Studies reporting union and/or complication rates of 10 or more TWA performed with a similar technique (analyzed as bone graft only, bone graft with minimal fixation, intramedullary, augmented intramedullary, plate, WAP, and other) were included. Studies with fewer than 10 TWA, studies reporting TWA where union or complications could not be analyzed separately, and studies without union and complication rates were excluded. Data extraction was performed independently by two English-speaking reviewers with a translator where required. Pooled prevalence estimates were made using a random-effects meta-analysis model and presented as a percent prevalence with 95% confidence and prediction intervals. RESULTS: One hundred and thirty-six studies with a total of 3,517 patients and 3,969 TWA were analyzed. No differences in union and complication prevalence were observed between TWA techniques and in TWA with different treatments of the CMCJ using plates and WAP. CONCLUSION: Using meta-analysis, we found no difference in union and complication prevalence between TWA techniques and TWA with different treatments of the CMCJ with plates and WAP. It must be acknowledged that this research included low-quality studies with high heterogeneity, and confidence in the precision of the estimates is low. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Injection Drug Use Frequency Before and After Take-Home Naloxone Training.

Importance: Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors. Objective: To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs. Design, Setting, and Participants: This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training. Exposure: In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis. Main Outcomes and Measures: Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs. Results: There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training. Conclusions and Relevance: This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.

Performance and feasibility of reactive surveillance and response strategies for malaria elimination in Vietnam: a mixed-methods study.

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.

Correlates of poor oral health related quality of life in a cohort of people who use methamphetamine in Australia.

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.

Anopheles diversity, biting behaviour and transmission potential in forest and farm environments of Gia Lai province, Vietnam.

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.

Foregone health care in adolescents from school and community settings in Indonesia: a cross-sectional study.

Background: Adolescence is a development period marked by the onset of a new set of health needs. The present study sought to quantify the prevalence of foregone care (not seeking medical care when needed) and identify which adolescents are at greater risk of having unmet healthcare needs. Methods: A multi-stage random sampling strategy was used to recruit school participants (grade 10-12) in two provinces in Indonesia. Respondent driven sampling was used to recruit out-of-school adolescents in the community. All participants completed a self-reported questionnaire which measured healthcare seeking behaviours, psychosocial wellbeing, use of healthcare services, and perceived barriers to accessing healthcare. Multivariable regression analysis was performed to examine factors associated with foregone care. Findings: A total of 2161 adolescents participated in the present study and nearly one in four adolescents reported foregone care in the past year. Experiences of poly-victimisation and seeking care for mental health needs increased the risk of foregone care. In-school adolescents who reported psychological distress [adjusted risk ratio (aRR) = 1.88, 95%CI = 1.48-2.38] or had high body mass index (aRR = 1.25, 95%CI = 1.00-1.57) were at greater risk of foregone care. The leading reason for foregone care was lack of knowledge of available services. In-school adolescents predominantly reported non-access barriers to care (e.g., perception of the health concern or anxiety about accessing care) whereas most out-of-school adolescents reported access barriers (e.g., did not know where to get care or could not pay). Interpretation: Foregone care is common among Indonesian adolescents, especially in adolescents with mental and physical health risks. Differences between in-school and out-of-school adolescents suggest that interventions to promote appropriate healthcare use will need tailoring. Further research is needed to determine causal relationships around barriers in access to healthcare. Funding: Australia-Indonesia Centre.

Reactive surveillance and response strategies for malaria elimination in Myanmar: a literature review.

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.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

The impacts of COVID-19 measures on drug markets and drug use among a cohort of people who use methamphetamine in Victoria, Australia.

BACKGROUND AND AIMS: Few studies of the impacts of the coronavirus disease 2019 (COVID-19) public health measures on drug markets and drug use patterns have used longitudinal data. We aimed to examine whether COVID-19 measures were associated with increases in methamphetamine price, decreases in methamphetamine use frequency and subsequent changes in secondary outcomes of other drug use frequency in metropolitan Melbourne and regional Victoria. DESIGN: Longitudinal analysis framework was used from a longitudinal cohort of people who use methamphetamine. SETTING: Victoria state, Australia. PARTICIPANTS: One hundred eighty-five VMAX study participants who reported a methamphetamine purchase after the onset of the pandemic were used for the price paid analysis. Methamphetamine or other drug use frequency analysis was performed using 277 participants who used methamphetamine during the pandemic or in the year before the pandemic. MEASUREMENTS: Price paid per gram of methamphetamine derived from the most recent purchase price and most recent purchase quantity. Frequency of methamphetamine and other drug use measured as the average number of days per week used in the last month. FINDINGS: Compared with pre-COVID-19 period, methamphetamine prices increased by AUD351.63 (P value <0.001) and by AUD456.51 (P value <0.001) in Melbourne and regional Victoria, respectively, during the period in which the most intense public health measures were implemented in Victoria. Although prices decreased after harder restrictions were lifted (by AUD232.84, P value <0.001 and AUD263.68, P value <0.001, in Melbourne and regional Victoria, respectively), they remained higher than pre-COVID-19 levels. A complementary 76% decrease was observed in relation to methamphetamine use frequency in regional Victoria (P value = 0.006) that was not offset by any changes in the frequency of use of other drugs such as alcohol, tobacco or other illicit drugs. CONCLUSION: COVID-19 public health measures in Victoria state, Australia, appear to have been associated with major price changes in the methamphetamine market and decreased frequency of use of the drug.

Discontinuation of opioid agonist treatment following release from prison in a cohort of men who injected drugs prior to imprisonment in Victoria, Australia: A discrete-time survival analysis.

BACKGROUND: Retention in opioid agonist treatment (OAT) following release from prison is associated with improved outcomes, however factors associated with post-release OAT discontinuation in Australia are poorly understood. We examined post-release OAT discontinuation in a cohort of men who engaged in approximately monthly injecting drug use (IDU) prior to imprisonment in Victoria, Australia. METHODS: Longitudinal data were used to calculate incidence of first-event post-release OAT discontinuation among men released from prison receiving OAT, and single-event discrete-time survival methods were used to estimate associations with post-release OAT discontinuation. RESULTS: Among 110 participants, 55 OAT discontinuations were observed in the two years post-release, an overall crude incidence rate (IR) of 46 per 100 person-years (PY) (95 % confidence interval [95 %CI]: 36-60 per 100PY). Incidence was greatest between release from prison and first follow-up (IR: 84 per 100PY, 95 %CI: 62-116 per 100PY). Initiating OAT during index imprisonment (versus transitioning from community OAT; adjusted hazard rate [AHR]: 2.17, 95 %CI: 1.14-4.13) and identifying as Aboriginal and/or Torres Strait Islander (AHR: 4.95, 95 %CI: 2.00-12.25) were associated with an increased hazard of OAT discontinuation. CONCLUSION: In a cohort of men with recent histories of IDU released from prison receiving OAT, half reported OAT discontinuation within two years of release from prison, with incidence of discontinuation greatest soon after prison-release. Targeted support for men who initiate OAT during episodes of imprisonment and Aboriginal and/or Torres Strait Islander peoples is necessary to reduce incidence of OAT discontinuation among people at greatest risk of discontinuation.

Reducing malaria transmission in forest-going mobile and migrant populations in Lao PDR and Cambodia: protocol for stepped-wedge cluster-randomised controlled trial.

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.

Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children.

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.

Level and correlates of social support in a community-based sample of Australians who primarily smoke methamphetamine.

Little is known about the level and correlates of social support amongst people who use methamphetamine. We aimed to describe, and determine characteristics associated with, social support amongst a community-recruited cohort of Australians who primarily smoked methamphetamine. A cross-sectional study was conducted with data from the Victorian Methamphetamine Cohort Study (VMAX). Adults (aged ≥18 years) who used methamphetamine were recruited from June 2016 to March 2020 across metropolitan and non-metropolitan areas using convenience, snowball, and respondent-driven sampling. Social support was measured using the seven-item Enhancing Recovery In Coronary Heart Disease (ENRICHD) Social Support Inventory (ESSI). Characteristics independently associated with ESSI quartiles were assessed via multivariable partial proportional odds regression. Overall, 718 participants were included for complete-case analysis. Their mean (standard deviation [SD]) age was 34.7 (9.7) years and 62% were male. The mean (SD) and median (lower quartile-upper quartile) ESSI scores were 22.6 (7.6) and 24 (16-29), respectively, on a scale of 8 to 34 where higher scores denote better self-perceived social support. Characteristics independently associated with lower ESSI included past-year homelessness (adjusted odds ratio [aOR] = 0.49, 95% confidence interval [CI] = 0.36-0.66), moderate/severe depression (aOR = 0.60, 95% CI = 0.42-0.86), increasing age relative to <30 years (aOR[30-39] = 0.61, 95% CI = 0.41-0.91; aOR[≥40] = 0.56, 95% CI = 0.35-0.91) and greater than fortnightly methamphetamine use (aOR = 0.69, 95% CI = 0.52-0.91). Characteristics independently associated with higher ESSI were employment (aOR = 1.51, 95% CI = 1.06-2.14) and female gender (aOR = 1.39, 95% CI = 1.00-1.92). Social support services for people who use methamphetamine could be targeted and tailored to subgroups defined by correlates of social support, such as those who experience homelessness, depression or unemployment.

The Global Epidemiological Transition in Cardiovascular Diseases: Unrecognised Impact of Endemic Infections on Peripheral Artery Disease.

An epidemiological transition in the prevalence of peripheral artery disease (PAD) is taking place especially in low- and middle-income countries (LMICs) where an ageing population and adoption of western lifestyles are associated with an increase in PAD. We discuss the limited evidence which suggests that infection, potentially mediated by inflammation, may be a risk factor for PAD, and show by means of an ecological analysis that country-level prevalence of the major endemic infections of HIV, tuberculosis and malaria are associated with the prevalence of PAD. While further research is required, we propose that scientists and health authorities pay more attention to the interplay between communicable and non-communicable diseases, and we suggest that limiting the occurrence of endemic infections might have some effect on slowing the epidemiological transition in PAD.