Search

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 particip

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 definin

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 Anophele

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.

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 ri

Abstract 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.

INTRODUCTION: In 2018, the first Medically Supervised Injecting Room in Melbourne, Australia was officially opened. This study assessed whether this facility attracted people who inject drugs, who were socially vulnerable, and who engaged in drug-related behaviors associated with increased morbidity and mortality risk. METHODS: This was a cross-sectional analysis of the frequency of Medically Supervised Injecting Room use during the first 18 months after opening (July 2018-December 2019) among 658 people who inject drugs participating in the Melbourne Injecting Drug User Cohort Study (SuperMIX). To examine the differences between no Medically Supervised Injecting Room use, infrequent use (<50% injections within the facility), and frequent use (≥50% of injections within the facility), RRRs were estimated using bivariate multinomial logistic regression analyses and postestimation Wald tests. Analyses were conducted in 2020. RESULTS: A total of 451 participants (68%) reported no Medically Supervised Injecting Room use, 142 (22%) reported infrequent use, and 65 (10%) reported frequent use. Participants who reported either infrequent or frequent use of the facility were more socially vulnerable (e.g., more often homeless) and more likely to report risky drug-related behaviors and poor health outcomes than those who reported no use. Participants who reported frequent use of the facility were also more likely to live close to the facility than those reporting infrequent use. CONCLUSIONS: The Melbourne Medically Supervised Injecting Room attracted socially marginalized people who inject drugs who are most at risk of harms related to injecting drug use and therefore who are most in need of the service. To determine the long-term impact use of this facility on key health outcomes such as overdose, future studies should consider the differences in vulnerability and risk behavior of people who inject drugs who use the Medically Supervised Injecting Room when examining the outco

BACKGROUND: Entomological surveillance for malaria is inherently resource-intensive and produces crude population-level measures of vector exposure which are insensitive in low-transmission settings. Antibodies against Anopheles salivary proteins measured at the individual level may serve as proxy biomarkers for vector exposure and malaria transmission, but their relationship is yet to be quantified. METHODS: A systematic review of studies measuring antibodies against Anopheles salivary antigens (PROSPERO: CRD42020185449). Multilevel modelling (to account for multiple study-specific observations [level 1], nested within study [level 2], and study nested within country [level 3]) estimated associations between seroprevalence with Anopheles human biting rate (HBR) and malaria transmission measures. RESULTS: From 3981 studies identified in literature searches, 42 studies across 16 countries were included contributing 393 study-specific observations of anti-Anopheles salivary antibodies determined in 42,764 samples. A positive association between HBR (log transformed) and seroprevalence was found; overall a twofold (100% relative) increase in HBR was associated with a 23% increase in odds of seropositivity (OR: 1.23, 95% CI: 1.10-1.37; p<0.001). The association between HBR and Anopheles salivary antibodies was strongest with concordant, rather than discordant, Anopheles species. Seroprevalence was also significantly positively associated with established epidemiological measures of malaria transmission: entomological inoculation rate, Plasmodium spp. prevalence, and malarial endemicity class. CONCLUSIONS: Anopheles salivary antibody biomarkers can serve as a proxy measure for HBR and malaria transmission, and could monitor malaria receptivity of a population to sustain malaria transmission. Validation of Anopheles species-specific biomarkers is important given the global heterogeneity in the distribution of Anopheles species. Salivary biomarkers have the potential to tr

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 ensu

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 evalua

INTRODUCTION: In the Greater Mekong Subregion, community health workers, known as malaria volunteers, have played a key role in reducing malaria in the control phase, providing essential malaria services in areas with limited formal healthcare. However, the motivation and social role of malaria volunteers, and testing rates, have declined with decreasing malaria burden and reorientation of malaria programmes from control to elimination. Provision of additional interventions for common health concerns could help sustain the effectiveness of volunteers and maintain malaria testing rates required for malaria elimination accreditation by the WHO. METHODS AND ANALYSIS: The Community-delivered Integrated Malaria Elimination (CIME) volunteer model, integrating interventions for malaria, dengue, tuberculosis, childhood diarrhoea and malaria Rapid Diagnostic Test (RDT)-negative fever, was developed based on global evidence and extensive stakeholder consultations. An open stepped-wedge cluster-randomised controlled trial, randomised at the volunteer level, will be conducted over 6 months to evaluate the effectiveness of the CIME model in Myanmar. One hundred and forty Integrated Community Malaria Volunteers (ICMVs, current model of care) providing malaria services in 140 villages will be retrained as CIME volunteers (intervention). These 140 ICMVs/villages will be grouped into 10 blocks of 14 villages, with blocks transitioned from control (ICMV) to intervention states (CIME), fortnightly, in random order, following a 1-week training and transition period. The primary outcome of the trial is blood examination rate determined by the number of malaria RDTs performed weekly. Difference in rates will be estimated across village intervention and control states using a generalised linear mixed modelling analytical approach with maximum likelihood estimation. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board, Myanmar Department of Medical Research (Ethic

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

Background: The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. Methods and findings: Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004–15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47–0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80–2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention. Conclusions: In t

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with the burden largely borne by people living in low- and middle-income countries. Adolescents are central to NCD control through the potential to modify risks and alter the trajectory of these diseases across the life-course. However, an absence of epidemiological data has contributed to the relative exclusion of adolescents from policies and responses. This paper documents the design of a study to measure the burden of metabolic syndrome (a key risk for NCDs) and poor mental health (a key outcome) amongst Indonesian adolescents. Using a mixed-method design, we sampled 16-18-year-old adolescents from schools and community-based settings across Jakarta and South Sulawesi. Initial formative qualitative enquiry used focus group discussions to understand how young people conceptualise mental health and body weight (separately); what they perceive as determinants of these NCDs; and what responses to these NCDs should involve. These findings informed the design of a quantitative survey that adolescents self-completed electronically. Mental health was measured using the Centre for Epidemiologic Studies Depression Scale-Revised (CESD-R) and Kessler-10 (both validated against formal psychiatric interview in a subsample), with the metabolic syndrome measured using biomarkers and anthropometry. The survey also included scales relating to victimisation, connectedness, self-efficacy, body image and quality of life. Adolescents were sampled from schools using a multistage cluster design, and from the community using respondent-driven sampling (RDS). This study will substantially advance the field of NCD measurement amongst adolescents, especially in settings like Indonesia. It demonstrates that high quality, objective measurement is acceptable and feasible, including the collection of biomarkers in a school-based setting. It demonstrates how comparable data can be collected across both i

BACKGROUND: Recent research has investigated the utility of mobile phone-delivered interventions for reducing risky single-occasion drinking, also known as binge drinking. In the past five years, focus has been placed on ecological momentary interventions (EMIs), which aim to deliver intervention content in correspondence to real-time assessments of behavior, also known as ecological momentary assessments (EMAs). OBJECTIVE: This study aims to assess the effect of a fully automated, tailored, mobile phone-delivered EMI termed Mobile Intervention for Drinking in Young people (MIDY) on young people's risky single-occasion drinking behavior. METHODS: We will use a three-armed randomized controlled trial design to determine the impact of MIDY on peak consumption of alcohol among young people. A list of mobile telephone numbers for random digit dialing will be generated, and researchers will telephone potential participants to screen for eligibility. Participants will be randomized into one of three intervention groups. For 6 weeks, EMI, EMA, and attention control groups will complete hourly EMA surveys on their mobile phones on Friday and Saturday nights. EMI participants will receive personalized feedback in the form of text messages corresponding to their EMA survey responses, which focus on alcohol consumption, spending, and mood. EMA participants will not receive feedback. A third group will also complete EMA and receive feedback text messages at the same time intervals, but these will be focused on sedentary behavior and technology use. All groups will also complete a short survey on Saturday and Sunday mornings, with the primary outcome measure taken on Sunday mornings. A more detailed survey will be sent on the final Sunday of the 6-week period, and then again 1 year after recruitment. RESULTS: The primary outcome measure will be an observed change (ie, reduction) in the mean peak number of drinks consumed in a single night over the 6-week intervention period betw

BACKGROUND: The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. METHODS AND FINDINGS: Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004-15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47-0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80-2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention. CONCLUSIONS: In this study, we obse

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

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

Pregnant women are highly susceptible to anaemia and iron deficiency due to the increased demands of pregnancy as well as other factors. Iron supplementation is recommended in pregnancy, yet the benefits on newborn outcomes are variable between populations, most likely due to the heterogeneity in the prevalence of iron deficiency, detrimental birth outcomes and infectious diseases. Furthermore, there are concerns regarding iron supplementation in malaria-endemic areas due to reports of increased risk of malaria in those receiving iron. This is compounded by limited knowledge of how iron deficiency, anaemia, malaria, and other infections may interact to influence birth outcomes. In a recent cohort study in Papua New Guinea, where there is a high burden of infections and iron deficiency, we found that iron deficiency in pregnancy was associated with a reduced risk of adverse birth outcomes. However, this effect could not be wholly explained by interactions between iron deficiency and malaria. We proposed that iron deficiency may confer a degree of protection against other infectious pathogens, which in turn caused improvements in birthweight. We argue that further studies in multiple populations are crucial to elucidate interactions between iron status, iron supplementation and birthweight as well as to understand the context-specific benefits of iron supplementation in pregnancy and inform public policy. Focus should be given to haematological studies on anaemia, haemodilution and iron absorption, as well as investigating infectious diseases and other nutritional deficiencies. This is a particular priority in resource-constrained settings where the prevalence of iron deficiency, poor nutrition, infections and poor birth outcomes are high. While current recommendations of iron supplementation and malaria prophylaxis to reduce the burden of poor pregnancy outcomes should be supported, the strength of evidence underpinning these must be improved and new insights should

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/AS02A 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

BACKGROUND: HIV and bacterial sexually transmissible infection (STI) notifications among men who have sex with men (MSM) have increased in Australia and many other countries. The relationship between HIV infection and other STIs has been demonstrated previously. However, the relationship between the cumulative history of STIs and subsequent HIV infection remains largely unexplored and limits our understanding of the mechanisms underpinning the elevated HIV risk. METHODS: Data from HIV-negative MSM who attended high-HIV caseload primary care clinics in Melbourne, Australia, from 2007 to 2014 with 2 or more HIV and STI tests were included. Controlling for sexual behaviors self-reported at clinic visits, discrete time survival analyses using generalized linear modeling estimated the effect of an STI at the prior test event and the cumulative history of STIs (none, 1, 2, or more [repeated]) on risk of HIV infection. RESULTS: A total of 8941 MSM met the study criteria; 227 (2.5%) were diagnosed with HIV over the follow-up period. Adjusting for sexual behaviors, a cumulative history of repeated rectal gonorrhea infections (adjusted hazard ratio [aHR], 6.27; 95% confidence interval [CI], 2.68-14.50) and a single rectal gonorrhea infection (aHR, 2.09; 95% CI, 1.15-3.79) were associated with increased HIV infection risk. CONCLUSIONS: Repeated and single rectal gonorrhea infections were independently associated with increased HIV infection risk. These findings suggest that MSM with any history of rectal gonorrhea, particularly repeat rectal gonorrhea, represent a group for whom preventive interventions for HIV should be emphasized.

INTRODUCTION AND AIMS: Once involved in the criminal justice system, people who inject drugs (PWID) have a high probability of multiple system encounters. Imprisonment typically fails to rehabilitate PWID, who upon return to the community are at considerable risk of returning to injecting drug use (IDU) and poor health and social outcomes. We examined the effect of IDU resumption, and a suite of other sociodemographic, criminogenic, health and behavioural indicators, on the timing of reincarceration among adults with a history of IDU following release from prison. DESIGN AND METHODS: Structured interviews were conducted with 561 PWID in Queensland, Australia prior to release from prison and approximately 1, 3 and 6 months post-release. Data were linked prospectively with correctional records and the National Death Index. Data collected at multiple time-points were treated as time-varying covariates. Kaplan-Meier survival estimates and Cox proportional hazards models were used to estimate the rate and hazards of reincarceration. RESULTS: Sixty-eight percent of participants (n = 350) were reincarcerated over a combined observation time of 1043.5 years, representing a rate of 33.5 per 100 person-years (95% confidence interval [CI] 30.2-37.2). Time-invariant predictors of reincarceration in PWID were: male gender (adjusted hazard ratio [AHR] = 1.62, 95% CI 1.19-2.21), older age at release (AHR = 0.97, 95% CI 0.95-1.00), previous adult (AHR = 2.00, 95% CI 1.41-2.84) or juvenile (AHR = 1.78, 95% CI 1.27-2.49) imprisonment, shorter imprisonment (≤90 days vs. >365 days, AHR = 2.09, 95% CI 1.30-3.34), release on parole (AHR = 2.29, 95% CI 1.82-2.88) and drug-related sentence (AHR = 1.84, 95% CI 1.34-2.53). Time-varying predictors included resumption of IDU (AHR = 2.04, 95% CI 1.60-2.61), unemployment (AHR = 1.53, 95% CI 1.07-2.19) and low perceived social support (AHR = 1.41, 95% CI 1.05-1.90). Very-high psychological distress at the most recent interview was protective agai

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm3 The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8; P = 0.001). No difference in performance was detected by cadre of health worker (P = 0.113) or between point-of-care versus laboratory-based testing (P = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.

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.

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: Thi

INTRODUCTION: New interventions are required to reduce unintended pregnancies among female sex workers (FSWs) in low- and middle-income countries and to improve their nutritional health. Given sex workers' high mobile phone usage, repeated exposure to short messaging service (SMS) messages could address individual and interpersonal barriers to contraceptive uptake and better nutrition. METHODS: In this two-arm cluster randomised trial, each arm constitutes an equal-attention control group for the other. SMS messages were developed systematically, participatory and theory-driven and cover either sexual and reproductive health (WHISPER) or nutrition (SHOUT). Messages are sent to participants 2-3 times/week for 12 months and include fact-based and motivational content as well as role model stories. Participants can send reply texts to obtain additional information. Sex work venues (clusters) in Mombasa, Kenya, were randomly sampled with a probability proportionate to venue size. Up to 10 women were recruited from each venue to enrol 860 women. FSWs aged 16-35 years, who owned a mobile phone and were not pregnant at enrolment were eligible. Structured questionnaires, pregnancy tests, HIV and syphilis rapid tests and full blood counts were performed at enrolment, with subsequent visits at 6 and 12 months. ANALYSIS: The primary outcomes of WHISPER and SHOUT are unintended pregnancy incidence and prevalence of anaemia at 12 months, respectively. Each will be compared between study groups using discrete-time survival analysis. POTENTIAL LIMITATIONS: Contamination may occur if participants discuss their intervention with those in the other trial arm. This is mitigated by cluster recruitment and only sampling a small proportion of sex work venues from the sampling frame. CONCLUSIONS: The design allows for the simultaneous testing of two independent mHealth interventions for which messaging frequency and study procedures are identical. This trial may guide future mHealth initi

Gastrointestinal diseases are major contributors to mortality among children globally, causing one in 10 child deaths. Although most deaths are in children aged ≤ 5 years, the burden of disease in school-aged children is still considerable and contributes to high rates of school absenteeism. This study investigates behavioral and structural risk factors associated with diarrhea and/or vomiting among schoolchildren in Myanmar. Cross-sectional data from a school-based multistage cluster sample of grade 4 and 5 students were analyzed to explore water, sanitation, and hygiene (WASH) facilities and hygiene-related practices of students in monastic schools in Myanmar. The outcome of interest was student self-reported diarrhea and/or vomiting in the past week. Random effects multinomial logistic regression models were used to explore correlates at the student and school level. A total of 2,082 students from 116 schools across eight states/regions were included. Of these, 11% (223) self-reported at least one episode of diarrhea only, 12% (253) at least one episode of vomiting only, and 12% (244) diarrhea and vomiting in the past week. Independent risk factors associated with the outcome included poor availability of handwash stations, no access to a septic tank toilet, inconsistent toilet use, and lower student grade. These findings highlight the importance of having an adequate number of handwash stations for students, the provision of septic tank toilets, and consistent toilet use. Future WASH programs need to target not only the provision of these WASH facilities but also their utilization, particularly among younger school-aged children.

INTRODUCTION: Ex-prisoners with a history of injecting drug use (IDU) experience disproportionate drug-related harm. Rapid resumption of substance use following prison release is common and evidenced in high rates of overdose mortality. However, few studies have documented the rate of IDU resumption following prison release or identified risk factors for relapse. METHODS: Structured interviews were conducted with 533 adults with a history of IDU in Queensland, Australia prior to release from prison and approximately 1, 3 and 6 months post-release. Incidence of self-reported IDU resumption was calculated overall and for each follow-up interval. Risk factors associated with time to resumption of IDU were estimated using discrete-time survival analysis. RESULTS: IDU resumption was reported by 41% of participants during a median of 98days of follow-up (IQR=94-121), an overall crude incidence of 1.06 per person-year. The highest rate was observed in the first month (23%; crude incidence 2.24 per person-year). In adjusted discrete-time survival analyses, being unemployed at the previous interview (AHR=1.59; 95%CI:1.10-2.30), shorter incarceration (≤90days vs. >365days; AHR=2.20; 95%CI:1.33-3.65), and IDU during the index incarceration (AHR=2.80; 95%CI:1.92-4.09) were significantly associated with time to IDU resumption; parole was protective (AHR=0.66; 95%CI:0.47-0.92). CONCLUSIONS: Evidence-based efforts to prevent IDU in prison and IDU resumption after release are important for both prisoner and public health. Enhancing opportunities for employment and capitalising on the short-term benefits of parole for ex-prisoners may delay resumption of IDU after release from prison. These strategies should complement rather than replace harm reduction efforts for this high-risk population.

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

Background Infection with herpes simplex virus type 2 (HSV-2) is common worldwide and an important risk factor for HIV infection. Aetiological diagnosis of HSV-2 is typically determined with the use of commercially available type-specific enzyme-linked immunosorbent assays (ELISAs). This study aimed to determine the prevalence of HSV-2 among people attending sexual health clinics in the Highlands of Papua New Guinea. The study also aimed to compare the performance of two type-specific ELISA assays, the Kalon and HerpeSelect glycoprotein G2 assays, in this context. Methods: Participants were recruited as part of a longitudinal sexual health study. Participants attended four appointments over a 12-month period and had blood taken for HSV-2 serology at each time point. Both the Kalon and HerpeSelect assays were performed as per manufacturer's instructions. Results: A total of 132 participants were tested for HSV-2 using the Kalon and HerpeSelect ELISAs. HSV-2 prevalence was 52% (95% CI, 43-60) and 61% (95% CI, 52-69) with Kalon and HerpeSelect assays respectively. There was high concordance (87%, ?≤0.75, P<0.001, n≤115) between the two assays at the manufacturer recommended index value cut-offs. For participants with discordant results at baseline, (n≤16), three sero-conversions were observed over the 12-month period when sequential sera was tested. Conclusions: A high HSV-2 prevalence was observed in this clinic-based population. Our longitudinal data indicate the higher prevalence of HSV-2 detected with the HerpeSelect ELISA was likely due to false positives rather than a higher sensitivity in the early stages of infection.