Early/innate PBMC responses to pRBC in vitro are informative as to cytokines/chemokines associated with SM. Predominant cellular sources are monocytes and γδ T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the etiology of SM.

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 pregnancyspecific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies). Conclusions: Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations. Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.

Background: Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations. Methods: We performed a systematic review with meta-analysis of population-based, cross-sectional, case-control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria.

Background Gay and bisexual men (GBM) are a key population affected by HIV and hepatitis C (HCV) co-infection. Providing HCV treatment scale-up across specialist and non-hepatitis specialist settings may eliminate HCV in this population. We aimed to (1) deliver and measure HCV treatment effectiveness, and (2) determine the population impact of treatment on HCV prevalence and incidence longitudinally. Methods The co-EC Study (Enhancing care and treatment among HCV/HIV co-infected individuals to Eliminate Hepatitis C transmission) was an implementation trial providing HCV direct-acting antiviral treatment in Melbourne, Australia, from 2016-2018. Individuals with HCV/HIV co-infection were prospectively enrolled from primary and tertiary-care services providing care for 85% of GBM with HIV in our jurisdiction. HCV-viraemic prevalence and HCV-antibody/viraemic incidence were measured using a state-wide, individually-linked, electronic surveillance system. Results Among 200 participants recruited, 186 initiated treatment during the study period. Sustained virological response among primary care participants (98%, 95%CI:93-100%) was not different to tertiary care (98%, 95%CI:86-100%). From 2012-2019, between 2434 and 3476 GBM with HIV-infection attended our primary-care sites annually providing 13,801 person-years of follow-up; 50-60% received an HCV test annually, 10-14% were anti-HCV positive. Among those anti-HCV positive, viraemic prevalence declined 83% during the study (54% to 9%; 2016 to 2019). HCV incidence decreased 25% annually from 1.7/100 person-years in 2012 to 0.5/100 person-years in 2019 (incidence rate ratio 0.75; CI:0.68-0.83;p<0.001). Conclusion High treatment effectiveness by non-specialists demonstrates the feasibility of treatment scale-up in this population. Substantial declines in HCV incidence and prevalence among GBM with HIV-infection provides proof-of-concept for HCV micro-elimination. Registration ClinicalTrials.gov (Identifier: NCT02786758).

BackgroundIdentifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations.MethodsWe performed a systematic review with meta-analysis of population-based, cross-sectional, case–control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria.ResultsThe majority of studies were published in South America (all from Brazil) and the rest from geographically diverse areas in the Asia-Pacific region. Considerable heterogeneity in estimates was observed, but IgG responses to PvCSP, PvMSP-119, PvMSP-9RIRII, and PvAMA1 were associated with increased odds of P. vivax infection in geographically diverse populations. Potential sources of heterogeneity included study design, different transmission intensities and transmigrant populations. Protective associations were observed for antibodies to PvMSP-119, PvMSP-1NT, PvMSP-3α and PvMSP-9NT antigens, but only in single geographical locations.ConclusionsThis systematic review revealed several antigen-specific antibodies that were associated with active infection and protective immunity, which may be useful biomarkers. However, more studies are needed on additional antigens, particularly cohort studies to increase the body of evidence for protective immunity. More studies representing diverse geographical regions encompassing varying P. vivax endemicities are needed to validate the generalizability of the findings and to provide a solid evidence base for the use of P. vivax antigens in vaccines and serosurveillance tools.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0150-1) contains supplementary material, which is available to authorized users.

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

Background 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

BackgroundTo 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.MethodsThe 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.DiscussionThis study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS.Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12616001434482). Retrospectively registered 14th October 2016.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3566-y) contains supplementary material, which is available to authorized users.