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Association between Charlson Comorbidity Index and positive blood cultures at a tertiary-care hospital in Indonesia

Blood culture (BC) tests are a scarce resource in low- and middle-income countries (LMICs); therefore, prioritization based on likelihood of positive results might be beneficial. We aimed to determine whether comorbidities in the Charlson Comorbidity Index (CCI) were associated with positive BC tests among patients with suspected hospital-acquired bacteremia. We analysed a retrospective cohort from health records at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia from 2015-2018. We applied multivariable logistic regression to identify associations between CCI score and the outcome of the first BC taken two calendar days after admission, adjusting for confounders. The primary analysis considered BCs positive for all pathogens. Of 3,875 adult patients who had their first BCs taken two calendar days after hospital admissions, 786 (20.3%) had their first BCs positive for any pathogen. Those included 371 patients who had their first BCs positive for Staphylococcus aureus (n = 133; 35.9%), Acinetobacter spp. (n = 84; 22.6%), Klebsiella. pneumoniae (n = 58; 15.6%), Escherichia coli (n = 63; 17.0%) and Pseudomonas aeruginosa (n = 33; 8.9%). There was no association between increasing CCI score and positive BC (OR 1.01, 95%CI: 0.96-1.06, p = 0.69) after adjustment for age, sex and other potential confounders. There was some indication that antibiotic use prior to BC test acted as an effect modifier between CCI score and positivity of BC (p = 0.17). In this single-hospital study, no significant association was observed between CCI score and positive BC taken two calendar days after hospital admission. We suggest that other factors need to be investigated to guide BC testing, and that improving diagnostic and antibiotic stewardship, including increasing resources for BC testing prior to antibiotics among hospitalized patients are needed in LMICs.

Piloting the options assessment toolkit with national malaria programme leaders from the Asia-Pacific countries: a meeting report.

Plasmodium vivax malaria remains a major challenge in the Asia-Pacific region, where National Malaria Programmes (NMPs) will need to determine optimal radical cure strategies given the availability of novel options, such as high-dose primaquine and tafenoquine. The Options Assessment Toolkit (OAT) was developed to assist NMPs to make decisions on the optimal combination of G6PD testing and radical cure drug regimen. This study reports on the piloting of OAT with NMP representatives during the APMEN Vivax Working Group Annual Meeting in December 2022. A total of 23 NMP representatives from 13 Asia-Pacific countries participated in facilitated discussions. Thematic analysis of qualitative data revealed that NMPs found the OAT useful and timely for structuring malaria policy discussions. However, concerns were raised regarding mismatches between OAT-generated scenarios and country-specific contexts, the inclusion of political and economic factors, and the feasibility of implementing expert-suggested options. Many NMPs expressed enthusiasm for single-dose tafenoquine, but preferred to await WHO recommendations before considering policy changes. Overall, the OAT was well received as a tool for initiating policy discussions on P. vivax radical cure. The OAT represents an important step toward accelerating evidence-based policy change in malaria-endemic countries, with further refinements enhancing its utility.

Why should we be concerned by internalised racism in global health?

Internalised racism constitutes an adoption of beliefs about one's inferiority, weaknesses or shortcomings as a function of racial hierarchy affecting one's identity and self-worth, thoughts, emotions and behaviours. Internalised racism stems from widely known and discussed institutional racial discrimination, which perpetuates epistemic injustice, social injustice and health inequities in global health. In this article, reflecting on our experiential knowledge from working on global health, we engage with relevant literature to (1) highlight the concepts associated with internalised racism, (2) explore the potential impacts of internalised racism on individuals, organisations and global health and (3) propose strategies to redress and mitigate its impact on global health practice.

Iron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells.

Iron is an irreplaceable co-factor for metabolism. Iron deficiency affects >1 billion people and decreased iron availability impairs immunity. Nevertheless, how iron deprivation impacts immune cell function remains poorly characterised. We interrogate how physiologically low iron availability affects CD8+ T cell metabolism and function, using multi-omic and metabolic labelling approaches. Iron limitation does not substantially alter initial post-activation increases in cell size and CD25 upregulation. However, low iron profoundly stalls proliferation (without influencing cell viability), alters histone methylation status, gene expression, and disrupts mitochondrial membrane potential. Glucose and glutamine metabolism in the TCA cycle is limited and partially reverses to a reductive trajectory. Previous studies identified mitochondria-derived aspartate as crucial for proliferation of transformed cells. Despite aberrant TCA cycling, aspartate is increased in stalled iron deficient CD8+ T cells but is not utilised for nucleotide synthesis, likely due to trapping within depolarised mitochondria. Exogenous aspartate markedly rescues expansion and some functions of severely iron-deficient CD8+ T cells. Overall, iron scarcity creates a mitochondrial-located metabolic bottleneck, which is bypassed by supplying inhibited biochemical processes with aspartate. These findings reveal molecular consequences of iron deficiency for CD8+ T cell function, providing mechanistic insight into the basis for immune impairment during iron deficiency.

Clinicians’ use of metaphoric language in conversations with families of critically ill patients in the intensive care unit

Objectives: During conversations with families of critically ill patients in intensive care units (ICUs), clinicians’ metaphoric language use may facilitate families’ understanding, but also has potential drawbacks. We sought to obtain insights regarding how ICU clinicians use metaphors regarding patients’ disease and treatment trajectory. Methods: We identified clinicians’ metaphor use in N=101 audio-recorded neonatal, pediatric, and adult ICU family conversations about life-sustaining treatments. Using qualitative content analyses, each metaphor's semantic domain, disease phase, and dialogical function were coded. Overarching themes and patterns were analyzed. Results: Journey metaphors (N = 140 in N = 54 conversations) most frequently referred to the semantic domains boundary, path and bridge. Although most functioned to convey clinical information (72 %), metaphors were mainly presented in an emotionally charged way, serving to manage families’ perceptions. As patients’ conditions deteriorated, metaphors more often functioned to prepare families for medical limits. Metaphors were sometimes potentially unclear. Others suggested high patient agency, starkly contrasting with patients’ unconscious state. Conclusions: Metaphors related to ICU patients’ disease and treatment trajectory are common. They may clarify information or strengthen clinicians’ arguments but can also cause confusion and thereby hinder decision-making. Practice implications: Enhancing clinicians’ awareness about their metaphor use may promote more effective information exchange and decision-making.

Pathogen-specific host response in critically ill patients with blood stream infections: a nested case–control study

Background: Knowledge of the contribution of the pathogen to the heterogeneity of the host response to infection is limited. We aimed to compare the host response in critically ill patients with a bloodstream infection (BSI). Methods: RNA profiles were determined in blood obtained between one day before and after a positive blood culture. Differential expression and pathway analyses were performed on independent patients’ samples by RNA sequencing (discovery) or microarray (validation). Additional patients were included for the discovery and validation of transcriptome classifiers of pathogen-specific BSIs. Twenty biomarkers reflecting key host response pathways were measured in blood. Findings: We included 341 patients, among which 255 with BSI, 25 with viral infection and 61 non-infectious controls. The cultured pathogen explained 41·8% of the blood transcriptomic variance in patients with BSI. Gene set enrichment analysis showed a global resemblance between monomicrobial BSIs caused by Streptococcus, Staphylococcus aureus and Escherichia coli, which were clearly different from BSI caused by coagulase-negative staphylococci or Enterococcus. BSI by Streptococcus was associated with the highest number of differentially expressed genes, indicating strong innate and adaptive immune activation. An eight-gene streptococcal classifier performed well across different Streptococcus species, and was validated in external cohorts. Plasma biomarker profiling showed that E. coli BSI was associated with the strongest response in the cytokine and systemic inflammation domain, and S. aureus BSI with the strongest endothelial cell activation. Interpretation: The causative pathogen explains a substantial part of the heterogeneity of the host response in critically ill patients with BSI. Funding: Center for Translational Molecular Medicine and the European Commission.

Acceptability and feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing using SD Biosensor by village malaria workers in Cambodia: a qualitative study.

INTRODUCTION: Plasmodium vivax is the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia. METHODS: Semistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowen et al's feasibility framework and Sekhon et al's acceptability framework. RESULTS: All stakeholders attributed value to the intervention. Acknowledging an intervention's different values can help discern policy implications for an intervention's successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test's repeated use. More is required to build policymakers' confidence, while some implementation challenges, including the test's regulatory approval, stability above 30°C and cost, need to be overcome. CONCLUSION: Implementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholders.

Transforming health in Nepal: a historical and contemporary review on disease burden, health system challenges, and innovations.

IntroductionNepal witnessed a tumultuous journey over past two centuries, marked by significant political, social, and cultural shifts. From fighting British colonial encroachments in 1800s, the dynastic Rana regime (1846-1951), and democracy movements in the late 1950s, 1990s and 2000s, Nepal became a federal republic in 2008. The main objective of this review is to lay out an interpretative summary on Nepal's epidemiological transition (includes general trends and disease specific topics) followed by discussion on health system development over key periods: historical period (-1950s), modern period (1950-1990), post-democracy (1991-2016), and post-federalization (2016-).MethodsWe conducted a scoping review of available literature using the Arksey and O'Malley framework to synthesize the key insights. Searches were performed in PubMed (via NLM), Embase and Google Scholar using a combination of search terms related to Nepal's health system, epidemiological transition, disease burden and emerging health issues. A total of 1204 records were identified, of which 123 documents - including peer-reviewed articles, government reports and grey literature - met the inclusion criteria.ResultsMajor advances in maternal and child health, nutritional health and reduction of infectious diseases have been observed in recent decades. The maternal mortality ratio (MMR) declined by 55% (1996-2016), and neonatal mortality halved (40 to 20 per 1000 live births) due to improved antenatal care, skilled birth attendance and family planning. Stunting rates fell from 66% (1996) to 25% (2022), yet rising non-communicable diseases (NCDs) pose new challenges. Communicable diseases, once dominant, have declined owing to expanded immunization and tuberculosis control. However, NCDs now account for over two thirds of deaths, driven by urbanization, ageing and lifestyle shifts. Health system gaps persist, with workforce shortages, rural-urban disparities and out-of-pocket health costs limiting access. Addressing rising health inequities, digital health innovations and service expansion is critical to achieving universal health coverage and sustaining Nepal's health gains.ConclusionsNepal's health care landscape has continuously evolved over the past centuries, coinciding with key demographic and political changes. Advances through innovation are necessary for the country's overstretched health system to reduce the cost of health services whilst increasing quality and access.

Co-design of a routine clinical review to improve the safety of high dose radical cure treatment for Plasmodium vivax malaria: findings from Cambodia and Ethiopia

Pneumococcal density and respiratory co-detection in severe pediatric pneumonia in Laos.

There is growing evidence on the importance of bacterial/viral interaction in the course of pneumonia. In Laos, no study has investigated respiratory pathogen co-detection. We conducted a study at Mahosot Hospital in Vientiane to determine whether bacterial/viral co-detection and pneumococcal density are associated with severe pneumonia. Between December 2013 and December 2016, 934 under 5 years old hospitalized children with ARI were enrolled. Swabs from the upper respiratory tract were collected and analyzed by real-time PCR. The most common co-detected microorganisms were Streptococcus pneumoniae/Haemophilus influenzae (24%), Respiratory Syncytial Virus (RSV)/S. pneumoniae (12%) and RSV/H. influenzae (16%). Pneumococcal density was 4.52 times higher in influenza virus positive participants. RSV/S. pneumoniae and RSV/H. influenzae co-detections were positively associated with severe pneumonia in univariate analysis (OR 1.86, 95%CI:1.22-2.81, p = 0.003 and OR 2.09, 95%CI:1.46-3.00), but not confirmed in adjusted analysis (aOR 0.72, 95%CI:0.38-1.6, p = 0.309 and aOR 1.37, 95%CI:0.73-2.58). In RSV positive patients, there was no association between pneumococcal density and severe pneumonia. Our findings confirmed an association between pneumococcal density and influenza but not RSV severe pneumonia in young children. Results highlight the complexity of the interaction of viral/bacterial pathogens, which might not have a simple synergistic action in the evolution of pneumonia.

A LC‐MS/MS Assay for Quantification of Amodiaquine and Desethylamodiaquine in Dried Blood Spots on Filter Paper

Artesunate–amodiaquine (ARS–AQ) is a first‐line antimalarial treatment recommended by the World Health Organization. AQ is the long acting partner drug in this combination, and therapeutic success is correlated with the terminal exposure to AQ. Dried blood spot (DBS) sampling for AQ is a convenient and minimally invasive technique, especially suitable for clinical studies in resource limited settings and pediatric studies. Our primary aim was to develop and validate a bioanalytical method for quantification of AQ and its active metabolite in capillary blood applied onto filter paper as a DBS sample. The separation was achieved using a reverse phase column (Zorbax SB‐CN 50 × 4.6 mm, I.D. 3.5 μm) and a mobile phase consisting of acetonitrile:ammonium formate 20 mM with 0.5% formic acid (15:85, v/v). A 50 μL DBS was punctured with five 3.2 mm punches from the filter paper, and the punches collected correspond to approximately 15 μL of dried blood. The blood was then extracted using a mixture of 0.5% formic acid in water:acetonitrile (50:50, v/v), along with stable isotope‐labeled internal standards (AQ‐D10 and desethylamodiaquine [DAQ]‐D5). Mass spectrometry was used for quantification over the range of 2.03–459 ng/mL for AQ and 3.13–1570 ng/mL for DAQ. The validation of the method was carried out in compliance with regulatory requirements. The intra‐ and interbatch precisions were below 15% and passed all validation acceptance criteria. No carryover and no matrix effects were detected. Normalized matrix factors (analyte/internal standard) ranged from 0.96 to 1.03 for all analytes, hence no matrix effects. AQ and DAQ were stable in all conditions evaluated. Long‐term stability in DBS samples was demonstrated for up to 10 years when stored at −80°C and for 15 months when stored at room temperature. The developed method was demonstrated to be reliable and accurate. This assay may be particularly useful in the context of resource limited settings and in pediatric field studies.

Global Immune Biomarkers and Donor Serostatus Can Predict Cytomegalovirus Infection Within Seropositive Lung Transplant Recipients.

BACKGROUND: Predicting which lung transplant recipients (LTR) will develop cytomegalovirus (CMV) infection remains challenging. The aim of this retrospective cohort study was to further explore the predictive utility of global immune biomarkers within recipient seropositive (R+) LTRs, focusing on the mitogen component of the QuantiFERON (QF)-CMV assay and the absolute lymphocyte count (ALC). METHODS: R+ LTR with QF-CMV testing performed at 5 mo posttransplant were included. ALC and mitogen were evaluated as predictors of CMV infection (>150 IU/mL) in plasma and/or bronchoalveolar lavage fluid using Cox regression, controlling for antiviral prophylaxis. Optimal cutoffs were calculated with receiver-operating characteristic curves. RESULTS: CMV infection occurred in 111 of 204 patients (54%) and was associated with donor seropositivity (80/111 [72%] versus 42/93 [45%], P 

Impact of Late HIV Diagnosis on Costs of Care in a Public Health Care Setting.

Despite increased HIV testing and access to treatment in Australia, presentations with advanced disease occur, placing a significant burden on the health system. We sought to describe costs associated with HIV care in the first year post diagnosis in a specialized, tertiary-level HIV service and identify factors predicting increased health care costs. People newly diagnosed with HIV from 2016 to 2020 were included in the study. Data were gathered regarding their demographics (age, gender, birthplace, and first language), HIV parameters (viral load [VL] and CD4 cell count), antiretroviral therapy start date, opportunistic illness history, and health care costs (inpatient, outpatient, and emergency) from 12 months of diagnosis. Multivariable modeling was used to identify factors associated with increased costs. We identified 147 people; median age 38 years, 90% male, median CD4 count at diagnosis 338 cells/µL with median initial cost of care AUD $22,929 (interquartile range $11,902-$39,175). Costs associated with advanced HIV diagnosis (CD4 < 200 cells/µL; n = 52) were more than double an early HIV diagnosis (CD4 ≧ 350 cells/µL; n = 69) (median $46,406 vs. $20,274; p < .001). In univariate analysis, older age, higher VL, low CD4 count, and VL >200 copies/mL after 6 months were associated with increased costs. In multivariate analysis, older age (p = .001) and CD4 count <200 cells/µL (p = .001) were the only factors predicting increased cost in the first year after HIV diagnosis. Prioritizing HIV testing strategies to allow earlier diagnosis of HIV would significantly reduce the financial burden of HIV care.

Injecting drug use is a risk factor for methicillin resistance in patients with Staphylococcus aureus bloodstream infections.

We investigated whether injecting drug use was a risk factor for methicillin resistance among inpatients with Staphylococcus aureus bloodstream infections (SABSIs) at an Australian health service. In 273 inpatients, 46 (16.9%) of SABSIs were methicillin-resistant S. aureus (MRSA). MRSA was more frequent in those who had injected drugs in the past 6 months (20.6%) compared with other inpatients (15.7%). Injecting drug use was associated with a 4.82-fold (95% confidence interval = 1.54-16.29) increased odds of MRSA after accounting for confounders.

Study protocol for ADAPT-TDM: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring.

IntroductionCritically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.Methods and analysisA beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.Ethics and disseminationThis study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.Trial registration numberAustralian New Zealand Clinical Trials Registry, ACTRN12623000032651.

Pilot study to evaluate the need and implementation of a multifaceted nurse-led antimicrobial stewardship intervention in residential aged care.

ObjectivesTo evaluate the need and feasibility of a nurse-led antimicrobial stewardship (AMS) programme in two Australian residential aged care homes (RACHs) to inform a stepped-wedged, cluster randomized controlled trial (SW-cRCT).MethodsA mixed-methods pilot study of a nurse-led AMS programme was performed in two RACHs in Victoria, Australia (July-December 2019). The AMS programme comprised education, infection assessment and management guidelines, and documentation to support appropriate antimicrobial use in urinary, lower respiratory and skin/soft tissue infections. The programme was implemented over three phases: (i) pre-implementation education and integration (1 month); (ii) implementation of the intervention (3 months); and (iii) post-intervention evaluation (1 month). Baseline RACH and resident data and weekly infection and antimicrobial usage were collected and analysed descriptively to evaluate the need for AMS strategies. Feedback on intervention resources and implementation barriers were identified from semi-structured interviews, an online staff questionnaire and researcher field notes.ResultsSix key barriers to implementation of the intervention were identified and used to refine the intervention: aged care staffing and capacity; access to education; resistance to practice change; role of staff in AMS; leadership and ownership of the intervention at the RACH and organization level; and family expectations. A total of 61 antimicrobials were prescribed for 40 residents over the 3 month intervention. Overall, 48% of antibiotics did not meet minimum criteria for appropriate initiation (respiratory: 73%; urinary: 54%; skin/soft tissue: 0%).ConclusionsSeveral barriers and opportunities to improve implementation of AMS in RACHs were identified. Findings were used to inform a revised intervention to be evaluated in a larger SW-cRCT.

Pregnant women as a sentinel population for genomic surveillance of malaria in the Democratic Republic of the Congo: a population-based study

Enhanced data quality to improve malaria surveillance in Papua, Indonesia

Abstract Background Papua has a high burden of malaria, with an annual parasite incidence 300 times the national average. A key component of malaria elimination strategies is robust surveillance which is essential for monitoring trends in case numbers, guiding public health interventions, and prioritizing resource allocation. This study aimed to enhance malaria surveillance in Central Papua, Indonesia, by improving data collection, record-keeping, and treatment practices. Methods The study was conducted at five public clinics in Central Papua province, Indonesia, as part of a wider health systems strengthening programme to promote safer and more effective anti-malarial treatment (The SHEPPI Study). Clinical and laboratory details of patients with malaria and their treatment were documented in clinic registers which were digitalized into an electronic database. Automated reports were generated each month and used to provide regular feedback to clinic staff. Continuous Quality Improvement (CQI) workshops were conducted with clinic staff using the Plan-Do-Study-Act approach to address challenges and drive sustained improvements. Results Between January 2019 and December 2023, a total of 314,561 patients were tested for malaria, of whom 41.9% (131,948) had peripheral parasitaemia detected. The first round of Continuous Quality Improvement (CQI) workshops were held in May 2019 and improved data quality significantly, increasing data completeness from 46.3% (4540/9802) in the initial period (Jan–May 2019) to 71.5% (9053/12,665) after the first CQI (Jun–Oct 2019), p < 0.001. The second CQI round reduced DHP prescribing errors from 17.1% (1111/6489) in the initial period to 5.7% (607/10,669) after the second CQI (Sep 2019–Jan 2020) and PQ prescribing errors from 17.4% (552/3175) to 3.4% (160/4659) over the same time interval, p < 001. In total, 347 patients were prescribed fewer than the recommended number of PQ tablets during the initial period, 89 (25.6%) of whom were erroneously given only a single dose. Over the 4 year study period, a total of 11 workshops were conducted, driving continuous improvements in data quality and prescribing practices. Conclusion One or two rounds of CQI, supported by regular follow-up, can enhance the quality of malariometric surveillance, however interventions needed to be tailored to address specific needs of participating clinics. Improvements in data quality and prescribing practices have potential to contribute to better malaria management, improved clinical outcomes, and strengthened trust in healthcare providers.

FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru.

BACKGROUND: Outside of sub-Saharan Africa, Plasmodium vivax has become the dominant species of malaria. Focal mass drug administration (fMDA) is a potential strategy to support elimination efforts, but controlled studies are lacking. METHODS: The FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME) study is a 3-year cluster randomized controlled trial to determine the impact and safety of fMDA to reduce P. vivax transmission. The study will be conducted in Loreto, Peru, where standard interventions have reduced P. vivax cases, but transmission persists due to a high proportion of subclinical infections. Thirty low transmission communities (API < 250 cases/1000 population) will be randomized 1:1 to fMDA versus control using a restricted randomization. All communities will receive Peruvian national standard malaria control measures. In the intervention arm, high-risk individuals (living within 200 meters of a P. vivax case reported in the prior two years) without contraindication to study medications, including G6PD deficiency, will receive three cycles of fMDA over a two-year period. Each cycle will include two rounds of directly observed therapy delivered 2 months apart. The fMDA regimen will include 25mg/kg chloroquine (CQ) plus a single 300mg dose of tafenoquine (TQ) for individuals age ≥16 years, and 25mg/kg of CQ plus 7 days of 0.5mg/kg/day of primaquine (PQ) if younger. The primary outcome is the cumulative incidence of symptomatic P. vivax malaria. The sample size provides 80% power to detect at least a 68% relative reduction in cumulative P. vivax incidence, based on alpha of 0.05 and a coefficient of variation (k) of 0.87. Secondary outcomes include safety, cost-effectiveness, and infection prevalence and seroprevalence which will be assessed in annual cross-sectional surveys. Safety will be assessed in passive and active pharmacovigilance, including post-treatment screening for G6PD-associated hemolysis by assessing for anemia and hematuria in a sample. DISCUSSION: The trial will generate evidence regarding fMDA for P. vivax and inform malaria elimination efforts in Peru and similarly endemic settings. Findings will be in peer-reviewed publications and through stakeholder meetings in Peruvian and international policy and research forums. TRIAL REGISTRATION: Clinicaltrials.gov NCT05690841. This trial was registered on 09 January 2023.

Using Abattoir-Based Surveillance to Establish Foot-and-Mouth Disease Non-Structural Protein Seropositivity in Cattle and Pigs in Cambodia

Foot-and-mouth disease (FMD) is a contagious transboundary animal disease that causes economic loss and obstacles to international trade. Frequent FMD outbreaks in Cambodia negatively impact farmers’ and smallholders’ incomes. This study aimed to estimate the seroprevalence of FMD Non-Structural Protein (NSP) antibodies, which are an indicator of FMD antibodies raised during a natural infection rather than those produced following vaccination, that were detected using a commercial enzyme-linked immunosorbent assay (ELISA). Sample collection from cattle and pigs (n = 2238) was performed at ten abattoirs in seven provinces between October 2019 and December 2020. Overall seroprevalence in cattle and pigs was 43.2% (363/839; 95% CI 39.8–46.7), and 0.6% (9/1399; 95% CI 0.2–1.2), respectively. Only the cattle dataset was included in the risk factor analysis, as the prevalence of sero-reactors was too low in the pig dataset to be analyzed. Significant risk factors identified by the logistic regression model included the province of origin (p = 0.02), body condition score (BCS) (p = 0.0002) and sex (p = 0.0007). Odds ratios of the significant risk factors were 7.05 (95% CI 1.43–34.67; p = 0.02) for cattle that originated from Kampong Thom, 1.41 (95% CI 1.05–1.89; p = 0.02) for female cattle, and 3.28 (95% CI 1.06–10.12; p = 0.04) for animals with BCS of 3/5. The study revealed that the seroprevalence of FMD NSP in cattle presented at the abattoirs was high, while the FMD NSP seroprevalence in abattoir pigs was very low. Further investigation is required to map the disease distribution in Cambodia, especially the serotypes and strains causing clinical disease. These findings call for the extension of work on effective disease prevention measures.