A Systematic Review of Methods for Estimating Productivity Losses due to Illness or Caregiving in Low- and Middle-Income Countries.

BACKGROUND: Productivity losses are often included in costing studies and economic evaluations to provide a comprehensive understanding of the economic burden of disease. Global guidance on estimating productivity losses is sparse, especially for low-and middle-income countries (LMICs) where informal and unpaid work remains dominant. This study aims to describe current practices for valuing productivity losses in LMICs. METHODS: We performed a systematic review of studies published before April 2022 using three databases, including PubMed, Cochrane Library and Web of Science Core Collection. We included any costing or economic evaluation study conducted in a LMIC that provided methodological details on how the monetary value for productivity losses was estimated. Two reviewers independently screened articles for inclusion, extracted data and assessed the quality of the studies. RESULTS: A total of 281 articles were included. While most studies did not specify the overall approach used to measure and value productivity losses (58%), the human capital approach was the most frequently used approach to measure productivity losses when this was clearly stated (39%). The most common methods to estimate a monetary value for productivity losses were market wages (51%), self-reported wages (28%) and macroeconomic measures (15%). CONCLUSION: Reporting standards for productivity losses in LMIC settings have room for improvement. While market wages were the most frequently used method to estimate the monetary value of productivity losses, this relies on context-specific data availability. Until a consensus is reached on if, when and how to include productivity losses in costing and economic evaluation studies, future studies could include a sensitivity analysis to explore the impact of different methods for estimating the monetary value of productivity losses.

Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial).

BACKGROUND: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. METHODS/DESIGN: The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. DISCUSSION: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05693545.

Potential Cost-Effectiveness of Maternal Influenza Immunisation in Low-Income Countries: An Explorative Modelling Study and Value of Information Analysis to Guide Future Clinical Research.

Maternal influenza immunisation (MII) is recommended for protecting pregnant women and infants under six months of age from severe disease related to influenza. However, few low-income countries have introduced this vaccine. Existing cost-effectiveness studies do not consider potential vaccine non-specific effects (NSE) observed in some settings, such as reductions in preterm birth. A decision tree model was built to examine the potential cost-effectiveness of MII in a hypothetical low-income country compared to no vaccination, considering possible values for NSE on preterm birth in addition to vaccine-specific effects on influenza. We synthesized epidemiological and cost data from low-income countries. All costs were adjusted to 2021 United States dollars (USD). We considered cost-effectiveness thresholds that reflect opportunity costs (USD 188 per disability-adjusted life year averted; range: USD 28-538). Results suggest that even a small (5%) NSE on preterm birth may make MII a cost-effective strategy in these settings. A value of information analysis indicated that acquiring more information on the presence and possible size of NSE of MII could greatly reduce the uncertainty in decision-making on MII. Further clinical research investigating NSE in low-income countries may be of high value to optimise immunisation policy.

Psychometric Properties of Child Health Utility 9D (CHU9D) Proxy Version Administered to Parents and Caregivers of Children Aged 2-4 Years Compared with Pediatric Quality of Life Inventory™ (PedsQL).

OBJECTIVE: This study examines the psychometric properties of the Child Health Utility 9D (CHU9D) proxy version administered to parents/caregivers of 2-4-year-old Australian children compared with Pediatric Quality of Life Inventory™ version 4.0 (PedsQL). METHODS: Data collected in 2021/2022 from parents/caregivers of 2-4-year-olds from the Australian pediatric multi-instrument comparison study were used. Feasibility, ceiling/floor effects, test-retest reliability, convergent validity, known-group validity, and responsiveness were assessed. RESULTS: A total of 842 caregivers completed the survey at baseline, with 513 completing the follow-up survey. The CHU9D did not demonstrate ceiling effects in the sample with special health care needs, with only 6% of respondents reporting best levels for all nine dimensions. CHU9D correlated with PedsQL moderately-to-strongly between comparable items (correlation coefficients 0.34-0.70). CHU9D was able to differentiate between groups with known health differences with moderate-to-large effect sizes (Cohen's d 0.58-2.03). Moderate test-retest reliability was found for CHU9D in those reporting no health change at a 2-day follow-up (ICC 0.52). A standard response mean (SRM) of 0.25-0.44 was found for children with changes in general health and a SRM of 0.72-0.82 for children who reported worsened health when developing new illnesses, indicating small-to-large responsiveness according to different definitions of health changes. Compared with PedsQL, CHU9D had similar known-group validity and responsiveness and slightly poorer test-retest reliability. CONCLUSION: The CHU9D was found to be valid and reliable to measure health-related quality-of-life in children aged 2-4 years, although with relatively low test-retest reliability in some dimensions. Further development and validation work is warranted.

Use of Utility and Disability Weights in Economic Evaluation of Pediatric Vaccines.

OBJECTIVE: To describe how utility weights and disability weights have been used in the context of quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs)-based cost-effectiveness analysis (CEA) of pediatric vaccines for infectious diseases and assess the comparability between weights. METHODS: A systematic review was conducted of CEAs of pediatric vaccines for 16 infectious diseases, published between January 2013 and December 2020 and using QALYs or DALYs as outcome measure. Data on values and sources of weights for the estimation of QALYs and DALYs were extracted from studies and compared across similar health states. Reporting was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Out of 2154 articles identified, 216 CEAs met our inclusion criteria. Of the included studies, 157 used utility weights and 59 used disability weights in their valuation of health states. In QALY studies, the source, background, who's preferences (adults'/children's) were applied and adjustments made to utility weights were poorly reported. In DALY studies, the Global Burden of Disease study was most often referenced. Valuation weights for similar health states varied within QALY studies and between DALY and QALY studies, but no systematic differences were identified. CONCLUSIONS: This review identified considerable gaps in the way valuation weights are used and reported on in CEA. The nonstandardized use of weights may lead to different conclusions about cost-effectiveness of vaccines and policy decisions.

How do common conditions impact health-related quality of life for children? Providing guidance for validating pediatric preference-based measures.

BACKGROUND: There is increasing interest in the validation of pediatric preference-based health-related quality of life measurement instruments. It is critical that children with various degrees of health-related quality of life (HRQoL) impact are included in validation studies. To inform patient sample selection for validation studies from a pragmatic perspective, this study explored HRQoL impairments between known-groups and HRQoL changes over time across 27 common chronic child health conditions and identified conditions with the largest impact on HRQoL. METHODS: The health dimensions of two common preference-based HRQoL measures, the EQ-5D-Y and CHU9D, were constructed using Pediatric Quality of Life Inventory items that overlap conceptually. Data was from the Longitudinal Study of Australian Children, a nationally representative sample with over 10,000 children at baseline. Seven waves of data were included for the analysis, with child age ranging from 2 to18 years. Impacts to specific health dimensions and overall HRQoL between those having a specific condition versus not were compared using linear mixed effects models. HRQoL changes over time were obtained by calculating the HRQoL differences between two consecutive time points, grouped by "Improved" and "Worsened" health status. Comparison among various health conditions and different age groups (2-4 years, 5-12 years and 13-18 years) were made. RESULTS: Conditions with the largest statistically significant total HRQoL impairments of having a specific condition compared with not having the condition were recurrent chest pain, autism, epilepsy, anxiety/depression, irritable bowel, recurrent back pain, recurrent abdominal pain, and attention deficit hyperactivity disorder (ADHD) for the total sample (2-18 years). Conditions with largest HRQoL improvement over time were anxiety/depression, ADHD, autism, bone/joint/muscle problem, recurrent abdominal pain, recurrent pain in other part, frequent headache, diarrhea and day-wetting. The dimensions included in EQ-5D-Y and CHU9D can generally reflect HRQoL differences and changes. The HRQoL impacts to specific health dimensions differed by condition in the expected direction. The conditions with largest HRQoL impacts differed by age group. CONCLUSIONS: The conditions with largest HRQoL impact were identified. This information is likely to be valuable for recruiting patient samples when validating pediatric preference-based HRQoL instruments pragmatically.

Cost-effectiveness of universal iron supplementation and iron-containing micronutrient powders for anemia among young children in rural Bangladesh: analysis of a randomized, placebo-controlled trial.

BACKGROUND: Universal provision of iron supplements or iron-containing multiple micronutrient powders (MNPs) is widely used to prevent anemia in young children in low- and middle-income countries. The BRISC (Benefits and Risks of Iron Interventions in Children) trial compared iron supplements and MNPs with placebo in children <2 y old in rural Bangladesh. OBJECTIVES: We aimed to assess the cost-effectiveness of iron supplements or iron-containing MNPs among young children in rural Bangladesh. METHODS: We did a cost-effectiveness analysis of MNPs and iron supplements using the BRISC trial outcomes and resource use data, and programmatic data from the literature. Health care costs were assessed from a health system perspective. We calculated incremental cost-effectiveness ratios (ICERs) in terms of US$ per disability-adjusted life-year (DALY) averted. To explore uncertainty, we constructed cost-effectiveness acceptability curves using bootstrapped data over a range of cost-effectiveness thresholds. One- and 2-way sensitivity analyses tested the impact of varying key parameter values on our results. RESULTS: Provision of MNPs was estimated to avert 0.0031 (95% CI: 0.0022, 0.0041) DALYs/child, whereas iron supplements averted 0.0039 (95% CI: 0.0030, 0.0048) DALYs/child, over 1 y compared with no intervention. Incremental mean costs were $0.75 (95% CI: 0.73, 0.77) for MNPs compared with no intervention and $0.64 ($0.62, $0.67) for iron supplements compared with no intervention. Iron supplementation dominated MNPs because it was cheaper and averted more DALYs. Iron supplementation had an ICER of $1645 ($1333, $2153) per DALY averted compared with no intervention, and had a 0% probability of being the optimal strategy at cost-effectiveness thresholds of $200 (reflecting health opportunity costs in Bangladesh) and $985 [half of gross domestic product (GDP) per capita] per DALY averted. Scenario and sensitivity analyses supported the base case findings. CONCLUSIONS: These findings do not support universal iron supplementation or micronutrient powders as a cost-effective intervention for young children in rural Bangladesh. This trial was registered at anzctr.org.au as ACTRN1261700066038 and trialsearch.who.int as U1111-1196-1125.

Associations between Indonesia's national health insurance, effective coverage in maternal health and neonatal mortality: a multilevel interrupted time-series analysis 2000-2017.

BACKGROUND: We assessed the effect of Indonesia's national health insurance programme (Jaminan Kesehatan Nasional (JKN)) on effective coverage for maternal and child health across geographical regions and population groups. METHODS: We used four waves of the Indonesia Demographic and Health Survey from 2000 to 2017, which included 38 880 women aged 15-49 years and 144 000 birth records. Key outcomes included antenatal and delivery care, caesarean section and neonatal and infant mortality. We used multilevel interrupted time-series regression to examine changes in outcomes after the introduction of the JKN in January 2014. FINDINGS: JKN introduction was associated with significant level increases in (1) antenatal care (ANC) crude coverage (adjusted OR (aOR) 1.81, 95% CI 1.44 to 2.27); (2) ANC quality-adjusted coverage (aOR 1.66, 95% CI 1.38 to 1.98); (3) ANC user-adherence-adjusted coverage (aOR 1.80, 95% CI 1.45 to 2.25); (4) safe delivery service contact (aOR 1.83, 95% CI 1.42 to 2.36); and (5) safe delivery crude coverage (aOR 1.45, 95% CI 1.20 to 1.75). We did not find any significant level increase in ANC service contact or caesarean section. Interestingly, increases in ANC service contact and crude coverage, and safe delivery crude coverage were larger among the poorest compared with the most affluent. No statistically significant associations were found between JKN introduction and neonatal and infant mortality (p>0.05) in the first 3 years following implementation. INTERPRETATION: Expansion of social health insurance led to substantial improvements in quality of care for maternal health services but not in child mortality. Concerted efforts are required to equitably improve service quality and child mortality across the population in Indonesia.

Comparing health gains, costs and cost-effectiveness of 100s of interventions in Australia and New Zealand: an online interactive league table.

BACKGROUND: This study compares the health gains, costs, and cost-effectiveness of hundreds of Australian and New Zealand (NZ) health interventions conducted with comparable methods in an online interactive league table designed to inform policy. METHODS: A literature review was conducted to identify peer-reviewed evaluations (2010 to 2018) arising from the Australia Cost-Effectiveness research and NZ Burden of Disease Epidemiology, Equity and Cost-Effectiveness Programmes, or using similar methodology, with: health gains quantified as health-adjusted life years (HALYs); net health system costs and/or incremental cost-effectiveness ratio; time horizon of at least 10 years; and 3% to 5% discount rates. RESULTS: We identified 384 evaluations that met the inclusion criteria, covering 14 intervention domains: alcohol; cancer; cannabis; communicable disease; cardiovascular disease; diabetes; diet; injury; mental illness; other non-communicable diseases; overweight and obesity; physical inactivity; salt; and tobacco. There were large variations in health gain across evaluations: 33.9% gained less than 0.1 HALYs per 1000 people in the total population over the remainder of their lifespan, through to 13.0% gaining > 10 HALYs per 1000 people. Over a third (38.8%) of evaluations were cost-saving. CONCLUSIONS: League tables of comparably conducted evaluations illustrate the large health gain (and cost) variations per capita between interventions, in addition to cost-effectiveness. Further work can test the utility of this league table with policy-makers and researchers.

Prevention of bacterial complications of scabies using mass drug administration: A population-based, before-after trial in Fiji, 2018-2020.

Background: Scabies is an important predisposing factor of impetigo which can lead to serious bacterial complications. Ivermectin-based mass drug administration can substantially reduce scabies and impetigo prevalence in endemic settings, but the impact on serious bacterial complications is not known. Methods: We conducted a before-after trial in the Northern Division of Fiji (population: 131,914) of mass drug administration for scabies control. Prospective surveillance was conducted from 2018 to 2020. Mass drug administration took place in 2019, involving two doses of oral ivermectin or topical permethrin, delivered alongside diethylcarbamazine and albendazole for lymphatic filariasis. The primary outcomes were incidence of hospitalisations with skin and soft tissue infections, and childhood invasive infections and post-streptococcal sequelae. Secondary outcomes included presentations to primary healthcare with skin infections and community prevalence of scabies and impetigo. Findings: The incidence of hospitalisations with skin and soft tissue infections was 17% lower after the intervention compared to baseline (388 vs 467 per 100,000 person-years; incidence rate ratio 0.83, 95% CI, 0.74 to 0.94; P = 0.002). There was no difference in incidence of childhood invasive infections and post-streptococcal sequelae. Incidence of primary healthcare presentations with scabies and skin infections was 21% lower (89.2 vs 108 per 1000 person-years, incidence rate ratio, IRR 0.79, 95% CI, 0.78 to 0.82). Crude community prevalence of scabies declined from 14.2% to 7.7% (cluster-adjusted prevalence 12.5% to 8.9%; prevalence ratio 0.71, 95% CI, 0.28 to 1.17). Cluster-adjusted prevalence of impetigo declined from 15.3% to 6.1% (prevalence ratio 0.4, 95% CI, 0.18 to 0.86). Interpretation: Mass drug administration for scabies control was associated with a substantial reduction in hospitalisations for skin and soft tissue infections. Funding: National Health and Medical Research Council of Australia and Scobie and Claire Mackinnon Trust.

Costs of mass drug administration for scabies in Fiji.

In 2019, the Murdoch Children's Research Institute in partnership with the Fiji Ministry of Health and Medical Services carried out an integrated mass drug administration (MDA) for the treatment of scabies and lymphatic filariasis in the Northern Division of Fiji (population estimate 131,914). We conducted a retrospective micro-costing exercise focused on the cost of scabies control in order to inform budgeting and policy decision making in an endemic setting. We collected detailed information on financial and economic costs incurred by both parties during the course of the MDA campaign (April 2018 to July 2019). We also conducted interviews with personnel involved in the financial administration of the MDA campaign. The economic cost of delivering two doses of ivermectin was US$4.88 per person. The cost of donated drugs accounted for 36.3% of total MDA costs. In this first large-scale MDA for the public health control of scabies, the estimated cost of delivering MDA per person for scabies was considerably more expensive than the costs reported for other neglected tropical diseases. The important cost drivers included the remuneration of health care workers who were extensively involved in the campaign, coverage of hard-to-reach, mainly rural populations and the two-dose regimen of ivermectin. These results highlight the importance of these cost determinants and can be used to plan current and future MDA programs.

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey.

BACKGROUND: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. METHODS: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017-2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. RESULTS: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. CONCLUSION: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. FUNDING: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Modeling the Cost-Effectiveness of Latent Tuberculosis Screening and Treatment Strategies in Recent Migrants to a Low-Incidence Setting.

Many tuberculosis (TB) cases in low-incidence settings are attributed to reactivation of latent TB infection (LTBI) acquired overseas. We assessed the cost-effectiveness of community-based LTBI screening and treatment strategies in recent migrants to a low-incidence setting (Australia). A decision-analytical Markov model was developed that cycled 1 migrant cohort (≥11-year-olds) annually over a lifetime from 2020. Postmigration/onshore and offshore (screening during visa application) strategies were compared with existing policy (chest x-ray during visa application). Outcomes included TB cases averted and discounted cost per quality-adjusted life-year (QALY) gained from a health-sector perspective. Most recent migrants are young adults and cost-effectiveness is limited by their relatively low LTBI prevalence, low TB mortality risks, and high emigration probability. Onshore strategies cost at least $203,188 (Australian) per QALY gained, preventing approximately 2.3%-7.0% of TB cases in the cohort. Offshore strategies (screening costs incurred by migrants) cost at least $13,907 per QALY gained, preventing 5.5%-16.9% of cases. Findings were most sensitive to the LTBI treatment quality-of-life decrement (further to severe adverse events); with a minimal decrement, all strategies caused more ill health than they prevented. Additional LTBI strategies in recent migrants could only marginally contribute to TB elimination and are unlikely to be cost-effective unless screening costs are borne by migrants and potential LTBI treatment quality-of-life decrements are ignored.

Association between 24-hour movement behaviors and health-related quality of life in children.

PURPOSE: To assess the associations between adherence to 24-hour movement behaviors guidelines and child general health and functional status measured by health-related quality of life. METHODS: The Longitudinal Study of Australian Children (2004-2016) a nationally representative sample with data available for children aged 2-15 years was used. Physical activity time, recreational screen time, and sleep time were calculated from time use diaries and classified as 'meeting guidelines' or 'not' based on the age-specific 24-h movement guidelines. Child general health and functional status were measured using the multidimensional Pediatric Quality of Life Inventory (PedsQL). Associations between meeting guidelines and PedsQL were assessed using linear mixed effects models. RESULTS: 8919 children were included. Each additional guideline met was associated with a 0.52 (95% confidence interval [CI] 0.39-0.65) increase in PedsQL total score. Compared with meeting no guidelines, the effect of meeting physical activity guidelines alone (ß = 0.93, 95% CI 0.42-1.44) was larger compared to meeting screen (ß = 0.66, 95% CI 0.06-1.27) or sleep time (ß = 0.47, 95% CI 0.04-0.89) guidelines alone. The highest increment was observed in meeting both screen time and physical activity guidelines (ß = 1.89, 95% CI 1.36-2.43). Associations were stronger in children from lower-income families (ß for meeting all versus none = 2.88, 95% CI 1.77-3.99) and children aged 14-15 years (ß = 4.44, 95% CI 2.49-6.40). CONCLUSIONS: The integration of screen time and physical activity guidelines is associated with the highest PedsQL improvement. The association between guidelines adherence and PedsQL appears stronger for adolescents and those from low-income families.

Health-related quality of life impact of scabies in the Solomon Islands.

BACKGROUND: Scabies causes intense itching and skin lesions. A small number of studies have shown that scabies impacts health-related quality of life (HRQoL), but no studies have been conducted in the Pacific region. We assessed the impact of scabies on HRQoL in a high-prevalence setting using the Children's Dermatology Life Quality Index (CDLQI) and Dermatology Life Quality Index (DLQI). We also assessed the validity of these tools in a Pacific Island population. METHODS: The study was conducted in the Solomon Islands. Participants with and without skin disease were randomly selected. HRQoL indices were scored on a scale of 0-30. RESULTS: We surveyed 1051 adults (91 with scabies) and 604 children (103 with scabies). Scabies had a small impact on HRQoL, with a median DLQI score of 2 (interquartile range [IQR] 0-6) and a CDLQI score of 2 (IQR 0-4). Scores increased linearly with severity. The greatest impact on QoL was due to itch, sleep disturbance and impacts on education and employment. CONCLUSIONS: Scabies has a small but measurable impact on HRQoL. The DLQI and CDLQI scores were discriminated between the skin-related QoL of patients with scabies and the control group, indicating that these tools are appropriate to measure skin-related QoL in the Solomon Islands.

Determinants and prediction of Chlamydia trachomatis re-testing and re-infection within 1 year among heterosexuals with chlamydia attending a sexual health clinic.

Background: Chlamydia trachomatis (chlamydia) is one of the most common sexually transmitted infections (STI) globally, and re-infections are common. Current Australian guidelines recommend re-testing for chlamydia 3 months after treatment to identify possible re-infection. Patient-delivered partner therapy (PDPT) has been proposed to control chlamydia re-infection among heterosexuals. We aimed to identify determinants and the prediction of chlamydia re-testing and re-infection within 1 year among heterosexuals with chlamydia to identify potential PDPT candidates. Methods: Our baseline data included 5,806 heterosexuals with chlamydia aged ≥18 years and 2,070 re-tested for chlamydia within 1 year of their chlamydia diagnosis at the Melbourne Sexual Health Center from January 2, 2015, to May 15, 2020. We used routinely collected electronic health record (EHR) variables and machine-learning models to predict chlamydia re-testing and re-infection events. We also used logistic regression to investigate factors associated with chlamydia re-testing and re-infection. Results: About 2,070 (36%) of 5,806 heterosexuals with chlamydia were re-tested for chlamydia within 1 year. Among those retested, 307 (15%) were re-infected. Multivariable logistic regression analysis showed that older age (≥35 years old), female, living with HIV, being a current sex worker, patient-delivered partner therapy users, and higher numbers of sex partners were associated with an increased chlamydia re-testing within 1 year. Multivariable logistic regression analysis also showed that younger age (18-24 years), male gender, and living with HIV were associated with an increased chlamydia re-infection within 1 year. The XGBoost model was the best model for predicting chlamydia re-testing and re-infection within 1 year among heterosexuals with chlamydia; however, machine learning approaches and these self-reported answers from clients did not provide a good predictive value (AUC < 60.0%). Conclusion: The low rate of chlamydia re-testing and high rate of chlamydia re-infection among heterosexuals with chlamydia highlights the need for further interventions. Better targeting of individuals more likely to be re-infected is needed to optimize the provision of PDPT and encourage the test of re-infection at 3 months.

Management of Chlamydia Cases in Australia (MoCCA): protocol for a non-randomised implementation and feasibility trial.

INTRODUCTION: The sexually transmitted infection chlamydia can cause significant complications, particularly among people with female reproductive organs. Optimal management includes timely and appropriate treatment, notifying and treating sexual partners, timely retesting for reinfection and detecting complications including pelvic inflammatory disease (PID). In Australia, mainstream primary care (general practice) is where most chlamydia infections are diagnosed, making it a key setting for optimising chlamydia management. High reinfection and low retesting rates suggest partner notification and retesting are not uniformly provided. The Management of Chlamydia Cases in Australia (MoCCA) study seeks to address gaps in chlamydia management in Australian general practice through implementing interventions shown to improve chlamydia management in specialist services. MoCCA will focus on improving retesting, partner management (including patient-delivered partner therapy) and PID diagnosis. METHODS AND ANALYSIS: MoCCA is a non-randomised implementation and feasibility trial aiming to determine how best to implement interventions to support general practice in delivering best practice chlamydia management. Our method is guided by the Consolidated Framework for Implementation Research and the Normalisation Process Theory. MoCCA interventions include a website, flow charts, fact sheets, mailed specimen kits and autofills to streamline chlamydia consultation documentation. We aim to recruit 20 general practices across three Australian states (Victoria, New South Wales, Queensland) through which we will implement the interventions over 12-18 months. Mixed methods involving qualitative and quantitative data collection and analyses (observation, interviews, surveys) from staff and patients will be undertaken to explore our intervention implementation, acceptability and uptake. Deidentified general practice and laboratory data will be used to measure pre-post chlamydia testing, retesting, reinfection and PID rates, and to estimate MoCCA intervention costs. Our findings will guide scale-up plans for Australian general practice. ETHICS AND DISSEMINATION: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (Ethics ID: 22665). Findings will be disseminated via conference presentations, peer-reviewed publications and study reports.

Socioeconomic inequalities in effective service coverage for reproductive, maternal, newborn, and child health: a comparative analysis of 39 low-income and middle-income countries.

BACKGROUND: Reducing socioeconomic inequalities in access to good quality health care is key for countries to achieve Universal Health Coverage. This study aims to assess socioeconomic inequalities in effective coverage of reproductive, maternal, newborn and child health (RMNCH) in low- and middle-income countries (LMICs). METHODS: Using the most recent national health surveys from 39 LMICs (between 2014 and 2018), we calculated coverage indicators using effective coverage care cascade that consists of service contact, crude coverage, quality-adjusted coverage, and user-adherence-adjusted coverage. We quantified wealth-related and education-related inequality using the relative index of inequality, slope index of inequality, and concentration index. FINDINGS: The quality-adjusted coverage of RMNCH services in 39 countries was substantially lower than service contact, in particular for postnatal care (64 percentage points [pp], p-value<0·0001), family planning (48·7 pp, p<0·0001), and antenatal care (43·6 pp, p<0·0001) outcomes. Upper-middle-income countries had higher effective coverage levels compared with low- and lower-middle-income countries in family planning, antenatal care, delivery care, and postnatal care. Socioeconomic inequalities tend to be wider when using effective coverage measurement compared with crude and service contact measurements. Our findings show that upper-middle-income countries had a lower magnitude of inequality compared with low- and lower-middle-income countries. INTERPRETATION: Reliance on the average contact coverage tends to underestimate the levels of socioeconomic inequalities for RMNCH service use in LMICs. Hence, the effective coverage measurement using a care cascade approach should be applied. While RMNCH coverages vary considerably across countries, equitable improvement in quality of care is particularly needed for lower-middle-income and low-income countries. FUNDING: None.

Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).