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Author(s): Xuecheng Yin 1,2,3,*, Yunfei Li 4, Minttu M. Rönn 4, Song Li 5, Yue Yuan 6, Thomas L. Gift 7, Katherine Hsu 8, Joshua A. Salomon 9, Yonatan H. [...], Background Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. Methods and findings We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. Conclusions Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

Author(s): Lyndon P. James 1,2,*, Fayette Klaassen 3, Sedona Sweeney 4, Jennifer Furin 5, Molly F. Franke 5, Reza Yaesoubi 6, Dumitru Chesov 7,8, Nelly Ciobanu 9, Alexandru Codreanu 9, [...], Background Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). Methods and findings The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova&apos;s national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. Conclusions Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

ObjectiveTo determine the cost-effectiveness of building and maintaining a dedicated pediatric operating room (OR) in Uganda from the societal perspective.BackgroundDespite the heavy burden of pediatric surgical disease in low-income countries, definitive treatment is limited as surgical infrastructure is inadequate to meet the need, leading to preventable morbidity and mortality in children.MethodsIn this economic model, we used a decision tree template to compare the intervention of a dedicated pediatric OR in Uganda for a year versus the absence of a pediatric OR. Costs were included from the government, charity, and patient perspectives. OR and ward case-log informed epidemiological and patient outcomes data, and measured cost per disability adjusted life year averted and cost per life saved. The incremental cost-effectiveness ratio (ICER) was calculated between the intervention and counterfactual scenario. Costs are reported in 2015 US$ and inflated by 5.5%.FindingsIn Uganda, the implementation of a dedicated pediatric OR has an ICER of $37.25 per disability adjusted life year averted or $3321 per life saved, compared with no existing operating room. The ICER is well below multiple cost-effectiveness thresholds including one times the country's gross domestic product per capita ($694). The ICER remained robust under 1-way and probabilistic sensitivity analyses.ConclusionOur model ICER suggests that the construction and maintenance of a dedicated pediatric operating room in sub-Saharan Africa is very-cost effective if hospital space and personnel pre-exist to staff the facility. This supports infrastructure implementation for surgery in sub-Saharan Africa as a worthwhile investment.

Background: With the proportion of tuberculosis cases that are extrapulmonary tuberculosis (EPTB) increasing in recent years, understanding and addressing factors contributing to the prolonged time to diagnosis (TTD) of EPTB patients is vital. Methods: We enrolled presumptive EPTB patients for a cohort study from 2018–2020 in Ujjain, India. Based on a structured questionnaire, the patients were interviewed for socio-demographic and clinical information, including previously visited health facilities (HF) for this illness. We analysed patients' TTD, healthcare access, and referral pathways. Findings: EPTB (54%) and non-TB (58%) patients visited dispensaries during their first visit to a formal HF. Patients visited multiple HFs, including dispensaries (54%) and regional hospitals (32%), during 1–4 visits but did not receive an appropriate diagnosis. Less than 2% of the patients accessed private HFs. Most of the adult EPTB (83%) and non-TB (76%) patients were self-referred to our study site, where they were diagnosed. Our statistical models highlighted low-middle income groups, longer distances and longer travel time to HFs, and potentially less-empowered occupations as housewives with a prolonged TTD. Patients with a longer wait, including travel time, had a shorter TTD. Conclusion: We found individual, societal-level, and structural barriers to healthcare access and utilisation and their association with diagnostic delay among adult and paediatric EPTB patients. [ABSTRACT FROM AUTHOR]

Background: Methods to present the result of cost-effectiveness analyses under parameter uncertainty include cost-effectiveness planes (CEPs), cost-effectiveness acceptability curves/frontier (CEACs/CEAF), expected loss curves (ELCs), and net monetary benefit (NMB) lines. We describe how NMB lines can be augmented to present NMB values that could be achieved by reducing or resolving parameter uncertainty. We evaluated the ability of these methods to correctly 1) identify the alternative with the highest expected NMB and 2) communicate the magnitude of parameter and decision uncertainty. Methods: We considered 4 hypothetical decision problems representing scenarios with high variance or correlated cost and effect estimates and alternatives with similar cost-effectiveness ratios. We used these decision problems to demonstrate the limitations of existing methods and the potential of augmented NMB lines to resolve these issues. Results: CEPs and CEACs/CEAF could falsely imply the lack of sufficient evidence to identify the optimal option if cost and effect estimates have high variance, are correlated across alternatives, or when alternatives have similar cost-effectiveness ratios. The augmented NMB lines and ELCs can correctly identify the option with the highest expected NMB and communicate the potential benefit of resolving uncertainties. Like ELCs, the augmented NMB lines provide information about the value of resolving parameter uncertainties, but augmented NMB lines may be easier to interpret for decision makers. Conclusions: Our analysis supports recommending the augment NMB lines as an important method to present the results of economic evaluation studies under parameter uncertainty. Highlights: The results of cost-effectiveness analyses (CEAs) when the cost and effect estimates of alternatives are uncertain are commonly presented using cost-effectiveness planes (CEPs), cost-effectiveness acceptability curves/frontier (CEACs/CEAF), and expected loss curves (ELCs). Although currently not often used, net monetary benefit (NMB) lines could present the results of cost-effectiveness to identify the alternative with the highest expected NMB values given the current level of uncertainty. Furthermore, NMB lines can be augmented to 1) show metrics of value of information, which measure the value of additional research to reduce or eliminate the decision uncertainty, and 2) display the confidence intervals along the NMB lines to ensure that NMB values are estimated accurately using a sufficiently large number of parameter samples. Using several decision problems, we demonstrate the limitation of existing methods to present the results of CEAs under parameter uncertainty and how augmented NMB lines could resolve these issues. Our analysis supports recommending augmented NMB lines as an important method to present the results of CEA under uncertainty since they 1) correctly identify the alternative with the highest expected NMB value given the current evidence, 2) provide information about the potential value of additional research to improve the decision by reducing or resolving uncertainty in model parameters, 3) assist the analysis to visually ensure that enough parameter samples are used to estimate the expected NMB of alternatives, and 4) are easier to interpret for decision makers compared with other methods. [ABSTRACT FROM AUTHOR]

Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of antibiotic resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective life span of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the United States to project the annual rate of reported gonorrhea cases and the effective life span of ceftriaxone, the recommended antibiotic for first-line treatment of gonorrhea, as well as 2 previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test that estimates susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid drug susceptibility test with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and nonsusceptibility status, could increase the combined effective life span of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective life span of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. Methods We developed a Markov model that simulates the natural history and management of syphilis. The model was parameterized by sex and sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to quantify health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. Results We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 (95% uncertainty interval [UI].03–.19). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13 349 (5071–31 360). Although per-case loss was the lowest among MSM (0.06), MSM accounted for 47.7% of the overall burden. For each case of congenital syphilis, we estimated 1.79 (1.43–2.16) and 0.06 (.01–.14) QALYs lost in the child and the mother, respectively. We projected 2332 (1871–28 250) and 79 (17–177) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. Conclusions Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases. [ABSTRACT FROM AUTHOR]

Author(s): Reza Yaesoubi 1,*, Caroline Trotter 2, Caroline Colijn 3,4, Maziar Yaesoubi 5, Anaïs Colombini 6, Stephen Resch 7, Paul A. Kristiansen 8, F. Marc LaForce 9, Ted Cohen 10 [...], Background The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. Methods and findings We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all circulating meningococcal serogroups can be aggregated into a single group; while this assumption is critical for model tractability, it would compromise the insights derived from our model if the effectiveness of the vaccine differs markedly between serogroups or if there are complex between-serogroup interactions that influence the frequency and magnitude of future meningitis epidemics. Conclusions Our results suggest that a vaccination strategy that includes a catch-up nationwide immunization campaign in young adults with a PMC vaccine and the addition of this new vaccine into EPI is cost-effective and would avert a substantial portion of meningococcal cases expected under the current World Health Organization-recommended strategy of reactive vaccination. This analysis is limited to Burkina Faso and assumes that polyvalent vaccines offer equal protection against all meningococcal serogroups; further studies are needed to evaluate the robustness of this assumption and applicability for other countries in the meningitis belt.