Evaluation of the routine implementation of pulse oximeters into integrated management of childhood illness (IMCI) guidelines at primary health care level in West Africa: the AIRE mixed-methods research protocol.

BACKGROUND: The AIRE operational project will evaluate the implementation of the routine Pulse Oximeter (PO) use in the integrated management of childhood illness (IMCI) strategy for children under-5 in primary health care centers (PHC) in West Africa. The introduction of PO should promote the accurate identification of hypoxemia (pulse blood oxygen saturation Sp02 < 90%) among all severe IMCI cases (respiratory and non-respiratory) to prompt their effective case management (oxygen, antibiotics and other required treatments) at hospital. We seek to understand how the routine use of PO integrated in IMCI outpatients works (or not), for whom, in what contexts and with what outcomes. METHODS: The AIRE project is being implemented from 03/2020 to 12/2022 in 202 PHCs in four West African countries (Burkina Faso, Guinea, Mali, Niger) including 16 research PHCs (four per country). The research protocol will assess three complementary components using mixed quantitative and qualitative methods: a) context based on repeated cross-sectional surveys: baseline and aggregated monthly data from all PHCs on infrastructure, staffing, accessibility, equipment, PO use, severe cases and care; b) the process across PHCs by assessing acceptability, fidelity, implementation challenges and realistic evaluation, and c) individual outcomes in the research PHCs: all children under-5 attending IMCI clinics, eligible for PO use will be included with parental consent in a cross-sectional study. Among them, severe IMCI cases will be followed in a prospective cohort to assess their health status at 14 days. We will analyze pathways, patterns of care, and costs of care. DISCUSSION: This research will identify challenges to the systematic implementation of PO in IMCI consultations, such as health workers practices, frequent turnover, quality of care, etc. Further research will be needed to fully address key questions such as the best time to introduce PO into the IMCI process, the best SpO2 threshold for deciding on hospital referral, and assessing the cost-effectiveness of PO use. The AIRE research will provide health policy makers in West Africa with sufficient evidence on the context, process and outcomes of using PO integrated into IMCI to promote scale-up in all PHCs. TRIAL REGISTRATION: Trial registration number: PACTR202206525204526 retrospectively registered on 06/15/2022.

Cost-effectiveness of hepatitis C virus test-and-treat and risk reduction strategies among men who have sex with men living with HIV in France.

INTRODUCTION: Studies suggest that hepatitis C virus (HCV) micro-elimination is feasible among men who have sex with men (MSM) living with human immunodeficiency virus (HIV), through treatment-as-prevention and interventions aimed at reducing risk behaviours. However, their economic impact is poorly understood. The aim of this study was to assess the cost-effectiveness of HCV screening and risk reduction strategies in France. METHODS: A compartmental deterministic mathematical model was developed to describe HCV disease transmission and progression among MSM living with HIV in France. We evaluated different combinations of HCV screening frequency (every 12, 6 or 3 months) and risk reduction strategies (targeting only high-risk or all MSM) from 2021 onwards. The model simulated the number of HCV infections, life-expectancy (LYs), quality-adjusted life-expectancy (QALYs), lifetime costs and incremental cost-effectiveness ratio (ICER) over a lifetime horizon (leading to an end of the simulation in 2065). RESULTS: All strategies increased QALYs, compared with current practices, that is yearly HCV screening, with no risk reduction. A behavioural intervention resulting in a 20% risk reduction in the high-risk group, together with yearly screening, was the least expensive strategy, and, therefore, cost-saving compared to current practices. The ICER per QALY gained for the strategy combining risk reduction for the high-risk group with 6-month HCV screening, compared to risk reduction with yearly screening, was €61,389. It also prevented 398 new HCV infections between 2021 and 2065, with a cost per infection averted of €37,790. All other strategies were dominated (more expensive and less effective than some other available alternative) or not cost-effective (ICER per QALY gained > €100,000). CONCLUSIONS: In the French context, current HCV screening practices without risk reduction among MSM living with HIV cannot be justified on economic grounds. Risk reduction interventions targeted to high-risk individuals-alongside screening either once or twice a year-could be cost-effective depending on the policymaker's willingness-to-pay.

Hepatitis C virus (HCV) incidence among men who have sex with men (MSM) living with HIV: results from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort study, 2014 to 2017.

BackgroundDespite the availability of highly effective direct-acting antivirals (DAAs) and the expected treatment as prevention (TasP) effect, transmission of hepatitis C virus (HCV) persists in men who have sex with men (MSM) who engage in high-risk sexual behaviours.AimWe aimed to estimate the incidence of primary HCV infection among MSM living with HIV in France when DAA was readily available.MethodsWe used data from a large French hospital cohort of persons living with HIV (ANRS CO4-FHDH) prospectively collected between 2014 and 2017. HCV incidence rates were calculated using person-time methods for HCV-negative MSM at inclusion who had serological follow-up from 1 January 2014 to 31 December 2017. Sensitivity analyses were performed by varying the main assumptions to assess their impact on the results.ResultsOf 14,273 MSM living with HIV who were initially HCV-seronegative, 330 acquired HCV during follow-up over 45,866 person-years (py), resulting in an overall estimated incidence rate of 0.72/100 py (95% CI: 0.65-0.80). HCV incidence significantly decreased from 0.98/100 py (95% CI: 0.81-1.19) in 2014 to 0.45/100 py (95% CI: 0.35-0.59) in 2017 (54% decrease; 95% CI: 36-67). This trend was confirmed by most of the sensitivity analyses.ConclusionThe primary incidence of HCV was halved for MSM living with HIV between 2014 and 2017. This decrease may be related to unrestricted DAA availability in France for individuals living with HIV. Further interventions, including risk reduction, are needed to reach HCV micro-elimination in MSM living with HIV.

Impact of the COVID-19 pandemic on the homeless: results from a retrospective closed cohort in France (March-May 2020).

OBJECTIVES: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization and fatality rates in residents of homeless shelters run by Samusocial of Paris. METHODS: We conducted a retrospective serological study between July and August 2020 on all residents and staff members of three homeless shelters run by Samusocial of Paris: two centres providing healthcare accommodation (HCA) and one a women's dormitory. We included all adults present in the shelters or who died of a proven SARS-CoV-2 infection during the first wave (March-May). SARS-CoV-2 antibodies were detected in serum samples using the SARS-CoV-2 IgG Architect (Abbott) test. Any participant with a positive PCR or serology was defined as a confirmed SARS-CoV-2 case. RESULTS: We included 100 residents and 83 staff members. The confirmed SARS-CoV-2 rate by PCR or serology was 72/100 (72.0%) for residents and 17/83 (20.5%) for staff members. Women accommodated in the dormitory had the highest infection rate (90.6%). The hospitalization rate in residents was 17/72 (23.6%) and the death rate 4/72 (5.6%). All hospitalizations and deaths occurred among HCA residents. Among the residents of HCA shelters, 34/68 (50%) presented at least two comorbidity factors associated with being at high risk for severe SARS-CoV-2 infection. CONCLUSION: The SARS-CoV-2 infection rate was high in residents of these homeless shelters (10.6% seroprevalence in the Île-de-France region during the first wave). Severe SARS-CoV-2 infection was highly associated with the prevalence of comorbidities. This population should be considered as a priority in vaccination campaigns and in access to individual housing units when at risk.

Impact of test-and-treat and risk reduction strategies on HCV transmission among MSM living with HIV in France: a modelling approach.

OBJECTIVE: Since the early 2000s, there has been an epidemic of HCV occurring among men who have sex with men (MSM) living with HIV, mainly associated with high-risk sexual and drug-related behaviours. Early HCV diagnosis and treatment, and behavioural risk-reduction, may be effective to eliminate HCV among MSM living with HIV. DESIGN: We developed a deterministic dynamic compartmental model to simulate the impact of test-and-treat and risk-reduction strategies on HCV epidemic (particularly on incidence and prevalence) among MSM living with HIV in France. We accounted for HIV and HCV cascades of care, HCV natural history and heterogeneity in HCV risk behaviours. The model was calibrated to primary HCV incidence observed between 2014 and 2017 among MSM living with HIV in care (ANRS CO4-French hospital database on HIV (FHDH)). RESULTS: With current French practices (annual HCV screening and immediate treatment), total HCV incidence would fall by 70%, from 0.82/100 person-years in 2015 to 0.24/100 person-years in 2030. It would decrease to 0.19/100 person-years in 2030 with more frequent screening and to 0.19 (0.12)/100 person-years in 2030 with a 20% (50%) risk-reduction. When combining screening every 3 months with a 50% risk-reduction, HCV incidence would be 0.11/100 person-years in 2030, allowing to get close to the WHO target (90% reduction from 2015 to 2030). Similarly, HCV prevalence would decrease from 2.79% in 2015 to 0.48% in 2030 (vs 0.71% with current practices). CONCLUSION: Combining test-and-treat and risk-reduction strategies could have a marked impact on the HCV epidemic, paving the way to HCV elimination among MSM living with HIV.

Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum ß-lactamase-producing Escherichia coli: a mathematical modelling study.

BACKGROUND: The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking. METHODS: We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon. RESULTS: The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0-5.6) or 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9-62.0) to 68.8% (68.3-69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%. CONCLUSIONS: The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.

Predicting Dengue Outbreaks in Cambodia.

In Cambodia, dengue outbreaks occur each rainy season (May-October) but vary in magnitude. Using national surveillance data, we designed a tool that can predict 90% of the variance in peak magnitude by April, when typically <10% of dengue cases have been reported. This prediction may help hospitals anticipate excess patients.

Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015-2016.

Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015-2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.

How Modelling Can Enhance the Analysis of Imperfect Epidemic Data.

Mathematical models play an increasingly important role in our understanding of the transmission and control of infectious diseases. Here, we present concrete examples illustrating how mathematical models, paired with rigorous statistical methods, are used to parse data of different levels of detail and breadth and estimate key epidemiological parameters (e.g., transmission and its determinants, severity, impact of interventions, drivers of epidemic dynamics) even when these parameters are not directly measurable, when data are limited, and when the epidemic process is only partially observed. Finally, we assess the hurdles to be taken to increase availability and applicability of these approaches in an effort to ultimately enhance their public health impact.

An algorithm applied to national surveillance data for the early detection of major dengue outbreaks in Cambodia.

Dengue is a national priority disease in Cambodia. The Cambodian National Dengue Surveillance System is based on passive surveillance of dengue-like inpatients reported by public hospitals and on a sentinel, pediatric hospital-based active surveillance system. This system works well to assess trends but the sensitivity of the early warning and time-lag to usefully inform hospitals can be improved. During The ECOnomic development, ECOsystem MOdifications, and emerging infectious diseases Risk Evaluation (ECOMORE) project's knowledge translation platforms, Cambodian hospital staff requested an early warning tool to prepare for major outbreaks. Our objective was therefore to find adapted tools to improve the early warning system and preparedness. Dengue data was provided by the National Dengue Control Program (NDCP) and are routinely obtained through passive surveillance. The data were analyzed at the provincial level for eight Cambodian provinces during 2008-2015. The R surveillance package was used for the analysis. We evaluated the effectiveness of Bayesian algorithms to detect outbreaks using count data series, comparing the current count to an expected distribution obtained from observations of past years. The analyses bore on 78,759 patients with dengue-like syndromes. The algorithm maximizing sensitivity and specificity for the detection of major dengue outbreaks was selected in each province. The overall sensitivity and specificity were 73% and 97%, respectively, for the detection of significant outbreaks during 2008-2015. Depending on the province, sensitivity and specificity ranged from 50% to 100% and 75% to 100%, respectively. The final algorithm meets clinicians' and decisionmakers' needs, is cost-free and is easy to implement at the provincial level.

The need for treatment scale-up to impact HCV transmission in people who inject drugs in Montréal, Canada: a modelling study.

BACKGROUND: HCV transmission remains high in people who inject drugs (PWID) in Montréal. New direct-acting antivirals (DAAs), highly effective and more tolerable than previous regimens, make a "Treatment as Prevention" (TasP) strategy more feasible. This study assesses how improvements in the cascade of care could impact hepatitis C burden among PWID in Montréal. METHODS: We used a dynamic model to simulate HCV incidence and prevalence after 10 years, and cirrhosis complications after 10 and 40 years. Eight scenarios of improved cascade of care were examined. RESULTS: Using a baseline incidence and prevalence of 22.1/100 person-years (PY) and 53.1%, implementing the current cascade of care using DAAs would lead to HCV incidence and prevalence estimates at 10 years of 9.4/100PY and 55.8%, respectively. Increasing the treatment initiation rate from 5%/year initially to 20%/year resulted in large decreases in incidence (6.4/100PY), prevalence (36.6%), and cirrhosis complications (-18%/-37% after 10/40 years). When restricting treatment to fibrosis level ≥ F2 instead of F0 (reference scenario), such decreases in HCV occurrence were unreachable. Improving the whole cascade of care led to the greatest effect by halving both the incidence and prevalence at 10 years, and the number of cirrhosis complications after 40 years. CONCLUSIONS: The current level of treatment access in Montréal is limiting a massive decrease in hepatitis C burden among PWID. A substantial treatment scale-up, regardless of fibrosis level, is necessary. While improving the rest of the cascade of care is necessary to optimize a TasP strategy and control the HCV epidemic, a treatment scale-up is first needed.

Hepatitis C treatment as prevention of viral transmission and liver-related morbidity in persons who inject drugs.

UNLABELLED: Hepatitis C virus (HCV) seroprevalence remains high in people who inject drug (PWID) populations, often above 60%. Highly effective direct-acting antiviral (DAA) regimens (90% efficacy) are becoming available for HCV treatment. This therapeutic revolution raises the possibility of eliminating HCV from this population. However, for this, an effective cascade of care is required. In the context of the available DAA therapies, we used a dynamic individual-based model including a model of the PWID social network to simulate the impact of improved testing, linkage to care, and adherence to treatment, and of modified treatment recommendation on the transmission and on the morbidity of HCV in PWID in France. Under the current incidence and cascade of care, with treatment initiated at fibrosis stage ≥F2, HCV prevalence decreased from 42.8% to 24.9% (95% confidence interval: 24.8-24.9) after 10 years. Changing treatment initiation criteria to treat from F0 was the only intervention leading to a substantial additional decrease in prevalence, which fell to 11.6% (95% CI: 11.6-11.7) at 10 years. Combining this change with improved testing, linkage to care, and adherence to treatment decreased HCV prevalence to 7.0% (95% CI: 7.0-7.1) at 10 years and avoided 15% (95% CI: 14-17) and 29% (95% CI: 28-30) of cirrhosis complications over 10 and 40 years, respectively. CONCLUSIONS: Major decreases in prevalent HCV infections occur only when treatment is initiated at early stages of fibrosis, suggesting that systematic treatment in PWID, where incidence remains high, would be beneficial. However, elimination within the 10 next years will be difficult to achieve using treatment alone, even with a highly improved cascade of care.

On computer-intensive simulation and estimation methods for rare-event analysis in epidemic models.

This article focuses, in the context of epidemic models, on rare events that may possibly correspond to crisis situations from the perspective of public health. In general, no close analytic form for their occurrence probabilities is available, and crude Monte Carlo procedures fail. We show how recent intensive computer simulation techniques, such as interacting branching particle methods, can be used for estimation purposes, as well as for generating model paths that correspond to realizations of such events. Applications of these simulation-based methods to several epidemic models fitted from real datasets are also considered and discussed thoroughly.

How to optimize hepatitis C virus treatment impact on life years saved in resource-constrained countries.

UNLABELLED: In resource-constrained countries where the prevalence of hepatitis C virus (HCV) disease is usually high, it is important to know which population should be treated first in order to increase treatment effectiveness. The aim was to estimate the effectiveness of different HCV treatment eligibility scenarios in three different countries. Using a Markov model, we estimated the number of life-years saved (LYS) with different treatment eligibility scenarios according to fibrosis stage (F1-F4 or F3-4), compared to base case (F2-F4), at a constant treatment rate, of patients between 18 and 60 years of age, at stages F0/F1 to F4, without liver complications or coinfections, chronically infected by HCV, and treated with pegylated interferon (IFN)/ribavirin or more-efficacious therapies (i.e. IFN free). We conducted the analysis in Egypt (prevalence = 14.7%; 45,000 patients treated/year), Thailand (prevalence = 2.2%; 1,000 patients treated/year), and Côte d'Ivoire (prevalence = 3%; 150 patients treated/year). In Egypt, treating F1 patients in addition to ≥F2 patients (SE1 vs. SE0) decreased LYS by 3.9%. Focusing treatment only on F3-F4 patients increased LYS by 6.7% (SE2 vs. SE0). In Thailand and Côte d'Ivoire, focusing treatment only on F3-F4 patients increased LYS by 15.3% and 11.0%, respectively, compared to treating patients ≥F2 (ST0 and SC0, respectively). Treatment only for patients at stages F3-F4 with IFN-free therapies would increase LYS by 16.7% versus SE0 in Egypt, 22.0% versus ST0 in Thailand, and 13.1% versus SC0 in Côte d'Ivoire. In this study, we did not take into account the yearly new infections and the impact of treatment on HCV transmission. CONCLUSION: Our model-based analysis demonstrates that prioritizing treatment in F3-F4 patients in resource-constrained countries is the most effective scenario in terms of LYS, regardless of treatment considered.

Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt.

BACKGROUND: Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis. METHODS: We used the "elicitation of expert opinions" method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback. RESULTS: We found substantial disparity between experts' answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity). CONCLUSIONS: Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners' difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.

Effectiveness and cost-effectiveness of immediate versus delayed treatment of hepatitis C virus-infected patients in a country with limited resources: the case of Egypt.

BACKGROUND: Because of logistical and economic issues, in Egypt, as in other resource-limited settings, decision makers should determine for which patients hepatitis C virus (HCV) treatment should be prioritized. We assessed the effectiveness and cost-effectiveness of different treatment initiation strategies. METHODS: Using a Markov model, we simulated HCV disease in chronically infected patients in Egypt, to compare lifetime costs, quality-adjusted life expectancy (QALE), and the incremental cost-effectiveness ratio (ICER) of different treatment initiation strategies. RESULTS: Immediate treatment of patients at stages F1/F2/F3 was less expensive and more effective than delaying treatment until more severe stages or not providing treatment (in patients diagnosed at F1: QALE = 18.32 years if treatment at F1 vs 18.22 if treatment at F2). Treatment of F4 patients was more effective than no treatment at all (QALE = 10.33 years vs 8.77 years) and was cost-effective (ICER = $1915/quality-adjusted life-year [QALY]). When considering that affordable triple therapies, including new direct-acting antivirals, will be available starting in 2016, delaying treatment until stage F2, then treating all patients regardless of their disease stage after 2016, was found to be cost-effective (ICER = $33/QALY). CONCLUSIONS: In Egypt, immediate treatment of patients with fibrosis stage F1-F3 who present to care is less expensive and more effective than delaying treatment. However, immediate treatment at stage F1 is only slightly more effective than waiting for disease to progress to stage F2 before starting treatment and is sensitive to the forthcoming availability of new treatments. Treating patients at stage F4 is highly effective and cost-effective. In Egypt, decision makers should prioritize treatment for F4 patients and delay treatment for F1 patients who present to care.

Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study.

BACKGROUND: In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients. METHODS: Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions. RESULTS: 1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing. CONCLUSIONS: Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.