Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

BACKGROUND: Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. OBJECTIVE: Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. METHODS: A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. RESULTS: For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $ 0.03 and $ 0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. CONCLUSION: The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

The facilitators of and barriers to antimicrobial use and misuse in Lalitpur, Nepal: a qualitative study.

BACKGROUND: Antimicrobial resistance (AMR) is a pressing global health concern driven by inappropriate antibiotic use, which is in turn influenced by various social, systemic, and individual factors. This study, nested within FIND's AMR Diagnostic Use Accelerator clinical trial in Nepal, aimed to (i) explore the perspectives of patients, caregivers, and healthcare workers (HCWs) on antibiotic prescription adherence and (ii) assess the impact of a training and communication (T&C) intervention on adherence to antibiotic prescriptions. METHODS: Using qualitative, semi-structured interviews, pre-intervention and Day 7 follow-up components, and the Behaviour Change Wheel process, we investigated the facilitators of and barriers to the use and misuse of antibiotic prescriptions. RESULTS: Results of the study revealed that adherence to antibiotic prescriptions is influenced by a complex interplay of factors, including knowledge and understanding, forgetfulness, effective communication, expectations, beliefs and habits, attitudes and behaviours, convenience of purchasing, trust in medical effectiveness, and issues of child preferences. The T&C package was also shown to play a role in addressing specific barriers to treatment adherence. CONCLUSIONS: Overall, the results of this study provide a nuanced understanding of the challenges associated with antibiotic use and suggest that tailored interventions, informed by behaviour frameworks, can enhance prescription adherence, may be applicable in diverse settings and can contribute to the global effort to mitigate the rising threat of AMR.

Impact of the Introduction of a Package of Diagnostic Tools, Diagnostic Algorithm, and Training and Communication on Outpatient Acute Fever Case Management at 3 Diverse Sites in Uganda: Results of a Randomized Controlled Trial.

BACKGROUND: Increasing trends of antimicrobial resistance are observed around the world, driven in part by excessive use of antimicrobials. Limited access to diagnostics, particularly in low- and middle-income countries, contributes to diagnostic uncertainty, which may promote unnecessary antibiotic use. We investigated whether introducing a package of diagnostic tools, clinical algorithm, and training-and-communication messages could safely reduce antibiotic prescribing compared with current standard-of-care for febrile patients presenting to outpatient clinics in Uganda. METHODS: This was an open-label, multicenter, 2-arm randomized controlled trial conducted at 3 public health facilities (Aduku, Nagongera, and Kihihi health center IVs) comparing the proportions of antibiotic prescriptions and clinical outcomes for febrile outpatients aged ≥1 year. The intervention arm included a package of point-of-care tests, a diagnostic and treatment algorithm, and training-and-communication messages. Standard-of-care was provided to patients in the control arm. RESULTS: A total of 2400 patients were enrolled, with 49.5% in the intervention arm. Overall, there was no significant difference in antibiotic prescriptions between the study arms (relative risk [RR]: 1.03; 95% CI: .96-1.11). In the intervention arm, patients with positive malaria test results (313/500 [62.6%] vs 170/473 [35.9%]) had a higher RR of being prescribed antibiotics (1.74; 1.52-2.00), while those with negative malaria results (348/688 [50.6%] vs 376/508 [74.0%]) had a lower RR (.68; .63-.75). There was no significant difference in clinical outcomes. CONCLUSIONS: This study found that a diagnostic intervention for management of febrile outpatients did not achieve the desired impact on antibiotic prescribing at 3 diverse and representative health facility sites in Uganda.

Impact of Point-of-Care Rapid Diagnostic Tests on Antibiotic Prescription Among Patients Aged <18 Years in Primary Healthcare Settings in 2 Peri-Urban Districts in Ghana: Randomized Controlled Trial Results.

BACKGROUND: Inappropriate antibiotic prescriptions are a known driver of antimicrobial resistance in settings with limited diagnostic capacity. This study aimed to assess the impact of diagnostic algorithms incorporating rapid diagnostic tests on clinical outcomes and antibiotic prescriptions compared with standard-of-care practices, of acute febrile illness cases at outpatient clinics in Shai-Osudoku and Prampram districts in Ghana. METHODS: This was an open-label, centrally randomized controlled trial in 4 health facilities. Participants aged 6 months to <18 years of both sexes with acute febrile illness were randomized to receive a package of interventions to guide antibiotic prescriptions or standard care. Clinical outcomes were assessed on day 7. RESULTS: In total, 1512 patients were randomized to either the intervention (n = 761) or control (n = 751) group. Majority were children aged <5 years (1154 of 1512, 76.3%) and male (809 of 1512, 53.5%). There was 11% relative risk reduction of antibiotic prescription in intervention group (RR, 0.89; 95% CI, .79 to 1.01); 14% in children aged <5 years (RR, 0.86; 95% CI, .75 to .98), 15% in nonmalaria patients (RR, 0.85; 95% CI, .75 to .96), and 16% in patients with respiratory symptoms (RR, 0.84; 95% CI, .73 to .96). Almost all participants had favorable outcomes (759 of 761, 99.7% vs 747 of 751, 99.4%). CONCLUSIONS: In low- and middle-income countries, the combination of point-of-care diagnostics, diagnostic algorithms, and communication training can be used at the primary healthcare level to reduce antibiotic prescriptions among children with acute febrile illness, patients with nonmalarial fevers, and respiratory symptoms. CLINICAL TRIALS REGISTRATION: NCT04081051.

Viewpoint: Antimicrobial Resistance Diagnostics Use Accelerator: Qualitative Research on Adherence to Prescriptions.

In this Viewpoint, the authors explore the determinants of patients' prescription adherence behaviors as part of FIND's Advancing Access to Diagnostic Innovation essential for Universal Health Coverage and AMR Prevention (ADIP) trials (ClinicalTrials.gov identifier: NCT04081051). Research findings from Burkina Faso, Ghana, and Uganda show that basic knowledge and understanding of prescription instructions are essential for adherence and can be improved through better communication. However, there are a range of other factors that influence adherence, some of which can be influenced through tailored communication messages from healthcare workers. These messages may contribute to changes in adherence behavior but may require other reinforcing interventions to be effective. Finally, there are some drivers of nonadherence centered around costs and time pressure that require other forms of intervention.

What Influences Patients' Adherence to Healthcare Worker Prescription in Primary Healthcare Facilities in Burkina Faso? A Qualitative Account of Barriers and Facilitators.

BACKGROUND: This study explores the factors influencing patients and caregivers' adherence to prescription of healthcare workers (HCWs). METHODS: The study was conducted in Temnaore and Pella, in the Nanoro health district in Burkina Faso. HCWs and community members were purposively recruited from 4 communities seeking care at the selected primary healthcare facilities for the clinical trial to attend in-depth interviews and focus group discussions on the factors influencing adherence to prescription. The Behaviour Change Wheel incorporating the Capability, Opportunity, and Motivation Behaviour approach was used. RESULTS: Factors influencing the ability of patients to obtain the prescribed medicine include the availability of medicines and money and the perception of consequences for not getting the medicine. Regarding compliance with the intake of medicines, communication was considered a key factor whose effectiveness depends on the performance of HCWs and on the attention of patients. It is followed by other factors such as adequate management of patients, social influences, the patient's beliefs regarding treatment, and memory. CONCLUSIONS: This research highlights factors influencing adherence to HCWs' prescription from the perspective of the community members and HCWs and therefore provides contextual enablers and barriers, which allows for the development of an intervention to support the clinical trial.

Understanding Health Worker and Community Antibiotic Prescription-Adherence Practices for Acute Febrile Illness: A Nested Qualitative Study in the Shai-Osudoku District of Ghana and the Development of a Training-and-Communication Intervention.

BACKGROUND: The aim was to explore behavioral factors relating to the prescription and communication of prescription-adherence messages for patients with acute febrile illness, from which to develop a training-and-communication (T&C) intervention to be delivered as part of a clinical trial. METHODS: The study undertook a content analysis of primary, qualitative data collection using in-depth interviews and focus group discussions, informed by the Capability, Opportunity, Motivation (COM-B) theory of behavior, the Theoretical Domains Framework (TDF), and Behavior Change Wheel (BCW) approach, in health facilities (39 health workers) and communities (66 community members) in the Shai-Osudoku District of Ghana. RESULTS: Health workers perceive that prescribers' and dispensers' communication with patients is influenced by the following factors: patient's educational level, existing disease conditions, health worker's workload, patient's religion, language barrier between health worker and patient, outcome of laboratory results, and medicine availability. Community members' adherence to prescription was influenced by the availability of money and affordability of medicine (outside of provision by the national health insurance scheme), the severity of the condition, work schedule, and forgetfulness. CONCLUSIONS: Our study contributes to knowledge on nesting qualitative methods in a clinical trial and reveals factors that affect the antibiotic prescription communication process. Tailored messages for patient-specific needs can shape antibiotic prescription adherence behavior and ultimately contribute to decreasing the incidence of antibiotic resistance.

A Qualitative Assessment of a Training and Communication Intervention on Antibiotic Prescription Practices Among Health Workers and Outpatients at Public Health Facilities in Uganda.

BACKGROUND: Antibiotic prescribing practices are 1 of the contributing causes of antimicrobial resistance (AMR). The study explored the key drivers and barriers to adherence to prescribing instructions among healthcare workers and outpatient attendees with the aim of developing a training and communication intervention to improve adherence to prescription. METHODS: Prior to randomized trials at 3 health centers in Uganda (Aduku, Kihihi, and Nagongera), a pre-intervention qualitative assessment was conducted to explore behavioral drivers for adherence to prescriptions and the communication of adherence messages. Based on the findings, a training and communication package was developed for healthcare workers and patients at Day 0 of the trial. During the trial's Day 7 patient follow-up, in-depth interviews were conducted to further investigate adherence behaviors. RESULTS: Five main themes were identified that acted as drivers or barriers to prescription adherence. Key drivers included: drug availability at health facility, health worker knowledge, and communication to patients. Barriers included: care-seeker use of treatment resorts and an inability by care-seeker to buy drugs. CONCLUSIONS: The T&C appeared to influence both health workers' and patients' behavior and improve adherence to prescription.The adapted T&C should be considered a toolkit to improve antibiotic use across health facilities accompanied with appropriate guidelines to mitigate AMR.

A Randomized Trial to Assess the Impact of a Package of Diagnostic Tools and Diagnostic Algorithm on Antibiotic Prescriptions for the Management of Febrile Illnesses Among Children and Adolescents in Primary Health Facilities in Burkina Faso.

BACKGROUND: Low- and middle-income countries face significant challenges in differentiating bacterial from viral causes of febrile illnesses, leading to inappropriate use of antibiotics. This trial aimed to evaluate the impact of an intervention package comprising diagnostic tests, a diagnostic algorithm, and a training-and-communication package on antibiotic prescriptions and clinical outcomes. METHODS: Patients aged 6 months to 18 years with fever or history of fever within the past 7 days with no focus, or a suspected respiratory tract infection, arriving at 2 health facilities were randomized to either the intervention package or standard practice. The primary outcomes were the proportions of patients who recovered at day 7 (D7) and patients prescribed antibiotics at day 0. RESULTS: Of 1718 patients randomized, 1681 (97.8%; intervention: 844; control: 837) completed follow-up: 99.5% recovered at D7 in the intervention arm versus 100% in standard practice (P = .135). Antibiotics were prescribed to 40.6% of patients in the intervention group versus 57.5% in the control arm (risk ratio: 29.3%; 95% CI: 21.8-36.0%; risk difference [RD]: -16.8%; 95% CI: -21.7% to -12.0%; P < .001), which translates to 1 additional antibiotic prescription saved every 6 (95% CI: 5-8) consultations. This reduction was significant regardless of test results for malaria, but was greater in patients without malaria (RD: -46.0%; -54.7% to -37.4%; P < .001), those with a respiratory diagnosis (RD: -38.2%; -43.8% to -32.6%; P < .001), and in children 6-59 months old (RD: -20.4%; -26.0% to -14.9%; P < .001). Except for the period July-September, the reduction was consistent across the other quarters (P < .001). CONCLUSIONS: The implementation of the package can reduce inappropriate antibiotic prescription without compromising clinical outcomes. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov; NCT04081051.

Community mask wearing as a COVID-19 preventive measure, its barriers, and motivators among rural households of Uganda: A mixed methods approach.

Adherence to mask wearing has the potential to reduce coronavirus disease 2019 acquisition risk. However, there is limited information about community mask wearing and its predictors among rural populations. This study aimed to assess the level of adherence to community mask wearing as a COVID-19 prevention measure, its barriers, and motivators among the Ugandan rural population of Wakiso District. This cross-sectional study utilised both quantitative and qualitative data collection methods. The quantitative component employed a semi-structured interviewer-administered questionnaire among 400 participants, to assess the level of adherence and associated predictors towards mask wearing. Modified Poisson regression with robust standard error estimates was used to obtain crude and adjusted prevalence ratios associated with mask wearing. Quantitative data analysis was performed using Stata 15.0 Statistical software. The qualitative component was used to further explore the barriers and motivators of community mask wearing whereseven focus group discussions among 56 community health workers were conducted. Data was analysed using a thematic approach with the help of Nvivo Version 12 software. The quantitative results showed that 70.8% (283/400) of the participants were adherent to mask wearing. Furthermore, reusable (cloth masks) were the most common form of face masks worn by the participants; 71.9% (282/400). Adequate knowledge about mask wearing as a COVID-19 prevention measure was positively associated with mask wearing (adjusted prevalence ratio (95% CI); 3.2 (1.19-8.56)). The qualitative results revealed; sensitization from health workers, provision of free masks, and fear of fines and arrests as motivators to mask wearing. Barriers to mask wearing included: inability to buy masks due to financial constraints, one-time provision of free masks, ill-fitting and worn-out masks, discomfort, and bribery. The practice of community mask wearing was sub-optimal among the study rural communities. Initiatives to scale up the practice need to be feasible for rural communities.

Capacity to provide care for common childhood infections at low-level private health facilities in Western, Uganda.

BACKGROUND: Low-level private health facilities (LLPHFs) handle a considerable magnitude of sick children in low-resource countries. We assessed capacity of LLPHFs to manage malaria, pneumonia, diarrhea, and, possible severe bacterial infections (PSBIs) in under-five-year-olds. METHODS: We conducted a cross-sectional survey in 110 LLPHFs and 129 health workers in Mbarara District, Uganda between May and December 2019. Structured questionnaires and observation forms were used to collect data on availability of treatment guidelines, vital medicines, diagnostics, and equipment; health worker qualifications; and knowledge of management of common childhood infections. RESULTS: Amoxicillin was available in 97%, parental ampicillin and gentamicin in 77%, zinc tablets and oral rehydration salts in >90% while artemether-lumefantrine was available in 96% of LLPHF. About 66% of facilities stocked loperamide, a drug contraindicated in the management of diarrhoea in children. Malaria rapid diagnostic tests and microscopes were available in 86% of the facilities, timers/clocks in 57% but only 19% of the facilities had weighing scales and 6% stocked oxygen. Only 4% of the LLPHF had integrated management of childhood illness (IMCI) booklets and algorithm charts for management of common childhood illnesses. Of the 129 health workers, 52% were certificate nurses/midwives and (26% diploma nurses/clinical officers; 57% scored averagely for knowledge on management of common childhood illnesses. More than a quarter (38%) of nursing assistants had low knowledge scores. No notable significant differences existed between rural and urban LLPHFs in most parameters assessed. CONCLUSION: Vital first-line medicines for treatment of common childhood illnesses were available in most of the LLPHFs but majority lacked clinical guidelines and very few had oxygen. Majority of health workers had low to average knowledge on management of the common childhood illnesses. There is need for innovative knowledge raising interventions in LLPHFs including refresher trainings, peer support supervision and provision of job aides.

Household air pollution and under-five mortality in sub-Saharan Africa: an analysis of 14 demographic and health surveys.

BACKGROUND: Globally, over four million deaths are attributed to exposure to household air pollution (HAP) annually. Evidence of the association between exposure to HAP and under-five mortality in sub-Saharan Africa (SSA) is insufficient. We assessed the association between exposure to HAP and under-five mortality risk in 14 SSA countries. METHODS: We pooled Demographic and Health Survey (DHS) data from 14 SSA countries (N = 164376) collected between 2015 and 2018. We defined exposure to HAP as the use of biomass fuel for cooking in the household. Under-five mortality was defined as deaths before age five. Data were analyzed using mixed effects logistic regression models. RESULTS: Of the study population, 73% were exposed to HAP and under-five mortality was observed in 5%. HAP exposure was associated with under-five mortality, adjusted odds ratio (OR) 1.33 (95% confidence interval (CI) [1.03-1.71]). Children from households who cooked inside the home had higher risk of under-five mortality compared to households that cooked in separate buildings [0.85 (0.73-0.98)] or outside [0.75 (0.64-0.87)]. Lower risk of under-five mortality was also observed in breastfed children [0.09 (0.05-0.18)] compared to non-breastfed children. CONCLUSIONS: HAP exposure may be associated with an increased risk of under-five mortality in sub-Saharan Africa. More carefully designed longitudinal studies are required to contribute to these findings. In addition, awareness campaigns on the effects of HAP exposure and interventions to reduce the use of biomass fuels are required in SSA.