WHO's essential medicines and AWaRe: recommendations on first- and second-choice antibiotics for empiric treatment of clinical infections.

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 clinical infections targeting both the primary health care and hospital facility setting. A further 257 antibiotics not included on the EML have been allocated an AWaRe group for stewardship and monitoring purposes. This article describes the development of AWaRe, focussing on the clinical evidence base that guided the selection of Access, Watch, or Reserve antibiotics as first and second choices for each infection. The overarching objective was to offer a tool for optimizing the quality of global antibiotic prescribing and reduce inappropriate use by encouraging the use of Access antibiotics (or no antibiotics) where appropriate. This clinical evidence evaluation and subsequent EML recommendations are the basis for the AWaRe antibiotic book and related smartphone applications. By providing guidance on antibiotic prioritization, AWaRe aims to facilitate the revision of national lists of essential medicines, update national prescribing guidelines, and supervise antibiotic use. Adherence to AWaRe would extend the effectiveness of current antibiotics while helping countries expand access to these life-saving medicines for the benefit of current and future patients, health professionals, and the environment.

High rates of kidney impairment among older people (≥ 60 years) living with HIV on first-line antiretroviral therapy at screening for a clinical trial in Kenya.

BACKGROUND: There is a paucity of data on kidney impairment among older people living with HIV (PLWH). We evaluated kidney function among PLWH age ≥ 60 years on first-line antiretroviral (ARV) therapy during screening for a clinical trial in Kenya. METHODS: The bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) Elderly Study is an open-label, randomized, active-controlled, non-inferiority trial conducted at two sites in Kenya. Potential participants were screened for study entry if they were at least 60 years old, had been on ARVs for at least 24 weeks and had no history of treatment failure. At screening, participants had samples collected for serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. RESULTS: Between January and April 2022, 714 participants were screened and had creatinine measured. All participants were black, 54.1% were female and the median age was 64 years (range 60 to 87 years). Most participants (666 [93.3%]) were on tenofovir disoproxil fumarate-containing regimens, 711 (99.6%) were on dolutegravir-containing regimens, and only 2 (0.3%) were on a regimen with a ritonavir-boosted protease inhibitor. Most participants (686 [96.6%]) were virally suppressed. Treatment for comorbidities was common, with 175 (24.5%) on treatment for hypertension and 39 (5.5%) on treatment for diabetes mellitus. The median eGFR was 64.7 mL/min/1.73m2, and 289 (40.5%) participants had an eGFR < 60 mL/min/1.73m2. In multivariate analysis, factors associated with lower eGFR were female gender (p<0.001), being on treatment for hypertension (p<0.001) and nadir CD4 count < 50 cells/µL (p = 0.008). CONCLUSIONS: Our study identified high rates of impaired kidney function among elderly PLHW in Kenya, which highlights the importance of routine assessment of kidney function and the need to address modifiable risk factors, use of appropriate ARVs, and management of kidney disease in this population.

Infectious disease modelling for SARS-CoV-2 in Africa to guide policy: A systematic review.

Applied epidemiological models have played a critical role in understanding the transmission and control of disease outbreaks. Their utility and accuracy in decision-making on appropriate responses during public health emergencies is however a factor of their calibration to local data, evidence informing model assumptions, speed of obtaining and communicating their results, ease of understanding and willingness by policymakers to use their insights. We conducted a systematic review of infectious disease models focused on SARS-CoV-2 in Africa to determine: a) spatial and temporal patterns of SARS-CoV-2 modelling in Africa, b) use of local data to calibrate the models and local expertise in modelling activities, and c) key modelling questions and policy insights. We searched PubMed, Embase, Web of Science and MedRxiv databases following the PRISMA guidelines to obtain all SARS-CoV-2 dynamic modelling papers for one or multiple African countries. We extracted data on countries studied, authors and their affiliations, modelling questions addressed, type of models used, use of local data to calibrate the models, and model insights for guiding policy decisions. A total of 74 papers met the inclusion criteria, with nearly two-thirds of these coming from 6% (3) of the African countries. Initial papers were published 2 months after the first cases were reported in Africa, with most papers published after the first wave. More than half of all papers (53, 78%) and (48, 65%) had a first and last author affiliated to an African institution respectively, and only 12% (9) used local data for model calibration. A total of 60% (46) of the papers modelled assessment of control interventions. The transmission rate parameter was found to drive the most uncertainty in the sensitivity analysis for majority of the models. The use of dynamic models to draw policy insights was crucial and therefore there is need to increase modelling capacity in the continent.

Epidemiological and clinical characteristics of patients hospitalised with COVID-19 in Kenya: a multicentre cohort study.

OBJECTIVES: To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality. SETTING: This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya. PARTICIPANTS: We enrolled 787 reverse transcriptase-PCR-confirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. RESULTS: Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30-53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons >60 years compared with those <60 years old; having comorbidities (HR 2.34 (1.68 to 3.25)) and among men (HR 1.76 (1.27 to 2.44)) compared with women. Elevated white cell count and aspartate aminotransferase were associated with higher risk of death. CONCLUSIONS: The risk of death from COVID-19 is high among older patients, those with comorbidities and among men. Clinical parameters including patient clinical signs, haematology and liver function tests were associated with risk of death and may guide stratification of high-risk patients.

The COVID-19 pandemic and disruptions to essential health services in Kenya: a retrospective time-series analysis.

BACKGROUND: Public health emergencies can disrupt the provision of and access to essential health-care services, exacerbating health crises. We aimed to assess the effect of the COVID-19 pandemic on essential health-care services in Kenya. METHODS: Using county-level data routinely collected from the health information system from health facilities across the country, we used a robust mixed-effect model to examine changes in 17 indicators of essential health services across four periods: the pre-pandemic period (from January, 2018 to February, 2020), two pandemic periods (from March to November 2020, and February to October, 2021), and the period during the COVID-19-associated health-care workers' strike (from December, 2020 to January, 2021). FINDINGS: In the pre-pandemic period, we observed a positive trend for multiple indicators. The onset of the pandemic was associated with statistically significant decreases in multiple indicators, including outpatient visits (28·7%; 95% CI 16·0-43·5%), cervical cancer screening (49·8%; 20·6-57·9%), number of HIV tests conducted (45·3%; 23·9-63·0%), patients tested for malaria (31·9%; 16·7-46·7%), number of notified tuberculosis cases (26·6%; 14·7-45·1%), hypertension cases (10·4%; 6·0-39·4%), vitamin A supplements (8·7%; 7·9-10·5%), and three doses of the diphtheria, tetanus toxoid, and pertussis vaccine administered (0·9%; 0·5-1·3%). Pneumonia cases reduced by 50·6% (31·3-67·3%), diarrhoea by 39·7% (24·8-62·7%), and children attending welfare clinics by 39·6% (23·5-47·1%). Cases of sexual violence increased by 8·0% (4·3-25·0%). Skilled deliveries, antenatal care, people with HIV infection newly started on antiretroviral therapy, confirmed cases of malaria, and diabetes cases detected were not significantly affected negatively. Although most of the health indicators began to recover during the pandemic, the health-care workers' strike resulted in nearly all indicators falling to numbers lower than those observed at the onset or during the pre-strike pandemic period. INTERPRETATION: The COVID-19 pandemic and the associated health-care workers' strike in Kenya have been associated with a substantial disruption of essential health services, with the use of outpatient visits, screening and diagnostic services, and child immunisation adversely affected. Efforts to maintain the provision of these essential health services during a health-care crisis should target the susceptible services to prevent the exacerbation of associated disease burdens during such health crises. FUNDING: Bill & Melinda Gates Foundation.

The WHO essential medicines list AWaRe book: from a list to a quality improvement system.

Antibiotics are often prescribed inappropriately, either when they are not necessary or with an unnecessarily broad spectrum of activity. AWaRe (AccessWatchReserve) is a system developed by WHO to classify antibiotics based on their spectrum of activity and potential for favouring the development of antibiotic resistance (Access: narrow spectrum/low potential for resistance; Watch: broader spectrum/higher potential for resistance; Reserve: last resort antibiotics to use very selectively). The WHO target is that by 2023, at least 60% of prescribed antibiotics globally should be from the Access category. The WHO AWaRe Book aims to improve empiric antibiotic prescribing by providing simple guidance for common infections based on the principles of AWaRe in alignment with the Model Lists of Essential Medicines for adults and children.

Empyema necessitans due to aspergillus in a 3-year-old paediatric patient at a referral hospital in Nairobi, Kenya.

We present a case of empyema necessitans due to aspergillus in a young child. The incidence of deep fungal mycoses in children, especially in developing countries is not known. There is paucity of data and access to diagnostics is usually limited. Our patient had received treatment for pulmonary tuberculosis which is endemic in Kenya for four months before diagnosis was made. We present this case to highlight the importance of considering alternative diagnosis when there is non-response to anti-tuberculous therapy.