COVID-19 and the law in Uganda: a case study on development and application of the public health act from 2020 to 2021.

BACKGROUND: Despite the discovery of vaccines, the control, and prevention of Coronavirus disease 2019 (COVID-19) relied on non-pharmaceutical interventions (NPIs). This article describes the development and application of the Public Health Act to implement NPIs for COVID-19 pandemic control in Uganda. METHODS: This is a case study of Uganda's experience with enacting COVID-19 Rules under the Public Health Act Cap. 281. The study assessed how and what Rules were developed, their influence on the outbreak progress, and litigation. The data sources reviewed were applicable laws and policies, Presidential speeches, Cabinet resolutions, statutory instruments, COVID-19 situation reports, and the registry of court cases that contributed to a triangulated analysis. RESULTS: Uganda applied four COVID-19 broad Rules for the period March 2020 to October 2021. The Minister of Health enacted the Rules, which response teams, enforcement agencies, and the general population followed. The Presidential speeches, their expiry period and progress of the pandemic curve led to amendment of the Rules twenty one (21) times. The Uganda Peoples Defense Forces Act No. 7 of 2005, the Public Finance Management Act No. 3 of 2015, and the National Policy for Disaster Preparedness and Management supplemented the enacted COVID-19 Rules. However, these Rules attracted specific litigation due to perceived infringement on certain human rights provisions. CONCLUSIONS: Countries can enact supportive legislation within the course of an outbreak. The balance of enforcing public health interventions and human rights infringements is an important consideration in future. We recommend public sensitization about legislative provisions and reforms to guide public health responses in future outbreaks or pandemics.

The road to achieving epidemic-ready primary health care.

Millions of avoidable deaths arising from the COVID-19 pandemic emphasise the need for epidemic-ready primary health care aligned with public health to identify and stop outbreaks, maintain essential services during disruptions, strengthen population resilience, and ensure health worker and patient safety. The improvement in health security from epidemic-ready primary health care is a strong argument for increased political support and can expand primary health-care capacities to improve detection, vaccination, treatment, and coordination with public health-needs that became more apparent during the pandemic. Progress towards epidemic-ready primary health care is likely to be stepwise and incremental, advancing when opportunity arises based on explicit agreement on a core set of services, improved use of external and national funds, and payment based in large part on empanelment and capitation to improve outcomes and accountability, supplemented with funding for core staffing and infrastructure and well designed incentives for health improvement. Health-care worker and broader civil society advocacy, political consensus, and bolstering government legitimacy could promote strong primary health care. Epidemic-ready primary health-care infrastructure that is able to help prevent and withstand the next pandemic will require substantial financial and structural reforms and sustained political and financial commitment. Governments, advocates, and bilateral and multilateral agencies should seize this window of opportunity before it closes.

Implementation of the 7-1-7 target for detection, notification, and response to public health threats in five countries: a retrospective, observational study.

BACKGROUND: Suboptimal detection and response to recent outbreaks, including COVID-19 and mpox (formerly known as monkeypox), have shown that the world is insufficiently prepared for public health threats. Routine monitoring of detection and response performance of health emergency systems through timeliness metrics has been proposed to evaluate and improve outbreak preparedness and contain health threats early. We implemented 7-1-7 to measure the timeliness of detection (target of ≤7 days from emergence), notification (target of ≤1 day from detection), and completion of seven early response actions (target of ≤7 days from notification), and we identified bottlenecks to and enablers of system performance. METHODS: In this retrospective, observational study, we conducted reviews of public health events in Brazil, Ethiopia, Liberia, Nigeria, and Uganda with staff from ministries of health and national public health institutes. For selected public health events occurring from Jan 1, 2018, to Dec 31, 2022, we calculated timeliness intervals for detection, notification, and early response actions, and synthesised identified bottlenecks and enablers. We mapped bottlenecks and enablers to Joint External Evaluation (second edition) indicators. FINDINGS: Of 41 public health events assessed, 22 (54%) met a target of 7 days to detect (median 6 days [range 0-157]), 29 (71%) met a target of 1 day to notify (0 days [0-24]), and 20 (49%) met a target of 7 days to complete all early response actions (8 days [0-72]). 11 (27%) events met the complete 7-1-7 target, with variation among event types. 25 (61%) of 41 bottlenecks to and 27 (51%) of 53 enablers of detection were at the health facility level, with delays to notification (14 [44%] of 32 bottlenecks) and response (22 [39%] of 56 bottlenecks) most often at an intermediate public health (ie, municipal, district, county, state, or province) level. Rapid resource mobilisation for responses (six [9%] of 65 enablers) from the national level enabled faster responses. INTERPRETATION: The 7-1-7 target is feasible to measure and to achieve, and assessment with this framework can identify areas for performance improvement and help prioritise national planning. Increased investments must be made at the health facility and intermediate public health levels for improved systems to detect, notify, and rapidly respond to emerging public health threats. FUNDING: Bill & Melinda Gates Foundation.

Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda.

Infectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings.

Improving water, sanitation, and hygiene (WASH), with a focus on hand hygiene, globally for community mitigation of COVID-19

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices—for example, hand hygiene—are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

Infection Prevention and Control Initiatives to Prevent Healthcare-Associated Transmission of SARS-CoV-2, East Africa.

The coronavirus disease pandemic has highlighted the need to establish and maintain strong infection prevention and control (IPC) practices, not only to prevent healthcare-associated transmission of SARS-CoV-2 to healthcare workers and patients but also to prevent disruptions of essential healthcare services. In East Africa, where basic IPC capacity in healthcare facilities is limited, the US Centers for Disease Control and Prevention (CDC) supported rapid IPC capacity building in healthcare facilities in 4 target countries: Tanzania, Ethiopia, Kenya, and Uganda. CDC supported IPC capacity-building initiatives at the healthcare facility and national levels according to each country's specific needs, priorities, available resources, and existing IPC capacity and systems. In addition, CDC established a multicountry learning network to strengthen hospital level IPC, with an emphasis on peer-to-peer learning. We present an overview of the key strategies used to strengthen IPC in these countries and lessons learned from implementation.

Support for the response to COVID-19 in Uganda: contribution of the global health security program at Makerere University's Infectious Diseases Institute.

Background: Outbreaks are occurring at increasing frequency and they require multisectoral and multi-stakeholder involvement for optimal response. The Global Health Security Agenda is a framework that governments and other stakeholders can use to strengthen countries' capacities to prevent, detect and respond to outbreaks but there are few examples of academic programs using this approach. Methods: This is a narrative review of contributions of Makerere University through the Global Health Security Program at the Infectious Diseases Institute (IDI). Information was sourced from peer-reviewed publications and grey literature highlighting work done between 2017 - 2021. Results: Aligned to GHSA, IDI made contributions to strengthen national and subnational capacities for biosafety and biosecurity, sample collection and transportation, electronic disease surveillance, infection prevention and control, case management prior to COVID-19 that were subsequently used to support response efforts for COVID-19 in Uganda. Conclusion: The IDI Global Health Security program provides a model that can be used by institutions to deliberately develop capacities relevant to outbreak preparedness and response.

An interactive voice response software to improve the quality of life of people living with HIV in Uganda: Randomized controlled trial

Background: Following the successful scale-up of antiretroviral therapy (ART), the focus is now on ensuring good quality of life (QoL) and sustained viral suppression in people living with HIV. The access to mobile technology in the most burdened countries is increasing rapidly, and therefore, mobile health (mHealth) technologies could be leveraged to improve QoL in people living with HIV. However, data on the impact of mHealth tools on the QoL in people living with HIV are limited to the evaluation of SMS text messaging;these are infeasible in high-illiteracy settings. Objective: The primary and secondary outcomes were to determine the impact of interactive voice response (IVR) technology on Medical Outcomes Study HIV QoL scores and viral suppression at 12 months, respectively. Methods: Within the Call for Life study, ART-experienced and ART-naive people living with HIV commencing ART were randomized (1:1 ratio) to the control (no IVR support) or intervention arm (daily adherence and pre-appointment reminders, health information tips, and option to report symptoms). The software evaluated was Call for Life Uganda, an IVR technology that is based on the Mobile Technology for Community Health open-source software. Eligibility criteria for participation included access to a phone, fluency in local languages, and provision of consent. The differences in differences (DIDs) were computed, adjusting for baseline HIV RNA and CD4. Results: Overall, 600 participants (413 female, 68.8%) were enrolled and followed-up for 12 months. In the intervention arm of 300 participants, 298 (99.3%) opted for IVR and 2 (0.7%) chose SMS text messaging as the mode of receiving reminders and health tips. At 12 months, there was no overall difference in the QoL between the intervention and control arms (DID=0.0;P=.99) or HIV RNA (DID=0.01;P=.94). At 12 months, 124 of the 256 (48.4%) active participants had picked up at least 50% of the calls. In the active intervention participants, high users (received >75% of reminders) had overall higher QoL compared to low users (received <25% of reminders) (92.2 versus 87.8, P=.02). Similarly, high users also had higher QoL scores in the mental health domain (93.1 versus 86.8, P=.008) and better appointment keeping. Similarly, participants with moderate use (51%-75%) had better viral suppression at 12 months (80/94, 85% versus 11/19, 58%, P=.006). Conclusions: Overall, there was high uptake and acceptability of the IVR tool. While we found no overall difference in the QoL and viral suppression between study arms, people living with HIV with higher usage of the tool showed greater improvements n QoL, viral suppression, and appointment keeping. With the declining resources available to HIV programs and the increasing number of people living with HIV accessing ART, IVR technology could be used to support patient care. The tool may be helpful in situations where physical consultations are infeasible, including the current COVID epidemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

An open-label, randomized, single intravenous dosing study to investigate the effect of fixed-dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR).

BACKGROUND: Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. METHODS: This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. DISCUSSION: This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. TRIAL REGISTRATION: ClinicalTrials.gov NCT04385719 . Registered 13 May 2020.

AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter.

BACKGROUND: There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. METHODS/DESIGN: AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. DISCUSSION: Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. TRIAL REGISTRATION: EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183  19 February 2021 ISRCTN reference: 27106947.

Safer primary healthcare facilities are needed to protect healthcare workers and maintain essential services: lessons learned from a multicountry COVID-19 emergency response initiative.

Healthcare workers (HCWs) are at increased risk of infection from SARS-CoV-2 and other disease pathogens, which take a disproportionate toll on HCWs, with substantial cost to health systems. Improved infection prevention and control (IPC) programmes can protect HCWs, especially in resource-limited settings where the health workforce is scarcest, and ensure patient safety and continuity of essential health services. In response to the COVID-19 pandemic, we collaborated with ministries of health and development partners to implement an emergency initiative for HCWs at the primary health facility level in 22 African countries. Between April 2020 and January 2021, the initiative trained 42 058 front-line HCWs from 8444 health facilities, supported longitudinal supervision and monitoring visits guided by a standardised monitoring tool, and provided resources including personal protective equipment (PPE). We documented significant short-term improvements in IPC performance, but gaps remain. Suspected HCW infections peaked at 41.5% among HCWs screened at monitored facilities in July 2020 during the first wave of the pandemic in Africa. Disease-specific emergency responses are not the optimal approach. Comprehensive, sustainable IPC programmes are needed. IPC needs to be incorporated into all HCW training programmes and combined with supportive supervision and mentorship. Strengthened data systems on IPC are needed to guide improvements at the health facility level and to inform policy development at the national level, along with investments in infrastructure and sustainable supplies of PPE. Multimodal strategies to improve IPC are critical to make health facilities safer and to protect HCWs and the communities they serve.

Leveraging investments in Ebola preparedness for COVID-19 in Sub-Saharan Africa.

The emergence of SARS-CoV-2 in China and transmission to more than 80 territories worldwide, including nine countries in Africa, presents a delicate situation for low-resource settings. Countries in Eastern and Central Africa have been on high alert since mid-2018 in anticipation of regional spread of the Ebola virus from the Democratic Republic of Congo. Significant investment has been made to support enhanced surveillance at point of entry and hospitals, infection control practices, clinical case management, and clinical research. With a new threat on the horizon, African countries have an opportunity to leverage the existing capacities for Ebola preparedness to brace for the imminent threat.

Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease.

BACKGROUND: Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. OBJECTIVES: The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. METHODS: Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 µm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. RESULTS: Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. CONCLUSIONS: This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.