Antimicrobial resistance (AMR) has reached an end point, prompting a worldwide scare as no new antibiotics are in the pipeline, particularly for treatment of Gram-negative bacteria. To prevent further development and spread of AMR and to inform empirical treatment guidelines, surveillance of AMR is necessary.
We aim to provide a framework for a stepwise approach toward implementation of laboratory-based surveillance for AMR in African countries.
Building up a surveillance system is a robust process that begins with a gap analysis in each participating country. This framework provides practical guidance on how to set up surveillance, identify responsibilities and set timelines in sustainable manner for African countries. It addresses sampling strategies, human resources, procurement and maintenance issues for AMR testing at routine clinical and national reference and public health laboratories involved in AMR surveillance. Key issues such as laboratory capacity building, training and continuous education, quality and diagnostic stewardship are discussed in detail.
There are several priorities for AMR surveillance that need to be addressed in a comprehensive manner at regional and national levels, whilst keeping in line with current and proposed initiatives for laboratory capacity building, in order for African countries to achieve goals for combatting the real and current threat of AMR.
Antimicrobial resistance (AMR) to bacterial pathogens is a global threat that ignores borders between countries. The emergence of multidrug-resistant bacteria means that very few effective antibiotics are available for the empirical or targeted treatment of many infectious diseases,
Strategic planning for antimicrobial resistance interventions aligned with the World Health Organization Global Action Plan.
Characteristics of strategies | National interventions |
---|---|
Surveillance for AMR | Requires accurate data collection strategies on antimicrobial susceptibility testing capacity and results at all levels, delineated in national policies and plans |
Economic assessment of sustainable investment for AMR surveillance | Requires commitment at national and international level |
Education of all professionals involved in dealing with antimicrobials | Requires commitment at local and national level |
Education of patients and public on inappropriate use of antimicrobials | Requires commitment at national level |
Rapid diagnosis of bacterial and viral infections | Requires infrastructure at facility levels |
Provide guidelines for antimicrobial susceptibility testing and implementation of accreditation for performing laboratories | Requires national commitment at facility levels |
Development of treatment guidelines to prevent inappropriate use of antimicrobial agents and development of policies to regulate prescription requirements, and other regulations | Requires national and facility involvement |
Development of antimicrobial stewardship programmes | At national and facilities levels |
Provide EPI programmes to all | National policy |
Improve nutrition in order to reduce susceptibility to infections | National and local |
Hand washing | National guidelines and facility levels implementation |
Isolation of patients with emerging AMR pathogens | National guideline and facility levels implementation |
Increase number of hospital beds | National level and facility levels implementation |
In emergence of resistance screening for new cases | National level and facility levels implementation |
AMR, antimicrobial resistance; EPI, expanded programme on immunisation.
Most information on AMR prevalence comes from high-income countries, and very little is known about AMR in African countries. A systematic review of AMR in sub-Saharan Africa by Leopold et al. revealed a high prevalence of AMR to commonly-used antibiotics in clinical bacterial isolates.
As one of its multifaceted responses to combat AMR, the first step proposed in the WHO GAP is to perform a baseline assessment of the AMR prevalence in all countries.
In general, an AMR strategy is a holistic approach that includes monitoring resistance trends, strengthening diagnostic laboratories, applying infection prevention and control measures to increase social awareness and international collaboration, strengthening drug regulation and supply chains and development of novel drugs. All of these factors are aimed at promoting antimicrobial stewardship and encouraging novel research in diagnostics and drug development. AMR surveillance is an important process for estimating the extent of the resistance burden in each country. AMR surveillance relies on diagnostic laboratories; in sub-Saharan Africa, the need for laboratory improvement is evident, with some countries in need of laboratory system built from the ground up. This prevalent lack of laboratory resources and the subsequent difficulty of obtaining accurate results on antimicrobial susceptibility testing is an important challenge to address when proposing a stepwise approach. In addition, an AMR strategy should consider surveillance for resistance of antibiotics used in animal feed and structure the strategy the same way as for humans. The WHO GAP emphasises the One Health approach,
Benefits of antimicrobial resistance surveillance.
AMR surveillance benefits | Action taken |
---|---|
Evidence based public health policy | Changing public health policy such as notifying MDRO |
Monitoring trends in AMR | Based on increase or decrease in trends of resistance recommendation is issued |
Public health intervention | Introduction of pneumococcal conjugate vaccine in EPI |
Treatment guidelines | Continuous updates based on AMR surveillance |
Continuous education and training | Integrated in antimicrobial stewardship programmes |
Epidemiological studies and research | Based on strain phylogeny pathogen emerging and outbreak detection |
AMR, antimicrobial resistance; MDRO, multidrug-resistant organism; EPI, expanded programme on immunisation.
The key objectives of AMR surveillance are to estimate trends in AMR rates and to detect the emergence and potential spread of AMR, in order to inform programmes that formulate guidelines for treatment and prevention of infections and prevention of AMR transmission. In Africa, the development and improvement of laboratory capacity, including standardised testing, external quality assessment programmes, procurement, and timely and cost effective reports, should eventually lead to the establishment of an integrated and coordinated surveillance system for AMR in the region, which will strengthen knowledge about AMR through surveillance and research. This surveillance should increase understanding of the implications of AMR and its epidemiology and allow for monitoring the effectiveness of guidelines and policy implementation. In addition, it would permit research and development of new diagnostics and novel technologies, optimisation of treatment, and other interventions as well as build human resource capacity as a secondary objective. Collaboration within a team of human and animal experts in AMR surveillance would allow for a One Health approach. This requires the establishment of coordinated surveillance in animals, the ability to control and regulate antibiotics use in animals, and the identification of alternative options for growth promoters in agriculture.
There are several approaches toward surveillance of AMR, including population-, sentinel- and laboratory-based surveillance. The general perception is that laboratory-based surveillance is currently the most efficient method of surveillance of AMR, which is what the WHO and GHSA advocate.
For laboratory-based surveillance to yield comprehensive data, a functional infectious disease diagnostic cycle is required. This cycle includes clinicians submitting samples for culture and susceptibility testing, a bacteriology laboratory that can generate quality culture and susceptibility test results, and a reporting system that includes not only the clinician requesting the test, but also a laboratory information system (LIS) that can inform the surveillance programme, which may be steered by a central body (
Laboratory processes in relationship to electronic collection of antimicrobial resistance data.
For a national laboratory-based surveillance programme to be successful, government commitment to support the surveillance programme for AMR at the country level is essential (
Surveillance programme summary.
Establishment of a national laboratory-based surveillance system at the country level, as established by each country’s National Department or Ministry of Health, also includes the establishment of a coordinating centre with the responsibility to systematically collect, analyse and share data at the national and international level. Governments may decide to set up their coordinating centres differently, but all will need expertise in epidemiology, clinical microbiology, infectious diseases, veterinary medicine, data management and governance. Such expertise may be built and subsequently sustained through continuous education programmes that take place locally or within the region. For example, South Africa, Kenya, Ghana, Uganda, Nigeria and Burkino Faso all provide a Field Epidemiology Training Programme.
Establishment of at least one reference laboratory that can undertake infectious disease diagnostics and antimicrobial susceptibility testing, and that has competence in phenotypic and genotypic confirmation of the presence of resistance genes, is required. Initially, in the absence of capacity to perform advanced phenotypical and molecular testing in the national reference laboratory, a clinical hospital bacteriology laboratory with demonstrated capacity to perform these functions, could be selected as a reference laboratory. In addition, instead of performing genotyping at the national level, molecular typing and gene characterisation could take place in another reference laboratory in the African region. National reference laboratories perform their role in close collaboration with provincial and district clinical laboratories, which generally receive samples directly from patients. Together, these laboratories form the national surveillance network. Countries should also consider including private laboratories in their network. Although specifics vary by country, such laboratories may receive large numbers of samples from a substantial proportion of the population. Strategies on how to involve and include private laboratories in national AMR surveillance networks must be developed to achieve this inclusion.
Setting up a regional network for AMR surveillance in Africa to provide locally relevant AMR data to serve as a bench mark may be the eventual goal. Whilst several regional networks exist, the Central Asia and Eastern European Surveillance of Antimicrobial Resistance network is one model for the African region. This network is a joint initiative of the WHO Regional Office for Europe, the European Society of Clinical Microbiology and Infectious Diseases, and the Dutch National Institute for Public Health and the Environment. The Central Asia and Eastern European Surveillance of Antimicrobial Resistance network includes all countries in the WHO European Region that are not part of the European Antimicrobial Resistance Surveillance Network, which is coordinated by the European Centre for Disease Prevention and Control in the European Union.
Laboratories that are participating in AMR surveillance as sentinel or reference sites should comply with baseline requirements as indicated under this heading. The quality of laboratory-based AMR surveillance data depends to a large extent on the microbiology laboratory. Firstly, the quality of a laboratory system should be assessed in order to identify gaps and areas for improvements. In order for participating laboratories to meet minimal quality standards requirement as defined by the network (e.g., accreditation, external quality assessment programme, and other standards), establishment of a laboratory quality system is essential. However, the logistical difficulties of joining external quality assessment programmes and receiving quality control materials present significant challenges to countries in sub-Saharan Africa, because of customs and other policies for shipment of samples and microorganisms between different countries.
Laboratory assessments should include pre-analytical, analytical and post analytical steps for reporting of antimicrobial susceptibility testing (AST) and its limitations. For the pre-analytical phase, diagnostic stewardship is critically important. Diagnostic stewardship is the process that guides and improves the use of microbiological tests to ensure they are timely, appropriate and accurate. Reports sent to clinicians should include a feedback form to help on-going improvements. To apply required standards for AST, laboratories must have the required infrastructure, equipment, supplies and staffing in place. Laboratories should be able to identify gaps and recommend improvements. For example, some laboratories may have all the equipment needed but no supply of reagents or other consumables needed for basic microscopy, culture and AST implementation. This, in turn, affects diagnostic stewardship as clinicians may lose confidence in laboratory reporting when timely, appropriate and accurate results cannot be achieved. A country’s national AMR surveillance plan and the regional AMR surveillance network may provide for policies and procedures that make timely ordering and receipt of consumables and other supplies feasible and affordable. ASLM could play an active role in such advocacy activities. Laboratory experts should be involved in ordering supplies to avoid receiving supplies that are irrelevant, not useful or of poor quality.
The use of a LIS is limited in most LMICs, which is unfortunate, as it improves AMR surveillance by reducing workload and errors, thus improving the overall quality of microbiology laboratories. Laboratories should use LIS to retrieve and share AST data with national and regional bodies (
As mentioned, national and regional networks will require (inter)national standardisation of methods. For standardisation of bacteriology test methods, guidelines are available and are often used, e.g. those from the Clinical and Laboratory Standards Institute
Human resource capacity may be the most challenging issue, as shortages of qualified and trained professionals can have a serious negative impact on the ability of laboratories to perform testing. Human resources are a weak spot in microbiology and have been ignored. Quality microbiology requires sufficient number of qualified technicians, as well as supervision by MD or MSc level clinical microbiologists who are capable of reporting results to clinicians. Finally, veterinarians should be involved in the process of developing surveillance systems to strengthen diagnostic stewardship in animal health, provide assistance about status of AMR in animal health, and implement preventative measures in animal health, if needed at a later stage. For capacity building that includes education, training and refresher courses and other forms of networking, the WHO and ASLM should be excellent sources of support.
The following components should be considered when designing an AMR surveillance plan (
Design summary for development of laboratory-based surveillance matrix.
Designations |
Target milestones |
Responsibilities |
---|---|---|
Establishment of a Coordinating Centre (CC) | Composition and development of terms of reference |
At national level |
Acceptance of the generic laboratory-based surveillance document on AMR WHO GLASS | Technical meeting for adoption of the key elements of the guide. This will allow staff involved in AMR surveillance to learn and comply with its objectives and content. (CLSI or EUCAST guidelines are subject to change annually). | National Coordinating Centre |
Designation of the national reference laboratory for AMR at country level | Selection of one national reference bacteriology laboratory with capacity for AST for bacterial organisms selected for surveillance in phased approach. |
Technical support to develop an appropriate base line level for surveillance |
Gap analysis |
Assessment of laboratory capacity using existing ISO standardised tools and proposed key activities needed to be supported, based on findings of the assessment and the requirements of the national guidelines on AMR | National Coordinating Centre |
Implementation of laboratory-based surveillance for AMR | Key action points: |
National Reference Laboratory |
Activities are presented in a stepwise approach starting with the first of a series of steps.
AMR, antimicrobial resistance; WHO, World Health Organization; GLASS, Global AMR Surveillance System; CLSI, Clinical and Laboratory Standards Institute; AST, antimicrobial susceptibility testing; ISO, International Organization for Standardization; SOP, standard operating procedure; PTS, proficiency testing schemes.
A gap analysis that includes all levels of the health system must be performed in order to implement or further expand existing AMR surveillance activities. For example, it was recently reported that many countries still lack reference to laboratories in their health policies and plans and do not consider laboratories at all in their health budgets.
There are currently several tools available to assess laboratory capacity and quality that could be used as a part of a gap analysis. These include the Stepwise Laboratory Improvement Process Towards Accreditation tools developed by WHO,
In order to ensure AMR surveillance of relevant pathogens, it is important to establish case definitions. For example, standard definitions should be established for patients with symptoms of syndromes that have high clinical importance, such as central nervous system infections and septicaemia. The selection of specimens should be directed according to local, national, and regional relevance, after considering site of infection, such as meningitis or bacteraemia. Isolates from cerebrospinal fluid and blood cultures, with particular pathogens of focus, including both Gram-negative and Gram-positive bacterial organisms, should be included. In addition, exclusion criteria, such as de-duplication based on one specimen per patient in 21 days or based on Global AMR Surveillance System criteria,
In addition, there are number of priority organisms and antibiotics recommended by WHO that should be considered in a stepwise process. These include
There are several types of surveillance and current recommendations are to perform laboratory-based surveillance. For each drug/bacteria combination, the approach toward laboratory-based surveillance should be decided on (
Surveillance methods.
For technical support and strategy advice, an AMR reference laboratory for African region should be established. The role of an African region AMR reference laboratory would be multi-faceted. Firstly, the regional reference laboratory should provide training of laboratory personnel from network member countries to help build capacity for development of surveillance systems in the trainees’ home countries. Secondly, the regional reference laboratory should take the lead in introducing and providing training on new techniques. Thirdly, it should provide confirmation of difficult AST results and offer advice when necessary. Finally, it should manage other laboratory networks in the region. A public/private partnership should be sought as the funding source.
Considering the growing impact of AMR worldwide and the lack of quality surveillance systems in the African region, an enormous effort must be undertaken through international and multi-sectorial collaboration. A recent report analysing the AMR surveillance capacity of the East Africa Public Health Laboratory Network by the Center for Disease Dynamics, Economics & Policy, commissioned by the World Bank, summarised the following key issues for laboratories to carry out AMR surveillance:
Lack of demand of bacteriology diagnostics from clinicians, related to length of time to get results (at least two days); lack of trust in results; lack of laboratory capacity for blood cultures, which are needed for many of the most serious, life-threatening infections.
Low priority given to bacteriology diagnostic supplies by hospitals and other decision makers who control purchasing.
The multi-component nature of bacterial culture and antimicrobial susceptibility testing, which makes it especially vulnerable to weak supply chains and frequent stock outs; results cannot be obtained if essential components are unavailable when testing is needed.
Lack of recognition that microbiology requires dedicated, trained personnel, leading some facilities and/or ministries of health to rotate staff in and out of microbiology.
Few options for automated testing relative to haematology, chemical pathology or HIV testing, which may be more satisfying to staff, leading to low morale.
Requirement for patients to pay out of pocket for diagnostic tests in many countries.
Whilst some of these may be generic to LMICs, others may be more specific to certain countries or settings.
In conclusion several key steps should be implemented for an AMR surveillance programme such as: assessment of laboratory capacity to perform surveillance for AMR; identification of gaps; adoption of the Global AMR Surveillance System manual or other guidelines; designation of national reference laboratories for AMR and organisation of advisory committees; implementation of laboratory-based AMR surveillance; and reporting to the Global AMR Surveillance System.
We thank ASLM and WHO AFRO for organising the meeting in Sierra Leone and initiating discussions about AMR in West African countries.
The authors declare that they have no financial or personal relationships which may have inappropriately influenced them in writing this article.
None.
O.P. was the project leader. O.P. and C.S. were both responsible for project design and writing of the manuscript.