The Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses (CHARM) was established in April 2017. CHARM hosts two national reference laboratories and is supported by an epidemiology section. The centre was designated as a World Health Organization (WHO) Collaborating Centre for AMR (WHO SOA-43) in June 2017.
Healthcare-associated infections (HAIs) are among the commonest complications of hospital admission, are costly for the patient and the overall healthcare system, and may lead to patient deaths. This is an important new focus area for the centre. Antimicrobial resistance (AMR) is estimated to be associated with over 700 000 deaths every year, a number which could rise as high as 10 million in 2050.
AMR is a major focus area of the South African Department of Health and the NICD. CHARM works on AMR in bacterial and fungal pathogens causing human infections in healthcare facilities and in the community, spanning the public- and private-health sectors. The centre is supporting the “One Health” programme including surveillance for AMR in humans and animals.
Fungal diseases (mycoses) are responsible for an estimated 1.5 to 2 million deaths annually, including nearly half of those dying of AIDS and many of those with sepsis. Over the last seven years, the centre has led the scaling up of a cryptococcal antigen screening and pre-emptive treatment intervention, nested within the South African HIV treatment programme. The centre is now involved in evaluating the effectiveness of this national intervention to reduce mortality through a US National Institutes of Health R01-funded grant.
The national stock culture collection (NSCC) was established in April 2004 and is housed within CHARM. The NSCC provides a quality-controlled and reliable source of reference bacterial, fungal and mycobacterial strains to the National Health Laboratory Service laboratories.
The objectives of CHARM are:
- To conduct surveillance of healthcare-associated infections and detect outbreaks;
- To conduct surveillance for antimicrobial-resistant bacterial and fungal pathogens at public- and private-sector laboratories across the country;
- To conduct surveillance and public health research for mycoses;
- To use surveillance data to support the development of standard treatment guidelines for certain infectious diseases and to evaluate relevant public health programmes;
- To improve access to essential medicines and diagnostics including identification of emerging pathogens;
- To provide reference laboratory functions for identification, susceptibility testing and genotyping of bacteria and fungi; and
- To serve as a repository of reference bacterial, fungal and mycobacterial strains.
- The Centre works on preventing life-threatening fungal diseases of public health importance in South Africa:
- Cryptococcal meningitis, a deadly brain infection that affects persons living with advanced HIV disease (AIDS);
- Other life-threatening opportunistic fungal infections that occur with AIDS;
- Candidaemia, a healthcare-associated bloodstream infection that occurs among critically-ill patients and patients with certain cancers; and
- Invasive and chronic infections caused by Aspergillus.
- Led efforts to implement and evaluate a laboratory-based reflex cryptococcal antigen screening programme across South Africa. This programme aims to prevent deaths associated with cryptococcal meningitis.
- Involved in developing South African and international clinical guidelines for management of fungal infections.
- Offers a specialised mycology reference service to diagnostic medical laboratories, including phenotypic and sequence-based identification of unusual or difficult-to-identify fungi and antifungal susceptibility testing of yeasts and moulds.
- Please consult the NICD handbook for a list of tests that are offered.
- Research activities are focused on developing and validating new diagnostic assays and defining risk factors for fungal diseases and antifungal drug resistance.
- The mycology reference laboratory holds a large collection of pathogenic fungi of medical importance.
Antimicrobial resistance poses a major threat to the health of individuals and populations worldwide. Antimicrobials are not only essential for the treatment of community-associated infections such as pneumonia and meningitis but also healthcare-associated infections. These infections are commonly caused by bacteria or fungi which are killed or inhibited by antibiotics or antifungals, unless they develop resistance due to inappropriate use or abuse of these agents.
In a healthcare setting, medical procedures such as the insertion of intravascular or urinary catheters, intubation or surgery break the body’s natural barriers to infection and allow pathogens direct access to sites such as the bloodstream, urinary tract, lung or abdominal cavity. Patients with healthcare-associated infections require prolonged care in hospitals, serving as a source of cross-infection to other patients.
The emergence and widespread occurrence of multidrug-resistant bacteria and fungi threatens the ability of antimicrobials to act against these bacteria and fungi.
New resistance mechanisms in bacteria and fungi are emerging and spreading across the world. Some bacteria are naturally resistant to antibiotics and others develop resistance through genetic changes. Misuse, overuse and inappropriate use of antibiotics accelerates this process.
Surveillance is a key component of the strategy to combat antimicrobial resistance. The centre leads the national effort to conduct surveillance for AMR infections through establishment of a national diagnostic laboratory surveillance network. Several approaches are currently used for laboratory-based surveillance:
- National or sentinel surveys: bacterial and fungal isolates cultured from patients with bloodstream infections are submitted to CHARM’s reference laboratories for identification, antimicrobial susceptibility testing and genotyping;
- Enhanced surveillance: detailed clinical information is collected from patients admitted to sentinel hospitals who meet the surveillance case definitions throughout GERMS programme; and
- Electronic surveillance: data from public- and private-sector diagnostic laboratory information systems are compiled annually and reported as tables and resistance maps.
The Centre was named a World Health Organization (WHO) Coordinating Centre for AMR in 2017. CHARM is a National Coordinating Centre for the WHO Global Antimicrobial Resistance Surveillance System. Senior members of the Centre represent NICD on the Ministerial Advisory Committee (MAC) for AMR and the WHO Strategic and Technical Advisory Group (STAG) for AMR.
The Centre uses several methods, including real time surveillance to detect outbreaks of healthcare-associated infections; reporting on relatedness between strain causing outbreaks and advising on responses. A team of trained epidemiologists within the centre investigate and respond to such outbreaks
The centre offers a specialised bacteriology and mycology reference service to diagnostic medical laboratories, including:
- Phenotypic, mass spectrometric and sequence-based identification of bacteria and unusual or difficult-to-identify fungi;
- Antibiotic susceptibility testing of bacteria and antifungal susceptibility testing of yeasts and molds;
- Genotyping of bacteria and fungi; and
- Molecular mechanisms of antimicrobial resistance.
Please consult the NICD handbook for a list of tests that are offered
The Antimicrobial Resistance Laboratory and Culture Collection in the Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses (AMRL-CC/CHARM) is designated as World Health Organization (WHO) Collaborating Centre (CC) for Antimicrobial Resistance (AMR) under the WHO reference number SOA-43.
One of its activities is to build microbiology laboratory capacity and to improve surveillance for AMR in the WHO African region. It is are committed to providing teaching, training and an External Quality Assessment Programme (EQAP) to facilitate good laboratory practice. EQA panels are sent twice a year to participants that are nominated by the Ministry of Health in each African country. Participating laboratories process samples sent and submit results for evaluation. Participants are assessed against the intended response, which is verified by referee laboratories.
Feedback on individual laboratory performance is provided to each participant along with the overall participant performance for the challenge in the survey. This programme is published in the WHO EQA Annual Report. EQA is a key element for the total Quality Management System (QMS) of a laboratory and is compulsory for laboratories who pursue accreditation
DESCRIBING THE BURDEN OF NEONATAL SEPSIS AT SECONDARY-LEVEL HOSPITALS IN SOUTH AFRICA
Worldwide, neonatal mortality remains high accounting for 46% of childhood deaths in 2015, with infectious diseases responsible for approximately 600 000 neonatal deaths. In sub-Saharan Africa, which carries a high burden of global childhood deaths, the aetiology of these infections and their resulting burden are not well understood. Studies in Africa have been limited to tertiary-level institutions, with few, if any, population-based surveillance studies reporting on incidence risks or rates. Some of the contributing factors to this lack of data include under-utilisation/ unavailability of health care services for neonates, suboptimal specimen-taking to confirm an infectious disease diagnosis, limited capacity of diagnostic pathology laboratories to detect, identify and characterise pathogens, absence of appropriate denominator data for calculating incidence risks or rates and limited resources for setting up and maintaining population-based surveillance studies.
We aim to improve neonatal and child health by gaining a deeper understanding of the burden and aetiological factors of neonatal sepsis in urban and rural sub-Saharan Africa through the development of a two-tiered surveillance programme, with a focus on neonatal sepsis occurring at secondary-level institutions. The primary outcome is to determine the national burden of neonatal sepsis in the public sector in South Africa and provide a detailed characterization of risk factors, outcomes and antimicrobial-resistant pathogens associated with neonatal sepsis at secondary-level facilities by setting up a sustainable and in-country-led surveillance system, in order to monitor the impact of future public health interventions aimed at reducing sepsis in these young children.
Ultimately, these surveillance data can be used to address Sustainable Development Goal 3 by aiming to improve neonatal and child health by using a two-tiered laboratory-based surveillance programme to gain a deeper understanding of the aetiology and burden of neonatal and infant sepsis – with a future aim of addressing these factors and thus reducing neonatal morbidity and mortality in low- and middle-income settings.
The impact of this project will be seen on a number of levels:
- Globally, this data will allow us to gain a better understanding of neonatal sepsis and the antimicrobial susceptibility and molecular relatedness of neonatal bacterial and fungal pathogens in a low- and middle-income country – particularly in secondary-level institutions serving less urbanised and rural communities.
- Locally, the National Department of Health in South Africa could use these data to understand the burden of neonatal sepsis, to design appropriate interventions (such as antimicrobial stewardship and infection prevention and control programmes), to prioritise facilities requiring urgent intervention and to tailor these interventions for those at highest risk of neonatal sepsis.
- The hospitals at which we will conduct enhanced surveillance will benefit from the additional information that will come from further characterisation of the isolates causing neonatal sepsis and gain a better understanding on how they can tailor their empiric antimicrobial regimens to better fit the spectrum of organisms that are being cultured.
- Individual neonates at these hospitals will benefit from the doctors adjusting their empirical therapy accordingly.
- We will strongly encourage enhanced surveillance sites to implement local antimicrobial stewardship and infection prevention and control programmes for neonatal units and will design facility-level dashboards based on their local surveillance data to allow them to monitor key indicators for neonatal sepsis.
- Policymakers can use the data on the burden of disease, mortality and risk factors associated with neonatal sepsis and the aetiological patterns of pathogens causing neonatal sepsis to align their strategies on the Continuum of Maternal and Newborn Care to help meet South Africa’s goal to reduce neonatal sepsis by 84% by the year 2025.
By setting up this surveillance programme, we will facilitate future sustainable funding of the project and we will be able to objectively record the change in the incidence of neonatal sepsis over time as new interventions are implemented. Ultimately, we hope that policies put in place through the data generated by this project will save the lives of many newborn babies and improve the quality of life of others in the years ahead.
Globally, an estimated 690,000 lives were lost to AIDS-related illnesses in 2019. Cryptococcal meningitis (CM), a rare but severe fungal infection of the brain and spinal column, is the second leading cause of AIDS deaths behind tuberculosis (TB).
If left untreated, CM almost certainly causes death, and even with treatment in low- and middle-income countries, mortality ranges from 30-80% depending on types of treatment available.
Cryptococcal antigen, or CrAg, is a highly specific biomarker for cryptococcal disease and is present in the bloodstream weeks to months prior to the onset of meningitis symptoms. Screening for and pre-emptively treating cryptococcal disease offers opportunity to reduce the burden of CM and CM-related deaths, particularly in low- and middle-income countries where incidence remains high and optimal treatment is often unavailable.
This CrAg screen-and-treat approach has been recommended by the WHO since 2011 and is a key part of care for people living with advanced HIV disease. South Africa became the first country to implement a national CrAg screening programme in 2016, automatically screening all individuals with a CD4 cell count below 100 cells/µL of blood.
NHLS/NICD surveillance data shows that the programme has achieved very high coverage, screening over 98% of all patients eligible for a CrAg test. However, clinical treatment and outcomes are not routinely reported, creating a challenge in measuring the impact of the programme and identifying areas for improvement.
The Cryptococcal Antigen Screen-and-Treat National Evaluation (CAST-NET) study is a National Institutes of Health (NIH)-funded project designed with two main objectives:
- To assess the performance of South Africa’s national reflex CrAg screening programme, and
- To subsequently design programmatic interventions to optimize implementation and patient outcomes.
CAST-NET will retrospectively evaluate the national programme primarily through patient chart review and abstraction for all patients screened CrAg-positive over a 25-month period (February 2017 – February 2019) at 468 facilities across a nationally representative sample of 27 sub-districts covering all 9 provinces.
In the first phase of CAST-NET, an enhanced retrospective surveillance is being implemented at all study sites. Nearly 4,500 patients have been screened positive at study sites over the 25-month enrolment period. Data capturers travel to study facilities and image charts for as many CrAg-positive patients as possible at each health facility. Chart images are then checked for quality and de-identification and subsequently abstracted by clinical study staff to determine primary and secondary endpoints.
The primary endpoint of the CAST-NET study is to estimate the 6-month cryptococcal meningitis-free survival of all patients with a CrAg-positive screening test result. Additional endpoints to be determined from chart abstraction include indicators such as 6-month retention in care, time from testing to treatment initiation, and proportion of patients’ CrAg test results appearing in their clinical chart.
Analysis of these endpoints aims to reveal weaknesses in the current national CrAg screening programme. The second phase of CAST-NET seeks to design programmatic interventions that address identified gaps, such as enhanced training or test result delivery and follow-up. These programmatic interventions will then be evaluated for impact using a pre/post study design in a subset of CAST-NET study sub-districts.n
Leadership and Team
Prof Nelesh Govender began his career in public health in 2006 when he joined the NICD as Head of GERMS surveillance. As head of the Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses he works closely with the National Department of Health to generate evidence that may guide government policy. His particular area of expertise is in medical mycology and antimicrobial resistance (AMR), in which his work has largely focused on the neglected area of antifungal resistance.
Govender is the Immediate Past President of the Federation of Infectious Diseases of Southern Africa, a member of Cryptococcal Meningitis Action Group and co-chair of the National Advanced HIV Disease Task Team and Neonatal Sepsis Task Force. He has chaired national and international guideline panels for fungal diseases, is a Professor in the School of Pathology at the University of the Witwatersrand and is an Honorary/Visiting Professor at the University of Cape Town, St. George’s University of London and the University of Exeter. His research has been funded through both the NICD and partly through grants received from the US National Institutes of Health, US Centers for Disease Control and Prevention (CDC), CDC Foundation, Bill and Melinda Gates Foundation, UK Medical Research Council, UK National Institute for Health Research and NHLS Research Trust.