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.

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