Wits scientists pioneer vaccine to safeguard pregnant women against stillbirth and infant death

6 November 2017 - Wits University

A global study of GBS, bacteria that cause stillbirth and infant death, shows that Africa has the highest incidence. Wits University is pioneering a vaccine.

Scientists at the Wits/Medical Research Council Respiratory and Meningeal Pathogens Research Unit (RMPRU) have contributed to the first comprehensive study of Group B Streptococcus (GBS), which are bacteria that infect pregnant women and cause stillbirths and severe invasive disease and death in infants.

Africa has the highest burden of GBS with 54% of estimated cases and 65% of stillbirths and infant deaths.

The GBS burden of disease analysis involved more than 100 researchers from around the world and the published supplement comprises 11 research papers. Conservative estimates show that GBS infection causes some 150,000 preventable stillbirths and infant deaths every year.

Professor of Vaccinology, Shabir Madhi, who is director of the RMPRU, the DST/NRF SARChI Chair in Vaccine Preventable Diseases, and Executive Director of the National Institute for Communicable Diseases, contributed to the study.

“This research is especially important for South Africa, where the highest incidence of invasive GBS in young infants globally has been reported for the past 20 years. Furthermore, we have shown recently that at least 1250 South African women will have a stillbirth due to GBS each year,” says Madhi.  

The GBS burden of disease analysis, funded by the Bill & Melinda Gates Foundation, includes data and estimates for the year 2015 from every country worldwide and includes outcomes for pregnant women, their babies and infants. Previous data on GBS burden focused on infant cases and high-income countries, but the impact of GBS disease worldwide, especially in Asia, was less clear. 

The new research found GBS colonise the rectum and vagina of pregnant women in all regions of the world, and an average of 18% of pregnant women worldwide carry (are colonised with) GBS, ranging from 11% in eastern Asia to 35% in the Caribbean, and totalling 21.7 million in 195 countries. 

Although several vaccines to prevent GBS are in development, none is currently available – this despite GBS accounting for more than the combined neonatal deaths from tetanus, pertussis, and respiratory syncytial virus, for which maternal vaccines are already in use or further advanced in development. 

The GBS burden of disease analysis shows for the first time that a maternal GBS vaccine, which was 80% effective and reached 90% of women, could potentially prevent 231,000 infant and maternal GBS cases. 

Madhi and his team at the Wits MRC Respiratory and Meningeal Pathogens Research Unit recently completed the first study of an investigational GBS vaccine in pregnant women, the results of which were published in the prestigious Lancet Infectious Diseases journal. The unit is also investigating the potential of other components of GBS as potential vaccine targets.

Dr Keith Klugman, Director of the Pneumonia Team at the Bill & Melinda Gates Foundation and Wits Medical School alumnus, says:  “The first few days and weeks of a baby's life are the most vulnerable by far. By filling in one of the great voids in public health data, this work provides crucial insight and shows the pressing unmet need for the development of an effective Group B Strep vaccine. Immunizing expectant mothers is a potentially ground-breaking approach that could dramatically reduce the number of maternal and child deaths.”

About Group B Streptococcus 

• GBS is carried by up to a third of adults, usually with no symptoms.
• In women, GBS can live harmlessly in the digestive system or lower vaginal tract, from where it can be passed to the unborn baby through the amniotic fluid or to newborns during labour.
• Babies are more vulnerable to infection as their immature immune systems cannot fight off the multiplying bacteria.
• If untreated, GBS can cause serious infections, such as meningitis and septicaemia, which may lead to stillbirths, and newborn and infant deaths. If they survive, babies can develop permanent problems including hearing or vision loss, or cerebral palsy.
• Current GBS prevention focuses on giving antibiotics to women in labour to reduce disease in infants at delivery. At least 60 countries have a policy for antibiotic use in pregnancy to prevent newborn GBS disease. Of those, 35 have a policy to test all pregnant women to see if they carry GBS, and the remaining 25 countries identify women with clinical risk factors. However, implementation of these policies varies around the world.

World-renowned Wits vaccines prof to chair SA medicine regulatory board

8 November 2017 - Wits University

The Minister of Health has appointed Wits Professor Helen Rees to chair the Board of the South African Health Products Authority.

Dr Aaron Motsoaledi appointed Professor Helen Rees, Executive Director of the Wits Reproductive Health and HIV Institute (Wits RHI) as Chair of the SAHPRA earlier this month.

SAHPRA, which replaces the Medicines Control Council (MCC), will ensure that the medicines in South Africa are safe, effective and of good quality.

Rees has extensive experience in the field of medicines regulation and on governance boards. She has served on many regulatory committees, including being the current and previous Chair of the MCC (1998-2002; 2014 to present). She is recognised by her peers to be an exceptional leader of the MCC.

Between 2011-2014, Rees chaired the SA Health Products Technical Task Team to advise the Director-General of Health and the Health Minister on the legal and operational transition from the MCC to SAHPRA, including prioritisation of the transformation agenda.

Her experience has given her extensive knowledge of medicines regulation, including as Chair of MCC’s Pharmacovigilance Committee (2001), Chair of MCC’s Clinical Trials Committee (1997-1998) and as a member of MCC’s Clinical Committee (1996-1998).

Telling Teeth

9 November 2017 - Wits University

More accurate aging of teeth could hold the key to identifying health-compromised children in Africa.

Population-based data on human biological growth and development processes are fundamental for assessing the health status of a community. For many populations in rural Africa, birth registry and eliciting date of birth are still challenges. Data on uncompromised development and growth variation in most developing populations are surprisingly lacking, and researchers typically compare growth in the population of interest to standards that are formulated for European or US children.

Wits University anatomical science and community dentistry researchers, however, believe that more accurate aging of teeth could hold the key to identifying health-compromised children on the African continent. The researchers, who are investigating dental development as a more reliable gauge for assessing the age of children and juveniles in forensic and anthropological contexts, recently published a systematic review of dental development assessment methods to determine the best and most accurate means to estimate chronological age in different populations. 

According to Professor Lynne A Schepartz, Associate Professor and Head of the Biological Anthropology Division at Wits and co-author of the paper, “It is important to accurately estimate chronological age from a sample of living children in the population of interest, because this information can then be used as a benchmark for evaluating the growth of health-compromised children. Our review illustrates that there is significant population-level variation in the tempo of dental development.”

Their review focused on studies investigating the predominant dental development assessment methods - the Demirjian and the Willems methods - in different populations with the aim of determining the more accurate method.  The findings conclude that the Willems method of dental age estimation provides a better and more accurate estimation of chronological age in different populations than the Demirjian method. Still, the ages of children in most populations are over-estimated using that method. 

The findings have implications for growth assessment in general, and the use of global standards that are largely untested in African populations. The research highlights the need for population-specific standards for age estimation, as their use extends beyond basic biological anthropology and health research.

The Wits researchers say the information from dental development may play a major role in determining many clinical decisions, including choices about treatment options and sequence of treatment in the future.

Wits leads innovative African laboratory network initiative

16 November 2017 - Wits University

The Wits-led African Innovation Laboratory Network (iLEAD) launched today with a mission to integrate and optimise laboratory systems to improve patient care.

Wits School of Pathology researcher, Professor Wendy Stevens and her team lead the African Innovation Laboratory Network - iLEAD (Innovation: Laboratory Engineered Accelerated Diagnostics) - an initiative to advance innovation in medical pathology laboratory systems and diagnostics.

iLEAD aims to integrate laboratory systems and tackle obstacles to often-neglected laboratory space in Africa. iLEAD will stimulate new ideas and processes for diagnostics and laboratory systems specifically as well as innovate across the laboratory value chain generally. 

“We hope that, in addition to diagnostic and pathology services, we can stimulate new approaches to unique patient identification, sample collection and logistics, as well as continuous quality monitoring and connectivity. We also intend to explore big data management and a variety of innovative pathology and molecular solutions,” says Stevens, who is an expert in laboratory medicine and a specialist in haematology and has driven multiple innovations in pathology services.

Her team of researchers established the first HIV laboratory in the National Health Laboratory Services (NHLS). Most recently the team implemented the WHO-endorsed TB diagnostic test, Gene Xpert, at scale across  64 centres, making this the leading global programme for molecular implementation of gene Xpert testing globally. 

The iLEAD network comprises three collaborating centres in South Africa, Mozambique and Senegal respectively.  Professor Souleymane Mboup will lead the centre in Senegal and Dr Ilesh Jani, Mozambique. Stevens, who is head of Molecular Medicine and Haematology at Wits, head of the National Priority Programme of the National Health Laboratory Services (NHLS), is responsible for the South Africa centre and for the overall project. These researchers are familiar with the unique implementation and maintenance of laboratory services required in Africa at scale.

iLEAD’s network merges expertise within the fields of basic science, research and development, clinical research, implementation and translational science, marketing and business development, to accelerate the introduction of novel solutions for African and global health security. iLEAD, which was established with seed funding from the Bill & Melinda Gates Foundation, will leverage public-private partnerships to help drive tailored innovations towards these goals. 

iLEAD will establish an Innovation Pipeline to help innovators develop products from ’concept and design’ through ’clinical validation for launch readiness’. As successful innovations exit the pipeline, they will be introduced to iLEAD’s network of implementing partners to drive real-world impact on patients.

New Centre of Centre of Excellence to focus on early human behaviour

15 November 2017 - Wits University

Collaboration between Wits and the new CoE at University of Bergen is essential to answer some of the most fundamental questions about our ancestry.

A new Centre of Excellence in early human behaviour at the University of Bergen in Norway will aim to address unanswered questions about our species.

Headed by Wits Professor, Christopher Henshilwood, the Centre for Early Sapiens Behaviour (SapienCE), was officially launched at the Bergen University’s Department of History, Archaeology, Cultural and Religious Studies recently.

“The Centre will directly address unanswered, first order questions about Homo sapiens, such as what defines the switch to ‘modern behaviour’, how exactly should this term be defined and why and how did this switch occur,” says Henshilwood.

“One of the other questions that we aim to answer is ‘were there changes in the human brain at that time that accelerated behavioural variability and how can these be measured now?’.” 

Henshilwood holds the South African NRF SARChI Chair in Modern Human Origins, which was recently renewed. The new CoE programme is operated by the Research Council of Norway, which finances  the activities of Norway’s foremost scientific environments in centres to achieve ambitious scientific objectives through collaboration and long-term basic funding. It has close links to Wits, with several staff members having links with Wits, including Professor Bruce Rubidge, who serves on the SapienCE board.

“The establishment of the SapienCE in Norway is a huge achievement for Professor Chris Henshilwood. As Director of the Centre of Excellence in Palaeosciences in South Africa I am excited about the close collaboration between these two centres of excellence. This will bring a great deal of local and international research attention to the remarkable Middle Stone Age sites of the Southwestern Cape which are providing ground breaking new understanding of early human behaviour,” says Rubidge.

Henshilwood believes his work in Blombos Cave and Klipdrift Shelter in the southern Cape has laid the foundation for the need to establish a Centre of Excellence in human origins research.

“Over the past 20 years, archaeological evidence from the Middle Stone Age in Africa has rapidly changed perceptions of the behavioural variability and adaptive strategies of these early humans,” says Henshilwood. “Our research in the southern Cape, since 1991, has uncovered unprecedented new evidence for the evolution of early Homo sapiens in southern Africa.”

Some of these major discoveries related to the advanced technology that early humans developed. It also included the earliest evidence for the making of a pigmented compound, as well as the first known use of a combination of heating and pressure flaking to create finely-crafted stone tools.

There are a lot of questions about our early development to still be answered by the SapienCE, says Henshilwood. The centre will focus on seven different research questions in the next 10 years.

“The starting point is simple. We all come from Africa. I am certain that in the next five or 10 years, we will have a completely new understanding of human behaviour.

Thinking big by burning small

20 November 2017 - Wits University

Creative management of grazing through the use small fires can draw back herbivores to grazing areas that are avoided by animals.

A recent paper by scientists from Wits University in South Africa shows how creative fire management can increase habitat for wildebeest and other grazing animals in national parks.

The work, published in the Journal of Applied Ecology (http://onlinelibrary.wiley.com/doi/10.1111/1365-2664.12956/full), shows that small, repeated fires can have a concentrating effect on animals, and create “grazing-lawn ecosystems” where food quality is higher and herbivores can see predators from further away.

The research was initiated through a collaboration between the University of the Witwatersrand and the South African National Parks (SANParks).  SANParks managers within Kruger National Park (South Africa’s largest protected area) have been managing fire since as early as 1957, with fires applied to achieve particular objectives.

However, recent self-analysis raised concerns that the fire-policy in the Kruger Park was resulting in a switch to fire-adapted grasses that excluded grazing animals who need higher quality graze such as wildebeest. Managers were specifically worried that large fires resulted in grazers spreading out into the large burn scars after a fire and reduced grazing pressure in the local area.

Navashni Govender from SANParks joined up with Prof. Sally Archibald from Wits University and Prof. Catherine Parr from the University of Liverpool. Together with a team of graduate students and technicians, and with the support of Working on Fire, Govender, Archibald and Parr set up a large-scale experiment near Satara Restcamp in the Kruger Park in 2013.

Over the following three years fires of varying sizes were lit annually in the early- and late-dry season of each year and the type and number of grazers visiting burns was monitored by looking for the presence of dung on burn sites. The response of grass to the grazing herds was also measured with plots that were never burnt used to compare any changes.

“After 5 years the results are conclusive,” says Archibald. “Our PhD student, Jason Donaldson, has shown that all grazers increase their use of small burns (<25ha) after a fire, and that the number of animals on these smaller burns is large enough to keep grass short and palatable for longer periods.”

Wildebeest remained on these small burns and actively selected them over areas where burns were absent, and grass was taller. The continued high number of wildebeest on small burn patches ultimately kept grass very short (

The collaborators are now investigating whether smaller animals, like grasshoppers, benefit from the management intervention, and have found three families that were unique to short-grazed patches, increasing biodiversity overall.

“The research adds to a growing understanding of the interactions between fire, grazers and grass structure and function in savannas and highlights the importance of understanding feedbacks between fire management policies and wild herbivores,” says Donaldson. “The collaborators have been testing this management tool in other ecosystems in Africa, and are also, with collaborators from the University of Pretoria, exploring what this means for rangeland systems, where, cattle, not wildebeest are the dominant grazers.”

Fire management may seem like a contradictory idea to some, who view it as a destructive force of nature, but humans have been making use of effect of fire on vegetation structure and animal movement since before the rise of modern man.

“In his book Sapiens, Yuval Noah Harari states: ‘Some human species may have made occasional use of fire as early as 800 000 years ago … A carefully managed fire could turn impassable barren thickets into prime grasslands teeming with game’,” says Donaldson.

Modern day land managers still rely heavily on fire to manage grasslands in Africa with commercial farmers and migratory pastoralists both burning savannas to provide fresh growth for livestock and to keep areas clear of thick brush.

“The research presented here adds a new layer to this story, as fire size has seldom been considered in these management decisions,” says Archibald.

The Kruger National Park is exploring the possibility of using this new insight to manage the southern Basalt plains, which are notoriously low in animals despite their high soil fertility.

Science and art

Archibald teamed up with visual artist Hannelie Coetzee to interpret this work through burning an artwork titled Locust and Grasshopper (2017) in a Highveld savannah landscape. Coetzee created the images of a locust and grasshopper facing each other, and used the savannah landscape as her canvas to plot them in, with 5D Surveys. With the assistance of fire management organization Working on Fire, they performed their work in a live-burn demonstration at the Nirox Sculpture Park in the Cradle of Humankind.

Through her art, Coetzee asks the question of how human behaviour impacts on our environment.

“Science and art are often conflicting schools of thought, but they can work in parallel, providing a meeting of the head and heart,” says Coetzee.

“The representation of the locust and grasshopper expands on the ideas of diversity, but also emphasizes the idea that something so small can play such a large role in our environment. It is only when we look at the intricate detail of these elements that we can communicate these complex issues to the public in a visual way.”

Gold Fields enter a three-year partnership with Wits

22 November 2017 - Wits University

Three-year funding will aim to further academic knowledge of mechanised mining and rock engineering in South Africa.

Wits University strengthened its partnership with the mining firm, Gold Fields, on Wednesday, with a R6 million sponsorship to improve knowledge in the fields of mechanised mining and rock engineering.

The funding follows on a long-standing partnership of over 10 years, in which Golf Fields sponsored the Wits School of Mining Engineering with R18 million.

The cheque was officially handed over to Wits Vice-Chancellor and Principal, Professor Adam Habib by Gold Fields CEO Nick Holland, who also re-opened the newly-renamed Gold Fields Laboratories at the Wits School of Mining Engineering.

Both Gold Fields and Wits University want to collaborate in developing young professionals with the knowledge and skills required to support mechanised, deep level gold mining,” said Habib. “Through this, we can undoubtably assist the mining industry in general and play our part in bringing South Deep to full production.”

Operated by Gold Fields, South Deep is one of the country’s largest and deepest underground, mechanised gold mines. The skills and expertise required to bring the mine, with an expected life of over 70 years, to full production are not in abundant supply in South Africa.

Holland said that even though the mining industry in South Africa is going through a “bumpy road”, there is still a future in mining, and that mining indirectly supports about 30 million people in South Africa.

“Our challenge is that when all of a sudden there is a mining boom, that we don’t have the skills and resources in place,’ he said. “Wits has for decades provided the skills needed to power South Africa’s mining industry. This latest sponsorship will ensure that they are in a position to do so for many years to come.”

A number of projects have already been identified for funding by Gold Fields during the three-year period. They are:

• Three postgraduate research projects, linked to the Chair of Rock Engineering;
• Two Geological Resource Modelling postgraduate research projects; and
• Two postgraduate drill and blast improvement and other productivity-related research projects.

Habib said Wits would like to partner with all the mining houses in the country, to assist in “rethinking” the economy in South Africa.

“Let’s go back to what we said in the 1930s and 1940s. (At the time), Wits partnered with the mining industry to pioneer a new different way of mining that lasted at least 40 years. Let us start again. Let’s start a new 15-year partnership that will stand for the next 40 years,” he said.

He said that not only does the mining industry need the skill sets to mechanise in the future, but that increased mechanising would lead to a change in social structure of existing miners who may need to be retrained and reskilled. This might need other academic support, such as sociologists, lawyers and other fields of the humanities.

“The historic challenge of our time is how to rethink a common humanity. We will pioneer ways in how to rethink mining; rethink humanity and rethink what it means to be both African and human,” he said.

Wits research on HIV viral load urges updates to WHO therapy guidelines

21 November 2017 - Wits University

The study shows that clinical interventions should take place at lower viral loads than those proposed by the current World Health Organization guidelines.

A large cohort study in South Africa has revealed that that low-level viraemia (LLV) in HIV-positive patients who are receiving antiretroviral treatment (ART) is an important risk factor for treatment failure.

Viraemia is a medical condition where viruses enter the bloodstream and thus have access to the rest of the body. 

The findings indicate that the current World Health Organization (WHO)-defined threshold for virological failure does not identify a large subset of patients who are at increased risk of poor outcomes of ART. Thus, clinical intervention should take place at lower viral loads than those proposed by the current WHO guidelines.

Viral load refers to the amount of HIV virus in the blood.

A team of scientists including Dr Sergio Carmona from the University of the Witwatersrand, Johannesburg and the National Health Laboratory Service; the Ndlovu Research Consortium in Limpopo Province; the University of California San Diego, USA; and the University Medical Center Utrecht in the Netherlands, published the study in Lancet Infectious Diseases in November 2017. 

Dr Sergio Carmona, in the division of Molecular Medicine and Haematology, School of Pathology at Wits University and Head of the Viral Load Unit at the National Health Laboratory Service, says: "This study provides clear evidence that clinical interventions should take place at lower viral loads than those proposed by the current WHO guidelines. We need to support the scale-up of viral load testing in low and middle-income countries as well as encourage adherence to ARVs and close follow-up of viral load results.” 

The WHO guidelines on HIV viral load for antiretroviral therapy 

The monumental response to the global HIV epidemic has led to an unprecedented number of patients on ART. The goal of ART in HIV positive patients is to suppress the viral load. From the start of the ART roll-out, South Africa has invested in laboratory capacity to enable routine viral load monitoring of all patients on ART. The implementation of viral load monitoring was done largely in accordance with WHO ART guidelines, which advises annual routine monitoring, and a threshold of 1000 copies/mL to define virological failure. 

In clinical guidelines for high-income settings, cut-offs for therapy failure are lower, and clinical intervention is already required above 50 copies/mL. Suppression below 50 copies prevents disease progression towards AIDS (Acquired Immune Deficiency Syndrome - the result of untreated HIV infection), prevents selection of resistance, and lowers the risk of transmission of the virus to others.

The South African large-scale viral load monitoring programme yields unique insights into crucial aspects of WHO ART guidelines, such as the WHO's current definition of virological failure. 

The study of over 70 000 patients attending 57 HIV treatment facilities has shown that patients presenting with detectable viral loads below the lenient 1000 copies/mL threshold are at an increased risk to develop virological failure - i.e. less than 1000 copies/mL. 

Study shows clinical intervention required at lower viral loads than proposed by the WHO

A quarter of the patients in this cohort, who were on first-line ART, experienced one or more episodes of LLV. Compared to patients with virological suppression, that is with less than 50 copies/ml, patients with LLV were threefold more prone to develop failure of ART. In patients with LLV of the highest range (400-999 copies/mL) this risk increased to nearly fivefold. The risk to change to second-line therapy was even more pronounced to 13 times.

Important conclusions can be drawn from this study. The findings indicate that the current WHO-defined threshold for virological failure fails to identify a large subset of patients who are at an increased risk of poor outcomes of ART.

A more active approach to low-level viremia is essential to prevent virological failure and subsequent selection of resistance. Such an approach should be implemented prior the introduction of integrase inhibitors which are the cornerstone of ART globally to preserve this powerful treatment for the coming decades.

“Sustainable virological suppression is an important part of the 90-90-90 targets defined by UNAIDS. This study shows that patients with low-level viraemia are at risk for therapy failure. A strong message from WHO regarding the risk of virological failure after LLV could motivate clinicians to act when LLV is encountered,” says Professor Francois Venter, deputy executive director, Wits Reproductive Health and HIV Institute (Wits RHI). 

90-90-90 refers to 90% of all people living with HIV knowing their status by 2020, 90% of those diagnosed be receiving ART bu 2020, and 90% of those on ART will have viral suppression by 2020.

Wits University scientists highly cited worldwide

28 November 2017 - Wits University

Two scientists from Wits University are on the list of Highly Cited Researchers in the world.

Paleoanthropologist Professor Lee Berger makes his debut on the list, while microbiologist Professor Lynn Morris retains her listing.

Berger and Morris are two of just five individuals who have a South African institution as their primary affiliation. 

Highly Cited Researchers is an annual list compiled by Clarivate Analytics that recognises leading researchers in the sciences and social sciences globally. The 2017 list features some 3 400 Highly Cited Researchers in 21 of these fields. 

Berger is a Highly Cited Researcher in social science (general) while Morris features in the field of microbiology. 

Professor Lee Berger (pictured right)

Berger is an award-winning researcher, author, speaker and paleoanthropologist. He is Research Professor in Human Evolution and the Public Understanding of Science at Wits University, and a National Geographic Explorer-in-Residence. He is the recipient of the National Geographic Society’s first Prize for Research and Exploration and is a Fellow of the Royal Society of South Africa, a Member of the Academy of Sciences of South Africa, and a Fellow of the Explorers Club.

His explorations into human origins in Africa over the past two-and-a-half decades have resulted in many new and notable discoveries, including the most complete early hominin fossils found so far, which belong to a new species of early human ancestor, Australopithecus sediba, and, in 2013, the richest early hominin site yet found on the continent of Africa. Among other positions, Berger serves on the advisory board of the Global Young Academy.  

Professor Lynn Morris (pictured left)

Morris holds a joint appointment as Research Professor in the Faculty of Health Sciences at Wits University and Research Associate at the Centre for the Aids Programme of Research in South Africa (CAPRISA). She is the Head of the HIV Virology Laboratory within the Centre for HIV & STIs based at the National Institute for Communicable Diseases at the National Health Laboratory Services.

Morris is internationally recognised for her work in understanding how the antibody response to HIV develops. The rapid mutability of the virus means that the ‘standard’ antibody response is quickly obsolete in an infected individual. Morris has been prominent in studying the rare appearance in some patients of so-called 'broadly neutralising antibodies', which can attack a broad range of mutated viruses. This work is currently one of the most promising leads towards the production of an effective anti-HIV vaccine. In June 2017, Morris received the prestigious Harry Oppenheimer Fellowship Award for her scholarship and research excellence. 

The Highly Cited Researcher list methodology

The Highly Cited Researcher list of 2017 focuses on contemporary research achievement. Only Highly Cited Papers in science and social sciences journals indexed in the Web of Science Core Collection from 2005-2015 were surveyed. 

Highly Cited Papers are defined as those that rank in the top 1% by citations for field and publication year in the Web of Science (an online subscription-based scientific citation indexing service). These data derive from Essential Science Indicators (ESI), which denote authors with the most papers designated as Highly Cited. 

The 21 fields also derive from Essential Science Indicators defined by sets of journals (and, in exceptional cases of multidisciplinary journals, such as Nature and Science) by a paper-by-paper assignment to a field. This percentile-based selection method removes the citation advantage of older published papers relative to recently published ones since papers are weighted against others in the same annual cohort. 

Researchers who published Highly Cited Papers within an ESI-defined field were judged as influential so the production of multiple top 1% papers is interpreted as a mark of exceptional impact.