Category: Diseases, Syndromes and Conditions

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Scientists Reveal how Drug Locks Hepatitis D Virus out of Liver Cells

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Colourised transmission electron micrograph of hepatitis B virus particles (colourised red and yellow). Credit: NIAID and CDC (Transmission electron micrograph image courtesy of CDC; colourisation by NIAID).

Over 12 million people worldwide suffer from a chronic infection with the hepatitis D virus. This most severe viral liver disease is associated with a high risk of dying from liver cirrhosis and liver cancer. It is caused by the hepatitis D virus (HDV), which uses the surface proteins of the hepatitis B virus (HBV) as a vehicle to specifically enter liver cells via a protein in the cell membrane – the bile salt transporter protein NTCP. This cell entry can be prevented by the active agent bulevirtide.

An international research team has now succeeded in deciphering the molecular structure of bulevirtide in complex with the HBV/HDV receptor NTCP at the molecular level. The research results published in the journal Nature Communications pave the way for more targeted and effective treatments for millions of people chronically infected with HBV/HDV.

The entry inhibitor bulevirtide is the first and currently only approved drug (under the drug name Hepcludex) for the treatment of chronic infections with the hepatitis D virus. The active agent effectively inhibits the replication of hepatitis D viruses and leads to a significant improvement in liver function. But the exact mechanism by which bulevirtide interacts with the virus entry receptor on the surface of the liver cells – the bile salt transporter protein NTCP (sodium taurocholate cotransporting polypeptide) – and thereby inhibits the entry of the viruses into the cells was previously unknown.

In order to understand the molecular interaction of bulevirtide and NTCP at the molecular level, the researchers first generated an antibody fragment that specifically recognises the NTCP-bulevirtide complex and makes it accessible for analysis when bound to nanoparticles. This complex was then analysed using cryo-electron microscopy, which allowed to visualise structural details with atomic resolution. The research results represent a milestone in understanding both the interaction of HBV and HDV with their cellular entry receptor NTCP and the mechanism of cell receptor blockade by bulevirtide.

How bulevirtide blocks the cell entry receptor NTCP

The analysis showed that bulevirtide forms three functional domains in the interaction with the HBV/HDV receptor NTCP: a myristoyl group that interacts with the cell membrane on the outside of the cell; an essential core sequence (‘plug’) that fits precisely into the bile salt transport tunnel of the NTCP like the bit of a key into a lock; and an amino acid chain that stretches across the extracellular surface of the receptor, enclosing it like a brace.

“The formation of a ‘plug’ in the transport tunnel and the associated inactivation of the bile salt transporter is so far unique among all known virus-receptor complexes. This structure explains why the physiological function of the NTCP is inhibited when patients are treated with bulevirtide,” says Prof Stephan Urban, DZIF Professor of Translational Virology and Deputy Coordinator of the DZIF research area Hepatitis, in whose laboratory at Heidelberg University the active agent bulevirtide was developed.

“Thanks to the structural details of the interaction with bulevirtide, we have also gained insights that enable the development of smaller active agents – so-called peptidomimetics – with improved pharmacological properties. Our structural analysis also lays the foundation for the development of drugs that are not only based on peptides and possibly enable oral administration,” adds the co-author of the study, Prof Joachim Geyer from the Institute of Pharmacology and Toxicology at Justus Liebig University Giessen.

Evolutionary adaptation of hepatitis B viruses to host species

The structural analysis also helped to decode an important factor in the species specificity of hepatitis B and D viruses. According to the findings of the analysis, the amino acid at position 158 of the NTCP amino acid chain plays an essential role in virus-receptor interaction. A change in the amino acid at this position prevents the binding of HBV/HDV. This explains why certain Old World monkeys, such as macaques, cannot be infected by HBV/HDV.

“Our findings enable a deeper understanding of the evolutionary adaptation of human and animal hepatitis B viruses to their hosts and also provide an important molecular basis for the development of new and targeted drugs,” adds co-author Prof Dieter Glebe, DZIF scientist at the Institute of Medical Virology at Justus Liebig University Giessen.

“Thanks to the structural details of the interaction with bulevirtide, we have also gained insights that enable the development of smaller active agents — so-called peptidomimetics — with improved pharmacological properties. Our structural analysis also lays the foundation for the development of drugs that are not only based on peptides and possibly enable oral administration,” adds the co-author of the study, Prof Joachim Geyer from the Institute of Pharmacology and Toxicology at Justus Liebig University Giessen.

Evolutionary adaptation of hepatitis B viruses to host species

The structural analysis also helped to decode an important factor in the species specificity of hepatitis B and D viruses. According to the findings of the analysis, the amino acid at position 158 of the NTCP amino acid chain plays an essential role in virus-receptor interaction. A change in the amino acid at this position prevents the binding of HBV/HDV. This explains why certain Old World monkeys, such as macaques, cannot be infected by HBV/HDV.

“Our findings enable a deeper understanding of the evolutionary adaptation of human and animal hepatitis B viruses to their hosts and also provide an important molecular basis for the development of new and targeted drugs,” adds co-author Prof Dieter Glebe, DZIF scientist at the Institute of Medical Virology at Justus Liebig University Giessen.

Source: German Center for Infection Research

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International Pompe Day

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Early diagnosis is key to transformative treatment in Pompe disease

Photo by National Cancer Institute on Unsplash

15 April is recognised as International Pompe Day, a time dedicated to increasing awareness about Pompe Disease – a rare, inherited disorder that leads to progressive muscle and heart weakness. The day emphasises global awareness with the message: “Together We Are Strong.”

Pompe Disease is a condition resulting from mutations in a gene responsible for producing acid alpha-glucosidase (GAA), the enzyme necessary for breaking down glycogen, a sugar the body uses for energy.1 These mutations lead to a reduced or absent production of this enzyme, causing an accumulation of glycogen that damages muscles and the heart. The impact of the disease, including its severity and the age when symptoms appear, depends on how much the enzyme’s activity is reduced.1

Pompe Disease is classified into two types2: the infantile form, characterised by severe GAA deficiency and symptoms appearing in the first months of life1, and the late-onset form, where symptoms may start in childhood or adulthood, usually without affecting the heart.1

Early diagnosis is vital for managing Pompe Disease effectively and improving outcomes.2 Kelly du Plessis, CEO and Founder of Rare Diseases South Africa (RDSA), says: “The rise in adult diagnoses stresses the importance of recognising symptoms such as difficulty walking, frequent chest infections, fatigue, muscle weakness, and frequent falls. Symptoms in infants include feeding problems, poor weight gain, breathing difficulties, muscle weakness, an enlarged heart, floppiness, and delayed milestones.”1

Obtaining a Pompe Disease diagnosis can be challenging. Du Plessis’ own path to finding a diagnosis for her son confirms the difficulties of identifying Pompe Disease. “The journey to a diagnosis is fraught with complexity because of the many ways in which the disease presents. I urge parents to trust their intuition and seek medical counsel without delay, as early intervention is critical.”

Although there is no cure for the disease, Enzyme Replacement Therapy (ERT), available since 2006, supplies the body with a version of the GAA enzyme that people with Pompe Disease lack, and has significantly improved outcomes for patients.3

Monique Nel, Medical Advisor for Rare Diseases at Sanofi South Africa, emphasises the importance of early screening and treatment to prevent or minimise complications. “Access to ERT in South Africa has been life-changing for patients, offering improved energy levels and quality of life,” says Nel. “Starting ERT before the onset of symptoms can prevent or slow the progression of the disease. This means patients may experience fewer complications and a slower decline in their condition over time.”

Some of the key benefits of ERT include:

Improvement in muscle function: ERT helps to break down glycogen, preventing its harmful accumulation in muscle cells. Patients often experience improvements in muscle strength and function2, which can enhance mobility and daily living activities.

Enhanced respiratory function: Many individuals with Pompe Disease suffer from respiratory complications due to muscle weakness. ERT can lead to improved respiratory function2, reducing the need for ventilatory support and decreasing the frequency of respiratory infections.

Cardiac benefits: In the infantile form of Pompe Disease, heart enlargement and dysfunction are significant concerns. ERT has been shown to improve heart function2, which can be life-saving for infants affected by the disease.

“By addressing some of the primary symptoms of Pompe Disease, ERT can significantly improve the quality of life for patients,” says Nel. “This includes increased energy levels, reduced fatigue, and the ability to participate more fully in social, educational, and professional activities.”

“We also encourage healthcare professionals to consider Pompe Disease when evaluating patients with muscle weakness, respiratory issues, or unexplained cardiac symptoms, to ensure early diagnosis. Early diagnosis facilitates timely intervention and treatment, optimising patient outcomes and quality of life.”

For more information, visit: www.rarediseases.co.za

References:

1. National Institute of Neurological Disorders and Stroke. Pompe disease. N.d. Available at: https://www.ninds.nih.gov/health-information/disorders/pompe-disease#, accessed 9 April 2024.
2. Bhengu, L, et al. Diagnosis and management of Pompe disease. South African Medical Journal, 2014; 104(4):273-274.
3. Ficicioglu, C, et al. Newborn screening for Pompe disease: Pennsylvania experience. International Journal of Neonatal Screening, 2020; 6: 89.

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Rise in Global Fungal Drug-resistant Infections

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Candida Auris

In a recent study published in Pathogens and Immunity, researchers issue a call to action over how rising antifungal resistance is worsening the problem of invasive fungal infections.

Fungal infections have become more than just Epidemiological data published in Microbial Cell indicates that a rise in severe fungal infections has resulted in over 150 million cases annually and almost 1.7 million fatalities globally.

Skin contact with microorganisms found in soil or on hard surfaces, such as common shower facilities, or exposure to infected pets, can result in fungal infections known as dermatomycoses. Rashes, itching, burning and skin irritation are among the symptoms of fungal infection.

Thomas McCormick and Mahmoud Ghannoum, professors of dermatology at the Case Western Reserve University School of Medicine and affiliated with University Hospitals Cleveland Medical Center, explained extent of the problem. “This is not just an issue that affects individual patients,” McCormick said.

“The World Health Organization has recognised it as a widespread threat that has the potential to impact entire healthcare systems if left unchecked.”

Based on their findings, the researchers issued precautions and a “call to action” for the medical community to help protect people from multidrug-resistant fungi, starting with awareness and education.

“Healthcare providers must prioritise the use of diagnostic tests when faced with an unknown fungal infection,” Ghannoum said.

“Early detection can make all the difference in improving patient outcomes.”

Patients treated with medications to protect the immune system after cancer and transplant procedures are more vulnerable to fungal infections – making them especially more vulnerable to infections from drug-resistant fungi, the researchers said.

The emergence of multidrug-resistant fungal species, such as Candida auris and Trichophyton indotineae, is especially troubling and requires urgent attention, they reported.

In a study recently published in Emerging Infectious Diseases, Ghannoum’s research team and the Centers for Disease Control and Prevention (CDC), detailed a case that demonstrated Trichophyton indotineae, in addition to becoming drug-resistant, was also sexually transmissible.

To address the growing health concern, McCormick and Ghannoum suggest several measures:

  • Increased awareness and education: Raising awareness in the general healthcare setting to obtain a more accurate understanding of the rise of antifungal-resistant infections.
  • Diagnostic Testing: Routine use of diagnostic tests can guide appropriate treatment strategies.
  • Antifungal Susceptibility Testing (AST): Improving insurance reimbursement rates for AST and increasing the number of qualified laboratories with the capacity to perform these tests.
  • Call to Action: Addressing the emerging challenge of antifungal resistance involves concerted efforts from healthcare professionals, researchers, policymakers and the pharmaceutical industry to develop and implement strategies for managing and preventing antifungal resistance.

“The ultimate goal of these measures,” Ghannoum said, “is to improve the quality of patient care by ensuring effective treatment and preventing further escalation of the problem.”

Source: Case Western Reserve University

Categories : Diseases, Syndromes and Conditions

Scientists Find Weak Points on Epstein-Barr Virus

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Photo by National Cancer Institute on Unsplash

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. Study findings were published in the journal Immunity.

Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx.

EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers.

Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis.

There is no vaccine to prevent EBV infection nor a specific treatment.

In this study, investigators examined a viral protein called gp42, which the virus must use to infect B cells. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells.

The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42.

The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42.

Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.

Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas.

The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma.

In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.

If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants.

People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus.

The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note.

Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.

Source: NIH/National Institute of Allergy and Infectious Diseases

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More Stem Cell Donors Needed to Increase the Aplastic Anaemia Survival Rate

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Photo by National Cancer Institute on Unsplash

Despite being one of the rarest blood disorders, Aplastic Anaemia is one of the deadliest, with about 70% of patients having a life expectancy of only one year if untreated.

Among the treatment options available, stem cell transplants offer hope, boasting a 96% survival rate that increases to 100% in children and adults under 40. Unfortunately, however, there are only 76 019 donors on the South African registry, meaning that the chances of Aplastic Anaemia patients finding a suitable match are slim.

“The chances are even slimmer for Black Aplastic Anaemia patients as only 33% of the registry is comprised of Black donors,” says Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa, who explains that a patient’s best chance of a match comes from within their own ethnic group.

Currently, the non-profit organisation is trying to find matching donors for at least seven South African Aplastic Anaemia patients between the ages of seven and 36. Some of these patients, like 21-year-old Kholiwe, have been on the waiting list since as far back as 2020.

During her matric year, she started experiencing symptoms and after being rushed to the hospital following a fainting spell, received the shocking diagnosis. Compounding the situation for the aspiring drama student was the withdrawal of support from her family, leaving her all alone to cope emotionally and financially with the disease. As she waits for a matching donor to be found, Kholiwe now has the challenge of finding permanent employment while simultaneously undergoing medical treatments to keep her alive. Despite these hardships, she remains hopeful about finding a matching stem cell donor. “Kholiwe’s future, and those of other Aplastic Anaemia patients, depends on this,” says Mokomele.

Explaining what Aplastic Anaemia is, she shares that, based on information gathered by DKMS Africa in conjunction with BLOODSA, the condition occurs when our bone marrow stops making enough blood cells. “This can lead to anaemia, a weak immune system, and an increased risk of bleeding and bruising.”

As for the cause of Aplastic Anaemia, Mokomele points out that this is due to bone marrow damage. “While some people are born with compromised bone marrow, others develop this as a consequence of pregnancy, genetic disorders, certain medicines or chemicals, an overactive immune system or viral infections such as HIV and Hepatitis.”

In light of Aplastic Anaemia Awareness Day on 4 March, she encourages all South Africans to familiarise themselves with the symptoms. “These include tiredness; feeling weak; pale skin and tongue; bruising and bleeding easily; rapid heartbeat; trouble breathing; frequent infections; headaches and dizziness.”

Similarly, 10-year-old Mesuli’s experience highlights the challenges faced by Aplastic Anaemia patients and their families. His journey began with drastic weight loss and constant fatigue. The once energetic and always bubbly little boy grew weak and started having severe nose bleeds. That’s when his aunt Nonhle, who is caring for him following the passing of his mother, consulted a doctor. With his illness forcing him to leave school, Mesuli’s new reality consists of going to the hospital every Wednesday for a blood transfusion.

“It hurts to see him in pain because it hurts me too. All I want is for him to grow and live out his dreams. I am begging each South African to think of Mesuli, spread the word and get your family and friends registered to help save the life of my boy. His life hangs in the hands of a perfect stranger,” pleads Nonhle.

Mesuli hopes to one day become a doctor and save lives, the same way he hopes his life will be saved.

“Bearing Aplastic Anaemia Awareness Day in mind, we encourage South Africans to pay close attention to their health and that of their loved ones, especially as the rarity of the disease does not diminish its severity. But, more importantly, we need those who are healthy to register as stem cell donors and save the lives of patients with this deadly disease,” concludes Mokomele.

Register today at https://www.dkms-africa.org/register-now

For more information, contact DKMS Africa on 0800 12 10 82.

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Promoting Access and Equity for People Affected by Rare Diseases

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Photo by Cottonbro on Pexels

The Third Biennial Rare Diseases Conference, Rare X 2024, took place at the Indaba Hotel in Johannesburg from 14 to 17 February, bringing together patients, healthcare professionals, and stakeholders in the rare disease community in a collaborative space to engage on rare diseases and their treatments. As a hub for South African, African, and international participants, the conference provided a platform for the exchange of ideas, offering academic and scientific insights while emphasising the importance of patient, caregiver, and support group experiences.

“The scarcity of genetic specialists, high costs, and limited access to advanced treatments make it challenging to manage rare diseases and congenital disorders in South Africa and on the continent,” said Kelly du Plessis, CEO & Founder of patient support group, Rare Diseases South Africa. “Rare X plays a pivotal role in advocating for the 4.1 million South Africans affected by these conditions, so that they can experience greater recognition, support, improved health services and better overall quality of life.”

Addressing the critical need for medical education programs in low- and middle-income countries,  Prof Christian Hendriksz, extra ordinary Professor of Paediatrics and Child Health at the Steve Biko Academic Unit, University of Pretoria, and extra ordinary Professor of Human Metabolomics,  North-West University, Potchefstroom, spoke about the significant step forward in healthcare equity and the provision of patient support in Africa.

Prof Hendriksz and his team have taken an inclusive and collaborative approach to addressing rare diseases on the continent. Meeting on virtual platforms, he has brought together people from 19 African countries, including clinicians, laboratory staff, and patient organisations. They found that there’s a noticeable lack of understanding about rare diseases among African political leaders, along with many misconceptions. A common belief is that rare diseases either don’t exist or are less important compared to major health issues like TB and HIV. This mindset hinders progress because without proper diagnosis, patients cannot be identified and treated. To change these views, there’s a need for education and awareness campaigns, along with the adoption of strategies that focus on the patients’ needs.

One of the major challenges Prof Hendriksz highlighted is the logistics of sample transportation and the urgent need for diagnostic services that are practical and sustainable. Through specialised training sessions at North-West University and the creation of a comprehensive network, significant advancements are being made in disease awareness, patient support, and diagnostic capabilities.

Looking ahead, Prof Hendriksz aims to enhance diagnostic and support pathways further, prioritising the development of local capacities.

Head Of Research at the Board of Healthcare Funders (BHF), Charlton Murove, explained that the BHF aims to ensure affordable access to healthcare services for all citizens. This is part of a broader initiative to improve the overall health system by establishing key relationships with various stakeholders and focusing on medical screenings and solutions for high-risk populations. The challenge lies in the complexity of conditions and the high costs associated with treatments, particularly for rare diseases. The BHF is exploring innovative solutions to mitigate these challenges, such as the creation of a pooled funding mechanism to smooth out the financial impact of high-cost treatments across participants. This approach aims to enhance efficiency, maintain funds within medical schemes, and ensure equitable access to necessary treatments.

According to Murove, the proposed system would allow for collective bargaining, potentially leading to negotiated price reductions and improved access to care. However, implementing such a system requires navigating legal, financial, and regulatory frameworks and a more cooperative attitude among medical schemes and stakeholders would be needed. The ultimate goal is to ease the financial burden on schemes and patients alike, ensuring sustainable access to critical treatments while promoting fairness and transparency in healthcare funding.

Meliska Volschenk, Head of Payer Solutions and National Accounts at global pharmaceutical company, Sanofi, and a participant in the Rare Diseases Access Initiative (RDAI) which aims to enhance equitable access to care for patients with rare diseases in South Africa, spoke of the need for collaboration across the healthcare spectrum to address the unique challenges faced by rare disease patients, such as life-threatening conditions, the need for specialised care, and often the lack of curative treatments.

“Recognising the significant impact of rare diseases on individuals, families, and the healthcare system, there is an urgent need for a national policy to ensure a coordinated approach to rare diseases,” said Volschenk. “South Africa, like many countries, lacks a comprehensive strategy to address these challenges effectively.”

To tackle the issues head-on, Volschenk said the Rare Disease Initiative (RDAI) has outlined six strategic priorities within a proposed national framework and strategy for rare diseases. These priorities include ensuring early and accurate diagnosis, improving access to treatments, enhancing data collection, providing coordinated care, improving access to services, and boosting collaborative research.

“The RDAI is working to improve healthcare for rare disease patients in South Africa by gradually introducing changes and involving different groups, including health organisations and government departments, in their efforts,” said Volschenk. “We are organising meetings and discussions with these groups to come up with practical changes and new policies aimed at better support and care for patients with rare diseases. This shows RDAI’s dedication to making the healthcare system fairer and more effective for people with rare conditions, ensuring they get the help and treatment they need.”

Overcoming the hurdles of rare disease care requires a united front, comprising healthcare professionals, policymakers, patient advocacy groups, and the pharmaceutical industry, said Prudence Selani, Head of Communications at Sanofi South Africa. The call to action is clear: to embrace a multifaceted approach that includes enhancing medical education, establishing a national policy for rare diseases, and developing a healthcare ecosystem that prioritises patient-centred strategies, affordability, and access to cutting-edge treatments. “That is how we can best contribute to a sustainable and equitable healthcare system for one of the most vulnerable patient groups,” said Selani.

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Researchers Map out Protein Pathways of MND Development

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Spinal neuron. Image by Scientific Animations CC4.0

For the first time, researchers from The University of Queensland (UQ) have mapped out the proteins implicated in the early stages of motor neurone disease (MND). This paper was published in Nature Communications.

Dr Rebecca San Gil, the study’s first author, has developed a longitudinal map of the proteins involved in MND across the trajectory of the disease, identifying potential therapeutic pathways for further investigation. This includes one protein, TDP-43, implicated in a number of MNDs.

“The map is a springboard for many more projects exploring the proteins activated and repressed during the onset, early and late stages of MND,” Dr San Gil said. “These proteins are biological factors that drive disease onset and progress its development over time.

“We measured differences in protein levels in the brain across the trajectory of the disease and collated this information into a longitudinal map.”

The map is now available for scientists worldwide and will accelerate investigations into MND.

Dr San Gil, in the lab of Associate Professor Adam Walker, has been working in mouse models of MND to understand the mechanisms driving TDP-43 pathology in the brain, which accounts for 95% of amyotrophic lateral sclerosis (ALS) cases and 50% of frontotemporal lobar degeneration (FTLD).

Building on the mapping project, Dr San Gil chose to focus on a protein-folding factor called DNAJB5.

“Before the onset of MND in mouse models, we observed a marked increase in protein groups responsible for physically assisting in the protein folding process. “One of these ‘chaperone’ proteins, DNAJB5, was particularly abundant early on, sparking our curiosity about its role in disease progression.

“In human brain tissue, we found DNAJB5 enriched in areas where TDP-43 aggregates. The short-term elevation of DNAJB5 is likely a protective mechanism by neurons in an attempt to control TDP-43 as it begins to dysfunction.

“This protective response to TDP-43 needs further investigation because it may help us identify preventative and therapeutic approaches to MND.”

A/ Prof Walker envisions that the lab will continue to follow other identified protein pathways, using gene therapy and repurposing medicine, to see if they can alter or prevent the disease.

Compiling the TDP map was a collaborative project with researchers from Macquarie University, the University of Auckland, and the Children’s Medical Research Institute.

Source: University of Queensland

Categories : Diseases, Syndromes and Conditions UrogenitalTags :

There is a ‘Worrying’ Resurgence of Sexually Transmitted Infections in Gauteng

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There’s a comeback of sexually transmitted infections (STIs) in South Africa and around the world. The Gauteng Department of Health recently reported an increase of newly acquired STIs, in particular gonorrhoea and chlamydia. This spike in cases call for management guidelines and awareness programmes to be reviewed, reports Ufrieda Ho.

A rise in reported cases of sexually transmitted infections in Gauteng in 2023 is a wake-up call that control and management strategies are not keeping pace with the growing disease burden in South Africa’s most populous province.

“The Gauteng information confirms the rise in STIs that we are seeing in South Africa and across the world, including in the United States and Canada,” said Dr Nomathemba Chandiwana, a director and principal scientist at Ezintsha Research Centre at Wits University. She is also a co-author of the 2022 guidelines on the management of sexually transmitted infections produced by the Southern Africa HIV Clinicians Society.

Chandiwana said any increase in STIs should raise alarms because it means “we simply don’t have control over the things we thought we had under control”.

The World Health Organization (WHO) in 2022 noted that countries reported low coverage for preventive, testing and treatment services related to  STIs, because of Covid-19 lockdown restrictions. The WHO confirmed that this had led to a “resurgence of STIs and the emergence of non-classical STIs [such as Shigella sonnei, hepatitis A, Neisseria meningitidis, Zika and Ebola] globally”. It also reported that currently more than 1 million new STIs are acquired around the world each day “posing a significant global health challenge”.

Since the middle of 2023, the WHO has pushed for low-cost point of care tests to be more readily available in low and middle income countries, saying this would improve screening and diagnosis, data collection and make STI services more effective. South Africa has not made such tests accessible, still relying on a syndromic approach, which is clinical diagnosis made by assessing a patient’s symptoms and other visible signs.

New public health threats

Chandiwana said a review of STI treatment and management guidelines is necessary because the rising numbers pose significant new public health threats. Of particular concern, she said, is that having  STIs pushes up a person’s risk to contract HIV, which is “a chronic and serious disease” as well as developing other long term or irreversible medical risks, including reproductive complications.

Earlier in February, the Gauteng Department of Health reported that the incidence of Male Urethritis Syndrome (MUS) in men aged 15 to 49 in the province had increased from 12% in 2020 to 15% in 2023. The department did not provide actual figures for the comparison, which is also somewhat complicated by the fact that in 2020 there were strict COVID-19 lockdowns and restrictions in place.

The department’s information from 2023 showed that 167 109 males aged 15 to 49 visited health facilities across the province from April to December. Of these patients, 67 400 (40% of the 167 109) were treated for MUS.

The diagnosis of MUS is an indicator of newly acquired STIs, in particular gonorrhoea and chlamydia, which according to the Gauteng Department of Health are the most prevalent STIs in South Africa.

Chandiwana said diagnosis of MUS in men and pelvic inflammatory disease (PID) among women, are made by assessing symptoms of pain, discomfort and genital discharge and sores. Conventionally, it’s treated with broad range antibiotics.

She explained South Africa’s guidelines to treatment and management is to make clinical decisions based on a patient’s symptoms and signs. “While this standard approach has worked, we are calling for a move to targeted diagnosis and targeted treatment. It’s because you want to know which STI someone has and to treat them for that particular disease,” said Chandiwana.

Different STIs can also result in different complications. Syphilis for instance, she said, can result in women giving birth to children who are deaf or blind or raises the risks for infertility. (Spotlight previously reported on congenital syphilis in South Africa in more depth here.)

“We also have STIs that are present but not visible, so asymptomatic STIs, including HPV (human papillomavirus­), which is the leading cause of cervical cancer in black women in South Africa,” Chandiwana said.

“Of course it’s complicated in a public healthcare system where we might not have lab services everywhere, and where there may be lab testing there is a long turnaround for results,” she added.

What to do

It means a multi-pronged approach is still necessary. This she said, has to include a shift from blaming and policing people’s sexual behaviour. Her comments are in response to Gauteng MEC for health and wellness Nomantu Nkomo-Ralehoko’s remarks in the same Gauteng Department of Health press release in which the MEC drew a link between a higher number of women coming forward to be initiated on Pre-Exposure Prophylaxis (PrEP) – an antiretroviral drug prescribed for HIV-negative people to stop HIV infection – and the higher recorded number of STIs. The MEC is quoted saying: “We believe that the high uptake of PrEP among women has led this group to having unprotected sex resulting in high incidence of MUS. The studies have reported that STI incidence is also high among young women receiving PrEP.”

Chandiwana dismissed the conclusion of a causal relationship. “PrEP is a very important tool because it’s something people can take to prevent HIV. But before we had PrEP it was not like people were using condoms – people were using nothing. So I disagree, the uptake of PrEP is not directly involved with the increase of STIs,” she said.

What’s needed instead, she said, is to ask why people are not using condoms more often and why South Africa is not creating STI friendly services that include differentiated care for key populations such as sex workers, men who have sex with men, or people who inject drugs. There should also be more peer navigators, services that are quick, efficient and confidential as well as investment and development of rapid testing kits, she added.

Preliminary findings from the Sixth South African National HIV Prevalence, Incidence, and Behaviour survey released by the Human Sciences Research Council in November indicated that condom use had dropped substantially among young people from 2017 to 2022. It did prompt MEC Nkomo-Ralehoko to call for more uptake of PrEP.  “We would like to encourage more males to get initiated on PrEP to protect themselves against STI. Additionally, both men and women who are on PrEP should use condoms to protect themselves against STIs, HIV and unwanted pregnancies,” she was quoted in the press release.

Role of medical male circumcision

Meanwhile, the NGO Right to Care is promoting voluntary medical male circumcision as another strategy to combat the rise in STI cases. “Uncircumcised men are more susceptible to STIs than men who are circumcised, especially STIs that cause ulcers or wounds,” said Dr Nelson Igaba, senior technical specialist for voluntary medical male circumcision at the NGO.

He described the Gauteng statistics as “worrying” and said it should be read as a prompt for more men to opt for circumcision. The NGO will connect men to their nearest public facility to have the procedure done for free. (They can be contacted at 082 808 6152.)

Dr Tendesayi Kufa-Chakezha, a senior epidemiologist at the Centre for HIV and STIs at the National Institute of Communicable Diseases (NICD), also homes in on the need for more awareness building.

“As a country we are not talking about STIs enough, among ourselves or with our children. More healthcare workers are needed and more training can be made available. We also need a massive campaign to educate communities on the causes of STI syndromes, symptoms, where to get treatment, types of treatments, complications and to go back to facilities if they don’t get better.”

Kufa-Chakezha said South Africa’s STI treatment guidelines do conform with existing WHO guidelines. She said the NICD regularly collects information and specimens from health facilities, which  allows them to determine the most common causes associated with the symptoms that are most commonly seen. The NICD uses these findings to inform the country’s STI management and treatment strategies that are based on diagnosis and treatment of the most prevalent STIs.

“If as a country we are not able to get more people with or without STI symptoms screened and treated, we will continue to have people acquiring STIs, developing symptoms associated with them, becoming ill and developing complications from them,” she added.

Republished from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : Diseases, Syndromes and Conditions Environmental EffectsTags :

Environmental Monitoring Offers Low-cost Tool for Typhoid Fever Surveillance

On By ModernMedia

Detection of the viruses that infect the typhoid fever bacterium in sewage indicates disease burden

Researchers can accurately track where typhoid fever cases are highest by monitoring environmental samples for viruses called bacteriophages that specifically infect the bacterium that causes typhoid fever. Senjuti Saha of the Child Health Research Foundation in Bangladesh and colleagues report these findings in a new study published February 15 in the open access journal PLOS Neglected Tropical Diseases.

Typhoid fever is a common infection in many low- and middle-income countries and causes an estimated 135 000 deaths and 14 million infections globally each year. The World Health Organization has prequalified two typhoid vaccines, but for policymakers to plan effective vaccination strategies, they need accurate, high-resolution estimates of where the burden is highest.

Traditionally, people have cultured the bacterium that causes typhoid fever from blood samples to determine where the infection is most common, but in the new paper, researchers tried a more cost-effective surveillance approach. They tested environmental water samples from sewage and other locations to detect bacteriophages specific to the water-borne pathogen that causes typhoid fever, Salmonella Typhi.

The team tested 303 water samples from two locations in Bangladesh: the urban capital city, Dhaka, and a rural district, Mirzapur. They found that bacteriophages specific for Salmonella Typhi were present in 31% of environmental samples in Dhaka, compared to just 3% of samples from Mirzapur. This corresponds to results from more than 8,400 blood cultures, in which 5% of cultures from Dhaka and 0.05% from Mirzapur tested positive.

The new results suggest that detecting bacteriophages specific for Salmonella Typhi may be a rapid environmental surveillance method that could help decision makers understand the presence of typhoid fever in the community. The researchers propose that environment monitoring of bacteriophage could be a simple, cost-effective and scalable tool to assist policy decisions on typhoid control.

The authors add: “Looking for bacteriophages in wastewater is a low-cost method for identifying typhoid hotspots without doing expensive blood cultures on thousands of people.”

Categories : Diseases, Syndromes and Conditions Medical Research & TechnologyTags :

Rare-X 2024 a Beacon of Hope for Those Living with Rare Diseases

On By ModernMedia
Source: Unsplash CC0

Amongst the intricacies of South Africa’s healthcare landscape, a silent but significant challenge lurks – the prevalence of rare diseases. Behind the curtain of mainstream medical discourse, millions grapple with the complexities of these often overlooked conditions, a stark reality often overshadowed by the glare of more prevalent health concerns. 

With more than 7000 identified rare diseases to date, they affect as many as 4.2 million South Africans, of which 50 – 70% are children1. These conditions are more prevalent than predicted, each posing unique and often debilitating challenges for patients and families alike. 

With 29 February commemorated as Rare Diseases Day, Rare Diseases South Africa (RDSA), is hosting its third biennial rare diseases conference, Rare-X 2024, at the Indaba Hotel in Fourways, from 14 to 17 February. 

More than just a conference, Rare-X 2024 will focus on patient advocacy, education, policy reform, and improving equitable access to ensure better outcomes and support for individuals living with rare diseases.

As the first in-person conference since the COVID-19 pandemic, the event brings together patients, policymakers, academics, government and pharmaceutical companies to discuss the plight of rare diseases and find collaborative ways to improve patients’ lives and treatment efforts. 

The conference will comprise several activities, including keynote speeches by renowned experts in rare diseases; interactive panel discussions; workshops and training sessions; scientific presentations; networking opportunities and policy roundtables. 

Some of the renowned speakers to share their insights and global developments on rare diseases include Prof Alex van den Heever, Chair of Social Security Systems Administration and Management Studies at the Wits School of Governance; Professor Fatima Suleman, Professor in the School of Health Sciences at the University of KwaZulu-Natal; and Professor Chris Hendriksz, Global Clinical Development Lead for Rare Diseases at Nestle Health Science, amongst others. Bringing a wealth of practical experience following his work with health professionals, will be traditional health practitioners (THPs), Mr Elliot Makhathini and Dr Conradie from North-West University’s Centre for Human Metabolomics, to name a few.

A rare disease relates to a condition that is considered rare when it affects one person in 20002. Currently, South Africa does not have its own definition of a rare disease, which is one of the major issues that need to be addressed by the government3.

As a patient-focused non-profit organisation, RDSA was launched in 2013 by CEO and Rare-X Director, Kelly du Plessis. The mother of a child with a rare condition, du Plessis realised the dire need for support for a highly under-acknowledged community, with the organisation advocating that people living with rare diseases and congenital disorders experience greater recognition, support, improved health services, and overall, a better quality of life. 

“Despite the need for increased representation, the rare diseases community remains vulnerable from a medical and policy perspective,” says du Plessis. “As part of our mandate, RDSA brings together international best practice and local medical innovation, driving a collective voice and playing a fundamental role in bridging the gap between vulnerable communities and medical advancement.”

To date, RDSA has successfully launched initiatives that have positively impacted the lives of over 6500 patients including engaging with various governmental departments, organs of state, industry players and strategic stakeholders to raise awareness and move rare disease policy forward.

For more information on the Rare-X conference, kindly visit www.rare-x.co.za 

References:

1. Marhebe, HL. Introducing the South African Rare Diseases Access Initiative. SAMJ. 2023;113(8).

2. Reserved IUA. Orphanet: About rare diseases [Internet]. [cited 2024 Feb 2]. Available from: https://www.orpha.net/consor/cgi-bin/Education_AboutRareDiseases.php?lng=EN

3. FAQs [Internet]. Rare Diseases SA. [cited 2024 Feb 2]. Available from: https://www.rarediseases.co.za/faqs