By measuring the proportions of certain immune cells in the cerebrospinal fluid when diagnosing amyotrophic lateral sclerosis (ALS), it is possible to predict the disease’s speed of progression, according to a study from Karolinska Institutet published in Nature Communications.
ALS is a rare, but fatal disease that affects the nerve cells and leads to paralysis of voluntary muscles and death. This new research offers a way to predict the course of the disease in ALS patients.
Between March 2016 and March 2020, researchers collected fresh blood and cerebrospinal fluid from 89 patients in Stockholm who had recently been diagnosed with ALS, and followed-up until October 2020.
The study shows that a high proportion of so-called effector T cells are associated with a low survival rate. At the same time, a high proportion of activated regulatory T cells indicate a protective role against the rapid disease progression. The findings provide new evidence for the involvement of T cells in the course of the disease and show that certain types of effector T cells accumulate in the cerebrospinal fluid of ALS patients.
“The study could contribute to the development of new treatments that target immune cells to slow down the course of the disease,” says study first author Solmaz Yazdani, a doctoral student at the Institute of Environmental Medicine at Karolinska Institutet.
The next step in her research is to study how T cells contribute to the course of the disease.
“We have plans to collect samples from these individuals to study changes in the immune cells over time. In addition, we want to study effector T cells in more detail to understand their role in ALS.”
A recent phase 2 clinical trial published in Arthritis & Rheumatologyhas reported promising results for deucravacitinib, an oral inhibitor tyrosine kinase 2 (TYK2) inhibitor, in patients with active lupus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by the presence of antinuclear autoantibodies and diverse clinical manifestations. Treatment often lacks efficacy for SLE patients, and current therapies are associated with undesirable side effects.
TYK2 is an intracellular kinase that mediates signalling of key cytokines involved in the pathogenesis of SLE. A biologic agent targeting the type I interferon (IFN) receptor has been approved in SLE. Deucravacitinib is an oral, selective, allosteric inhibitor of TYK2 that binds the regulatory domain and locks the enzyme in an inactive state distinguishing it from JAK inhibitors that bind the highly conserved active domain
For the trial, adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomised 1:1:1:1 to receive deucravacitinib 3mg twice daily, 6mg twice daily, 12mg once daily, or placebo. The primary endpoint was SRI-4 and secondary outcomes were assessed on a variety of disease activity measures.
At week 32, the percentage of patients experiencing benefits was 34% with placebo compared with 58%, 50%, and 45% with the respective deucravacitinib regimens.
Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported.
Some cases of tuberculosis (TB) can be successfully treated in as little as two months – a third of the current standard of six months in South Africa and most other countries. This is according to early findings from the landmark TRUNCATE TB trial presented at last week’s Union World Conference on Lung Health.
Nick Paton, a professor of Infectious Diseases at the National University of Singapore and the chief investigator of the TRUNCATE trial, explains that the standard six-month treatment for drug-susceptible TB (DS-TB) is actually overtreating a lot of people who have the disease. The reason for the six-month mark for TB treatment is that a minority of TB patients need the long treatment regimen to avoid relapse, but the majority would be cured before the six-month mark.
Essentially, it’s a blunt, but generally, effective instrument used to protect a minority of TB patients.
The TRUNCATE trial set out to see if a two-month (eight weeks) novel combination of TB regimens would be feasible when compared to the standard six-month (24 weeks) treatment regimen. According to Paton, trial participants in the experimental arms of the study were initially given eight weeks of treatment, with the option of extending treatment to 10 to 12 weeks if they had persistent clinical disease after the eight-week treatment. If there was still active TB after that, participants were switched to the standard six-month treatment.
Study participants were monitored regularly through follow-up visits, which included TB symptom screening once a month and sputum smear tests every one to three months.
“The core [of the strategy] is it’s a very short period of initial treatment, plus you then do the monitoring and pick up people [who relapsed] early,” Paton says.
A total of 674 trial participants were recruited from March 2018 to March 2022 across 18 sites in Thailand, Indonesia, the Philippines, Uganda, and India. Four patients withdrew from the trial and 10 participants died during the trial.
Paton tells Spotlight that the overall death rate was low and there was no difference in the death rate between the standard treatment arm and the TRUNCATE strategy arms. The causes of death were mixed, he adds, and often the precise cause was unknown
For the final results, 660 participants were evaluated at week 96. In other words, about two years of follow-up occurred.
Encouraging results
Paton explains that the trial used the TRUNCATE strategy, which initially involved using four treatment arms containing a novel combination of TB drugs and comparing the results to a control arm consisting of the standard six-month treatment. Later, two TRUNCATE strategy arms were selected to complete the latter half of the study. He notes that it was a pragmatic decision to stop two of the arms, to ensure better data.
“You do substantially cut down the amount of time on treatment overall.”
Professor Nick Paton, chief investigator of the TRUNCATE trial.
In the first of the two remaining experimental arms, 184 study participants received a regimen consisting of high-dose rifampicin (35mg per kg, reduced to 20mg per kg as a precaution following a liver injury-related death), isoniazid, pyrazinamide, ethambutol, and linezolid (600mg). In the second, 189 study participants received a regimen consisting of bedaquiline (400mg/d for two weeks then 200mg three times a week), isoniazid, pyrazinamide, ethambutol, and linezolid (600mg). The standard treatment arm had 181 participants.
In the standard treatment arm, 98% completed treatment and 3% had to be re-treated before week 96.
In the TRUNCATE strategy arms, overall, 91% completed the eight-week treatment and stopped treatment by week 12. 17%, (ranging from 13 to 23% by arm) had re-treatment, and 2% of participants did not complete initial treatment due to withdrawing from the trial, death, or defaulting on treatment.
A comparison of the two experimental TRUNCATE arms with the standard treatment arm showed that the TRUNCATE arm with bedaquiline and linezolid was non-inferior to the standard treatment arm, while the high dose rifampicin and linezolid arm fell just short of meeting the non-inferiority criteria. Efficacy was calculated based on the proportion of unsatisfactory outcomes at week 96. Unsatisfactory outcomes were classified as death, still having active TB, or still being on TB treatment at week 96.
“The idea was that if we added those [unsatisfactory outcomes] up and that was the same in the standard treatment arm as the TRUNCATE strategy arm then that shows that this strategy in principle, can work,” Paton tells Spotlight.
The mean total days on treatment were reduced in the TRUNCATE strategy arms when compared to the standard treatment arm, which was 180 days. For high-dose rifampicin-linezolid, the average total days on treatment was 106 days, and in the bedaquiline-linezolid arm, it was 85 days.
“So, clearly the net effect is to decrease the average time on treatment,” Paton says. “You do substantially cut down the amount of time on treatment overall.”
He adds that the proportion of participants that had Grade 3 or 4 adverse events, serious adverse events, or who died did not differ between the standard treatment arm and the TRUNCATE strategy arm. The proportion of participants with respiratory disability at week 96 also did not differ.
The only cases of acquired drug resistance were two cases observed in the bedaquiline and linezolid arm. This is a frequency of 1.1% according to Paton. One of these participants missed several treatment doses, while the other did not miss any doses. Both were successfully re-treated.
Initially, they wanted to enroll participants who were co-infected with HIV in the later stages of the trial, but none could be enrolled in time, so currently there is no data on how well it works in people living with HIV who also have TB, says Paton.
“The trial has shown that alternatives to systematically over-treating the large majority of people with TB can be successful. This is an important new research direction which has the promise to improve outcomes for patients and programmes,” Paton says. “The strategy may be refined in future to improve outcomes using alternative drug regimens or alternative approaches to monitoring. Ongoing analysis from the trial will further enhance our understanding.”
PK and safety data
At last week’s conference, Christopher Cousins, project leader of the TRUNCATE trial presented the first level of pharmacokinetic (PK) analysis from the trial. The PK results were taken from week eight of the study.
AUC for the high-dose rifampicin was four to six times higher than in the standard dose and exceeded the proposed efficacy targets in the majority of patients.
After fasting overnight, participants took an observed dose of their medication at the trial site and had blood sampling done over a 12-hour period. The data is based on 96 participants in the two experimental arms.
He says the AUC (which represents total drug exposure over time – AUC = area under the curve) for the high-dose rifampicin was four to six times higher than in the standard dose and exceeded the proposed efficacy targets in the majority of patients. This supports the hypothesis that high-dose rifampicin would enhance treatment sterilisation in the eight-week regimen.
The data also showed what seems to be a drug-drug interaction between rifampicin and linezolid, but this didn’t appear to be significant enough to abolish anti-mycobacterial efficacy.
According to Cousins, the bedaquiline concentrations at the end of week eight in the bedaquiline and linezolid arm were comparable to the concentrations seen after 24 weeks of treatment for drug-resistant TB (currently both bedaquiline and linezolid are part of the standard treatment for DR-TB, but not for DS-TB).
When asked how well monitoring participants in the TRUNCATE arms after they stopped treatment was able to detect those who still had active TB disease, Paton tells Spotlight that further analysis of the sputum smears samples will be able to tell us more. The trial used a relatively low-technology approach where a symptom screening and a sputum smear test were used to determine if a participant still had active TB and needed to be re-treated.
“We need to run additional biomarkers, interrogate the data set in more detail to figure out who was cured, who wasn’t cured, over what duration and how well do these other things [sputum smear test and symptom screening] pick it [TB] up,” he says.
He adds that this was a starting point, “but we are likely to be able to do better if we use some of the new biomarker technologies for monitoring”.
Implications of findings
“These results are very exciting as proof of concept – they show it’s possible to shorten treatment for drug-sensitive TB even further,” says Lindsay McKenna, TB Project Co-Director at New York-based Treatment Action Group (TAG). “But we need to optimise the regimen and study this treatment strategy in broader populations, including people living with HIV – none were enrolled in the study – and [in] programme contexts,” she says.
“There are other trials that are being planned that look to proactively (for example, at time of treatment initiation) determine who might benefit from shorter versus longer treatment based on available indicators or risk factors known to be correlated with treatment outcomes, such as disease severity, BMI, and HIV status (called a stratified medicine approach), and to tailor the duration of treatment accordingly,” she adds. “If the latter stratified medicine approach is proven, it will be very interesting to see how these two approaches compare and are viewed by programmes and affected communities.”
Feasibility of shortened regimens
Nerissa Donato the site co-investigator for the Truncate TB trial from the Lung Centre in the Philippines outlined the feasibility and acceptability of the TRUNCATE strategy at last week’s conference. This was based on participant questionnaires, clinician surveys, description data from the trial, and observations from Donato.
“The TRUNCATE strategies were acceptable and feasible in the context of the clinical trial. It can be successfully implemented provided that it is supported by the NTP (national treatment programme) and embraced by trained clinicians,” she says.
She explains the main challenges to implementing the strategy were patients’ concerns about potential side effects and the greater pill burden, but after some discussion participants were comfortable with the regimen due to the possibility of a much shorter treatment regimen. The close following up of participants and follow-up visits required was different from the normal procedure of treating for six months and being discharged from care. But she says participants were generally happy to come back for the follow-up visits.
Clinicians who participated were initially sceptical of whether the regimen was safe and would work but after the trial, they had a more positive view, according to Donato.
She says that in order to implement the strategy in the real world, it would need to be adopted by the NTPs, which will likely require more data on cost-effectiveness.
Need better treatment approaches and regimens
Paton tells Spotlight that somewhere between the two extremes of overtreating TB patients and personalised medicine as seen in high-income countries, there can lie a better treatment option for TB patients. An approach that is less monolithic and instead based on reacting to individual patient needs and responses.
“We need to look at how do we personalise it [TB treatment], but in a way that’s not so high tech so it becomes impossible for programmes,” he says. “At least if you’re monitoring [patients] you’ve got a safety net. If you get it wrong, you just make sure you pick the person up early and re-treat and there shouldn’t be serious harm from that.”
Additional data from the trial will be released in the coming months.
Figure 1. The epidemiological curve of measles outbreak cases, Greater Sekhukhune and Mopani Districts, Limpopo province, September to November 2022 (*Two sporadic cases in Vhembe District are not included). Source: NICD
As of 10 November, the National Institute of Communicable Diseases reported 35 laboratory-confirmed measles cases in Limpopo, with 14 new cases on 8 and 9 November, all in Mopani district. Thus far, most of the laboratory-confirmed cases (25 of 35) fall within the 13 month to 9 year age range.
With these new cases, the Mopani district with 19 cases has overtaken the Greater Sekhukhune district which remains at 16 (see Figure 1). Only seven cases are known to be vaccinated; eight are either unvaccinated or partially vaccinated; vaccination status of the remaining 20 is unknown.
According to a recent study published in BMC Public Health, measles has been experiencing a resurgence in South Africa. Over 2015–16, measles had remained largely under the elimination target of under one case per million in South Africa, but rose above this threshold from 2017–2019. Cases fell below the threshold in 2020 with the onset of COVID, but the pandemic also saw normal vaccination efforts slipping. The article authors also noted a measles vaccine effectiveness of only 80% among 1–4 year olds, compared to the 95% rate found in large datasets.
Those cases reported in the Mopani district were in the Greater Giyani, Ba-Phalaborwa, and Ga-Kgapane sub-districts. Epidemiological investigations showed that in the Mopani district, two siblings with measles infection had contact with cases in the Greater Sekhukhune district when they travelled there for a family funeral.
While two cases were reported in Vhembe District, they were considered sporadic as they had not links to the other cases and are not included in the outbreak tally.
The laboratory-confirmed measles infections have been identified in 19 males and 16 females ranging in age from 6 months and 24 years in the Greater Sekhukhune district, while cases range from 2 to 42 years in the Mopani district (Table 1), with increasing cases in the 5–9 year age range. Two children were hospitalised but no deaths or other complications from measles have been reported.
According to the NICD, the affected districts are continuing with the public health response activities and tracing and vaccinating contacts. Measles catch-up doses are also being given to children who have missed vaccinations.
One dose of a new monoclonal antibody safely protected healthy, non-pregnant adults from malaria infection during the malaria season in Mali. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published in The New England Journal of Medicine.
The only WHO-recommended vaccine against vaccine, RTS,S (Mosquirix), provides partial protection against clinical malaria during the early years of life when given to children aged 5 to 17 months in four doses over a 20-month period. Other drugs consisting of small chemical compounds that effectively prevent malaria infection are also available for infants and young children as well as travellers. The requirement for frequent dosing of these drugs can limit adherence, however, and the emergence of drug resistance may also limit their usefulness. Thus, there is an urgent need for new, fast-acting, infrequently dosed interventions that safely provide strong protection against malaria infection.
Malaria is caused by Plasmodium parasites, which mosquitos inject into into the skin and bloodstream in a form called sporozoites. These travel to the liver, where they mature and multiply before spreading throughout the body via the bloodstream to cause illness. P. falciparum is the Plasmodium species most likely to result in severe malaria infections, which, if not promptly treated, may lead to death.
The Phase 2 NIAID-USTTB trial evaluated the safety and efficacy of a one-time, intravenous infusion of a monoclonal antibody called CIS43LS. This antibody was previously shown to neutralise the sporozoites of P. falciparum in the skin and blood before they could infect liver cells. Researchers led by Robert A. Seder, MD, isolated a naturally occurring form of this antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream.
The study team for the Phase 2 trial enrolled 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum transmission typically occurs from July through December each year.
The first part of the trial assessed the safety of three different intravenous doses of CIS43LS – 5mg/kg of body weight, 10 mg/kg and 40 mg/kg – in 18 study participants, with six participants per dose level. The study team followed these participants for 24 weeks and found the antibody infusions were safe and well-tolerated.
The second part of the trial assessed the efficacy of two different doses of CIS43LS compared to a placebo. Three hundred and thirty participants were assigned at random to receive either 10mg/kg of the antibody, 40mg/kg, or a placebo by intravenous infusion. No one knew who was assigned to which group until the end of the trial. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.
The investigators analysed the efficacy of CIS43LS two ways. Based on the time to first P. falciparum infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.
“These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women,” Dr Seder said. “We hope monoclonal antibodies will transform malaria prevention in endemic regions.”
Dr Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, that is much more potent than CIS43LS and therefore can be administered in a smaller dose as a more convenient subcutaneous injection. An early-phase NIAID trial of L9LS in the United States found that the antibody was safe and prevented malaria infection for 21 days in 15 out of 17 healthy adults exposed to P. falciparum in a carefully controlled setting. Two larger, NIAID-sponsored Phase 2 trials assessing the safety and efficacy of L9LS in infants, children and adults are underway in Mali and Kenya.
Scientists investigating why people who have had shingles have an increased stroke risk now believe the answer lies within, exosomes, lipid vesicles called that shuttle proteins and genetic information between cells. Their study, published The Journal of Infectious Diseases, details the mechanisms behind the link between shingles and strokes.
“Most people know about the painful rash associated with shingles, but they may not know that the risk of stroke is elevated for a year after infection,” said the study’s lead author Andrew Bubak, PhD, assistant research professor in the Department of Neurology at the University of Colorado School of Medicine. “Importantly, the rash is often completely healed and individuals feel normal but nonetheless are walking around with this significant elevation in stroke risk.”
Herpes zoster (HZ) or shingles is caused by the varicella zoster virus which causes chicken pox. The virus lingers in the ganglionic neurons and can reactivate, causing excruciating pain. But researchers have found that shingles can also increase the risk of stroke especially for those under age 40 where the shingles vaccine is not typically recommended.
The risk is greatest in people with the rashes on their faces, perhaps due to the proximity to the brain.
To better understand how this works, Bubak and his team began looking more closely at exosomes.
“Exosomes carry pathogenic cargo that can cause thrombosis and inflammation distant from site of actual infection,” Bubak said. “That could ultimately lead to a stroke in patients.”
Researchers collected plasma samples from 13 patients with shingles and 10 without. The samples were taken at time of infection and at 3-month follow-ups for a subset of patients and exosomes were extracted from the plasma.
The researchers found prothrombotic exosomes which could cause blood clots in those with the infection. They also discovered proinflammatory exosomes that also pose risks for stroke at the 3-month follow-up.
Bubak said the findings suggest that in a subset of people with shingles, the virus may not return to latency or the circulating exosomes that induce a prolonged prothrombotic state may persist even after therapy is done and the rash is gone. He said using antiviral agents longer with the addition of antiplatelet and anti-inflammatory agents could help.
“As well as initiatives to increase HZ vaccine uptake to decrease stroke risk, particularly in individuals with known preexisting stroke risk factors,” said Bubak. “If these findings are confirmed with a larger longitudinal study, then this could change clinical practice.”
Most physicians are unaware of the connection between shingles (which has an effective vaccine) and stroke.
“But it’s really important and so easily mitigated,” Bubak said. “Send them home with antiplatelet agents.”
The award was based on strides made by ASASA towards improving the quality of life of people living with AxSpa, as well as training done to build awareness in the medical fraternity around AxSpA in the country. With 36 posters entered into the awards by organisations across the globe, ASASA came out tops.
When asked about the award, van Dam said, “This was a real honour to represent South Africa at PARE. 2022 is also the first year that an African country was invited to attend PARE. Winning this award sheds light on our country and our unique problems. The delay to diagnosis of 10.8 years is just unacceptable. The access to the correct medication in both the private and public sector is also not sufficient for a debilitating, progressive disease that can lead to disability if left untreated.”
ASASA estimates that there are approximately 160 000 people suffering from the AxSpA in South Africa, with many of these sufferers undiagnosed. ASASA has made significant strides this year in the training of over 100 General Practitioners and over 250 optometrists around AxSpA diagnosis and the effects it can have on other parts of the body, like the eyes. In addition, ASASA, along with other partners, assisted in gathering data from South African respondents in the first ever live patient survey, called the International Map of Axial Spondyloarthritis (IMAS) survey, which is run by the Axial Spondyloarthritis International Federation that surveys people diagnosed with AxSpA and assesses the impact and burden that AxSpA has on the lives of patients, from their perspective.
Van Dam concluded, “There is still a lot we can do in South Africa and ASASA is busy growing its team of volunteers to help to build awareness around AxSpA in the country. We aim to continue to build support structures for patients in the country, as well as continually working with the medical fraternity, assisting with early diagnosis and access to treatment.”
Haemophilia A, the most common severe form of haemophilia, affects almost exclusively males and can usually be with factor VII injections, but not for all sufferers, as the immune system may treat the factor as an intruder. New research has uncovered an important immune mechanism that targets B cells, which is crucial in making the the therapy effective. The study is published online in the Journal of Clinical Investigation.
Haemophilia A patients have a defect in factor VIII, a protein key for clotting. Most patients therefore receive an intravenous injection of the functional clotting factor every few days as treatment. But frequently, and especially at the start of treatment, the immune system recognises the injected agent as foreign to the body and attacks it. This is the most serious complication of haemophilia treatment because factor VIII can then no longer work.
In these cases, immune tolerance therapy, which was also developed at the University Hospital Bonn (UKB) more than 40 years ago, often helps. This involves regularly injecting the haemophilia sufferers with a high dose of factor VIII over several months, letting the immune system learn to tolerate it. The underlying immune mechanisms are unknown. “However, this doesn’t always work,” explains Prof Dr Johannes Oldenburg at the UKB. “In about 30 percent of patients, tolerance induction does not lead to success. So your body’s own defences continue to attack and destroy the factor VIII protein, which means that factor VIII cannot be used for treatment. We wanted to know the reason for this.”
To this end, the team looked at two cell types in the immune system, B cells and regulatory T cells. B cells recognise foreign molecules in the body and produce antibodies against them, which switch off the function of the molecule. For factor VIII, this means that it is no longer effective in haemophilia treatment.
Brake in the immune system
Regulatory T cells moderate the strength and duration of the immune response. The researchers have now found a new type of Treg cell that can act specifically against certain B cells rather than the overall immune response. “We were able to show that immunotolerance therapy results in the generation of regulatory T cells that exclusively induce B cells against factor VIII to commit suicide,” says Dr Janine Becker-Gotot of the Institute of Molecular Medicine and Experimental Immunology (IMMEI) at UKB. “These T cells have a sensor that allows them to recognise and attach to the corresponding B cells. In addition, they have the ability to push the self-destruct button on the surface of B cells.”
This button is a molecule called PD-1 which, on activation, leads to apoptosis. Every active B cell has this button. “Our experiments enabled us for the first time to detect regulatory T cells that can activate this self-destruct button only in very specific B cells, in order to specifically prevent unwanted immune responses,” explains IMMEI Director Prof Dr Christian Kurts.
The more PD-1 buttons the B cells against factor VIII carry on their surface, the easier it is for them to be driven to suicide by immune tolerance therapy. “The amount of PD-1 varies from person to person,” Becker-Gotot explains. “If it’s very low to begin with, there’s a good chance that many inhibitor-producing B cells will survive and continue to neutralise the injected factor VIII.”
Test to show in whom immunotolerance therapy is useful
Interestingly, B cells also produce more PD-1 once they come into contact with regulatory T cells. “We can now test how strong this reaction is,” the researcher says. “If PD-1 levels go up shortly after starting immune tolerance therapy and then stay up, that’s a clear sign that the treatment is going to be successful.” The team is currently developing a blood test that can be used to detect whether or not immune tolerance therapy is working in patients during the prolonged treatment.
“Our findings have great basic scientific value,” explains Prof Kurts. “And not just for haemophilia, but also for other congenital disorders where missing proteins are replaced therapeutically. In the long term, they could also be used to develop new treatments.”
Since 11 October 2022, the National Institute for Communicable Diseases (NICD) seven measles cases have been detected in Greater Sekhukhune District in Limpopo province within 30 days, as of 21 October.
Infected individuals ranged from 9 months to 24 years. One child was fully vaccinated for measles, with two measles doses given in 2019. One child was unvaccinated, and the other five measles cases had unknown vaccination history. One measles case was hospitalised while one other had a complication that led to pneumonia.
District and provincial health officials have started a public health response. This includes enhanced surveillance for measles, contact tracing, screening for suspected cases using a case definition followed by collection of blood and throat swabs for measles diagnostic testing, and reviewing medical records to pick up missed cases. Vaccinations are underway for those exposed to suspected or confirmed cases.
The measles immunisation coverage data for the Greater Sekhukhune district showed a decrease of 87% to 64% for measles dose 1 and 86% to 60% for measles dose 2 from 2017 to 2022. This is below the 95% coverage needed to achieve herd immunity. A survey is being done to validate the vaccination data provided to the province and investigate factors that might be contributing to the measles outbreak. Community awareness and health promotion by healthcare workers is continuing in the district to inform the public about the spread of measles and interventions to prevent disease. Measles vaccination has been initiated for children under 15 years to increase the measles immunity in the community and to prevent further spread of measles.
Clinicians should continue to be on the alert for measles cases, especially in Limpopo Province, as large measles outbreaks are occurring in sub-Saharan Africa, including in neighbouring countries.
Signs and Symptoms
Measles is a highly contagious disease caused by a virus of the paromyxovirus family. Patients with measles present with fever and a rash. The rash looks like small, red, flat spots over the body. The rash does not form blisters, nor is it itchy or painful. Other signs include cough, conjunctivitis and coryza. Complications of measles can include diarrhoea, dehydration, encephalitis, blindness and death. Other measles complications are pneumonia, scarring of the cornea (kerato-conjunctivitis), and rarely encephalitis. Complications are more serious in very young children (under 2 years) or who are malnourished.
Clinicians and caregivers should check children’s road-to-health booklets to ensure measles vaccinations are up to date. Suspected measles cases should be notified on the NMC system. Click here to access the Case Notification form
Researchers in the American Journal of Epidemiology report that wastewater surveillance of diseases that infect humans should work in most cases. But more research is needed to apply the science for public health benefit, the research team concluded.
Led by epidemiologist David Larsen from Syracuse University, the team’s work published examined all peer-reviewed scientific articles of wastewater surveillance published through July 2020. The team identified a variety of pathogens that can be found in wastewater, including almost all infectious diseases that the World Health Organization has classified as a Public Health Emergency of International Concern (PHEIC) such as Ebola virus and Zika virus.
But despite this positive finding, few studies relate what is found in the wastewater to public health and the amount of disease that is circulating.
“Testing the wastewater is only one component of this powerful science,” said Dr Larsen, an associate professor of public health at Syracuse University. “Understanding the results and implications for public health is just as challenging. We need interdisciplinary teams working together to maximise the benefit of wastewater-based epidemiology.”
Wastewater-based epidemiology is the science of taking what is found in wastewater and using that information to understand population-level health trends. Most of the articles reviewed looked at what they could find in the wastewater and omitted the second step of relating the findings to other measures of population-level health, such as numbers of cases, test positivity, or hospitalisations.
Wastewater-based epidemiology of COVID has enjoyed substantial availability of clinical COVID data, and results from wastewater surveillance are more easily understood in terms of COVID transmission. However, the research team determined that more work is needed to be done for other pathogens, including monkeypox and polio, to increase the utility of wastewater surveillance to benefit public health.
