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Daily Maverick
8 hours ago
- Health
- Daily Maverick
After US funding cuts, Mozambican children died — who bears responsibility?
Last month, Spotlight and GroundUp published a two-part exposé showing how US aid cuts led to the deaths of children in Mozambique. Here, Jesse Copelyn considers what led to this tragedy and who should bear responsibility for it. After the US Agency for International Development (USAID) abruptly terminated billions of dollars in overseas aid grants, the health system in central Mozambique was left in tatters. Earlier this year, I travelled to two badly hit provinces of the country to describe the toll. In one article, I reported how thousands of orphaned and vulnerable children in Sofala province had been abandoned by their USAID-funded case workers. Many of these children are HIV-positive and had relied on case workers to bring them their medicines or accompany them to hospital. Without them, some children stopped taking their treatment and died. In a second piece, I reported how USAID had cut funding for contractors transporting medicines and diagnostic tests to health facilities in Manica province. This led to shortages of HIV drugs at hospitals in the area, which also led to the deaths of children. Amid all this chaos, I was often curious to know from people on the ground who they held accountable for this situation and who they believed needed to solve the problem. My assumption was that they would call for the Mozambican government to help them out. I was surprised to find that in the affected villages which I visited, this was far from anyone's expectation. In fact, for most it was simply unthinkable that their government could do anything to save them. 'You mentioned the government,' one community leader said after I asked whether the state should intervene. 'But even these chairs we're sitting on are stamped with USAID logos. So what help can we expect from the government?' Indeed, the more I learnt about governance in Mozambique, the more understandable this attitude became. Throughout the country, core government functions have been outsourced to a combination of foreign governments, aid agencies, interstate bodies and private companies. For instance, many of the country's essential medicines are procured by a large international financing body called the Global Fund to Fight Aids, Tuberculosis and Malaria. Up until January, the transportation of these medicines to hospitals was overwhelmingly financed by US aid agencies, as were the paycheques of many health workers. Outside of the healthcare sector, the story is similar. The main highway that I travelled along to reach different villages was built and paid for by Chinese corporations and banks. To keep hydrated I relied on bottled water supplied by private companies since the taps either didn't run or produced contaminated water. In many of the impoverished rural settlements that I visited, there was virtually no state infrastructure, and people received no financial support from the government. Instead, they primarily depended on aid organisations. The country's national budget has historically been heavily supplemented by foreign bodies, including the International Monetary Fund (IMF) and European Union. (Though much of this support was suspended in 2016/17.) Even national defence has been partially outsourced. When Islamist militants began rampaging through the northern province of Cabo Delgado, the government struggled to contain it and contracted Russian and South African mercenary groups. When that failed, they authorised a military intervention by the Southern African Development Community (SADC) and invited a parallel mission by the Rwanda Defence Forces. It is thus no surprise that Mozambicans have virtually no expectation that their own government will come to the rescue when facing an emergency. Instead, they look outward. As one community leader in a rural village told me, 'Here, we depend on Trump.' Cash-strapped and corrupt Mozambique has 35 million people. About 2.5-million live with HIV, the second-highest HIV-positive population in the world after South Africa. Life expectancy is well under 60. The country is extremely poor: eight in 10 people live on less than $3 per day. The government is also deeply cash-strapped. The South African government spends 10 times more per citizen than the Mozambican government does. A large chunk of its spending goes towards paying off debt. At present, Mozambique simply doesn't have the money to build an effective health system, though had it spent its limited budget reserves more effectively over the years it could have developed a health system that was at least a bit more independent of donor support. Instead, the country's budgetary resources have often been wasted on corruption. Mozambique currently ranks 146th out of 180 in the world on Transparency International's Corruption Perceptions Index. This has directly played a role in its public health woes. One clear example of this is the Tuna Bonds scandal, in which state-owned companies took out $2-billion worth of loans, backed by secret state guarantees. This was supposedly to finance large fishing and maritime security projects. In reality, much of the money was siphoned off to enrich political elites, including the then-finance minister (who is now in prison). As a result of those decisions the country was swallowed by debt. And when the extent of the corruption was publicised in 2016, the IMF pulled its financial support for Mozambique. A detailed 2021 report found this directly led to a fall in economic growth and government spending. It states: 'Comparing the three-year average of 2016-18 to the three previous years, spending on health and education fell by USD 1.7 billion – entirely due to the debt.' The country's governance crisis is further demonstrated by the political unrest that engulfed the country after the October 2024 elections, triggered by accusations of election fraud. The accusations are likely to have been overblown, but international observers said the election was not free and fair. Even during the brief week I spent in central Mozambique, signs of corruption and mismanagement filtered into my interactions with officials. For instance, before I embarked on a multiday tour of one province, government officials told me that someone from the provincial health department would need to accompany me on my trip. This was apparently to make formal introductions to district-level officials that I hadn't asked to meet. For this apparently vital service, the man would need to be paid a per diem of roughly R500 a day for two days, they said. The civil servant in question was a very senior person in the provincial health department. Despite facing a collapsing health system in the wake of the US cuts, he was apparently ready to drop everything he had going for the rest of that week to follow me around. When I explained that I wouldn't pay a government official to stalk me, I was told that saying no wasn't an option. This is unfortunately the way things are done around these parts, said a local who helped arrange the tour. (Neither GroundUp, Spotlight nor I paid the bribe, incidentally.) US responsibility Against this backdrop, it is perhaps no surprise that defenders of the current US government have often resorted to arguments about moral responsibility when justifying the decision to abruptly slash aid. It is reasonable to ask why the American taxpayer should bear any of the brunt of Mozambique's public health system when so many of its problems have been caused by the Mozambican government itself. But it's not so simple. The Mozambican civil war from 1977 to 1992 destroyed the country. The anti-communist Renamo insurgency likely received millions of dollars of support from US evangelists, despite committing numerous atrocities. It is strongly suspected that the US government also materially supported Renamo. So the US's involvement in Mozambique has not been innocent. It could be argued that its aid spending was the least the US could do to make amends for its role in the war. Moreover, Mozambique didn't develop its high level of dependency in isolation. For more than two decades the US actively took responsibility for core functions of the country's health system. Up until January, the US government continued to sign numerous contracts with local organisations, pledging millions of dollars to help run life-saving health programmes for years into the future. The health system was consequently built around these commitments. If the US was going to take that much responsibility for the wellbeing of some of the world's most vulnerable people, then it had a duty to at least provide notice before pulling the plug. Instead, it chose to slash the funds instantly, and in a manner that needlessly maximised damage and confusion. Stop-work orders were issued overnight which required that people who were doing life-saving work down their tools immediately. Organisations decided to adhere to these instructions rigidly in the hope that their funding would be reinstated. At that point the Trump administration said it was only pausing aid funding pending a review, and no one wanted to give the reviewers a reason to terminate their programmes. The consequence was complete chaos. Orphaned children in extremely rural parts of Mozambique waited for their case workers to bring them their medicines, but often they simply never came. Many of these children had no idea why they had been abandoned. When certain case workers decided to defy the stop-work order and continue their work voluntarily, they were forced to do so in secret. To add fuel to the fire, the Trump administration routinely provided contradictory information to its former recipients and to the public. The initial executive order signed in January said all foreign development assistance would be suspended for 90 days, pending a review, and might be restored after this time. Then, Secretary of State Marco Rubio issued a waiver which stated that the suspension wouldn't apply to life-saving humanitarian services. Rubio told the public that organisations providing these life-saving services could instantly resume their work under this order. Yet the organisations themselves received different instructions from their USAID officers. Rather than immediately continuing their work, they were told to submit revised budgets that only covered life-saving services and to wait for approval. Organisations rushed to submit these budgets by the deadline. But in the end, the green light never came and their funds remained frozen. This was not only the case in Mozambique; researchers estimated that virtually no funds were released under Rubio's waiver globally. In the meantime, Rubio stated that organisations that hadn't resumed life-saving activities were clearly unable to understand instructions or were simply trying to make a political point. Later on, the organisations received explicit termination notices, ending their programmes. Despite this, US embassies and several large media outlets continued to reference Rubio's order as if it was actually implemented en masse. Even as I write this, the on-again, off-again US aid story is unfinished. This mixed messaging created an enormous amount of confusion for staff of these organisations and the recipients of their work, ultimately for no clear benefit to the American people. There was simply never any reason to act this callously towards health organisations to whom USAID had pledged its support. In contrast to the rampant corruption which has plagued the Mozambican government, these organisations were heavily audited in order to continue receiving funding. The work they were doing was clearly making a material difference to some of the poorest people on Earth. In the far-flung settlements that I visited, villagers told me about how their lives had been transformed by these organisations. Many were only put on life-saving HIV treatment because of them. Whatever arguments one may want to advance about the importance of self-sufficiency and national responsibility, none of this justifies the US government administering the aid cuts in such a callous and confusing manner. DM
Buzz Feed
4 days ago
- Entertainment
- Buzz Feed
33 Cosplay Struggles That Drive Creators Crazy
Coming into the community as a complete newbie, it felt instantly welcoming. Complete strangers take photos with each other, simply because they admire each other's costumes. There's no bad blood if someone's dressed the same and so many groups come together over a shared love for different shows, games, movies and books. It's so wholesome. As Australia's cons and cosplay scene continue to grow, with more and more people embracing their fandoms and nerding out, I was curious to find out more about what it really takes to stay in costume all day. "Justifying spending hundreds of dollars — trips to Bunnings, Spotlight, every trip is at least 100 bucks. Swallowing that, when we get nothing out of it other than a bit of fun." "As you're making it, you've got to solve all the problems, whether it be creative — how it's going to look, how things are going to line up — and learning new skills. Sewing, something I'd never done before, a skill I don't have, gotta learn it for this. Finishing 3D prints — [have to] learn what works and what doesn't. It's fun, it's stressful." — Jacob McCredie as John Helldiver "The spanx, but maybe that's just coming from someone who's actually wearing them." "Ordering food, they can't hear me most of the time but I appreciate all the work they do." — Sushipool Cosplay as Deadpool "Getting the courage to put yourself out there [and] stay in character." — Bea and Shawn as The Lorax (x2) "The construction of the outfit" — Jacob as Alpha Legionnaire "My shoulders get sore when I cosplay for some reason, it mainly happens when I carry weapons..." "Either that, or the hair can get a little bit itchy."— Caleb as Ultra Ego Vegeta "The heat [and] putting [the costume] on." — Beau the Husky "The wigs always fall off." "I actually wanted to do a wig today but I didn't have the bobby pins nor the skill to put on the hair net, it just kept falling off." — Carmen as Maki "Moving around." "For me, it's making sure you have a cosplay that is navigable around the convention and make sure you're not accidentally hitting anyone. With this giant axe it's a little bit hard but you things we do for the things we love." — Leora as Kikoru Shinomiya "The planning process and getting all the materials required for a cosplay." "I think it's the first step, honestly. Deciding to just go outside in this is pretty rough." "Other than that, it's fine." — Manasavi as Gear Five Luffy "Being inside the costume for eight hours." — Bunny Rabbit "It's very expensive and time consuming." "Even though its just pants, it like a $200 costume. The working out and stuff, that also costs a lot." — Nelson as Ultra Instinct Goku "Public transport." — Britt as Lucy Heartfilia "The preparation to make sure everything flows together as one nice piece." "Planning ahead to make sure everything is done before schedule." — Michael and Anita as DIO Stand/The World "The dedication to get started. I can't really get [out]." — Kevin as RX-78-4 Gundam "A couple of hours in the wig and the fatigue of the day." "The excitement kinda gets you through it." — Chloe S as Sophie "Painting — you have to wait for it to dry, it takes a lot of time." — Maricris as Reze "The stamina." "I feel like I'm coming along with age now so it's really, really difficult for me to stay in cosplay for a long time but other than that it's really fun. I really enjoy it." — Kanon as Saber "Putting on the wig — with a lot of characters the wig is the make-or-break-it part. It makes a lot of characters recognisable." "If you can put the wig on, it's what matters the most." — Murtaza as Naoyo Zenin "It's contact lenses." "I have my friend put them in and out and it's a five minute process every time." — Denzel as Choso "With making a crochet cosplay, it's making the crochet work with you." "A lot of the time you don't have a pattern. Like with normal cosplay, it's trying to figure out how to make the character accurate but also trying to figure out how to make that in the real world." — Shelsea as Fizzarolli "Learning how to style wigs, especially to do it well." "It's taken me four years to get to this point. It takes a lot of practise." — Ebeff as Vi "Just starting it was pretty hard because I didn't know what I was doing." "Sewing is really hard." "Wig styling is the most diffcult — lots of practise, lots of practise and YouTube videos and TikTok Videos, they'll help you out." — Grace as Dante "I don't have hair as long as Dr Ratio, having a wig and hair in my face is annoying but you get used to it." "Getting the outfit prepared is the hardest."— Kieran as Dr Ratio "Acting would be the hardest [part] — staying in character all day." — Chris Wermert as Taro Sakomoto "The fear of being seen and finding the confidence to get started." — Angeline as Super Saiyan Vegeta "Not procrastinating — sometimes I'm like 'I should test this out tonight' and then I don't do it." "I hate wig styling but I've gotten better at it."— Jade as Misato "The fine details." — Eden as Barbatos Lupus Rex "The wig making, that's always the last minute thing for me." — Jordan as Nelliel Tu "The tedious nature behind getting a 3D print ready. Sometimes it feels like your fingers are about to fall off." And finally, "The wig — I'm very much a perfectionist so I like every part to be very detailed." — Lily as Marcille Dark Version What are your cosplaying gripes?
TimesLIVE
4 days ago
- Entertainment
- TimesLIVE
What's new at Nu Metro cinemas, a feast of films at Durban festival, and a hook-handed stalker is back
Spotlight is our bite-sized entertainment snapshot featuring new releases in South Africa, exclusive film trailers and more. New episodes come out every Thursday on Sunday Times Lifestyle, Sowetan Entertainment and YouTube, plus you can follow Spotlight on Facebook. This week Spotlight shines a light on industry news, including the 46th Durban International Film Festival, splendid developments and offers for all film lovers at Nu Metro cinemas. It also takes a peek at the remake of a slasher favourite. Cinema lovers can look forward to extraordinary developments at Nu Metro cinemas, including 270° wraparound screens with sound quality to deliver top immersive movie experiences. Mini Bounce play areas are on the cards for Kidz cinemas, and premium screen formats and a wide range of partners will ensure more affordable cinema visits, more often. A jam-packed film festival is awaiting African and international film enthusiasts and industry professionals from July 17 to 27 in Durban. Filled with premieres, masterclasses, Q&A sessions and workshops centred on the world of storytelling, a record number of attendees are expected at this year's 46th Durban International Film Festival. Look out for groundbreaking local films such as Lucky Fish, Don't Let's Go to the Dogs Tonight and many more. Get ready for a modern take on the popular throwback thriller I Know What You Did Last Summer, delivering new chills for the legacy slasher remake. Directed by Jennifer Kaytin Robinson, the film sees returning cast members Jennifer Love Hewitt and Freddie Prinze Jnr with new faces including Madelyn Cline and Nicholas Alexander Chavez. Five friends, one deadly secret and a hook-handed stalker who knows exactly what they did last summer. Time to head to cinemas. For full interviews, breaking news, trailers and clips visit our Spotlight Facebook page. See you at the movies. Presenter Collette Prince is styled and dressed by Claris by Gerrit Pienaar when attending premieres and special events. Facebook @Claris by Gerrit Pienaar/Instagram: gerritpienaardesigns. Competition and giveaways Send us your favourite Nu Metro cinema name and stand a chance to win a double VIP Nu Metro cinema voucher. For full competition details and the questions, go to the Spotlight SA Facebook page and DM your answers and contact details by July 23. Terms and conditions apply. Winners will be drawn randomly and notified by SMS after the competition has closed. Entrants' personal details will not be retained for marketing purposes. Winners have to provide proof of age (ID/driving licence) and cover their own travel and accommodation expenses. By entering, participants agree to have their names published on TimesLIVE, SowetanLIVE and Spotlight SA on Facebook. Employees of Ar ena Holdings and their family members are not eligible to enter.
Daily Maverick
6 days ago
- Health
- Daily Maverick
TB's tight grip: Why this curable disease is so hard to treat
TB can be cured, but ridding the body of the bug often takes many months and usually requires taking four or more medicines. In this special briefing, Spotlight zooms in on what makes the TB bacterium so hard to beat. There are many things we've learned from studying the ancient Egyptians. One especially fascinating discovery was evidence of skeletal deformities in mummies, which serve as silent markers of a tenacious bug still stalking us today: tuberculosis (TB). With about 10.8 million people around the world getting sick with TB in 2023, it remains the leading infectious disease on the planet, according to the World Health Organization (WHO). In just South Africa, it claims more than 50,000 lives a year. In this Spotlight special briefing, we take a closer look at the bacterium that causes TB and why, even now in an era where TB is curable, beating it still requires months of treatment with multiple medicines. Adapted for survival The mystery of TB's staying power starts with the bug itself. As explained by Dr Jennifer Furin, Mycobacterium tuberculosis is well adapted to survive on multiple fronts. Furin is an infectious diseases clinician and medical anthropologist who specialises in TB. First, she explains, there is its size. TB is spread through the air when someone who has the bacterium in their lungs coughs it up. It's then contained in small amounts of fluid called droplet nuclei. This droplet is precisely the right size to hang in the air, allowing TB to survive for hours and even days. These droplets can then be inhaled by other people and are just the right size to travel to their lungs. 'It is really amazing from an evolutionary point of view and would be absolutely fascinating if it did not lead to such a horrible disease,' says Furin. Secondly, the bacteria themselves are well adapted to avoid being killed, sporting a thick, slimy coating called mycolic acid. This coating makes it difficult for drugs or immune system cells to get into the organism to kill it. The bacteria also have some clever ways of getting around the human immune system, which allows them to 'persist in the body for years and years'. Furin says one way it's able to stay in the body for so long is the bacterium's ability to go into a 'metabolically quiet state' when the immune system starts coming after it. In this state, it stops multiplying until the pressure from the immune system quiets down. It is this combination of being able to pass from person to person and lay dormant in the body when challenged by the immune system that enables TB to thrive in humans. How the body fights back Though hard to estimate with great accuracy, it is thought that only in the region of one in 10 people who inhale the TB bacterium and become infected actually fall ill with TB disease. In fact, some people's immune response is so good that even though they've been exposed to TB, there's no evidence that it was ever able to establish an infection in the lungs. For everyone else exposed to TB, one of two things happens. Either the body mounts an immune response that contains and may eventually kill the bug, or the bacteria get past the immune system and cause illness. To make people ill, the bug needs to get past the first line of defence and get a foothold in the lungs. Unfortunately, the antibodies relied on to kill other bacteria or viruses don't work against TB. Instead, Furin explains, special pulmonary macrophages recognise TB as a threat and 'gobbles it inside them'. Macrophages work by 'swallowing' bugs and then neutralising them by 'digesting' them. But the bacterium's thick, slimy mycolic acid layer prevents the macrophages from killing it. The macrophages with the TB inside, along with other essential immune system cells called CD4 and CD8 cells, then signal more macrophages to help out. These cells then work together to build a wall around the bacteria to keep it contained. Furin compares the CD4 and CD8 cells to foremen who oversee the building of a wall called a granuloma, while the macrophages are like the bricks and cement that form the actual structure. This wall around the TB bacteria needs to be constantly maintained by the immune system. If the immune system is weakened, Furin says the walls break down and the bacterium escapes, coming out of its dormant state and starts multiplying again. If this happens, TB could spread beyond the lungs to other parts of the body. If the walls are built right and maintained, then eventually the bacterium is starved to death. Yet, this process can take a long time, sometimes years, because of the bacterium's ability to go dormant. 'Double-edged sword' The 'interaction between TB and the immune system is a double-edged sword', says Professor Graeme Meintjes, an infectious diseases specialist with a research interest in HIV and TB at the University of Cape Town. 'The immune system is trying to contain and kill TB. But at the same time, TB is using the immune system to perpetuate infection from one person to the other,' he says. Meintjes explains that TB has evolved alongside people and developed special proteins and molecules that cause the immune system to react to it. It needs this reaction to cause damage in the lungs, leading to its being released during coughing or even breathing, which helps spread it to other people. 'The TB excites the immune response that causes damage [to the lungs] and that allows it to be released into the airway and either coughed or breathed out. So, there's some evidence that TB has evolved to elicit the immune response in order to achieve that,' he says. Adding to this, for some people cured of TB, Furin says that a condition known as post-TB lung disease can in part be caused by the granulomas grouping together, which causes cavities to form in the lungs. This can lead to scarring and sometimes surgery is required to remove these areas of destroyed lung tissue. The immune system can also start 'over-functioning' if it senses the bacterium has escaped from the granulomas and is spreading. This causes the immune system to send out special chemicals called cytokines that can cause indiscriminate killing of the lung cells around it. She says this is like the immune system going after one target with the intention to kill it, but then blowing up the whole neighbourhood. TB works differently in different people The complex interplay between the immune system and TB makes it difficult to predict which individuals will become sick with TB and who won't, although there are some clear trends. Meintjes says factors like malnutrition, poverty, overcrowded living or working conditions and multiple exposures to TB are some of the biggest drivers of infection and disease. Factors like genetics, the amount of TB someone is exposed to, or a person's initial immune response are also thought to play a role. 'But still, in a given setting where you have two people living in a household, one of them might go on to develop TB disease with the same exposure and the other not. And there are factors that are not fully explained about why some people will develop TB and others won't,' he says. Probably the most important risk factor for TB in South Africa over the past three decades has been untreated HIV. Because HIV targets specifically CD4 cells, it was the worst thing that could have happened in a world with TB, Furin says. HIV infiltrates and kills a person's CD4 cells, which means the immune system then has fewer of the cells ready to fight TB. In 2024, over half (58%) of all adults receiving TB treatment in South Africa were also living with HIV, according to estimates from Thembisa, the leading mathematical model of HIV and TB in the country. Another group that is at high risk of TB disease is children, particularly those younger than two. The good news is that there is a vaccine that reduces this risk. As Furin explains, the BCG (bacillus Calmette-Guérin) vaccine works by showing the CD4 and CD8 cells how to build the 'protective wall' against TB, because the immune systems of children are still too 'immature' to know how to do it without help. 'It [the BCG vaccine] only works for a little bit of time, but it works great to protect kids against those very severe forms of disease, while their own immune systems are learning [how to fight TB],' says Furin. Because the vaccine protects children only for a short time, the WHO recommends that one dose be given at birth for children in countries with a high TB burden. Despite many research efforts to find another vaccine, and a promising candidate being studied in a phase 3 trial, BCG remains the only TB vaccine in use for now. A brief history of TB treatment Though TB has been making humans sick for many centuries, the bug that causes the illness was identified only in 1882, by the German physician and microbiologist Robert Koch. It would be roughly another 60 years before the first effective treatments would become available. Until the 1940s, TB treatment mainly involved staying in a sanatorium. The first drugs to treat TB with any success were the antibiotics streptomycin and para-aminosalicylic acid. These two drugs had significant side effects, and using only two drugs often led to TB becoming resistant to the treatment. As described in this excellent overview, what followed was a 'great flurry of drug discovery research' that lasted from the 1940s to the 1960s. The four drugs used to treat most cases of TB today – isoniazid, rifampicin, pyrazinamide, and ethambutol – were all first used to treat TB in this period. After the 1960s, there was a lull in investment in TB research for several decades, probably because TB rates in wealthy countries had declined, and what cases there were could generally be cured with the new treatments. 'The Global North was very much of the perspective that it's [TB] a disease that's waning and 'it's no longer our problem',' Meintjes says. 'It was seen as a disease of poverty; a disease of other countries, and money was put into diseases that are common in the Global North.' This all changed around the turn of the century with the HIV epidemic and a resurgence of TB, particularly drug-resistant TB (DR-TB) in Europe and North America, says Meintjes. By definition, DR-TB means that some of the standard drugs used to treat TB no longer work. The renewed interest in TB resulted in a new flurry of TB drug discovery. Maybe most notably, in the 2010s, a drug called bedaquiline replaced older DR-TB drugs that were associated with hearing loss. A slightly older antibiotic called linezolid also became a cornerstone of DR-TB treatment. Today, in South Africa, 'normal' drug-susceptible TB (DS-TB) in adults is treated with a six-month treatment course – consisting of four drugs for two months and then two drugs for the next four months. A four-month treatment course has been shown to work in a clinical trial, but is not yet routinely provided in the country. Kids are typically treated for four or six months. DR-TB is treated with anything from three to six drugs, for any time from six to 24 months. How someone's TB is classified is largely determined by which drugs their particular strain of TB is resistant to. Lindsay McKenna, co-director of the TB Project at the Treatment Action Group, suggests thinking of it as a ladder. If the standard four drugs all work for your TB, then you don't have to climb any rungs. If rifampicin doesn't work for you, you have rifampicin-resistant TB (RR-TB) and must climb to the first rung to find drugs that work. If both rifampicin and isoniazid no longer work, you have multi-drug-resistant TB (MDR-TB) and must climb another rung. If you have resistance to even more drugs and you have pre-extensively drug-resistant TB and after that, extensively drug-resistant TB. (In practice, TB programmes often classify RR-TB and MDR-TB together since the same medicines are used to treat them.) All of the above treatments are for people who are ill with TB disease. There is also so-called TB preventive therapy, which aims to kill the TB bacteria in the lungs of someone who is infected, but who hasn't yet become ill with TB disease. These preventive treatments typically involve taking one or two medicines for one to six months, depending on the specific treatment regimen. It is possible that new long-acting formulations could allow for an entire course of preventive therapy to be administered as a single injection, though that research is still at an early stage. How the treatments work One reason for the complexity of TB treatment is the bacterium's large and complex genome. Meintjes says that HIV has nine genes, while TB has around 4,000. Having so many genes means the bug has lots of potential to bypass the effect of drugs targeting certain molecules or pathways and still survive. On the other hand, the many genes, at least in theory, provide many potential targets for antibiotics to attack. As noted, to cure TB, one typically has to attack the bug with at least three or four drugs. Meintjes says it is like a group of lions taking down a large buffalo – each one targeting a different part of the buffalo. Along these lines, TB drugs can broadly fit into different categories based on which part of the bacterium they target. Some drugs attack the way the bacterium builds its cell wall, others disrupt how the bug makes its protein, yet others interfere with how the bacterium produces or gets energy, and finally, some sabotage the way TB replicates. As Meintjes explains, isoniazid targets the cell wall of the bacterium by affecting the formation of molecules within the wall, ultimately causing it to leak and die. Rifampicin targets the genetic mechanisms of the TB bacterium, which prevents it from replicating. Bedaquiline works by targeting the mechanisms that allow the bug to metabolise energy, essentially starving it of fuel. A class of antibiotics called fluoroquinolones, specifically levofloxacin and moxifloxacin, target the TB bacteria's DNA while it's trying to copy itself and stops that process, explains Furin. Another drug, linezolid, interferes with how the bacterium makes proteins, which it needs to survive. It is not entirely clear how some other drugs, like clofazimine and pyrazinamide, work, says Furin. Even when attacking TB with several drugs and from multiple angles like this, it can still take months for all the bacteria in someone's body to be killed and for them to be cured. This is because, according to Furin, sometimes the protective wall formed by the immune system to contain the TB becomes too thick for the drugs to get through. And the environment inside the wall is often very acidic and deactivates some of the drugs that do manage to get in. How treatment could improve Novelist George Orwell, who was diagnosed with TB in 1947, was one of the first people to be treated with streptomycin. 'I am a lot better, but I had a bad fortnight with the secondary effects of the streptomycin. I suppose with all these drugs it's rather a case of sinking the ship to get rid of the rats,' he wrote in a letter at the time. More than 75 years later, TB treatments have improved massively, but drug side effects remain a real problem, especially when treating DR-TB. Some older treatments for TB involved injections of toxic drugs and had horrible side effects, including hearing loss and kidney damage. While newer drugs are better, there are still issues. Linezolid, for example, can cause peripheral neuropathy (painful tingling in the hands and feet) and anaemia. McKenna says none of the TB drugs is 'necessarily a walk in the park' and all come with side effects. This is because of the drugs themselves, the dosages required to kill the TB bacterium, and how long the drugs need to be taken. Because of this, much of the focus in TB research has been on finding drug combinations that can reduce the duration of treatment and the severity of side effects. For Furin, an ideal future regimen includes 'fewer pills' – she's hoping for one pill once a day for no more than eight weeks, 'fewer side effects', and doing away with the one-size-fits-all approach. Her reference to the 'one size fits all approach' points to one of the central tensions in TB treatment programmes. People with TB often do not get optimal treatment based on the specific characteristics of their own illness. For example, in countries with limited testing for drug resistance, people might be treated with medicines that their specific strain of TB is resistant to. They might thus suffer the side effects of that medicine without any of its benefits. This is less of an issue in South Africa than elsewhere, since the country's health system provides routine testing for resistance against several of the most important TB drugs. There are also questions about whether everyone really needs to be treated for six months to be cured. A landmark study called Truncate has shown that many people can be cured in two months. The difficulty is that we can't currently predict who will be cured after two months and who will need the full six months, or even longer. Figuring this out, as McKenna points out, would enable more personalised care that would mean fewer people are over- or under-treated. Some in the TB world have argued for the development of a pan-TB regimen – a combination of three or so drugs that nobody is resistant to and that accordingly could be given to everyone with TB, no matter what strain of TB they have. The benefit of such a pan-TB regimen would be that it would dramatically simplify the treatment of TB if it worked. But the experts interviewed by Spotlight agree that resistance is likely to develop against the drugs in such a regimen, and as such, testing people for drug resistance will remain necessary, as will alternative treatment regimens. Furin also points out that pharmaceutical companies have a greater incentive to invest in a pan-TB regimen since its potential market share is bigger than for drugs in a more fragmented treatment model. A hard task, getting harder One of the biggest obstacles in the way of finding new TB treatments is that there really aren't any reliable shortcuts when it comes to doing the research. With HIV, one can get a good idea as to whether a treatment is working by looking at biomarkers such as a person's viral load and CD4 count. TB, by contrast, doesn't have any similarly clear biomarkers that tell us whether a treatment is working or not. Arguably, the most promising biomarker for TB is bacterial load – essentially, how many bacteria are left in someone's sputum a while after treatment has begun. Having a high TB bacterial load is associated with a poor treatment outcome, but the problem is that it is difficult to measure reliably. Without a good biomarker, the only way to measure how well treatment is working is to follow patients for a long time and see if they are cured, and if they are, whether they suffer a relapse. Because of this, TB treatment trials often take several years to complete. Despite these challenges, there has been a good deal of activity in recent years. 'There are about 20 different new drugs in clinical trials at the moment – either early or later phase,' says Meintjes. But much of that momentum might now be lost because of the United States' abrupt slashing of research funding, including much TB research. The US government has until now been the largest funder of TB research by some distance. It spent $476-million or over R8.7-billion through its agencies on TB research in 2023, according to a report by TAG. Many ongoing US-funded TB clinical trials have already been affected, according to McKenna, although there have recently been indications that some research funding might be restored. Where does this leave us? That most people with TB can be cured is something worth celebrating. That treatment for DR-TB has become a lot better and shorter over the past two decades is also something to be grateful for. But as we have shown in this Spotlight special briefing, TB is a tough and ancient adversary and keeps adapting. The treatments at our disposal today are far from as good as we'd like them to be. The treatment side effects are often horrible, and many people find it very hard to take these drugs for month after month. We didn't linger on it, but many people who are cured struggle with post-TB lung disease for the rest of their lives – meaning the bug might be gone, but that person's lungs are never the same again. The scientific search for better TB treatments is not a matter of convenience. It is critical to reducing the suffering that several million people will endure just this year. It is also vital for reducing the number of lives that are still being claimed by this age-old disease. And of course, TB will keep mutating, and we will likely see more and more resistance developing against the drugs that we are depending on today. That is why it is imperative that governments, donors, and pharmaceutical companies all maintain and increase their investment in the search for better TB treatments. After all, TB claims more lives than any other single infectious agent on the planet. If that alone doesn't warrant more investment, what does? But there is also a case to be made that we should change the way we conduct TB research. Ideally, more research should be driven, and informed by, what actually matters to people with TB and to people in the communities where TB is rampant. After all, when given the choice, who wouldn't opt for more personalised and more respectful treatment and care? 'The TB community keeps making the same mistakes over and over and then acts mystified when things do not turn out the way they want,' says Furin. 'All the new drugs and new regimens in the world will never be enough if we do not listen to what impacted communities need, and follow their lead.' DM Additional reporting by Marcus Low.
Sydney Morning Herald
6 days ago
- Sydney Morning Herald
Inside the search for missing backpacker Carolina Wilga
Police found the 1995 Mitsubishi Delica had run into mechanical problems, and believed Wilga had tried to use recovery board and bits of wood to free the car, which had become bogged in a patch of mud. However, like in Podmore's case, there was no sign of the backpacker. Details about the ensuing days remain a mystery, but the hunt for Wilga came to an end on Friday when she was rescued by a station owner returning from Beacon along a remote bush road. Tania Henley told media Wilga stumbled out from the bushes and waved her down. Wilga has offered little insight into her 11 nights in the bush, but said she survived by sleeping in a cave, drinking from puddles and using the sun as her guide. Loading Bush survivalist instructor Mike Cook said it was clear the backpacker had luck on her side. 'It's a harsh environment, and it's quite difficult to navigate without aids … it's difficult to get any sort of sense of where you are, if you're not familiar with solar navigation,' he said. 'It sounds like she had some idea about trying to sort of pick a direction and head west after she decided to leave her car.' Cook said any traveller looking to drive east in WA should be conscious of the lack of water in the region as it borders the desert. 'You have to go with the mindset that if you did break down, you should be right for a solid week, at least with sufficient water and stuff like that,' he said. Wilga's van was stocked with days' worth of food and water. The traveller said she was disorientated when she decided to walk away from the area carrying no supplies. Searchers confirmed the bushland was hard going, with low shrubbery and very little distinct terrain to help someone who was lost. Posting to social media from Fiona Stanley Hospital on Tuesday, Wilga joked she would need to gain '12 kilos back' after her ordeal, but still has not spoken about what she went through. Celebrity agent and public relations expert Max Markson said the backpacker, who spent her fifth night in hospital on Tuesday, would probably be fielding calls from media outlets across the country wanting to share her story, with Nine's 60 Minutes and Seven's Spotlight showing interest. Loading 'They're the ones who would do the story and do it properly – as opposed to 15 minutes, they'd do 30 minutes of television,' he said. Markson said Wilga could ask for between $50,000 and $100,000 to exclusively share her ordeal. 'I think it's really important to have someone who can not just represent her for this deal, but for other deals that will happen – I'm sure there'll be a magazine deal at one stage,' he said.
