H5N1

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries

Via The Lancet Global Health: Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study. The summary:

Background 

COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. 

Methods 

Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. 

Findings 

In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. 

Interpretation 

Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic.

What the growing rift between the US and WHO means for COVID-19 and global health

Via Nature.com: What the growing rift between the US and WHO means for COVID-19 and global health. Excerpt:

Experts in health policy are contending with the real possibility that the United States will pull away from the World Health Organization (WHO), fracturing a relationship that began in the wake of the Second World War. 

They say that the repercussions could range from a resurgence of polio and malaria, to barriers in the flow of information on COVID-19. Scientific partnerships around the world would also be damaged, and the United States could lose influence over global health initiatives, including those to distribute drugs and vaccines for the new coronavirus as they become available, say researchers.  

A fissure between the US and the international health agency opened further last week, when US President Donald Trump tweeted a letter to WHO director-general Tedros Adhanom Ghebreyesus, threatening to make permanent the US freeze on WHO funding that began in April, unless the organization “can actually demonstrate independence from China” within 30 days. He added that he will reconsider the United States’ membership of the organization. “I don’t think this is an idle threat,” says Kelley Lee, a global health-policy researcher at Simon Fraser University in Burnaby, Canada. 

Proposals for new US-led initiatives for pandemic preparedness abroad do little to quell researchers' concerns. Some say these efforts might even add incoherence to the world's response to COVID-19, and global health more generally, if they're not connected to a fully-funded WHO. “It’s surreal to even be having this conversation, since it’s so hard to get one’s head around the massive implications,” says Rebecca Katz, director of the Center for Global Health Science and Security at Georgetown University in Washington DC. 

The acrimony is poorly timed, given the need for international coordination and cooperation to contend with the coronavirus. “In this pandemic, people have said we’re building the plane while flying,” Katz says. “This proposal is like removing the windows while the plane is mid-air.”  

Balance due 

Trump’s letter, which he tweeted on 18 May, alleges that the WHO intentionally ignored reports that COVID-19 was spreading between people in Wuhan, China, in December. “I cannot allow American taxpayer dollars to continue to finance an organization that, in its present state, is so clearly not serving America’s interests,” he wrote. A few of Trump's points were immediately debunked. For example, he claimed that the medical journal The Lancet had published on the new coronavirus in December. The next day, the journal issued a statement calling the claim factually incorrect because their first reports on COVID-19 were published on 24 January. The journal also refuted other allegations in the letter, concluding that the claims are "damaging to efforts to strengthen international collaboration to control this pandemic." 

Tedros has reiterated his commitment to a comprehensive and independent evaluation of the WHO's response to COVID-19, and an assessment of the organization's operations in the first part of 2020 is already public. But when reporters asked Tedros about additional, immediate investigations in response to Trump's allegations at a WHO press briefing, he said, “Right now, the most important thing is fighting the fire, saving lives.”

Trump does not need Congressional approval to withhold funds from the WHO, and global health researchers say the gap left by the US is a big deal. Last year, the US government gave the WHO roughly US$450 million. Nearly 75% of that was voluntary, and the other quarter was mandatory — a sort of membership fee expected from the 194 member countries, adjusted by the size of their economies and populations. 

The United States is the biggest donor, representing about 15% of the WHO budget. So far this year, it has paid about one-quarter — $34 million — of its membership dues, according to a WHO spokesperson. Voluntary funds are more complicated because a large portion were paid last year, however the spokesperson says that the freeze has put a hold on new agreements, meaning that the full-blown effects of the decision will be felt in 2021. 

The US government provides 27% of the WHO’s budget for polio eradication; 19% of its budget for tackling tuberculosis, HIV, malaria and vaccine-preventable diseases such as measles; and 23% of its budget for emergency health operations. If these initiatives shrink, researchers say, death and suffering will surge. David Heymann, an epidemiologist at the London School of Hygiene and Tropical Medicine, says this will also amount to squandered investment for the United States, particularly for polio. Gains won through vaccination campaigns that cost hundreds of millions of dollars would be lost, he says.

Report 19: The potential impact of the COVID-19 epidemic on HIV, TB and malaria in low- and middle-income countries

MRC has published Report 19 - The Potential Impact of the COVID-19 Epidemic on HIV, TB and Malaria in Low- and Middle-Income Countries. The summary:

COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. 

In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely high health system demand; for TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic.

In high burden settings, the impact of each type of disruption could be significant and lead to a loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.

The invisible victims of China’s coronavirus crisis

Via Sixth Tone: The Invisible Victims of China’s Coronavirus Crisis. Excerpt:

The day before the central Chinese city of Wuhan went into lockdown, Ye Bing received an ominous message from the hospital where his father-in-law was being treated for tuberculosis: He would have to leave.  

“They were forcing all of the patients to leave the hospital, saying the government had ordered the wards to be cleared out to treat coronavirus patients,” 

Ye told Sixth Tone just over a month after Hubei’s provincial capital restricted the movement of some 14 million people to contain the spread of COVID-19. Ye said Wuhan Pulmonary Hospital didn’t even suggest what to do with his father-in-law after he was discharged. They didn’t know which hospital to visit next, or what treatment to seek.  

The COVID-19 epidemic that originated in Wuhan late last year has choked the city’s health system, killing over 2,600 people and infecting nearly 80,000 worldwide. To cope with the overwhelming number of patients infected with the coronavirus, the city has converted many of its general and specialist hospitals, as well as public venues, into facilities for treating COVID-19 cases.  

Wuhan Pulmonary Hospital was one of the first to be repurposed, and there are currently 48 medical facilities in the city that have been designated for treating coronavirus patients. However, with the focus concentrated on containing the epidemic, patients with other diseases say they have struggled to get medical attention, becoming “invisible victims” of COVID-19.  

After Wuhan Pulmonary Hospital told Ye to make alternative arrangements, he tried to contact other hospitals in the city, but to no avail. Some told him they had run out of beds, while others said they were unable to treat his condition. 

“We tried everything — calling an ambulance, begging doctors, asking friends and relatives for help, seeking help on social media,” Ye said. “Nothing worked.”  

With no alternative, Ye took his sick father-in-law home, where he is now hooked up to a respirator. He hasn’t eaten for the past five days, and his condition is deteriorating.  

“We cannot do anything but wait at home for him to die,” Ye said. “I feel so helpless. I don’t even know what to do if he dies. It’s like there’s no way to live, and there’s no way to die.” 

Also caught in the coronavirus crossfire are people with HIV. With the ongoing restrictions on movement, many are holed-up in their homes, unable to access antiretroviral therapies that would help them enjoy longer, healthier lives.  

Huang Haojie, director of the Wuhan LGBT Center, told Sixth Tone that the center has received a flood of messages from concerned individuals. “The sudden lockdown in Wuhan has made it extremely difficult for HIV patients to get medicine,” he said.  

In China, HIV medications are only accessible in specific hospitals where individuals are registered. Many living with HIV refrain from seeking help from family and friends due to the stigma associated with the disease. 

“People are afraid of going without the medicine, but they are more afraid of (their disease) being discovered by their family,” Huang said, adding that some people with HIV were visiting their families for the Lunar New Year and are likely still with them.  

Though China’s National Center for AIDS/STD Control and Prevention temporarily allowed patients to get their monthly dose of HIV medication without registering, Huang said such a “quick response” to the epidemic doesn’t completely address the problem. For many in rural areas, a total shutdown of transportation during the lockdown means they cannot travel to get their drugs. 

“One HIV patient from the countryside told our center that he set off from his village at 6 a.m. and returned home at 6 p.m. — he walked all day to get the medicine,” Huang said.  

Earlier this month, a video of a mother frantically trying to take her daughter out of Hubei for treatment made headlines in China, underscoring the plight of people who feel helpless as they struggle to take care of sick family members. In the video, the woman is seen pleading with police, saying her daughter with leukemia isn’t able to get chemotherapy because of the surge in coronavirus patients.  

To address the needs of patients other than the ones diagnosed with COVID-19, the Hubei provincial government announced a list of hospitals for such patients last week. The 50 hospitals in Wuhan have been designated for critically ill patients, pregnant women, infants, and those who require dialysis.  

Li Hua, who asked to use a pseudonym to protect her privacy, told Sixth Tone that the coronavirus epidemic has been a “nightmare” for her as she tries to get treatment for her mother, who was diagnosed with late-stage lymphoma in early January. Though the provincial government’s designated hospitals have made it easier to secure a bed at the Hubei Cancer Hospital, she is still uncertain how long they’ll be able to stay there.

Beyond borders: The best books about pandemics

Via The Guardian, the author of an excellent history of Spanish flu writes: Beyond borders: the best books about pandemics. The list and then a comment:

With cases of coronavirus reported on four continents, health experts are concerned it could become a pandemic. The world is currently in the grip of two others – Aids and tuberculosis – while measles is on the rise again and polio stubbornly resists eradication. When smallpox was wiped out, some in the medical community were so high on their success they thought other infectious diseases would soon be licked. Fifty years later, this triumph remains unique.  

David Quammen’s Spillover serves as a rousing wake-up call, because he conjures up the complex web of microbial ecosystems through which humanity stumbles blindly. Mostly the microbes mind their own business, but occasionally we blunder into their finely tuned arrangements for survival and provoke the spillover of a pathogen from its usual animal host to us. It takes time for them to find a sustainable way to colonise their new host, or hosts, so the initial fallout can be carnage – a trail of gorilla carcasses in an African forest, for example, that heralds an outbreak of Ebola in people. 

Not all pathogens acquire the ability to spread easily between humans, but if they do, then a pandemic – an epidemic that encompasses several countries or continents – becomes possible. In the 14th century, long before people connected infection with germs, one or more varieties of plague reduced the population of Europe by as much as half. Philip Ziegler’s classic account of that disaster, The Black Death, shines a light into the medieval mind, revealing how mystical and often paranoid explanations produced cults of self-flagellation and the burning of Jews.

Stigmatisation of the other has always accompanied pandemics, but so have compassion and heroism. A literary sub-genre is dedicated to the doctors and scientists who have ventured to the centre of pandemics to take on the invisible enemy, and in this category Tracy Kidder’s Mountains Beyond Mountains stands out. It is the story of Paul Farmer, a Harvard professor of health who finds his vocation fighting Aids and TB in impoverished communities in Haiti, and who sleeps no more than a couple of hours a night because, as he tells Kidder, while he’s sleeping, people are dying.  

The curious thing about pandemics is that novelists don’t seem to know what to do with them. You would think they would find rich material in a menace that brings out the best and worst in people, and that makes a mockery of all the ways we divide ourselves up – by colour, faith or postcode. But when they have written memorably about them, it tends to have been as allegories for something else – fascism, say, or war. 

There are exceptions, and Philip Roth’s novel Nemesis is one. Polio is on the prowl in Newark in the summer of 1944, and teacher Bucky Cantor’s girlfriend begs him to leave the city for the polio-free summer camp where she is working. Duty obliges him to stay with the kids in his charge, however, and when he finally does reach the camp, the disease follows him.  

Another exception is Pale Horse, Pale Rider, Katherine Anne Porter’s jewel of a novel based on her experience of falling ill during the 1918 flu pandemic. Fifty million died – but she did her writerly duty, and gave us a glimpse of the suffering behind that number. Above all, she managed to convey the grief and in some cases the guilt of survivors who woke into “the dead cold light of tomorrow”.

Spinney's own book Pale Rider is the best history of the Spanish flu pandemic I've read, and I reviewed it here.

Wuhan Health Commission coronavirus update, January 16

Thanks to Helen Branswell for tweeting about this. The Wuhan Health Commission has published an update for January 16. The Google translation:

At 04:00 on January 15, 2020, there were no new cases of pneumonitis infected with new coronavirus in our city. Five patients were discharged from the hospital and one new death was reported. 

The deceased Xiong Moumou, male, 69 years old, became ill on December 31, 2019, became worse on January 4, 2020, and was transferred to Wuhan Jinyintan Hospital for treatment. He was admitted with severe myocarditis (myocardial enzymes reached 20 times normal, electrocardiographic abnormalities); abnormal renal function; severe damage to multiple organ functions; chest CT showed pulmonary fibrous lesions and pleural effusion and pleural thickening. Considering tuberculosis and pleural tuberculosis, died at 00:45 on January 15 due to ineffective rescue.  

As of now, the city has reported a total of 41 cases of pneumonia caused by new coronavirus infection, 12 cases have been cured and discharged, 5 cases are being treated in severe cases, and 2 cases have died. The remaining patients are in stable condition. All patients received isolation treatment at designated medical institutions in Wuhan. A total of 763 close contacts have been tracked, 644 medical observations have been lifted, and 119 medical observations are still underway. Among the close contacts, no related cases were found.

Dr. Tedros: Why is the world losing the fight against history's most lethal disease?

Via The Guardian, a November 14 op-ed by Dr. Tedros Adhanom Ghebreyesus: Why is the world losing the fight against history's most lethal disease? Excerpt:

Tuberculosis has killed more people than any other disease in history. Last year, 1.5 million people died from TB and 10 million more acquired it. A shocking one-quarter of the world’s population is infected. That’s not much better than 1993, when one-third of the world was infected and the World Health Organization declared TB a global emergency. We are losing the battle. 

Earlier this month, experts gathered in Hyderabad for the 50th Union World Conference on fighting the disease. When the first such gathering was held in 1867, TB was the leading cause of death in industrialised nations. Today, it still ranks in the top 10 worldwide. Why, despite all the progress in medicine and public health over the past 150 years, is TB still the most common and lethal of all infectious diseases?  

First, TB has a singular capacity for contagion. When someone with active TB coughs or sneezes, they launch respiratory droplets containing the bacteria into the air. These droplets can stay suspended for hours, turning shared spaces – homes, schools, public transport, hospital waiting rooms – into transmission hot spots. And unlike some diseases, such as measles, which can be caught only once, this “smart” pathogen can cause disease multiple times. 

But easy as TB is to catch, it is hard to diagnose. Once someone is infected, either the body’s immune system defeats it, it becomes dormant (latent TB) or it develops into the active disease.

The chief symptoms – cough, fever, and weight loss – come on slowly and are common to many other diseases.  

Most diagnostic tests are more than a century old and not very effective. Sputum microscopy has been used since Robert Koch discovered Mycobacterium tuberculosis in 1882. It only picks up half the cases of active TB. The skin, or Mantoux, test, also dating from the 19th century, which can detect latent TB, doesn’t pick up anything for two months after exposure. 

Modern, more accurate tests are prohibitively expensive. Bacterial culture, the gold standard, takes weeks for results. False negatives or long waits delay getting people into treatment; when they are, it takes just 72 hours for them to stop being infectious.

Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis

Via NEJM, encouraging news: Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. The abstract:

BACKGROUND Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity.  

METHODS From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). 

Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo.  

RESULTS A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). 

The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.  

CONCLUSIONS Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years.

Global routine vaccination coverage, 2018

Via MMWR: Global Routine Vaccination Coverage, 2018. The summary:

What is already known about this topic?  

Since 1974, global coverage with vaccines to prevent tuberculosis, diphtheria, tetanus, pertussis, poliomyelitis, and measles has increased from <5% to 86%. 

What is added by this report?  

Global coverage with the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine has not increased above 86% since 2010. Coverage varies across regions and countries, with lower coverage in lower-income countries.  

What are the implications for public health practice? 

Equitable access to immunization to achieve and sustain high coverage can be enhanced through financial and technical support for program strengthening and vaccine introductions in lower-income settings, community engagement to increase vaccination acceptance and demand, collection and use of vaccination data, and commitment to improving immunization services.

FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs

A news release from the US Food and Drug Administration: FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs. Excerpt:

The U.S. Food and Drug Administration today approved Pretomanid Tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs. 

“The threat of antimicrobial-resistant infections is a key challenge we face as a public health agency,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D. 

“The bacterium that causes tuberculosis can develop resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections. 

"This approval also marks the second time a drug is being approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway, advanced by Congress, to spur development of drugs targeting infections that lack effective therapies. We hope we continue to see more development of antibacterial drugs for treating serious or life-threatening infections in limited populations of patients with unmet medical needs.”  

Pretomanid in combination with bedaquiline and linezolid is approved for treating a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary TB. Multidrug-resistant TB and extensively drug-resistant TB are difficult to treat due to resistance to available therapies. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.  

The safety and effectiveness of Pretomanid, taken orally in combination with bedaquiline and linezolid, were primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs). Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of extensively drug resistant TB.

The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes (transaminases and gamma-glutamyltransferase), indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.  

Pretomanid used in combination with bedaquiline and linezolid should not be used in patients with hypersensitivity to bedaquiline or linezolid.