Melvin is a curious lifelong learner. He studied biology, medicine, health economics, infectious diseases, clinical development, and public policy. He writes about global health, vaccines, outbreaks, and pathogens.
TPOXX’s effectiveness against smallpox was established by studies conducted in animals infected with viruses that are closely related to the virus that causes smallpox, and was based on measuring survival at the end of the studies. More animals treated with TPOXX lived compared to the animals treated with placebo. TPOXX was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.
Smallpox, an acute contagious disease caused by the variola virus, was one of the most devastating diseases known to humanity and caused millions of deaths before it was eradicated. It is believed to have existed for at least 3,000 years.
The smallpox vaccine, created by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that a similar inoculation could be used to prevent smallpox in other people.
The World Health Organization (WHO) launched an intensified plan to eradicate smallpox in 1967. Widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. The WHO declared smallpox eradicated in 1980, but since then many nations have expressed concerns that the variola virus, which causes smallpox, could be used as a bioweapon.
Similar to TPOXX, the FDA also approved Tembexa under its Animal Rule. Human safety data on Tembexa was based on clinical trials involving primarily patients who were treated with the drug after they received hematopoietic stem cell transplants.
In the animal study for Tembexa (brincidofovir), the efficacy was defined by measuring the animals’ survival by the end of the studies. Results demonstrated that more animals with smallpox who were treated with brincidofovir survived compared with animals who were treated with the placebo.
In a recent study published in JAMA Pediatrics, an international team of researchers from Argentina, Brazil, Egypt, France, Ghana, India, Indonesia, Italy, Japan, Mexico, Nigeria, North Macedonia, Pakistan, Russia, Spain, Switzerland, the US and led by investigators from the University of Oxford (UK) studied 2,130 pregnant women age 18 and older and their newborns at 43 different institutions in 18 different countries from March to October 2020, as part of the observational INTERCOVID Multinational Cohort Study. For each woman who tested positive for COVID-19 before delivery, two unmatched, uninfected women of similar gestational age (±2 weeks) were enrolled.
The 706 COVID-19 patients were at much higher risk than their 1,424 uninfected counterparts for preeclampsia/eclampsia (eclampsia is a serious condition where high blood pressure results in seizures during pregnancy), pregnancy-related high blood pressure, infections requiring antibiotics, intensive care unit (ICU) admission, referral to a higher level of care, preterm delivery, medically indicated preterm delivery, severe neonatal illness, and severe perinatal illness and death.
Women with COVID-19 diagnosis, already at high risk of preeclampsia and COVID-19 because of preexisting overweight, diabetes, hypertension, and cardiac and chronic respiratory diseases, had almost 4 times greater risk of developing preeclampsia/eclampsia, which could reflect the known association with these comorbidities and/or the acute kidney damage that can occur in patients with COVID-19.
Compared with uninfected women, those who tested positive for COVID-19 had a lower rate of spontaneous labor but higher rates of cesarean birth and preterm delivery and fetal distress (signs before and during childbirth indicating that the fetus is not well). The most common indications for preterm delivery among women with a COVID-19 diagnosis were preeclampsia/eclampsia (24.7%), small fetus for gestational age (15.5%), and fetal distress (13.2%).
Of the COVID-19 patients, 13% of their 416 newborns tested were also positive for coronavirus. Exclusive breastfeeding and newborn test positivity were not linked.
Cesarean birth was linked to an increased risk of newborn infection, while breastfeeding was not. Mean maternal age was 30.2 years, and 48.6% of infected women were overweight early in pregnancy, compared with 40.2% of uninfected women.
Of the women with a coronavirus diagnosis, 1.6% died (maternal death ratio, 159 per 10,000 births); four of them died of severe preeclampsia, three of respiratory failure requiring mechanical ventilation, and one of a pulmonary embolism. Five women had worsening respiratory failure before delivery, two of whom underwent cesarean delivery and later died, and two developed cough, shortness of breath, and fever within 7 days after a normal delivery and died. Among the uninfected women, one died due to preexisting liver cancer and cirrhosis.
Women infected with SARS-CoV-2 stayed in the ICU for, on average, 3.73 days longer than uninfected women. Increased risk of serious maternal complications in COVID-19 patients was tied to fever and shortness of breath, as were complications in newborns. But the 44.0% of infected women with no symptoms were at higher risk for only maternal illness and preeclampsia.
This multinational cohort study showed that COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications.
Two thirds of the cohort (67.6%) took infliximab, while the remainder took vedolizumab. Patients’ median age was 39 years.
The study found that people with COVID-19 infections who also used the inflammatory bowel disease (IBD) drug infliximab had significantly fewer detectable antibodies than those who used vedolizumab, which treats IBD without the immune suppression, according to a study published in the journal Gut.
Lower antibody presence was seen in those who took infliximab, raising the researchers’ concerns about reinfection risk. Researchers note that 3.4% of the infliximab-treated group had SARS-CoV-2 seroprevalence, compared to 6.0% of the vedolizumab-treated group did. Those who were on additional immunomodulators such as thiopurines and methotrexate also had a reduced likelihood of being seropositive.
Of people with confirmed COVID-19 infections, only 48.0% of the 81 treated with infliximab demonstrated seroconversion, compared with 83.3% of the 36 on vedolizumab.
An impaired immune response may boost susceptibility to recurrent COVID-19 and may drive the evolution of new variants of SARS-CoV-2, warn the researchers. However, they are encouraging people to continue to take their medication as the overall COVID-19 risk remains low. Careful monitoring of patients with IBD treated with infliximab, who have been vaccinated against COVD-19, will be needed to ensure they mount a strong enough antibody response to ward off the infection, they advise.
CLARITY study lead, Professor Tariq Ahmad, of the University of Exeter Medical School, said:
“The poor antibody responses observed in patients treated with infliximab raise the possibility that some patients may not develop protective immunity after COVID-19 infection, and might be at increased risk of reinfection. What we don’t yet know is how the use of anti-TNF drugs will impact antibody responses to vaccination.”
The burden of inflammatory bowel disease is rising globally. The incidence of IBD is approximately 0.5-24.5 cases per 100,000 person-years for ulcerative colitis and 0.1-16 cases per 100,000 person-years for Crohn disease. Overall, the prevalence for IBD is 396 cases per 100,000 persons annually.
Around two million people worldwide are prescribed anti-tumour necrosis factor (anti-TNF) drugs, which include infliximab. Anti-TNF drugs are effective treatments for immune-mediated inflammatory diseases, but by suppressing the immune system, they can reduce vaccine effectiveness and increase the risk of serious infection.
A small randomized, double-blind clinical trial published in RMD Open showed colchicine to be safe and effective in treating moderate to severe COVID-19 infections in hospitalized patients. In the study, patients who took the inexpensive drug required supplemental oxygen and hospitalization for less time. This is the first randomized controlled trial (RCT) on colchicine for COVID-19.
Colchicine is most commonly used to prevent attacks of gout or pseudogout arthritis, which are types of arthritis caused by a buildup of crystals in the joints. Blood cells travel to these areas of inflammation, causing pain and swelling. Colchicine prevents white blood cells from traveling into these areas and therefore helps to reduce pain and tenderness.
Colchicine can also be used to treat acute attacks when nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen or ibuprofen cannot be used for safety reasons or have been ineffective. Colchicine is an alkaloid naturally occurring in Colchicum autumnale a plant of Liliaceae family.
Now, it has also been shown to be effective against COVID-19.
From April 11 to August 30, 2020, 72 Brazilian patients received either a placebo or 0.5 milligrams of colchicine three times a day for 5 days followed by the same dose twice a day for 5 days in addition to a standard COVID-19 treatment of azithromycin, hydroxychloroquine, heparin, and (after the RECOVERY Collaborative Group results were announced) glucocorticoid. Methylprednisolone was given if supplemental oxygen was 6 liters per minute or higher.
The most common side effect was diarrhea (16.7%), and colchicine doses were adapted if the patient weighed at least 176 pounds (80 kilograms) or had chronic kidney disease. Those on colchicine needed oxygen for an average of 4 days and stayed in the hospital for an average of 7 days; whereas, the control group needed oxygen for 6.5 days and stayed 9 days. The drug’s effect on ICU admission or mortality rate was not quantified, although the researchers note that 1 patient in the colchicine group went to the ICU compared with 3 in the placebo group. Two patients died in the study, both in the placebo group.
While the researchers acknowledge these results are not yet generalizable (34 of 35 patients receiving colchicine were overweight or obese), they concluded colchicine’s ability to slow systemic inflammation is promising. Systemic inflammation is the hallmark of hospitalized patients due to COVID-19. There is no specific treatment but supportive care and attempts to control the immune activation improve the clinical picture. By diminishing the activation of leucocytes, colchicine may be an intervention worthy of being tested further in more patients.
Most bats do not have rabies. According to the US Centers for Disease Control and Prevention (CDC), even among bats submitted for rabies testing, only about 6% had rabies. Rabies can only be confirmed in a laboratory but any bat that is active by day or is found in a place where bats are not usually seen like in your home or on your lawn or attic could be rabid. A bat that is weak and unable to fly could potentially be sick.
A man died of rabies in Limoges, in southwest central France, most probably after being bitten or scratched by a bat, as reported recently by the Institut Pasteur. This is a first in mainland France. The sixty-year-old succumbed to encephalitis, an inflammation of the brain of unexplained origin, in August 2019. A partnership established between the Necker hospital and the Pasteur Institute, aimed at identifying the causes of undocumented encephalitis, led to the genetic analysis of post-mortem samples. These analyzes at Necker Hospital in Paris showed that he had contracted a lyssavirus, European Bat LyssaVirus type 1 (EBLV-1), sheltered by bats.
“This shows that there are cases of rabies that we can miss”
“It is thanks to this retrospective diagnosis that this case was brought to light. This shows that there are cases of rabies that can be missed, ” explained Laurent Dacheux, deputy head of the national reference center for rabies at the Institut Pasteur.
“The trace of this virus was identified at that time, in November 2020. In the midst of the coronavirus , and this discovery went unnoticed”, continues Laurent Dacheux. This exceptional case was finally mentioned in a popular science article on the Mesvaccins.net site and highlighted by the regional daily Le Populaire du Center .
In contact with bats
“It has been thirty-five years since a death of this type has occurred in the world. And in mainland France, this is indeed a first,” assures Laurent Dacheux.
In 2019, a 21-year-old man died of rabies after coming into contact with a bat on Vancouver Island in the Canadian province of British Columbia. Health official Bonnie Henry confirmed that the man came into contact with a rabid bat in mid-May, began showing symptoms six weeks later, and died in July 2019.
Why don’t people get the rabies vaccine?
Rabies is a fatal disease. Each year, tens of thousands of people are successfully protected from developing rabies through vaccination after being bitten by an animal like a bat that may have rabies.
In some cases, people who died of rabies knew they were bitten by a bat. They did not go to a doctor to seek medical help because they were not aware that bats can have rabies and transmit it through a bite. In other cases, it is also possible that young children may not fully awaken due to the presence of a bat (or bite) or may not report a bite to their parents. Most bats have small teeth which may leave marks that can disappear quickly.
Which animals can be infected with rabies?
Any mammal can contract rabies. Rabies is most often reported in mammals that tend to come in contact with humans or live near human settlements, including bats, raccoons, skunks, and foxes. Cases of rabies have also been reported in deers, woodchucks, mongoose, opossums, coyotes, wolves, and monkeys. Pets and domesticated animals that are mammals can easily get the disease if bitten by another animal that is already infected. Cases in pets and other domesticated animals have been reported in dogs, cats, cows, horses, and rabbits.
If you are bitten by an animal – or if infectious material (such as saliva) from an animal gets into your eyes, nose, mouth, or a wound – it is important to wash the affected area thoroughly with soap and water and get medical advice immediately. Whenever possible, the animal should be captured and sent to a laboratory for rabies testing.
The new tuberculosis vaccine MTBVAC takes a new step as a candidate for universal vaccination against tuberculosis and an alternative to the current Bacillus Calmette–Guérin (BCG) vaccine, according to the results of the research published in the journal NPJ-Vaccines which shows the protection results of the MTBVAC vaccine compared to the current BCG vaccine in a model of respiratory tuberculosis in rhesus macaques.
The currently used BCG vaccine, based on a live attenuated form of Mycobacterium bovis isolated from cows and which, this year 2021, will make a 100 years since its first use in humans as a tuberculosis vaccine, continues to be the only licensed vaccine against the disease. After decades of research in this field, MTBVAC is the first and only vaccine based on the human pathogen Mycobacterium tuberculosis that has entered human clinical evaluation, a historic milestone in human vaccinology.
In this recently published study led by Dr. Sally Sharpe from Public Health England, a single dose of the MTBVAC vaccine administered intradermally has been found to confer significantly better protection against aerosol exposure to M. tuberculosis in Rhesus macaques when compared to BCG by the same route and dose of administration. Vaccination with MTBVAC resulted in a significant reduction in disease pathology induced by M. tuberculosis infection as measured by medical scan imaging in vivo, macroscopic pathological lesions examination, and pathological anatomy study of the frequency and severity of pulmonary granulomas.
This study consolidates previous preclinical and clinical safety and immunogenicity studies and represents a strong proof of concept of the efficacy of MTBVAC in the macaque model, the most relevant model of efficacy against respiratory tuberculosis, supporting and urging the clinical development of studies to demonstrate the efficacy of MTBVAC as a prophylactic vaccine against respiratory tuberculosis in humans. This would make MTBVAC an essential tool in the fight against tuberculosis.
Despite WHO’s declaration of tuberculosis as “global health emergency” in 1993, today the disease continues to be one of the leading causes of mortality caused by infectious diseases worldwide. The WHO Global tuberculosis report 2020 estimates that 1.4 million people died of tuberculosis in 2019 and it is estimated that as a consequence of the COVID-19 pandemic deaths from tuberculosis could increase by up to twenty per cent (20 %) in the next five years.
Our current understanding of SARS-CoV-2 immunity is mainly based on previous experiences with SARS-CoV (2003) and recent studies in patients infected with and recovered from SARS-CoV-2 (2020).
Similar to the SARS-CoV infection, the main antibody targets in SARS-CoV-2 are the spike and nucleocapsid proteins (NCP) — and this is where the vaccines also strike. However, it’s not clear if lasting immunity against the novel coronavirus can be achieved because serum antibodies seem to decline. Since this pandemic is still relatively new, we haven’t had much time to explore just how long antibodies and immunity lasts — but new results are coming in.
Two new studies published recently demonstrate that COVID-19 antibodies last as long as 8 months, or potentially even more, giving some good news for a mass vaccination campaign.
A study published in Science Immunology followed a small cohort of Australians from day 4 to day 242 after infection. All patients demonstrated the presence of memory B cells — immune cells that “remember” viral proteins and can trigger rapid production of antibodies when re-exposed to the virus — as long as 8 months after the initial infection.
Researchers took blood samples from 25 confirmed COVID-19 patients with a range of disease severities and 36 healthy control patients from March to September, evaluating each patient’s antibody status and levels of virus-specific immune cells. The study showed that by day 6 post-infection, all patients showed immunoglobulin G (IgG) antibodies for the viral receptor-binding domain (a protein on the viral surface that binds to cell receptors, allowing entry and infection) and the nucleocapsid protein. The immunoglobulin G levels began declining 20 days after symptom onset. However, memory B cell levels continued to rise up to 150 days post-infection and remained detectable 240 days post-symptom onset, suggesting that patient immune systems were primed to respond to reinfection.
According to the authors, cellular immunity could explain why there are few documented cases of reinfection with SARS-CoV-2 and why immunity can last longer than the antibody levels would suggest it.
Another study investigated antibody responses in 58 confirmed COVID-19 patients in South Korea 8 months after asymptomatic or mild SARS-CoV-2 infection.
The team used 4 commercially-available immunoassays:
Except for the anti-N IgG ELISA, all of these immunoassays have been granted Emergency Use Authorization by the US Food and Drug Administration.
For 3 of 4 immunoassays used, seropositivity rates were high (69% to 91.4%; P < 0.01). These results, published in Emerging Infectious Diseases, are contradictory to both the first study’s antibody data and previous research that showed antibodies waning after 20 days, but the authors suggest that variations in immunoassay test characteristics and manufacturing may be responsible for the difference.
Increasingly, the scientific evidence seems to suggest
Researchers at the University of Maryland School of Medicine showed COVID-19 patients who were taking a daily low-dose aspirin for cardiovascular disease had a significantly lower risk of complications and death compared to those who were not taking aspirin.
The researchers looked through the medical records of 412 COVID-19 patients, age 55 on average, who were hospitalized over the past few months due to complications of SARS-CoV-2 infection. About a quarter of the patients were taking a daily low-dose aspirin (usually 81 milligrams) before they were admitted or right after admission to manage their cardiovascular disease.
The researchers found aspirin use was associated with a 44 percent reduction in the risk of being put on a mechanical ventilator, a 43 percent decrease in the risk of ICU admission, and — most important of all — a 47 percent decrease in the risk of dying in the hospital compared to those who were not taking aspirin. The patients in the aspirin group did not experience a significant increase in adverse events such as major bleeding while hospitalized. The study definitely showed an association or correlation but remember correlation does not mean causation.
Nevertheless, this is promising because if this finding is confirmed (through clinical trials with larger sample size), it would make aspirin the first widely available, over-the-counter medication to reduce mortality in COVID-19 patients. Aspirin is a very potent antiplatelet agent. As soon as aspirin interacts with a platelet, that platelet becomes inactivated and can no longer create clots.
In July a study published in the Journal of the American College of Cardiology reviewed the effect of anticoagulant drugs on outcomes among hospitalized Covid-19 patients. Like the recent aspirin study, the investigators found that anticoagulants significantly reduced the risk of death among certain groups of people with Covid-19. Although these studies are encouraging, we need to wait for further studies to be done. Aspirin came into being in the late 1890s in the form of acetylsalicylic acid when chemist Felix Hoffmann at Bayer in Germany used it for his father’s rheumatism but salicin, which comes from the bark of the willow plant has been widely used hundreds of years before that.
Now, aspirin Is not only used to reduce pain, fever, or inflammation but is also the cornerstone of therapy to prevent a heart attack or a stroke since 1970s but the drug is not without risks. The greatest risk associated with aspirin is gastrointestinal bleeding so people who have a history of peptic ulcers or bleeding from the stomach should not take it.
The good news is the United Kingdom’s Recovery Trial, a large randomized controlled clinical study of potential COVID-19 treatments, will investigate aspirin as a possible therapy. Why aspirin? Patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. Platelets, small cell fragments in the blood that stop bleeding, seem to be hyperreactive in COVID-19 and may be involved in the clotting complications.
Aspirin is already widely used to prevent blood clots in many other conditions but enrolling patients in a randomized clinical trial is the best way to assess whether there are clear benefits for patients with COVID-19 and whether those benefits outweigh any potential side-effects such as the risk of bleeding. At least 2,000 patients are expected to get 150mg of aspirin daily along with the usual regimen. Hopefully, in a few months, we’ll know whether aspirin is indeed good for patients with COVID-19.
The Recovery trial was the first to show that dexamethasone, a steroid that is also cheap and widely available, could save the lives of people severely ill with Covid-19. It also showed that the anti-malarial drug hydroxychloroquine provided no benefit in treating COVID-19 patients.
Over 2 years since the Kivu Ebola epidemic began in August 2018, the US Food and Drug Administration (FDA) approved the first antibody cocktail for the treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients.
The drug, called Inmazeb, was developed by Regeneron — a biotech company also testing an antibody treatment for COVID-19. In clinical trials, patients who took Inmazeb were far less likely to die from Ebola virus disease.
In the clinical trial conducted during the outbreak in the North Kivu region, those treated with Inzameb experienced 33.5% mortality after 28 days. The World Health Organization (WHO) reports the virus’ mortality rate can be as high as 90%, depending on the outbreak.
The PALM trial, Pamoja Tulinde Maisha (meaning “together save lives”), is a randomized, controlled trial of four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3, now called Inmazeb) for the treatment of patients with Ebola virus disease.
To help control the Ebola virus outbreak, Inmazeb is being administered for free in the DRC with the support of the Biomedical Advanced Research and Development Authority (BARDA), and Regeneron has stated that it is working with non-governmental organizations and public health agencies to make sure the treatment is accessible to low- and middle-income countries.
This trial and other studies done during Ebola outbreaks over the past decade showed that it was possible and operationally feasible to conduct scientific research during an epidemic. Researchers are now applying those lessons during the COVID-19 pandemic. One of the US-based trials for the antiviral remdesivir, which the FDA authorized for emergency use, was modeled after the PALM trial.
“Today’s approval highlights the importance of international collaboration in the fight against Ebola virus,” said John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, in a press release.
Zaire ebolavirus, commonly known as Ebola virus, is one of four Ebolavirus species that can cause a potentially fatal human disease. Ebola virus is transmitted through direct contact with blood, body fluids and tissues of infected people or wild animals, as well as with surfaces and materials, such as bedding and clothing, contaminated with these fluids. Individuals who provide care for people with Ebola virus, including health care workers who do not use correct infection control precautions, are at the highest risk for infection. Ervebo, the first vaccine for the prevention of Ebola was approved by the European Medicines Agency in October 2019 and the US FDA in December 2019.
Two retrospective studies in Blood Advances add evidence for an association between blood type and COVID-19 risk, indicating that people with blood type O could be less susceptible to infection and experience milder disease. But this does not necessarily confirm causation. Further investigations on the mechanism of the different susceptibility to COVID-19 between blood group A and O individuals are needed and regardless of your blood type, you need to follow public health recommendations.
The first study from Denmark compared data from around 473,000 COVID-19–positive individuals with a control group of 2.2 million people in the general population, finding fewer infected people with blood type O and more people with A, B, and AB types. No associations were found between non-O blood groups and comorbidities that might explain infection rate differences.
The authors hypothesize that the presence of virus-neutralizing anti-A and anti-B antibodies on mucosal surfaces of some type O individuals may explain the relative protection for this blood type.
The second study from Vancouver, Canada on 95 critically ill COVID-19 patients in a hospital found that—after adjusting for sex, age, and comorbidities—patients with blood types A or AB were more likely to require mechanical ventilation than patients with types O or B (84% vs 61%, P = 0.02), indicating higher rates of lung damage.
Patients with blood types A and AB also had higher rates of dialysis for kidney failure, suggesting increased organ dysfunction or failure due to COVID-19 (32% vs 95%, P = 0.004). Patients with blood types A and AB did not have longer hospital stays than those with types O or B, but they did experience longer intensive care unit stays, which may signal greater COVID-19 severity.
A study in June looking at patients in Italy and Spain found that blood type O had a 50 percent reduced risk of severe coronavirus infection (i.e. needing intubation or supplemental oxygen) compared to patients with other blood types. A study published in July looking at patients in five major hospitals in the state of Massachusetts found that people with blood type O were less likely to test positive for COVID-19 than those with other blood types. Another study in April (pre-print and awaiting peer-review) found that among 1,559 coronavirus patients in New York City, a lower proportion than would be expected had Type O blood. Earlier in March, a study of over 2,100 coronavirus patients in Wuhan and Shenzhen (also not peer-reviewed) found that people with Type O blood had a lower risk of infection.
It’s important to emphasize that the type of reduction in risk achieved with appropriate physical distancing, wearing a mask, and hand hygiene are significantly better than depending on your blood group for protection, so people with blood type O should not be complacent about public health advice.
Trachoma is caused by the bacterium called Chlamydia trachomatis. In its early stages, trachoma causes conjunctivitis (pink eye) with symptoms appearing within five to 12 days of exposure to the pathogen. As the infection progresses, it causes eye pain and blurred vision.
If left untreated, scarring occurs inside the eyelid leading to the eyelashes turning inward toward the eye (a condition called trichiasis). As the eyelashes scratch against the cornea, it becomes irritated and eventually turns cloudy and can lead to corneal ulcers and vision loss. Generally, it takes years before trachoma can cause vision loss. In the early stages of the disease, antibiotics are very effective but more advanced cases may need surgery to help limit further scarring of the cornea and prevent further loss of vision. A corneal transplant can help if the cornea is so clouded that vision is significantly impaired.
Trachoma is the leading infectious cause of blindness globally and has long been considered a major public health problem in the Southeast Asian nation, with the first Trachoma Control Project initiated in 1964 by the Ministry of Health and Sports, with support from WHO and the United Nations Children’s Fund (UNICEF).
In 2005, trachoma was responsible for 4% of all cases of blindness in Myanmar. From 2010 to 2015, the annual period prevalence of blindness from all causes in the total population was very low in all regions and states, ranging from 0% to 0.023%. By 2018, this prevalence dropped to 0.008%. The WHO Weekly Epidemiological Record in July also reported the number of people at risk of trachoma has been reduced by 91% — from 1.5 billion in 2002, to 136.9 million in May 2020.
In order to eliminate trachoma as a public health problem, there is a WHO-recommended “S.A.F.E.” strategy which includes: Surgery for trichiasis, Antibiotics to clear Chlamydia trachomatis infection, Facial cleanliness, and Environmental improvement to reduce transmission. Community-based interventions also include improved access to water, sanitation and hygiene (WASH), and health education promoting behavior change to decrease transmission.
“This remarkable achievement reminds us of the importance of strong political commitment to implement integrated disease elimination measures, public engagement and disease surveillance,” said Dr. Mwelecele Ntuli Malecela, WHO Director, Department of Control of Neglected Tropical Diseases. “The new neglected tropical disease road map for 2021–2030, which will foster these processes globally, should allow us to anticipate more such success stories from countries using WHO-recommended strategies.”
Myanmar is the tenth country worldwide following Cambodia, China, Ghana, the Islamic Republic of Iran, Lao People’s Democratic Republic, Mexico, Morocco, Nepal, and Oman to reach this milestone. It remains a public health problem in 44 countries and is responsible for the blindness or visual impairment of an estimated 1.9 million people, most of whom are extremely poor. Regular post-validation trachoma surveys are also planned to provide post-validation surveillance. Successful validation of elimination of trachoma as a public health problem in Myanmar will encourage other health ministries and their partners to continue their efforts against this painful blinding disease.
We are learning more about how COVID-19 affects people every day, and this new find confirms what we’ve been fearing: asymptomatic people can pass the virus with the same ease.
We know that SARS-CoV-2, the virus causing COVID-19, is transmitted through direct contact with respiratory droplets of an infected person (generated through coughing and sneezing). Individuals can also be infected from and touching surfaces contaminated with the virus and touching their face (e.g., eyes, nose, mouth). The COVID-19 virus may survive on surfaces for several hours, but simple disinfectants can kill it.
Available evidence from contact tracing reported by countries suggests that asymptomatically infected individuals are much less likely to transmit the virus than those who develop symptoms. However, researchers from South Korea reported in JAMA Internal Medicinethat patients with confirmed asymptomatic COVID-19 infections shed virus at similar levels to those who are experiencing symptoms. “Viral shedding” refers to the release of the virus from an infected host. The investigators concluded that “isolation of infected persons should be performed regardless of symptoms.”
Their cohort study involved 303 patients who were isolated at a community treatment center in Cheonan in March. Healthcare workers carefully tracked patients’ symptoms during isolation. Among the group, 193 (63.7%) had symptoms at the start of isolation and 21 (19.1%) of the asymptomatic patients went on the develop symptoms. Healthcare workers also conducted reverse transcription polymerase chain reaction (RT-PCR) tests on lower and upper respiratory tract samples on multiple days at doctor discretion. Cycle threshold values for SARS-CoV-2 were similar for both asymptomatic and symptomatic patients. Viral shedding lasted about 17 days in asymptomatic patients and 19.5 days for symptomatic and pre-symptomatic patients.
Why are some people asymptomatic while others are not? SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Using the spike-like protein on its surface, the SARS-CoV-2 virus binds to ACE2 – like a key being inserted into a lock – prior to entry and infection of cells. Hence, ACE2 acts as a cellular doorway.
The ACE2 receptors appear to be more prevalent in older people and those who are obese than in younger and healthier people. That may partly explain why so many young people have not been as badly affected by the virus as those older than 60. Previous exposure to other coronaviruses, which can give people “T-cell immunity” to similar viruses, receiving a lower viral load of COVID-19 and other lucky genetic variations may also contribute to why some people having less severe or not symptoms to infection.
Togo, officially the Togolese Republic (République togolaise), a country in West Africa has received validation from the World Health Organization (WHO) for having eliminated human African trypanosomiasis or “sleeping sickness” as a public health problem, becoming the first country in Africa to reach this milestone. It gets its nickname ‘sleeping sickness’ because symptoms can include a disturbed sleep pattern.
What is African sleeping sickness?
Sleeping sickness is caused by parasites that are transmitted by infected tsetse flies and is only found in 36 countries in sub-Saharan Africa. If left untreated sleeping sickness is almost always fatal. In 1995, about 300,000 cases were estimated to have gone undetected, with 60 million people estimated to be at risk of infection. In 2019, fewer than 1,000 cases were found.
What are the two forms of sleeping sickness?
There are two forms of sleeping sickness. The first, due to Trypanosoma brucei gambiense, is found in 24 countries in west and central Africa and accounts for more than 98% of cases. The second form, due to Trypanosoma brucei rhodesiense, is found in 13 countries in eastern and southern Africa and represents the rest of cases. WHO and partners are targeting the elimination as a public health problem of the gambiense form of the disease from all endemic countries by 2030. Benin, Burkina Faso, Cameroon, Cote d’Ivoire and Ghana have started the validation process with the support of WHO.
How did Togo eliminate African sleeping sickness?
Togo has not reported any cases in the past 10 years. Togo’s achievement comes after more than two decades of sustained political commitment, surveillance and screening of cases. Beginning in 2000, the country’s public health officials implemented control measures. In 2011, the country established surveillance sites at hospitals in the cities of Mango and Tchamba, which cover the main areas at risk of the disease. Public health officials have since maintained heightened disease surveillance in endemic and at-risk areas. Neighboring countries are not at the same phase and so surveillance must continue to avoid a resurgence of this disease.
Togo first applied for certification of elimination of sleeping sickness in 2018 and a team of WHO experts studied the data, made recommendations and requested a revision by the country before giving their approval. A WHO-led global collaboration supported these efforts by facilitating the donation of medicines and resources from pharmaceutical companies, which helped strengthen local capacity and ensure the sustained availability of tools required to control the disease. Wiping out the gambiense form of sleeping sickness will require maintaining the commitment of endemic countries and of donors, as well as integrating control and surveillance activities into the regular health systems.
Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic disease that attacks the central nervous system, causing severe neurological disorders and death if left untreated. It is transmitted by the bite of the ‘Glossina’ insect, commonly known as the tsetse fly.
The disease mostly affects poor populations in rural areas where agriculture, fishing, animal husbandry, or hunting are the main source of livelihood. Typically, HAT is not found in urban areas, although cases have been reported in suburban areas of big cities in 36 sub-Saharan African countries where the disease is endemic. Travelers also risk becoming infected if they go to regions where the insect is common.
HAT wreaked havoc in Africa at different times in the 20th century but over the past twenty years, huge efforts made by a broad coalition of stakeholders, curbed the last epidemic.
Human African trypanosomiasis takes two forms, depending on the parasite involved: Trypanosoma brucei gambiense, found in 24 countries in west and central Africa, accounts for 98% of reported cases of sleeping sickness and causes a chronic infection.
A person can be infected for months or even years without major signs or symptoms of the disease. When more evident symptoms emerge, the patient is often already in an advanced disease stage.
Trypanosoma brucei rhodesiense is found in 13 countries in eastern and southern Africa. This form represents under 2% of reported cases and causes an acute infection that invades the central nervous system.
977 cases of HAT were reported in 2018, down from 2,164 in 2016.
The area at moderate or high risk of HAT has shrunk to less than 200,000 square kilometres. More than half of this area is in the Democratic Republic of the Congo. In the last 10 years, over 70% of reported cases occurred in the Democratic Republic of the Congo.
Health facilities providing diagnosis and treatment for HAT have increased since the last survey, meanwhile active screening is maintained at similar levels.
The number of cases, the main global indicator, is already well within the 2020 target (i.e. 2,000 cases). The areas at moderate or higher risk (i.e. > 1 case/10,000 people/year) are also nearing the 2020 target. The reliability of these data is backed by a reinforced coverage of the populations at risk by surveillance and control activities, providing strong evidence that global elimination of the disease is advancing.
There is no vaccine or drug for prophylaxis and preventive measures are aimed at minimizing contact with tsetse flies. Sleeping sickness is curable with medication but is fatal if left untreated. Surveillance networks, such as ProMED-mail and TropNetEurop should be maintained and expanded to ensure access to institutional databases. Due to the success of surveillance systems in Western countries, the possibility of introducing similar ‘alarm’ systems for HAT in Africa should be explored. Innovation in HAT control and surveillance is still needed but the 2030 goal of elimination as interruption of HAT transmission is on track.
“COVID toes” are not a sign of COVID-19 infection but a result of sedentary lifestyles linked to community lockdown measures, walking around barefoot at home, and a lack of warm footwear – at least according to two small studies published JAMA Dermatology.
The study from Belgium, led by Dr. Anne Herman, investigated the purplish-red chilblain-like lesions on the feet of 29 patients and the hands of 3 patients of individuals seen at a Brussels dermatology clinic from Apr 10 to 17. They found that COVID-19 is not the cause of these inflammations.
For starters, none of the patients tested positive for SARS-CoV-2, the virus that causes COVID-19, or had antibodies against the virus on serologic testing.
Biopsies of 22 skin samples also showed no evidence of the virus. Twenty of 31 patients (64%) reported mild symptoms characteristic of coronavirus, and 3 (10%) reported contact with a person who tested positive for COVID-19.
Doctors had assumed that COVID-19 is somehow at play, but it turns out that the assumption was not true. So what was the cause?
Nine of 31 patients (29%) had a history of chilblains, and 4 (13%) had Raynaud’s syndrome (discoloration of the fingers or the toes due to changes in temperature or emotional events).
In addition, 64% said they had been less physically active than normal while in lockdown, and most said they remained in socks or barefoot most of the day.
The other study from Spain, led by Dr. Ignacio Torres-Navarro from the University Hospital of la Fe Polytechnic in Valencia, analyzed “COVID toes” in 20 children hospitalized in Spain from Apr 9 to 15 with lesions on the hands and feet.
They had no clinical signs of COVID-19, tested negative on RT-PCR, and had no antibodies against the virus on serologic testing. So again, the coronavirus was not causing the toe injuries.
Histologic testing revealed that the lesions were chilblains. Nine of 20 patients (45%) had a history of Raynaud’s syndrome or chilblains, and 15 (75%) said they walked barefoot around their house during quarantine. Furthermore, only 2 lived in a home with heat.
“Other studies with improved microbiologic tests or molecular techniques aimed at demonstrating the presence of SARS-CoV-2 in the skin may help to clarify this problem,” the authors wrote.
So the symptom does not appear to be caused by COVID-19, but rather by chilblains.
A chilblain is a painful inflammatory condition that results from defective blood circulation on exposure to cold. The skin may first become itchy, then red and swollen with a burning sensation and very tender to touch. An infection may occur should the skin break down.
Another potential cause is Raynaud’s syndrome: a narrowing of the small arteries that supply blood to the skin in response to cold temperatures or stress.
Having chilblains does not necessarily mean that you have Raynaud’s. However, as both conditions are related to the circulation many people with Raynaud’s also have chilblains.
A study published mid-April reported that people infected with SARS-CoV-2, the coronavirus causing COVID-19, might be most contagious during the period before they have symptoms. Two studies published in late May showed that a high percentage of people with COVID-19 could be without symptoms.
In one study, Australian researchers reported that 104 of 128 people (81 percent) on a cruise ship who tested positive for the novel coronavirus were asymptomatic. In another study, researchers in Wuhan, China reported that 33 of 78 people (42 percent) who tested positive for COVID-19 were without symptoms.
The study involved 100 asymptomatic and 411 symptomatic coronavirus patients in hospitals in 21 cities and 47 counties or districts from Jan 25 to Feb 20. The investigators also found that patients without symptoms were younger and came from higher-altitude areas with less resident mobility and more defined epidemiologic history than patients with symptoms but had similar rates of underlying conditions.
Of the 100 well-documented asymptomatic cases, 17 (27.4%) later developed symptoms, two of the older patients developed severe symptoms during hospitalization. No asymptomatic patients died. One patient was believed to have transmitted the virus during the incubation period.
Of the more than 4,000 confirmed cases linked to the event, 19 from Brunei tested positive for COVID-19 and infected 52 others. According to the researchers, this is the first report documenting the role of asymptomatic SARS‐CoV‐2 transmission in the propagation of a large superspreading event.
The authors said that their findings support the use of testing and longitudinal surveillance of asymptomatic close contacts, as well as widespread testing at mass gatherings in places with known community spread.
All these studies strengthen the argument for people to wear masks. After first telling the public there was no need for people to wear a mask unless they were sick or coughing, the US CDC revised their position. Since early April, the agency has recommended that in addition to physical distancing measures, people should wear a face covering if they go to a public place in settings where physical distancing measures are difficult to maintain (e.g., grocery stores and pharmacies) especiallyin areas of significant community-based transmission. They have posted instructions on how to properly wear a cloth mask.
For many infectious diseases, women are at higher risk and experience a more severe course of illness than men. In some southern African countries, for example, young women are up to eight times more likely to have HIV than men of the same age, which is thought to be due, in part, to gender inequity, gender-based violence, age-disparate relationships, and not simply because of biological differences.
But in the case of COVID-19, that’s not the case — in this case, it’s men that seem to bear the brunt of the damage.
Men are more likely than women to die of the coronavirus. This is particularly pronounced in Italy, where men represent nearly 70% of the country’s deceased patients. Scientists suspect unhealthy habits like smoking and underlying health issues among men could be influencing this trend.
According to a study
in Frontiers in Public Health, men
are 2.4 times as likely to die from COVID-19 than women, regardless of age. Moreover,
older men with underlying medical conditions are much more likely than their
female counterparts to have poor outcomes from COVID-19 infection, according to
a small retrospective study
published in PLOS Pathogens.
Investigators in the Frontiers study extracted data from a case series of 43 COVID-19 patients hospitalized in Wuhan, China; a public data set from the first 37 patients who died of the virus and 1,019 survivors in China; and information from 524 SARS (severe acute respiratory syndrome) patients, including 139 who died, in 29 Beijing hospitals in early 2003 to compare the two diseases.
In the case series, 37.2% of patients had one or more underlying conditions, such as high blood pressure, diabetes, cardiovascular diseases, and chronic lung disorders. Male COVID-19 patients had elevated levels of serum creatinine (indicating kidney damage), white blood cells (indicating immune response), and neutrophils (indicating inflammation). Of the 43 patients in the case series, 13 (30.2%) had mild or moderate pneumonia, while 14 (32.6%) had severe pneumonia, 16 (37.2%) had critical pneumonia. Chi-square (χ2) test for trend showed that men tended to have more serious illnesses than women (P = 0.035).
Advanced age and a
high number of underlying diseases were linked to more severe disease and death
in patients who had either COVID-19 or SARS. In the case series, men tended to
have more serious disease than women (P
= 0.035), while the public data set revealed that men were 2.4 times more
likely than women to die of COVID-19 (70.3% versus 29.7%; P = 0.016).
Of the 37 non-survivors
in the public data set, 70.3% were men, 29.7% were women, and 64.9% had one or
more underlying conditions. These patients were significantly older, at 65 to
81 years, with 83.8% of them age 65 and older, versus survivors, who were 35 to
57 years old, with 13.2% 65 and older.
In patients with
SARS, the proportion of males in the group who died was higher than that of the
surviving group (P = 0.015). In
this group, 57.0% of patients had one or more underlying conditions. Median age
of non-survivors was much higher than that of survivors (57 versus 32; P < 0.001), and non-survivors
were also more likely than survivors to have underlying disease (57.0% versus
17.9%; P < 0.001).
The percentage of men was higher in the non-surviving group (53.2%) than in the
surviving group (42.3%) (χ2 test; P = 0.027). Men were also significantly more likely to die
than women (31.2% vs 22.6%; hazard ratio, 1.47; 95% confidence interval [CI],
1.05 to 2.06; P =
In the PLOS Pathogenscase series, researchers studied the data of 168 patients with the novel coronavirus admitted consecutively to Tongji Hospital in Wuhan, China, from Jan 16 to Feb 4. Overall, 17 patients (8.9%) died, while 136 (81%) were released from the hospital. Eleven (12.8%) of the 86 male patients died, while 65 (75.6%) were released from the hospital. Six (7.3%) of the 82 female patients died, while 71 (86.6%) were released. Fifty-seven patients had underlying conditions (33.7%). Median time from illness onset to hospital admission was 9 days for males and 7 days for females.
Of male patients, 36.0% had a chronic underlying illness, especially diabetes and cardiovascular and cerebrovascular diseases. After adjusted logistic regression analysis, males with underlying illnesses were more vulnerable to critical illness than those without comorbidities.
This was not the case for females. After adjustment for confounding factors, males 80 years and older were more likely to become critically ill than those younger than 59. But this wasn’t true for females.
Men and women differ in both innate and adaptive immune responses. These disparities may be attributed to steroids and X-linked gene activity, which both regulate the immune response to viruses. The authors said that future studies are needed to identify the different pathways and cellular responses between the two sexes.
Increasingly, it is being shown that COVID-19 tends to spread faster and easier indoor than outdoor.
Previous studies have demonstrated that SARS-CoV-2, the virus that causes COVID-19, is stable on surfaces for extended periods of time, under indoor conditions.
A research from China showed that coronavirus transmission still takes place despite changing weather conditions in different parts of the country — ranging from cold and dry to warm and humid. A study in Hong Kong using SARS-CoV-2 in a lab solution showed that increasing temperature decreased the amount of viable virus that could be detected. No infectious virus remained after 30 minutes at 56° Celsius and five minutes at 70°C was enough to inactivate the pathogen.
Now, a new study by researchers at the National Biodefense Analysis and Countermeasures Center, a government biodefense research laboratory created by the U.S. Department of Homeland Security, shows that natural sunlight can rapidly inactivate SARS-CoV-2 on surfaces.
The findings, which come with caveats, suggest that the potential for fomite transmission may be significantly reduced in outdoor environments exposed to direct sunlight.
Sunlight vs COVID
To evaluate the influence of simulated sunlight on the persistence of SARS-CoV-2 on surfaces, the researchers exposed concentrated virus suspended in either simulated human saliva or culture media and then dried on stainless steel coupons mounted in a chamber to a light spectrum designed to represent natural sunlight. The coupons were exposed to the simulated sunlight for differing exposures, ranging from 2 to 18 minutes, to allow estimation of the viral inactivation rate. For comparison, the researchers also exposed a series of contaminated coupons in the chamber with no simulated sunlight for 60 minutes.
The results showed that under levels of simulated sunlight representative of midday on the summer solstice at 40°N latitude (the 40th Parallel), 90% of infectious virus is inactivated every 6.8 minutes in simulated saliva dried on a surface and every 14.3 minutes in cultured media dried on a surface. Significant inactivation also occurred under lower simulated light levels but at a slower rate. Inactivation rates were near zero on the coupons not exposed to sunlight.
The inactivation rate of SARS-CoV-2 was approximately two-fold greater in simulated saliva than in culture media. However, the researchers say it is unclear if the viral concentrate in simulated salvia is representative of contaminated saliva from an infected individual. This is good news but do not assume that summer months will be safer.
Sunlight has been in the COVID-19 news cycle for another reason – it is a great natural source of vitamin D, which has several health benefits, including an increased resistance to infectious diseases. When it comes to COVID-19, research is limited but clinical trials have started in Spain and France to see if vitamin D improves outcomes for COVID-19 patients. Both studies are expected to end in July 2020. In the meantime, continue to take appropriate steps to protect yourself and those around you.
A phase 2 trial has shown that a 2-week course of triple antiviral therapy with (1) interferon beta-1b (used to treat the relapsing-remitting and progressive forms of multiple sclerosis), (2) lopinavir-ritonavir (for the treatment of HIV/AIDS) and (3) ribavirin (used to treat chronic hepatitis C and other flavivirus infections) is safe and better at shortening COVID-19 viral shedding than lopinavir-ritonavir alone (average 7 days vs. 12 days) in patients with mild to moderate illness if treatment is started within 7 days of symptom onset.
A Phase 3 study needs to be done and submitted to regulatory agencies for this regimen to be approved. Phase 3 study is a large, properly powered human clinical trial, typically featuring hundreds or thousands of people. To move forward with the trial, investigators need to demonstrate that the medication is at least as safe and effective as existing treatment options. The phase 3 trial will be designed to evaluate whether this specific 3-drug combo is better than the other treatment, 2-drug combo, in patients infected with SAR-CoV-2, the coronavirus causing COVID-19.
The prospective study, published in The Lancet, involved 127 adult COVID-19 patients (mean age, 52 years) admitted to six Hong Kong hospitals from February 10 to March 20, 2020. Eighty-six patients were randomly assigned to receive 2 weeks of the triple-drug regimen every 12 hours plus as many as three doses of injectable interferon beta-1b every other day, while 41 received lopinavir-ritonavir alone every 12 hours.
The investigators detected
no live coronavirus on nose-throat swabs within, on average, 7 days after the triple-drug
combination started, 5 days earlier than with lopinavir-ritonavir alone (hazard
ratio, 4.37; 95% confidence interval, 1.86 to 10.24; P = 0.0010). The 3-drug
combination also reduced the mean time to complete symptom relief into half (4
versus 8 days) and Sequential Organ Failure Assessment score of 0 (3 versus 8
days) and shortened the mean hospital stay from 14.5 to 9 days.
The findings also suggest
that interferon beta 1-b may be a key component of the combination and is worth
further investigation for the treatment of COVID-19. Interferons are naturally
occurring proteins, produced in response to viral infection and interferon
beta-1b could potentially boost the body’s ability to fight SARS-CoV-2.
However, while patients who
received the combination therapy within 7 days of symptom onset did better than
those in the control group, there was no difference when they were treated 7 or
more days after the start of symptoms. The researchers said that the results
suggest that the 3-drug combination may minimize the risk of antiviral
resistance and decrease risks to healthcare workers by reducing the duration
and quantity of viral shedding.
The BCG (Bacillus Calmette–Guérin) vaccine, discovered by Albert Calmette and Camille Guérin, is one of (if not) the most widely used vaccine worldwide. Next year will mark the 100th anniversary of the first time this live, attenuated (weakened) version of a virulent bovine strain of tubercle bacillus was administered to a person.
The BCG vaccine protects against tuberculosis, also known as TB, a serious infection that affects the lungs and sometimes other parts of the body, such as the bones, joints and kidneys. The World Health Organization (WHO) recommends BCG vaccination as soon as possible after birth in countries with a high incidence of tuberculosis
This century-old vaccine is in the spotlight the past weeks because of a few ecological studies (pre-prints, not peer-reviewed at this stage) that claim a strong correlation between BCG vaccination and protection against SARS-CoV2, the coronavirus causing COVID-19.
Ecological studies are inherently limited since they take aggregate data and try to make inferences at the individual level. Such ecological studies are prone to significant bias from many confounders, including differences in national demographics and disease burden, testing rates for COVID-19 virus infections, and the stage of the pandemic in each country.
Some of these analyses were done over a month ago. Since then, COVID-19 cases and deaths have spiked up in many low and middle-income countries where BCG vaccination is administered to all newborns. Many of the countries with BCG in their national immunization programs seriously under-test for COVID-19.
There is experimental evidence from both animal and human studies that the BCG vaccine has non-specific effects on the immune system. However, these effects have not been well characterized and their clinical relevance is unknown.
There are two registered protocols for clinical trials — BCG-CORONA (The Netherlands) and BRACE (Australia) — both of which aim to study the effects of BCG vaccination given to health care workers directly involved in the care of patients with COVID-19. Results from these studies will provide more information whether or not the BCG vaccine indeed protects against COVID-19.
BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in neonates not being vaccinated, resulting in an increase of disease and deaths from tuberculosis.
Researchers and journalists need to be responsible not to raise false hopes based on weak evidence. In the absence of clear and robust evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis.