tuberculosis travel vaccine

TB Information for International Travelers Fact Sheet

Tuberculosis information for international travelers, what is tuberculosis (tb).

Tuberculosis (TB) is a disease caused by bacteria that are spread from person to person through the air. TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine. In most cases, TB is treatable and curable; however, persons with TB can die if they do not get proper treatment.

What is multi-drug resistant tuberculosis (MDR TB)?

Multidrug-resistant TB (MDR TB) is TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampin. These drugs are considered first-line drugs and are used to treat all persons with TB disease.

What is extensively drug-resistant tuberculosis (XDR TB)?

Extensively drug resistant TB (XDR TB) is a rare type of MDR TB. XDR TB is defined as TB which is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Because XDR TB is resistant to the most powerful first-line and second-line drugs, patients are left with treatment options that are much less effective.

XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB.

How is TB spread?

Drug-susceptible TB and drug-resistant TB are spread the same way. TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. These bacteria can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB bacteria can become infected.

TB is not spread by

• shaking someone’s hand
• sharing food or drink
• touching bed linens or toilet seats
• sharing toothbrushes

How does drug resistance happen?

Resistance to anti-TB drugs can occur when these drugs are misused or mismanaged. Examples include when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or length of time for taking the drugs; when the supply of drugs is not always available; or when the drugs are of poor quality.

Are international travelers at risk of getting drug-resistant TB while traveling?

Although MDR and XDR TB are occurring globally, they are still rare. HIV-infected travelers are at greatest risk if they come in contact with a person with MDR or XDR TB. All travelers should avoid high risk settings where there are no infection control measures in place.

Documented places where transmission has occurred include crowded hospitals, prisons, homeless shelters, and other settings where susceptible persons come in contact with persons with TB disease.

Air travel itself carries a relatively low risk of infection with TB of any kind.

What is the risk of acquiring TB on an airplane?

The risk of acquiring any type of TB depends on several factors, such as extent of disease in the patient with TB, duration of exposure, and ventilation. Most important, there must be someone with infectious TB disease on the same flight to present any risk. If someone on the flight does have TB disease, persons on flights lasting 8 hours or longer are at greater risk than persons on shorter flights.

How can TB be prevented?

Travelers should avoid close contact or prolonged time with known TB patients in crowded, enclosed environments (for example, clinics, hospitals, prisons, or homeless shelters).

Travelers who will be working in clinics, hospitals, or other health care settings where TB patients are likely to be encountered should consult infection control or occupational health experts. They should ask about administrative and environmental procedures for preventing exposure to TB. Once those procedures are implemented, additional measures could include using personal respiratory protective devices.

Is there a vaccine to prevent TB?

Yes, there is a vaccine for TB disease called Bacille Calmette-Gurin (BCG) . It is used in some countries to prevent severe forms of TB in children. However, BCG is not generally recommended in the United States because it has limited effectiveness for preventing TB overall.

What should I do before traveling internationally?

Travelers who anticipate possible prolonged exposure to persons with TB (for example, those who expect to come in contact routinely with clinic, hospital, prison, or homeless shelter populations) should have a tuberculin skin test (TST) or TB blood test before leaving the United States. If the reaction to the TST or TB blood test is negative, they should have a repeat test 8 to 10 weeks after returning to the United States. Additionally, annual testing may be recommended for those who anticipate repeated or prolonged exposure or an extended stay over a period of years. Because persons with HIV infection are more likely to have an impaired response to both the TST and TB blood test, travelers who are HIV positive should tell their physicians about their HIV infection status.

What should I do if I think I have been exposed to someone with TB disease?

If you think you have been exposed to someone with TB disease, you should contact your doctor or local health department about getting a TB skin test or TB blood test. And tell the doctor or nurse when you spent time with this person.

What are the symptoms of TB disease?

The general symptoms of TB disease include feelings of sickness or weakness, weight loss, fever, and night sweats. The symptoms of TB disease of the lungs also include coughing, chest pain, and the coughing up of blood. Symptoms of TB disease in other parts of the body depend on the area affected. If you have these symptoms, you should contact your doctor or local health department.

Where can I find other health information about my travel destination?

CDC’s Travelers’ Health website lists health information for travelers by destination.

CDC issues travel notices when there is a health threat to travelers. These notices describe levels of risk for the traveler and recommended preventive measures to take at each level of risk. Travel notices are organized by disease and by travel destination.

Additional Information

CDC. Questions and Answers About TB .

CDC. Tuberculosis: General Information (2006).

CDC. Tuberculin Skin Testing (2006).

CDC. BCG Vaccine (2006).

CDC. Health Information for International Travel – The “Yellow Book”: Chapter 3 – Infectious Diseases Related to Travel: Tuberculosis (2012) .

WHO. Tuberculosis and Air Travel: Guidelines for Prevention and Control (PDF).

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Tuberculosis Vaccine: In the United States and Around the World

There are several reasons it’s not available in the United States

• History and Modern Use

Which Countries Use It?

• In the U.S.

Efficacy and Side Effects

• Vaccine Ingredients

Frequently Asked Questions

The tuberculosis vaccine, also known as the bacille Calmette-Guérin (BCG) vaccine, is used to protect against tuberculosis (TB) and related complications. 

The BCG vaccine is no longer routinely given in the United States and isn’t recommended for the general population by the Centers for Disease Control and Prevention (CDC). However, it’s still given to babies and young children in many countries worldwide. The tuberculosis vaccine may also be considered in the United States for certain people with significant risk factors for prolonged exposure to TB.

In this article, we’ll go over the history and use of the tuberculosis vaccine, including which countries use it, age recommendations, effectiveness, side effects, and more.

Teka77 / Getty Images

History and Modern Use of Tuberculosis Vaccine

Tuberculosis is an infection caused by the bacterium Mycobacterium tuberculosis . Usually, M. tuberculosis bacteria attack the lungs, which causes pulmonary TB. Symptoms of pulmonary tuberculosis include a severe, persistent cough, chest pain, and coughing up blood. Other symptoms of TB may include:

• Night sweats
• Lack of appetite
• Unwanted weight loss

In some cases, M. tuberculosis bacteria can attack other body parts, such as the spine, brain, or kidneys. Many people who are infected with TB don’t have any symptoms. This is known as latent TB infection (LTBI). People with LBTI can’t spread TB to others.

However, about 5 to 10% of people with LTBI develop active TB. People with TB disease have symptoms and can spread M. tuberculosis through actions like coughing, speaking, and singing. Screening for LTBI is recommended for anyone at greater risk of exposure to TB.  

If left untreated, TB can be serious and even fatal. Tuberculosis is especially dangerous for immunocompromised people, including people with human immunodeficiency virus (HIV).

In the early 1900s, the BCG vaccine was developed by researchers Albert Calmette and Camille Guérin to protect against tuberculosis and related complications. It was in wide use by the 1920s but fell out of favor after the Lübeck disaster in 1930 in which 73 infants tragically died in the first year after receiving a contaminated version of the vaccine. More than a decade later, the BCG vaccine came back in response to rising global tuberculosis rates after World War II.  

However, the tuberculosis vaccine is no longer routinely administered in the United States. Studies have shown mixed results in terms of the vaccine’s effectiveness. Some people who have received the vaccine may also get a false positive result on a tuberculin skin test (TST), which can complicate treatment plans and lead to confusion.

While BCG vaccination may cause a false-positive skin test result (when the test indicates that the disease is present when it is not), getting the BCG vaccine will not cause a false-positive TB blood test.

Additionally, the risk of TB in the United States is so low that the benefits of getting vaccinated may not outweigh the potential downsides.

Mandatory BCG vaccination is now somewhat controversial, but many countries with a high incidence of TB cases continue to vaccinate newborns just after birth. Globally, around 2 million–3 million people die from TB disease and related complications yearly. Deaths from tuberculosis are particularly common in developing countries and countries with high rates of HIV, as well as in environments like nursing homes, prisons, homeless shelters, and hospitals.  

In the United States, the CDC recommends that the BCG vaccine be considered only for the following groups:

• Children: Some children with a high risk of developing TB may benefit from BCG vaccination. This includes children who cannot be treated for tuberculosis and who live with adults who have untreated, ineffectively treated, or drug-resistant TB.
• Healthcare workers: Healthcare workers who are employed in settings where a large number of patients have drug-resistant TB and/or where tuberculosis treatments have failed may consider BCG vaccination, if recommended by their healthcare provider.

The BCG vaccine is given to infants on a regular basis in over 180 countries. According to the World Health Organization (WHO), many countries in Southeast Asia, sub-Saharan Africa, and the former Soviet Union have high rates of TB disease. There are also high TB rates in other parts of Europe, Africa, and Asia, as well as parts of the Americas.

Examples of countries where there is a high incidence of tuberculosis include:

• Democratic Republic of the Congo
• Philippines

Tuberculosis Vaccine Travel Restrictions and Requirements

The risk of developing drug-resistant TB disease is extremely rare while traveling internationally. However, your healthcare provider may recommend that your child receive the BCG vaccine if you are planning to travel to a country with high rates of TB if your child is under 5 years old.  If you plan to travel to a country with high rates of tuberculosis, especially drug-resistant tuberculosis, the CDC recommends a tuberculin skin test or blood test first. If you test negative, you should get another test eight to 10 weeks after returning to the United States. Make sure to take any recommended precautions against infection if you spend time in a high-risk environment, such as a healthcare setting.

Age Recommendations

The BCG vaccine is most effective in babies and children under 5. Older children and adults may not benefit as much from receiving it. However, people of all ages may still be considered for the vaccine if they have certain risk factors.

In areas where the BCG vaccine is routinely administered, it’s usually given to newborns. For example, the BCG vaccine is recommended for all newborns as part of the Hong Kong Childhood Immunisation Programme.

How Effective Is the Tuberculosis Vaccine in Children Ages 5 and Up?

Recent research suggests that the tuberculosis vaccine is only significantly effective in preventing severe disease in children under age 5. Among kids age 5 and up who haven’t had a positive TB test, some studies indicate that BCG vaccination doesn’t offer reliable protection against TB disease and related complications.

Tuberculosis Cases in the United States

In the United States, tuberculosis cases are relatively rare. In total, 8,300 TB cases were reported to the CDC’s National Tuberculosis Surveillance System in 2022. Rates of TB disease in the United States decreased consistently from 1993–2019.

They briefly declined sharply (by 19.9%) during the beginning of the COVID-19 pandemic in early 2020 and rose by 9.4% in 2021. Still, the overall number of U.S. TB cases in 2022 was lower than in 2019.

Evidence of the effectiveness of the tuberculosis vaccine is somewhat mixed. According to a 2022 systematic review and meta-analysis, the BCG vaccine was found to be 18% effective overall in protecting against tuberculosis disease and related complications.

It is primarily effective in infants and young children. It is, however, very effective in preventing young children from getting severe forms of tuberculosis like tuberculosis meningitis and miliary tuberculosis.

The most common side effects of the BCG vaccine are:

• Swollen glands in the armpit near the injection site
• A sore at the site of injection, which often releases discharge, scabs over, and leaves behind a scar
• Other skin reactions

Very rarely, BCG vaccination can lead to serious complications, such as abscesses or bone inflammation.

You shouldn’t get the tuberculosis vaccine if you:

• Are pregnant
• Are living with HIV
• Are immunocompromised
• Are allergic to any of the vaccine ingredients

BCG Vaccine Ingredients

The BCG vaccine is a live vaccine . It uses a weakened strain of Mycobacterium bovis (M. bovis), a bacterium closely related to the one that causes TB. Other ingredients include:

• Citric acid
• Magnesium sulfate
• Iron ammonium citrate
• Potassium phosphate

As with other vaccines, the tuberculosis vaccine has been thoroughly tested and vetted for safety.

The bacille Calmette-Guérin (BCG) vaccine, or tuberculosis vaccine, is used in certain countries worldwide to prevent tuberculosis (TB) infection and complications. Typically, the vaccine is given as a shot in the upper arm to infants just after birth. The tuberculosis vaccine is safe, but evidence of its effectiveness in protecting against TB is relatively mixed.

The BCG vaccine is no longer widely used in the United States. However, according to the CDC, the BCG vaccine may be considered for children and adults with a high risk of tuberculosis exposure. Examples include healthcare workers and children who are regularly cared for by adults with drug-resistant tuberculosis or untreated TB.

The TB shot is not given routinely in the United States. However, you can ask your healthcare provider about getting the vaccine if you have a significant risk factor for TB disease.

They may be able to give you the vaccine themselves in their office, or they may recommend that you visit a different clinic or local health agency to be vaccinated. A nearby TB control program may also offer vaccination.

In the United States, the TB vaccine is sometimes considered for people who test negative for TB and are continuously exposed to it regularly. Some examples of high-risk groups include certain healthcare workers and children who live with adults with drug-resistant TB. People who live or work in communal, crowded settings, such as prisons, homeless shelters, and certain hospitals, may also be at risk.

Up to 97% of people who receive the TB vaccine will develop a small scar at the injection site (typically the upper arm). Around two to four weeks after getting the vaccine, you may notice a raised “bubble” on the skin, which usually scabs over and heals within a few months. This is because of the skin’s reaction to the weakened form of Mycobacterium bovis , a bacterium closely related to the one that causes TB disease.

Correction - September 1, 2023: This article was updated to correct the BCG vaccine ingredients.

U.S. Centers for Disease Control and Prevention. BCG vaccine fact sheet .

U.S. Centers for Disease Control and Prevention. Basic TB facts .

U.S. Centers for Disease Control and Prevention. Signs & symptoms: TB .

U.S. Centers for Disease Control and Prevention. How TB spreads .

US Preventive Services Task Force, Mangione CM, Barry MJ, et al. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement .  JAMA . 2023;329(17):1487-1494. doi:10.1001/jama.2023.4899

World Health Organization. BCG vaccine .

Luca S, Mihaescu T. History of BCG vaccine . Maedica (Bucur) . 2013;8(1):53-8. PMID: 24023600; PMCID: PMC3749764.

Food and Drug Administration. BCG vaccine package insert .

World Health Organization. 2.1 TB incidence .

NSW Health. Overseas travel with children .

U.S. Centers for Disease Control and Prevention. TB information for international travelers fact sheet .

Martinez L, Cords O, Liu Q, et al. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis .  Lancet Glob Health . 2022;10(9):e1307-e1316. doi:10.1016/S2214-109X(22)00283-2

Family Health Service. Bacille Calmette-Guerin (BCG) Vaccine .

Schildknecht KR, Pratt RH, Feng PI, Price SF, Self JL. Tuberculosis — United States, 2022 . MMWR Morb Mortal Wkly Rep 2023;72:297–303. doi:10.15585/mmwr.mm7212a1

Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness .  The Lancet . 2006;367(9517):1173-1180. doi:10.1016/S0140-6736(06)68507-3

National Health Service. BCG (TB) vaccine side effects .

Mohamed L, Madsen AMR, Schaltz-Buchholzer F, Ostenfeld A, Netea MG, Benn CS, Kofoed PE. Reactivation of BCG vaccination scars after vaccination with mRNA-Covid-vaccines: Two case reports . BMC Infect Dis . 2021;21(1):1264. doi:10.1186/s12879-021-06949-0

By Laura Dorwart Dr. Dorwart has a Ph.D. from UC San Diego and is a health journalist interested in mental health, pregnancy, and disability rights.

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Tuberculosis Information for International Travelers

This information sheet discusses TB and the risk for international travelers. It explains TB transmission, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of the disease, and how drug resistance occurs. The information sheet considers whether international travelers are at risk of MDR or XDR TB while traveling, the risk of acquiring TB on an airplane, how TB can be prevented, TB vaccine, and what an individual should do before traveling internationally and if an individual thinks that he/she may have been exposed to someone with TB disease. It lists the symptoms of TB disease and where to find other health information about a travel destination. Contact information is provided for additional resources.

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Vaccines for Travelers

Vaccines protect travelers from serious diseases. Depending on where you travel, you may come into contact with diseases that are rare in the United States, like yellow fever. Some vaccines may also be required for you to travel to certain places.

Getting vaccinated will help keep you safe and healthy while you’re traveling. It will also help make sure that you don’t bring any serious diseases home to your family, friends, and community.

On this page, you'll find answers to common questions about vaccines for travelers.

Which vaccines do I need before traveling?

The vaccines you need to get before traveling will depend on few things, including:

• Where you plan to travel . Some countries require proof of vaccination for certain diseases, like yellow fever or polio. And traveling in developing countries and rural areas may bring you into contact with more diseases, which means you might need more vaccines before you visit.
• Your health . If you’re pregnant or have an ongoing illness or weakened immune system, you may need additional vaccines.
• The vaccinations you’ve already had . It’s important to be up to date on your routine vaccinations. While diseases like measles are rare in the United States, they are more common in other countries. Learn more about routine vaccines for specific age groups .

How far in advance should I get vaccinated before traveling?

It’s important to get vaccinated at least 4 to 6 weeks before you travel. This will give the vaccines time to start working, so you’re protected while you’re traveling. It will also usually make sure there’s enough time for you to get vaccines that require more than 1 dose.

Where can I go to get travel vaccines?

Start by finding a:

• Travel clinic
• Health department
• Yellow fever vaccination clinic

Learn more about where you can get vaccines .

What resources can I use to prepare for my trip?

Here are some resources that may come in handy as you’re planning your trip:

• Visit CDC’s travel website to find out which vaccines you may need based on where you plan to travel, what you’ll be doing, and any health conditions you have.
• Download CDC's TravWell app to get recommended vaccines, a checklist to help prepare for travel, and a personalized packing list. You can also use it to store travel documents and keep a record of your medicines and vaccinations.
• Read the current travel notices to learn about any new disease outbreaks in or vaccine recommendations for the areas where you plan to travel.
• Visit the State Department’s website to learn about vaccinations, insurance, and medical emergencies while traveling.

Traveling with a child? Make sure they get the measles vaccine.

Measles is still common in some countries. Getting your child vaccinated will protect them from getting measles — and from bringing it back to the United States where it can spread to others. Learn more about the measles vaccine.

Find out which vaccines you need

CDC’s Adult Vaccine Quiz helps you create a list of vaccines you may need based on your age, health conditions, and more.

Take the quiz now !

Get Immunized

Getting immunized is easy. Vaccines and preventive antibodies are available at the doctor’s office or pharmacies — and are usually covered by insurance.

Find out how to get protected .

Available travel vaccines

The following vaccinations are available for people travelling abroad.

Cholera vaccination

Vaccination against  cholera isn't routinely needed for most travellers.

But in some cases it may be recommended for aid workers and people likely to have limited access to medical services – for example, people working in refugee camps or after natural disasters.

Most cases of cholera are confined to regions of the world with poor sanitation and water hygiene, such as parts of:

• South America

The vaccine is usually given as a drink in 2 separate doses, taken 1 to 6 weeks apart.

Children aged 2 to 6 years old should have a third dose taken 1 to 6 weeks after the second dose.

You should make sure you have the final dose of this vaccine at least a week before you travel.

A single booster dose or full revaccination is usually recommended if you have previously been vaccinated against cholera and you're planning to travel to an area where the infection is common.

Diphtheria vaccination

A combined vaccination that protects against diphtheria , polio and tetanus is routinely given to all children in the UK.

You should make sure you and your children are up-to-date with your routine vaccinations before travelling.

Further booster doses are usually only recommended if you're going to visit parts of the world where diphtheria is widespread and your last vaccination dose was more than 10 years ago.

Diphtheria is more common in parts of the world where fewer people are vaccinated, such as:

• Central and Southeast Asia
• Eastern Europe

Additional doses of the vaccination are given in a single 3-in-1 Td/IPV (tetanus, diphtheria and polio) injection.

Hepatitis A vaccination

Vaccination against  hepatitis A is recommended if you're travelling to countries where there are poor levels of sanitation and hygiene, and hepatitis A is common.

Ask your GP, pharmacy or travel clinic if you should have the hepatitis A vaccine if you're travelling to:

• Sub-Saharan and North Africa
• the Middle East
• South and Central America

The vaccination against hepatitis A is usually given as a single initial injection, with a second dose 6 to 12 months later. Two doses should protect you for at least 25 years.

You should preferably have the initial dose at least 2 weeks before you leave, although it can be given up to the day of your departure if needed.

Jabs that offer combined protection against hepatitis A and hepatitis B or typhoid are also available if you're likely to also be at risk of these conditions.

Hepatitis B vaccination

Vaccination against  hepatitis B is recommended if you're travelling in parts of the world where hepatitis B is common, especially if you'll be doing activities that increase your risk of developing the infection.

Hepatitis B is spread through blood and body fluids. Things like having sex, injecting drugs or playing contact sports on your travels can increase your risk.

Anyone travelling for long periods or who's likely to need medical care while abroad is also at increased risk.

Hepatitis B is found worldwide, but it's more common in parts of:

• Sub-Saharan Africa
• Southern and Eastern Europe

The hepatitis B vaccination generally involves a course of 3 injections. Depending on how quickly you need protection, these may be spread over a period as long as 6 months or as short as 3 weeks.

A combined hepatitis A and hepatitis B jab is also available if you're likely to be at risk of both these conditions while travelling.

Japanese encephalitis vaccination

Vaccination against  Japanese encephalitis  is usually recommended if you're planning a long stay (usually at least a month) in a country where you could get the condition.

It's particularly important if:

• you're visiting during the rainy season or there's a year-round risk because of a tropical climate
• you're going to visit rural areas, such as rice fields or marshlands
• you'll be taking part in any activities that may increase your risk of becoming infected, such as cycling or camping

Japanese encephalitis is found throughout Asia and beyond. The area it's found in stretches from the western Pacific islands in the east, across to the borders of Pakistan in the west.

It's found as far north as Northeastern China and as far south as the islands of the Torres Strait and Cape York in Northeastern Australia.

Despite its name, Japanese encephalitis is now relatively rare in Japan because of mass immunisation programmes.

Find out more about risk areas on the Travel Health Pro website

Vaccination against Japanese encephalitis usually consists of 2 injections, with the second dose given 28 days after the first.

Ideally, you need to have the second dose a week before you leave.

Meningococcal meningitis vaccination

Vaccination against some types of meningococcal meningitis  is usually recommended if you're travelling to areas at risk and your planned activities put you at higher risk – for example, if you're a long-term traveller who has close contact with the local population.

High-risk areas for meningococcal meningitis include:

• parts of Africa
• Saudi Arabia during the mass gatherings of Hajj or Umrah

All travellers to Saudi Arabia for the Hajj or Umrah pilgrimages are required to show proof of vaccination.

If travelling to a high-risk area, you should be vaccinated against meningococcal meningitis with a MenACWY vaccine , also known as the quadrivalent meningococcal meningitis vaccine.

This is a single injection that should be given 2 to 3 weeks before you travel. Babies under a year old need 2 injections.

You should have the MenACWY vaccine before travelling to high-risk areas, even if you had the  meningitis C vaccine as a child.

Read more about the  meningococcal meningitis vaccines .

Measles, mumps and rubella (MMR) vaccination

The MMR vaccine that protects against measles ,  mumps and  rubella is routinely given to all children in the UK. 

You should make sure you and your children are up-to-date with routine vaccinations, including MMR, before travelling.

If you haven't been fully vaccinated against these conditions or you're not already immune, you should ask about MMR vaccination before you travel.

The MMR vaccine is given as 2 injections. These are usually given when a child is 3 years and 4 months old.

But if vaccination has been missed previously, adults can have the doses 1 month apart, and children can have them 3 months apart if necessary.

Read more about the MMR vaccine .

Polio vaccination

A combined vaccination that protects against diphtheria,  polio and tetanus is routinely given to all children in the UK.

Further booster doses are usually only recommended if you're going to visit parts of the world where polio is, or has recently been, present and your last vaccination dose was more than 10 years ago.

Currently the condition is most common in Pakistan and Afghanistan, but it's also a risk in other regions of the world.

Read more about the  Td/IPV (3-in-1) vaccine .

Rabies vaccination

Vaccination against rabies is advised if you're travelling to an area where you could get rabies, particularly if:

• you're staying for a month or more
• there's unlikely to be quick access to appropriate medical care
• you plan to do activities that could put you at increased risk of exposure to rabies, such as cycling or running

Rabies can be found in many parts of the world. GOV.UK provides a detailed list of countries that have rabies in domestic animals or wildlife .

Vaccination involves a course of 3 injections before you travel, usually given over a period of 28 days.

If you're bitten, licked or scratched by an animal in a country where rabies is a problem, further doses of rabies vaccine (with or without a special anti-rabies injection given around the wound) may be required as emergency treatment.

Find out more about the rabies vaccine

GOV.UK: Rabies risks for travellers

Tetanus vaccination

A combined vaccination that protects against diphtheria, polio and tetanus is routinely given to all children in the UK.

Further booster doses are usually only recommended if:

• you're travelling to areas where access to medical services is likely to be limited and your last vaccination dose was more than 10 years ago
• you've not had two booster doses

Read more about the Td/IPV (3-in-1) vaccine .

Tick-borne encephalitis vaccination

Vaccination against  tick-borne encephalitis (TBE)  is usually recommended for anyone who plans to live or work in a high-risk area, or hike and camp in these areas during late spring or summer.

The ticks that cause TBE are mainly found in forested areas of central, eastern and northern Europe, although at-risk areas also include eastern Russia and some countries in east Asia, including some regions of China and Japan.

The vaccination requires a course of 3 injections for full protection. The second dose is given 1 to 3 months after the first and provides immunity for about a year.

A third dose, given 5 to 12 months after the second, provides immunity for up to 3 years.

The course can sometimes be accelerated if necessary. This involves 2 doses being given 2 weeks apart.

Booster doses of the vaccine are recommended every 3 years, if necessary.

Tuberculosis (TB) vaccination

The BCG vaccine (which stands for Bacillus Calmette-Guérin vaccine) protects against tuberculosis , which is also known as TB.

The BCG vaccine isn't given as part of the routine NHS vaccination schedule. It's given on the NHS only when a child or adult is thought to have an increased risk of coming into contact with TB.

When preparing for travel abroad, the BCG vaccine is recommended for any unvaccinated people under 16 who'll be living or working with friends, family or local people for more than 3 months in a country where TB is common or the risk of multi-drug resistant TB is high.

The BCG vaccine is given as a single injection.

Areas of the world where the risk of TB is high enough to recommend BCG vaccination for previously unvaccinated travellers include:

• parts of South and Southeast Asia

Read more about the BCG vaccine .

Typhoid vaccination

Vaccination against typhoid fever is recommended if you're travelling to parts of the world where the condition is common, particularly if you'll: 

• have frequent or prolonged exposure to conditions where sanitation and food hygiene are likely to be poor
• be staying or working with local people

High-risk areas include:

• parts of South and Central America

Two main vaccines are available for typhoid fever in the UK. One is given as a single injection, and the other is given as 3 capsules to take on alternate days.

It's also possible to have a combined hepatitis A and typhoid jab.

Ideally, the typhoid vaccine should be given at least 1 month before you travel, but it can be given closer to your travel date if necessary.

Booster vaccinations are recommended every 3 years if you continue to be at risk of infection.

Read more about the typhoid vaccine .

Yellow fever vaccination

Vaccination against yellow fever is advised if you're travelling to areas where there's a risk of getting yellow fever.

Some countries require a proof of vaccination certificate before they let you enter the country.

Yellow fever occurs in some areas of tropical Africa and Central and South America. More information about yellow fever and areas where it's found is available on Travel Health Pro .

A single dose of the yellow fever vaccine is thought to provide lifelong protection. For most people, a booster dose is no longer recommended.

You must have a yellow fever vaccination at least 10 days before you travel. You will also need to complete a yellow fever vaccination checklist to make sure you can have the vaccine.

Find out more about the yellow fever vaccination checklist on the Travel Health Pro website

You should be issued with an International Certificate of Vaccination or Prophylaxis when you have the vaccine. This certificate is valid for life.

Some people cannot have the yellow fever vaccine.

Read more about the  yellow fever vaccine and who can have it .

When to get further advice

Speak to your GP before having any vaccinations if:

• you're planning to get pregnant
• you're pregnant
• you're breastfeeding
• you have an immune deficiency
• you have any allergies

Page last reviewed: 16 March 2023 Next review due: 16 March 2026

TB vaccine: WHO expert explains why it’s taken 100 years for a scientific breakthrough, and why it’s such a big deal

Regional Adviser, Immunisation, WHO Regional Office for Africa, Stellenbosch University

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Charles Shey Wiysonge previously received funding from the South African Medical Research Council.

Stellenbosch University provides funding as a partner of The Conversation AFRICA.

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The BCG vaccine for TB has been used for 100 years. It is largely effective for children under five, but less so in older people and can’t be used on patients who have certain medical conditions. Today we’re the closest we’ve ever been to discovering a vaccine that might replace or complement it. Charles Shey Wiysonge, the World Health Organization’s Regional Adviser for Immunisation, discusses the latest developments in the fight against one of the world’s deadliest diseases.

Why has it taken so long?

We do not yet have a new vaccine for TB. But, for the first time, there are several vaccine candidates that are at advanced stages of clinical development.

Vaccine development usually takes decades and unfolds step by step. Experimental vaccine candidates are created in the laboratory and tested in animals before moving into progressively larger human clinical trials.

Clinical trials are research studies that test an intervention such as a vaccine in human beings and occur in phases, from phase 1 to phase 3. We say vaccines are in clinical development when they reach the clinical trial stage.

A phase 1 trial is a first-in-human study which recruits a small number of healthy people (usually fewer than 100), to assess whether a candidate vaccine is safe.

Phase 2 trials are typically conducted among several hundred participants, to assess whether the candidate vaccine produces an immune response.

For phase 3 trials, thousands of people are enrolled to assess whether the vaccine is efficacious and safe. Phase 3 TB vaccine trials are currently going on in Gabon, Kenya, Russia, South Africa, Tanzania and Uganda.

Even though we are still, at best, three years away from broad regulatory approval of a new TB vaccine, the scientific community can do a lot now to prepare for its use, and to inform the public so that the vaccine may be accepted when it becomes available.

TB vaccines are very challenging to develop. The bacterium that causes the disease is complex, and is proficient at evading the human immune system. We don’t yet have a full understanding of how to appropriately target the bacterium or what kind of immune responses are needed to induce immunity. But there are some interesting approaches in the pipeline and there have been some encouraging data from clinical trials that are providing clues.

Why do we need a new TB vaccine?

TB is a global health emergency. About 2 billion people are currently infected with Mycobacterium tuberculosis , and of those, 5% to 10% may become ill with TB and will potentially transmit the bacterium.

In 2021 , nearly 10.6 million people developed TB disease and 1.6 million died. We urgently need new tools to fight TB, including new and improved vaccines.

The Bacille Calmette-Guérin (BCG) vaccine has saved tens of millions of lives and is effective in children under the age of five in preventing TB deaths and severe forms of the disease.

The vaccine has variable efficacy for protection against pulmonary TB (TB affecting the lungs) in adolescents and adults – and it is pulmonary TB that’s responsible for the majority of TB transmission. So new and improved vaccines that are effective in preventing pulmonary TB in adolescents and adults are essential to control TB, and to reduce transmission to all, including newborn babies.

TB is the leading cause of death among people living with HIV. People living with HIV have up to 20 times higher risk of developing TB disease compared to those without HIV infection. The current BCG vaccine is not recommended for use in people living with HIV, for safety reasons. Although BCG is a safe vaccine in immunocompetent infants (those whose immune systems are working properly), severe adverse events can occur in HIV-infected infants following vaccination with BCG.

These adverse events include a rare but life threatening condition known as disseminated BCG disease . However, new TB vaccine candidates are being developed and evaluated to offer clinical benefit in people living with HIV.

How effective has the BCG vaccine been?

BCG vaccines are given to more than 100 million children every year worldwide, at birth or soon after. The effectiveness of BCG can vary depending on several factors, including the prevalence of TB in a given area, the strain of the BCG vaccine used, and the age at which BCG was administered.

Several studies have shown that the effect of the BCG wanes as children approach adolescence. People may become infected with TB but not be aware of it.

What will happen to the BCG vaccine?

The BCG vaccine will not be replaced by another TB vaccine until and unless there is compelling data on the safety and efficacy of an alternative. Most of the current vaccines in advanced stages of clinical trials are tested in adolescents and adults. Their safety and efficacy would need to be proven in newborn infants to be able to replace BCG.

In addition, BCG vaccination has nonspecific beneficial effects on overall mortality and leads to more reductions in child mortality than would be expected by just protecting against tuberculosis. There is thus a great possibility that BCG would remain in use.

What will a new vaccine mean for the fight against TB?

This depends on what the clinical trial data for the new vaccine candidates show. Most importantly, any new vaccine will need to be safe, and it will need to offer clear clinical benefit to populations at risk. We hope that the TB vaccine candidates that are in the pipeline will be effective at reducing TB infection, TB disease and TB transmission and can become part of a combination of tools in the fight against TB.

This article is part of a media partnership between The Conversation Africa and the 2023 Conference on Public Health in Africa.

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Therapeutic Vaccines for Tuberculosis: An Overview

Tuberculosis (TB), caused by Mycobacterium tuberculosis is the world’s deadliest bacterial infection, resulting in more than 1.4 million deaths annually. The emergence of drug-resistance to first-line antibiotic therapy poses a threat to successful treatment, and novel therapeutic options are required, particularly for drug-resistant tuberculosis. One modality emerging for TB treatment is therapeutic vaccination. As opposed to preventative vaccination – the aim of which is to prevent getting infected by M. tuberculosis or developing active tuberculosis, the purpose of therapeutic vaccination is as adjunctive treatment of TB or to prevent relapse following cure. Several candidate therapeutic vaccines, using killed whole-cell or live attenuated mycobacteria, mycobacterial fragments and viral vectored vaccines are in current clinical trials. Other modes of passive immunization, including monoclonal antibodies directed against M. tuberculosis antigens are in various pre-clinical stages of development. Here, we will discuss these various therapeutics and their proposed mechanisms of action. Although the full clinical utility of therapeutic vaccination for the treatment of tuberculosis is yet to be established, they hold potential as useful adjunct therapies.

Introduction

Until the Covid-19 pandemic, Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) was the leading cause of death from a single infectious agent, ranking above HIV or malaria. With the disruption to public health services as a result of the Covid-19 pandemic, the number of deaths due to TB rose for the first time in over 20 years ( 1 , 2 ), setting back decades of albeit slow, progress. Further threats to eradication of TB as a major public health tragedy include the rise of drug-resistant tuberculosis (DR-TB). There are over half a million cases of rifampicin-resistant TB annually. Lack of access to, and the general lower efficacy of second-line therapeutic regimens results in a disproportionate contribute of DR-TB to poor outcomes ( 3 ), and as access to newer agents such bedaquiline and delaminid increases, it will inevitably be associated with a rise of resistance to these agents also ( 4 ). It is thought that, globally, there are 19 million individuals living with latent rifampicin-resistant tuberculosis further threatening future control strategies ( 5 , 6 ). In addition to the specific concerns with respect to DR-TB, and despite the current lengthy standard regimen for drug-sensitive TB (~ 6 months of multiple drugs), approximately 2-10% of patients fail initial therapy or relapse ( 7 ), necessitating re-treatment. Treatment of HIV-TB co-infection also has specific considerations, with frequent drug-drug interactions, especially with the keystone rifamycin class and worse outcomes overall. All these considerations have renewed interest in non-antibiotic treatment modalities for tuberculosis.

The usual consideration for immunization is prevention of an infection or disease. Therapeutic vaccination is when an immunomodulatory agent (the vaccine) is administered in the context of already-established disease, either to improve outcomes, shorten treatment duration, or, in the case of TB, prevent relapse ( 8 ). In 2018, the WHO defined the target product profile for therapeutic vaccines for TB. They should: (1) reduce the rate of recurrence caused by drug-sensitive and resistant TB, following completion of a full course of drug therapy; (2) increase the proportion of cured patients, in particularly for rifampicin-resistant and extensively drug-resistant TB; (3) shorten therapy duration with the goal of improving compliance and reduce the likelihood of developing drug-resistance ( 9 ) and See Figure 1 . A further possible definition of therapeutic vaccination in the context of tuberculosis is the administration of a vaccine given to people with evidence of M. tuberculosis exposure, e.g. by a positive interferon-gamma release assay (IGRA+ve), to prevent progression to active tuberculosis. The WHO states that the target population for therapeutic vaccines should include all TB patients, regardless of age, drug sensitivity and co-morbidities. We will survey therapeutic vaccines currently in clinical trials ( Table 1 ), as well as some potential future treatment modalities. Therapeutic TB vaccines in current clinical development fall into several categories: whole killed - and fragmented-cell vaccines; live attenuated vaccines, adjuvanted protein subunit vaccines and viral vectored vaccines.

Overview of selected therapeutic TB vaccines in the clinical pipeline. The initial stages of TB infection involve inhalation of Mtb bacilli into the lung and phagocytosis by resident alveolar macrophages. The human immune system can contain or eliminate Mtb infection in the majority of cases, only a small proportion of exposed individuals go on to develop active tuberculosis. Therapeutic TB vaccines serve as immunotherapeutic adjuncts to chemotherapy and act through modulating host anti-TB immunity. These vaccines are either administrated to potentiate treatment during treatment of active disease (middle) or to prevent recurrence or relapse after standard treatment (right), or to prevent reactivation of latent tuberculosis to active tuberculosis (left). Vaccines that are being developed to improve treatment outcomes in active TB comprise M. vaccae , RUTI, MIP and AERAS-402. Vaccines that prevent relapse and reinfection include H56:IC31 and ID: GLA-SE subunit vaccines, RUTI, BCG, the recombinant BCG vaccine VPM1002 as well as MVA-85A. These candidates are currently in phase 2 or 3 clinical trials in TB patients during or after completion of treatment.

Table 1

Therapeutic vaccines used in clinical trials.

Killed Whole-Cell/Fragmented Vaccine Candidates

Mycobacterium vaccae.

Mycobacterium vaccae (MV), originally discovered in milk and dung from cattle (hence vaccae , cow), is a rapidly growing environmental mycobacterium with poor pathogenic potential in humans. The vaccine was developed using a strain of M. vaccae isolated in a region of Uganda, where it was associated with enhanced protective efficacy of BCG immune responses to tuberculosis ( 27 ). Heat-killed preparations of M. vaccae (MV or SRL72) have been extensively studied as adjuncts to standard anti-tuberculous drug therapy for more than decade. It was hypothesized that inactivated MV works by stimulating the host immune responses to antigens shared with Mtb. Preclinical studies showed that mice injected with inactivated MV provoked either a predominantly Th1, or a mixed Th1/Th2 immune response, as well as potentially protective cytotoxic CD8+ T cells that could kill Mtb-infected macrophages ( 10 , 12 , 28 ). Administration of multiple doses series (2-5 doses) of MV, was shown to be safe and immunogenic in a Phase I and II clinical trials in HIV-infected children and adults primed or not with BCG vaccine conducted across multiple sites ( 29 ). Moreover, these studies showed that MV vaccination induced relevant immune responses in HIV-infected patients and that may be explained by the decrease of HIV loads in BCG primed and MV recipient individuals suggesting immunization with whole cell vaccine is a promising strategy for the prevention of HIV-associated TB. In an early small, randomized trial, 120 HIV seronegative newly diagnosed pulmonary TB patients were randomized to a single dose of MV versus placebo in addition to standard TB chemotherapy. MV therapy was associated with more rapid sputum culture conversion (i.e. clearance of viable Mtb), and improved radiological markers of disease ( 27 ). In addition to markers of cell-mediated immunostimulation, individuals treated with MV had increased antibody titers to the heat shock proteins HSP60 and HSP70 – which are known to be immunostimulatory ( 30 ) – in the first month of treatment, as well as raised levels of the cytokines IL-4, IL-10 and TNF-α from ex vivo stimulated PBMCs with inactivated Mtb ( 11 ). Of the therapeutic vaccines under consideration, MV is the most advanced in the clinical pipeline. After the initial set of small-scale studies, a single dose of intradermally delivered MV was felt to be insufficient for a robust clinical response, and trial protocols were modified to include multiple doses.

To facilitate delivery, a tablet form of heat-killed MV (termed V7) was formulated and evaluated in a small (but designated phase III) placebo-controlled efficacy trial. Patients with either drug-sensitive or drug-resistant TB were randomized to V7 or placebo daily for the first month of therapy. MV therapy was again associated with rapid sputum culture clearance of Mtb. Notably, MV therapy was also associated with weight gain in patients, and improved markers for drug-induced hepatoxicity. Given that both TB-related weight loss ( 31 ) and hepatoxicity ( 32 ) are thought to have inflammatory components, these findings are further support of the immunomodulatory effect of MV. The largest study of MV: a phase III trial conducted in China with 10,000 tuberculin skin test positive enrollees to measure efficacy in preventing progression to active tuberculosis completed enrollment in 2017 ( {"type":"clinical-trial","attrs":{"text":"NCT01979900","term_id":"NCT01979900"}} NCT01979900 ) but is yet to report its findings.

In summary, MV has proven immunomodulatory activity in both animal preclinical studies as well as multiple, albeit small, clinical studies. The observed effect on decreasing time to sputum culture clearance appears robust, in multiple studies in many different patient populations. However, definitive evidence for MV in treatment outcome in large-scale studies is still awaited.

Mycobacterium indicus pranii

MIP comprises killed M. indicus pranii , previously known as Mw – a non-pathogenic mycobacterium closely related to M. avium ( 33 ) . MIP has been studied as an adjunct therapy for leprosy and has been shown to have both immunoprophylactic and immunotherapeutic effects and the duration of multi-drug therapy in leprosy patients by improving the immune responses to M. leprae ( 34 ). In keeping with other whole-cell mycobacterial vaccines, preclinical evaluation was confirmed to reduce organ Mtb bacillary burden in small animal models, associated with increased early cell-mediated immunity, including, notably, increased cytotoxic T cells and followed by a balanced Th1/Th2 responses in later part of the chemotherapy ( 14 ).

Clinical studies have focused on “category II TB”, i.e. patients that have either failed therapy, relapsed, or otherwise been lost to follow-up. These patients have high rates of treatment failure, as well as risk to progression to drug-resistant TB ( 15 ). In a phase II study of 890 sputum smear positive category II patients, patients were randomized to 6 injections of MIP or placebo. Unfortunately, 248 patients (equally distributed between the intervention and control arms) failed to complete the treatment regimen and were excluded from per protocol analysis. There was a subtle decrease in time to sputum culture conversion in the MIP arm. However, there was no statistically significant different in cure rates – possibly because the high rates of cure (94% in MIP arm and 90% in placebo arm) meant the study was underpowered to detect a small difference. In the two years of follow-up, a total of 34 patients in the MIP arm and 26 in the placebo arm relapsed, which again, was not statistically significant ( 15 ). There is an ongoing phase III efficacy and safety trial for preventing pulmonary TB among healthy-household contacts of sputum positive TB patients in India and first results are expected soon ( 18 ). In summary, MIP has shown robust evidence of immunostimulation. Evidence of efficacy, however, is still lacking or awaited in either treatment, or prevention of active TB following high risk exposure.

RUTI is composed of liposomes containing detoxified fragments of Mtb that was cultured under conditions of hypoxia/stress, which are known to induce expression of a wide-range of stress-related proteins ( 35 ). The rationale is that by inducing an immune response to these antigens, RUTI will have improved efficacy against non-replicating bacteria (NRB), that are hypothesized to contribute to the requirement of prolonged treatment, as well as relapse ( 36 ).

In endemic settings, populations at increased risk for latent TB infection can be treated using Isoniazid Preventive Therapy (IPT) for 6-12 months. Although IPT has been demonstrated to reduce the risk of reactivation by 70% in high-risk groups, later studies have shown waning protection as soon as 18 months after short-term INH based regimens in high endemic settings ( 37 ). This could be due to the low adherence rates, or re-infection. It is thought that Mtb bacilli in individuals with latent infection survive within foamy macrophages in necrotic granulomata that represent an important immunosuppressive barrier ( 38 ). Antibiotic treatment is required to kill replicating bacteria as well as eliminate the outermost layer of foamy macrophages and may allow the egress of new phagocytes. Administration of RUTI in this context was proposed to induce a broad of T cells response that would prevent the reactivation of, or kill the remaining NRB ( 35 ).

In small animal studies, administration of RUTI to Mtb-infected guinea pigs and mice, following incomplete chemotherapy resulted in increased Mtb-specific CD4+and CD8+ cellular responses and antibody production, and was associated with decreased bacillary organ burden and lung pathology ( 39 ). Furthermore, reduction in post-chemotherapy relapse was reported, in which passive immunization with sera, obtained from mice treated with RUTI, exerted significant protection against reactivation of Mtb infection in SCID mice ( 40 ). In human studies, a combined phase I/II clinical trial was conducted to test the tolerability and immunogenicity of different RUTI doses in HIV positive and negative patients after completion of one-month INH treatment ( 13 , 41 ). The results demonstrated that RUTI vaccination was tolerated and that one inoculation of 25μg of RUTI resulted in poly-antigenic responses, especially against the 16 kDa and 38 kDa antigens, which are biomarkers associated with LTBI. There are no reported efficacy data for RUTI, but small phase II trials ( {"type":"clinical-trial","attrs":{"text":"NCT04919239","term_id":"NCT04919239"}} NCT04919239 , {"type":"clinical-trial","attrs":{"text":"NCT02711735","term_id":"NCT02711735"}} NCT02711735 , {"type":"clinical-trial","attrs":{"text":"NCT05136833","term_id":"NCT05136833"}} NCT05136833 ) are currently underway to evaluate RUTI as adjunctive therapy for drug sensitive and rifampicin-resistant tuberculosis.

Live Attenuated Vaccines

Vpm1002 (bcg Δurec::hly).

VPM1002 is recombinant BCG-ΔureC::hly, i.e. in which the urease C gene, ureC has been deleted and replaced with the listeriolysin O (LLO) gene from Listeria monocytogenes . Urease was known to reduce phagolysosome acidification and promotes mycobacterial survival ( 17 ) Listeriolysin O is a thiol-activated, cholesterol-dependent cytolysin that is only active in acidic environments. Hence deletion of ureC would increase LLO activity ( 17 ). In Listeria , LLO is absolutely required for virulence ( 42 ), and functions to disrupt the phagosome membrane to allow pathogen escape to the cytosol ( 43 ). It has now been demonstrated that Mtb can disrupt the phagosome membrane, in an Esx-1-dependent mechanism ( 44 ). Esx-1 is a type VII secretion machinery that is essential for Mtb virulence ( 45 , 46 ) and is missing in BCG. Hence BCG, unlike Mtb, cannot engage in phagolysosomal escape. By expressing LLO, BCG acquires phagolysosomal escape via a different mechanism, and consequently improves antigen accessibility, in particular for loading onto MHC class I. VPM1002 was demonstrated to enhance both innate and adaptive immunity in animal models, in part via inducing apoptosis, autophagy and stimulation of the NRLP3 inflammasome. Compared with wild-type BCG, VPM1002 also resulted in greater stimulation of humoral immunity and germinal center activation ( 17 ). Although the initial clinical studies for VPM1002 have been as a candidate preventative vaccine, one animal study suggests potential as a therapeutic vaccine. Mice were infected with Mtb and then treated with antibiotics for 40 days until viable Mtb was no longer recovered from organs. Mice were then treated with BCG, VPM1002 or saline. When organ bacterial burdens were evaluated at 250 days post initial infection, VPM1002 was clearly superior to BCG or saline, although no mice achieved sterile cure ( 16 ). A phase II/III clinical trial with VPM1002 is currently ongoing in India to for the prevention of recurrence of active TB in adults following completion of standard therapy ( {"type":"clinical-trial","attrs":{"text":"NCT03152903","term_id":"NCT03152903"}} NCT03152903 ).

Bacillus Calmette Guérin

Bacillus Calmette-Guerin, a live attenuated strain of Mycobacterium bovis ( M. bovis is part of the M. tuberculosis complex and responsible for cattle TB), is the only licensed TB vaccine and was developed a century ago. It is the world’s most extensively used vaccine. BCG has a wide variation in reported efficacy as a preventative vaccine. Despite expert opinion that BCG may be ineffective as a therapeutic in established active TB infection, possibly because active infection masks BCG-induced immunity ( 47 ), several animal studies have suggested that BCG may enhance antibiotic activity in experimental M. tuberculosis infection. In an early study, Dhillon and Mitchinson showed that BCG immunization paradoxically decreased the bactericidal activity of isoniazid in Mtb-infected mouse spleens, but not lungs, and had no effect on rifampicin-mediated killing. However, in the guinea-pig model, BCG increased the activity of both drugs in both lungs and spleens ( 48 ). In another guinea-pig study, animals immunized +/- BCG were infected with M. tuberculosis and then treated with a combination of rifampicin, isoniazid and pyrazinamide (RHZ), the core of the standard TB regimen. Although BCG immunization had no additional effect on bacterial organ burden on top of antibiotics, it did prolong survival of the infected animals compared with drug-treatment alone and the combination of BCG and drug treatment was also superior to antibiotics alone in reducing pathology ( 49 ).

In the context of clinical studies, a secondary analysis of either BCG or rifampicin alone or in combination for the prevention of leprosy transmission in 21,711 close contacts of 1037 index leprosy patients was performed. The original study was designed to determine the efficacy of rifampicin (against placebo), but the observation that ~40% of participants had a history of BCG vaccination given at infancy (well-balanced in both arms of the trial, although in both arms, a larger proportion of young enrollees had a history of BCG vaccination) allowed for the secondary analysis. BCG given at infancy and rifampicin post contact exposure (in the absence of BCG) had an efficacy of 57 and 58% respectively for prevention of leprosy in contacts. However, the combination of BCG and rifampicin had an increased efficacy of 80% ( 50 ). Although no efficacy data are available for TB, BCG revaccination is safe and well tolerated in individuals with evidence of LTBI ( 51 ). In a phase I study of 82 HIV-ve adults with a strongly positive tuberculin skin test, indicative of LTBI, and who had visible evidence (by scar) of prior BCG vaccination, participants were randomized either to isoniazid preventative therapy (IPT) followed by BCG revaccination, or BCG revaccination followed by IPT ( 19 ). IPT had negligible impact on mycobacteria-specific T cell responses. However, BCG revaccination (regardless of IPT order) was associated with the stimulation of a durable, BCG-reactive NK cell response, which was also detected in BCG-immunized infants ( 19 ). Given that BCG revaccination was associated with a moderate reduction in primary infection with M. tuberculosis ( 52 ), the relevance of these BCG-reactive NK cells on restricting M. tuberculosis , and whether they are relevant in the context of active or recently treated TB warrant further investigation.

Subunit Vaccines

Id93+gla-se.

ID93 is comprised of four Mtb proteins expressed in tandem. The candidate antigens were identified in a screen of immunodominant human T cell epitopes that were also immunogenic in mice ( 53 ). ID93 is formulated with a synthetic toll like receptor 4 (TLR-4) agonist in a stable oil-in water emulsion known as glucopyranosyl lipid A stable emulsion (GLA-SE). In initial studies as a preventative vaccine either alone or as a booster to priming by BCG, ID93-GLA-SE vaccination induced robust polyfunctional Th1 responses, characterized by antigen-specific IFNγ, TNF-α and IL-2 CD4+ T cells, and was superior to BCG alone in both mice and guinea-pigs ( 54 ). In a subsequent study, ID-93+GLA-SE was evaluated for therapeutic vaccination in a mouse model as well as cynomologous macaques. The murine studies used SWR/J mice that, unlike the more widely used C57/BL6 mice do not develop chronic infection, but instead progressively sicken and die after ~100 days unless rescued with antibiotic therapy. Adjunctive treatment with vaccination both increased survival of the mice and shortened the length of antibiotics required to rescue the mice ( 20 ). Treatment of the non-human primates with 1 month of rifampicin and isoniazid was insufficient to completely resolve infection when given alone, but when combined with three doses of ID-93+GLA-SE following antibiotic treatment, resolved radiographic evidence of disease ( 20 ). Building on these studies, ID-93+GLA-SE has been evaluated in an early-stage phase IIa study for prevention of recurrence/relapse in HIV-positive patients who had recently completed a four-month course of standard chemotherapy for pulmonary tuberculosis ( 21 ). The vaccine was well tolerated and induced antigen specific CD4-T cell responses in stimulated whole blood and PBMCs. Moreover, IgG-ID93 specific responses were predominantly IgG1 and IgG3. Since only 61 patients were evaluated in all arms, the study was not powered for efficacy ( 21 ).

H56:IC31 is a recombinant fusion protein comprised of three Mtb antigens. The vaccine is formulated in a stabilizing agent containing a TLR-9 agonist as adjuvant and designed to drive Th1 immune response against replicating and non-replicating bacilli ( 6 ). H56:IC31 has been shown to prevent Mtb reactivation in nonhuman primates ( 55 , 56 ). A phase 1 clinical trial, carried out with 25 adults, HIV negative, with or without latent TB infection, showed that H56 vaccine induced a polyfunctional CD4+T cells with memory phenotype that persisted for up to 210 days post vaccination ( 22 ). Following evidence of both safety and immunogenicity in a phase I study conducted in HIV negative adults who had recently been successfully treated for drug-sensitive pulmonary TB ( 23 ), H56:IC31 underwent a phase I/II study to evaluate it as a host-directed therapy alone or in combination with the cyclooxygenase-2 inhibitor (COX2i) etoricoxib. COX inhibition had been shown to both reduce or exacerbate experimental Mtb infection ( 57 ). H56:IC31 was safe and immunogenic, as was etoricoxib, but the combination of vaccination with COX2i resulted in blunted immune responses, suggested the two may be antagonistic as host-directed therapies ( 58 ). As with ID93, efficacy data is not yet available, although a phase II study of 900 HIV negative TB patients who have recently completed treatment is currently underway ( {"type":"clinical-trial","attrs":{"text":"NCT03512249","term_id":"NCT03512249"}} NCT03512249 ).

M72 is a subunit vaccine comprising a recombinant fusion protein of two Mtb-derived proteins, Mtb32A and Mtb39A; delivered with the adjuvant AS01 E , which has been used in the clinically approved malaria vaccine RTS,S as well as the zoster vaccine Shingrix. A phase IIb trial of 3573 adult participants that were HIV-ve and IGRA+, of whom 3289 were included in the per-protocol efficacy calculation, received either the vaccine or placebo. A total of 39 cases of active tuberculosis were detected in the participants, of which 13 were in the vaccine arm, resulting in a vaccine efficacy of ~50% ( 59 ). This was the first demonstration of vaccine efficacy for tuberculosis against development of active TB in the post BCG era, and validated that protein subunit vaccines, which have been developed successfully against viral and extra-cellular bacterial (e.g. the acellular pertussis vaccine) infections, could potentially be effective against an intracellular pathogen. Although the mechanisms of protection are not known, both CD4+ T cell and antibody responses were associated with protection ( 59 ).

Viral-Vectored Therapeutic Vaccines

One potential silver lining from the Covid-19 pandemic has been the remarkable progress in novel vaccine platforms. For the first time, both viral- and mRNA-delivered subunit vaccines (against SARS-CoV-2 spike protein) have not only been evaluated in clinical trials but found to be effective and approved ( 60 ). Although mRNA vaccine platforms are only now starting to be investigated for TB, virus-delivered subunit vaccines have been investigated in both preclinical and clinical studies.

Modified Vaccinia Ankara 85A

MVA is a viral vector comprising a recombinant replication-deficient modified vaccinia virus, Ankara (MVA) that allows insertion of large immunogenic sequences, up to 10kbp, and is efficient at induction of specific T cell responses. Given their safety and immunogenicity profile, MVA vectors have been extensively tested as prophylactic vaccine platform in endemic settings ( 61 ). MVA expressing antigen 85A (MVA85A) was shown to induce a robust Ag85A-specific CD4+ and CD8+ T cell responses and protected animals to the same extent as BCG following low-dose aerosol infection ( 62 ). The first phase 1 study using MVA85A was performed in healthy volunteers and was found to promote polyfunctional CD4+ T cells, likewise, the vaccine was deemed to be safe in infants, HIV positive individuals and LTBI subjects in endemic populations from Gambia, South Africa and Nigeria ( 63 – 65 ). MVA85A completed phase II clinical trials to evaluate its safety and protective effect in a prime boost regimen in infants of HIV infected mothers followed by selective BCG boost at 8 weeks for HIV negative infants ( {"type":"clinical-trial","attrs":{"text":"NCT01650389","term_id":"NCT01650389"}} NCT01650389 ). The data showed that MVA85A prime vaccination of HIV uninfected newborns was safe and induced a modest antigen specific immune response. A phase I clinical study in UK to investigate the effect of MVA85A, administrated by the aerosol inhaled or intramuscular route in healthy LTBI+ was terminated due to challenges with recruitment in the UK sites ( {"type":"clinical-trial","attrs":{"text":"NCT02532036","term_id":"NCT02532036"}} NCT02532036 ). However, the vaccine has completed a small non-randomized phase I study to evaluate its safety and immunogenicity in 12 healthy volunteers latently infected with TB ( {"type":"clinical-trial","attrs":{"text":"NCT00456183","term_id":"NCT00456183"}} NCT00456183 ) ( 25 ). Although this trial was limited by the heterogeneity of the population used and the small sample size, it showed that MVA85A is immunogenic in LTBI individuals as well as in BCG vaccinated but Mtb-uninfected individuals. Moreover, the vaccine induced a persistent Ag85A-specific polyfunctional T cell response until week 24 post vaccination. MVA85A is yet to be tested as an adjunct to standard drugs in MDR/XDR subjects, however in a chronic post-exposure mouse model, it was shown that combination of an antibiotic regimen with MVA harboring ten Mtb antigens (MVATG18598), each representative of different phases of TB disease, induced a robust Th1 response and improved the efficacy of chemotherapy ( 66 ).

Adenoviruses remain the most widely utilized platform for vaccine design, given their safety, high efficiency gene transduction and induction of robust immune responses. Human adenovirus serotype 35 (AdHu35) has been used extensively as a preventative vaccine (AERAS-402). The vaccine is a replication deficient adenovirus serotype 35 containing DNA encoding fusion proteins of three Mtb antigens: Ag85A, Ag85B and TB10.4. Both mucosal (intranasal) and intra-muscular administration of AERAS-402 conferred protective immunity against Mtb infection in mice ( 67 ). However, despite eliciting a robust immune response in immunized macaques, aerosol administration of AERAS-402 failed to protect the primates from high-dose (~275 colony forming units) challenge with M. tuberculosis ( 68 ). To determine the safety and immunogenicity of AERAS-402 in TB patients and to exclude the possibility of vaccine-induced immunopathology, a dose-escalation study in 72 adults who were either in the middle of treatment of active tuberculosis or had recently completed treatment was performed. Overall, the vaccine was well-tolerated and highly immunogenic. One study participant died, but from unrelated causes (broncheoalveolar carcinoma) ( 26 ). Nonetheless, immunogenicity does not imply functional immune responses. In a study of BCG-primed, AERAS-402 boosted participants, robust antigen-specific CD4+ and CD8+ T cells were identified in the vaccinated arm. However, the cytotoxic (CD8+) T cells were unable to recognized Mtb-infected dendritic cells ( 69 ). These findings are in keeping with other studies suggesting that M. tuberculosis engages in evasion of immunity, possibly via immunodominant responses ( 70 ), which further complicates effective vaccine design and discovery. To our knowledge, AERAS-402 is no longer in active clinical development.

Studies with a different adenoviral vector, this time chimpanzee adenovirus serotype-68 (ChAd-68) expressing Mtb antigen 85A was effective as adjunct to chemotherapy in the Balb/C mouse model of infection – but only when given intra-nasally and not when given intra-muscularly ( 71 ). These data suggest that route as well as formulation of viral-vectored vaccines may be an important consideration of potential efficacy.

Passive Therapeutic Immunization With Monoclonal Antibodies?

Vaccines: whether cell- or subunit-based, deliver immunogens that then evoke potentially protective immune responses. Alternatively, passive transfer of immune effectors, such as antibodies, can bypass the need to elicit an appropriate immune response. Recombinantly expressed monoclonal antibodies (mAbs) have been used extensively for non-infectious diseases, but their use in infection prior to Covid-19 had been restricted to a few instances such as for respiratory syncytial virus ( 72 ), in part due to the cost of goods and manufacture. The efficacy of virus-specific and neutralizing mAbs for Covid-19, especially if given early in onset of the disease has now been amply demonstrated. However, translating these Covid successes to TB is not entirely straightforward. For decades, there was controversy with regards to the potential role of antibody-mediated immunity to TB. Recent evidence, from studies of human antibodies specific for Mtb, suggest that antibodies may well be protective in TB (reviewed in ( 73 )). However, unlike viral infections, where neutralization of virus is the single most, albeit not complete ( 74 ) mechanism mediating antibody efficacy, protective anti-TB antibodies rely on Fc-mediated effector functions ( 75 , 76 ). Since recombinant mAbs may have different Fc properties than naturally occurring antibodies, for example with regards to glycosylation ( 77 ), mAbs may possess different effector functions than the original natural antibodies from which they are derived. We recently demonstrated that recombinant mAbs directed against a subunit of the Mtb phosphate transporter were still protective both in human ex vivo as well as murine assays ( 76 ), suggesting that recombinant mAbs may be potentially useful tools. Nonetheless, treatment of an acute respiratory infection (i.e. Covid-19) and a chronic pulmonary disease such as TB are not directly comparable, not least due to the requirement for repeated dosing and the associated increased costs. There is also the potential for detrimental immunopathology that would need to be investigated carefully in both preclinical, and eventually, clinical studies.

Concluding Remarks

The idea of therapeutic immunization is not new. Convalescent plasma/serum therapy was one of the most widely used therapeutics for infectious diseases prior to the discovery of antimicrobial drugs ( 78 , 79 ). There are a plethora of data to support therapeutic vaccination from preclinical models of tuberculosis. Moreover, trials to assess efficacy of therapeutic vaccines are easier and less costly to design than for preventative vaccines, since they can use much smaller numbers of enrollees due to higher event rates. Despite this, hard evidence supporting a role for therapeutic vaccination for clinically-relevant endpoints such as cure and relapse are still lacking. What is clear is that therapeutic vaccination can influence host immune responses. Given that even in cured TB patients, long-term sequelae of disease due to immunopathology is present in a substantial proportion of patients ( 80 , 81 ) revisiting therapeutic vaccination through the lens of modifying post-cure pathology may offer a new path for using these reagents for treatment of the world’s deadliest bacterial disease.

Author Contributions

RB and BJ conceived and wrote the manuscript together. All authors contributed to the article and approved the submitted version.

This work was supported in part by INV-038660 from the Bill & Melinda Gates Foundation. BJ is an Investigator of the Wellcome Trust (207487/C/17/Z).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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• tuberculosis

Some tuberculosis cases confirmed among migrants in Chicago, health department says

City increasing budget with Favorite Healthcare, firm that's been helping with migrant health care

CHICAGO (WLS) -- On Tuesday, the Chicago Health Department confirmed there are some cases of tuberculosis among migrants newly arrived in the city.

They are not saying exactly how many cases there are, but did say it's a "small number."

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The city pointed out that many residents of Central America and South America have latent TB infections, which means they can't pass the illness, but it does cause a positive test result.

The health department said it is taking steps to keep these infections contained.

It does not have any confirmed reports of anyone catching TB due to new arrivals.

These cases come as the city is increasing its budget with the firm that's been helping with migrant health care.

SEE ALSO | 1st measles case confirmed in suburban Cook County as Chicago's total rises to 52

The city extended its contract with Favorite Healthcare late last month for an additional $85 million.

It's the third multi-million dollar increase to this contract since late December.

A spokesperson for the mayor said this is all part of an approved city council budget that appropriated $150 million.

But according to this latest contract, the city has given Favorite Healthcare more than $234 million so far.

Multiple alderpeople told ABC 7 on Tuesday night they were not aware of this latest increase.

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US tuberculosis cases were at the highest level in a decade in 2023

This 2006 electron microscope image provided by the Centers for Disease Control and Prevention shows Mycobacterium tuberculosis bacteria, which causes the disease tuberculosis. The number of U.S. tuberculosis cases in 2023 was the highest in a decade, according to a report released by the CDC on Thursday, March 28, 2024. (Janice Carr/CDC via AP)

This 1966 microscope photo provided by the U.S. Centers for Disease Control and Prevention shows Mycobacterium tuberculosis bacilli, the organism responsible for causing the disease tuberculosis. The number of U.S. tuberculosis cases in 2023 were the highest in a decade, according to a report released by the CDC on Thursday, March 28, 2024. (Elizabeth S. Mingioli/CDC via AP)

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NEW YORK (AP) — The number of U.S. tuberculosis cases in 2023 were the highest in a decade, according to a new government report.

Forty states reported an increase in TB , and rates were up among all age groups, the Centers for Disease Control and Prevention said Thursday. More than 9,600 cases were reported, a 16% increase from 2022 and the highest since 2013.

Cases declined sharply at the beginning of the COVID-19 pandemic, but have been rising since.

Most U.S. TB cases are diagnosed in people born in other countries. Experts say the 2023 number is in part a combination of a surge in TB cases internationally — the World Health Organization said TB was behind only COVID-19 in infectious fatal diseases worldwide in 2022. And there are also increases in migration and post-pandemic international travel.

But other factors are also at play, including other illnesses that weaken the immune system and allow latent TB infections to emerge.

CDC officials expected TB numbers would rise, but the 2023 count “was a little more than was expected,” said Dr. Philip LoBue, director of the agency’s Division of Tuberculosis Elimination.

Despite the jump, the number and rate of new TB cases each year remains smaller than it was in the past, and the U.S. has a lower rate of new TB cases than most countries.

Tuberculosis is caused by bacteria that usually attack the lungs, and is spread through the air when an infectious person coughs or sneezes. If not treated properly, it can be fatal. In the late 1800s, TB killed one out of every seven people living in the United States and Europe. But the development of antibiotics and public health efforts succeeded in treating infections and tracking down those they infected, leading to cases falling for decades.

The new CDC statistics are not a count of how many people were newly infected in 2023, but rather of how many people developed a cough or other symptoms and were diagnosed.

An estimated 85% of the people counted in 2023 were infected at least a year or two earlier and had what’s called latent TB, when the bacteria enters the body and hibernates in the lungs or other parts of the body. Experts estimate as many as 13 million Americans have latent TB and are not contagious.

When the immune system is weakened — by certain medications or other illnesses like diabetes and HIV — the TB wakes up, so to speak. Nicole Skaggs said she was infected in 2020, but didn’t develop symptoms until 2022 — after she got sick from COVID-19.

“Anything that can take out or lower your immune system can put you at risk,” said Skaggs, 41, a property manager in Bothell, Washington.

CDC officials called the idea that COVID-19 has played a role in increased reactivation of TB “an important question.” Scientists are still learning what causes latent TB to reactivate and “I would consider it an unknown at this point,” LoBue said.

“It’s too early to tell” what will happen to TB trends in the next few years, he also said.

There are TB vaccines being developed, and public health workers that were focused on COVID are now back to trying new approaches to preventing TB. New York City, which saw cases jump 28% last year, is hiring TB case managers and community health workers and increasingly using video monitoring of patients taking medications to keep treatment rates high, said Dr. Ashwin Vasan, the city’s health commissioner.

On the other hand, federal TB funding for state and local health department efforts has been flat, and one of the key antibiotics used against TB has been in short supply in recent years. Plus, drug-resistant TB infections have popped up in a fraction of cases.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

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Yellow fever vaccine: Holidaymakers issued travel warning as fatal disease surges - symptoms and how to reduce risk

UK holidaymakers are being warned of a potentially fatal disease that is hitting some popular tourist hotspots.

Travel Health Pro, an official government advice site used by the Foreign Office, has highlighted the rise of yellow fever, a disease that became well known in the 18th century when it was frequently called ‘Yellow Jack’.

It caused huge fatalities among soldiers and sailors serving overseas, especially in the tropics. It is spread by mosquitos and can cause a serious haemorrhagic illness which can be fatal for humans.

Tourists heading to the Caribbean, parts of Africa, Central and South America are being warned to be vigilant. Countries which have experienced recent outbreaks include Trinidad in the Caribbean, Burkina Faso, Cameroon, Central African Republic, Chad, Republic of the Congo, Côte d’Ivoire, Democratic Republic of the Congo, Guinea, Niger, Nigeria, South Sudan, Togo and Uganda.

Seven confirmed yellow fever cases included four fatalities in South America which were reported between January 1 and March 19 this year. There have also been three fatal cases in Colombia, two cases in Guyana and two cases in Peru - which included one death. Brazil has reported confirmed yellow fever in monkeys indicating it is circulating in the country.

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Tuberculosis breaks out at Chicago migrant shelters following measles cases

Chicago health officials have announced that a "small number" of tuberculosis (TB) cases have been reported at some migrant facilities following a recent outbreak of measles among migrants living in the Windy City's shelters.

The Chicago Department of Public Health (CDPH) said the TB cases were reported in "a few different shelters" in the city. However, officials did not disclose the exact number of confirmed cases or which shelter locations they originated from, Fox 32 Chicago reports . 

The agency says its medical teams are ramping up contact tracing to address the health issue. Tuberculosis is an infectious bacterial disease that mainly affects the lungs.

READ MORE OF FOX NEWS' COVERAGE OF THE BORDER CRISIS

The confirmed tuberculosis cases come as more than 55 measles cases have now been confirmed in Chicago, with the majority of those cases being reported in the Pilsen migrant shelter on Halsted Street.

"CDPH is aware of a small number of cases of TB among new arrivals in a few different shelters over the course of the response," the health agency said in a statement to Fox 32.

READ ON THE FOX NEWS APP

The health body said that between 10 to 20% of Central and South American residents have a latent TB infection, which is asymptomatic and not transmissible to others. It does, however, result in a positive TB test, CDPH says. 

CDC SENDS RESPONSE TEAM TO CHICAGO MIGRANT SHELTER AMID MEASLES OUTBREAK

CDPH says TB is curable with antibiotics and is not particularly infectious . It typically requires several hours or more of prolonged close contact between individuals to spread.

"TB is not a novel or rarely seen illness in Chicago, as the Chicago Department of Public Health typically expects to see between 100-150 cases of tuberculosis in Chicago residents in an average year," the CDPH statement reads. "We will continue to offer treatment to individuals as necessary and take the proper precautions to eliminate spread, but we do not consider this a matter presenting a substantial threat to the public."

ILLINOIS REPORTS FIRST MEASLES CASE SINCE 2019: ‘ONE OF THE MOST CONTAGIOUS DISEASES KNOWN’

Raymond Lopez, a Chicago Alderman, told Fox and Friends on Thursday morning that this outbreak could have been prevented had the migrants been required to follow the same vaccination rules as U.S. citizens.

"This is a crisis we could have avoided, just like with the measles, if we had simply instituted the American standard of vaccines upon all those migrants being shipped to the city of Chicago," Lopez said. 

"Many of these individuals come with children, they are in our schools and all of those vaccination requirements that our kids are responsible for are waved for the migrant asylum seeker children. And that is putting the people, families and communities at risk."

The TB vaccine, known as BCG, is not widely used in the U.S. but it is often given to infants and small children in other countries where TB is common, the CDC website says. The CDC says it does not always protect people from getting TB. 

Dr. Aniruddha Hazra, associate professor of medicine at the University of Chicago, says the vaccine is not really effective. 

"There is no effective vaccine against tuberculosis," Hazra told Fox 32 Chicago. "These outbreaks happen in close quarters, people who are living close to one another."

Hazra says that while the situation is cause for concern, the public has no reason to panic.

"The people who are most at risk of tuberculosis are the other migrants living in that shelter," said Hazra, who added that measles, however, is preventable through vaccination.

The TB outbreak comes after the number of  U.S. tuberculosis cases  in 2023 were the highest in a decade, according to the CDC.

Cases increased from 8,320 in 2022 to 9,615 in 2023, an increase of 1,295 cases with numbers going up among all age groups. Data from the agency shows nearly 10,000 infections in 2013.

Fox News’ Greg Norman contributed to this report. 

Original article source: Tuberculosis breaks out at Chicago migrant shelters following measles cases

Vaccine Protects Cattle from Bovine Tuberculosis; May Eliminate Disease

Tue april 02, 2024.

Bovine Tuberculosis (TB) results in large economic losses to animal agriculture worldwide. The disease can also transmit to humans and cause severe illness and death. Researchers from Penn State, Addis Ababa University and the University of Cambridge have now demonstrated that a vaccine for TB currently used in humans significantly reduces infectiousness of vaccinated livestock, improving prospects for elimination and control. The study is published in the journal Science.

The spillover of infection from livestock has been estimated to account for about 10% of human tuberculosis cases. While such zoonotic TB (zTB) infections are most commonly associated with gastrointestinal infections related to drinking contaminated milk, zTB can also cause chronic lung infections in humans. Lung disease caused by zTB can be indistinguishable from regular tuberculosis but is more difficult to treat due to natural antibiotic resistance in the cattle bacteria.

“For over a hundred years, programs to eliminate bovine tuberculosis have relied on intensive testing and slaughtering of infected animals,” said Vivek Kapur, professor of microbiology and infectious diseases and Huck Distinguished Chair in Global Health at Penn State and a corresponding author of the study. “This approach is unimplementable in many parts of the world for economic and social reasons, resulting in considerable animal suffering and economic losses from lost productivity, alongside an increased risk of spillover of infection to humans. By vaccinating cattle, we hope to be able to protect both cattle and humans from the consequences of this devastating disease.”

In the study, carried out in Ethiopia, the researchers examined the ability of the vaccine, Bacillus Calmette-Guérin (BCG), to directly protect cattle that receive it, as well as to indirectly protect both vaccinated and unvaccinated cattle by reducing transmission. They placed vaccinated and unvaccinated animals into enclosures with naturally infected animals in a novel crossover design performed over two years.

“Our study found that BCG vaccination reduces TB transmission in cattle by almost 90%,” said Andrew Conlan, associate professor of epidemiology at the University of Cambridge and a corresponding author of the study. “Vaccinated cows also developed significantly fewer visible signs of TB than unvaccinated ones. This suggests that the vaccine not only reduces the progression of the disease, but that if vaccinated animals become infected, they are also substantially less infectious to others.”

Next, using livestock census and movement data from Ethiopia, the team developed a transmission model to explore the potential for routine vaccination to control bovine tuberculosis.

“Results of the model suggest that vaccinating calves within the dairy sector of Ethiopia could reduce the reproduction number of the bacterium, arresting the projected increase in the burden of disease and putting herds on a pathway toward elimination of TB,” Conlan said.

The team focused their studies in Ethiopia, a country with the largest cattle herd in Africa and a rapidly growing dairy sector that has a growing burden of bovine tuberculosis and no current control program, as a representative of similarly situated transitional economies.

“Bovine tuberculosis is largely uncontrolled in low- and middle-income countries, including Ethiopia,” said Abebe Fromsa, associate professor of agriculture and veterinary medicine at Addis Ababa University in Ethiopia and the study’s co-lead author. “Therefore, vaccination of cattle has the potential to provide significant benefits in these regions.”

Professor James Wood, the Alborada Professor of Equine and Farm Animal Science from the Department of Veterinary Medicine at the University of Cambridge noted that despite being more prevalent in lower-income countries, the United Kingdom, Ireland and New Zealand also experience considerable economic pressures from the disease which continues to persist despite intensive and costly control programs.

“For over 20 years, the U.K. government has pinned hopes on cattle vaccination for bovine tuberculosis as a solution to reduce the disease and the consequent costs of the controls,” Wood said. “These results provide important support for the epidemiological benefit that cattle vaccination could have to reduce rates of transmission to and within herds.”

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Guest Essay

I’m a Doctor. Dengue Fever Took Even Me by Surprise on Vacation.

By Deborah Heaney

Dr. Heaney is a physician in Ann Arbor, Mich.

I hate mosquitoes so much that I take my own bug repellent to parties. But in early March, on a trip with my partner to the idyllic island of Curaçao off Venezuela, I was caught off guard by insect bites after our bed-and-breakfast hosts said that mosquitoes didn’t usually appear until late summer.

Near the end of the vacation, my legs began to ache. After I couldn’t keep up with my partner on a snorkeling adventure, he pulled me from the water. My ribs felt broken, as if I’d been smashed against large boulders in the sea. Later that day came intense fever, alternating with shaking chills.

Back in Michigan — weak, nauseated and dehydrated from explosive diarrhea — I ended up in the emergency department. Tests showed worrisome white blood cell levels and abnormal liver numbers. The physician assistant who saw me was perplexed; she gave me IV fluids and medication for nausea and sent me home.

A few days later I developed itching so severe that I couldn’t sleep. A bright red rash spread over both thighs and up my lower back. My brain was foggy, and my balance was so impaired that I would have failed a sobriety test. My primary care doctor had no answers. But as my head began to clear, it occurred to me to request a dengue fever test.

Two days later, the test was positive.

Despite my training in medicine, I was blindsided. Dengue, a mosquito-borne illness, is surging through Latin America and the Caribbean, including in Puerto Rico, where a public health emergency was declared last week. This year is likely to be the worst on record, in part because of El Niño-driven temperature spikes and extreme weather linked to climate change. As temperatures rise and precipitation patterns grow more erratic, the problem will get only worse.

But neither the traveling public nor our frontline health workers are prepared. Without urgent reforms to how we educate travelers, doctors, nurses and others — as well as reforms to public health surveillance and early warning systems — we will be doomed to miss textbook cases like mine. That means those infected with dengue will miss out on timely treatment, possibly even spreading the virus to areas where it was never found before.

The dengue virus, which is primarily transmitted by the Aedes aegypti mosquito, infects up to 400 million people every year in nearly every region of the world, but it is most prevalent in Latin America, South and Southeast Asia and East Africa. Most cases are asymptomatic or, like mine, are considered mild, although the aptly nicknamed breakbone fever often doesn’t feel that way. Some 5 percent of cases progress to a severe, life-threatening disease including hemorrhagic fever.

One malicious feature of dengue is that when someone is infected a second time with a different type of the virus, the risk of severe illness is higher. A vaccine exists, but the Centers for Disease Control and Prevention recommends it only for children ages 9 to 16 who had dengue before and live in places where the virus is common. That’s because, paradoxically, if you’ve never had dengue, the vaccine puts you at greater risk of severe illness your first time.

Dengue outbreaks, which, in the Americas, tend to occur every three to five years , now appear to be expanding their geographic reach as temperatures climb . The Aedes aegypti mosquito has typically had difficulty surviving and reproducing during the winter in temperate climates. But in parts of Brazil, which is experiencing a dengue emergency , the thermometer no longer dips as low in the winter as it once did, allowing the bugs to reproduce year-round. Overall, Latin America and the Caribbean have had three times the number of cases this year as reported for the same period in 2023, which was a record year. Higher temperatures are also helping the virus develop faster inside the mosquito, leading to a higher viral load and a higher probability of transmission. And mosquitoes are benefiting from standing water from rains and floods that are growing more extreme in a warming world.

As the virus spreads globally, travelers are bringing infections back to the continental United States. Based on 2024 numbers to date, this year should show a clear increase of cases here at home compared with 2023, given that the typical dengue season hasn’t even started yet. There could also be local outbreaks in places like Florida, Texas and California, which experienced small ones in the past. As Dr. Gabriela Paz-Bailey, the chief of the C.D.C.’s dengue branch, told me by email, “Increased travel to places with dengue risk could lead to more local transmission, but the risk of widespread transmission in the continental United States is low.”

But since testing is done only on a small fraction of cases, many are going uncounted. I was the one who requested that I be tested. Had I not been given a diagnosis, I would not be aware of my increased risk of severe illness if I am reinfected. Getting a diagnosis is crucial to inform those infected in areas where the Aedes mosquito lives so that the virus doesn’t spread further.

The growing risk means travelers to regions with dengue must be savvier: They can check local news and U.S. State Department advisories, bring an effective insect repellent and protective clothing and book lodging with air-conditioning or screens on the windows and doors. Though Aedes aegypti mosquitoes now live year-round in many locations and are pushing northward into new regions , thanks to climate change and other factors, there are still seasons when the risk is greater, and travelers might consider avoiding trips during those periods. Travel insurance with medical coverage may also be a useful precaution.

For medical professionals, this should be a warning. We need to start thinking about dengue as a possible diagnosis, not just a piece of textbook trivia. We should ask about recent travel when treating patients presenting with symptoms, especially symptoms not easily explained by other diagnoses.

Medical schools are gradually integrating climate change effects into curriculums . This is essential, since malaria, Lyme, West Nile and other insect-borne diseases are on the rise, as are other conditions like heat illness, asthma and allergies that are worsened by climate change. This work must accelerate, and training must include those of us who are already practicing. State medical boards should consider mandating continuing education on tropical emerging illnesses, as they do on many other pertinent topics.

After receiving my positive test result, I called the emergency department to leave a message for my previous provider about my diagnosis, assuming she had never before seen dengue. If we continue on this trajectory, I’m certain this won’t be her last case.

Deborah Heaney is a preventive, occupational and environmental health physician practicing in Ann Arbor, Mich. She also holds a master’s degree in public health.

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An earlier version of this article included an incorrect reference to the mosquitoes that spread dengue. They are members of the Aedes genus, not species.

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