Antibiotic Resistance: What Is It

Antibiotic Resistance: What Is It, Complications and Treatment

What is antibiotic resistance?

Antibiotic resistance occurs antibiotic resistance bacteria evolve and develop the ability to defeat the drugs designed to kill them. This means that infections caused by these resistant bacteria become harder to treat, as the antibiotics lose their effectiveness. The resistance typically arises due to overuse or misuse of antibiotics, such as taking them for viral infections or not completing prescribed courses of treatment. As bacteria evolve, they can acquire resistance through mutations or by acquiring resistance genes from other bacteria, leading to the spread of "superbugs" that are difficult to treat with existing antibiotics. This poses a significant public health challenge globally.

What causes antibiotic resistance?

Antibiotic resistance is primarily caused by several key factors related to both natural bacterial evolution and human practices. Here are the main causes:

Overuse of Antibiotics:

 Frequent or unnecessary use of antibiotics, such as for viral infections like the flu or common cold (where they are ineffective), accelerates the development of resistance.

Incomplete Courses of Treatment:

 When patients do not finish the full course of antibiotics, some bacteria may survive and develop resistance, as they have been exposed to but not fully eliminated by the drug.

Improper Prescribing: 

Sometimes, antibiotics are prescribed when they are not needed, or broad-spectrum antibiotics are used when a narrow-spectrum drug would suffice. This promotes the development of resistance in a wider range of bacteria.

Use in Agriculture: 

Antibiotics are commonly used in livestock to prevent disease and promote growth. This can lead to resistant bacteria being transferred to humans through food consumption or environmental exposure.

Poor Infection Control and Hygiene: 

In healthcare settings, improper infection control measures can lead to the spread of resistant bacteria. Poor sanitation and hygiene practices in the community can also contribute to the spread.

Horizontal Gene Transfer: 

Bacteria can share genetic material, including resistance genes, through mechanisms like conjugation, transformation, or transduction. This allows resistance to spread between different bacterial species.

Lack of New Antibiotics:

 The slow development of new antibiotics combined with the rapid adaptation of bacteria to existing ones has contributed to the resistance problem, as the options for treatment become limited over time.

Together, these factors contribute to the growing public health threat of antibiotic resistance.

Who is most at risk for antibiotic-resistant infections?

Certain groups of people are more vulnerable to antibiotic-resistant infections due to their health conditions, environments, or frequent exposure to antibiotics. Those at highest risk include:

Hospitalized Patients: 

People in healthcare settings, particularly those with weakened immune systems, recent surgeries, or invasive devices (e.g., catheters, ventilators), are at higher risk of contracting resistant infections like MRSA (methicillin-resistant Staphylococcus aureus).

People with Chronic Illnesses:

 Those with chronic diseases such as diabetes, kidney disease, or cancer often require frequent medical care and antibiotics, increasing their risk of exposure to resistant bacteria.

Elderly Individuals:

 Older adults tend to have weaker immune systems and are more likely to be hospitalized or in long-term care facilities, where resistant infections are more common.

People with Weakened Immune Systems: 

Those with conditions like HIV/AIDS, or who are undergoing chemotherapy, organ transplants, or long-term steroid treatments, have compromised immune systems, making them more susceptible to antibiotic-resistant infections.

Frequent Antibiotic Users:

 Individuals who take antibiotics often, either for frequent infections or for chronic conditions, are at a higher risk of developing resistant infections due to repeated exposure to antibiotics.

Residents of Long-Term Care Facilities:

 Nursing homes and similar facilities often house individuals with multiple health issues, and resistant bacteria can spread easily due to close living quarters and frequent antibiotic use.

Agricultural Workers: 

Those who work with livestock or in farming environments where antibiotics are used for animal growth promotion or disease prevention may come into contact with resistant bacteria.

Travelers to Areas with High Antibiotic Resistance:

 In some parts of the world, resistant infections are more prevalent due to less regulated antibiotic use, increasing the risk for travelers to bring resistant bacteria back home.

Preventing antibiotic-resistant infections in these groups involves limiting unnecessary antibiotic use, improving hygiene and infection control, and monitoring and managing antibiotic-resistant outbreaks closely.

Why is antibiotic resistance a problem?

Antibiotic resistance is a serious global problem for several key reasons:

1. Limited Treatment Options:

 As bacteria become resistant to antibiotics, it becomes harder to treat infections. Many of the antibiotics that were once effective no longer work, which limits the available treatment options, especially for severe infections.

2. Longer and More Severe Illnesses:

 Infections caused by resistant bacteria often last longer and may require more intensive care. Patients may suffer from prolonged illness or complications that could have been prevented if the infection had been treated effectively from the start.

3. Higher Medical Costs: 

Treating antibiotic-resistant infections is more expensive. Patients may need longer hospital stays, more follow-up care, and more expensive or toxic alternative medications. In some cases, surgery or other invasive procedures may be required to remove the infection.

4. Increased Mortality Rates: 

Resistant infections can lead to higher death rates. When antibiotics are ineffective, infections like sepsis, pneumonia, and bloodstream infections can become life-threatening. According to the World Health Organization (WHO), antibiotic resistance contributes to millions of deaths each year.

5. Spread of Resistance:

 Resistant bacteria can spread between people, animals, and the environment. This means that antibiotic resistance can impact not only individual patients but also entire communities and even countries. The global spread of "superbugs" that resist multiple drugs, such as MRSA and carbapenem-resistant Enterobacteriaceae (CRE), is a significant concern.

6. Threat to Medical Advances: 

Many modern medical treatments, such as organ transplants, cancer chemotherapy, and surgeries, rely on effective antibiotics to prevent or treat infections. Antibiotic resistance undermines the success of these procedures, making them riskier and less effective.

7. Public Health Threat: 

Without effective antibiotics, infections that were once easily treatable could again become major public health threats. Diseases that are currently under control, such as tuberculosis, could re-emerge with resistant strains that are far more difficult to treat.

8. Impact on Vulnerable Populations:

 The most vulnerable, such as infants, the elderly, and those with weakened immune systems, are at greatest risk from resistant infections, leading to higher health disparities.

In summary, antibiotic resistance threatens to reverse decades of medical progress, making it one of the most urgent health challenges facing the world today.

Which antibiotic-resistant bacteria are deadliest?

Some of the deadliest antibiotic-resistant bacteria, often referred to as "superbugs," pose significant threats due to their resistance to multiple antibiotics. These bacteria cause serious infections that are difficult or sometimes impossible to treat. Here are some of the most dangerous:

1. Carbapenem-resistant Enterobacteriaceae (CRE):

 CRE includes bacteria such as Klebsiella and Escherichia coli (E. coli) that are resistant to carbapenems, a class of last-resort antibiotics. CRE infections have a high mortality rate (up to 50%) because they are resistant to most available antibiotics and often occur in healthcare settings, leading to serious infections like sepsis, pneumonia, and urinary tract infections (UTIs).

2.nMethicillin-resistant Staphylococcus aureus (MRSA):

 MRSA is resistant to methicillin and other commonly used antibiotics. It can cause severe infections, including bloodstream infections, pneumonia, and surgical site infections. MRSA is particularly dangerous in hospitals, nursing homes, and among people with weakened immune systems, but it can also spread in the community.

3. Vancomycin-resistant Enterococci (VRE):

 Enterococci are bacteria that normally live in the intestines but can cause serious infections in the blood, urinary tract, and wounds. VRE are resistant to vancomycin, one of the antibiotics used to treat severe enterococcal infections, making these infections difficult to manage, especially in hospitalized patients.

4. Multidrug-resistant Pseudomonas aeruginosa: 

This bacterium is known for causing serious infections in immunocompromised individuals, especially those in hospitals or on ventilators. It is resistant to many types of antibiotics, including carbapenems, and is associated with high mortality rates in patients with severe infections, such as pneumonia or bloodstream infections.

5. Drug-resistant Neisseria gonorrhoeae: 

This bacterium causes gonorrhea, a sexually transmitted infection (STI). In recent years, strains of Neisseria gonorrhoeae have emerged that are resistant to nearly all antibiotics used to treat gonorrhea, including ceftriaxone, the last-line treatment. Untreated gonorrhea can lead to severe reproductive complications and increase the risk of HIV transmission.

6. Multidrug-resistant Acinetobacter baumannii:

 This bacterium is particularly dangerous in hospitals, where it can cause pneumonia, bloodstream infections, and wound infections, especially in patients in intensive care units (ICUs). It is resistant to many antibiotics, including carbapenems, and has a high mortality rate in critically ill patients.

7. Drug-resistant Mycobacterium tuberculosis (MDR-TB and XDR-TB): 

M. tuberculosis causes tuberculosis (TB), a deadly respiratory infection. Multidrug-resistant tuberculosis (MDR-TB) is resistant to at least two of the most potent TB drugs (isoniazid and rifampicin). Extensively drug-resistant TB (XDR-TB) is even more dangerous, as it is resistant to several second-line treatments as well, making it extremely difficult to treat and control.

8. Clostridioides difficile (C. diff): 

While not traditionally resistant to antibiotics in the same way as the other bacteria listed, C. difficile infections often arise after antibiotic use, as the drugs disrupt normal gut flora, allowing C. diff to proliferate. Some strains have become more virulent and harder to treat, leading to severe diarrhea, colitis, and, in some cases, death.

These bacteria are particularly concerning due to their ability to cause life-threatening infections and their resistance to multiple treatment options.

What are superbugs?

Superbugs are strains of bacteria, viruses, fungi, or parasites that have developed resistance to multiple antibiotics or other antimicrobial agents that are typically used to treat infections. These organisms have evolved mechanisms that allow them to survive and multiply even in the presence of drugs designed to kill them, making infections caused by superbugs extremely difficult to treat.

The term "superbug" is most commonly used to describe bacteria that are resistant to several types of antibiotics, but it can also refer to drug-resistant viruses and fungi. Here are some key features and examples:

Characteristics of Superbugs:

1. Multidrug Resistance: 

Superbugs are resistant to multiple antibiotics, particularly those that are considered first-line or broad-spectrum treatments.

2. Evolved Resistance Mechanisms: 

These organisms have developed various ways to defend themselves against antibiotics, such as:

● Producing enzymes that neutralize or break down antibiotics (e.g., beta-lactamases that degrade penicillins).

● Altering their cell structures to prevent antibiotics from entering.

● Pumping antibiotics out of their cells using efflux pumps.

● Mutating target sites within their cells so antibiotics can no longer bind effectively.

3. Spread in Healthcare Settings: 

Superbugs are most commonly associated with hospitals and long-term care facilities, where antibiotic use is frequent, and patients may have weakened immune systems.

4. Harder to Treat: 

Infections caused by superbugs often require more potent, expensive, or toxic drugs, and in some cases, there are few or no effective treatments left.

Examples of Superbugs:

1. Methicillin-resistant Staphylococcus aureus (MRSA): 

Resistant to methicillin and many other antibiotics, MRSA is a major cause of hospital-acquired infections and can lead to severe skin infections, pneumonia, and bloodstream infections.

2. Carbapenem-resistant Enterobacteriaceae (CRE): 

Bacteria like Klebsiella and E. coli that are resistant to carbapenems, a class of last-resort antibiotics, are known for causing deadly infections in healthcare settings.

3. Vancomycin-resistant Enterococci (VRE): 

Enterococci bacteria resistant to vancomycin, often causing serious infections in hospital patients.

4. Multidrug-resistant Pseudomonas aeruginosa: 

Common in hospital infections, this superbug is resistant to many antibiotics and can cause life-threatening pneumonia and bloodstream infections.

5. Extensively Drug-resistant Mycobacterium tuberculosis (XDR-TB): 

A form of tuberculosis that is resistant to most of the drugs used to treat TB, making it extremely difficult to cure.

6. Drug-resistant Neisseria gonorrhoeae:

 This bacterium causes gonorrhea, and many strains are now resistant to nearly all antibiotics used to treat the sexually transmitted infection.

Superbugs are a significant public health concern because their resistance to multiple drugs makes them harder to control, leading to longer hospital stays, increased medical costs, and higher mortality rates. Their rise is largely driven by overuse and misuse of antibiotics, both in healthcare and agriculture, and they pose a threat to modern medicine by undermining the effectiveness of existing treatments for bacterial infections.

How can we combat antibiotic resistance?

Combating antibiotic resistance requires a coordinated effort across various sectors, including healthcare, agriculture, and public health, as well as individual actions. Here are key strategies to address this growing problem:

1. Prudent Use of Antibiotics

■ Only Use Antibiotics When Necessary: 

Antibiotics should only be prescribed for bacterial infections, not for viral illnesses like the flu or the common cold. Avoiding unnecessary prescriptions can help reduce the chance of bacteria developing resistance.

■ Complete the Full Course: 

Patients should always complete their prescribed antibiotic course, even if they start feeling better. Stopping treatment early can allow resistant bacteria to survive and multiply.

■ Avoid Misuse in Livestock: 

Reducing the use of antibiotics for growth promotion and disease prevention in agriculture can limit the development of resistant bacteria that can spread to humans through food or the environment.

2. Develop New Antibiotics and Treatments

■ Invest in Research and Development: 

New antibiotics, alternative therapies (e.g., bacteriophages), and diagnostic tools are essential to stay ahead of evolving resistant bacteria. Governments and private sectors should support and invest in the development of new drugs.

■ Encourage Innovation: 

Offering incentives, such as subsidies, tax breaks, or fast-track approvals, can encourage pharmaceutical companies to develop novel antibiotics and antimicrobial treatments.

3. Strengthen Infection Prevention and Control

■ Promote Hygiene and Sanitation: 

Improving hygiene, including frequent handwashing, can reduce the spread of infections and decrease the need for antibiotics. Clean water and proper sanitation in healthcare settings and communities are also crucial.

■ Infection Control in Healthcare Settings: 

Hospitals and healthcare facilities must implement strict infection prevention protocols, including the isolation of patients with resistant infections, proper sterilization of equipment, and rigorous hand hygiene practices by healthcare workers.

■ Vaccination: 

Vaccines can prevent infections and reduce the need for antibiotics. For example, pneumococcal and influenza vaccines can help prevent illnesses that might otherwise require antibiotic treatment.

4. Promote Antimicrobial Stewardship Programs

■ Optimized Antibiotic Prescribing: 

Healthcare facilities should implement antimicrobial stewardship programs that ensure antibiotics are prescribed only when necessary and with the correct dose and duration. This helps prevent overuse and reduces resistance.

■ Educate Healthcare Providers and Patients:

 Raising awareness among doctors, pharmacists, and patients about the dangers of overusing antibiotics and the importance of following guidelines is crucial to reducing resistance.

5. Surveillance and Monitoring

■ Track Resistance Patterns: 

Effective monitoring and reporting systems are needed to track antibiotic resistance globally. This helps identify outbreaks of resistant infections and informs healthcare providers and policymakers on where to focus interventions.

■ Global Coordination: 

Since antibiotic resistance knows no borders, international collaboration is essential. Countries must share data on resistance trends, ensure consistent standards for antibiotic use, and work together on public health strategies.

6. Reduce Antibiotic Use in Agriculture

■ Regulate Antibiotic Use in Farming: 

Governments should limit the use of antibiotics in agriculture to treating sick animals rather than for growth promotion or routine disease prevention. Good farming practices and alternatives like vaccines or improved animal housing should be promoted to reduce the need for antibiotics.

■ Implement Sustainable Farming Practices: 

Healthier environments for livestock, reduced crowding, and better nutrition can help reduce the incidence of infections and the subsequent need for antibiotics.

7. Public Awareness and Education

■ Educate the Public: 

It’s crucial to raise awareness about antibiotic resistance through public health campaigns. People need to understand the importance of using antibiotics responsibly and the risks of misuse.

■ Combat Misconceptions: 

Many people mistakenly believe that antibiotics are effective against viral infections. Clear communication from healthcare providers and public health campaigns can help correct this misunderstanding.

8. Research into Alternative Treatments

■ Explore Non-Antibiotic Therapies: 

Research into alternatives such as bacteriophages (viruses that kill bacteria), antimicrobial peptides, probiotics, or immunotherapies can offer new ways to combat infections without relying on traditional antibiotics.

■ Develop Rapid Diagnostic Tools: 

Faster, more accurate diagnostic tests can help healthcare providers distinguish between bacterial and viral infections, ensuring that antibiotics are only prescribed when truly necessary.

By addressing antibiotic resistance through these combined strategies, we can slow its spread and preserve the effectiveness of antibiotics for future generations.

How do healthcare providers treat antibiotic-resistant bacteria?

Treating infections caused by antibiotic-resistant bacteria is more challenging, but healthcare providers have several strategies to manage and treat these infections. Here’s how they approach the issue:

1. Use of Alternative or Stronger Antibiotics

● Last-Resort Antibiotics:

 When first-line antibiotics fail, doctors turn to more potent antibiotics, such as carbapenems, colistin, or tigecycline. However, some bacteria are resistant to even these drugs, so they are used cautiously due to their toxicity and side effects.

● Combination Therapy:

 In some cases, doctors use combinations of antibiotics to try and overcome resistance. By attacking the bacteria from multiple angles, combination therapy can prevent bacteria from surviving and adapting.

2. Individualized Treatment Based on Sensitivity Testing

● Antibiotic Susceptibility Testing: 

When a patient is diagnosed with an infection, doctors often run lab tests (culture and sensitivity tests) to determine which antibiotics the bacteria are resistant to and which ones may still be effective. This allows for targeted therapy, using the most appropriate antibiotic for the specific infection.

● Adjusting Treatment Based on Results: 

Once sensitivity results are available, healthcare providers may adjust the patient’s treatment plan to focus on antibiotics that are effective against the identified strain of resistant bacteria.

3. Use of Higher Doses or Prolonged Treatment

● Optimized Dosing:

 In some cases, using higher doses of antibiotics or extending the duration of treatment can help overcome partial resistance. However, this approach is carefully managed to avoid toxicity and side effects.

● Extended Infusions:

 For some antibiotics, administering them over a longer period (extended infusion) rather than as a quick dose can help increase their effectiveness, particularly in serious infections like sepsis.

4. Non-Antibiotic Therapies

● Phage Therapy: 

Bacteriophages are viruses that specifically target and kill bacteria. Although still experimental in most countries, phage therapy has been used successfully in some cases to treat antibiotic-resistant infections.

● Antimicrobial Peptides: 

These are small proteins that can kill bacteria by disrupting their cell membranes. Research into antimicrobial peptides is ongoing, and they may provide new options for treating resistant infections.

● Immunotherapies: 

Boosting the patient’s immune response to help fight off infections is another approach. This can involve the use of monoclonal antibodies or immune system stimulants.

● Probiotics and Fecal Microbiota Transplant (FMT): 

For infections like Clostridioides difficile (C. diff), restoring healthy gut bacteria through probiotics or FMT (transplanting healthy stool) can help resolve the infection without the use of antibiotics.

5. Surgical Interventions

● Removing Infected Tissue or Devices: 

In some cases, surgery may be necessary to remove the source of the infection. For example, if an infection is associated with an implanted medical device (such as a catheter or prosthetic), the device may need to be removed to fully clear the infection.

● Drainage of Abscesses: 

For certain resistant infections that lead to abscess formation (pockets of pus), surgical drainage may be required to remove the infected material, especially when antibiotics alone are insufficient.

6. Strict Infection Control Measures

● Isolation of Infected Patients: 

To prevent the spread of antibiotic-resistant bacteria, hospitals may isolate patients with resistant infections (e.g., MRSA or CRE). Healthcare workers take extra precautions, including wearing gowns, gloves, and masks, and practicing stringent hand hygiene.

● Antimicrobial Stewardship Programs: 

These programs help ensure that antibiotics are prescribed appropriately and only when needed, to prevent the development of resistance and reduce the spread of resistant bacteria.

7. Supporting the Immune System

● Supplementary Treatments:

 In severe infections, especially in patients with weakened immune systems, doctors may use other therapies to support the immune response. These could include treatments to enhance white blood cell function or immunoglobulin therapy to provide antibodies that can help the body fight off infection.

8. Close Monitoring and Supportive Care

● Intensive Care for Critical Cases:

 For life-threatening infections, patients may need to be placed in an intensive care unit (ICU) to receive close monitoring and supportive care (e.g., ventilation, fluids, and medications to maintain blood pressure). In these cases, treatment focuses not only on fighting the infection but also on managing the symptoms and complications caused by the resistant bacteria.

● Monitoring for Treatment Efficacy: 

Throughout treatment, healthcare providers carefully monitor the patient's response, adjusting medications as needed to ensure the infection is being controlled and there are no signs of worsening.

9. Research into New Treatments

● Clinical Trials: 

Patients with resistant infections may be enrolled in clinical trials testing new antibiotics or alternative therapies. This offers hope for patients who have exhausted traditional treatment options, while also advancing medical knowledge on how to combat resistant infections.

By employing these strategies, healthcare providers aim to manage antibiotic-resistant infections while minimizing the risks to patients and preventing the further spread of resistant bacteria.

What is an antibiotic-resistant UTI?

An antibiotic-resistant urinary tract infection (UTI) is a UTI caused by bacteria that have developed resistance to one or more of the antibiotics typically used to treat it. UTIs are common infections that affect the urinary system, which includes the bladder, kidneys, ureters, and urethra. They are usually caused by bacteria, with Escherichia coli (E. coli) being the most frequent culprit.

When the bacteria causing the UTI are resistant to antibiotics, standard treatments become ineffective, making the infection harder to cure. This can lead to more severe symptoms, prolonged illness, and the need for more potent, and often more expensive or toxic, antibiotics.

Causes of Antibiotic-Resistant UTIs:

1. Overuse or Misuse of Antibiotics:

 Repeated or unnecessary use of antibiotics, especially broad-spectrum antibiotics, increases the likelihood that bacteria will develop resistance.

2. Incomplete Treatment Courses:

 Not finishing a prescribed course of antibiotics can leave some bacteria alive, which may adapt and develop resistance.

3. Frequent UTIs: 

People who suffer from frequent or recurrent UTIs may develop resistance as their bacteria are exposed to antibiotics more often.

4. Healthcare-Associated Infections:

 UTIs acquired in hospitals or other healthcare settings, often due to the use of catheters, are more likely to involve resistant bacteria like MRSA, CRE, or Pseudomonas aeruginosa.

Common Bacteria in Resistant UTIs:

■ Extended-spectrum beta-lactamase (ESBL)-producing bacteria:

 These bacteria produce enzymes that make them resistant to a wide range of antibiotics, including penicillins and cephalosporins.

■ Carbapenem-resistant Enterobacteriaceae (CRE):

 These bacteria are resistant to carbapenems, a last-line antibiotic used for severe infections.

■ Multidrug-resistant E. coli strains:

 Some strains of E. coli, which are the most common cause of UTIs, have developed resistance to multiple antibiotics, including fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim).

Symptoms of an Antibiotic-Resistant UTI:

The symptoms of antibiotic-resistant UTIs are the same as those of regular UTIs, but they may be more severe or persistent due to the difficulty in treating the infection:

■ Frequent, urgent need to urinate

■ Pain or burning sensation during urination (dysuria)

■ Cloudy, bloody, or strong-smelling urine

■ Lower abdominal or pelvic pain

■ Fever, chills, or back pain if the infection has spread to the kidneys

Treatment of Antibiotic-Resistant UTIs:

1. Antibiotic Sensitivity Testing: 

When a resistant UTI is suspected, doctors will often order a urine culture and sensitivity test to identify the specific bacteria causing the infection and determine which antibiotics will still be effective.

2. Use of Alternative Antibiotics:

 For resistant UTIs, doctors may prescribe alternative or last-resort antibiotics, such as fosfomycin, nitrofurantoin, or carbapenems, depending on the bacteria involved.

3. Extended Courses of Antibiotics: 

Resistant UTIs may require longer treatment durations to fully clear the infection.

4. Intravenous Antibiotics:

 In severe cases, especially if the infection has spread to the kidneys or bloodstream, patients may need to receive antibiotics intravenously in a hospital setting.

5. Preventive Measures: 

For patients prone to frequent UTIs, doctors may recommend preventive strategies such as low-dose antibiotics, probiotics, or lifestyle changes to reduce the risk of future infections.

Prevention of Antibiotic-Resistant UTIs:

■ Use Antibiotics Responsibly: 

Only take antibiotics when prescribed, and follow the complete treatment plan as directed by a healthcare provider.

■ Maintain Good Hygiene:

 Proper personal hygiene, such as wiping from front to back and urinating after sexual activity, can help prevent bacterial spread.

■ Stay Hydrated: 

Drinking plenty of water helps flush bacteria out of the urinary tract and can reduce the risk of infection.

■ Catheter Care:

 For individuals who use urinary catheters, strict hygiene and proper handling can prevent catheter-associated UTIs, which are often resistant.

Antibiotic-resistant UTIs are becoming increasingly common, making prevention, early detection, and proper management essential to reducing their impact on health.