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Archive for the ‘Epidemiology’ Category

Pathogen of the month: Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tuberculosis), a non-motile, obligately aerobic, intracellular bacterium known to cause Tuberculosis (TB), was discovered by Robert Koch in 1882 [1]. TB primarily affects the lungs along with the abdomen, bones, nervous system, reproductive system, liver, and lymph glands [2].

Pulmonary Tuberculosis ( TB ) : Chest x-ray show alveolar infiltration at both lung due to mycobacterium tuberculosis infectio
Pulmonary Tuberculosis ( TB ): Chest x-ray shows alveolar infiltration at both lungs due to Mycobacterium tuberculosis infection

 

Global Burden of Tuberculosis

The World Health Organization (WHO) has reported a 22% decrease in TB-related mortality between 2000-2015, with a gradual 1.5% decrease in the annual rate. However, despite this trend and successful control of disease transmission, TB continues to have a significantly higher rate of morbidity. In 2015, six countries (China, India, Nigeria, Pakistan, Indonesia, and South Africa) accounted for 60% of TB-related deaths [3].

 

Global cases of Tuberculosis between 1965-2019

Worldwide Tuberculosis cases and rates, 1965 - today

 

Pathogenicity of Mycobacterium tuberculosis

Mycobacterium tuberculosis is transmitted in the form of droplet nuclei exhaled by individuals affected with laryngeal/pulmonary TB. It enters the body via the nasal cavity/mouth and travels to the alveoli of the lungs, where it recruits macrophages to the lung surface, in turn transporting the bacteria to the deeper tissues [4]. Another round of macrophage recruitment to the originally infected locus forms an organized aggregate of differentiated macrophages and immune cells called a granuloma. The infected granuloma undergoes necrosis, promoting bacterial growth and transmission to the next host [5].

Diagnosis of TB

Some patients with TB may present with non-specific findings such as anemia, weight loss, fever of unknown origin, and fatigue; while others may be asymptomatic and show no abnormalities on physical examination [6]. Thus, the physician should collect body fluids/tissues for Acid-Fast bacilli (AFB) smear and culture.  Only a positive culture can confirm the diagnosis of TB.

Confirmatory and diagnostic tests for TB:

– Culture, followed by Ziehl-Neelsen (AFB) staining

– A Chest X-ray to confirm the diagnosis in case of positive culture, indicating active disease

– Gene-based tests and nuclear amplification to identify the bacterial strains using DNA-based molecular techniques, such as GeneXpert [7].

 

Ziehl-Neelsen staining

AFB staining is the traditional method of TB diagnosis, as it is inexpensive and provides rapid results [8]. Mycobacterium species retain dyes when heated and treated with acidified organic compounds. The most common acid-fast staining method for M. tuberculosis is the Ziehl-Neelsen stain method, in which a specimen is fixed, stained with carbol-fuchsin dye, and decolorized with an acid-alcohol mixture. After counter-staining the smear with methylene blue or a similar dye, AFB appear red against a contrasting blue background [9].  In general, a sputum sample must contain at least 10,000 organisms/mL to visualize these bacteria at 100x magnification. 

Symptoms and ways of infection of tuberculosis. Medical vector infographics, poster

Latent TB vs. Active TB

Latent TB represents the condition where the body’s immune system restricts the growth of M. tuberculosis bacterium, making the individual appear asymptomatic [10].

An individual with latent TB infection shows

– no symptoms.

– is not infectious (cannot spread TB).

– tests positive for TB blood/skin tests.

– may eventually develop active TB if the immune system weakens.

Active TB represents a condition where the body’s immune system is unable to restrict the growth of M. tuberculosis, rendering patients both ill and contagious. 

The symptoms of TB depend on the affected area.

a. General symptoms include:

  1. Night sweats
  2. Weight loss
  3. Prolonged fever
  4. Loss of appetite
  5. Fatigue

b. Symptoms of Pulmonary TB (infected lungs):

  1. Shortness of breath, which progressively worsens
  2. A persistent cough that produces phlegm and sometimes blood, persisting  > 3 weeks. 

c. Symptoms in the case when other areas of the body are infected:

  1. Swellings in the neck or other regions
  2. Pain in a joint or affected bone
  3. Abdominal pain
  4. Headache
  5. Confusion
  6. Seizures

 

Treatment

According to the World Health Organization (WHO), first-line treatment for TB may include combinations of five essential drugs: Rifampicin (R), Isoniazid (H), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S) [11].  Patients with TB undergo a standardized treatment for 6 to 9 months, including an initial two-month course of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol, followed by another 4-month course of Isoniazid and Rifampicin [12].

For patients with Multi Drug-Resistant Tuberculosis (MDR-TB), directly-observed therapy (DOT) is used. In DOT, drugs are administered at least six days/week under the direct observation of the physician [13, 14]

BCG vaccine

Bacillus Calmette-Guerin (BCG), a vaccine for TB, was introduced in 1921 to control tuberculosis in humans. It is administered at birth, primarily in regions with a high disease burden, such as India, South Africa, and Pakistan [15]. Widespread immunization using BCG vaccine has facilitated a reduction in TB cases globally [16].

 

Risk factors

Five-to-ten percent of people with latent TB who do not receive appropriate treatment will eventually develop active TB disease [17]

Individuals at a higher risk of contracting TB include:

– Those who have traveled to or are living in a country with a high prevalence of TB. 

– Those living in crowded conditions

– Those who have been in close contact with a person infected with TB

– Children ages <= 5 years who have tested positive for TB

– People who reside or work with persons at high risk for TB, such as those in hospitals, correctional facilities, homeless shelters, residential homes for HIV-infected individuals, and nursing homes

Additionally, immune dysfunction associated with diabetes mellitus, HIV infection, cancer chemotherapy, malnutrition, and advanced age is associated with an increased risk of contracting TB. 

Additional conditions associated with high risk for tuberculosis include silicosis, substance abuse, malignancy, organ transplantation, corticosteroid therapy, Crohn’s disease, and rheumatoid arthritis.

Tuberculosis and HIV

Co-infection by TB and HIV places a diagnostic and therapeutic burden on the health care system. HIV infection has been shown to increase the risk of reactivation of latent TB by 20-fold. [18].

 

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References

  1.     K. R, Die Aetiologie der Tuberculose [The aetiology of Tuberculosis.], Berlin: Berliner Klinische Wochenschrift, 1882.
  2. F. K. Dye C, Disease Control Priorities in Developing Countries, New York:: Oxford University Press, 2006.
  3. Z. J. B. Q. H. H. B. L. Y. J. L. Q. L. J. Pan Z, “The Gap Between Global Tuberculosis Incidence and the First Milestone of the WHO End Tuberculosis Strategy: An Analysis Based on the Global Burden of Disease 2017 Database.,” 2020.
  4. CDC, How TB Spreads, CDC, 2016.
  5. G. M. J. Jr., “Microbial pathogenesis of Mycobacterium Tuberculosis: dawn of a discipline,” Cell, no. 104, pp. 477-485, 2001.
  6. J. D. E, Mycobacterial diseases of the lung and bronchial tree: Clinical and laboratory aspects of Tuberculosis, Boston: Brown and Company, 1974.
  7. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK441916/.
  8. B. J. R. Elizabeth A. Talbot, Molecular Medical Microbiology, 2015.
  9. R. l. Kradin, Diagnostic Pathology of Infectious Disease, 2018.
  10. World Health Organization, Guidelines on the management of latent Tuberculosis infection, Geneva: WHO, 2015.
  11. World Health Organization, Implementing the WHO Stop TB Strategy: A Handbook for National Tuberculosis Control Programmes.
  12. Gideononline, “www.gideonoline.com,” Gideon, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/Tuberculosis-12470.
  13. A. F. Z. L. F. E. Terracciano E, [Tuberculosis: an ever present disease but difficult to prevent], Ig Sanita, 2020.
  14. M.-R. K. R. R. C. R. Chaulk CP, Eleven years of community-based directly observed therapy for Tuberculosis, JAMA, 1995.
  15. “www.journals.plos.org,” [Online]. Available: https://journals.plos.org/plosmedicine/article/figures?id=10.1371/journal.pmed.1001012.
  16. Z. a. Lancione, “Using data science to improve knowledge around a century old vaccine,” The BCG Atlas, 2020.
  17. CDC. [Online]. Available: https://www.cdc.gov/tb/topic/basics/risk.htm.
  18. G. C. G. R. N. P. Getahun H, “HIV infection-associated Tuberculosis: the epidemiology and the response,” Pubmed, 2010.

Diagnosing Emerging Infectious Diseases Early: How Epidemiology Can Help Clinicians on the Frontline

Doctor wearing protective gloves working on laptop computer,analyzing Coronavirus info data,COVID-19 response case info,U.S. state rank cases per capita,percent infected info and population numbers
Patient travel history or epidemiological data is the missing link in the differential diagnosis

 

by Chandana Balasubramanian

In 2019, a crew of nine pilots and astronauts broke a world record. They flew around the Earth in just 46 hours. More incredible is that they did not fly in a never-before-seen, advanced aircraft prototype. They flew a commercially available jet plane.

The future is already here.

It’s a small world; it’s getting smaller by the minute

Based on the new world record, it could take less than a weekend for an emerging infectious disease to spread all over the globe. And chances are, it may take a week or more before it gets detected based on the incubation period.

Unfortunately, healthcare providers at the frontlines of infectious disease management face a significantly higher risk of infection. The risk extends beyond healthcare workers to their families and communities.

As the world grapples with the impact of COVID-19 and its mutations, it’s a good time to ask: What can health systems worldwide do to detect emerging infectious diseases imported from other countries early?

1. Think beyond the travel ban

Recent research empirically demonstrated that local outbreaks of various Infectious Diseases could “quickly spread to other countries through the international movement of people and goods, with potentially disastrous health consequences [1].”

While this fact may not be news to clinicians and Infectious Disease specialists, the study also shows a close spatial dependence between the health conditions in one country and another – a spillover effect. The study used GIDEON (Global Infectious Disease and Epidemiology Online Network), a database covering all Infectious Disease outbreaks.

An epidemic in one country can become a pandemic in others – irrespective of travel and other physical barriers to entry. Studies of previous epidemics show that even a 90% travel restriction between countries merely delays the arrival of an emerging infection by a few weeks. Another study by Quilty et al. reported that airport-based screening measures to detect COVID-19 missed 46% of cases because of the incubation period [2].

So, while a travel ban and thermal screening can help a country buy some time to prepare for an outbreak, epidemic, or pandemic, they cannot stop or prevent a new infection from spreading to foreign shores.

***

2. Record travel history as standard protocol

Travel has always been one of the fastest ways to introduce a pathogen to a new environment. And as two clinicians, Trish Perl and Connie Savor Price, argue in a recent ‘Annals of Internal Medicine’ article, travel history must be treated as the fifth vital sign in emergency rooms and all physician evaluations [3].

The doctors make a strong case that including a patient’s travel history as part of a vital signs check can “help put symptoms of infection in context and trigger us to take a more detailed history, do appropriate testing, and rapidly implement protective measures.”

Monkeypox in the UK, 2021

For example, in May 2021, the World Health Organization received notification from the United Kingdom of a confirmed case of monkeypox in an individual who had just traveled from Nigeria. Monkeypox has an incubation period of six to thirteen days, but according to WHO, it can range anywhere from five to twenty-one days. Eventually, the infection spread to another family member, and they were isolated. Differential diagnosis considerations for monkeypox include chickenpox, measles, bacterial infections, scabies, syphilis, and medication-associated allergies. In such a case, taking the patient’s travel history can help healthcare workers take the necessary precautions even before the PCR results.

COVID-19 in the United States, 2019

The first case of COVID-19 in the US was reported in Washington when the patient returned from Wuhan, China. Based on the patient’s travel history and symptoms, healthcare professionals could isolate and send clinical specimens to be tested by the CDC overnight. Hospitals in the United States were already on alert for patients from Wuhan presenting with symptoms, and testing could be prioritized accordingly.

Ebola in the United States, 2014

Let’s look at an example where a patient’s travel history would have helped protect healthcare professionals. In 2014, a man traveled from West Africa and admitted himself into a hospital in Dallas with fever, abdominal pain, dizziness, headache, and nausea. Without an integral piece of the puzzle – his travel history – he was treated for sinusitis and sent home. The hospital suspected Ebola only when he returned three days later with persistent fever, abdominal pain, and diarrhea. Unfortunately, within this time, this patient had infected healthcare professionals, ambulance transport personnel, and the patient’s caregivers.

Monkeypox and Ebola are not as contagious as COVID-19 and its variants, and Ebola is not contagious until symptoms appear, making containment easier. But emerging infectious diseases and their variants might be.

Infectious Disease specialists, clinicians, researchers, and medical librarians will need to be vigilant against the next outbreak. Epidemiological data plays an integral role in facilitating improved clinical decisions and saved lives.

***

3. Identify initial cases of known diseases in new settings

In a GIDEON survey of 363 clinicians in the US, UK, and Canada, 35% stated that they would consult a colleague for a second opinion before making clinical decisions. As a close second, 30% indicated that they trust their judgment. This means that 65% of the survey respondents trusted human judgment over Point-of-Care tools.

Twitter survey of clinicians and use of differential diagnosis tools

But the stakes are higher when dealing with highly transmissible emerging infections. The importance of first-time diagnosis accuracy is compounded due to the rising urgency to prevent the next epidemic or pandemic.

Consider the dramatic difference in transmission rates between SARS-CoV-2 and its variants:

  • The B.1.1.7, the ‘Alpha’ SARS-CoV-2 variant, is 43% to 90% more transmissible than its predecessor and led to a surge in hospitalizations across the UK and 114 more countries in a mere few months [4].
  • 1.617.2 or the ‘Delta’ variant is estimated to be 40% to 60% more infectious than the Alpha, estimated by disease modelers at Imperial College, London, with an R0 as high as 8 [5].

Here are some comparisons of how newer, emerging pathogens and their variants compare to older, Infectious Diseases.

Pathogen Transmissibility Rate (R0)
B.1.617.2, SARS-CoV-2 Delta variant 5-8
B .1. 1. 7, SARS-CoV-2 Alpha Variant 4-5
SARS-CoV-2 (COVID-19) 2.5
SARS-CoV 2.4
Measles 1.5 (1.5-2.0)

In other words, an outbreak may already be well underway before an Infectious Disease specialist is consulted for assistance on differential diagnosis or a medical librarian is requested for location-specific disease symptoms.

As pathogens mutate, traditional methods of differential diagnosis need an upgrade. Clinicians, Infectious Disease specialists, and researchers need data from local outbreaks anywhere in the world at their fingertips to help drive decision-making and advance the global effort against Infectious Disease.

***

4. Use a differential diagnosis (DDx) tool like GIDEON’s First Case Scenario to identify Infectious Diseases – faster and more accurately

Drs Perl and Price champion the need for greater access to digital resources that integrate electronic health records with patient travel histories and can “suggest specific diagnoses in febrile returning travelers.”

One of the more well-known DDx tools is GIDEON with its First Case Scenario feature, created in partnership with the World Health Organization (WHO) after the West Nile Fever outbreak in the United States.

Using a DDx platform such as GIDEON helps:

  • narrow down possibilities,
  • lead to a faster result,
  • reduce the margin of error at the point-of-care, and
  • elevates peer-to-peer knowledge sharing on a global scale

Why is this important? Because, for example, in respiratory viral illnesses, early detection is the critical step to mitigate disease transmission but is often delayed [3]. Depending on the type of pathogen, this could lead to a greater number of hospitalizations, more morbidity, a burden on healthcare systems, and have significant ramifications on a country, its people, and the economy.

Locations marked with pins on world map, global communication network, closeup. Asking patients about their travel history can help prevent emerging infectious diseases introduction into country
Asking patients about their travel history can help prevent emerging infectious diseases introduction into the country

Having a differential diagnosis platform that incorporates a patient’s travel history can make a huge difference in how the world manages emerging infectious diseases.

Here’s an example. Suppose a patient presents with elevated body temperature, severe headache, chills, myalgia, diarrhea, and malaise.

These are nonspecific presentations and could be representative of a variety of diseases.  With international transmission now the norm, no clinician can be expected to keep track of every single emerging disease and its symptoms.

Example: Diagnosing Ebola using a DDx platform

Step 1: Focusing on most likely diseases based on symptoms and travel information
Entering a patient’s symptoms and the locations and dates of travel in a tool like GIDEON’s Bayesian analysis-driven Probability engine can help identify what diseases are most likely to correspond to the data entered. The illustration below shows Ebola as a high probability based on the patient’s symptoms and travel location.

Step 2: Conduct a differential diagnosis
The screenshot of the First Case Scenario feature below shows a 95% probability that the patient has Ebola. What if there were fewer symptoms at presentation, the likelihood of Ebola was 65%, and another disease was 25% probable? You could conduct a differential analysis by comparing the two disease symptoms on the platform, download the comparison, and order the requisite laboratory tests to confirm.

Step 3: First Case Scenario

Imagine it is 2014, and you haven’t heard of Ebola. A patient walks in with the symptoms listed above. You enter the symptoms and the patient’s travel history. Using GIDEON’s First Case Scenario, you can determine how likely it is that your patient is the first in the country to present with Ebola.

GIDEON web application screenshot displaying 95% probability of Ebola in the First Case Scenario feature
Illustration of diagnosing Ebola in a Point-of-Care setting (Screenshot: GIDEON First Case Scenario DDx tool)

***

5. Train an army of global clinicians to battle Infectious Diseases

Based on a GIDEON survey of 230 clinicians in the US, UK, and Canada, while clinicians were open to using a DDx tool to help diagnose Infectious Diseases, a lack of budget was the primary reason they did not.

One physician even stated, “I would use them every day if my institution would offer.”

But an interactive platform with a robust database of Infectious Disease symptoms that incorporates patient locations, exposure to disease-causing elements, and comparisons between two or more similar diseases can offer benefits beyond what a seasoned clinician can accomplish.

It can train the next generation of Infectious Disease-fighting doctors and healthcare professionals. For example, take GIDEON’s step-by-step Bayesian analysis toolkit. Teaching institutions, medical librarians, medical students, residents, researchers, and more can use DDx tools to help hone their diagnoses of emerging as well as well-known infectious diseases.

The tool helps you list symptoms, patient travel information (if any), and any exposure to disease-causing elements (if known). For example, the patient ate chicken in a region that recently had a Salmonella outbreak.

The tool offers a list of probable diseases in descending order of probability. It helps that the tool is dynamic because what if the patient forgot a symptom and told you about it later? A new list of probable diseases is re-calculated automatically. An added benefit is that the DDx tool is integrated with the First Case Scenario to determine if a patient’s symptoms are the first in a specific location.

Health systems and medical colleges and universities may benefit greatly from such a diagnostic solution.

Conclusion

War often provides an opportunity for innovation. After all, the internet was invented because computers at the time were enormous, and it was incredibly difficult to physically transport military intel from the United States to soldiers deployed around the world [6]. And clinicians are actively in a battle against the spread of infectious pathogens.

A global platform that offers timely location-specific intelligence about emerging infectious diseases and helps speed up clinical decisions is invaluable to future-proof the world against outbreaks, epidemics, and pandemics and save thousands of lives.

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References

[1] R. Desbordes, “Spatial dynamics of major Infectious Diseases outbreaks: A global empirical assessment,” J. Math. Econ., vol. 93, no. 102493, p. 102493, 2021.

[2] B. J. Quilty, S. Clifford, S. Flasche, R. M. Eggo, and CMMID nCoV working group, “Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV),” Euro Surveill., vol. 25, no. 5, 2020.

[3] T. M. Perl and C. S. Price, “Managing emerging Infectious Diseases: Should travel be the fifth vital sign?” Ann. Intern. Med., vol. 172, no. 8, pp. 560–561, 2020.

[4] N. G. Davies et al., “Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England,” Science, vol. 372, no. 6538, p. eabg3055, 2021.

[5] Scientific Advisory Group for Emergencies, “Imperial College London: Evaluating the roadmap out of lockdown – modelling Step 4 of the roadmap in the context of B.1.617.2 (Delta), 9 June 2021,” Gov.uk, 14-Jun-2021. [Online]. Available: https://www.gov.uk/government/publications/imperial-college-london-evaluating-the-roadmap-out-of-lockdown-modelling-step-4-of-the-roadmap-in-the-context-of-b16172-delta-9-june-2021. [Accessed: 15-Jun-2021].

[6] B. Tarnoff, “How the internet was invented,”  The Guardian, 15-Jul-2016.

Preventing Foodborne Illness

Food quality control expert inspecting specimens of groceries in the laboratory
Food quality control expert inspecting groceries in the laboratory

 

Since 2019, World Food Safety Day is celebrated each year on the 7th of June,  to promote awareness regarding the need to develop and maintain food safety standards. These efforts are being done both to reduce the burden of foodborne disease and to minimize its impact on socio-economic systems.

Foodborne diseases constitute a major health issue worldwide. The World Health Organization (WHO) estimates that approximately 10% of the global population is infected by foodborne pathogens each year (1). Similar to other diseases, the severity of the foodborne illness varies with the type and the amount of exposure to the causative microorganism, as well as the disease-fighting potential of the affected individual.

 

Clinical Presentation of Foodborne Illnesses

Foodborne illnesses might manifest as acute diarrhea, nausea, etc., which usually resolves within 7 to 10 days; or as chronic and potentially fatal diseases such as botulism or typhoid fever.

Botulism, a common and potentially fatal disease, is caused by Clostridium botulinum. Signs and symptoms usually appear within 18 to 36 hours of food ingestion Bacterial toxins can persist in the patient’s blood for up to 12 days. Common findings include respiratory failure and neurological symptoms, such as blurred vision, paralysis, etc. (2). 

 

Foodborne cases of botulism in the United States 1979-2019

 

Botulism cases in US, 1979 - 2020, GIDEON graph

 

Prevention and Management of Foodborne Illnesses

irradiated spinach_byMikeLichtContamination of food or food products can occur at various stages of production, including growth, processing, transportation, or storage. Thus, there is a critical need to adopt appropriate measures that correspond to these variable conditions to maximize food safety and minimize the transmission of foodborne illnesses.

 

1.     Decontamination of Fresh Produce

With rapid globalization, fresh produce is now available worldwide throughout the year in the form of frozen food.  Fresh produce must undergo proper decontamination before being frozen – to prevent such diseases as norovirus infection and hepatitis A (3, 4). Some of the common techniques used for decontamination include (5):

a.     Application of antibiotics during the growth stage

b.     Proactive sampling for detection of pathogens

c.     Bacteriocins (bacteria-generated toxins to kill the competitive strains)

d.     Antimicrobial natural products and nanoparticles

e.     Bacteriophages

f.      Irradiation 

Alternatively, consumers might receive probiotics and relevant vaccines to protect them from relevant foodborne illnesses.

 

2.     Development of Public Health Surveillance Systems

A competent public health surveillance system should be implemented by the Governmental and related organizations to identify impending outbreaks in order to facilitate effective policies and goals (6, 7). Such systems help control and prevent extensive transmission by collecting and analyzing epidemiological and clinical data that provide guidelines to take appropriate measures.

 

3.     Prophylactic Measures for People with Increased Susceptibility to Foodborne Illnesses

People who are vulnerable to foodborne infections, such as older adults, infants – and individuals with prior diseases of the immune system, liver, gastrointestinal tract, etc. should be particularly vigilant and observed preventive measures (8) including: 

a.   Adherence to a low-microbial diet and avoidance of undercooked meat, unpasteurized milk, etc.

b.  Consumption of  bottled natural water

c.   Infants should be preferably given sterile ready-to-eat formula; powdered formula should be reconstituted in boiling water and given in boiled water-  sterilized bottles

d.  Antimicrobial may be administered prophylactically during transplantation and other high-risk treatments.

 

4.     Food Safety Measures

In general, people should adopt safe food practices wherever they cook and consume food or food products (9). The cooking utensils/surfaces should be properly cleaned and sanitized. Raw and undercooked foods should be stored separately to avoid cross-contamination. Food should be cooked or reheated thoroughly, meats and seafood should be cooked to appropriate temperatures. Cooked food should be stored at < 5°C, and not for prolonged periods. Only clean, purified water should be used for cooking food to minimize any chances of waterborne infection. Raw fruits and vegetables should be properly washed before consumption.

Woman washing carrots and pomegranate in a metal sink
Raw fruits and vegetables should be properly washed before consumption.

 

At the Public Health level, comprehensive integration of government-issued guidelines and self-monitoring are needed to prevent and control foodborne illnesses.

 

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References

  1.     “Foodborne diseases”, World Health Organization. [Online]. Available: https://www.who.int/health-topics/foodborne-diseases#tab=tab_1.
  2.     “Botulism”, GIDEON Informatics, Inc, 2021 [Online]. Available: https://app.gideononline.com/explore/diseases/botulism-10230.
  3.     Nasheri N, Vester A, Petronella N. Foodborne viral outbreaks associated with frozen produce. Epidemiol Infect. 2019 Oct;147:e291. doi: 10.1017/S0950268819001791.
  4.     Chapman B, Gunter C. Local Food Systems Food Safety Concerns. Microbiol Spectr. 2018 Apr; 6(2). doi: 10.1128/microbiolspec.PFS-0020-2017.
  5.     Yang SC, Lin CH, Aljuffali IA, Fang V. Current pathogenic Escherichia coli foodborne outbreak cases and therapy development. Arch. Microbiol. 2017 June; 199(6): 811-825. doi.org/10.1007/s00203-017-1393-y.
  6.     Ward H, Molesworth A, Holmes S, Sinka K. Public health: surveillance, infection prevention, and control. Handb Clin Neurol. 2018; 153:473-484. doi: 10.1016/B978-0-444-63945-5.00027-1.
  7.     Hoelzer K, Moreno Switt AI, Wiedmann M, Boor KJ. Emerging needs and opportunities in foodborne disease detection and prevention: From tools to people. Food Microbiol. 2018 Oct; 75:65-71. doi: 10.1016/j.fm.2017.07.006.
  8.     Lund BM, O’Brien SJ. The occurrence and prevention of foodborne disease in vulnerable people. Foodborne Pathog Dis. 2011 Sep; 8(9):961-73. doi: 10.1089/fpd.2011.0860.
  9.     “Five keys to safer food manual”, World Health Organization [Online]. Available: https://www.who.int/foodsafety/publications/consumer/manual_keys.pdf

Pathogen of the Month: Vibrio cholerae, the Causative Agent of Cholera

Vibrio cholerae
This blog was written by Dr. Jaclynn Moskow

 

Vibrio cholerae (V. cholerae) is a species of Gram-negative facultatively anaerobic bacteria of curved rod-shaped with single polar flagella. V. Cholerae has been classified into approximately 200 serogroups. Strains belonging to serogroups O1 and O139 cause the vast majority of cholera cases (1).

Vibrio cholerae is found naturally in brackish riverine, estuarine, and coastal waters. Recognized hosts of the organism include algae, shellfish, chironomid egg masses, fish, waterfowl, amebae, and copepods (2). V. cholerae colonies can form biofilms on both biotic and abiotic surfaces – including on shells, zooplankton, macroalgae, ship hulls, and plastic pollution (3-5). 

 

Cholera Transmission and Disease Severity 

Cholera is primarily transmitted through the consumption of fecally contaminated water and food. Foodborne outbreaks are most frequently linked to fish, shellfish, crabs, oysters, clams, rice, millet gruel, and vegetables (6).

Most V. cholerae infections are asymptomatic or mild in nature. Individuals with asymptomatic infections may still shed bacteria in their feces and infect others (7). Approximately 10% of V. cholerae infections will progress to severe disease (8). In endemic settings, the most severe infections occur in children, while in epidemic settings, severe disease occurs in adults as frequently as it does in children (9). 

Individuals with blood type O are more likely to suffer from severe V. cholerae infection (10). The use of drugs that reduce stomach acid, such as antacids, histamine receptor blockers, and proton pump inhibitors, also increases the risk of severe infection (11). 

 

Vibrio cholerae bacteria on agar
Vibrio cholerae isolated from feces obtained from a patient with profuse diarrhea who had traveled to India. Photo courtesy of Nathan Reading

 

 

Signs and Symptoms of Cholera

Cholera has an average incubation period of 1-5 days. Patients will experience a sudden onset of painless, watery diarrhea that may be accompanied by vomiting. The diarrhea is often characterized as having a “rice water” appearance and fishy odor. Fever is uncommon in adults, but often present in children (12).

In severe cases, dehydration may lead to the rapid progression to acidosis and electrolyte imbalance. Coma may occur. Without the replacement of fluids and electrolytes, hypovolemic shock and death ensue (12).

If left untreated, cholera has a 25-50% mortality rate. Proper treatment reduces the mortality rate to less than 1% (13).

Cholera vector illustration. Labeled infection structure and symptoms scheme. Educational infographic with unsafe water and food vibrio microorganism that causes diarrhea, vomiting and dehydration.

Diagnosis and Treatment of Cholera

Cholera is diagnosed via stool culture. When a case is suspected, healthcare and medical laboratory personnel should follow stool precautions.

Mild and moderate cases of cholera can be successfully treated with oral rehydration salts, while severe cases require rehydration with intravenous fluids (14). The World Health Organization (WHO) recommends reserving antibiotics as a treatment for severe cases only, as antibiotic use has no proven effect on controlling the spread of the disease and may contribute to antimicrobial resistance (15). In severe cases, tetracycline, doxycycline, azithromycin, erythromycin, or ciprofloxacin may be used (12). Most people who recover from V. cholerae infection incur long-lasting immunity (16).

 

Cholera Prevalence

Cholera originated in India and spread across the world during the 19th century (17). Since that time, there have been seven cholera pandemics, including one that is ongoing today (18). 

Currently, approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases occur annually, resulting in an estimated 95,000 deaths (19).

Over the last decade, the countries reporting the most cases of cholera have included Yemen, Somalia, the Democratic Republic of Congo, Mozambique, Bangladesh, and Haiti. If you have a GIDEON account, click here to explore the Cholera outbreak map. Cholera is exceedingly rare in Europe and the United States.

 

Cholera cases by region, 1953 – 2018

Cholera-cases-by-region-1953-2018

 

Cholera Prevention

Cholera cases by region, 1953 - 2018

When traveling to an area where cholera is endemic, precautions should include adherence to proper hand hygiene, drinking only bottled water, and avoiding uncooked food.

Ongoing worldwide efforts to end the current cholera pandemic center on increasing access to clean water and sanitation and expanding accessibility to existing cholera vaccines.

 

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References 

(1) Morris, “Infections due to non-O1/O139 Vibrio cholerae”, Uptodate.com, 2019. [Online]. Available: https://www.uptodate.com/contents/infections-due-to-non-o1-o139-vibrio-cholerae

(2) “Cholera: Environmental Reservoirs and Impact on Disease Transmission”, One Health, pp. 149-165, 2014. Available: 10.1128/microbiolspec.oh-0003-2012

(3) B. Wucher, T. Bartlett, M. Hoyos, K. Papenfort, A. Persat and C. Nadell, “Vibrio cholerae filamentation promotes chitin surface attachment at the expense of competition in biofilms”, Proceedings of the National Academy of Sciences, vol. 116, no. 28, pp. 14216-14221, 2019. Available: 10.1073/pnas.1819016116

(4) C. Lutz, M. Erken, P. Noorian, S. Sun and D. McDougald, “Environmental reservoirs and mechanisms of persistence of Vibrio cholerae”, Frontiers in Microbiology, vol. 4, 2013. Available: 10.3389/fmicb.2013.00375 

(5) J. Moskow, “What Do Plastics Have To Do With Infectious Diseases and the Immune System?”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://www.gideononline.com/2021/04/22/what-do-plastics-have-to-do-with-infectious-diseases-and-the-immune-system/ 

(6) G. Rabbani, W. Greenough. “Food as a vehicle of transmission of cholera”, J Diarrhoeal Dis Res, vol. 17, no. 1, pp. 1-9, 1999

(7) J. Lewnard, M. Antillón, G. Gonsalves, A. Miller, A. Ko and V. Pitzer, “Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak”, PLOS Medicine, vol. 13, no. 1, p. e1001947, 2016. Available: 10.1371/journal.pmed.1001947

(8) Cholera – Vibrio cholerae infection: General Information”, Centers for Disease Control and Prevention (CDC0, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online] Available: https://www.cdc.gov/cholera/general/index.html

(9) J. Harris, R. LaRocque, F. Qadri, E. Ryan and S. Calderwood, “Cholera”, The Lancet, vol. 379, no. 9835, pp. 2466-2476, 2012. Available: 10.1016/s0140-6736(12)60436-x

(10) J. Harris and R. LaRocque, “Cholera and ABO Blood Group: Understanding an Ancient Association”, The American Journal of Tropical Medicine and Hygiene, vol. 95, no. 2, pp. 263-264, 2016. Available: 10.4269/ajtmh.16-0440

(11) S. Handa, “Which classes of medications increase the risk of cholera infection?”, Medscape.com, 2018. [Online]. Available: https://www.medscape.com/answers/962643-54708/which-classes-of-medications-increase-the-risk-of-cholera-infection 

(12) “Cholera”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/cholera-10390

(13) J. Fournier and M. Quilici, “Choléra”, La Presse Médicale, vol. 36, no. 4, pp. 727-739, 2007. Available: 10.1016/j.lpm.2006.11.029 

(14) “WHO | WHO position paper on Oral Rehydration Salts to reduce mortality from cholera”, Who.int, 2021. [Online]. Available: https://www.who.int/cholera/technical/en/

(15) “Cholera”, Who.int, 2021. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/cholera 

(16) J. Harris, “Cholera: Immunity and Prospects in Vaccine Development”, The Journal of Infectious Diseases, vol. 218, no. 3, pp. S141-S146, 2018. Available: 10.1093/infdis/jiy414

(17) D. Lippi, E. Gotuzzo and S. Caini, “Cholera”, Paleomicrobiology of Humans, pp. 173-180, 2016. Available: 10.1128/microbiolspec.poh-0012-2015 

(18) S. Handa, “What are the 7 pandemics of cholera”, Medscape.com, 2018. [Online]. Available: https://www.medscape.com/answers/962643-54700/what-are-the-7-pandemics-of-cholera

(19) M. Ali, A. Nelson, A. Lopez and D. Sack, “Updated Global Burden of Cholera in Endemic Countries”, PLOS Neglected Tropical Diseases, vol. 9, no. 6, p. e0003832, 2015. Available: 10.1371/journal.pntd.0003832

Yellow Fever: Past and Present

1942, Innoculating eggs with yellow fever vaccine. USPHS (United States Public Health Service) Rocky Mountain Laboratory, Hamilton, Montana
Inoculating eggs with yellow fever vaccine, 1942. USPHS (the United States Public Health Service) Rocky Mountain Laboratory, Hamilton, Montana. Photographer: John Vachon

 

written by Dr. Jaclynn Moskow

What is Yellow Fever?

The yellow fever virus, a flavivirus, is transmitted via the bites of various mosquito species. The disease has an average incubation period of 3 to 6 days. The clinical presentation of yellow fever can vary greatly, ranging from a self-limited flu-like illness to overwhelming hemorrhagic fever – with a case fatality rate of 50%. Approximately 55% of yellow fever infections are asymptomatic, 33% are categorized as mild, and 12% severe (1).

Diagram of Symptoms of Yellow fever patient

Yellow fever generally manifests with the acute onset of fever, headache, backache, myalgia, and vomiting. Conjunctival infection may be seen, accompanied by facial flushing, relative bradycardia (Faget’s sign), and leukopenia. In some cases, fever and other symptoms may remit for a few hours to several days. Upon return of symptoms, icteric hepatitis and a hemorrhagic diathesis may follow with epistaxis, bleeding from the gums and gastrointestinal tract, and petechial and purpuric hemorrhages. Weakness, prostration, protracted vomiting, and albuminuria may also be noted. At this stage, patients will experience renal failure, myocardial dysfunction, necro-hemorrhagic pancreatitis, and seizures.

Yellow fever has a case fatality rate of 10 to 60% within 7 days of disease onset (1).

 

 

The Origin and Spread of Yellow Fever

Phylogenetic analyses indicate that yellow fever originated in Africa within the last 1,500 years. Its spread to the Americas coincided with the trans-Atlantic slave trade that began during the 16th century. It is likely that mosquitoes carrying yellow fever were imported into the Americas via slave ships (2). Significant outbreaks followed as the virus was introduced into populations with no pre-existing immunity. During the 18th and 19th centuries, approximately 25 major outbreaks claimed the lives of hundreds of thousands in New York City, Philadelphia, Baltimore, and New Orleans (3). Yellow fever also arrived in Europe during this time, with notable outbreaks occurring at Spanish, Portuguese, French, and British seaports (4).

It is estimated that for every soldier who died in battle during the Spanish-American War, 13 died of yellow fever (5). Yellow fever also killed many thousands during the construction of the Panama Canal. 

William C. Gorgas (1854-1920), on the site of Panama Canal construction.
William C. Gorgas (1854-1920), on the site of Panama Canal construction. As a U.S. Army surgeon during the Spanish American War, he established methods for eradicating mosquitoes hence reducing yellow fever and malaria among soldiers in Cuba. In 1904 he applied these techniques to control disease among the Panama Canal workers. Ca. 1910.

 

 

Development of a Vaccine for Yellow Fever

USA - CIRCA 1940: A stamp printed in USA shows portrait of Dr. Walter Reed, series Scientists, circa 1940

Early attempts to develop a vaccine for yellow fever resulted in the deaths of several test subjects and researchers. In 1900, a team led by Major Walter Reed traveled to Cuba to study the disease. At this point, the medical community was largely dismissive of the theory that mosquitos were the vectors of transmission for yellow fever. Working under the assumption that the mosquito theory was indeed incorrect, Reed’s team began experimenting with mosquitos and volunteers. After receiving criticism about using human test subjects, some team members decided to instead experiment on themselves. Unfortunately, this resulted in the death of physician-scientist Dr. Jesse Lazear – but with his death, the mosquito theory began to gain acceptance (6). 

Despite the death of Dr. Lazear, yellow fever research on human test subjects continued. The Reed team conducted a second and third set of mosquito experiments, offering financial compensation in the form of gold to study participants (6). After learning that none of these latest Reed study participants had died, Cuban physician Dr. John Guiteras began his own experiments. Unfortunately, three of his 42 test subjects succumbed to the illness, and with this, yellow fever research in Cuba came to a halt (7).

Subsequent efforts to control yellow fever centered on reducing mosquito populations as opposed to vaccine development, until 1918 when the Rockefeller Foundation began conducting yellow fever research. Within a year, Japanese scientist Dr. Hideyo Noguchi, who was working with the Foundation, announced that he had successfully developed a vaccine. Individuals in the United States, Latin America, and the French African colonies began receiving his vaccine, but the legitimacy of the studies leading to its development were soon called into question, and ultimately the vaccine was pulled (7).

The Rockefeller Foundation continued its efforts, and in 1925, they sent investigators to Lagos to determine if the African and South American diseases were caused by the same pathogen. Unfortunately, this trip resulted in three more investigators contracting and dying from yellow fever, including Dr. Noguchi. Nonetheless, the Rockefeller Foundation persisted, and a few years later, another candidate vaccine was developed – this time from efforts led by Dr. Max Theiler (7).

Despite the history of physician deaths related to yellow fever experimentation, Brazilian physician Dr. Bruce Wilson volunteered to receive the first dose of the Theiler vaccine. It was designated a success, and mass production began. Soon after, the Pasteur Institute developed their own vaccine, and for the next several years, the Rockefeller Foundation vaccine was used in the West as well as in England, and the Pasteur Institute vaccine used in France and its African colonies (7).

During World War II, the Rockefeller Foundation vaccine was given to almost all US soldiers. Unfortunately, the vaccine contained blood serum, and vaccination efforts resulted in approximately 330,000 soldiers contracting hepatitis B virus infection (8). Blood serum was subsequently removed as a component of the vaccine, and in 1953 a yellow fever vaccine was licensed for civilian use in the US (9). Use of the Pasteur Institute vaccine eventually ceased due to cases of postvaccinal encephalitis, but a variant of the Rockefeller foundation vaccine is still used today. Dr. Theiler received the Nobel Prize in Physiology or Medicine for his critical role in its development.

 

Yellow Fever in 2021

Yellow fever vaccination est. coverage 1980 - 2019

Today, the Centers for Disease Control and Prevention (CDC) recommends vaccination against yellow fever for individuals 9 months and older and who are traveling to or living in areas at risk in Africa and South America (10). It is a live attenuated vaccine, and thus contraindicated in patients who are immunocompromised. The vaccine is highly effective, with a median seroconversion rate of 99% (range 81–100%) in clinical trials (11).

Yellow fever is currently estimated to affect 200,000 people each year, resulting in 30,000 deaths, with 90% of cases occurring in Africa (12). Recent outbreaks have occurred in Brazil, Angola, Nigeria, and the Democratic Rep. of Congo. If you have a GIDEON account, click here to explore the Yellow Fever outbreak map. There are ongoing efforts to expand accessibility to the vaccine in these regions, as well as to implement additional vector control programs. 

The last outbreak of Yellow Fever in the United States occurred in 1905 (13). Yellow fever outbreaks ceased in Europe after World War II, when, for unknown reasons, the Aedes aegypti mosquito disappeared (14).

The absence of yellow fever in Asia is not fully understood. Some have speculated that differences in mosquito species may play a role. Another theory is that there may be a cross-immunity between yellow fever and other flaviviruses endemic to Asia, such as dengue fever. A third theory is that yellow fever has simply never been introduced into Asia (2).

 

 

 

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References

(1) “Yellow fever”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/yellow-fever-12650

(2) Cathey and J. Marr, “Yellow fever, Asia and the East African slave trade”, Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 108, no. 5, pp. 252-257, 2014. Available: 10.1093/trstmh/tru043 

(3) F. Douam and A. Ploss, “Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe”, Trends in Microbiology, vol. 26, no. 11, pp. 913-928, 2018. Available: 10.1016/j.tim.2018.05.012 

(4) M. Morillon, B. Marfart, and T. Matton, “Yellow fever in Europe in 19th Century”, Ecological Aspects of Past Settlement in Europe. P. Bennike, pp. 211-222, 2002.

(5) Staples, “Yellow Fever: 100 Years of Discovery”, JAMA, vol. 300, no. 8, p. 960, 2008. Available: 10.1001/jama.300.8.960 

(6) “Politics of Participation: Walter Reed’s Yellow-Fever Experiments”, AMA Journal of Ethics, vol. 11, no. 4, pp. 326-330, 2009. Available: 10.1001/virtualmentor.2009.11.4.mhst1-0904

(7) J. Frierson. “The yellow fever vaccine: a history”, Yale J Biol Med, vol. 83, no. 2, pp. 77-85, 2010

(8) M. Furmanski. “Unlicensed vaccines and bioweapon defense in World War II”, JAMA, vol. 282, no. 9, p. 822, 1999

(9) “Historic Dates and Events Related to Vaccines and Immunization”, Immunize.org, 2021. [Online]. Available: https://www.immunize.org/timeline/

(10)”Yellow Fever Vaccine Recommendations”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD), 2021. [Online]. Available: https://www.cdc.gov/yellowfever/vaccine/vaccine-recommendations.html

(11) J. Staples, A. Barrett, A. Wilder-Smith and J. Hombach, “Review of data and knowledge gaps regarding yellow fever vaccine-induced immunity and duration of protection”, npj Vaccines, vol. 5, no. 1, 2020. Available: 10.1038/s41541-020-0205-6 

(12) “Yellow Fever”, Centers for Disease Control and Prevention, Global Health, 2018. [Online]. Available: https://www.cdc.gov/globalhealth/newsroom/topics/yellowfever/index.html

(13) K. Patterson, “Yellow fever epidemics and mortality in the United States, 1693–1905”, Social Science & Medicine, vol. 34, no. 8, pp. 855-865, 1992. Available: 10.1016/0277-9536(92)90255-o 

(14) “Facts about yellow fever”, European Centre for Disease Prevention and Control, 2021. [Online]. Available: https://www.ecdc.europa.eu/en/yellow-fever/facts

 

 

How Vaccines Work

Development and manufacture process of a new vaccine. Final production of filled vials of Covid-19 vaccine. Bio science 3D illustration.

 

You may know they save lives, but have you ever wondered how vaccines work? As mass vaccination programs in response to the COVID-19 pandemic are underway, there is a heightened interest in understanding vaccines and their mechanism of action.

Vaccines stimulate the immune system to recognize and respond to specific pathogens. Differing vaccines accomplish this through a variety of mechanisms. Vaccines can be divided into five basic categories: live attenuated vaccines, inactivated vaccines, subunit vaccines including toxoids, mRNA vaccines, and viral vector vaccines.

 

Live Attenuated Vaccines

Live attenuated vaccines contain live viruses or bacteria that have been weakened to reduce virulence. Following ingestion or injection, the body mounts an immune response that is similar to what would occur if it were to encounter the natural disease. Since the pathogens used in live attenuated vaccines have been weakened, they cause only mild symptoms – or no symptoms at all. Live attenuated vaccines generally provide the longest-lasting immunity of any vaccine type.

Examples of live attenuated viral preparations include measles, mumps, rubella, varicella, rotavirus, yellow fever, oral polio vaccine, and intranasal influenza vaccine. Live attenuated bacterial vaccines include the BCG vaccine for tuberculosis and the oral cholera vaccine. In general, viral vaccines have greater efficacy than bacterial vaccines.

The eradication of smallpox was accomplished through a live attenuated vaccine, which contained a related virus (vaccinia). In the veterinary world, widespread use of a live attenuated vaccine led to the eradication of Rinderpest, also known as ‘cattle plague’, caused by a morbillivirus of the family Paramyxoviridae. 

Live attenuated vaccines are generally contraindicated in pregnant women and immunocompromised patients, such as those receiving immunosuppressive therapy or living with HIV/AIDS or congenital immunodeficiency. 

It is extremely rare for a live attenuated vaccine virus to mutate into a more virulent form and cause disease. Cases of this phenomenon have been documented with oral polio vaccine, at a reported rate of one case per 750,000 children receiving their first dose (1). As a result of these rare instances, in many countries (including the United States), the oral polio vaccine is no longer used and has been replaced by inactivated preparations.

 

How inactivated vaccines work

Inactivated vaccines, also known as killed vaccines, prime the immune system with bacteria or viruses that have been inactivated to remove all virulence. They cannot cause the disease they protect against and are generally considered safe for immunocompromised and pregnant patients. The protection provided by inactivated vaccines does not usually last as long as that provided by live attenuated vaccines, and booster doses are often recommended. 

Examples of inactivated vaccines include hepatitis A, rabies, intramuscular influenza, intramuscular polio, and variants of the pertussis vaccine. Several inactivated SARS-CoV-2 vaccines have been developed, including China’s “Sinovac”, India’s “Covaxin”, and Russia’s “CoviVac”.

 

How vaccines work: inactivated vaccine
Inactivated vaccine mechanism of action

 

How subunit vaccines work

Subunit vaccines contain fragments of a pathogen (i.e., a polypeptide or polysaccharide) often bound to other molecules. As with inactivated vaccines, these cannot produce the disease itself and are generally considered safe for immunocompromised and pregnant patients. Booster doses are often required.

Examples of subunit vaccines include hepatitis B, human papillomavirus (HPV), Haemophilus influenzae type B (HiB), herpes zoster, meningococcus B, pneumococcal, and one variant of the pertussis vaccine. Occasionally, the subunit used in these vaccines is an attenuated toxin (toxoid).  Examples of toxoid vaccines include tetanus and diphtheria.

There are several subunit vaccines for SARS-CoV-2 in various stages of clinical trials around the world.

 

Messenger RNA (mRNA) – a new type of vaccine

mRNA vaccines are a new type of vaccine and contain fragments of mRNA that encode a piece of protein from the pathogen of interest. After being vaccinated with such a vaccine, the body’s own cells incorporate the mRNA and produce the protein, which the immune system then recognizes as foreign. The Pfizer-BioNTech and Moderna COVID-19 vaccines are both mRNA vaccines. There are several additional mRNA vaccines currently in development. 

 

How vaccines work: mRNA vaccine schematic illustration
mRNA vaccine mechanism of action

 

How viral vector vaccines work

Viral vector vaccines use modified versions of viruses as “vectors” to deliver a nucleic acid of the pathogen of interest into the cell. Once inside the cell, the DNA is transcribed into mRNA, and the mRNA is translated into protein. The body then recognizes this protein as foreign and mounts an immune response, similar to that which occurs with mRNA vaccines. The Johnson & Johnson COVID-19 vaccine works in this manner.

 

How vaccines work: viral vector vaccine
Viral vector vaccine mechanism of action

 

 

Dr. Steve Berger on Vaccines

GIDEON co-founder Dr. Steve Berger, reflects on vaccines: “Vaccines continue to save millions of lives and have prevented untold misery to the human species. Although the effectiveness of individual vaccines may vary, and most may cause occasional side effects, the cost of non-vaccination – in both death and suffering – will always be much higher.”

 

Optimizing Immunity

Proper nutrition, exercise, ample sleep, and adequate levels of Vitamin D have been shown to enhance the efficacy of vaccines as well as strengthen the immune system as a whole. This is discussed in more detail in our blog: Strengthen Your Immune System! Your Guide to the Ultimate 2021 New Years Resolution

 

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References:

(1) “Poliomyelitis Prevention in the United States: Introduction of A Sequential Vaccination Schedule of Inactivated PoliovirusVaccine Followed by Oral Poliovirus Vaccine; Recommendations of the Advisory Committee on Immunization Practices (ACIP)”, Cdc.gov, 1997. [Online]. Available: https://www.cdc.gov/mmwr/preview/mmwrhtml/00046568.htm.

Chagas Disease

by Dr. Jaclynn Moskow

Trypanosoma cruzi parasite, 3D illustration. A protozoan that causes Chagas' disease transmitted to humans by the bite of triatomine bug
Trypanosoma cruzi parasite, the etiologic agent of Chagas disease

 

In 1909, Brazilian physician Carlos Chagas learned of a local phenomenon in which blood-sucking insects were biting people on the face during sleep. On April 14, he dissected one such insect and found parasitic euglenoids living inside of it (1). Dr. Chagas named the parasite Trypanosoma cruzi (T. cruzi) and, in this moment, discovered both the causative agent and vector of “Chagas Disease.”

On April 14, 2021, we recognize the second annual World Chagas Disease Day (2). Chagas disease, also known as American Trypanosomiasis, is endemic to Latin America. It can lead to severe cardiac, neurologic, and gastrointestinal disease  – and in some cases is fatal, causing about 12,000 deaths each year (3).

The Chagas disease represents the third-largest tropical disease burden worldwide, after malaria and schistosomiasis (4). It has likely been with us for thousands of years, as T. cruzi DNA has been recovered from ancient mummies and bone fragments (1).

Transmission

Triatomine bugs, also known as “kissing bugs”, “cone-nosed bugs”, or “bloodsuckers”, are the vectors for Chagas disease. They acquire T. cruzi after biting infected animals or humans and transmit the parasite to others through their feces. There are over 150 species of domestic and wild animals that serve as reservoirs for Chagas disease (5), including dogs, cats, pigs, rabbits, raccoons, rats, bats, armadillos, and monkeys.

 

The kissing bug. Blood sucker, infection is known as Chagas disease.
‘Kissing bug’,  vector of Chagas disease

 

Triatomine bugs are commonly found in rural areas, in houses made from materials such as mud, adobe, straw, and palm thatch (6). They feed at night. If they defecate on an individual and T. cruzi gains access to the body via a mucus membrane or break in the skin, the transmission of Chagas disease may occur.

Vertical transmission of Chagas disease is possible during pregnancy. Chagas disease can also be transmitted via blood transfusion and organ transplantation, and there is some evidence that it may be transmitted through sex and in rare instances through consumption of game meat. It can also be acquired by consuming food or water contaminated with insect remains (4).

 

Clinical Presentation

The incubation period for Chagas disease depends upon the mode of transmission. Vectorially transmitted cases usually manifest in one-to-two weeks, while orally transmitted cases may take up to 3 weeks – and transfusion-based cases up to 120 days (5).

Chagas disease has an acute and chronic phase. The acute phase is often asymptomatic or mild in nature and usually resolves spontaneously (5). The acute phase may begin with the development of a “chagoma” – an indurated area of erythema and swelling with local lymph node involvement (7). “Romana’s sign” consists of painless edema of the eyelids and periocular tissues (resulting from conjunctival inoculation) and is usually unilateral. Patients in the acute phase may develop fever, malaise, and anorexia. Generalized lymphadenopathy and mild hepatosplenomegaly may be present. Rarely, meningoencephalitis or severe myocarditis with arrhythmias and heart failure may occur.

10% to 30% of acute infections will progress to chronic disease. Chronic disease may present years or decades after the initial infection. Cardiac manifestations include arrhythmias, thromboembolism, and cardiomyopathy. Arrhythmias may present as episodes of vertigo, syncope, or seizures. Congestive heart failure may develop, leading to death. Cerebral disease can also occur and is characterized by headache, seizures, focal neurological deficits, and evidence of ischemia and infarct. Gastrointestinal manifestations include megaesophagus and megacolon. Dysfunction of the urinary bladder is also reported. Chagas disease has an overall case-fatality rate of 10% (7).

Patients with chronic Chagas disease who become immunosuppressed may experience a reactivation of the infection. In individuals with concurrent HIV/AIDS and Chagas disease, the central nervous system is the most commonly affected site, and space-occupying lesions often occur. (8).

 

Diagnosis and Treatment

Chagas disease may be diagnosed through visualization of protozoa in blood or tissue, serology, xenodiagnosis, or PCR. The anti-parasitic medications Nifurtimox or Benznidazole can be used for treatment. Treatment is curative in approximately 50-80% of acute-phase cases, and 20-60% of chronic phase cases (9). Treatment is curative in greater than 90% of congenital cases when given within the first year of life (10). Treatment of pregnant women is not recommended (11).

Prevalence 

Vector-borne transmission of Chagas disease only occurs in the Americas. Approximately 121 million individuals are at risk in Central and South America and Mexico. If you have a GIDEON account, click here to explore our Chagas disease outbreak map. An estimated 8 million people are currently infected (12).  

Vector-borne transmission of Chagas disease is exceedingly rare in the United States, with 28 cases documented between 1955 and 2015 (13). About 300,000 people are currently living in the United States with Chagas disease that was acquired in Latin America (14). In Europe, the prevalence of T. cruzi infection among Latin American migrants is approximately 6% (4).

In 2007, two notable outbreaks occurred as the result of ingestion of sources contaminated with T. cruzi. 166 cases occurred in Brazil from contaminated food and 128 cases in Venezuela from contaminated juice (4). 

 

Prevention

Vector-control programs centered around the widespread use of insecticides have led to some success in decreasing the prevalence of Chagas disease. This progress, however, has been recently complicated by the emergence of insecticide-resistant vectors.

 

Falling death rates of Chagas disease (Trypanosomiasis – American), 1990 – 2016

 

Trypanosomiasis – American is otherwise known as Chagas disease

 

Individuals living in endemic areas can decrease their risk of contracting the disease by completing home improvement projects aimed at disrupting triatomine bug nests. These nests are commonly found beneath porches, between rocky surfaces, in wood/brush piles, rodent burrows, and chicken coops (15). Individuals traveling to endemic areas can decrease their risk of contracting the disease by applying insect repellent, wearing protective clothing, and using bed nets.

The screening of blood products for Chagas disease is another important prevention strategy. In most endemic countries, all blood donations are tested for T. cruzi antibodies. In countries in which cases are imported, screening strategies vary (16, 17). In the United States, all first-time blood donors are tested. In Canada, the UK, and Spain, only donors considered “at-risk” are tested (such as those who previously lived in, or recently traveled to, Latin America). In Sweden, individuals who lived in endemic countries for more than five years are precluded from donating blood, while in Japan, only individuals with a known history of Chagas disease are excluded. In China, blood donors are not currently screened for Chagas disease.

Recently, a new surveillance system for Chagas disease has been implemented in some countries where malaria is also endemic; microscopy technicians have been trained to identify T. cruzi in malaria films (18).

 

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References 

(1) D. Steverding, “The history of Chagas disease”, Parasites & Vectors, vol. 7, no. 1, p. 317, 2014. Available: 10.1186/1756-3305-7-317

(2) “World Chagas Disease Day: raising awareness of neglected tropical diseases”, World Health Organization, 2019. [Online]. Available: https://www.who.int/neglected_diseases/news/world-Chagas-day-approved/en/

(3) B. Lee, K. Bacon, M. Bottazzi and P. Hotez, “Global economic burden of Chagas disease: a computational simulation model”, The Lancet Infectious Diseases, vol. 13, no. 4, pp. 342-348, 2013. Available: 10.1016/s1473-3099(13)70002-1 

(4) “Trypanosomiasis – American Worldwide Distribution”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/trypanosomiasis-american-12460/worldwide

(5) A. Rassi, A. Rassi and J. Marin-Neto, “Chagas disease”, The Lancet, vol. 375, no. 9723, pp. 1388-1402, 2010. Available: 10.1016/s0140-6736(10)60061-x

(6) “Parasites – American Trypanosomiasis (also known as Chagas Disease): Detailed FAQs”, Centers for Disease Control and Prevention, Global Health, Division of Parasitic Diseases and Malaria, 2021. [Online]. Available: https://www.cdc.gov/parasites/chagas/gen_info/detailed.html#intro

(7) “Trypanosomiasis – American”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/trypanosomiasis-american-12460

(8) A. Vaidian, L. Weiss, and H. Tanowitz, “Chagas’ disease and AIDS”, Kinetoplastid Biol Dis, vol. 3, no. 1, p.2, 2004. Available: 10.1186/1475-9292-3-2

(9) J. Guarner, “Chagas disease as example of a reemerging parasite”, Seminars in Diagnostic Pathology, vol. 36, no. 3, pp. 164-169, 2019. Available: 10.1053/j.semdp.2019.04.008

(10) F. Machado et al., “Chagas Heart Disease”, Cardiology in Review, vol. 20, no. 2, pp. 53-65, 2012. Available: 10.1097/crd.0b013e31823efde2

(11) E. Howard, P. Buekens and Y. Carlier, “Current treatment guidelines for Trypanosoma cruzi infection in pregnant women and infants”, International Journal of Antimicrobial Agents, vol. 39, no. 5, pp. 451-452, 2012. Available: 10.1016/j.ijantimicag.2012.01.014

(12) “Chagas disease (American trypanosomiasis): Epidemiology”, World Health Organization, 2021. [Online]. Available: https://www.who.int/chagas/epidemiology/en/

(13) S. Montgomery, M. Parise, E. Dotson and S. Bialek, “What Do We Know About Chagas Disease in the United States?”, The American Journal of Tropical Medicine and Hygiene, vol. 95, no. 6, pp. 1225-1227, 2016. Available: 10.4269/ajtmh.16-0213

(14) “Parasites – American Trypanosomiasis (also known as Chagas Disease): Epidemiology & Risk Factors”, Centers for Disease Control and Prevention, Global Health, Division of Parasitic Diseases and Malaria, 2019. [Online]. Available: https://www.cdc.gov/parasites/chagas/epi.html

(15) “Parasites – American Trypanosomiasis (also known as Chagas Disease): Triatomine Bug FAQs”, Centers for Disease Control and Prevention, Global Health, Division of Parasitic Diseases and Malaria, 2020. [Online]. Available: https://www.cdc.gov/parasites/chagas/gen_info/vectors/index.html

(16) A. Angheben et al.,”Chagas disease and transfusion medicine: a perspective from non-endemic countries”, Blood Transfus, vol. 13, no. 4, pp. 40-50, 2015. Available: 10.2450/2015.0040-15

(17) V. Mangano, M. Prato, A. Marvelli, G. Moscato and F. Bruschi, “Screening of at‐risk blood donors for Chagas disease in non‐endemic countries: Lessons from a 2‐year experience in Tuscany, Italy”, Transfusion Medicine, vol. 31, no. 1, pp. 63-68, 2020. Available: 10.1111/tme.12741 

(18) “Chagas disease (American trypanosomiasis): Prevention of Chagas Disease”, World Health Organization, 2021. [Online]. Available: https://www.who.int/chagas/disease/prevention/en/

Occupational Infectious Diseases

by Dr. Jaclynn Moskow

Occupational health: Manufacturer working at storage tanks in brewery

 

In recognition of World Health Day 2021, which falls on April 7, the WHO points out that “some people are able to live healthier lives and have better access to health services than others – entirely due to the conditions in which they are born, grow, live, work, and age.”

Many of us spend a significant portion of our lives engaged in work. Unfortunately, certain working conditions put us at increased risk of poor health. For example, some occupations involve repeated exposure to respiratory irritants and carcinogens, while others are associated with musculoskeletal injury or hearing loss. Many professions put workers at risk of contracting an infectious disease.

Textbook of Occupational Medicine Practice (1) outlines five primary modes of transmission for occupational infections:

  1. Contact with animals and animal products (zoonoses)
  2. Exposure to vectors 
  3. Care of patients 
  4. Environmental sources, exposure to soils 
  5. Occupational skin infections

 

Occupational Zoonoses

Farmer with cow

Individuals who work with animals and animal products are at risk of contracting zoonotic diseases. Such occupations include farmworkers, ranch workers, butchers, veterinary workers, and zoo workers. There are currently over 200 recognized zoonoses (2).

Brucellosis is a zoonotic infectious disease caused by Brucella spp. Reservoirs for Brucella include pigs, cattle, sheep, goats, dogs, coyotes, and caribou. Brucellosis can be acquired via direct contact with these animals, or by processing their meat. Symptoms include prolonged fever, hepatosplenomegaly, lymphadenopathy, arthritis, and osteomyelitis (3). A study of occupationally acquired Brucella in Russia found that factors increasing the risk of infection include lack of awareness amongst workers regarding the disease and absence of regular inspections of working conditions (4).

Individuals who work with cats are at increased risk of acquiring bartonellosis, also known as “cat scratch disease.” As the name implies, the disease is caused by species of Bartonella and transmitted via cat scratches. Clinical manifestations include tender suppurative regional adenopathy and fever. Occasionally, systemic infection occurs involving such sites as the liver, brain, endocardium, and bones (5). A recent study of veterinary personnel detected Bartonella in 28% of subjects, compared to 0% of a control group (6).

A review of the incidences of campylobacteriosis and cryptosporidiosis in Nebraska between 2005-2015 identified occupational animal exposure as the cause in 16.6% and 8.7% of cases, respectively (7). Most of these cases were acquired by farmers, ranchers, and those working in animal slaughter and processing facilities; and the most common animal source was determined to be cattle. Additional occupational zoonotic infectious diseases include salmonellosis, Escherichia coli O157 infection, and Q-fever.

 

Occupational Infections Acquired Via Exposure to Vectors

Woman digging hole with shovel to plant saplings in forest. Forester planting new small trees in deforested area. Vector-borne diseases are occupational hazards for forestry workers.

Individuals working in areas infested with ticks, fleas, and mites are at an increased risk for infectious diseases carried by these arthropods. Occupations at risk include agricultural workers, forestry workers, military personnel, veterinary workers, and pest control workers.

Diseases that may be spread to workers via tick bites include Lyme disease, babesiosis, ehrlichiosis, Colorado tick fever, Rocky Mountain spotted fever, tularemia, and Powassan virus encephalitis. In the United States, Lyme disease is the most common tick-borne illness. It is caused by Borrelia spp. and characterized by the presence of erythema migrans, neurological, musculoskeletal, and cardiac manifestations.

Individuals working around fleas may acquire flea-borne (murine) typhus, caused by Rickettsia typhi, or Plague caused by Yersinia pestis. Additionally, exposure to mites could lead to the development of rickettsialpox, caused by Rickettsia akari, or scrub typhus, caused by Orientia spp.

 

Occupational Infections Acquired Via Care of Patients

Female nurse tying surgical mask in operation theater

 

Caring for patients while working in hospitals, ambulatory clinics, diagnostic laboratories, nursing homes, and the home carries an increased risk for several infectious diseases.

Each year, healthcare workers experience approximately 600,000–800,000 exposures to HIV, hepatitis B, and hepatitis C (8). Exposures may occur via needle-stick injury or via blood and other bodily fluids which accidentally contact mucous membranes. Healthcare workers can decrease their risk of contracting bloodborne pathogens by adhering to universal precautions.

Airborne pathogens are also of concern to healthcare workers. Respiratory diseases that can be acquired while caring for patients include tuberculosis, influenza, and COVID-19. Healthcare workers are also at increased risk of contracting methicillin-resistant Staphylococcus aureus (MRSA). Approximately 4.6% of healthcare workers carry MRSA (9), compared to 1% of the general population (10).

Vaccinations recommended to healthcare workers to help prevent occupationally acquired infections include hepatitis B, MMR, and influenza. 

 

Occupational Infections Acquired Via Exposure to Soils

Close-up low section of woman standing with fork on dirt

Individuals engaged in plowing, digging, and excavating soil at work may be exposed to a variety of infections. Such occupations include construction and demolition work, oil and gas extraction, agriculture workers, landscaping, and archaeology.

Workers exposed to soils are at an increased risk of endemic mycoses, including histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, and blastomycosis. These infections are generally acquired by inhaling fungal spores that become airborne as the soil is disrupted. An example of this occurred between 2011 and 2014 when an outbreak of coccidioidomycosis occurred among workers constructing solar power-generating facilities in San Luis Obispo County, California. A total of 44 cases were documented, including nine hospitalizations (11). 

The paradigm disease associated with soil contact is tetanus, caused by Clostridium tetani. Tetanus is acquired when bacterial spores found in soil are introduced to the body via a breach in the skin. Clinical manifestations of tetanus include trismus (lockjaw), facial spasm, opisthotonos, recurrent tonic spasms of skeletal muscle, and tachycardia. Tetanus has a case fatality rate of 10 to 40% (12). Tetanus cases can be prevented through vaccination…and the CDC reports that the efficacy of the tetanus vaccine is nearly 100% (13).

 

Occupational Skin Infections

Butchers may catch occupational skin infections by exposure to raw meat

There are a wide variety of professions in which occupational exposure to skin infections may occur. These include farmers, fisherman, butchers, veterinary workers, aquarium workers, swimming pool cleaners, healthcare workers, and salon workers. 

Many occupational skin infections result from exposure to animals and animal tissue. For example, farmers and butchers are at an increased risk of contracting cutaneous anthrax, caused by Bacillus anthracis. Cutaneous anthrax usually begins with pruritus at the affected site and is followed by a small, painless papule that progresses to a vesicle. The lesion erodes and becomes necrotic, and secondary vesicles are sometimes observed. Lymphadenopathy, fever, and headache may also occur. When left untreated, approximately 20% of cases are fatal (14).

Erysipeloid, caused by Erysipelothrix rhusiopathiae, can also occur when working with animals and animal tissues. The infection is characterized by rash, local pain, swelling, and occasionally fever. One report described an outbreak of erysipeloid amongst workers at a shoe factory (15). The source of the bacteria was determined to be raw leather.

Exposure to water is another common source of occupational skin infections. Fish tank granuloma, an infection caused by Mycobacterium marinum, is often acquired by aquarium workers. Fishermen are at risk of contracting Vibrio vulnificus infection through contact with contaminated ocean water or fish.

Other infections of the skin that can be acquired at work are caused by fungi. Examples include candidiasis, dermatophytosis, chromomycosis, and sporotrichosis. Scabies, a parasitic skin infestation caused by a mite, is often reported among healthcare workers, daycare workers, and correctional facility employees.

 

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References

(1) D. Koh and T. Aw, “Textbook of Occupational Medicine Practice”, 2017. Available: 10.1142/10298

(2) “Other Neglected Zoonotic Diseases”, World Health Organization, 2021. [Online]. Available: https://www.who.int/neglected_diseases/zoonoses/other_NZDs/en/

(3) “Brucellosis”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/brucellosis-10260

(4) A. Tarkhov,  et al., “The Working Conditions At Animal Farm Complexes of Workers With Occupational Brucellosis”, Med Tr Prom Ekol, vol. 5, pp. 5-9, 2012.

(5) “Bartonellosis – Cat Borne”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/bartonellosis-cat-borne-10320

(6) P. Lantos et al., “Detection of Bartonella Species in the Blood of Veterinarians and Veterinary Technicians: A Newly Recognized Occupational Hazard?”, Vector-Borne and Zoonotic Diseases, vol. 14, no. 8, pp. 563-570, 2014. Available: 10.1089/vbz.2013.1512

(7) C. Su, D. Stover, B. Buss, A. Carlson and S. Luckhaupt, “Occupational Animal Exposure Among Persons with Campylobacteriosis and Cryptosporidiosis — Nebraska, 2005–2015”, MMWR. Morbidity and Mortality Weekly Report, vol. 66, no. 36, pp. 955-958, 2017. Available: 10.15585/mmwr.mm6636a4

(8) N. Swanson, C. Ross and K. Fennelly, “Healthcare-related Infectious Diseases1”, Emerging Infectious Diseases, vol. 10, no. 11, pp. e3-e3, 2004. Available: 10.3201/eid1011.040622_03

(9) W. Albrich and S. Harbarth, “Health-care workers: source, vector, or victim of MRSA?”, The Lancet Infectious Diseases, vol. 8, no. 5, pp. 289-301, 2008. Available: 10.1016/s1473-3099(08)70097-5

(10) “MRSA and the Workplace”, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 2015. [Online]. Available: https://www.cdc.gov/niosh/topics/mrsa/default.html

(11) G. Sondermeyer Cooksey et al., “Dust Exposure and Coccidioidomycosis Prevention Among Solar Power Farm Construction Workers in California”, American Journal of Public Health, vol. 107, no. 8, pp. 1296-1303, 2017. Available: 10.2105/ajph.2017.303820

(12) “Tetanus”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/tetanus-12330

(13) “Tetanus”, Centers for Disease Control and Prevention, Epidemiology and Prevention of Vaccine-Preventable Diseases, 2008. Available: https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf

(14) “Anthrax”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/anthrax-10100

(15) V Popugaĭlo VM, et al., “Erysipeloid as an occupational disease of workers in shoe enterprises”, Zh Mikrobiol Epidemiol Immunobiol, vol. 10, pp. 46-9, 1983.

World Tuberculosis Day 2021

by Dr. Jaclynn Moskow

Doctor with magnifier looking at bacteria in lungs. Tuberculosis, mycobacterium tuberculosis and world tuberculosis day concept on white background. Bright vibrant violet vector isolated illustration

Each year on March 24th, we recognize “World Tuberculosis Day” in an effort to build global awareness about the ongoing tuberculosis epidemic. Tuberculosis is an infectious disease caused by bacteria of the Mycobacterium tuberculosis complex, including Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium bovis (1). Worldwide, tuberculosis is the leading cause of death from an infectious agent (2).

“World Tuberculosis Day” occurs on March 24th as it was on this date, in 1884, that Dr. Robert Koch announced that he had discovered the causative agent of this disease (3).

 

Transmission

Tuberculosis is generally spread via the inhalation of droplet nuclei expelled by individuals with the active pulmonary or laryngeal disease. Less commonly, humans may also acquire tuberculosis from consuming unpasteurized dairy products. The incubation period of tuberculosis ranges from 4w-12w.

 

Clinical Manifestations

Clinical manifestations of tuberculosis vary depending on the site of mycobacterial proliferation (4). Most infections represent reactivation of a dormant focus in a lung and present with chronic fever, weight loss, nocturnal diaphoresis, and productive cough (5). Approximately 8% of patients with pulmonary tuberculosis will experience hemoptysis (6). Tuberculosis can also cause extrapulmonary disease in sites including the bone, joints, muscles, central nervous system, gastrointestinal system, hepatobiliary system, genitourinary system, eyes, breasts, and skin.

Individuals with latent tuberculosis infection (LTBI) do not experience symptoms but are carriers of the disease. They cannot spread the disease to others unless it becomes reactivated. The lifetime risk of reactivation for a person with documented LTBI is estimated to be 5–10% (7). Immunocompromised individuals are much more likely to experience tuberculosis reactivation.  

 

Diagnosis and Treatment

A definitive diagnosis of tuberculosis is made by the identification of the Mycobacterium tuberculosis complex in a clinical sample. Since the culture of these bacteria can be time-consuming, treatment may be initiated based on clinical suspicion alone. Tuberculosis skin tests and blood tests can be used to identify whether an individual has been infected, but cannot be used to distinguish between active and latent infections. Radiographic and other imaging techniques may also be useful in identifying patients, including those with asymptomatic active disease.

 

Mantoux test, positive result. Author: Grook da Oger.
Mantoux test, positive result. Author: Grook da Oger.

 

Typical pulmonary infection is treated with two months of Isoniazid, Rifampin, and Pyrazinamide (with Ethambutol pending results of susceptibility testing), followed by four months of Isoniazid and Rifampin alone. Treatment of multidrug-resistant tuberculosis generally includes the use of five drugs (including Pyrazinamide and/or Rifampin) for at least 6 months, followed by four drugs for 18-24 months (5).

Patients suspected of having active tuberculosis should be isolated, and healthcare personnel should observe relevant precautions.

The Centers for Disease Control and Prevention recommends treating individuals with latent tuberculosis that are at a high risk of progressing to an active infection. Included in the “high risk” designation are individuals with HIV/AIDS and other diseases that weaken the immune system, individuals who became infected with tuberculosis in the last two years, infants and young children, the elderly, and injecting drug users (8).

 

Prevalence 

In 2018, approximately 1.7 billion individuals were infected with Mycobacterium tuberculosis – roughly 23% of the world’s population (9). In 2019, approximately 10 million individuals experienced symptomatic tuberculosis, and approximately 1.4 million died as a result of the disease (10). Tuberculosis is found worldwide, but over 95% of cases and deaths occur in developing countries (10). Eight countries currently account for two-thirds of new tuberculosis cases: India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa (10). If you have a GIDEON account, click here to explore our tuberculosis outbreak map.

 

Tuberculosis cases and rates Worldwide, 1965 – today

Worldwide Tuberculosis cases and rates, 1965 - today

Vaccination 

Currently, Bacille Calmette-Guerin (BCG) vaccine remains the only licensed vaccine for the prevention of tuberculosis. It provides some protection against childhood tuberculosis but is less effective in preventing adult disease (11). BCG is commonly given to children in countries in which tuberculosis is prevalent, and is estimated to decrease the risk of contracting the disease by 50% (12).

 

Prevention for High-Risk Travelers

The Centers for Disease Control and Prevention recommend that “travelers who anticipate possible prolonged exposure to people with tuberculosis (for example, those who expect to come in contact routinely with clinic, hospital, prison, or homeless shelter populations) should have a skin or blood test before leaving the United States. If the test reaction 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.” (8)

 

The Future

In 2014, the World Health Organization announced that they seek to end the global tuberculosis epidemic by 2035. They defined this goal “with targets to reduce tuberculosis deaths by 95% and to cut new cases by 90%, and to ensure that no family is burdened with catastrophic expenses due to tuberculosis.”  WHO called on the cooperation and collaboration of governments, and suggested a strategy that focuses on highly vulnerable populations (such as migrants) (13). 

In 2020, they announced that the COVID-19 pandemic has stalled progress, as a result of resources being reallocated (2). They noted, for example, that many diagnostic testing machines have been used to test for COVID-19 instead of for tuberculosis. Hopefully, robust testing efforts for the disease will resume soon, as the identification of cases is critical to ending the epidemic.

 

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References

(1) M. Rowe and J. Donaghy, “Mycobacterium bovis: the importance of milk and dairy products as a cause of human tuberculosis in the UK. A review of taxonomy and culture methods, with particular reference to artisanal cheeses”, International Journal of Dairy Technology, vol. 61, no. 4, pp. 317-326, 2008. Available: 10.1111/j.1471-0307.2008.00433.x

(2) “Global Tuberculosis Report”, World Health Organization, 2020. [Online]. Available: https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf

(3) “The Clock Is Ticking: World TB Day 2021”, World Health Organization, 2021. [Online]. Available: https://www.who.int/campaigns/world-tb-day/world-tb-day-2021

(4) W. Cruz-Knight and L. Blake-Gumbs, “Tuberculosis”, Primary Care: Clinics in Office Practice, vol. 40, no. 3, pp. 743-756, 2013. Available: 10.1016/j.pop.2013.06.003

(5) “Tuberculosis”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/tuberculosis-12470

(6) U. Seedat and F. Seedat, “Post-primary pulmonary TB haemoptysis – When there is more than meets the eye”, Respiratory Medicine Case Reports, vol. 25, pp. 96-99, 2018. Available: 10.1016/j.rmcr.2018.07.006

(7) “Latent tuberculosis infection (LTBI): FAQs”, World Health Organization, 2021. [Online]. Available: https://www.who.int/tb/areas-of-work/preventive-care/ltbi/faqs/en/

(8) “Tuberculosis: Basic TB Facts: TB Prevention”, Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, 2016. [Online]. Available: https://www.cdc.gov/tb/topic/basics/tbprevention.htm

(9) “Global Health: Newsrooms: Global Health Topics: Tuberculosis”, Centers for Disease Control and Prevention, Global Health, 2020. [Online]. Available: https://www.cdc.gov/globalhealth/newsroom/topics/tb/index.html

(10) “Tuberculosis: Key Facts”, World Health Organization, 2020. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/tuberculosis

(11) S. Fatima, A. Kumari, G. Das, and V. Dwivedi, “Tuberculosis vaccine: A journey from BCG to present”, Life Sciences, vol. 252, p. 117594, 2020. Available: 10.1016/j.lfs.2020.117594

(12) G. Colditz, “Efficacy of BCG Vaccine in the Prevention of Tuberculosis”, JAMA, vol. 271, no. 9, p. 698, 1994. Available: 10.1001/jama.1994.03510330076038

(13) “WHO End TB Strategy”, World Health Organization, 2021. [Online]. Available: https://www.who.int/tb/post2015_strategy/en/

Springtime Diseases: From Spring Fever to Lyme Disease

by Dr. Jaclynn Moskow

March 20th marks the Spring Equinox when the sun crosses the equator and spring officially begins in the Northern Hemisphere. We generally associate spring with melting snow, blooming flowers, and mating animals; but did you know it is also associated with an increase in the incidence of certain diseases?

There are many factors that cause some infectious diseases to follow seasonal patterns. Changes in temperature and precipitation influence biotic and abiotic environments, disease vectors and hosts, and human behavior, including the amount of time spent outdoors (1). On a molecular level, the numbers of circulating lymphocytes and other immune cells have been observed to vary depending on the season. This may occur as a result of the circadian nature of adrenocortical hormones coupled with fluctuating vitamin D and melatonin levels (2). Additionally, temperature, moisture, and UV light can affect the infectivity of pathogens. The disease pathogens themselves, and their animal and plant reservoirs, insect vectors, and other factors ebb and flow with changes in temperature, rainfall, and many other influences. 

Young pretty girl blowing nose in front of blooming tree. Spring allergy concept

 

Spring Fever

There is actually a historical basis to the term “spring fever.” During the 18th century, individuals sometimes became ill during the springtime, experiencing weakness, joint swelling, loose teeth, and poor wound healing: the clinical manifestations of scurvy (3). As societies became more urbanized, those living in cities were faced with a lack of fruits and vegetables during the winter months, leading some to develop vitamin C deficiency.

Today, scurvy is quite rare. When seen, it is usually among alcoholics or individuals following very extreme diets (4), as opposed to city dwellers lacking access to food sources. The term “spring fever” is now used colloquially to describe a feeling of restlessness and excitement that accompanies the start of spring. “Spring fever” is a disease of the past, but other diseases of springtime remain.

 

Seasonal Allergies/Asthma

Allergies occur when the immune system is triggered by a non-pathogenic substance, resulting in signs and symptoms of inflammation. Many of the same substances that can trigger allergies can also trigger asthma.

Trees, grasses, and weeds produce pollen during the springtime that can instigate allergies and asthma. Additionally, certain molds that are allergenic for some people may increase in number during the spring. Individuals with allergies to pet dander may also see an increase in symptoms, as animals shed their winter coats.

Signs and symptoms of seasonal allergies include congestion, sneezing, coughing, sore throat, post-nasal drip, and headache. Eyes may become red, itchy, watery, and/or swollen. Skin rashes may also be present, as may lymphadenopathy. In extreme cases, anaphylaxis may occur. Asthma is characterized by difficulty breathing, tightness in the chest, wheezing and coughing.

It is estimated that 10–30% of the global population are affected by allergic rhinitis (5). Asthma is less common, affecting about 300 million people worldwide (6.) Those suffering from seasonal allergies will find relief by avoiding known triggers. Utilization of a HEPA filter may be of benefit, as may keeping windows and doors closed. Masks can be worn when gardening and mowing the lawn, and taking a shower immediately after these activities may also provide relief. Frequently brushing and grooming pets and vacuuming dander may also help. 

Oral antihistamines and decongestants can be used, and in extreme cases, corticosteroids may be warranted. Allergy shots are also a key option. Asthmatic attacks can be managed with a number of medications, including corticosteroids, leukotriene modifiers, beta-agonists, theophylline, ipratropium, and various immunomodulators.

Woman with a spring allergy or a cold sneezing with tissue

Rhinoviruses

Rhinoviruses are the most common causes of the common cold. Unlike influenza, which peaks in the winter, rhinovirus cases peak during the fall and spring (7). Rhinoviruses are members of the genus Enterovirus of the family Picornaviridae. Rhinovirus infection has an incubation period of 1-9 days (8).

Rhinovirus infection can resemble seasonal allergies, causing congestion, sneezing, coughing, sore throat, and headache. Unlike with seasonal allergies, muscle aches are also common, and low-grade fever may occur. Rhinoviruses can cause ear infection, and bronchiolitis/bronchitis can develop, especially in children. Rarely, pneumonia may occur. Rhinovirus may also instigate asthma attacks.

Rhinovirus infection is generally self-limiting. Patients may obtain symptomatic relief using nasal decongestants, cough suppressants, and NSAIDs. Many of the same strategies being employed to limit the spread of SARS-CoV-2 can also reduce rhinovirus transmission, including frequent hand washing, avoiding contact with those who are ill and isolating patients.

 

Lyme Disease

Lyme disease is caused by Borrelia spp. and transmitted to humans through the bites of infected Ixodes ticks, often referred to as black-legged ticks/deer ticks. Most cases are acquired from immature ticks (nymphs) which are small (less than 2 mm), and difficult to see. They feed during the spring and summer months (9) – the peak season of Lyme disease (10).

The tick Ixodes ricinus crawling on human skin. This kind of animal is a distributor of Borrelia spp, an agent of Lyme disease
Ixodes ricinus tick is a distributor of Borrelia spp., an agent of Lyme disease

 

Lyme disease has an incubation period ranging from 2-180 days, with most cases manifesting within 7 to 14 days. About 25% of patients recall a recent tick bite. Erythema migrans is present in 75% of cases and is usually neither pruritic nor painful. Multiple skin lesions may occur in 20% to 50% of cases. A nodule in the nipple or ear lobe (borrelial lymphocytoma) may be present. Acrodermatitis chronicum atrophicans can also occur, typically seen on the hands and feet (11). 

Neurological manifestations occur in 10-15% of patients (12). The most common of these include lymphocytic meningitis, cranial neuritis, mononeuropathy multiplex, and painful radiculoneuritis. The range of joint involvement includes tendonitis, myositis, and bursitis, which wax and wane. The cardiac disease may be characterized by arrhythmia, heart block, chest pain, and pericarditis or myopericarditis. Rarely, other organs may become involved. 

Doxycycline, Ceftriaxone, Amoxicillin, and Cefuroxime can be used as a treatment, with dosage, route, and duration varying according to patient age and the nature and severity of the disease.

About 30,000 cases of Lyme Disease are reported to the Centers for Disease Control and Prevention (CDC) each year, but they estimate that as many as 476,000 people will actually contract the disease (13). Most cases occur in Pennsylvania, New York, Connecticut, and other states in the Northeastern United States. The disease is also common in Wisconsin and Minnesota. Lyme disease has been reported in Asia: in China, Korea, Japan, Indonesia, Nepal, and eastern Turkey. In Europe, most Lyme disease cases occur in Scandinavian countries, Germany, Austria, and Slovenia (14).

The CDC recommends that individuals spending time in wooded and grassy areas perform daily “tick checks.” By removing a tick within 24 hours, Lyme disease transmission is greatly decreased. It is important to contact a health professional before attempting to remove a tick. When outdoors, covering skin by wearing long clothing can also reduce transmission. 

Stay safe and Happy Spring!

 

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References

(1) M. Martinez, “The calendar of epidemics: Seasonal cycles of infectious diseases”, PLOS Pathogens, vol. 14, no. 11, p. e1007327, 2018. Available: 10.1371/journal.ppat.1007327

(2) A Fares A, “Factors influencing the seasonal patterns of infectious diseases”, Int J Prev Med, vol. 4, no. 2, pp. 128-32, 2013.

(3) P. Janson, “When Spring Fever Was a Real Disease”, Emergency Medicine News, vol. 38, p. 1, 2016. Available: 10.1097/01.eem.0000484361.70086.35

(4) M. Weinstein, P. Babyn and S. Zlotkin, “An Orange a Day Keeps the Doctor Away: Scurvy in the Year 2000”, PEDIATRICS, vol. 108, no. 3, pp. e55-e55, 2001. Available: 10.1542/peds.108.3.e55

(5) C. Schmidt, “Pollen Overload: Seasonal Allergies in a Changing Climate”, Environmental Health Perspectives, vol. 124, no. 4, 2016. Available: 10.1289/ehp.124-a70

(6) “Asthma”, Who.int, 2021. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/asthma

(7) A. Monto, “The seasonality of rhinovirus infections and its implications for clinical recognition”, Clinical Therapeutics, vol. 24, no. 12, pp. 1987-1997, 2002. Available: 10.1016/s0149-2918(02)80093-5

(8) Lessler, N. Reich, R. Brookmeyer, T. Perl, K. Nelson and D. Cummings, “Incubation periods of acute respiratory viral infections: a systematic review”, The Lancet Infectious Diseases, vol. 9, no. 5, pp. 291-300, 2009. Available: 10.1016/s1473-3099(09)70069-6

(9) “Lyme disease: Transmission”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD), 2020. [Online]. Available: https://www.cdc.gov/lyme/transmission/index.html

(10) S. Moore, R. Eisen, A. Monaghan and P. Mead, “Meteorological Influences on the Seasonality of Lyme Disease in the United States”, The American Journal of Tropical Medicine and Hygiene, vol. 90, no. 3, pp. 486-496, 2014. Available: 10.4269/ajtmh.13-0180

(11) “Lyme disease”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/lyme-disease-11360

(12) J. Halperin, “Neurologic Manifestations of Lyme Disease”, Current Infectious Disease Reports, vol. 13, no. 4, pp. 360-366, 2011. Available: 10.1007/s11908-011-0184-x

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