Hot on the heels of the COVID-19 virus and its variants, another infectious virus recently landed in the United States. On July 9th, 2021, a passenger with monkeypox flew from Lagos in Nigeria to the United States, ultimately landing in Dallas, Texas. The Centers for Disease Control and Prevention, CDC confirmed the case of Monkeypox on July 15th – the first case of monkeypox in the United States in almost 20 years. While rare, the Monkeypox virus is contagious and kills one in ten people that it infects.
“…we are only a plane ride away from any global infectious disease.”
– Dr. Philip Huang, Director of the Dallas County Health and Human Services.
A few fortunate events prevented a Monkeypox outbreak in the United States this time around.
Symptoms Presented Early: Symptoms of monkeypox are similar to those of smallpox and can take anywhere from 7 to 14 days to appear after getting infected (incubation period). Luckily, symptoms presented earlier, and the patient visited a hospital within four days of entry into the country.
Early Detection by Frontline Clinicians: The symptoms of monkeypox include fever, headache, backache, swollen lymph nodes, chills, and fatigue. Within three days of the onset of fever, a rash appears on the face and spreads to other parts of the body. Doctors and healthcare workers at the Dallas hospital were able to identify and diagnose monkeypox quickly, so the infected patient was isolated early.
Mask Mandates and Social Distancing: Monkeypox can spread from person to person through respiratory droplets and body fluids. In this instance, a huge silver lining is that due to COVID-19 mandates, everyone, including the patient, other passengers, airline and airport staff, and others wore masks. This helped prevent the spread.
Monkeypox is transmitted to humans through infected animals or other humans. Animals can share it through bites, scratches, or direct contact with body fluids. Human transmission is mostly through respiratory droplets and body fluids but also contact with contaminated clothes.
While there was no outbreak this time, there have been a few in prior years.
In 2018-2019, five cases of monkeypox were reported in Israel, Singapore, and London. The UK also had one additional case in May 2021. Worldwide, Monkeypox cases are on the rise. In 2020, almost 4,500 cases of monkeypox were reported in the Democratic Republic of Congo in just nine months.
According to the GIDEON (Global Infectious Diseases and Epidemiology Network) country note on Monkeypox in Nigeria, there were six cross-border events of monkeypox from Nigeria to other countries and two notable outbreaks. In the latest one from 2017-2021, 446 people in Nigeria were infected with Monkeypox.
Diagnosing Monkeypox Accurately
Monkeypox has specific symptoms that distinguish it from other diseases. Swollen lymph nodes and a telltale rash help diagnose it more accurately, but misdiagnosis is possible.
Let’s look at the illustration below. When we add patient travel history from Nigeria and the symptoms of monkeypox like fever, headache, generalized lymphadenopathy, skin lesions or rash, and others into the GIDEON infectious disease diagnostic probability engine, Varicella is also a strong contender. But the presence of ‘severe illness’ and the type of rash signifies a greater probability of Monkeypox.
GIDEON’S side-by-side comparison of the clinical features of Monkeypox and Varicella helps narrow down and confirm the Monkeypox diagnosis based on patient presentation.
As Monkeypox has no cure, saving lives relies on early detection and control of spread. Although there is some evidence that vaccination against smallpox may also prevent monkeypox, the Smallpox vaccine is no longer used. Another outbreak could happen anywhere, anytime.
Are we prepared to detect the next infectious disease that crosses our shores early?
Detecting Foreign Infectious Diseases Early
Regarding the July 2021 Monkeypox case in Dallas, Dr. Philip Huang, the Director of the Dallas County Health and Human Services, stated, “This is another demonstration of the importance of maintaining a strong public health infrastructure, as we are only a plane ride away from any global infectious disease.”
Indeed, as the COVID-19 pandemic demonstrated, it is easy for emerging infectious diseases to spread rapidly worldwide. As seen in the Texas Monkeypox case, if patient travel history is considered at first presentation and symptoms are detected early, we can stop the spread of a disease-causing pathogen.
Healthcare providers are our first line of defense against infectious diseases. Unfortunately, clinicians, nurses, emergency room workers, paramedics, and ambulance drivers in clinics and hospitals are also some of the first casualties from infection. The World Health Organization (WHO) recently reported that 115,000 healthcare workers have died from COVID-19. With the Delta variant on the loose, the pandemic is very much underway, and this number may rise. Protecting our borders and healthcare workers from emerging infectious diseases requires better access to advanced diagnostic tools with epidemiological data.
When frontline clinicians have doubts about their initial assessment, they can conduct a differential diagnosis by comparing a patient’s symptoms with other diseases or consult infectious disease specialists. However, if they do not, or cannot, refer to a specialist or use an infectious disease platform for differential diagnosis (DDx), the disease-causing virus or bacteria may be misidentified and spread unchecked.
Doubt strikes fear into the hearts of many. But it is a powerful tool in the hands of medical professionals and researchers. Being uncertain is the impetus that drives truth-seeking peer-to-peer verification and differential diagnoses that can help save lives.
Take Legionnaires’ disease. It is one of the leading causes of pneumonia worldwide . If left untreated without the right antibiotics, it can be fatal. In the United States alone, the economic burden of just one year of Legionnaires’ disease cases can be over 800 million US dollars .
Surprisingly, it is often overlooked. So much so that even the World Health Organization or WHO states, “Since many countries lack appropriate methods of diagnosing the infection or sufficient surveillance systems, the rate of occurrence is unknown. In Europe, Australia, and the USA, there are about 10–15 cases detected per million population per year .”
A great place to begin addressing these challenges is if clinicians are willing to embrace doubt when faced with diagnosing pneumonia-like symptoms.
What causes Legionnaires’ Disease or Legionellosis?
There were many historical events in 1976. NASA unveiled their first space shuttle, Apple Computers was born, and the first Rocky movie was released. Unfortunately, it was also the year a tragic event led to the discovery of Legionnaires’ disease.
On July 21st, 1976, 4000 delegates from the American Legion, America’s largest veterans’ service organization, traveled to Philadelphia for a convention. Within a few weeks, almost 200 got sick with an upper respiratory illness, and 29 died. It took nearly five months of investigations to identify the pathogen – Legionella – as the cause .
Legionnaires’ disease or Legionellosis is caused by the bacteria Legionella.It lives in water and soil and can cause health issues when it grows in showerheads and faucets, hot tubs, and in stagnant water and air conditioning systems in large buildings. We are susceptible to infection by Legionella when we inhale water droplets with the bacteria in it or come in contact with contaminated soil. Legionellosis is not spread through direct human-to-human transmission. It has an incubation period of 2 to 10 days.
Legionella is widely found in warm water environments, so most cases of Legionnaires’ occur in the summer and early autumn. Legionnaires’ is a public health issue. Cassell et al. caution that utmost care must be taken when COVID-19 restrictions are lifted worldwide. Going back to work or school in buildings left unoccupied or unused during lockdowns is a risk factor for Legionellosis .
Why is Legionnaires’ Disease often misdiagnosed or overlooked?
According to Reller et al. , a wrong Legionellosis diagnosis is often due to:
The inability to distinguish Legionnaires’ disease from other types of pneumonia, clinically and radiographically,
Failure to order diagnostic tests for Legionella infection, and
Inadequacies in current diagnostic tests and protocols.
The majority of Legionnaires’ disease cases each year remain undiagnosed; the world still awaits better diagnostic tests and protocols for Legionellosis. But the issue of “failure to order diagnostic tests for Legionella infections” can be fixed. The Urine Antigen Test (UAT) and sputum tests prescribed for Legionella are inexpensive, so cost is not the issue.
The solution lies in training medical professionals to embrace doubt and challenge their confirmation biases. Clinicians who take a few minutes to input a patient’s pneumonia and accompanying symptoms on a robust, clinical decision support tool like GIDEON (Global Infectious Diseases and Epidemiology Network)can better understand how to proceed.
For example, when the COVID-19 pandemic hit, experts cautioned clinicians to be on the alert for Legionellosis as well. The concern was that clinicians might repeatedly be testing community-acquired pneumonia patients for COVID-19 but not Legionellosis – which would delay diagnosis and treatment. Since initial clinical presentations for the two are similar, clinical decision tools can be extremely useful.
Legionnaires’ disease, misdiagnosed as Malaria, can be fatal because malarial drugs do not work against Legionella. It is even more critical to get the right diagnosis early.
Legionellosis Misdiagnosed as Malaria
Take the example of theagricultural expert from Israel wrongly diagnosed with malaria instead of Legionellosis. He had traveled to India to work on a farming project in 2005. A week later, when he returned to Israel, he developed fever, headache, vomiting, and muscle pain. In two days, he felt better, but the symptoms reappeared but with cough, shortness of breath, and rigors in tow. The patient was highly lethargic, hypotensive, and blood tests showed elevated bilirubin and creatinine levels.
Because of his recent travel to India, doctors thought it was Malaria. He was started on malarial medication while laboratory tests were being processed. But when blood smears proved negative for Malaria, his doctors wondered if it was Dengue.
Luckily for him, his doctors decided to challenge their cognitive biases and conducted a differential diagnosis. They entered the patient’s symptoms in the popular DDx or differential diagnosis tool, GIDEON. To their surprise, neither Malaria nor Dengue showed up as possibilities. But given the symptoms and the incubation period, Legionellosis turned out to be the prime (and accurate) suspect. This saved his life because standard malarial therapy does not work against Legionellosis.
Misdiagnosing Legionnaires’ disease can be fatal, lead to a public health crisis, and add hundreds of millions to an already astronomically high healthcare burden. One of the main reasons it is often overlooked is that clinicians may not think about testing for Legionellosis when treating a patient with pneumonia.
Equipping clinicians with the right clinical diagnosis tools can help them validate their assumptions. Not only that, using a tool like GIDEON, clinicians can also challenge their confirmation biases and learn why a diagnosis does not apply to a specific set of symptoms.
Getting to the correct answer starts with harboring and encouraging healthy doubt in initial diagnoses. As the famous philosopher, Voltaire said, “Doubt is not a pleasant condition, but certainty is absurd.”
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Mycobacterium tuberculosis (M. tuberculosis), a non-motile, obligately aerobic, intracellular bacterium known to cause Tuberculosis (TB), was discovered by Robert Koch in 1882 . TB primarily affects the lungs along with the abdomen, bones, nervous system, reproductive system, liver, and lymph glands .
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 .
Global cases of Tuberculosis between 1965-2019
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 . 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 .
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 . 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 .
AFB staining is the traditional method of TB diagnosis, as it is inexpensive and provides rapid results . 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 . In general, a sputum sample must contain at least 10,000 organisms/mL to visualize these bacteria at 100x magnification.
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 .
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:
Loss of appetite
b. Symptoms of Pulmonary TB (infected lungs):
Shortness of breath, which progressively worsens
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:
Swellings in the neck or other regions
Pain in a joint or affected bone
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). 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 .
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]
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 . Widespread immunization using BCG vaccine has facilitated a reduction in TB cases globally .
Five-to-ten percent of people with latent TB who do not receive appropriate treatment will eventually develop active TB disease 
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. .
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K. R, Die Aetiologie der Tuberculose [The aetiology of Tuberculosis.], Berlin: Berliner Klinische Wochenschrift, 1882.
F. K. Dye C, Disease Control Priorities in Developing Countries, New York:: Oxford University Press, 2006.
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.
CDC, How TB Spreads, CDC, 2016.
G. M. J. Jr., “Microbial pathogenesis of Mycobacterium Tuberculosis: dawn of a discipline,” Cell, no. 104, pp. 477-485, 2001.
J. D. E, Mycobacterial diseases of the lung and bronchial tree: Clinical and laboratory aspects of Tuberculosis, Boston: Brown and Company, 1974.
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 .”
While this fact may not be news to clinicians and Infectious Disease specialists, the study also shows a close spatialdependence 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 .
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 .
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.
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 .
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 .
Here are some comparisons of how newer, emerging pathogens and their variants compare to older, Infectious Diseases.
Transmissibility Rate (R0)
B.1.617.2, SARS-CoV-2 Delta variant
B .1. 1. 7, SARS-CoV-2 Alpha Variant
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 . 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.
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.
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.
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 . 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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 R. Desbordes, “Spatial dynamics of major Infectious Diseases outbreaks: A global empirical assessment,” J. Math. Econ., vol. 93, no. 102493, p. 102493, 2021.
 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.
 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.
 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.
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 Trypanosomacruzi (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).
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.
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).
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).
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).
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
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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(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
(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
(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
(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/
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 Mycobacteriumtuberculosis, Mycobacteriumafricanum, and Mycobacteriumbovis (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).
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 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.
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).
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
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)
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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(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
(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
(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
Fungi are similar in many ways to bacteria – both have a cell nucleus and complex cell walls. Unlike bacteria, species of fungi include both single-celled organisms (yeasts) and multicellular forms (molds). Molds resemble plants and often consist of filaments, spores, root structures, etc. Fungal infections (mycoses) include candidiasis, dermatophytosis, blastomycosis, coccidioidomycosis, histoplasmosis, cryptococcosis, paracoccidioidomycosis, aspergillosis, zygomycosis, and pneumocystosis.
Candidiasis refers to infections caused by yeasts of the genus Candida. Candida is the most common cause of fungal infections worldwide; and is part of the normal flora of the mouth, GI tract, vagina, and skin. Candidiasis occurs when an imbalance in the amount of Candida in these areas results in signs and symptoms of inflammation, or when Candida colonizes parts of the body in which it is not normally present. All forms of candidiasis are more common in individuals who are immunocompromised.
Vulvovaginal candidiasis fungal infection, commonly referred to as a “yeast infection,” is estimated to affect 70-75% of women at least once during their lifetimes (1). Symptoms may include itching, burning, soreness, redness, swelling, pain during intercourse or urination, and a thick, white discharge that is usually odorless and may resemble cottage cheese. Factors that predispose to vulvovaginal candidiasis include the use of antibiotics, douches, and other vaginal products, diabetes, hormonal changes such as those seen with pregnancy and menopause, contraceptives, immune deficiency, including HIV / AIDS, and certain genetic factors. A variety of topical and systemic azole agents can be used for treatment.
Oropharyngeal candidiasis commonly referred to as “thrush,” occurs from Candida overgrowth on the lining of the mouth, tongue, gums, tonsils, and lips. The condition may cause visible white or yellow patches, soreness, an unpleasant taste, and occasionally a “cotton-like sensation.” It is much more common in infants and toddlers than in adults. Predisposing factors in adults include smoking, dentures, antibiotic and corticosteroid use, and hormonal changes. 80-90% of HIV patients will experience oropharyngeal candidiasis (2). Proper dental hygiene may help protect against oropharyngeal candidiasis. Various azole mouthwashes, gels, and lozenges can be used for treatment, as well as oral antifungal medications.
Common sites of cutaneous candidiasis include the axilla (armpit), the area under the breast, the groin region, the intergluteal cleft, and on the hands and feet. Candida is a common cause of “diaper rash.”
Invasive candidiasis (“deep candidiasis”) occurs when Candida affects the bloodstream, heart, brain, eyes, bones, or other organs. It may occur in patients that are immunocompromised, or as a result of fungal infection introduced by vascular lines, prosthetic cardiac valves, and urinary catheters. Systemic symptoms may result, including fever, chills, pain, hypotension, and neurological deficits. The condition can be fatal. One strain, in particular, Candidaauris, poses a threat in hospitals, as it is often multidrug-resistant and difficult to identify using standard laboratory methods (3).
Dermatophytosis (“tinea”) is a fungal infection of keratinized tissue, including the skin, hair, and nails. Fungal causes include Ascomycota, Euascomycetes, Onygenales: Epidermophyton, Microsporum, Trichophyton, Trichosporon spp., and Arthroderma (4). Dermatophytosis is contracted by contact with infected humans or animals, or contact with contaminated objects, flooring, or soil.
The nomenclature of these conditions derives from the body region that is affected. For example, Tinea manuum is a dermatophyte infection of the hands, while Tinea barbae is an infection of the beard or mustache. Tinea pedis affects the feet, Tinea unguium the nails, Tinea cruris the groin, Tinea corporis the trunk, Tinea capitis the scalp, and Tinea faciei the non-bearded area of the face.
Tinea corporis is commonly referred to as “ringworm.” It presents as a red, annular, scaly patch, often with central clearing. The condition is usually pruritic and is very common – especially among children. High rates are seen in Africa, India, and urban areas of the Americas (5). A common source of adult infection is through handling puppies and kittens. A wide variety of creams, ointments, gels, and sprays are available for treatment.
Tinea pedis is commonly referred to as “athlete’s foot”; and is the most common form of dermatophytosis in adults (6). The condition can cause itching, stinging, and burning of the feet – often with redness, blisters, and peeling. Tinea pedis is often acquired from wet floor surfaces such as showers, locker rooms, and pool areas. Wearing foot protection in these areas can help prevent transmission.
The same fungal species that cause Tinea pedis can also cause Tinea cruris, commonly known as “jock itch.” Tinea cruris presents as a red, pruritic, and often annular rash in the crease of the groin. The condition may spread to the upper thigh in a “half-moon” shape. The condition can be acquired by sharing contaminated towels or clothing. Both Tinea pedis and Tinea cruris usually respond well to topical antifungals.
Endemic mycoses refer to a diverse group of fungal infections found in distinct geographical regions. They can cause significant morbidity and mortality in immunocompromised individuals, and may also affect healthy people.
Blastomycosis is caused by the fungus Blastomyces. It mainly affects people living in regions of the United States and Canada surrounding the Ohio and Mississippi River valleys and the Great Lakes (7). Blastomycosis is acquired through inhalation of spores, often after participating in activities that disturb the soil. Symptoms are “flu-like” and may include fever, fatigue, muscle aches, night sweats, and cough. A chronic disease may affect the lungs, skin, bones, joints, genitourinary tract, or central nervous system. Amphotericin B is the treatment of choice.
Coccidioidomycosis (“Valley Fever”) is caused by Coccidioidesimmitis and Coccidioidesposadasii. The condition is found in the Southwestern United States and parts of Mexico and Central and South America. Like blastomycosis, coccidioidomycosis follows the inhalation of spores from the soil. Symptoms are similar to coccidioidomycosis and are flu-like. A rash on the upper body or legs is commonly encountered. Most people with coccidioidomycosis improve without treatment, but fluconazole and similar antifungals can be used (8).
Histoplasmosis, caused by Histoplasma, is acquired by inhaling spores – usually from soil containing bird- or bat-droppings. The condition is found in the Ohio and Mississippi River valleys and parts of Central and South America, Africa, Asia, and Australia (9). Histoplasmosis is also characterized by a flu-like illness and is usually self-limiting.
Cryptococcosis is caused by various species of Cryptococcus, yeasts that are found in the soil and on certain trees. Cryptococcusgattii is found in California, Oregon, Washington, Canada, Australia, Papua New Guinea, and South America (10). Cryptococcusneoformans is found in all countries. Cryptococcus is often associated with pneumonia or meningitis. The current global incidence is estimated at 1 million cases per year, with 50% mortality (11). Most of these cases occur in individuals with HIV / AIDS. Treatment consists of Amphotericin B and Flucytosine, followed by Fluconazole.
Paracoccidioidomycosis is caused by Paracoccidioides, found in parts of Central and South America (12). It can cause lesions in the mouth and throat, rash, lymphadenopathy, fever, cough, and hepatosplenomegaly. Talaromycosis, formally known as sporotrichosis, is an endemic mycosis caused by Talaromycesmarneffei and other species. The condition is found in Southeast Asia, Southern China, and Eastern India (13). Clinical manifestations include fever, cough, lymphadenopathy, hepatosplenomegaly, diarrhea, and abdominal pain.
Most people inhale mold spores every day without becoming ill, but occasionally severe disease can result. Infection by Aspergillus (aspergillosis) may present as an allergic reaction. The fungus can also cause infection of the sinuses and lungs. Formation of “fungal ball” (aspergillomas) may occur in patients with pre-existing lung diseases. Aspergillus can also infect the eyes, skin, cardiac valves, brain, gastrointestinal tract, and genitourinary tract. Treatment options include Voriconazole, Amphotericin B, and Isavuconazole (14).
Zygomycosis (“mucormycosis”) is caused by a group of molds called Mucormycetes. This fungal infection is commonly associated with hyperglycemia, metabolic (diabetic, uremic) acidosis, corticosteroid therapy, and neutropenia, transplantation, heroin injection, and administration of deferoxamine (15). Common sites of infection include the paranasal sinuses and contiguous structures, cranial nerves, cerebral arteries, lungs, and skin. Treatment may include intravenous Amphotericin B, followed by oral Posaconazole or Isavuconazole.
Other molds that can cause allergies and infections in humans include Stachybotryschartarum, Alternariaalternata, Lomentosporaprolificans, Scedosporiumapiospermum, Cladosporium, and Penicillium.
Pneumocystis pneumonia (PCP) is caused by the fungus Pneumocystisjirovecii. Until recent years, the organism had been classified as a protozoan parasite. Pneumocystis pneumonia usually occurs in individuals with severe immune suppression, including HIV / AIDS. Presenting symptoms include shortness of breath, fever, and a nonproductive cough. Extrapulmonary infection is rare but can occur. Treatment options include Sulfamethoxazole / Trimethoprim, Pentamidine, Dapsone + Trimethoprim, Atovaquone, or Primaquine + Clindamycin (16).
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(2) Patil S, Majumdar B, Sarode SC, Sarode GS, Awan KH. Oropharyngeal Candidosis in HIV-Infected Patients-An Update. Front Microbiol. 2018 May 15;9:980. doi: 10.3389/fmicb.2018.00980.
(3) “General Information about Candida auris”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2019. [Online]. Available: https://www.cdc.gov/fungal/candida-auris/candida-auris-qanda.html
(13) “Talaromycosis (formerly Penicilliosis)”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/other/talaromycosis.html
Chikungunya refers to an infection caused by the Chikungunya virus, an alphavirus of the Togaviridae family. Like its close relative, the Semliki Forest virus, the Chikungunya virus is transmitted from human to human via mosquito bites.
Chikungunya is characterized by fever, joint and muscle pain, and rash. The disease was discovered in Tanzania in 1952, and since that time has been identified in over 60 countries around the world. The word “Chikungunya” means “that which bends up” in the Makonde language, spoken by a group indigenous to Tanzania and Mozambique. It is thought that this term was coined to describe the posture of patients affected with severe disease.
Mosquito species that carry Chikungunya include Aedesaegypti in the tropics, Aedesalbopictus in the tropics and colder areas, and approximately one dozen Aedes species in Africa, including Aedesfurcifer and Aedestaylori. Transmission occurs after a mosquito bites someone infected with Chikungunya and then subsequently bites someone else. Mosquitos pick up the Chikungunya virus from human blood, the virus then replicates inside the mosquito and can be transmitted via their salvia. Once a mosquito acquires the virus, it will likely carry it for the rest of its life. There is evidence that some animals, including non-human primates, rodents, and birds, may act as reservoirs for the Chikungunya virus.
Signs and Symptoms
Signs and Symptoms of Chikungunya develop after a 2-12 day incubation period. Cases vary in severity, and asymptomatic infection may occur. The rate of asymptomatic cases is estimated to be between 4% and 28%.
Cases often begin with an abrupt onset of fever. Polyarthralgia occurs in 70% of cases, usually involving small joints. Swelling of joints may also occur, typically without fluid accumulation. In greater than 50% of cases, a maculopapular rash on the palms, soles, limbs, torso, and/or face is present. This rash may progress to desquamation. Fever generally resolves within one week, but joint pain may persist for months. Sometimes, a “saddle-back fever curve” is seen, with fever resolving and then returning. Moderate to severe lymphopenia is often noted. Thrombocytopenia, leukopenia, elevated liver enzymes, anemia, and elevated creatinine may also be observed.
Facial and neck erythema and conjunctival suffusion may be noted. Headache, photophobia, retro-orbital pain, pharyngitis, nausea, and vomiting can occur. Sometimes, pneumonia and dry cough are seen. Pruritus is common. Patients may complain of exhaustion and insomnia. Symptoms of Chikungunya can persist from one week to several months. Residual chronic joint pain may continue in some cases. Chronic disease is more common in older patients and patients with prior rheumatological disease.
Chikungunya can also cause neurological and ophthalmologic complications. Eye involvement may include retinitis, retinal detachment, optic neuritis, uveitis, dendritic lesions, and Fuchs heterocyclic iridocyclitis. Neurological manifestations can include altered mental function, encephalitis, seizures, myelopathy, Guillain-Barré syndrome, bulbar palsy, acute flaccid paralysis, focal neurological deficit, and sudden sensorineural hearing loss.
Additional rare complications of Chikungunya include hemorrhagic syndrome, cardiovascular shock, arrhythmias, myopericarditis, renal failure, rhabdomyolysis, and thrombocytopenic purpura.
Children with Chikungunya are more likely to experience neurological and dermatological symptoms, and less likely to have arthralgia. Transplacental transmission of the virus can occur and may result in neonatal encephalopathy, neonatal respiratory distress, sepsis, necrotizing enterocolitis, and cardiologic complications. Infants who become infected during the perinatal period may experience fever, rash, peripheral edema, lymphopenia, and thrombocytopenia. Congenital and perinatal infections are associated with poor neurodevelopmental outcomes. Transmission of Chikungunya via breastfeeding has not been noted.
Fatalities from Chikungunya are rare, occurring in about 1 per 1,000 cases. Fatalities are more common in newborns and individuals with multiple medical comorbidities. The use of NSAIDs prior to hospitalization is associated with an increase in disease severity. Infection with Chikungunya is likely to protect against future disease.
Diagnosis and Treatment
A diagnosis of Chikungunya should be considered in individuals living in – or having traveled to – areas with known outbreaks presenting with acute onset of fever and joint pain. Dengue fever and Zika virus infection should be considered in a differential diagnosis of Chikungunya, as they are also carried by Aedes species mosquitoes and may present with similar signs and symptoms.
PCR, serology, and viral culture can be used for laboratory confirmation of Chikungunya. Chikungunya is classified as a biosafety level-3 pathogen, and samples should be handled accordingly. Blood-borne transmission from patients to healthcare workers and laboratory personnel has been documented.
Patients with Chikungunya are treated with supportive care, including hydration and pain management. It is important to prevent mosquito bites during the first week of illness, in order to prevent additional transmission.
Between 1952 and 2013, Chikungunya virus outbreaks were identified in Africa, Asia, Europe, and the Indian and Pacific Oceans. In 2013, cases were first identified in the Americas and nations of the Caribbean, and today the majority of cases occur in these locations – where populations have no preexisting immunity.
Between 2004 and 2006, an outbreak of Chikungunya that began in Kenya resulted in 500,000 cases in countries of the Indian Ocean, including one-third of the population of La Reunion Island. This outbreak spread to India, where almost 1.5 million people were infected. Ongoing outbreaks have been occurring in Brazil since 2014, with over 300,000 cases occurring in 2016. It is thought that a mutation occurred around 2005 that enabled the virus to survive in Aedesalbopictus;and that having this additional species as a vector has fueled recent outbreaks.
Local transmission was reported for the first time in Europe in 2007, with 197 cases occurring in north-eastern Italy. The source of this outbreak was traced to a single individual who had returned from India with the infection. A second outbreak occurred in Europe in 2014, centered mainly in France and the UK and resulting in about 1500 cases.
In 2014, local transmission of the Chikungunya virus was identified in the territories of the United States for the first time, with 4,659 cases occurring between American Samoa, Puerto Rico, the U.S. Virgin Islands, and Florida. Since that time, the rate of local transmission in the United States has decreased each year, with 179 cases occurring in 2016, 8 cases in 2018, and no cases in 2020.
There is currently no vaccine to prevent Chikungunya. The CDC recommends the use of the Environmental Protection Agency (EPA)-registered insect repellents when traveling to areas with outbreaks. Wearing long sleeves and pants can also reduce transmission, as can sleeping in places with air conditioning and window and door screens. The CDC also recommends using 0.5% permethrin to treat clothing and gear to repel mosquitos.
During outbreaks, measures should be taken to control mosquito populations by reducing both natural and artificial water-filled habitats where they may breed. Any items that may hold water, such as pools, buckets, planters, and trash containers, should be regularly emptied and cleaned.
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Hospital-acquired infections, also known as “healthcare-associated infections” or “nosocomial infections,” refer to infections that were not present before seeking medical care and were acquired in a healthcare setting. Hospital-acquired infections can be contracted in hospitals, ambulatory clinics, surgical centers, nursing homes, long-term care facilities, dialysis centers, and diagnostic laboratories.
Hospital-acquired infections are defined by symptoms presenting 48-or-more hours after hospital admission, within three days of discharge, or 30 days postoperatively (1). The vast majority of hospital-acquired infections are caused by bacteria, and the propagation of these infections is worsened by the increasing presence of multi-drug resistant bacterial strains.
Prevalence of hospital-acquired infections
In the United States, approximately 1 in 25 hospitalized patients will contract an infection (2). Data collected by the Centers for Disease Control and Prevention identified an estimated 1.7 million hospital-acquired infections in the United States during 2002, resulting in 99,000 associated deaths (3).
Estimates from the UK place the prevalence of hospital-acquired infections at approximately 1-in-10 patients (1). In developing nations, the prevalence is higher and may occasionally exceed 25% (4).
CDC data show that urinary tract infections make up approximately 36% of all hospital-acquired infections in the ICU, surgical site infections 20%, pneumonias 11%, bloodstream infections 11%, and other infections 22% (3).
Immunocompromised individuals, such as those undergoing chemotherapy, are at an increased risk for hospital-acquired infection. Geriatric patients are also at increased risk, as are those with multiple medical comorbidities. The incidence of hospital-acquired infections increases as the length of hospital stay increases. Patients in the ICU, receiving mechanical ventilator support, undergoing surgery, and having indwelling devices are also at increased risk.
One large study that examined 231,459 patients across 947 hospitals in Europe found that 19.5% of patients in the ICU experienced at least one hospital-acquired infection (5).
Catheter-associated urinary tract infections are the most common forms of hospital-acquired infection. Approximately 75% of all UTIs contracted in the hospital are associated with catheter use, and the most important risk factor for developing a catheter-associated urinary tract infection is prolonged catheter use (6). Common pathogens identified in catheter-associated urinary tract infections include Escherichia coli, Enterococcus species, Staphylococcusaureus, Pseudomonasaeruginosa, Proteusmirabilis, Klebsiellapneumoniae, Morganellamorganii, and Candida albicans. Some organisms, including Pseudomonas and Proteus, can form biofilms around catheters.
Surgical Site Infections (SSI)
Surgical site infections occur postoperatively in the skin, internal organs, or implanted materials involved in the surgery. Diabetic patients are at an increased risk of developing surgical site infections. The incidence of surgical site infections increases as procedure duration increases and the use of antimicrobial prophylaxis decreases the risk of such infections. Common causes of surgical site infections include Staphylococcusaureus (including MRSA), coagulase-negative Staphylococcus, Escherichiacoli, Enterococcusfaecalis, Pseudomonasaeruginosa, Klebsiellapneumoniae, and Acinetobacterbaumannii. In developed nations, between 2-5% of all patients who undergo surgery develop a surgical site infection; and in developing nations, between 12%-39% do (4).
Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)
The Infectious Diseases Society of America (IDSA) defines hospital-acquired pneumonia as “pneumonia that occurs 48 hours or more after admission to the hospital and did not appear to be incubating at the time of admission”; and defines ventilator-associated pneumonia as “pneumonia that develops more than 48 to 72 hours after endotracheal intubation.” Common bacterial causes of both hospital-acquired pneumonia and ventilator-associated pneumonia include Staphylococcusaureus (including MRSA), Streptococcuspneumoniae, Haemophilusinfluenzae, Escherichiacoli, Pseudomonasaeruginosa, and Klebsiellapneumoniae. Common viral causes include rhinovirus, parainfluenza virus, influenza virus, respiratory syncytial virus, and coronavirus.
The incidence of ventilator-associated pneumonia in patients who require mechanical ventilation for more than 48 hours is estimated at 25-to-30% (7).
Central Line-Associated Bloodstream Infection (CLABSI)
Central line-associated bloodstream infections occur at the site of central venous catheters. The mortality rate for central line-associated bloodstream infections is between 12% and 25% (8). Common causes of central line-associated bloodstream infections include coagulase-negative Staphylococci, Staphylococcusaureus (including MRSA), Enterobacte, Klebsiellapneumoniae, and Candida albicans. Central lines can be placed in the neck, chest, arm, or groin. The use of femoral-site lines is associated with an increased risk of infection and is no longer recommended (9). Antibiotic lock therapy can reduce the incidence of central line-associated bloodstream infections.
Clostridium Difficile Infections (CDI)
An estimated 12.1% of all hospital-acquired infections are caused by Clostridiumdifficile, making Clostridiumdifficile the most common cause of hospital-acquired infections (10). Approximately 75% of all Clostridiumdifficile infections are hospital-acquired (11), and an estimated 2.3% of all US hospital costs are related to these infections (12). Click to see how you can use Gideon to explore Clostridiumdifficile.
The incidence of hospital-acquired COVID-19 remains unknown. A meta-analysis of studies examining COVID-19 cases in China found that 44% of cases were likely to have originated from a healthcare setting (13). A hospital in South Africa reported that a single case led to six major outbreak clusters in several hospital wards, a nursing home, and a dialysis unit. Ultimately this episode resulted in 135 infections and 15 deaths (14). Up to 1-in-4 cases of COVID-19 in the UK are likely to have been hospital-acquired (15).
In contrast, a recent study from the United States suggests that hospital-acquired COVID-19 is actually quite uncommon when rigorous infection-control measures are followed. This study looked at all patients admitted to Brigham and Women’s Hospital in Boston, Massachusetts, between March 7 and May 30, 2020. They determined that of 697 COVID-19 diagnoses, only two were hospital-acquired, including one case that likely resulted from a visit by a pre-symptomatic spouse (16).
The World Health Organization estimates that healthcare workers may comprise as many as one-in-seven COVID-19 cases (17), reflecting a high incidence of hospital-acquired disease. The CDC is not currently collecting data on hospital-acquired COVID-19, as hospitals are required to report to the U.S. Department of Health and Human Services.
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(1) Inweregbu, K., Dave, J. and Pittard, A., 2005. Nosocomial infections. Continuing Education in Anaesthesia Critical Care & Pain, 5(1), pp.14-17.
(2) Magill SS, Edwards JR, Bamberg W, et al., 2014. Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of healthcare-associated infections. N Engl J Med, 27;370(13), pp. 1198-208.
(3) Klevens, R., Edwards, J., Richards, C., et al., 2007. Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002. Public Health Reports, 122(2), pp.160-166.
(4) Allegranzi, B. and Pittet, D., 2007. Healthcare-Associated Infection in Developing Countries: Simple Solutions to Meet Complex Challenges. Infection Control & Hospital Epidemiology, 28(12), pp.1323-1327.
(5) European Centre for Disease Prevention and Control, 2013. Point-prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. Stockholm: EDC.
(7) Cornejo-Juárez, P., González-Oros, I., Mota-Castañeda, P., Vilar-Compte, D. and Volkow-Fernández, P., 2020. Ventilator-associated pneumonia in patients with cancer: Impact of multidrug resistant bacteria. World Journal of Critical Care Medicine, 9(3), pp.43-53.
(8) Dumont, C. and Nesselrodt, D., 2012. Preventing central line-associated bloodstream infections CLABSI. Nursing, 42(6), pp.41-46.
(11) Louh, I., Greendyke, W., Hermann, E., e al., 2017. Clostridium Difficile Infection in Acute Care Hospitals: Systematic Review and Best Practices for Prevention. Infection Control & Hospital Epidemiology, 38(4), pp.476-482.
(12) Jump, R., 2013. Clostridium difficile infection in older adults. Aging health, 9(4), pp.403-414.
(13) Zhou, Q., Gao, Y., Wang, X., et al., 2020. Nosocomial infections among patients with COVID-19, SARS and MERS: a rapid review and meta-analysis. Annals of Translational Medicine, 8(10), pp.629-629.
(14) Lessells, R., Moosa, Y. and de Oliviera, T., 2020. Report into a nosocomial outbreak of coronavirus disease 2019 (COVID‐19) at Netcare St. Augustine’s Hospital. [online] Available at: https://www.krisp.org.za/manuscripts/.
In the early days of the outbreak, the novel coronavirus (COVID-19) was repeatedly compared to the flu (influenza) and even to the common cold (rhinoviruses, et al). This was due to an initial impression of shared symptoms.
The differences between these conditions are particularly important as we kick off National Influenza Vaccination Week (NIVW) and the ‘flu season’. So, how can we tell which of these diseases we are dealing with in a given patient?
Let’s start with the common cold, a condition that can be caused by over 200 different strains of viruses. On average, an adult will contract a cold two to three times yearly – making the total number of cases incalculable. Symptoms are almost always mild and may include a runny nose, fatigue, chills, coughing, sneezing, sore throat, and a headache. Children – but not adults – often experience a low-grade fever.
Most cases clear without medication in less than one week, although the cough can persist for up to 18 days. Bottom line: symptoms are mild. Your normal activity may diminish, and you might even spend a few days in bed, but you should not feel short of breath or unable to complete basic tasks.
Influenza (flu) was once one of the most feared diseases, worldwide – and was responsible for the largest and most deadly outbreak in the 20th century (the ‘Spanish flu’), In more recent years, the disease is largely manageable, thanks to advancements in medicine and technology. Billions of doses of influenza vaccine may be administered in a given year, and several effective antiviral drugs are widely available. Nevertheless, the disease is still responsible for hundreds of thousands of deaths every year.
Influenza symptoms are similar to those of the common cold (fatigue, chills, coughing, etc) but much more acute, typically with high fever and pain in the back and muscles. Fatigue and even exhaustion may follow and pain medication is often required. The symptoms may persist for a few days to over a week.
Occasionally, influenza may be complicated by pneumonia due to bacteria, or to the influenza virus itself. A fatal outcome may ensue, particularly in the elderly or in patients with underlying chronic conditions.
COVID-19 has evolved into the iconic disease of the 21st century, with tens of millions of cases reported worldwide in a period of only 10 months. The media inundate us all with a seemingly endless list of potential symptoms, signs, and complicating conditions, so here are some more common signs and symptoms which might differentiate the latest coronavirus from other respiratory diseases.
In most cases, the illness will begin as if you do have a cold or the flu, with coughing, fever, and fatigue. A common early symptom is the loss of the senses of smell or taste, which has been reported in the majority of cases in many reports. After a few days, you may feel short of breath and experience pain in the muscles. At this point, you should have already contacted your local doctor or clinic. Even if symptoms are relatively mild, you must seek medical attention if you are over the age of 65 or have a history of high blood pressure, diabetes, heart or lung disease, cancer, or other ongoing illness.
Thankfully, effective and accurate tests for COVID-19 are widely available, and there is no need to “self-diagnose.” A variety of drugs are already in use for the disease, and several promising vaccines are due to be released in the coming weeks.
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