In 2009, a 70-year-old woman in Tokyo, Japan was hospitalized with an ear infection that did not seem to improve with antibiotics . The doctors found a fungus when they swabbed her ear and identified a new species of yeast, Candida auris. The first strain of the yeast was actually discovered in South Korea in 1996 but was not named until 2009 . Little did epidemiologists know at the time just how devastating the yeast would become in healthcare settings. No one knew where it came from or how to prevent its spread . Dr. Tom Chiller, chief of mycotic diseases at the United States Center for Disease Control and Prevention (CDC), says it is the most difficult pathogen they have seen - as it is more infectious and more difficult to kill than even the Ebola virus . Due to the increasing number of infections identified around the world, the CDC now calls Candida auris an emerging fungal pathogen that has become a global health threat .
Yeasts are fungi that are naturally found in the environment, usually inhabiting warm and damp environments . Yeasts normally only infect the people they inhabit. However, C. auris developed the ability to survive on cool external skin and object surfaces. This allows it to act like nosocomial bacteria, contaminating hospital surfaces and tools, spreading easily between humans and becoming increasingly difficult to eradicate even in hospitals with extensive infection control methods . C. auris is an ascomycetous fungus, growing as a yeast, forming smooth, pale grey viscous colonies on its host . But in the case of C. auris, it behaves like a bacterium, has the ability to adapt to its environment, spreads like a bacterium and resists antifungal drugs. In these ways, it appears to be a cross-species shift .
C. auris is the most invasive of the Candida species, causing the most severe fungal infections currently in existence . It causes bloodstream infections, wound infections, and ear infections. It has been isolated in respiratory and urine samples, but it is unclear if it causes infections in the lung or bladder . C. auris can infect the bloodstream and lead to fungemia, capable of spreading throughout the body and damaging the central nervous system and internal organs, which can lead to organ failure, coma and death . In 30-40% of C. auris cases, the infections have been fatal. Case fatality appears to be dependent on the previous health condition of the patient . Symptoms of C. auris infection include fever and chills, sepsis, coma, organ failure, and lack of response or improvement following antifungal treatment .
A different Candida species, Candida albicans, is the most frequently isolated Candida species in clinical settings, but differs from C. auris in several ways . C. albicans, a common yeast that lives in the gut without causing harm, has mild symptoms compared to C. auris, and cannot be transmitted between people. Although overgrowth can cause digestive problems, skin conditions, hormonal disruption and vaginal thrush, this can all be treated with a variety of antifungal medicines or with a special diet. C. auris became more easily identified recently as it grew more resistant to antifungal drugs compared to its counterpart C. albicans.
Since the first identified C. auris infection in Japan in 2009, more patients across the world have developed the same infection, equally resistant to antifungals; the yeast spread around the world with no connection between any of the patients . The CDC performed whole genome sequencing of C. auris to provide detailed DNA of strains from eastern Asia, southern Asia, southern Africa and South America . These strains were found to be genetically similar within regions, but different across continents. This suggests the yeast did not spread by transmission but that it evolved independently in multiple areas across the world at about the same time. C. auris has now become a global threat because it has spread to 27 countries . This worldwide spread of resistant C. auris is due to increased resistance toward antifungal drugs, explained by the widespread over-prescription of antifungal medication. Microbes, including yeasts, can adapt in ways that allow them to become resistant, and those that become stronger and resistant have the opportunity to survive, reproduce, and spread .
Individuals at Risk:
It is very unlikely that routine travel to countries with previous C. auris infections would increase someone’s chance of getting infected, unless they were seeking medical care or foreign hospitalization . Infections of this yeast occur primarily in patients who are hospitalized or who are immunocompromised. In fact, most infected patients, and all those who died from C. auris infection, had been previously hospitalized for another illness . Those most at risk for C. auris infections are patients who have been hospitalized for a long time and are immunocompromised, regardless of age . Those with central venous catheters or other lines or tubes entering the body, such as breathing, feeding tubes or intravenous fluids are particularly susceptible. Other risk factors for infection include patients with recent surgeries, transplants, or with diabetes or cancer , those living in nursing homes and previous use of antibiotics or antifungal medications .
Despite the threat of C. auris, only a limited population - those hospitalized or in nursing homes - is at risk of infection, and those patients should be getting the costliest protection . However, facilities may not be able to hire adequate health workers or enforce infection-protection procedures, making it difficult to detect C. auris in patients before the yeast enters their facility.
Medication & Treatment: 
When patients are diagnosed with C. auris infections, they are provided with fast-acting antifungal medication and must be closely monitored with treatment because of the yeast’s ability to be highly resistant to medication and develop resistance quickly . Patients must also be monitored because the yeast can live on skin after treatment, requiring continued protective hygiene practices.
According to the CDC, 90% of global C. auris infections are resistant to azoles, 30% are resistant to amphotericin, and up to 20% are resistant to last-option echinocandins . Fungal infections are not a high priority in medical research, so few drugs have been created or approved to treat them. As mentioned, there exist only three drug classes for antifungals, with a few drugs each, compared to a dozen classes and hundreds of antibiotics for bacteria. In cases of C. auris infection, the CDC recommends combination treatments with three antifungals: anidulafungin, caspofungin and micafungin , and in some cases, the yeast is already resistant to all three . Azoles are the first-choice antifungal treatment, with amphotericin as the backup option, administered only intravenously. Unfortunately, amphotericin is so toxic – causing severe fever and chill reactions – that use is avoided if possible . The last class of intravenous antifungal drugs available to use against C. auris is echinocandins. Echinocandins include caspofungin (Merck’s Cancidas), anidulafungin (Pfizer’s Eraxis) or micafungin (Astellas’ Mycamine), if those do not work, toxic amphotericin B is used .
Patients with C. auris infections are often already very ill, making it difficult to distinguish their symptoms from other medical conditions . C. auris infections, like other Candida infections, are usually diagnosed by blood or body fluid cultures . But C. auris is harder to identify because it can be confused with other types of yeasts. Studies have shown that among patients who carried the yeast, more than 80% were misidentified at first, presumed to have another type of yeast . Recently, the CDC published a guide for laboratories, explaining the mistakes made by seven different testing methods for identifying the yeast. To identify C. auris, a special lab test called matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) is used . However, it takes several days to test for C. auris with special equipment, and in that time it can easily spread to others .
Considering how highly resistant C. auris is, hospitals will have to turn to high standards of hygiene to avoid spread of the yeast . Simple solutions such as cleanliness may be the most effective and practical, including wearing gloves and gowns and washing hands . However, good hygiene may be harder to enforce in hospital facilities with large staff, especially compared to the ease of treating infections with medication. Unfortunately, even the best hygiene practices may not be enough. An outbreak of the C. auris in a London hospital in 2015 serves as an example of just how pervasive the yeast can be . The hospital identified cases of infection and took all necessary precautions; these included wearing gloves and gowns, patient isolation, swabbing those in contact or in the same room as the patient, bathing the patient twice a day with disinfectant including mouthwash and dental gel, washing the patient’s room three times a day with diluted bleach, and after patient discharge, using a bomb with hydrogen peroxide vapor to sanitize the room and equipment. Despite all precautions taken, the yeast still persevered. Some of the last defenses to use against C. auris include patient isolation and use of chlorine bleach to kill C. auris. Evidence suggests quaternary ammonium cleanser commonly used in hospital disinfectants does not work . Other protective steps include using disinfectant effective against Clostridium difficile spores – the strongest available disinfectant. The most important steps to prevention include protecting those most vulnerable to infection – specifically those who are immunocompromised or who have tubes entering the body – and limiting over-prescription of antibiotics and antifungals to patients because they weaken the immune system and lead to resistance .
Despite the possible hygiene and prevention strategies to use against the yeast, C. auris still poses a great challenge for the future of healthcare facilities. The CDC is highly concerned with three aspects of the yeast . First, that C. auris is resistant to multiple antifungals classes commonly used to treat Candida infections. Second, that it is difficult to identify C. auris with standard lab methods and that it can easily be misidentified without very specific lab technology, leading to inappropriate management of infections. And finally, that it causes outbreaks in healthcare settings where it is extremely important to correctly identify the yeast to take special precautions against it .
On 11 September 2018, HealthMap noted a news- media report of a mystery disease in Kanchanrup Municipality of Saptari in Nepal. The original report specified 3 deaths and 400 affected, presenting with high fever, cough, joint pain, headache, and muscle cramps within the last 15 days of the report. More information on the source of illness, other symptoms, confirmation of case count, and disease identification were sought through the EpiCore system’s Request for Information (RFI). HealthMap is a partner organization of EpiCore, a virtual community of health professionals using innovative surveillance methods to verify outbreaks of infectious diseases. When information on possible, rumored, or yet-to-be-confirmed outbreaks is brought into the HealthMap surveillance system, our data analysts have the option of sending an RFI, requesting more information from EpiCore members on the ground, and therefore speeding the time to outbreak detection and confirmation.
A response to the Epicore RFI was received on 12 September 2018. The response confirmed the initial news- media report of 3 deaths and more than 400 affected. The response further indicated that samples were collected by a team at the Epidemiology and Disease Control Division (EDCD). The EDCD suspected the illness to be Scrub Typhus or Influenza. A second response to the RFI was received on 13 September 2018, which further verified the outbreak via national daily newspapers. A third response further confirmed the EDCD’s suspicion of an influenza outbreak. The response indicated that swine flu (H1N1) and Hong Kong flu (H3N2) had been reported. Additional reports indicated 10 reports of Hong Kong flu and a report of swine flu from 24 samples sent to Kathmandu. As of 15 September 2018, the number of deaths total from the outbreak had risen to 5. Case management, prevention awareness, and treatment are ongoing. The Kanchanrup Municipality has declared the area a ‘disaster- hit’ zone and has also encouraged all to “remain alert and conscious” with regard to the outbreak of these diseases.
This public health event was confirmed, thanks to contributions by EpiCore members and simultaneously confirmed via news-media reports. The HealthMap team will continue to post about public health events that have been verified via the EpiCore platform, so please follow along here on Disease Daily.
On 5 September 2018, HealthMap noted multiple news-media reports and twitter posts of sick passengers on an Emirates flight, which had landed at John F. Kennedy airport in New York and originated from Dubai. Original reports specified 100 sick passengers, presenting with fever and cough. The plane was being quarantined while awaiting CDC. More information on source of illness, other symptoms, confirmation of case count, and possible exposures were sought through the EpiCore system's Request For Information (RFI). HealthMap is a partner organization of EpiCore, a virtual community of health professionals using innovative surveillance methods to verify outbreaks of infectious diseases. When information on possible, rumored, or yet-to-be-confirmed outbreaks is brought into the HealthMap surveillance system, our data analysts have the option of sending an RFI, requesting more information from EpiCore members on the ground, and therefore speeding the time to outbreak detection and confirmation.
As a response to the EpiCore RFI sent at 10:32AM EST, almost immediate follow-up was received from an EpiCore member indicating that three passengers were taken to the hospital reporting "burning of the throats" and confirmed that CDC involvement and testing would ensue. Following the receipt of the first confirmation of the public health event via the RFI, other news-media reports began to indicate that the number of cases on the flight was now reported to be 10. A second response to the RFI was received on the EpiCore platform on 6 September 2018, indicating that three passengers and seven Emirates crew members had been taken to the hospital. The RFI response also indicated that test results initially confirmed H3 strain influenza virus(es). Also on 6 September 2018, news-media sources reported "A majority of the tests showed common viruses such as influenza and the common cold...The Centers for Disease Control and Prevention said in a statement that the patients are being treated by the hospital, including receiving antivirals. Other passengers who develop symptoms should call their doctor." The press secretary for NYC mayor tweeted: "All the passengers are off and have been evaluated. 19 sick. 10 to hospital and 9 refused medical attention."
This public health event was confirmed, thanks to contributions by EpiCore members and simultaneously confirmed via news-media reports and Twitter posts. The HealthMap team will continue to post about public health events that have been verified via the EpiCore platform, so please follow along here on Disease Daily. These confirmed influenza cases are also a friendly reminder to get your flu shot and to stay home if you are feeling ill.
Since the 2014 West African Ebola outbreak that claimed more than 11,000 lives, the mere mention of Ebola hemorrhagic fever is enough to send the public health world into a frenzy. The thought of another outbreak is alarming enough, but an actual confirmed epidemic calls for immediate action. Since May 2018, there have been two confirmed outbreaks of Ebola in the Democratic Republic of the Congo (DRC). The first occurred in the northwest region of the country, with 54 cases and was declared over on July 24, 2018 (1). Relief swept through the health community, but this was short-lived because on August 1, 2018, a new Ebola outbreak was confirmed by the World Health Organization (WHO), in the northeast region of the country (2). More than a month into this current epidemic, the number of cases has surpassed the previous outbreak, with no definite end in sight.
As of September 11th, 2018, nine cities have reported cases of Ebola, including Masereka, Kalunguta, Beni, Butembo, Goma, Oicha, Mabalako and Musienene in North Kivu, and Mandima in Ituri. There have been 102 confirmed cases of Ebola in the North Kivu and Ituri provinces along the Ugandan border, 61 of which have died from the infectious disease (3). Simultaneously, there are 31 probable cases and 19 suspected cases, of which 31 have died (3). Promisingly, there have been 37 cases of Ebola that have been cured (3). Most Ebola cases have been reported in Mabalako, where there have been 66 confirmed cases and 43 confirmed deaths (3).
Despite advances in the development of a vaccine for the treatment of Ebola, this particular outbreak has a unique challenge. Physicians and public health workers during this outbreak face red zones around the city of Oicha and the Ituri province, making infiltration dangerous. A red zone is a region deemed unsafe to travel by the United Nations, with a high risk of attack and the recommendation that people should not enter the area under any circumstance. Both Oicha and Ituri are active militant zones. However, with this outbreak, there is no choice but to risk safety in order to deliver life-saving care and begin work on tracking the disease. For protection, World Health Organization workers require an armed escort through these to deliver vaccines and prepare outposts for controlling the epidemic (4). The UN peacekeeping force, which has around 20,000 personnel in the DRC has provided critical support in allowing medical teams to reach these regions (5).
On September 3, 2018, the World Health Organization (WHO) reported a single confirmed case of Middle East Respiratory Syndrome coronavirus (MERS Co-V or MERS) in a male resident who had recently traveled to Saudi Arabia (1). He sought medical care at a hospital in Leeds, where he was put into isolation and was transferred to the care of infectious disease specialists in Liverpool (1). This is the fifth case of MERS in the UK, after four cases occurred in 2012 and 2013 (1).
Following this report comes a confirmed case of MERS in a South Korean man, marking the first case of MERS in South Korea since July 2015 (2). He was reportedly in Saudi Arabia from August 16 to September 6, 2018 and was hospitalized immediately after his return and was a confirmed case of MERS by September 8, 2018 (3). A total of 20 contacts, including flight crews and medical staff have been placed under isolation in their homes until it can be confirmed whether they have contracted MERS from the patient (3).
Clinical presentation of MERS includes fever, cough, shortness of breath, acute upper respiratory illness and rapidly progressive pneumonitis, respiratory failure, septic shock and multi-organ failure (4, 5). Some cases of MERS have gastrointestinal symptoms, including nausea and diarrhea (4). Approximately 30-40% of MERS cases result in death, though most deaths also had underlying medical issues (4). There is no specific treatment for MERS, rather treatment focuses on alleviating symptoms, so it is critical to seek medical care if any symptoms occur (6).
With the world continually becoming more accessible through travel, public health officials need to be ready for anything. Important events, which result in mass gatherings, bring people from around the globe to a single location for a period of time and can be a potential risk for disease spread. Of note, the Hajj just took place in August in Mecca, Saudi Arabia and may be involved with the current MERS cases (7). Every year, the Hajj attracts two to three million people each year in the holy Muslim city. This mass increase to a singular location poses unique health risks as untreated infectious diseases can spread from one person to another as people are in close contact with one another. Once people leave, there becomes the potential for a multi-location outbreak as those journeying to the Hajj come from locations around the globe. The incubation period for MERS is 2 to 14 days, which means a person has ample opportunity to potentially expose great numbers of people to the disease before exhibiting symptoms of disease themselves (5).
The WHO reports that most cases of human-to-human transmission occur when people are in close contact with an infected person for a sustained period of time, but there is low risk of transmission if adequate prevention and control protocols are taken (1). It is expected that there will be sporadic cases reported throughout the Middle East and in other countries, as early symptoms of MERS are non-specific (1).
This week’s NTD is a condition that is produced by a bacterium belonging to the same family of microbes that cause leprosy and tuberculosis. Buruli ulcer is an infection caused by Mycobacterium ulcerans, which releases a toxin in the body causing destruction of soft tissues and skin (1). As the toxin continues to be released, ulcers form on the surface of the skin, typically on the upper and lower extremities, and can become serious enough to cause long-term disability (1).
Initial signs of disease include the formation of nodules and painless swelling of the legs, arms and face (1). Within four weeks of infection, if untreated, the classic ulcers associated with the disease will form (1). The ulcers can extend down to the level of the bone, causing severe disability and typically do not take a specific shape—they can be rugged and asymmetrical or more rounded depending on the individual infection. There are three categories of ulcer formation: category I, being a single small lesion making up 32% of cases; category II, having non-ulcerative and ulcerative plaque formation making up 35% of cases; and, category III, extending into bones and joints making up 33% of cases (1). For 80% of category I infections, a course of antibiotic medications is required. However, as severity of infection increases there is an increased risk of needing surgery to remove dead tissue and to correct deformities caused by the ulcers (2, 3).
Buruli ulcer is found in at least 33 countries globally, located primarily in countries surrounding the equator in Africa (4). Côte d’Ivoire, Democratic Republic of the Congo and Ghana report the most cases each year, with more than 1,000 reported cases a year, however, in recent years, Australia has reported an increasingly larger number of cases (4). In May 2018, health officials from Victoria, Australia reported an increase in Buruli ulcer infections since 2015, but there is no certain cause for this increase (5). In 2017, there were 275 reported cases in Victoria, compared to 182 cases in 2016 (5). In 2018, there were 28 cases as of May 4, as compared to 31 cases at the same time in 2017 (5). Everyone is susceptible to infection, however, those in endemic regions are at a higher risk of contracting the bacteria (5). Furthermore, the age of infection varies across all affected regions. In Australia, 10% of all cases are in children under the age of 15, whereas in Africa, 48% of cases are under the age of 15 (4). Of the 33 countries that have reported cases of Buruli ulcers, only 15 report statistics to the World Health Organization (WHO) (2). Between 2002 and 2015, there were over 55,000 cases identified among the reporting countries (2).
A key reason it is difficult to control Buruli ulcer is because the transmission of disease is still unknown (6). It is not believed to be contagious and there is no proven link between humans and animals with the bacterium, though it hypothesized that insects in water may transmit the bacteria to humans (6). Horses, dogs, alpacas, koalas and opossums are all known to carry the bacteria based on laboratory tests conducted in Victoria, Australia (6). Without knowing how people get infected, it is very difficult to prevent infection, so most work focuses on identifying and treating the disease instead.
The current WHO strategy for the control and research of Buruli ulcer is “to minimize the morbidity, disability and socio-economic burden” by focusing on early detection and antibiotic treatments (7). Four key activities are used in this plan: community-level, including early case detection and community education; strengthening of the health system; standardized case management, including standardized laboratory confirmation, antibiotic regimen and wound care; and supportive activities, including advocacy, research and monitoring the control activities (7).
Buruli ulcer is a notable member of the neglected tropical disease family. Its stomach-churning lesions and painful swelling are only amplified due to the lack of knowledge surrounding its transmission and need for high doses of antibiotics. The next step is critical: researching the disease more in order to understand its mode of transmission. Without this knowledge, there is no way to effectively prevent disease, and work towards its elimination.
Summer is the time of year when public health messaging reminds us of foodborne infections from bacteria like Salmonella, E.coli and Listeria. While these are some of the most widespread foodborne infections, particularly in the United States, it is critical to remember there are many more species beyond the bacteria that cause illness in our food and water supply. Amongst them is a class of neglected tropical diseases known as foodborne trematode infections. Foodborne trematodiasis is group of NTDs that includes four infections: clonorchiasis, opisthorchiasis, fascioliasis and paragonimiasis—all of which are parasitic flatworms, or flukes, which cause severe disease globally.
The first two in the group, clonorchiasis, caused by the parasitic worm Clonorchis sinensis, and opisthorchiasis, caused by two different flukes, Opisthorchis viverrini or O. felineus, cause disease through the consumption of fish (1). The natural final hosts of infection for clonorchiasis and opisthorchiasis are dogs and cats, respectively, as well as other fish-eating carnivores (1). Fascioliasis, caused by Fasciola hepatica and F. gigantica, is acquired through the consumption of aquatic vegetables, making sheep, cattle and other herbivores the natural final hosts of infection (1). Finally, paragonimiasis, caused by Paragonimus fluke, is contracted through the consumption of crustaceans, including crabs and crayfish (1). Cats, dogs and crustacean-eating carnivores are the natural final hosts of infection (1). It is important to note that while humans are not the natural final hosts of the four flukes, there are approximately 200,000 human infections and 7,000 human deaths per year worldwide due to the trematodes, resulting in more than two million healthy years of life lost (1).
The global impact of each disease varies. Clonorchiasis and opisthorchiasis are only found Asia, while paragonimiasis is found in Africa; fascioliasis, however, is found globally (1). While the presence of the infections is widespread, with most cases are reported in Asia and South America (1). If contracted, the prescription medications Praziquantel and Triclabendazole are available to treat foodborne trematode infections (1,2).
The lifecycle of the trematodes relies on the interrelationship of humans, animals and the environment. Larvae in freshwater enter aquatic snails as an intermediate host, where they grow and subsequently are released when they are developed enough to be free-swimming (3). As they further develop, they invade fish, crustaceans and aquatic vegetables, where they are able to be transmitted to humans or animals who eat raw or undercooked freshwater species (3). Poor waste practices, leading to infected feces entering the water as waste or fertilizers, propels the cycle of trematode infections through the interaction of humans and animals with the environment (3).
Beyond the burden of disease on humans, the economic loss in endemic regions from livestock deaths is significant. Furthering the cycle of poverty, when people’s livelihood depends on being able to raise and sell livestock, losing their commodities to parasitic disease threatens their financial survival and pushes them further into poverty. Therefore, control and prevention methods utilize an approach focusing on the relationship between humans, animals and the environment. Education on proper food preparation is a critical piece for preventing transmission to humans because raw and undercooked meats are a main mechanism of transmission of the parasites. Identifying clean water sources and making hygienic food storage practices accessible help address the human and animal components of foodborne trematode infections. Current practices focus on the treatment and prevention of disease in animals and humans, with the hope that in the future, once hygienic practices are established, the control and prevention of trematodes in the environment can be addressed.
To further our NTD discussion from last week, this week we will be discussing soil-transmitted helminthiases. These are intestinal infections caused by parasitic worms, which includes Ascariasis, Hookworm and Whipworm. Together, the three infections are classified as neglected tropical diseases due to the crippling disability they can cause despite being able to be controlled or eliminated (1). Globally, there are approximately 807-1,121 million Ascaris infections, 604-795 million living with whipworm infections and 576-740 million living with hookworm infections (1).
Ascariasis and whipworm infections are often transmitted to humans through the use of animal fertilizers, or when people touch contaminated soils and then touch their mouth or eat vegetables without properly washing them first (2). When infected, the parasites survive in the intestines and lay eggs that are released through feces (2). Ascariasis infections, caused by the Ascaris lumbricoides worm, can potentially cause intestinal blockage or impair growth (2). Often, those infected with the worms show no symptoms or have a minor cough as the worm and its larvae moves through the body (2). Whipworm infections, caused by the Trichuris trichiura worm, often have no signs or symptoms, however, severe infections can cause painful passage of stool, that can be a combination of mucus, water and blood, or severe diarrhea (3).
Hookworm infections are caused by two species of worms: Ancylostoma duodenale and Necator americanus. Compared to ascariasis and whipworm, there is a slightly different mode of transmission. Soil contamination is similar, as hookworm is passed through feces that typically are used for fertilizer, but rather than accidental consumption of the parasite, hookworm eggs can also penetrate the skin of humans, especially when walking barefoot (4). Rash at the site of exposure and itching are the common symptoms of hookworm, but severe infection can cause abdominal pain, weight loss, fatigue and anemia, which may lead to impaired cognitive function and physical growth in children (4).
When diagnosed, any of the helminth infections are treatable through anthelminthic medication, including albendazole and mebendazole (5). However, since many infections do not present with symptoms initially, the worms can reproduce causing more severe infections and increased risk of disease spread before people realize that there is an issue. To combat this, public health organizations are working towards controlling and eliminating soil-transmitted helminthiases through mass drug administration campaigns. Since risk groups for these infections are able to be identified, and the medications used to treat infections are safe to use and relatively inexpensive, public health officials are able to offer preventative treatment to the entire group of people who may have been exposed to the parasite. These treatment campaigns are conducted in populations at risk, regardless of whether or not they have an active infection (4). This allows for controlling the spread of the parasite as those who have undiagnosed infections receive medications that can prevent them from contaminating soil sources.
Soil-transmitted helminthiases are circulating at huge rates globally, with approximately two billion infections a year between the three types of helminths. In order to effectively control and eliminate these neglected tropical diseases, dedicated efforts for mass drug administrations, which requires substantial man power, education and medication access, must be available to make sure at-risk groups are properly targeted.
On July 10th, 2018, the U.S. Food and Drug Administration (FDA) reinforced the warning of drug safety information by making changes to the safety labels for fluoroquinolones . Fluoroquinolones are a class of antibiotics approved for the treatment or prevention of certain bacterial infections, and are used in animal husbandry. This class of antimicrobials include gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin, and ciprofloxacin, the latter of which is one of the most widely used antibiotics across the world. Fluoroquinolones are the only class of antibiotics for clinical used which directly inhibit bacterial DNA synthesis . The most commonly reported side effects associated with fluoroquinolones includes rash, hypoglycemia, hyperglycemia, and effects on tendons, gastrointestinal tract, and central nervous system . The most frequent adverse effect involves gastrointestinal toxicity, followed by adverse effects involving the central nervous system .
The FDA prioritized updating safety labels for fluoroquinolones because use of the drug may result in a significant decrease of blood glucose or even mental health side effects. According to FDA Drug Safety Communication, the drug labels should become consistent across the entire class of fluoroquinolones, both taken by mouth and given intravenously .
The changes to the safety labels required by FDA are based on a comprehensive review of the FDA’s adverse event reporting system (FAERS) and case reports published in medical literature, specifically including life-threatening low blood sugar side effects and reports of additional mental health side effects . Blood sugar disturbance is already existing in the current drug label; however, the FDA states that low blood sugar level, or hypoglycemia, may lead to hypoglycemic coma, a serious side effect which needs to be added to boxed warnings. Patients who take hypoglycemic agents to reduce their blood glucose level are more likely to be at risk of a hypoglycemic coma when taking fluoroquinolones. Additionally, mental health side effects will be more clearly differentiated from other central nervous system side effects, and will be labeled more consistently. Previous labels only differed by individual drug. The mental health side effects from fluoroquinolone include disturbances in attention, disorientation, agitation, nervousness, memory impairment, and a severe disturbance called delirium .
The FDA has issued several changes regarding the drug safety of fluoroquinolones since 2008. In July 2008, the FDA added the boxed warning of increased risk of tendon damage . In 2011, the risk of worsening symptoms was indicated for the patients with myasthenia gravis, and in 2013, a label change was required to better describe the potential risk of peripheral neuropathy . The warning was enhanced by the FDA in 2016, when patients with conditions of acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections, were advised against being prescribed fluoroquinolones by healthcare providers because it was determined that the risk outweighs the benefits of use .
To ensure safety, the FDA advises patients to disclose to healthcare professionals if they are taking medication to treat diabetes, particularly when the providers are considering to prescribe fluoroquinolones. Patients are also advised to let their providers know if they suspect they have symptoms of low blood sugar. Additionally, healthcare professionals should be aware of the potential risk of hypoglycemia and hypoglycemic coma, and offer patients a Medication Guide with each time of fluoroquinolone prescription. If a patient reports serious adverse effects relating to their tendons, muscles, joints or nerves issue, healthcare providers should stop fluoroquinolone treatment immediately and consider other available antibiotic options .
As we continue to dive into the world of neglected tropical diseases, we find ourselves examining schistosomiasis, a parasitic disease whose impact reaches 200 million people globally and is second only to malaria as the most devastating parasite affecting humans (1). The parasitic Schistosoma worm is found in freshwater when infected individuals urinate or defecate into the water, releasing eggs into the water source (2). After the eggs hatch, the parasites find freshwater snails, in which they can develop (2). As it matures, the parasite leaves the snail and enters the water, where it can survive up for to 48 hours. During this time, the larvae penetrates the skin of people who are swimming, bathing or consuming the water (2). When in the body, the parasite reaches full maturity, where it lives in the blood vessels of the body and produces eggs, allowing the life cycle of the Schistosoma worm to continue (2).
There are six species of parasitic worms that cause human schistosomiasis globally: Schistosoma mansoni, found throughout Africa, South America and some areas of the Caribbean; S. haematobium, found throughout Africa and the Middle East; S. japonicum, found in Indonesia, China and Southeast Asia; S. mekongi, found in Cambodia and Laos; and, the related S. intercalatum and S. guineensis, which are both found in rain forest areas of Central and West Africa (3, 4). S. mansoni, S. japonicum, S. mekongi, S. intercalatum and S. guineensis cause intestinal schistosomiasis and S. haematobium causes urogenital schistosomiasis (4).
The first symptoms of infection are not caused by the worms themselves, rather, they are from the body’s reaction to the worm egg’s presence (5). The eggs are laid in the intestines and bladder, and if they do not pass through the digestive system, they can cause inflammation and scarring (5). Furthermore, they can cause malnutrition and permanent damage to the liver, intestines, spleen, lungs and bladder (5). Typical symptoms of disease include rash, fever, chills, cough and muscle aches, whereas chronic disease can lead to abdominal pain, enlarged organs and blood in the stool or urine (5). The most common symptom of infection is blood in the urine (5). Additionally, urogenital infection caused by S. haematobium worms is considered to be a risk factor for HIV, especially in women (4). Furthermore, infection can lead to an increased risk of bladder cancer. In rare cases, eggs can be found in the brain and spinal cord, where they can cause seizures, paralysis and death due to disease complications (5). Approximately 200,000-300,000 deaths a year are attributed to schistosomiasis infections (2, 4).
Treatment of schistosomiasis includes a short course of a medicine called praziquantel, that kills adult worms (6). However, this medicine is only effective in killing worms in the adult stage, so any eggs or worms that are still developing are unaffected and require repeated treatment (7). Furthermore, in some regions, praziquantel is not available or has very limited supply so if an outbreak occurs, the area has to rely on the World Health Organization (WHO) to be able to supply medication (4). Current strategies include research on the worms and the snails that host them to understand the lifecycle further, in order to be able to develop better treatments and potentially a vaccine to prevent disease.
With climate change, rising water temperatures and increased travel, especially through ecotourism, the fear now is that the worms can potentially make their way to water sources in Europe and North America (8). This would put more of the world’s population at risk as more freshwater sources become contaminated. Without having a way to ensure zero transmission will occur, it is imperative for individuals to minimize their risk of contraction through avoiding swimming in freshwater sources where schistosomiasis is endemic, boiling water before showers, drinking safe water and seek medical testing if potentially exposed (9).
Considering the global impact of schistosomiasis, as a society, we need to improve efforts to ensure those less fortunate have basic needs met. The burden of schistosomiasis could be drastically reduced simply by making sure that every person has safe and clean water for consuming and bathing. This is something that many take for granted every day, yet for 2.5 billion people worldwide, clean water and sanitation is not assessible. Without clean water, schistosomiasis is just one of many disparities faced by this population. However, preventing this parasitic disease could make a huge and invaluable global impact.