Cryptosporidiosis, a leading cause of diarrhea among infants, is caused by apicomplexan parasites classified in the genus Cryptosporidium. The lack of effective drugs is motivating research to develop alternative treatments. With this aim, the impact of probiotics on the course of cryptosporidiosis was investigated.
The native intestinal microbiota of specific pathogen-free immunosuppressed mice was initially depleted with orally administered antibiotics. A commercially available probiotic product intended for human consumption was subsequently added to the drinking water. Mice were infected with Cryptosporidium parvumoocysts.
On average, mice treated with the probiotic product developed more severe infections. The probiotics significantly altered the fecal microbiota, but no direct association between ingestion of probiotic bacteria and their abundance in fecal microbiota was observed. These results suggest that probiotics indirectly altered the intestinal microenvironment or the intestinal epithelium in a way that favored proliferation of C. parvum.
Probiotic product enhances susceptibility of mice to cryptosporidiosis
Applied and Environmental Microbiology, 10.1128/AEM.01408-18
According to The Canberra Times, the current drought affecting parts of Australia could lead to a spike in gastro cases around the country, a population health scientist from The Australian National University has warned.
The warning comes from the results of a study, published in the Journal of Water and Health, found reported cases of cryptosporidiosis, rose significantly in parts of Queensland and the Australian Capital Territory along the Murray Darling Basin during the drought that ended in 2009.
Lead researcher Dr Aparna Lal, from the ANU Research School of Population Health, said the study estimated the risk of the gastro bug dropped by 84 per cent in the ACT and by 57 per cent in Queensland once the drought ended.
She said 385 cases of the gastro bug were reported in the ACT and 527 in Queensland, out of 2048 cases in the Murray Darling Drainage Basin, from 2001 until 2012.
“Cryptosporidiosis is one of the most common water-related parasitic diseases in the world, and Australia reports the second highest rate of the illness in humans among many developed countries,” Dr Lal said.
Children under five years old are particularly at risk from cryptosporidiosis, and it can cause developmental problems such as stunted growth.
Dr Lal said droughts reduced river volume and flow, thereby potentially increasing the concentration of pathogens such as those that cause gastro.
“As these gastro bugs can also be spread from livestock, land-use change may also contribute to this pattern, due in part to access around waterways,” she said.
Crypto, which commonly refers to both the parasite and the diarrheal disease that it causes, cryptosporidiosis, infects humans and animals. It is a serious problem in developing countries, where it is a leading cause of life-threatening diarrhea in children under two. Now cases reported in the U.S. are increasing.
Swallowing one mouthful of crypto-contaminated water can cause illness. While most people recover after a few weeks of significant gastrointestinal upset, young children, the elderly, and the immunosuppressed can face chronic infection, wasting, cognitive impairment, and even death.
No vaccine exists, and the sole FDA-approved drug for crypto is, paradoxically, ineffective in people with weakened immune systems.
A major roadblock to developing drugs is the fact that crypto oocysts—the infectious form of the parasite that thrives in the small intestine—are impossible to cultivate under laboratory conditions, explained Saul Tzipori, distinguished professor of microbiology and infectious diseases at Cummings School, who has made the study of crypto and other intestinal diseases his life’s work.
To produce oocysts for scientific investigation, crypto must therefore be grown in host animals. The process is expensive, time-consuming, and cumbersome.
“To evaluate and optimize prototype vaccines and test them in humans we need to use the same source, age, viability, quality, and quantity of oocysts. This is impossible with available methods, which necessarily involve variation,” said Tzipori, who is also the Agnes Varis Chair in Science and Society and chair of the Department of Infectious Disease and Global Health.
Now Tzipori and his team, in collaboration with researchers at Massachusetts General Hospital, have developed a way to rapidly freeze crypto oocysts, preserve their infectiousness indefinitely, and thaw them as needed for study. The researchers recently published their discovery, which was supported by the Bill & Melinda Gates Foundation, in Nature Communications.
For the past forty years, scientists have tried to keep crypto oocysts for later use by freezing them—a process called cryopreservation—using slow cooling, “but those methods didn’t yield infectious oocysts,” explained the paper’s co-first author, Justyna Jaskiewicz, a veterinarian who is pursuing a Ph.D. in biomedical sciences as a member of Tzipori’s lab. The group discovered that the oocysts’ impermeable walls kept out cryoprotective agents—chemicals that are typically used to prevent formation of harmful ice crystals by replacing intracellular water. As a result, sharp ice crystals formed, which punctured and damaged the oocysts’ infectious interior.
To help tackle this problem, Tzipori’s team tapped the expertise of Massachusetts General’s Center for Engineering in Medicine, whose co-founder, Mehmet Toner, is widely known for advances in low-temperature biology and tissue stabilization.
The solution turned out to be bleaching the oocysts to make their walls permeable before soaking them in protective chemical agents.
Oocysts in solution were then loaded into cylindrical glass microcapillaries about three inches long and 200 microns in diameter—the diameter of about four human hairs—and plunged into liquid nitrogen at -196 degrees Celsius (about -320 Fahrenheit). Almost immediately, the oocyst solution morphed into a glasslike solid free of ice crystals.
“Unlike standard cryopreservation, where cells are slowly cooled, our technique vitrified the oocysts almost instantaneously. Vitrification is an ice-free method that cools cells so rapidly that crystals don’t form,” said Rebecca Sandlin, an investigator at the Center for Engineering in Medicine and co-first author on the paper.
Oocysts thawed three months later were 50 to 80 percent viable and still infectious in mice. The researchers believe such cryopreservation will last indefinitely. They hope to increase the volume of oocysts frozen and test the methodology with other strains of the parasite.
The discovery is just the latest from Tzipori’s far-ranging research on a host of globally important infectious diseases, from E. coli to dengue fever.
Tzipori believes ultrafast cooling will benefit scientists worldwide in addition to advancing his own work on crypto drug discovery and vaccine development.
“For the first time, we can produce the crypto parasite—including unique or genetically modified strains—in large quantities, without need for constant passage through animals, uniformly cryopreserved, and ship it to other investigators in liquid nitrogen that can be stored indefinitely and used at any time,” he said. “This capability has existed for other pathogens, but never for crypto.”
Cryptosporidium is a protozoan parasite that causes the diarrheal disease, cryptosporidiosis. Although many species have been identified, the majority of human disease worldwide is caused by two species; Cryptosporidium parvum and Cryptosporidium hominis.
In Australia, data from the National Notifiable Diseases Surveillance System (NNDSS) show that cryptosporidiosis outbreaks occur every few years. To better understand the transmission, trends and nature of cryptosporidiosis outbreaks in Western Australia, epidemiological and genomic data from three cryptosporidiosis outbreaks in 2003, 2007 and 2011 were reviewed.
The 2007 outbreak was the largest (n = 607) compared with the outbreaks in 2003 (n = 404) and 2011 (n = 355). All three outbreaks appeared to have occurred predominantly in the urban metropolitan area (Perth), which reported the highest number of case notifications; increases in case notifications were also observed in rural and remote areas. Children aged 0–4 years and non-Aboriginal people comprised the majority of notifications in all outbreaks. However, in the 2003 and 2007 outbreaks, a higher proportion of cases from Aboriginal people was observed in the remote areas. Molecular data were only available for the 2007 (n = 126) and 2011 (n = 42) outbreaks, with C. hominis the main species identified in both outbreaks. Subtyping at the glycoprotein 60 (gp60) locus identified subtype IbA10G2 in 46.3% and 89.5% of C. hominis isolates typed, respectively, in the 2007 and 2011 outbreaks, with the IdA15G1 subtype was identified in 33.3% of C. hominis isolates typed in the 2007 outbreak. The clustering of cases with the IdA15G1 subtype in the remote areas suggests the occurrence of a concurrent outbreak in remote areas during the 2007 outbreak, which primarily affected Aboriginal people.
Both the C. hominis IbA10G2 and IdA15G1 subtypes have been implicated in cryptosporidiosis outbreaks worldwide; its occurrence indicates that the mode of transmission in both the 2007 and 2011 outbreaks was anthroponotic. To better understand the epidemiology, sources and transmission of cryptosporidiosis in Australia, genotyping data should routinely be incorporated into national surveillance programmes.
Comparison of three cryptosporidiosis outbreaks in Western Australia: 2003, 2007 and 2011
The protozoan Cryptosporidium is a leading cause of diarrhoea morbidity and mortality in children younger than 5 years. However, the true global burden of Cryptosporidium infection in children younger than 5 years might have been underestimated in previous quantifications because it only took account of the acute effects of diarrhoea. We aimed to demonstrate whether there is a causal relation between Cryptosporidium and childhood growth and, if so, to quantify the associated additional burden.
The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2016 was a systematic and scientific effort to quantify the morbidity and mortality associated with more than 300 causes of death and disability, including diarrhoea caused by Cryptosporidium infection. We supplemented estimates on the burden of Cryptosporidium in GBD 2016 with findings from a systematic review of published and unpublished cohort studies and a meta-analysis of the effect of childhood diarrhoea caused by Cryptosporidium infection on physical growth.
In 2016, Cryptosporidium infection was the fifth leading diarrhoeal aetiology in children younger than 5 years, and acute infection caused more than 48 000 deaths (95% uncertainty interval [UI] 24 600–81 900) and more than 4·2 million disability-adjusted life-years lost (95% UI 2·2 million–7·2 million). We identified seven data sources from the scientific literature and six individual-level data sources describing the relation between Cryptosporidium and childhood growth. Each episode of diarrhoea caused by Cryptosporidium infection was associated with a decrease in height-for-age Z score (0·049, 95% CI 0·014–0·080), weight-for-age Z score (0·095, 0·055–0·134), and weight-for-height Z score (0·126, 0·057–0·194). We estimated that diarrhoea from Cryptosporidium infection caused an additional 7·85 million disability-adjusted life-years (95% UI 5·42 million–10·11 million) after we accounted for its effect on growth faltering—153% more than that estimated from acute effects alone.
Our findings show that the substantial short-term burden of diarrhoea from Cryptosporidium infection on childhood growth and wellbeing is an underestimate of the true burden. Interventions designed to prevent and effectively treat infection in children younger than 5 years will have enormous public health and social development impacts.
Morbidity, mortality, and long-term consequences associated with diarrhoea from cryptosporidium infection in children younger than 5 years: A meta-analyses study
During 2000–2014, 493 outbreaks associated with treated recreational water caused at least 27,219 cases and eight deaths. Outbreaks caused by Cryptosporidium increased 25% per year during 2000–2006; however, no significant trend occurred after 2007. The number of outbreaks caused by Legionella increased 14% per year.
The aquatics sector, public health officials, bathers, and parents of young bathers can take steps to minimize risk for outbreaks. The halting of the increase in outbreaks caused by Cryptosporidium might be attributable to Healthy and Safe Swimming Week campaigns.
Outbreaks associated with treated recreational water — United States, 2000–2014
Centers for Disease Control and Prevention
Michele C. Hlavsa, MPH; Bryanna L. Cikesh, MPH; Virginia A. Roberts, MSPH; Amy M. Kahler, MS; Marissa Vigar, MPH; Elizabeth D. Hilborn, DVM; Timothy J. Wade, PhD; Dawn M. Roellig, PhD; Jennifer L. Murphy, PhD; Lihua Xiao, DVM, PhD; Kirsten M. Yates, MPH; Jasen M. Kunz, MPH; Matthew J. Arduino, DrPH; Sujan C. Reddy, MD; Kathleen E. Fullerton, MPH; Laura A. Cooley, MD; Michael J. Beach, PhD; Vincent R. Hill, PhD; Jonathan S. Yoder, MPH
I had recently started the Food Safety Network, which was bringing daily updates to scientists and public health folks who usually had to wait 6 months for the U.S. Centers for Disease Control’s Morbidity and Mortality Weekly to arrive.
It may seem trivial now, but it was a big deal in its day.
Lotsa posers and copycats over the years, so we went to barfblog.com.
Later that year, cryptosporidiosis would sicken hundreds in Kitchener-Waterloo, where I was living with my young family.
Somehow, I was speaking about this to our home-renovator-contractor-and-therapist yesterday while he unplugged our kitchen faucet.
With decades of work in public health, Davis was the perfect person to figure out a little-known parasite cryptosporidiosis could be the culprit that sickened more than 400,000 people.
As state epidemiologist for the past four decades, Davis was Wisconsin’s doctor.
He was a medical sleuth who figured out the connection between toxic shock syndrome and tampons and helped determine the infectious agent transmitted by ticks that causes Lyme disease.
Davis, 72, died of pneumonia in Madison Jan. 16.
“Jeff’s knowledge of the literature helped identify the (Cryptosporidium) outbreak earlier. Cryptosporidiosis at that point was a pretty rare pathogen,” said State Public Health Veterinarian James Kazmierczak.
Knowing about a similar waterborne outbreak elsewhere in the U.S., Davis asked to see data on water quality in Milwaukee and noticed a spike in turbidity at the same time that people began to get sick. At the time, city water supplies were not tested for Cryptosporidium.
“Because of Jeff’s knowledge of what happened earlier with cryptosporidiosis, that became the leading suspect,” said Kazmierczak.
Davis grew up in Whitefish Bay and earned an undergraduate degree in chemistry in 1967 at University of Wisconsin-Madison and his medical degree in 1971 at the University of Chicago. He did his internship and residency in pediatrics in Florida and from 1973 to 1975 worked for the U.S. Centers for Disease Control and the South Carolina Department of Health.
After a stint at Duke University Medical Center, he returned to Wisconsin in 1978 as state epidemiologist and chief of the division of acute and communicable diseases. In 1991, his job title changed to chief medical officer and state epidemiologist for communicable diseases.
“He loved being a sleuth and medical detective, leading investigations of all sorts, from toxic shock syndrome to Legionnaires’ outbreaks, to the Cryptosporidium water supply outbreak, which was huge,” said his wife Roseanne Clark.
“He really was passionate about trying to figure out the source to reduce the impact on as many people as possible. He cared about the health of the people of Wisconsin.”
Potable water and the U.S. Centers for Disease Control: two things we take for granted.
CDC reports that during 2013–2014, a total of 42 drinking water–associated outbreaks were reported, resulting in at least 1,006 cases of illness, 124 hospitalizations, and 13 deaths. Legionella was responsible for 57% of outbreaks and 13% of illnesses, and chemicals/toxins and parasites together accounted for 29% of outbreaks and 79% of illnesses. Eight outbreaks caused by parasites resulted in 289 (29%) cases, among which 279 (97%) were caused by Cryptosporidium and 10 (3%) were caused by Giardia duodenalis. Chemicals or toxins were implicated in four outbreaks involving 499 cases, with 13 hospitalizations, including the first outbreaks associated with algal toxins.
To provide information about drinking water–associated waterborne disease outbreaks in the United States in which the first illness occurred in 2013 or 2014 (https://www.cdc.gov/healthywater/surveillance/drinking-surveillance-reports.html), CDC analyzed outbreaks reported to the CDC Waterborne Disease and Outbreak Surveillance System through NORS (https://www.cdc.gov/nors/about.html) as of December 31, 2015. For an event to be defined as a waterborne disease outbreak, two or more cases must be linked epidemiologically by time, location of water exposure, and illness characteristics; and the epidemiologic evidence must implicate water exposure as the probable source of illness. Data requested for each outbreak include 1) the number of cases, hospitalizations, and deaths; 2) the etiologic agent (confirmed or suspected); 3) the implicated water system; 4) the setting of exposure; and 5) relevant epidemiologic and environmental data needed to understand the outbreak occurrences and for determining the deficiency classification.§ One previously unreported outbreak with onset date of first illness in 2012 is presented but is not included in the analysis of outbreaks that occurred during 2013–2014.
One outbreak reported during 2013–2014 in an individual system led to 100 estimated illnesses associated with a wedding. The public health challenges highlighted here underscore the need for rapid detection, identification of the cause, and response when drinking water is contaminated by infectious pathogens, chemicals, or toxins to prevent and control waterborne illness and outbreaks.
Thanks to our Norwegian correspondent, we now know the Norwegian Food Safety Authority was notified on September 26, 2017, of a Cryptosporidium outbreak, and after talking to the sick, they could narrow the time of infection to 14-16. September,
The Food Safety Authority believes the people were infected at the Taqueros Taco & Tequila restaurant (because when I think Norway, I think tacos and tequila, not schnapps and raw fish).
The restaurant decided to shut one day to wash the premises when they heard about the outbreak and that the infection came from them.
The source of the infection was not found, but the Norwegian Food Safety Authority emphasizes that they do not discourage people from eating at the restaurant.
Specialist warden Erik Wahl in Mattilsynet in Trondheim and surroundings said, “We have reason to believe that the infection is now gone, as no people who have become ill after September 16 have not been reported. We have no reason to discourage people to eat at this restaurant.”