Hope for future drugs? Exploring vulnerabilities of Cryptosporidium

Cryptosporidium parvum is a gastrointestinal parasite that can cause moderate to severe diarrhea in children and adults, and deadly opportunistic infection in AIDS patients.

crypto.glcolysisBecause C. parvum is resistant to chlorine disinfectant treatment, it frequently causes water-borne outbreaks around the world. A study published on Nov. 12th in PLOS Pathogens provides a detailed analysis of a C. parvum protein that is central to glycolysis — the only pathway by which the parasite can generate energy — and identifies it as a potential drug target.

Guan Zhu and colleagues, from Texas A&M University in College Station, USA, study the parasite’s metabolism during its complicated life-cycle. C. parvum exists both in free stages (where parasites are in the environment or in the host’s digestive tract) and intracellular stages following host cell invasion, during which the parasite occupies a specialized compartment — the parasitophorous vacuole — which is delineated by a host-cell derived border called the parasitophorous vacuole membrane (PVM).

For this study, the researchers focused on lactate dehydrogenase (LDH), an enzyme central to glycolysis. Glycolysis is the only metabolic process by which organisms like C. parvum — that lack functional mitochondria to derive energy from oxygen — can generate ATP, the universal biological energy storage molecule. They found that the C. parvum LDH (CpLDH) protein is found inside the parasite’s cells during the free stages, but is then transferred to the PVM during intracellular development, indicating involvement of the PVM in parasite energy metabolism, and specifically, in lactate fermentation. They also demonstrate that two known LDH inhibitors, gossypol and FX11, can inhibit both CpLDH activity and parasite growth.

The researchers summarize that their observations “not only reveal a new function for the poorly understood PVM structure in hosting the intracellular development of C. parvum, but also suggest LDH as a potential target for developing therapeutics against this opportunistic pathogen, for which fully effective treatments are not yet available”. Acknowledging that the ultimate validation of CpLDH as a drug target requires tools for knockout or knockdown of genes of interest in Cryptosporidium, they say recent advances towards this goal raise hope that such validation will be possible in the near future.

Overall, they conclude that “the present data, together with the fact that C. parvum relies on glycolysis for producing ATP, support the notion that CpLDH is worth exploring as a potential target for the development of anti-cryptosporidial therapeutics.”

70 now sick: E. coli or Cryptosporidium linked to apple cider at Illinois fair

Apple cider served at the Pike Country Color Drive that happened in Pike County, Illinois has now sickened at least 70 people.

powell_kids_ge_sweet_corn_cider_00Health officials have already sent out a warning to those purchasers during the event and even advised health care providers to check for E. coli and Cryptosporidium, as these could be the reasons as well. As of the moment, they haven’t confirmed any information regarding the exact cause of those foodborne illnesses

A list of cider and juice-related outbreaks — 84 outbreaks leading to over 3,500 illnesses going back to 1924 – is available here.

30 now sick: Cider at Illinois fair

The Pike County Health Department and the Adams County Health Department along with the Illinois Department of Public Health (IDPH) is investigating a cluster of gastrointestinal (GI) illness associated with the Pike County Color Drive, a large fall festival that spans several communities in Pike County, IL.

powell_kids_ge_sweet_corn_cider_00There have been 30 suspect cases of GI illness identified in attendees of the festival who consumed apple cider purchased from vendors at two locations. The etiologic agent has not yet been confirmed; health care providers should be encouraged to test for E. coli and Cryptosporidium until further information is available.

Ill individuals have reported symptoms including profuse diarrhea, bloody diarrhea, abdominal cramping and vomiting. Onset dates range from October 20 – 28. Persons have been hospitalized as a result of this illness, and additional illnesses continue to be reported. Further laboratory testing is pending. Symptoms usually last about 1 to 2 weeks (with a range of a few days to 4 or more weeks) in persons with healthy immune systems. Occasionally, people may experience a recurrence of symptoms after a brief period of recovery before the illness ends. Symptoms can come and go for up to 30 days. People who are especially vulnerable to this illness include: pregnant women, children under 2 years, elderly and immunocompromised individuals. If you attended the festival or consumed apple cider purchased from vendors at the festival and feel that you have these symptoms, contact your health care provider.

Investigators are seeking additional cases of GI illness that attended the Pike County Color Drive during October 17-18 and consumed apple cider purchased during the event. If you have apple cider that was purchased during the event that is fresh or frozen for future use, do not consume it. Contact your local health department so that the cider can be tested. Pike County Health Department: 217/285.4407 Adams County Health Department: 217.222.8440. Health officials who identify cases with this exposure history are asked to contact the IDPH Communicable Disease Control Section at 217-782-2016 or email justin.albertson@illinois.gov.

Cider again? 6 sick with crypto linked to Illinois fair

After attending the same event in Barry, Illinois, Oct. 17, Adams County Health Department says there’s been an outbreak of cryptosporidiosis disease in Pike County, Illinois.

pike.county.fall.color.driveAdams County Health Department Director of Clinical and Environmental Services Shay Drummond says the health department is helping Pike County Health Department investigate the parasitic illness that has infected six people.

County Health Department RN, BSN Jan Bleich says everyone infected had been at the Pike County Fall Color Drive. The source, she says, may have been apple cider.

Bleich says some of the people were hospitalized.

Drummond says the disease is caused by microscopic parasites called cryptosporidium, which is found in water, food, soil or on surfaces or dirty hands that have been contaminated with human or animal feces that are infected.

Cryptosporidium can be spread by swallowing contaminated water from swimming pools, fountains, lakes and rivers. The parasite can survive for long periods of time in chlorinated drinking and swimming pool water. It can also be spread by swallowing water, ice or drinks contaminated with poop from infected people or animals, or by eating undercooked food or drinking unpasteurized or raw apple cider or milk that is contaminated. People can also get it from touching their mouths with contaminated hands.

Don’t poop in pools: when it happens, take action

The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues.

diaper.poolBecause of the parasite’s extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities).

In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4–∞) but not with another venue or setting.

The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.

Preventing community-wide transmission of Cryptosporidium: a proactive public health response to a swimming pool-associated outbreak – Auglaize County, Ohio, USA

Epidemiology and Infection / Volume 143 / Issue 16 / December 2015, pp 3459-3467



15 sick: Wisconsin football team stricken with Cryptosporidium

Milton School District says they now have three confirmed cases of Cryptosporidium at the Milton High School.

north.dallas.fortyMilton football coach Bill O’Leary told 27 News Tuesday he has “lots” of sick kids on his team. Health officials are trying to get samples from those who are ill to either confirm or deny they have Cryptosporidium.

According to WKOW-TV, two community meals among the football players have led to the outbreak.

The health department and school are taking precautionary measures and the high school will be closed for 24 hours for disinfection.

3 sick: Crypto outbreak in Tenn.

Some Scott County parents are on edge after two local children have been hospitalized with a gastrointestinal illness caused by a common microscopic parasite.

crypto.Public-Pool-Dangers-800Cryptosporidiosis is being blamed for at least three illnesses in Scott County children this week, creating a sense of alarm on social media as news of their sickness has spread.

The first local child to be admitted to the hospital was a young girl from Oneida. Initially fearing an appendicitis attack, her mother, Tracy Shoopman, drove her to East Tennessee Children’s Hospital in Knoxville on Tuesday. There, doctors admitted her for testing, and on Wednesday confirmed a diagnosis of cryptosporidiosis.

The same day, another child from Scott County — a student at Huntsville Elementary School — was also diagnosed with cryptosporidiosis by doctors after being hospitalized at Children’s Hospital. Her mother, Mindy Wagaman, told the Independent Herald that her daughter was hospitalized late Tuesday night after she started vomiting blood.

Both children remained hospitalized Thursday.

Also on Wednesday, a third child, also a student at Huntsville Elementary, was diagnosed with the illness by Children’s Hospital doctors. However, she was treated in the hospital’s emergency room and released.

A fourth child, a student at Huntsville, was being tested for the illness.

At first glance, there was no apparent connection between the four cases of the illness — which health officials say is most commonly caught from contaminated water sources. According to the CDC, the illness can be caught by swimming in contaminated bodies of water, which can include streams or lakes but can also include treated water sources, such as pools or splash pads. Because the parasite is resistant to common water treatment methods, it can survive in pools after being unknowingly introduced to the water by someone who is sick.

Knoxville’s WBIR reported last week that East Tennessee health officials are seeing a major spike in crypto cases this year. The story quoted Darci Hodge, Children’s Hospital’s director of quality and infection control, as saying the hospital has confirmed 29 cases of crypto this year — far higher than the next highest single-year number of five cases.

Crypto cases spike in Tenn.

East Tennessee health officials are seeing a major spike in reported cryptosporidium cases, a water-dwelling parasite that most commonly contaminates public water sources.

diaper.pool“It is a parasite that lives in the bowels of people who are infected with it,” said Darci Hodge, director of quality and infection control at East Tennessee Children’s Hospital. “It can live in animals and it can be passed on by people or animals in living water for a short period of time, and that’s often how you and I will get it.”

Hodge said Children’s Hospital confirmed 29 reported cases of cryptosporidium this year, the biggest number of cases it’s seen in years.

Within the past five years, the second highest number of reported cases of the disease at Children’s Hospital was only five.

“It was significant enough because the Health Department and we, here, really talked a lot about it because it was odd to see so many cases,” Hodge said.

The Knox County Health Department has 34 reported cases on record this year.

“It only takes one person with this illness to have a little spill in the pool, you might say,” said Connie Cronley, an epidemiology nurse at the Health Department. “It could infect lots of folks.”

Cronley said the parasite comes with many symptoms, but not all of them may appear serious enough to contact a doctor.

Crypto compensation: United Utilities faces £15m bill

United Utilities accepts it is facing a colossal compensation bill for the first cryptosporidium contamination of drinking water in the North West UK this century.

poop-in-poolBut the company has reassured consumers the payouts – estimated already at £15m and mounting – will not be offset by a rise in water bills.

“Bills will not increase to cover the cost of compensation,” insisted a spokesman.

“This cost will be borne by the company.”

With more than 300,000 households and businesses hit by the scare, now into its third week, United Utilities has declined to put a figure on how much the crypto invasion will amount to.

But in a recent case in Bolton, where consumers had to boil their drinking water for five days after supply problems, the company paid out £15 per house to cover the cost.

With the inconvenience to customers in Preston, South Ribble, Chorley, the Fylde Coast and villages like Samlesbury, Mellor and Mellor Brook at least three times that already, claims could amount to at least £45 a household, or £13.5m in total.

With businesses set to lodge much higher demands for compensation after providing bottled water to all employees during the scare – BAE Systems is thought to have spent more than £100,000 already on keeping its 10,000-strong workforce in Lancashire hydrated – the bill is estimated to be rising by £1m a day.

At least 3 sick with crypto from Kansas pool

Johnson County is taking some protective measures at specific pools after multiple residents were recently diagnosed with cryptosporidiosis, the Johnson County Department of Health and Environment (JCDHE) said in a news release.

caddyshack.pool.poop-1“At this time, we have three confirmed cases and are tracking a few more possible cases in the community,” said Lougene Marsh, JCDHE director, in the news release. “We encourage everyone to wash their hands frequently and ensure their children take frequent breaks from the pool to prevent accidents.”

JCDHE is working closely with pool operators in Overland Park and Shawnee for cautionary measures to close and/or treat swimming pools with which infected individuals had contact.