Tag: epidemiology

The MIDAS touch: NIGMS Propels Infectious Disease Research To Golden Age via Computational Modeling

The National Institute of General Medical Sciences (NIGMS), a part of the US National Institutes of Health (NIH), was established in 1962 via an Act of Congress for the “conduct and support of research and research training in the general or basic medical sciences and related natural or behavioral sciences”, especially in areas which are interdisciplinary for other institutes under the Act, or alternatively, which fall under no institute’s purview. In these 52 years, the NIGMS has acquitted itself laudably as one of premier funding agencies that support basic research into understanding biological processes, disease diagnostics, treatment and prevention. At any given time, NIGMS supports close to 5000 research grants, accounting for more than 1 in every 10 grants funded by NIH as a whole, and has the distinction of funding the Nobel Prize-winning research of 75 scientists.

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Spotlight on the recent outbreak of cyclosporiasis, a food- and water-borne parasitic disease

A balanced diet should contain fresh fruits and vegetables, whose long-term health benefits are indisputable. Simultaneously, it is crucial for continued good health to remember the importance of hygiene and safe handling of fruits and vegetables, as underscored by some recent findings of the Centers for Disease Control and Prevention (CDC) during an investigation into the suspected outbreak of a food-borne illness, called cyclosporiasis.

Cyclosporiasis is most common to tropical and subtropical regions; it has been found in Ghana, Guatemala, Egypt, Turkey, Nepal, Peru, and Haiti from water samples and human disease. Although it is not considered endemic to the continental United States, it is by no means unknown in this country; during 1990-95 three small outbreaks were reported in North America. Major outbreaks, confirmed by molecular methods, have been documented since c.1996, often associated with fresh produce – raspberries, lettuce, basil, and snow peas – mostly imported from countries endemic for the disease. Apart from multi-state outbreaks in 1996, 1997, and 2000, more than 1100 sporadic cases of confirmed cyclosporiasis occurred during 1997-2008, involving twelve US states. About a third of these cases were likely associated with international travel to endemic regions. In response, cyclosporiasis was made a nationally notifiable disease in January 1999; as of 2008, it is a reportable condition in 37 states, New York City (NYC), and the District of Columbia.

Earlier this year (June-August 2013), an unusually large number of cyclosporiasis reports were communicated to the CDC, involving more than 600 individuals from 25 states (with high numbers in Texas, Iowa, and Nebraska) and NYC. Epidemiologic and traceback investigations conducted jointly by the CDC, the Food and Drug Administration (FDA), and state and local public health officials revealed the possibility of two outbreaks; cases in Iowa and Nebraska were associated with restaurants, and involved a salad mix (iceberg and romaine lettuce, red cabbage, carrots) sourced from Taylor Farms de Mexico, whereas cases in Texas were associated with uncooked (but not cooked) cilantro sourced from Puebla, Mexico.

Cyclosporiosis outbreak case map October 2013
A total of 631 cases of cyclosporiasis were reported from 25 states and New York City: Texas (270), Iowa (140), Nebraska (87), Florida (33)¶, Wisconsin (18), Arkansas (16)†, Illinois (14)†, New York City (8)‡, Georgia (5), Missouri (5)†, Kansas (4)‡, New Jersey (4)†, Louisiana (3)‡, Massachusetts (3)†, Minnesota (3), Ohio (3), Virginia (4), Connecticut (2), New York (2)†, California (1)†, Michigan (1)†, New Hampshire (1), Pennsylvania (1), South Dakota (1), Tennessee (1), and Wyoming (1). † Includes one case that may have been acquired out of state. ‡ Includes two cases that may have been acquired out of state. ¶ May include one international travel-associated case. [Source: CDC]

Human cyclosporiasis is a disease caused by the single-celled apicomplexan protozoal parasite Cyclospora cayetanensis. Parasites of the genus Cyclospora have been found in nature in many members of the animal kingdom, including certain terrestrial arthropods (such as, centipedes), snakes, rodents, moles (a subterranean mammal), cattle (recently discovered in China), as well as in certain non-human primates (colobus monkeys, green monkeys, baboons and chimpanzees). Although there are about 18 different species of Cyclospora currently known, the four that infect non-human primates appear to be specific to these animals, and so far Cyclospora cayetanensis has been discovered only in humans. Attempts to create non-human animal models of C. cayetanensis infection have been unsuccessful, again suggesting host-specificity.

Cyclospora cayetanensis in stool sample; modified Acid-fast stain
Four Cyclospora cayetanensis oocysts in fresh stool sample in 10% Formalin, variably stained with Acid-fast stain. Image courtesy: PHIL/CDC/DPDx – Melanie Moser.

Cyclospora transmission occurs via the fecal-oral route. In excreted fecal matter, Cyclospora exists in the form of oocysts (a thick-walled structure containing immature, dormant parasite spores), a product of sexual reproduction of the parasite. Interestingly, these are non-infectious, although highly resistant to common disinfectants used in food- and water-processing industries. However, within two weeks, the spores mature – making the oocysts infectious. Neither the natural environments of this process, nor the exact manner of transmission, are yet known, but contamination of water and/or food (such as raw produce) with oocyst-containing fecal matter likely contributes to the dissemination. Epidemiological studies indicate that higher risks of infection are associated with consumption of untreated water and/or food, lack of adequate sanitation, and the presence of animals in the household.

This parasite primarily targets the small intestines, and an infection often causes gastro-intestinal symptoms, such as watery diarrhea, abdominal cramping, anorexia (loss of appetite), flatulence (gas) and bloating, along with nausea, fatigue, weight-loss, sometimes accompanied by low-grade fever. In absence of proper treatment, some of these symptoms may continue for weeks on end, while some may be temporarily relieved, only to recur. The good news is that the infection is not generally life-threatening and people with healthy immune systems may not require treatment. However, in children and in the elderly, as well in individuals with compromised immunity (such as AIDS or cancer patients), untreated cyclosporiasis may cause severe, and occasionally fatal, illness.

The anti-protozoal antimicrobial Trimethoprim/sulfamethoxazole is currently the drug of choice for Cyclospora infection. Anti-diarrheal medication, taken under medical supervision, may help reduce diarrhea. However, for an effective preventative, the CDC strongly advises that general fruit and vegetable safety recommendations – covering washing, preparation, and storage – be followed by consumers.

[An abridged version of this post was published in The Conversation UK.]

Suggested reading

  1. Bern C, et al. (1999) Epidemiologic Studies of Cyclospora cayetanensis in Guatemala. Emerg Infect Dis, vol.5, No.6: doi:10.3201/eid0506.990604
  2. Ynés R. Ortega and Roxana Sanchez (2010) Update on Cyclospora cayetanensis, a Food-Borne and Waterborne Parasite. Clin Microbiol Rev, 23(1): 218–234; doi:10.1128/CMR.00026-09
  3. Centers for Disease Control and Prevention (2011) Surveillance for Laboratory-Confirmed Sporadic Cases of Cyclosporiasis – United States, 1997-2008. MMWR, 60(No. SS-2):1-11; URL: CDC/MMWR
  4. US Food and Drug Adminstration (2013) FDA Investigates Multistate Outbreak of Cyclosporiasis. Report dated: October 23, 2013. Last accessed: November 1, 2013. URL: FDA
  5. Centers for Disease Control and Prevention (2013) Notes from the Field: Outbreaks of Cyclosporiasis — United States, June–August 2013. MMWR, 62(43):862; URL: CDC/MMWR

Cryptococcus gattii Gone Wild on World Tour


By now you know, dear readers, that Cryptococcus gattii (CG), the deadly fungal pathogen and a native of tropical and subtropical regions of the world, has stealthily charted itself a course of world domination, starting with the Pacific Northwest of North America. I have also alerted you to the possibilities about its transmission – (a) that CG may have spread as a result of human activity, human and avian migration, and other natural means of dispersal; and (b) that slow, but sustained, elevation of global temperatures and corresponding changes in the long-term climate of different regions may have created micro-climates suitable for CG growth within zones with a temperate climate ordinarily considered inhospitable to the fungus.

Well, it is emerging that CG‘s plans are rather grandiose, total world domination – if possible.

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Mystery of Disappearing Teaspoons

Things I learn from Twitter!!

Someone in my rapidly-flowing Twitter-stream posted a link to this brilliant 2005 study from Australia; my apologies for not remembering who posted the link. If someone knows, do let me know and I shall correct the attribution here.

The study by Lim et al., of the Centre for Epidemiology and Population Health Research, Macfarlane Burnet Institute for Medical Research and Public Health, in Melbourne, Australia, was published in the British Medical Journal (BMJ), and is freely accessible via PubMed Central: BMJ (2005) 331 (7531): 1498–1500.

The case of the disappearing teaspoons: longitudinal cohort study of the displacement of teaspoons in an Australian research institute

This group of epidemiologists decided to apply time-honored epidemiological tools to a seemingly intractable and mystifying problem – the disappearance of stainless steel teaspoons from the tea-room of the institute, framed elegantly by the authors in the paper as “Where have all the bloody teaspoons gone?”.

The authors’ urge to do a systematic study to make some sense of the phenomenon of teaspoon loss was spurred on, it appears, by inexplicable betrayals by Google, Google Scholar, and Medline searches, all of which – probably in on the conspiracy – refused to reveal any pertinent information in response to the keywords “teaspoon”, “spoon”, “workplace”, “loss” and “attrition”. Aiming to answer two questions,

  1. To figure out the overall rate of loss (defined, rather sweetly, as ‘displacement’) of teaspoons at the institute, and
  2. To find if any possible correlation exists between the said displacement and the relative value of the teaspoons or type of tearoom,

the authors designed a longitudinal (involving repeated observations of the same variables over a period of time) cohort study, employing 70 teaspoons, discreetly numbered and placed in tearooms around the institute, and observed weekly over a period of 20 weeks, a total of 5668 teaspoon days (teaspoon days = sum of all the days on which the teaspoons were observed). They proceeded with great planning – doing first a small pilot study to determine feasibility, followed by a main study with a larger cohort.

During the main study, half of the total teaspoons disappeared permanently (defined as the ‘half life of the teaspoons’) in 81 days. The type of tearoom setting (communal vs. isolated rooms linked to specific departmental programs) affected the rate of loss, with more spoons leaving the former than the latter. Surprisingly, the quality of the material (stainless steel) of the spoon was not a factor in the rate of loss – an observation which adequately allays my suspicion that this study was covertly funded by the Association of Cutlery Plasticware Manufacturers of Australia. (Not that I am aware of the existence of such an entity; nevertheless…)

The authors discovered that the incidence of teaspoon loss was high enough to warrant an annual purchase of estimated 250 teaspoons, in order to maintain a practical institute-wide population of 70 teaspoons, and concluded that office teaspoons, in their institution, are under constant threat of disappearance. Which is perhaps not surprising, given that, in a follow-up questionnaire, 38% of respondents (from a pool of 90-odd employees) admitted to stealing a teaspoon at least once in their lifetime, and 17% disagreed that stealing teaspoons is wrong.

Attempting to explain the phenomenon of uncontrollable teaspoon displacement, the authors have drawn a parallel with noted ecologist Garrett Hardin’s essay, The Tragedy of the Commons, an instance of over-exploitation of shared resources by individuals, who – in spite of being aware that the depletion of shared resources is ultimately detrimental to all users – nevertheless persist in that behavior finding no harm in the fractional loss via their own agency. To me, this also hearkens back to the story (of uncertain provenance, heard during childhood) of a king who had urged his people to donate a jar of milk, one jar from each household, to the royal pond during the night. Everyone thought that one could simply pour, unnoticed, a jar of water in the pond, since everyone else was sure to bring milk. The following morning pond was only filled with water, since everyone was driven by the exact same thought of self-entitlement.

The authors have, as a result, recommended the development of effective control measures to deter the migration of teaspoons, ranging from designing (or renovating) tearooms – which, in my opinion, should probably be equipped with continuously monitored surveillance equipment – to tagging individual teaspoons via Microchips and Global Positioning Satellite (GPS)-based tracking systems. Other intriguing possibilities, proffered subsequently by other distinguished researchers with experience of similar predicaments, include:

  • Immobilisation, or altogether non-provision of the teaspoons as alternative solutions to manage their disappearance [T Watts, BMJ (2006) 332 (7533): 121]
  • The reappearance of truant teaspoons on their own following a day of complete unavailability of the said items, which may reduce the anticipated need for repurchase [K Darton, BMJ (2006) 332 (7533): 121]
  • Inherent flexibility in the very definition of ‘teaspoons’ (given the various modes in which spoons may be utilized) which may invalidate the very premise of the study [D Silver, BMJ (2006) 332 (7533): 121]
  • Potential confounding factors, which have not been considered in the design or analysis of the study, including the numbers of tea-bags, forks, and the ratio of tea-drinkers vs. instant coffee drinkers [A Woodall, BMJ (2006) 332 (7533): 121]

In a comment, B Herer, a physician from France, alerted to the possibility that this may be not an Australian or English, but a global, phenomenon, given the observation at his hospital near Paris that approximately 1800 spoons disappeared during lunchtime from the hospital cafeteria during first five months of 2001 [B Herer, BMJ (2006) 332 (7533): 121].

The cynic in me can’t help feeling that this is a sad commentary on the greed and selfishness of human individuals – an idea reinforced by the revelation, in the article, that as many as five potentially lost teaspoons reappeared after the results were disclosed internally. Nevertheless, the authors have brought up two intriguing (albeit speculative) alternative possibilities in the discussion:

  1. Resistentialism, the belief that inanimate objects have a natural antipathy towards humans, driven by which the teaspoons are migrating and disappearing on their own, or
  2. Escape to a spoonoid planet; in their words:

Somewhere in the cosmos, along with all the planets inhabited by humanoids, reptiloids, walking treeoids, and superintelligent shades of the colour blue, a planet is entirely given over to spoon life-forms. Unattended spoons make their way to this planet, slipping away through space to a world where they enjoy a uniquely spoonoid lifestyle, responding to highly spoon oriented stimuli, and generally leading the spoon equivalent of the good life.

Any scientific paper, which references the Hitchhiker’s Guide to the Galaxy by the inestimable Douglas Adams (referred in the article in support of the spoonoid proposition), is an absolute winner in my book!

Or, perhaps, there is no spoon?

Oh, and fun stuff I learned from the paper: the word ‘flunky’ – for a research assistant – can be unabashedly incorporated in a scientific paper. Now I simply have to find a context to use it in my next paper.