Tag: public health

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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Addressing TB disease, a global burden

Bacteria, fungi, viruses, protozoan parasites; we share our world with countless agents of infectious, disease-causing bugs. Globally, infectious (or ‘communicable’) diseases of various stripes – respiratory infections, HIV/AIDS, diarrheal diseases, malaria, tuberculosis, and meningitis among them – together remain the fourth leading cause of death, with people from lower-income countries being disproportionately more affected. Children form an especially vulnerable group; according to the World Health Organization (WHO), 6.6 million children under 5 years died worldwide in 2012, and over two-thirds of these deaths were attributable to infectious causes.

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Bugging city communities with impunity: this is the Staph of legend


Whether we know it or not, the human skin is a veritable garden of micro-organisms. The outermost layer (‘epidermis’) of the skin, the shafts of hair follicles, as well as the soft surface inside the nose (‘nasal mucosa’), making up for approximately 1.8 square meter of surfaces, is home to about 1000 species of bacteria among other things. Most of these don’t ordinarily cause disease; some are there for the ride, and some even offer benefits by warding off other nasty bugs from latching on.

“Faith Healing”, medical neglect by another name

In Scientio Veritas is my blog for talking about professional matters, related to science in health and disease, and so forth; and long-time readers (if any!) may know that I don’t like to bring in discussions on the controversial (and – I think – personal to many) issue of religion or religious faith, unless the specific issue impinges upon scientific and/or public health matters. Today, two of my scientist-blogger friends highlighted via social media a particular case of the latter kind, which screams to be commented upon because of its serious public health implications. So I shall endeavor to do so as best as I can.

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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

Occupational Health and the Law: UK vs. US; I ask a question


A UK case report on Occupational Health and Safety, published in August, came to my attention today. Two NHS Occupational Health investigators from UK, Charles Poole of the Northern General Hospital, Sheffield, and M Wong of the Dudley & Walsall NHS Trust Health Center, presented two clinical cases associated with a relatively new occupational industry in that nation: “The separation of garden waste from domestic waste, its collection and processing in industrial composting sites, so as to reduce biodegradable waste going to landfill“.

It is well known that any kind of disturbance created in a given environment, for any reason, can often potentially release harmful substances in air in form of aerosols, or minute particles capable of floating in air. We have seen that with the yeast-like fungal pathogen, Cryptococcus gattii, which was found, via environmental studies, to be present in high concentrations in the soil of Vancouver Island (British Columbia, Canada), and to spread during dry summer weather likely as airborne particles (a.k.a. “propagules”). Release and dispersal of spores of various molds during large-scale air-disturbing activities such as construction, renovation and/or demolition of buildings is a well-studied phenomenon in the fields of Infection Control and Epidemiology; for example, see Krasinski et al., 1985; Streifel et al., 1983. The waste separation, collection and processing appear to be no different. The investigators write:

The process of composting organic matter encourages the production of bacteria, fungi, spores and endotoxins, which may be released to air in bioaerosols. Levels of bacteria and fungi up to 106 colony forming units/m3 in ambient air have been reported in relation to composting…

The problem has not been studied well at all in the population of waste-composting workers, because – as the investigators indicate – reports of illness in these workers are relatively rare. As a result, no safe levels of exposure to such potentially hazardous aerosols have been defined in this context, nor have been the exact conditions conducive to exposure; we don’t know if, and/or how much of, the exposure depends on variables such as composition of the compost, weather conditions, steps and systemic controls engaged during the separation and collection process.

In the existing clinical literature, one of the major culprits implicated in these environment-related diseases is the ubiquitous, spore-producing mold, Aspergillus, in form of its various species, mostly commonly Aspergillus fumigatus which is the etiological agent behind various diseases involving the upper (nose and upper part of the air-tube) and lower (lower part of the air-tube and the lungs) respiratory tract. Untreated or incompletely treated, these diseases can be severe and chronic. One particularly important manifestation is the Allergic Broncho-Pulmonary Aspergillosis (ABPA, in short), which is a complex or multi-component, immunologic, inflammatory response similar to allergies or hypersensitivities – which if not detected and treated early (with antifungals and steroid immune-suppressants) can lead to serious lung damage. ABPA is generally observed in people with certain debilitating conditions, such as cystic fibrosis, or immunosuppression, but rarely in otherwise healthy individuals. In ABPA, apart from classical respiratory symptoms, reduction in lung functions, and lung abnormalities observed under X-ray, certain allergy-related responses are noted in blood (more precisely, serum) – such as:

  • Type I hypersensitivity to bits and pieces of Aspergillus (all recognized as antigens by the immune system), leading to the excessive generation of allergy-associated antibody, called Immunoglobulin E (IgE). By its action, IgE causes release of highly inflammatory mediators, such as histamine, leukotriene, and prostaglandin, from immune cells, which have both immediate and long term deleterious effects.
  • Type III hypersensitivity to Aspergillus antigens, in which small complexes of these antigens with antibody run amok through the body, depositing in blood vessels, kidneys and joints – eventually leading to immune-mediated destruction of tissues at those sites.
  • Eosinophilia, in which eosinophils, a type of white blood cells, markedly increase in number in blood and/or tissues, a common occurrence in allergy and asthma, and in parasitic (worm) infections. Activated eosinophils, a member of immune defence, are capable of causing tissue damage by various mechanisms.

The UK case report describes two late-thirties, early-forties patients, both garden waste collectors by profession, and both diagnosed with ABPA at occupational health clinics; both responded to treatment and were released with the advice not to work with waste and compost. Another member of their team, who though not ill had symptoms of asthma and tested positive for high serum IgE to Aspergillus antigens (indicating exposure) was given the same advice.

The investigators go on to make some recommendations at the end of the report. They write:

Until the results of large epidemiological studies of garden waste collectors and industrial compost workers are known, the few case reports of ABPA […] would indicate that workers with asthma who are sensitized to A. fumigatus or who have cystic fibrosis, bronchiectasis or are immunosuppressed should not work with garden waste or compost, unless their exposure to airborne fungi can be controlled. Whether asthmatics who are SPT positive or specific IgE positive to A. fumigatus will go on to develop ABPA is unknown, but they should be made aware of the theoretical risk.

Annual health surveillance by way of a respiratory questionnaire and skin prick testing is also recommended for these workers. Other cases of ABPA or EAA in garden waste and compost workers should be sought and reported, until such time that the results of a national study of UK compost workers are known.

The recommendations gave rise to some germane questions in my mind. These are, of course, valid from a clinical standpoint, and made keeping the health and welfare of the patients in mind. But given that these are related to occupational health, how do these situations play out from the perspective of the employer? How are these situations different in the UK as opposed to in the United States? For example:

  • Can/should the employers (say, a waste management firm) mandate pre-employment testing for Aspergillus-specific IgE and skin prick hypersensitivity testing?
  • Can/should the employers refuse employment to a person who tests positive for IgE and hypersensitivity because of a theoretical risk? Relatedly, can/should such an employee be made aware of this theoretical risk?
  • Should such an employee choose to ignore this theoretical risk and accept the job (or continue on the job after a diagnosis) and become inflicted with ABPA, can/should the employee be able to claim occupational exposure and Worker’s Compensation?
  • Specifically in the US context, can a Health Insurance company demand the results of these surveillance tests for a person engaged in the waste management profession, and if positive, treat this as a pre-existing condition and refuse payment in the event the employee becomes ill and needs treatment?

I don’t have the answers to any of these questions. Perhaps someone conversant with labor and/or occupational health-related laws would care to illuminate me in the comments?

Poole CJ, & Wong M (2013). Allergic bronchopulmonary aspergillosis in garden waste (compost) collectors–occupational implications. Occupational medicine (Oxford, England) PMID: 23975883

Sequestration Risks to Science and Public Health Programs: ASM Legislative Alert

This morning I received a legislative alert from the American Society for Microbiology (ASM, the world’s oldest and largest scientific membership organization), of which I am a member, via their Public and Scientific Affairs Board. I am not a citizen of the United States, the country I live and work in, and therefore, have no voting rights. But I am keenly aware of the current economic realities, as well as the politics and public policy-making surrounding them. And I think it is absolutely imperative for scientists, researchers and administrators to be aware of the direness of the situation – and to do their bit – because if not, the impact on scientific research and public health programs, both points of pride of this nation, is going to be devastating. I wanted to share this important missive for the sake of awareness.

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Fluoride in drinking water, yea or nay?

The effects of fluoride on human health has long been a matter of controversy. In small quantities, fluoride has beneficial effects on oral health, especially in preventing dental caries in children, which is a major public health concern in the industrialized countries as well as others. Therefore, the Oral Health program of the WHO supports fluoride containing toothpastes and mouth-rinses, as well as fluoridation of drinking water where necessary. As indicated in a 2004 report, systematic reviews of available datasets concluded that there was no credible evidence of adverse health effects of water fluoridation, and WHO Water Quality Guidelines recommended a maximum fluoride level of 1.5mg/L.

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