United States Agency for International Development

Pakistani quakes leave scientists debating tech’s role.

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 In the wake of a series of large earthquakes that have struck Pakistan over the past few weeks, the country’s scientists are debating howtechnology might help limit the devastation caused by future disasters.
 
A day before the first quake, which hit southwest Pakistan on 24 September, a collaboration between US and Pakistani geoscientists was announced. The project, which has been allocated US$451,000 over three years by the US Agency for International Development, will unite researchers to study the Chaman Fault — the location of the recent earthquakes.
 

Shuhab Khan, associate professor of geology at the University of Houston, United States, is leading the US side of the project. “There have been multiple big earthquakes in the area over the last 35,000 years,” he says. “The city of Quetta is particularly in danger as it lies near the fault. Bigger earthquakes could even affect the wider area — Karachi and its surroundings, and possibly some cities in Afghanistan as well.”
 
He hopes that modern technology — including lidar, a form of radar that uses laser radiation — will help Pakistan prepare better for earthquakes.
 
“This technology has been used successfully to identify the direction of movement and major cracks in faults,” Shuhab Khan tells SciDev.Net. “So if we can use it to study the Chaman Fault, it should help Pakistan understand the risks of earthquakes better and prepare better.”
 
Currently, the Chaman Fault is one of the least studied in the world, he says.
 
Zahid Rafi, director of the National Seismic Monitoring Centre at the Pakistan Meteorological Department in Islamabad, says that he and his team have been working to improve their understanding of local seismic activity.
 
Before the devastating earthquake that struck Kashmir in 2005, Rafi says his department was using manual seismometers, but since then they have introduced automated seismometers, accelographs and GPS (global positioning systems) worth 500 million Pakistan rupees (around US$4.7 million). These are all networked with a central databank in Islamabad.
 
But Shuhab Khan remains unconvinced that the national network of seismometers set up after the 2005 quake has helped matters. “I haven’t seen much improvement in seismic research in Pakistan,” he says.
 
Asif Khan, the director of the National Centre of Excellence in Geology at the University of Peshawar, Pakistan, says the establishment of the countrywide network of seismological stations is a “healthy sign” for future earthquake mitigation measures. But there is still a “lack of seismological research and records,” he adds.
 
“Academic research was being hampered by a lack of seismic technologies. Productive research in this area needs old and new seismic data but, unfortunately, Pakistan’s old seismic data is either not reliable or of poor quality,” he says.
 
Ali Rashid Tabrez, director general of the National Institute of Oceanography in Karachi, says that “data gathering with new seismic gadgets will enable the government to create a seismic databank. This should help identify quake hot spots and seismic activity on the seabed while informing building codes and disaster management strategies.”
 
According to its ten-year National Disaster Management Plan, Pakistan’s National Disaster Management Authority is starting a US$1.4 billion project to produce national earthquake hazard maps, contingency plans and risk assessments.
 

Source: SciVx

Regulatory approval opens the way for European launch of new single-size contraceptive diaphragm.

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The device is safe, comfortable, and easy to use, expanding nonhormonal contraceptive options for women

Seattle, June 20, 2013—Soon, women in Europe may be taking a new look at one of the world’s oldest forms of contraception. European regulators have granted the single-size SILCS Diaphragm a CE marking, allowing the product to be sold throughout Europe. The launch is also an important step toward expanding nonhormonal contraception options for women worldwide.

SILCS is the first new cervical barrier method to receive regulatory approval and enter the market in more than a decade. It was designed through a unique collaboration between PATH, a Seattle, Washington-based global health nonprofit; CONRAD, a reproductive health product development organization operated through the Eastern Virginia Medical School in Norfolk, Virginia; the United States Agency for International Development (USAID); and other partners. In 2010, PATH licensed the SILCS design to Kessel Marketing & Vertriebs GmbH (Kessel), a private-sector company in Frankfurt, Germany, to accelerate women’s access to the technology.

This June, Kessel will launch SILCS in six European countries. The product, marketed as the Caya™ contoured diaphragm and sold through health providers and pharmacies, will later be expanded to additional markets.

“PATH has more than 35 years of expertise developing and introducing new and overlooked approaches to global health challenges, so we knew that a well-designed and marketed diaphragm could have real health benefits for women worldwide,” said Steve Davis, president and CEO of PATH. “This multiyear process has taken the persistence and dedication of a remarkable group of public- and private-sector partners. Our work is by no means over, but this launch moves us one step closer to expanding women’s options for contraception.”

Worldwide, many women who don’t want to become pregnant aren’t using existing contraceptive methods for a number of reasons, including concerns about the side effects of hormonal contraception; wanting a method that can be used only when they need protection; or finding it difficult to negotiate condom use with their partners. Often, women have difficulty reaching a health care provider to discuss, initiate, or maintain other methods. The SILCS Diaphragm could help address the needs of these women.

Women and their partners in the Dominican Republic, South Africa, Thailand, and the United States validated the design of SILCS through user acceptability studies. CONRAD validated the safety, acceptability, and effectiveness of SILCS in clinical studies for safety and effectiveness. “[Our] pivotal study showed that the SILCS Diaphragm used with contraceptive gel is as effective as the traditional diaphragm used with contraceptive gel,” said Marianne Callahan, deputy director of clinical research at CONRAD. “The advantage of SILCS is that women do not need a pelvic exam to determine their diaphragm size, which can be an obstacle to access. Studies also show that this single-size device fits most women.” CONRAD has a long history of collaborating with organizations like PATH to create new methods of contraception and HIV prevention for women.

Together, these improved features have the potential to make SILCS a valuable option not only in Europe but for the estimated 222 million women worldwide who still have an unmet need for modern family planning. Introducing the method in developed countries, where traditional diaphragms are still available as part of family planning programs, will inform future introduction in low-resource settings where diaphragms have not been available in recent decades. A single-size device, rather than a diaphragm that comes in multiple sizes, will be easier to supply and provide.

These efforts, and continuing work to expand SILCS, have been funded primarily by USAID. “This woman-initiated, nonhormonal contraceptive barrier method has great potential to improve women’s reproductive health options by addressing several of the reasons for unmet contraceptive need,” said Judy Manning, team lead for contraceptive research and development at the agency. Manning added that the device may fill another needed role by “serving as a delivery method for gels that help protect against HIV and other sexually transmitted infections—it could be our first true multipurpose prevention product.”

The next step for the SILCS team is regulatory submission to the United States Food and Drug Administration for market approval in the United States. “It is vitally important to expand access in the United States to methods that improve women’s pregnancy and STI prevention options,” said Wayne C. Shields, president and CEO at the Association of Reproductive Health Professionals (ARHP). “ARHP supports the availability of as many safe, effective prevention options as possible, since each woman’s sexual and reproductive health needs are unique and vary over her life span.”

PATH and its research partners in Uganda, India, and South Africa are also gathering information on opportunities and challenges for introducing SILCS in low-resource settings. Marleen Temmerman, director of the Department of Reproductive Health and Research at the World Health Organization (WHO), noted the promise of these efforts: “The SILCS barrier method has the potential to avert health outcomes from unintended pregnancies, particularly for women in resource-poor settings, and will form part of the WHO’s strong commitment to achieving universal access to reproductive health through expanding choice and method mix.”

The European regulatory approval and launch announced this week mark important progress toward these goals.

About PATH

PATH is an international nonprofit organization that transforms global health through innovation. PATH takes an entrepreneurial approach to developing and delivering high-impact, low-cost solutions, from lifesaving vaccines, drugs, and devices to collaborative programs with communities. Through our work in more than 70 countries, PATH and our partners empower people to achieve their full potential.

About CONRAD

CONRAD was established in 1986 and is a Division of the Department of Obstetrics and Gynecology at Eastern Virginia Medical School (EVMS) in Norfolk, VA, where it has laboratories and a clinical research center. The main office is located in Arlington, VA, with additional offices in West Chester, PA, and collaborators around the world. CONRAD is committed to improving reproductive health by researching and developing new contraceptive options and products to prevent HIV and STI infections. www.conrad.org

About KESSEL

KESSEL was established in 1987 as the Sales Division of the German Familia Planning Organization PRO FAMILIA. Today, KESSEL is a small private entity and certified producer of medical devises for contraception and sexual healthcare products based at Frankfurt/Germany.

About USAID

President John. F. Kennedy created the United States Agency for International Development by executive order in 1961 to further America’s interests while improving lives in the developing world. USAID is the largest supporter of the development of safe, effective and acceptable contraceptives and multipurpose prevention technologies designed specifically for provision and use in low resource settings. www.usaid.gov

Source:PATH

The Ecology of Disease – How Environmental Sustainability Can Make or Break Animal and Human Health.

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The featured article is a rare gem that highlights the interrelatedness of humans with the environment, pointing out that most epidemics, such as AIDS, Ebola, West Nile, SARS, and Lyme disease, just to name a few, are a direct result of man’s failure to live in harmony with nature. By severely disrupting our environment, we create our own demise.

A project financed by the United States Agency for International Development has made its goal to determine the ecology of disease – a project that, if successful, will aid health officials in determining where the next disease outbreak may occur. While lack of food sources, water and sanitation play a key part in disease, they know that in developing countries disease also hinges heavily on the types of wildlife in an area, destruction of wildlife and forest areas, and the diseases and bacteria the wildlife may be carrying.

As reported by the New York Times:1

“There’s a term biologists and economists use these days – ecosystem services – which refers to the many ways nature supports the human endeavor. Forests filter the water we drink, for example, and birds and bees pollinate crops, both of which have substantial economic as well as biological value.

…By mapping encroachment into the forest you can predict where the next disease could emerge, So we’re going to the edge of villages, we’re going to places where mines have just opened up, areas where new roads are being built. We are going to talk to people who live within these zones and saying, ‘what you are doing is potentially a risk.'”

Project PREDICT

Our modern lifestyle has largely separated us from nature, and few stop to consider the immense impact environmental destruction has on our individual health. We simply cannot extricate ourselves from the symbiotic relationship we have with nature, and that includes both the environment and wildlife, big and small.

According to the featured article, some 60 percent of emerging infectious diseases in humans originate in the animal kingdom, and environmental destruction promotes this animal-to-human transfer of disease.

A new project called Predict, funded by the United States Agency for International Development, aims to determine where new diseases are likely to emerge, based on how the landscape is altered by human activities. The project will also study forest-, wildlife- and livestock management to prevent the spread of pandemic disease.

As the New York Times explains:

“The Nipah virus in South Asia, and the closely related Hendra virus in Australia, both in the genus of henipah viruses, are the most urgent examples of how disrupting an ecosystem can cause disease. The viruses originated with flying foxes, Pteropus vampyrus, also known as fruit bats…
[O]nce the virus breaks out of the bats and into species that haven’t evolved with it, a horror show can occur, as one did in 1999 in rural Malaysia.

It is likely that a bat dropped a piece of chewed fruit into a piggery in a forest. The pigs became infected with the virus, and amplified it, and it jumped to humans. It was startling in its lethality. Out of 276 people infected in Malaysia, 106 died, and many others suffered permanent and crippling neurological disorders.”

According to experts, the answer to preventing these kinds of pandemics lies in understanding how leaving nature intact can protect against the emergence of disease. For example, according to a study cited in the featured article, a four percent increase in deforestation in the Amazon increased malaria by nearly 50 percent! The reason for this non-linear increase in disease in response to cutting down of forest is because disease-spreading mosquitoes thrive in a mix of water and sunlight, which is in ample supply in deforested areas.

Lyme disease is another disease produced by man’s interference with nature. By reducing and fragmenting large swaths of forests, larger predators such as wolves, foxes, and hawks, for example, have been pushed out. As a result, certain kinds of mice that are the primary carriers of Lyme bacteria have been given free rein to multiply.

According to the New York Times:

“‘When we do things in an ecosystem that erode biodiversity – we chop forests into bits or replace habitat with agricultural fields – we tend to get rid of species that serve a protective role,’ [Lyme disease researcher] Dr. Ostfeld told me. ‘There are a few species that are reservoirs and a lot of species that are not. The ones we encourage are the ones that play reservoir roles.'”

The One Health Initiative

In response to these findings, a worldwide program called the One Health Initiative2 launched a couple of years ago, involving a number of medical, veterinarian and agricultural organizations and federal agencies, along with more than 600 scientists and other professionals in both human and veterinary medicine. Its mission statement reads:

“Recognizing that human health (including mental health via the human-animal bond phenomenon), animal health, and ecosystem health are inextricably linked, One Health seeks to promote, improve, and defend the health and well-being of all species by enhancing cooperation and collaboration between physicians, veterinarians, other scientific health and environmental professionals and by promoting strengths in leadership and management to achieve these goals.”

Sustainability is at the heart of this holistic view. And the creation of such a global program comes not a moment too late, as the ever increasing spread of genetically engineered crops and plants now threatens sustainability everywhere.

Genetically Engineered Plants – One of the Most Dire Threats to Sustainability

As explained by Dr. Don Huber – an expert in soil-borne diseases, microbial ecology, host-parasite relationships, and GE toxicity – it’s essential to understand that agriculture is a complete system based on inter-related factors. In order to maintain ecological balance and health, you must understand how that system works as a whole. Any time you change one part of that system, you change the interaction of all the other components, because they work together.

It is simply impossible to change just one minor aspect without altering the entire system, and this is why genetically engineered crops pose such a dire threat not just to the environment, but also to wildlife, livestock, and humans, and do so in more ways than one.

Dr. Huber’s research, which spans over 55 years, has been devoted to looking at how the agricultural system can be managed for more effective crop production, better disease control, improved nutrition, and safety. The introduction of genetically engineered crops has dramatically affected and changed all agricultural components:

  • The plants
  • The physical environment
  • The dynamics of the biological environment, and
  • Pests and diseases (plant, animal, and human diseases)

Food Quality is Related to Soil Quality

One of the major modifications done to genetically engineered (GE) food crops is the introduction of herbicide resistance. Monsanto is the leader in this field, with their patented Roundup Ready corn, cotton, soybean and sugar beets, which can survive otherwise lethal doses of glyphosate – the active ingredient in Roundup.

The introduction of glyphosate-resistance has had a direct impact on soil microbes, which in turn decreases the food quality. While the link between an herbicide (which is directed toward plants) and soil microbes may not be immediately apparent, this ripple effect occurs because, again, it’s an inter-related system.

In a nutshell, herbicides are chelators that form a barrier around specific nutrients, preventing whatever life form is seeking to utilize that element from utilizing it properly. That applies both to plants and soil microbes – as well as animals and humans. This may actually be one of the primary reasons why genetically engineered foods appear to be able to cause such profound health problems in those who consume them. According to Dr. Huber, the nutritional efficiency of genetically engineered (GE) plants is profoundly compromised. Micronutrients such as iron, manganese and zinc can be reduced by as much as 80-90 percent in GE plants!

The quality of the food is almost always related to the quality of the soil. The most foundational and critical components of the soil are the microorganisms that thrive there – more so than the necessary nutrients, because it’s the microorganisms that allow the plants to utilize those nutrients.

According to Dr. Huber:

“The plant can only utilize certain [reduced] forms of all the nutrients… The way that it becomes reduced in the soil is through those beneficial microorganisms. We also have microorganisms for legumes like soybeans, alfalfa, peas, or any of the other legumes that can fix up to 75 percent of their actual nitrogen for protein in amino acid synthesis that actually comes from the air through the microorganisms in the soil.

Glyphosate is extremely toxic to all of those organisms. What we see with our continued use and abuse of this powerful weed killer is that it is also totally eliminating many of those organisms from the soil. We no longer have the same balance that we used to have.”

The result of this imbalance in soil organisms is disease – in plants, animals, and humans. As just one example, toxic botulism is now becoming a more common cause of death in dairy cows whereas such deaths used to be extremely rare. The reason it didn’t occur before was because beneficial organisms served as natural controls to keep the Clostridium botulinum in check. Glyphosate, and glyphosate-resistant crops decimate beneficial organisms not just in soil, but also in animal and human intestines. As a result, the Clostridium botulinum is allowed to proliferate in the animal’s intestines and produce lethal amounts of toxins.

Putting Your Money Where Your Mouth is… Some Food for Thought

As Dr. Huber states:

“When future historians come to write about our era they are not going to write about the tons of chemicals we did or didn’t apply. When it comes to glyphosate they are going to write about our willingness to sacrifice our children and to jeopardize our very existence by risking the sustainability of our agriculture; all based upon failed promises and flawed science. The only benefit is that it affects the bottom-line of a few companies. There’s no nutritional value.”

Unfortunately, due to lack of labeling, many Americans are still unfamiliar with what genetically engineered foods are. We now have a great opportunity to change that, and I urge you to participate and to continue supporting the California ballot initiative – which will require labeling of genetically engineered foods and food ingredients, and eliminate the routine industry practice of labeling and marketing such foods as “natural.”

The voting takes place in November. Remember, since California is the 8th largest economy in the world, a win for the California Initiative would be a huge step forward, and would likely affect ingredients and labeling nation-wide, as large companies are not likely going to label their products as genetically engineered when sold in California, but not when sold in other states. Doing so would be a PR disaster.

But it’s an enormous ongoing battle, as the biotech industry will outspend us by 100 to 1, if not more, for their propaganda. Needless to say, the campaign needs funds, as there are no deep corporate pockets funding this citizen’s initiative. So, please, if you have the ability, I strongly encourage you to make a donation.

Some good news: the California “Yes on 37” Right to Know campaign recently received the endorsement of the California Labor Federation and U.S. Senators Barbara Boxer and Mark Leno.

“Senator Boxer said, ‘California consumers have the right to know if their food has been genetically engineered. This basic information should be available for consumers on the label the way it is in 50 other countries around the world.’ The Digital Journal reported on July 27.3

State Senator Mark Leno said, ‘The people of California want to know what’s in their food. More than half the people in the world live in countries that already require labeling of genetically engineered foods. Californians deserve to have this information too.’

Steve Smith, Communications Director for the California Labor Federation, said, ‘Working people deserve the right to know what is in the food we are feeding our families. Prop 37 is a commonsense measure that ensures our families are able to make educated choices about the food we purchase. We’re proud to join with millions of Californians in supporting the right to know what’s in our food.'”

I urge you to get involved and help in any way you can. Be assured that what happens in California will affect the remainder of the U.S. states, so please support this important state initiative, even if you do not live there!

  • Join the CA RightToKnow campaign, and tell everyone you know in California to vote YES on Proposition 37.
  • Whether you live in California or not, please donate money to this historic effort through the Organic Consumers Fund.
  • Talk to organic producers and stores and ask them to actively support Proposition 37.  It may be the only chance we have to label genetically engineered foods.

Source: .mercola.com

CDC Grand Rounds: the TB/HIV Syndemic.

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CDC Grand Rounds: the TB/HIV Syndemic.

This is another in a series of occasional MMWR reports titled CDC Grand Rounds. These reports are based on grand rounds presentations at CDC on high-profile issues in public health science, practice, and policy. Information about CDC Grand Rounds is available at http://www.cdc.gov/about/grand-rounds.

Since Robert Koch‘s 1882 discovery of Mycobacterium tuberculosis, substantial progress has been made in tuberculosis (TB) control. Nevertheless, in the latter part of the 20th century, a long period of neglect of both quality program implementation and research led to persistently high TB incidence rates and failure to develop new tools to adequately address the problem. Today, most of the world continues to rely on the same diagnostic test invented by Koch approximately125 years ago and on drugs developed 40 years ago. The world now faces a situation in which approximately 160 persons die of TB each hour (1.45 million died in 2009), in which a quarter of all deaths in persons with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (PWHA) are caused by TB, and in which the evolution of the bacteria has outpaced the evolution of its treatment to such an extent that some forms of TB are now untreatable (1). More recently, renewed attention has been given to reducing the global burden of TB (2), but much remains to be done.

Misconceptions Regarding TB

Misconceptions about TB infection and disease impede patient care, program implementation, and policy innovation. The first misconception is that TB infection and TB disease are the same. For TB disease prevention and control purposes, the global population can be divided into three discrete groups: those without TB infection, those with TB infection, and those whose TB infection has developed into TB disease. The lifetime risk that a person with TB infection will develop TB disease is 5%–10%; that risk is much higher among PWHA (3,4). A successful control strategy must, therefore, address each group.

A second misconception about TB is that it is no longer a major public health problem. In fact, of the 7 billion persons in the world, 2.3 billion are already infected with TB, and about 9 million develop TB disease each year. Furthermore, TB causes about 1.4–2 million deaths annually (Figure 1) (1).

A third misconception is that TB can be diagnosed easily by a physician or laboratory. To diagnose TB infection, only two tests are validated currently: the tuberculin skin test (TST) and the interferon gamma blood test. Unfortunately, TST is neither sensitive nor specific for TB infection, and both tests can be difficult to implement in resource-limited settings. To diagnose TB disease, most laboratories examine sputum with a microscope to look for TB bacilli, the same approach that Koch invented. In PWHA, the sensitivity of microscopic examination is low, approximately 40% (5–7). Given the high risk for death in PWHA who have untreated TB, this low sensitivity is a critical challenge that must be addressed. Culture of sputum for M. tuberculosis is considered the gold standard test, but it is difficult to use and, in resource-limited settings, challenging to implement. Culturing M. tuberculosis, a slow-growing airborne pathogen, requires laboratories that employ high levels of biosafety and specialized technicians. In 2010, the Xpert MTB/Rif assay, a sensitive, easy-to-use, polymerase chain reaction (PCR)–based test was validated. With no need for sophisticated biosafety or specialized technicians and a turn-around time of 2 hours for both TB diagnosis and detection of drug resistance, this assay has the potential to improve TB control in the developing world (8). Limiting its current use is the relatively high cost of the necessary equipment and supplies, a lack of evidence that the assay’s use is feasible in routine practice, and the fact that it has not yet been demonstrated to improve patient outcomes in resource-limited settings.

TB/HIV Syndemic*

TB and HIV act synergistically within a population to cause excess morbidity and mortality. PWHA are more likely to develop TB disease because of their immunodeficiency; HIV infection is the most powerful risk factor for progressing from TB infection to disease (4). Diagnosing TB disease among PWHA is particularly challenging because PWHA who have pulmonary TB frequently have negative sputum smears and up to one third might have completely normal chest radiographs (5). Furthermore, TB in PWHA often occurs outside the lungs, evading traditional diagnostic tests. Because TB is both common and difficult to diagnose, many PWHA feel ill but are unaware that they have TB. A recent review found that when systematic efforts were undertaken to diagnose TB, approximately 8% of patients who went to HIV care and treatment facilities were found to have TB disease (9), although the exact proportion varies substantially depending on the epidemiology of TB in the area. Finally, TB is a frequent cause of death for PWHA, particularly if HIV disease is advanced and antiretroviral therapy (ART) has not yet been initiated. Persons with both diseases must adhere to complex drug regimens that might interact with each other and might have overlapping toxicities.

Combating the Dual Burden of Disease

TB disease and death can be prevented in PWHA by early TB diagnosis and effective treatment of both diseases. Early diagnosis and treatment ensure that TB treatment is provided before the illness reaches an advanced stage, thereby decreasing mortality, and ensures that the duration of infectiousness is limited, thereby reducing transmission of TB to others. TB disease also can be prevented by treating persons with TB infection. Treatment of TB infection requires reliably excluding the presence of TB disease to avoid the development of drug resistance; drug resistance could emerge if a patient receives a single drug to treat TB infection when the patient, in fact, requires a multidrug regimen to treat TB disease.

Until recently, no internationally accepted, evidence-based, sensitive approach existed to screen PWHA for TB disease, although some preliminary data had begun to suggest that commonly used approaches were inadequate. CDC investigators partnered with the U.S. Agency for International Development (USAID), ministries of health, and nongovernmental organizations in three Southeast Asian countries to derive a TB screening algorithm that would solve this problem. This study concluded that asking patients about three symptoms (i.e., cough, fever of any duration, or night sweats lasting longer than 3 weeks) accurately categorized PWHA for targeted interventions. Patients with none of these three symptoms can be considered free of TB disease and offered treatment to prevent TB disease, if indicated; patients with at least one of these symptoms should have further diagnostic tests performed for TB disease (5,6) These criteria mark a significant improvement over the 2007 World Health Organization (WHO) guidelines in which screening was based primarily on the presence of chronic cough (10). Screening for cough lasting more than 2 weeks was only 33% sensitive for TB disease in this study; screening for the combination of symptoms increased sensitivity to 93% (Figure 2) (5). The increased sensitivity under the new criteria will lead to fewer missed diagnoses of TB disease, at the cost of requiring TB diagnostic evaluation for more people.

Although this approach simplifies TB screening, a comparable approach for simplifying diagnosis of TB disease remains elusive. In the same study, investigators learned that adding liquid culture of two sputum specimens more than doubled the yield of TB case detection among PWHA, compared with microscopic examination alone of the same two sputum specimens, as recommended by WHO at the time (76% versus 31% sensitivity) (6). Unfortunately, liquid culture is not widely available in resource-poor settings and requires high levels of training, biosafety, and supervision. It is hoped that introduction of the Xpert MTB/Rif assay, which is more sensitive than smear but less sensitive than liquid culture, along with other emerging diagnostic techniques, will improve diagnostic accuracy in PWHA who have symptoms of TB (8).

In persons who screen negative for TB disease, treatment of TB infection should be considered. The tuberculin skin test (TST) identifies persons with TB infection who can benefit from isoniazid preventive therapy (IPT), a regimen that involves ingesting isoniazid daily for at least 6 months. In the pre-ART era, clinical trials confirmed that IPT was effective in reducing the development of TB disease in TST-positive PWHA by 64% (11). Subsequently, in 1998, WHO recommended that all PWHA living in TB-endemic countries receive 6 months of IPT, and that TST screening generally was not needed in countries with a high burden of TB. Follow-up studies found that the benefit of IPT waned as early as 6 months after completion of IPT. In 2009, only 0.3% of PWHA globally received IPT (1). ART also can reduce the risk for TB disease in PWHA by 54%–92% and might have a synergistic effect when used with IPT (12). In collaboration with the Botswana Ministry of Health, and with funding from CDC and USAID, CDC conducted a clinical trial in Botswana to evaluate how much better TB could be prevented with a 36-month regimen of IPT in PWHA who had access to government-provided ART. This study found that among those with positive TSTs, 36 months of IPT reduced TB incidence by 74%, compared with persons receiving only 6 months IPT. When the analysis was limited to TST-positive trial participants randomized to the 36-month IPT arm who successfully completed the initial 6 months of IPT, the reduction in TB was 92%. As with previous studies, no significant benefit from IPT was observed for TST-negative participants (Figure 3). ART provided an added benefit to IPT’s protective effect, reducing TB risk a further 50% in all groups (13).

These findings have enormous implications for controlling the TB epidemic in countries with a high burden of HIV. If 36 months of IPT were provided to all TST-positive PWHA in Botswana, countrywide TB incidence would decline 45%†(Figure 4). A cost-effectiveness model of 10,000 PWHA in Botswana demonstrated that providing 36 months of IPT for PWHA with a positive TST result, in addition to ART for those with CD4 <250 cells/µL, could avert more incident TB cases with fewer resources than increasing the threshold for ART initiation alone (CD4 <350 or 500), suggesting any cost-effective TB prevention strategy should include the provision of IPT for TST-positive PWHA.

From Evidence to Guidance to Global TB Control

The strong evidence provided by the studies described above has been combined with results from other studies to update the global guidelines for TB screening and prevention (14). A recent WHO publication outlines four updated recommendations for resource-constrained settings: 1) PWHA should be screened with the new symptom-based algorithm, and those who do not report current cough, fever, weight loss, or night sweats are unlikely to have active TB and should be offered IPT (a minor modification to the algorithm developed in the CDC Southeast Asia study); 2) PWHA who report any of the aforementioned symptoms are considered suspects for TB disease and should be evaluated further for TB and other diseases as clinically indicated; 3) PWHA who are TST positive or have unknown TST status and are unlikely to have TB disease based on symptom screening should receive IPT for at least 6 months; and 4) in settings where feasible, PWHA should receive IPT for at least 36 months, or even lifelong. Where feasible, TST should be used to help identify those who would benefit most from IPT (15).

TB control relies on an international strategy known as “DOTS” (directly observed treatment, short course) that includes finding as many highly infectious patients with TB as possible, initiating effective treatment, directly observing drug ingestion to ensure adherence, and standardized monitoring, evaluation, and reporting. DOTS has saved approximately 7 million lives globally since 1990 (1). In the United States, the experience in New York City provides an example of the progress that can be made through full implementation of the DOTS strategy (16). However, although TB prevalence and deaths around the world did fall in the period after widespread global DOTS implementation, treatment programs generally have not resulted in a rapid reduction in global TB incidence (17). Multiple factors explain this phenomenon: insufficient resources and commitment to implement DOTS, in part because TB occurs predominantly in the poorest populations; a focus entirely on treatment of TB disease but not TB infection; the HIV epidemic; the emergence of multidrug resistant TB strains; and limited attention to the social determinants of sustained TB transmission and reactivation. Modeling studies suggest that detecting more infectious TB cases and successfully treating them will, on its own, be insufficient to drive down TB incidence and prevalence quickly and that the global TB strategy must address the large burden of latent TB infection that exists globally (18). The simplified symptom-based screening approach derived in the Southeast Asian study and the effective approach to chemoprophylaxis documented in the Botswana clinical trial help address this need.

The Way Forward

In a 2010 “call to action,” global leaders in TB control outlined crucial areas that must be addressed to accelerate the decline in global TB incidence to more than 1% per year and to meet the target for the 2015 Millennium Development Goal (Figure 5) (19). Achieving this will require fully implementing the DOTS strategy globally, and it will also require going far beyond that to address the limited impact that would be expected with DOTS alone, as outlined in WHO’s latest STOP TB strategy (20). WHO calls for improvements in TB screening and diagnosis, including the use of newer TB diagnostic assays. In addition to these steps, treatment of latent TB infection also is needed (18). In settings with a high prevalence of HIV infection, implementing IPT can reduce TB incidence greatly. Finally, scientific advances are needed in three key areas to develop 1) an effective TB vaccine; 2) a shorter, simpler anti-TB drug regimen with efficacy against both drug-susceptible and drug-resistant TB; and 3) new diagnostic tests that can simply and accurately diagnose both TB infection and disease (21).

The fundamentals of TB control are early and accurate TB diagnosis, effective treatment, and prevention. The gap between what we know and what we need to know is large, but the gap between what we know and what we are implementing in practice is both larger and more harmful. By closing both our knowledge gap and our implementation gap, we can eliminate this deadly syndemic.

Reported by

Haileyesus Getahun, MD, PhD, Mario Raviglione, MD, World Health Organization, Geneva, Switzerland. Jay K. Varma, MD, Global Disease Detection Br, Center for Global Health; Kevin Cain, Div of Tuberculosis Elimination, Taraz Samandari, Div of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Tanja Popovic, MD, PhD, Thomas Frieden, MD, Office of the Director, CDC. Corresponding contributor: Kevin Cain, kcain@cdc.gov, 404-639-2247.

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* Additional information available at http://www.cdc.gov/nchhstp/programintegration/definitions.htm.

† Assuming provision of antiretroviral therapy to all PWHA if CD4 <200 cells/µL.

Three recent studies highlight the importance of maintaining a healthy gut to avoid disease and optimize your health. The first, published in the journal Celli, shows that “host-specific microbiota appears to be critical for a healthy immune system.”

Source: CDC.