Tiny particles of pure silica coated with an active material could be used to remove toxic chemicals, bacteria, viruses, and other hazardous materials from water much more effectively and at lower cost than conventional water purification methods, according to researchers writing in the current issue of the International Journal of Nanotechnology.

Peter Majewski and Chiu Ping Chan of the Ian Wark Research Institute, at the University of South Australia, explain that the availability of drinking quality water is fast becoming a major socio-economic issue across the globe, especially in the developing world. However, water purification technology is often complicated, requires sophisticated equipment and is expensive to run and maintain. Moreover, it usually requires a final costly disinfection stage. The Australian team suggests that nanotechnology could provide a simple answer to the problem.

The researchers have investigated how silica particles can be coated easily with a nanometer-thin layer of active material based on a hydrocarbon with a silicon-containing anchor. The coating is formed through a chemical self-assembly process so involves nothing more than stirring the ingredients to make the active particles.

These active particles, so called Surface Engineered Silica (SES), were then tested to demonstrate that they could remove biological molecules, pathogens such as viruses like the Polio virus, bacteria like Escherichia coli, and Cryptosporidium parvum, which is a waterborne parasite.

"The results clearly show that organic species can efficiently be removed at pH ranges of drinking water by stirring the coated particles in the contaminated water for up to one hour and filtering the powder," the researchers say. They point out that the filtration process occurs through an electrostatic attraction between the pathogens and the surface engineered particles.

The recent report entitled 'Water for People - Water for Life' of the World Water Assessment Program of the UNESCO says that more than 6000 people die every day due to water-related diseases, including diarrhea, worm infections, and infectious diseases. In addition, organic pollutants from industrial waste water from pulp and paper mills, textiles and leather factories, steel foundries, and petrochemicals refineries, are a major cause of illness in parts of the world where regulations do not necessarily protect people from such industrial outflows.

The team's nanotech approach to water purification could help prevent disease and poisoning for potentially millions of people.

Historically, the prevalence of smoking among women in the developing world has been very low, in part because of strong cultural constraints against women’s tobacco use. “This study indicates that public health officials in developing nations should take immediate steps to prevent and reduce tobacco use and secondhand smoke exposure among pregnant women,” said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development (NICHD). “This should include efforts to better understand the scope of the problem, so as to best direct public health interventions.”

The study was conducted by an international team of investigators, including researchers from the National Cancer Institute (NCI) and NICHD, two NIH institutes. The researchers conducted the study at ten sites in the NICHD Global Network for Women’s and Children’s Health Research, which focuses on improving maternal and child health in the developing world. Approximately 8,000 pregnant women were surveyed at five sites in Latin America (Argentina, Uruguay, Ecuador, Brazil and Guatemala), two sites in Africa (Zambia and the Democratic Republic of the Congo) and three sites in Asia (two in India and one in Pakistan). The survey looked at pregnant women’s use of tobacco products (cigarettes and smokeless tobacco), their perceptions of the social acceptability of tobacco use for women, and exposure to secondhand smoke experienced by them and their young children.

“Preventing an increase in tobacco use by women in the developing world is widely recognized as a significant public health opportunity,” said lead author Michele Bloch, M.D., Ph.D., of NCI’s Tobacco Control Research Branch. “Our results demonstrate that pregnant women’s tobacco use and exposure to secondhand smoke threaten to impede or reverse ongoing efforts to improve maternal and child health in the developing world.”

Because few studies have looked at tobacco use and secondhand smoke exposure among pregnant women in low and middle-income countries, the researchers conducted this investigative survey in nine developing nations to get a preliminary look at the magnitude of the problem. The researchers found as many as 18 percent of pregnant women currently smoked cigarettes, up to one-third used smokeless tobacco, and as many of half were regularly exposed to secondhand smoke in the nations studied. The researchers also found evidence that in some countries where pregnant women’s tobacco use is currently low, rates of smoking during pregnancy could increase dramatically if barriers to women’s tobacco use were removed.

Uruguay and Argentina had the highest levels of smoking during pregnancy across all ten study sites (18 percent and 10 percent respectively). While the three other Latin American sites reported fewer women smoking during pregnancy, all had large numbers of respondents who had tried cigarettes at least once. If women’s smoking were to become more culturally acceptable, these other sites would be poised for much higher levels of smoking by pregnant women.

In the Indian sites, one-third of all pregnant women used smokeless tobacco in Orissa and about twenty percent of pregnant women in Karnataka were often exposed to secondhand smoke. The highest levels of secondhand smoke exposure were found in Pakistan, where about half of all pregnant women and their young children were frequently or always exposed to secondhand smoke. About one in ten pregnant women at the site in Pakistan reported that they had tried cigarette smoking.

In the Democratic Republic of the Congo, 40 percent of respondents reported that they had tried smokeless tobacco at least once, and six percent had used smokeless tobacco while pregnant. About 14 percent of women in the Democratic Republic of the Congo had tried cigarettes, as had about seven percent of women from Zambia.

The researchers recognize that the study has some limitations. For example, the data were collected by self-report through face-to-face interviews, and because tobacco use by women is a heavily stigmatized behavior, the study findings may actually underestimate the scope of the problem. Differences among study participants in geographic setting, literacy levels, employment status, and the presence of tobacco users in the household may also have contributed to differences in reported tobacco exposure.

Pregnant women are a priority population for tobacco prevention efforts because tobacco use poses serious risks to fetal and maternal health. Smoking during pregnancy causes a number of problems, including preterm delivery, low birth weight and sudden infant death syndrome. For the mother, cigarette use can lead to lung and other cancers, coronary heart disease, stroke, and chronic obstructive pulmonary diseases. Smokeless tobacco use can lead to oral and pancreatic cancers. Secondhand smoke causes lung cancer and heart disease in adults, and can lead to serious illnesses, such as bronchitis and pneumonia in infants and children.

“Where tobacco use rates are still low, we have the opportunity to avert an increase in tobacco use among women, especially pregnant women, in the developing world,” said Linda Wright, M.D., Scientific Director of the Global Network, in NICHD’s Center for Research for Mothers and Children. “These data highlight the urgent need to adopt proven measures to prevent and control tobacco use -- both cigarettes and smokeless tobacco -- and secondhand smoke exposure of women and girls worldwide.”

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Funding for this research came from NICHD, NCI, the U.S. Department of Health and Human Service’s Office on Women’s Health, and the Bill and Melinda Gates Foundation.

Bloch M, Althabe F, Onyamboko M, Kaseba-Sata C, Castilla EE, Freire S, Garces AL, Parida S, Goudar SS, Kadir MM, Goco N, Thornberry J, Daniels M, Bartz J, Hartwell T, Moss N, Goldenberg R. Tobacco Use and Secondhand Smoke Exposure During Pregnancy: An Investigative Survey of Women in 9 Developing Nations. American Journal of Public Health, Vol. 98, No. 4. Published online February 28, 2008.

Author affiliations: Michele Bloch, NCI; Nancy Moss, NICHD; Fernando Althabe is with the Hospital de Clínicas, Montevideo, Uruguay; Marie Onyamboko is with the Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo; Christine Kaseba-Sata is with the University Teaching Hospital, Lusaka, Zambia; Eduardo E. Castilla is with the Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (Latin-American Collaborative Study of Congenital Malformations), Rio de Janeiro, Brazil; Salvio Freire is with the Hospital das Clinicas, Federal University of Pernambuco, Recife-Pernambuco, Brazil; Ana L. Garces is with the Multidisciplinary Health Institute, Guatemala City, Guatemala; Sailajanandan Parida is with the Sriram Chandra Bhanj Medical College, Cuttack, India; Shivaprasad S. Goudar is with the Karnatak Lingayat Education Society’s Jawaharlal Nehru Medical College, Belgaum, India; Muhammad Masood Kadir is with the Aga Khan University, Karachi, Pakistan; Norman Goco, Jutta Thornberry, Magdalena Daniels, Janet Bartz, and Tyler Hartwell are with Research Triangle Institute, Research Triangle Park, NC; and Robert Goldenberg is with Drexel University College of Medicine, Philadelphia, Pa.

For more information on Bloch’s research, please go to http://cancercontrol.cancer.gov/tcrb/pubs_bloch.html.

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov.

The findings, presented today for the first time, are a significant boost to HIV prevention efforts focused on the potential of "next-generation" microbicides to curb infection rates in women. Globally, nearly half of those living with HIV/AIDS are women, and between 70 and 90 percent of all HIV infections in women are due to heterosexual intercourse. In India and many other parts of the world, even married women and women with steady partners are at risk.

In this Phase II study, called HPTN 059, researchers wanted to understand if tenofovir was safe to use every day for six months compared to its use prior to each act of sex, and if women were able to adhere, or follow, each regimen. Researchers found both approaches equally safe and women’s adherence to product use similar. Interestingly, most participants also said they would be willing to apply gel, including daily, if one were found effective to prevent against getting HIV from their sexual partners.

Microbicides are products designed to prevent the sexual transmission of HIV when applied topically on the inside of the vagina or rectum. Tenofovir gel is among a newer class of candidate microbicides that differ from early types because they have specific action against HIV. In addition, because tenofovir gel and similar products are longer acting, their use may not be required before each act of sex, which is not always practical or desirable for some women.

“Finding that daily use is both safe and feasible is important because we believe a daily approach may provide more sustainable protection against the virus in women who can’t always predict when they will have sex. Based on what we have learned we can proceed with greater confidence on a path that will answer whether tenofovir gel and other gels with HIV-specific compounds will be able to prevent sexual transmission of HIV in women when other approaches have failed to do so. It is a critical time for all of us engaged in HIV prevention, and I truly believe we are turning a corner,” said Sharon L. Hillier, Ph.D., professor and vice chair for faculty affairs, and director of reproductive infectious disease research in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, who is MTN principal investigator and led the study.

According to UNAIDS, women represent nearly half, or 46 percent, of the 33.2 million people living with HIV/AIDS worldwide, and they are more than twice as likely as men to acquire HIV through sexual intercourse, due to both biological and cultural factors. Although correct and consistent use of male condoms has been shown to prevent HIV infection, women often cannot successfully negotiate condom use with their male partners.

HPTN 059 involved 200 sexually active HIV-negative women: 52 were enrolled at the University of Alabama at Birmingham (UAB) in Birmingham, Alabama; 48 at Bronx-Lebanon Hospital Center, Bronx, New York; and 100 women entered the study at the National AIDS Research Institute in Pune, India. The mean age was 32 and 64 percent of the women were married. All but one of the women at the Indian site were married compared to 28 percent of the women at the two U.S. sites.

Once enrolled, women were randomly assigned to one of four groups: tenofovir gel applied daily; tenofovir gel applied up to two hours before sex; placebo gel (without an active drug) used every day; or placebo gel applied prior to sex. Because the tenofovir and placebo gels look the same, neither researchers nor participants knew who had been assigned to use which gel during the six-month study period. Women were assessed at one month, three months and six months. Throughout the study, participants received free condoms and HIV risk-reduction counseling as well as routine testing and treatment for sexually transmitted infections.

The study found no differences in liver, blood and kidney function between the groups of women using either regimen of tenofovir gel and the groups assigned to use placebo, nor were there differences in these safety measures between groups using daily gel and groups using gel with sex. Likewise, researchers report no statistical differences in the development of genital symptoms such as itching and burning, which are considered minor. One woman became pregnant and stopped gel use. No participants acquired HIV during the study.

Adherence to treatment was also similar. According to structured interviews, 80 percent of the women instructed to use gel within two hours of having sex said they complied with the regimen. Of the women in the daily-use groups, an average of 83 percent reported study gel use in the past week. The two most cited reasons women gave for not using gel was menstruation (41 percent) and forgetting (23 percent).

Overall, 41 percent of the women indicated there was nothing they disliked about using the gel and 39 percent said it was easy to use. Other attributes of the gel women identified included its potential for protecting against HIV (19 percent), its smell and appearance (14 percent) and that it made sex more pleasurable (12 percent). Thirty-two percent didn’t like that the gel was messy, but none of the women said sex was made less pleasurable because of the gel.

Importantly, when asked if they would use the gel if it were found to help prevent people from getting HIV, 90 percent of the women who had been assigned to use the gel at the time of sex and 96 percent of the women who had been asked to use gel daily said yes.

“Women are definitely willing to use a gel to protect against sexual transmission of HIV. That’s very encouraging,” Dr. Hillier commented.

HPTN 059 also evaluated how the active ingredient in the gel was absorbed from the vagina into the blood and vaginal tissue; and looked at the effects of prolonged use on vaginal flora, the vagina’s naturally protective population of microorganisms; and whether the activity of certain immune system molecules called cytokines could serve as a useful measure, or marker, for assessing the safety of microbicides. Results of these evaluations are not yet available.

HPTN 059 was conducted by the Microbicide Trials Network (MTN), a clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health (NIH). Prior to the establishment of the MTN, HPTN 059 study was led by the NIAID-funded HIV Prevention Trials Network (HPTN), from which the study gets its name.

At the site level, HPTN 059 was led by Smita Joshi, MBBS, in Pune, India; Jessica Justman, M.D., at Bronx-Lebanon Hospital; and Craig Hoesley, M.D., UAB.

In its pill form, tenofovir is a mainstay of one of the most widely used regimens for treating HIV. The active ingredient in tenofovir gel belongs to a class of anti-retroviral drugs called nucleotide reverse transcriptase inhibitors, which act against HIV by targeting a key enzyme the virus needs to copy itself before taking over a host cell. The topical gel form of tenofovir was not developed as treatment for HIV but as an approach to prevent the sexual transmission of HIV. Both oral and topical formulations were developed by Gilead Sciences, Inc., of Foster City, California, which assigned a royalty-free license for the topical gel to the International Partnership for Microbicides of Silver Spring, Maryland, and CONRAD, of Arlington, Virginia, in December 2006.

MTN will launch a series of other trials that will further evaluate the safety and adherence of tenofovir gel as well as look at its effectiveness for preventing HIV. Researchers will soon begin enrolling participants into MTN-002, the first trial of a candidate microbicide in pregnant women that seeks to understand the extent of drug absorption during pregnancy and the degree to which the active ingredient in tenofovir gel can be transferred to the fetus. Another trial, MTN-001, will be the first direct comparison of oral and vaginal gel preparations of tenofovir – looking at differences in drug absorption (systemically and locally) and adherence and acceptability of each approach separately and in combination. Finally, the VOICE Study (Vaginal and Oral Interventions to Control the Epidemic) will be the first effectiveness trial of a microbicide that women use every day instead of at the time of sexual intercourse. Moreover, VOICE will be the only trial evaluating two promising HIV prevention approaches in the same study: tenofovir gel and pre-exposure prophylaxis, or PrEP, an HIV prevention approach that involves daily use of oral anti-retrovirals.

Currently, tenofovir gel is being evaluated in a Phase IIb study being conducted at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban. The study, known as CAPRISA 004, will enroll 980 women. Unlike VOICE, researchers are evaluating a dosing strategy timed around sexual intercourse.

Other microbicide products have been or are currently being tested in clinical trials, although none is yet approved or available for use by women.

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In addition to Drs. Hillier, Justman, Joshi and Hoelsley, other authors of the HPTN 059 study presented at Microbicides 2008 are Elena Cyrus-Cameron, M.P.H., Family Health International, Research Triangle Park, North Carolina; Benoît Mâsse, Ph.D., Statistical Center for HIV/AIDS Research & Prevention at the Fred Hutchinson Cancer Research Center, University of Washington, Seattle; and Craig Hendrix, M.D., Johns Hopkins University, Baltimore, Maryland.

The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). The MTN brings together international investigators, community and industry partners who are devoted to reducing the sexual transmission of HIV through the development and evaluation of microbicides, working within a unique infrastructure specifically designed to facilitate research required to support licensure of topical microbicide products for widespread use. Based at the University of Pittsburgh and Magee-Womens Research Institute, MTN’s principal investigator is Sharon Hillier, Ph.D. MTN’s core operations are supported by a network laboratory at the University of Pittsburgh, a statistical and data management center housed within the Statistical Center for HIV/AIDS Research & Prevention at the Fred Hutchinson Cancer Research Center, and Family Health International, a global organization with expertise conducting clinical protocols. It receives its funding from three NIH institutes: NIAID, the National Institute of Mental Health and the National Institute of Child Health and Human Development. More information can be found at www.mtnstopshiv.org.

Montreal, February 28, 2008 - Data from the ADVANCE Study, involving 11,140 high-risk patients with type 2 diabetes, provides no evidence of an increased risk of death among those patients receiving aggressive treatment to lower blood glucose.

This contrasts findings from the 10,251 patient ACCORD trial which halted the intensive glucose control arm of the study 18 months early because a data review revealed that patients who received intensive treatment to lower blood glucose are at higher risk for death. While the trial will continue, patients will be transitioned from the intensive treatment arm (targeting A1c levels of <6.0 %) to the less intensive, standard treatment arm (targeting A1c levels of 7.0 to 7.9%).

“Unlike what we saw in ACCORD, a rigorous review of ADVANCE data by the Data and Safety Monitoring Committee shows that the treatment strategy of intensively lowering blood sugar does not pose greater risk to our patients with type 2 diabetes”, says Canadian lead investigator and member of ADVANCE Management Committee Dr. Pavel Hamet, professor of Medicine, Canada Research Chair of Predictive Genomics at Université de Montréal and Chief, Gene Medicine Services at Centre Hospitalier de l’Université de Montréal. “ADVANCE is a landmark study and will continue as planned to completion. The results will provide crucial information to help us better reduce the significant health risks associated with type 2 diabetes.”

Type 2 diabetes increases the risk of many complications, especially cardiovascular disease, which is the leading cause of death in people with diabetes. Both the ADVANCE and ACCORD studies examined the effects of intensive blood glucose and blood pressure control on the risk of cardiovascular events such as heart attack, stroke, or death from cardiovascular disease in patients with type 2 diabetes. A successful reduction in overall and cardiovascular mortality in the intensive blood pressure arm has been reported from the ADVANCE trial and published in The Lancet in September 2007.

In ADVANCE and ACCORD, the intensive treatment arm targeted blood glucose levels below those recommended in current treatment guidelines because previous studies suggest that reducing blood sugar to levels to those found in non-diabetic adults may reduce the rate of cardiovascular disease in patients with diabetes.

In the ADVANCE trial, which involves 20 countries worldwide including Canada, the intensive blood glucose lowering program aimed to reduce levels of hemoglobin A1c (a marker of long term blood glucose control) to ≤6.5%. Treatment included a sulfonylurea drug, gliclazide modified release, for all patients, and a number of other agents for those patients unable to reach target blood glucose levels. The ADVANCE trial was started in 2001 and patients were followed for an average of five years.

Because the A1c targets in ACCORD and ADVANCE are similar, and the intensive blood glucose control arm of ACCORD was stopped early, the ADVANCE mortality data was reviewed by the Data and Safety Monitoring Committee to determine if there was a similar excess risk of mortality. This committee advised that data did not provide any confirmation of the adverse mortality trend reported from ACCORD.

“Final patient visits have been completed and the ADVANCE study data base is close to finalization. We expect to have definitive results soon,” said Study Director, Dr. Anushka Patel, from The George Institute in Sydney, Australia. “At this stage, the Data Monitoring and Safety Committee have reviewed results that are more than 99% complete, so we are confident that the interim findings are a reliable guide to the final results.”

Final data from the ADVANCE trial is expected to be promising in terms of risk minimization but multiple analyses are required before conclusions can be drawn regarding the effects of intensive glucose control on patient outcomes. Additional data will be available specifically from ADVANCE, and Dr. Hamet’s team, in collaboration with Prognomix in Montréal, is performing genomic studies of the risk of complications of diabetes in this unique worldwide patient cohort.

The ADVANCE trial was conducted by an independent collaborative group of medical researchers with support from the National Health & Medical Research Council of Australia and the Institut de Recherche Internationales Servier. The results of the blood pressure control arm of ADVANCE were presented at the annual meeting of the European Society of Cardiology in Vienna, Austria in September 2007. Final results of the glucose control arm of the ADVANCE trial will be released earlier than expected, by the middle of 2008.

While the annual number of new detected cases of African sleeping sickness has been falling since the late 1990s, there could still be a resurgence of the disease unless control efforts are maintained, say tropical disease experts in this week's PLoS Medicine.

Although elimination of the disease is considered feasible, say Pere Simarro (World Health Organization) and colleagues, there is a risk that the disease could suffer the "punishment of success," receiving lower priority by public and private health institutions with the consequent risk of losing the capacity to maintain disease control.

"While waiting for new tools for sleeping sickness control," say the authors, "the greatest challenge for the coming years will be to increase and sustain the current control efforts using existing tools."

Citation: Simarro PP, Jannin J, Cattand P (2008) Eliminating human African trypanosomiasis: Where do we stand and what comes next? PLoS Med 5(2): e55.

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