Cientistas criam técnica que protege fígado em casos de câncer de cólon

Tratamento genético, combinado com quimioterapia, ajuda a preservar o órgão de metástases

PAMPLONA, ESPANHA - Uma equipe de cientistas espanhóis desenvolveu uma técnica de tratamento genético que, com a combinação de imunoterapia e quimioterapia, ajuda a proteger o fígado de pacientes com câncer de cólon, já que é comum que a doença se expanda para esse órgão.

Por enquanto, os resultados foram obtidos apenas em testes com animais, informaram na última quinta-feira os responsáveis pela pesquisa, Jesús Prieto e Rubén Hernández, da Universidade de Navarra, no norte da Espanha.

O câncer de cólon apresenta uma tendência de se expandir para o fígado, de modo que mais da metade dos pacientes tem metástases hepáticas, o que limita suas opções de cura, afirmam os pesquisadores.

Nos estágios iniciais, as metástases podem ser eliminadas por cirurgia, mas na maioria dos casos isso não é possível, ou as metástases reaparecem depois de um tempo - por isso, a quimioterapia muitas vezes é a única alternativa, embora sua eficácia a longo prazo seja limitada.

Segundo os responsáveis pelo estudo, "esse tratamento combinado elimina metástases pré-existentes e protege o fígado contra possíveis recidivas". De acordo com Prieto e Hernández, "os resultados obtidos em animais confirmam que é uma modalidade terapêutica sumamente promissora que poderia ser eficaz em pacientes com tumores de cólon com metástase de fígado".

Na fase atual, o trabalho se concentra em aperfeiçoar os mecanismos para produzir meios de tratamento genético com um rendimento compatível a sua aplicação clínica. Além disso, propõe-se a validar os resultados em outros modelos experimentais, para prever seu possível efeito em humanos. 



Teste de vacina contra malária mostra proteção de longa duração

Uma vacina experimental contra a malária da GlaxoSmithKline oferece a crianças africanas uma proteção duradoura, embora sua eficácia diminua ligeiramente ao longo do tempo, de acordo com dados de um estudo inacabado, publicado na sexta-feira (14). Os experimentos foram conduzidos no Instituto de Pesquisa Médica do Quênia.

Segundo os pesquisadores, os resultados mostram que a vacina oferece 46% de proteção por 15 meses.

A malária é uma doença infecciosa transmitida por mosquitos que ameaça mais da metade da população mundial. A maioria das vítimas são crianças menores de 5 anos que vivem em países pobres da África subsaariana.

O último relatório da OMS (Organização Mundial de Saúde) sobre a doença encontrou avanços na última década, como a queda da estimativa de mortes, de quase um milhão em 2000 para 781.000 em 2009.

O estágio avançado de testes da vacina da GSK --conhecido como RTS, S ou Mosquirix-- está em andamento com 16.000 crianças em sete países da África. A imunização termina no próximo mês.

Se os dados mostrarem que a vacina é realmente eficaz, ela poderá ser licenciada e lançada em 2015.

O estudo, realizado entre março de 2007 e outubro de 2008, envolveu 894 crianças com idade superior a cinco meses, no Quênia e na Tanzânia.

Os primeiros resultados, publicados em 2008, mostraram que a vacina deu 53% de proteção contra a malária, pelo menos por oito meses, mas pesquisadores liderados por Ally Olotu, no instituto em Kilifi, Quênia, querem averiguar se a proteção durararia mais tempo.

Os resultados publicados na revista "The Lancet" mostraram que após 15 meses de acompanhamento, a eficácia da vacina não tinha diminuído muito. As crianças vacinadas ainda tinham 46% menos probabilidade de contrair a doença em relação àquelas que não tinham sido imunizadas.

"Mais estudos são necessários para estabelecer a eficácia da vacina, por exemplo, em crianças infectadas pelo HIV ou desnutridas", disse Olotu no estudo. Ele ainda acrescentou que devem ser feitos novos testes em locais com intensidade diferente de transmissão para confirmar os resultados.

O diretor do laboratório GSK (GlaxoSmithKline) Andrew Witty, disse que, se a eficácia da vacina for demonstrada, ela será vendida a um preço acessível a quem mais precisa dela. A empresa informou que está planejando uma margem de lucro de 5% sobre o custo de fabricação, que seriam reinvestidos em novas vacinas contra a malária e outras doenças negligenciadas.

Danos genéticos são causados logo após inalação de fumo, diz estudo

Cientistas 'seguiram' substância tóxica que provoca mutações. Alterações do DNA podem causar câncer de pulmão.

Pesquisadores da Universidade de Minnesota, nos EUA, dizem ter descoberto que a fumaça do cigarro começa a causar danos genéticos minutos após a inalação das substâncias tóxicas.

Cerca de 3 mil pessoas morrem por dia de câncer
de pulmão.

Os cientistas apontam que o câncer de pulmão mata cerca de 3 mil pessoas por dia, e grande parte dessas vidas se perdem por causa do cigarro. O fumo também está ligado a outros 18 tipos de câncer.

Evidências científicas mostram que substâncias danosas presentes no tabaco, os chamados hidrocarbonetos aromáticos policíclicos (HAPs), são um dos culpados pelo câncer de pulmão. Até agora, contudo, os cientistas não haviam detalhado como os HAPs causavam estragos no DNA humano.

Na experiência, os cientistas acompanharam o caminho da substância fenantreno (um tipo de HAP) em 12 voluntários fumantes. Eles descobriram que esse hidrocarboneto rapidamente forma uma substância tóxica no sangue, que estraga o DNA das células, causando mutações que podem causar câncer.

Os fumantes desenvolveram níveis máximos dessa substância em um tempo que surpreendeu os pesquisadores: entre 15 a 30 minutos aos a inalação da fumaça. Segundo os cientistas, é um efeito tão rápido que equivale a injetar a substância tóxica diretamente na corrente sanguínea.

“Os resultados reportados servem como um aviso severo a quem está considerando começar a fumar”, indicam os pesquisadores no estudo, divulgado na publicação científica “Chemical Research in Toxicology”.

Cientistas descobrem que agente causador da vaca louca é transmitido pelo ar

Estudos mostraram que 100% dos ratos que foram fechados em câmaras especiais e expostos a aerossóis com príons (agente infeccioso que causou a epidemia vaca loca), durante um minuto, adoeceram.

ZURIQUE - Um príon, agente patogênico do mal da vaca louca, pode ser transmitido pelo ar, ao contrário do que se pensava até agora, segundo um estudo suíço-alemão, que recomenda precaução a laboratórios, matadouros e fábricas de ração para animais.

O professor Adriano Aguzzi e uma equipe de cientistas das universidades de Zurique (Suíça) e Tübingen (Alemanha) e do hospital universitário de Zurique publicam seu estudo na revista PLoS Pathogens.

Os resultados, que segundo Aguzzi foram "totalmente inesperados", mostraram que 100% dos ratos que foram fechados em câmaras especiais e expostos a aerossóis com príons durante um minuto adoeceram.

Segundo o estudo, quanto mais tempo durou a exposição a este patogênico menor foi o tempo de incubação nos ratos e mais cedo se manifestaram os sintomas clínicos de uma doença causada por príons - que degenera o sistema nervoso central.

Um príon - proteína carente de genoma e ácidos nucleicos - é o agente infeccioso que causou a epidemia da vaca louca, também conhecida como encefalopatia espongiforme bovina, que provocou a morte de 280 mil vacas nas últimas décadas.

Cientistas encontram bactérias vivas enterradas em sal há 34 mil anos

Segundo estudos, a base da sobrevivência desses micro seres é um organismo unicelular, chamado alga Dunaliella. Essa alga produz carvão que servem de sustento às bactérias, que vivem durante períodos imprevisíveis

WASHINGTON - Um complexo ecossistema de bactérias devoradoras de sal sobrevive há 34 mil anos enterrado em fluidos no interior de minerais de Death Valley e Saline Valley, no estado americano da Califórnia, tal como revela um estudo publicado nesta quinta-feira, 13.

A halita, como se denomina o mineral formado por cristais de cloreto de sódio, foi o lar dessas bactérias, procariotas e eucariotas, durante dezenas de milhares de anos, segundo o estudo, publicado na edição de janeiro da revista da Sociedade Geológica Americana, GSA Today.

Segundo o autor do texto, o cientista Brian A. Schubert, do Departamento de Estudos Geológicos da Universidade do Estado de Nova York, as bactérias estão vivas, mas a vida delas é limitada à sobrevivência, pois não usam energia para nadar e nem para se reproduzirem.

A base de sua sobrevivência é um organismo unicelular, chamado alga Dunaliella, presente em muitos sistemas salinos. Esse organismo produz carvão e outros metabolitos que servem de sustento às bactérias.

Assim, os organismos podem sobreviver, durante períodos imprevisíveis, flutuando em fluidos no interior dos minerais.

"A parte mais emocionante (da pesquisa) foi quando pudemos identificar as células de Dunaliella nos cristais, porque eram indícios de que poderia haver uma fonte de alimento", explicou Schubert ao site Our Amazing World.

O rápido crescimento dos cristais de sal, que envolvem todos os fluidos em pequenas borbulhas protegidas em seu interior, é outra das razões da surpreendente longevidade das bactérias, segundo o estudo.

A pesquisa de Schubert e sua equipe não é a primeira descoberta de organismos tão antigos, pois já foram publicados inclusive estudos que falam de bactérias vivas de mais de 250 milhões de anos, mas é a primeira em que os cientistas comprovaram suas conclusões repetindo os testes.

Segundo Schubert, a prova de que seu estudo não é manipulado é que conseguiu fazer com que os organismos voltassem a crescer uma segunda vez, e quando enviou os cristais a outro laboratório, obteve os mesmos resultados.

Os cientistas ainda não determinaram, no entanto, como as bactérias conseguiram sobreviver durante tantos milhares de anos com o sustento tão mínimo que a alga lhes proporcionava.

A equipe pretende agora aprofundar essa pesquisa e contrastá-la com outros estudos que exploram a vida microbiana na terra e no sistema solar, onde existem materiais de inclusive bilhões de anos de idade que são potencialmente capazes de abrigar microorganismos.

Por enquanto, Schubert e seus colegas conseguiram algo pouco comum: que bactérias se reproduzam pela primeira vez em milhares de anos.

Cinco dos 900 cristais de sal analisados pela equipe produziram novas bactérias vivas, indicou Schubert. Segundo ele, os micróbios demoraram cerca de dois meses e meio para "despertar" de seu estado de letargia antes de começar a se reproduzir.

Airborne Pathogens Can Induce Mad Cow Disease, New Findings Suggest

ScienceDaily (Jan. 14, 2011) — Airborne prions are also infectious and can induce mad cow disease or Creutzfeldt-Jakob disorder, new findings suggest. This is the surprising conclusion of researchers at the University of Zurich, the University Hospital Zurich and the University of Tübingen. They recommend precautionary measures for scientific labs, slaughterhouses and animal feed plants.

The prion is the infectious agent that caused the epidemic of mad cow disease, also termed bovine spongiform encephalopathy (BSE), and claimed the life of over 280,000 cows in the past decades. Transmission of BSE to humans, e.g. by ingesting food derived from BSE-infected cows, causes variant Creutzfeldt-Jakob disease which is characterized by a progressive and invariably lethal break-down of brain cells.

It is known that prions can be transmitted through contaminated surgical instruments and, more rarely, through blood transfusions. The consumption of food products made from BSE-infected cows can also induce the disease that is responsible for the death of almost 300 people. However, prions are not generally considered to be airborne -- in contrast to many viruses including influenza and chicken pox.

A high rate of infection

Prof. Adriano Aguzzi's team of scientists at the universities of Zurich and Tübingen and the University Hospital Zurich have now challenged the notion that airborne prions are innocuous. In a study, mice were housed in special inhalation chambers and exposed to aerosols containing prions. Unexpectedly, it was found that inhalation of prion-tainted aerosols induced disease with frightening efficiency. Just a single minute of exposure to the aerosols was sufficient to infect 100% of the mice, according to Prof. Aguzzi who published the findings in the Open-Access-Journal "PLoS Pathogens." The longer expo-sure lasted, the shorter the time of incubation in the recipient mice and the sooner clinical signs of a prion disease occurred. Prof. Aguzzi says the findings are entirely unexpected and appear to contra-dict the widely held view that prions are not airborne.

The prions appear to transfer from the airways and colonize the brain directly because immune system defects -- known to prevent the passage of prions from the digestive tract to the brain -- did not prevent infection.

Protecting humans and animals

Precautionary measures against prion infections in scientific laboratories, slaughterhouses and animal feed plants do not typically include stringent protection against aerosols. The new findings suggest that it may be advisable to reconsider regulations in light of a possible airborne transmission of prions. Prof. Aguzzi recommends precautionary measures to minimize the risk of a prion infection in humans and animals. He does, however, emphasize that the findings stem from the production of aerosols in laboratory conditions and that Creutzfeldt-Jakob patients do not exhale prions.

Virus Might Fight Brain Tumors Better If Armed With Bacterial Enzyme, Study Shows

ScienceDaily (Jan. 14, 2011) — New research shows that oncolytic viruses, which are engineered to destroy cancer cells, might be more effective in treating deadly brain tumors if equipped with an enzyme that helps them penetrate the tumor.

The enzyme, called chondroitinase, helps the cancer-killing virus clear its way through the thickets of protein molecules that fill space between cells and impede the virus's movement through the tumor, say researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute who conducted the study.

When tested in animals transplanted with a human glioblastoma, the most common and deadly form of brain cancer, the enzyme-armed virus improved survival by 52 percent compared with controls and in some cases eliminated the tumor entirely.

The findings were published online in the journal Clinical Cancer Research.

"Our results show for the first time that an oncolytic virus with this enzyme can spread more effectively through the tumor and underscores the potential of using chondroitinases to enhance the capacity of oncolytic viruses to destroy cancer cells," says study leader Balveen Kaur, associate professor of neurological surgery.

The enzyme is derived from the intestinal bacteria called Proteus vulgaris. The enzyme removes sugar chains that branch from molecules called proteoglycans, which fill the narrow spaces between cells. By cutting away these branches, the enzyme clears a path that helps the virus spread through the tumor.

During this study, Kaur and her collaborators injected human glioblastoma cells under the skin of eight animals, and then, after tumors developed, treated the tumors with the enzyme-armed virus. These mice survived an average of 28 days, with two remaining tumor-free after 80 days. Control animals, treated with a virus that lacked the enzyme, survived 16 days.

In another experiment, mice with human gliobastomas transplanted into the brain survived 32 days versus 21 days for control animals, an improvement of 52 percent. Again, two animals lived more than 80 days and showed no trace of the tumor afterward.

Additional studies showed that the enzyme-laden virus had penetrated tumors in the animals' brain significantly better than the enzyme-free control virus.

"Overall, our results indicate that an oncolytic virus armed with this enzyme can have a significantly greater anticancer effect compared with a similar virus without the enzyme," Kaur says.

Funding from the National Institute for Neurological Disorders and Stroke supported this research.

Other researchers involved in this study were Nina Dmitrieva, Lianbo Yu, Mariano Viapiano and E. Antonio Chiocca of Ohio State University; Timothy P. Cripe of Cincinnati Children's Hospital Medical Center and the University of Cincinnati; and J. Glorioso of the University of Pittsburgh.

Why PSA Levels Reflect Prostate Cancer Progression

ScienceDaily (Jan. 14, 2011) — Researchers at the Duke Cancer Institute who have been studying prostate cancer cells for decades now think they know why PSA (prostate-specific antigen) levels reflect cancer progression.

"This is the first demonstration of a mechanism that explains why PSA is a bad thing for a tumor to produce," said senior author Sal Pizzo, M.D., Ph.D., chair of the Duke Department of Pathology. "I am willing to bet there is also a connection in cancerous cell growth with this particular biological signaling mechanism happening in other types of cells."

Using human prostate cancer cells in a laboratory culture, the team found that an antibody reacts with a cell surface receptor called GRP78 on the cancer cells to produce more PSA. The PSA arises inside of the cancer cell and then moves outside of the cell, where it can bind with the same antibody, called alpha2-macroglobulin (α2M).

The PSA forms a complex with the antibody that also binds to the GRP78 receptor, and that activates several key pathways which stimulate cancer cell growth and cell movement and block cell death.

The study bolsters the case for measuring PSA as a marker of tumor progression, as well as for monitoring for α2M antibody levels.

"The use of PSA to make the initial diagnosis of prostate cancer has become controversial over the past decade," Pizzo said. "I personally believe PSA is more useful as a progression marker, particularly with a baseline value on record at the time of the original therapy. A rapidly rising value and/or a very high value is reason for concern. I also believe that monitoring the serum for the appearance of antibodies directed against GRP78 is also a good marker of progression."

Pizzo said that the findings could yield cancer therapies that block the α2M-PSA complex from stimulating the cell receptor signaling cascade, and that his laboratory is investigating possibilities. He said the findings also might yield new kinds of early-detection tests for prostate cancer.

The study will be published in the Jan. 14 edition of the Journal of Biological Chemistry.

Pizzo credits lead author and signaling pathway expert, biochemist Uma Misra, Ph.D., with deducing that PSA may be involved in a signaling feedback loop that promotes more aggressive behavior in the human prostate cancer cells.

"If you were a cancer cell, you would like to turn on cell growth, turn off the process of death by cell apoptosis and you'd like to be able to migrate, and when the α2M antibody binds with the protease PSA molecule, all of that happens," Pizzo said.

Years ago, Misra discovered the GRP78 receptor on the prostate tumor cell surface, the receptor that binds the α2M antibody and the α2M-PSA complex.

"We were surprised to find that this complex binds with the protein GRP78, because we thought the GRP78 molecule only lived deep inside the cell, where it was busy taking improperly folded proteins and helping them to fold properly," Pizzo said. "It was a surprise to find GRP78 on the cell surface, with other functions. Based on the dogma of the time, we didn't think that GRP78 could function as a receptor. Even when we identified it, I doubted our findings."

Pizzo said that since Misra first made the observation about GRP78 working as a receptor, "it has turned into a cottage industry. GRP78 receptors have been discovered on many other cancer cells, including breast, ovary, liver, colon, melanoma and lung cancer cells."

"This is going to be a generic phenomenon to tumors," predicted Pizzo, who is also working to learn more about this receptor in other types of cancer cells. "Not all tumors will express GRP78 on their cell surfaces, but when they do, it probably will be a harbinger of a bad outcome."

"I think we will find that nature favors conservation and it makes sense that the body uses the same types of molecules for different purposes," Pizzo said. "We are beginning to see more of this in other studies, and I predict we will see many more instances."

The other co-author on this paper is Sturgis Payne, also of the Duke Department of Pathology. Funding for the current study came from a small fund from the Duke Department of Pathology.

'Longevity' Protein SIRT1 May Ward Off Precursor to Prostate Cancer

ScienceDaily (Jan. 14, 2011) — Researchers from the Kimmel Cancer Center at Jefferson and two other institutions have discovered new evidence that suggests the "longevity" protein SIRT1, known for its life-spanning effects in different species, can inhibit the development of a known precursor to prostate cancer, prostatic intraepithelial neoplasia (PIN).

Results from the study could lead to new cancer prevention drugs that could not only block prostate cancer but promote longevity.

The study, published in the February 1 issue of Cancer Research, found that deletion of the Sirt1 gene in mice resulted in PIN lesion formation associated with reduced autophagy, which is the necessary degradation of a cell's own components and most likely essential for tumor suppression.

"Prostate cancer is one of the malignancies that has a very direct relationship to aging," says Richard G. Pestell, M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer Biology at Thomas Jefferson University. "And these results provide a direct link for the first time between the onset of prostate cancer and the Sirt1 gene that regulate aging."

The results suggest that the Sirt1 gene promotes autophagy and further highlight the role of the protein SIRT1 (the human homologue of the yeast Silent Information Regulator 2 (Sir2) gene) as a tumor suppressor in the prostate. According to Dr. Pestell, "if you inactivate this gene, then you get the prostate cancer precursor, known as PIN. So it tells you that this 'longevity' gene is normally blocking prostate cancer."

Previous studies have found that SIRT1 -- which was discovered about 15 years ago and found to have various life-spanning effects in yeasts, worms, mice and possibly humans -- can both inhibit tumor growth in certain cancers as well as promote it by inactivating the tumor suppressor p53, but its role in regulating prostate gland development and androgen signaling in vivo was unknown.

To better understand SIRT1's role in the development of androgen-responsive tissues, such as the prostate, researchers from Thomas Jefferson University in Philadelphia, worked with the Herbert Irving Comprehensive Cancer Center at Columbia University in New York and the Ottawa Health Research Institute at the University of Ottawa. Dr. Pestell's laboratory carried out a genome-wide microarray, pathway analysis and histology on Sirt1 positive and negative transgenic mice and littermate controls.

The team found that deletion of the Sirt1 gene in mice resulted in PIN formation; features included cellular hyperplasia, increased Ki67 staining, hyperchromatic nuclei and prominent nucleoli, as well as a reduced size in prostate. Gene expression analysis further demonstrated that loss of endogenous Sirt1 inhibited autophagy, which regulates normal gland development.

Dr. Pestell's laboratory was the first to show that the androgen receptor is regulated by the deacetylase enzyme (SIRT1) in cell lines in a tissue culture. "So then we asked the question, 'if you take prostate cancer cell lines, and if the androgen receptor promotes growth, and acetylation promotes growth, does the deacetylase inhibit growth?'" After establishing that it in fact did, researchers applied their mouse model to establish the same relationship on the animal level.

Since the results of the study suggest that drugs that activate Sirt1 could block prostate cancer, Dr. Pestell explains, his team is now working to test various prevention drugs they've screened for testing in human prostate cancer cells.

Researchers Discover Way to Halt Lung Inflammation in Animal Models

ScienceDaily (Jan. 14, 2011) — Acute inflammation of the lung is a poorly recognized human disease that develops in surprising and unexpected ways. The acute lung injury (ALI) or adult respiratory distress syndrome (ARDS) is a vital new concern for soldiers, but it can develop in anyone during a systemic infection, after severe trauma, as a result of bone fracture, following severe burns and in many other ways as well-- the initial cause may have nothing apparent to do with the lung itself. However, an answer to halting lung inflammation may have been discovered, thanks to a University of Colorado School of Medicine researcher and his team.

Recent studies show that between 60,000 and 100,000 people die each year in the United States from ALI/ARDS, more than twice as many fatalities as those from breast cancer. Recognition that the disease represents an uncontrolled inflammation of the lung has led to some important developments for treatment but even today mortality hovers around 60 percent for those people in whom the disease was identified early enough to initiate treatment.

In a study titled "Xanthine Oxidoreductase Promotes the Inflammatory State of Mononuclear Phagocytes through Effects on Chemokine Expression, Peroxisome Proliferator-activated Receptor-γ Sumoylation, and HIF-1α" publishing January 14 in The Journal of Biological Chemistry,researchers use animal models of ALI/ARDS to show that the aggressive inflammatory state of specific immune cells can be switched off to control the runaway inflammation.

"We now know that cells of the so called innate immune system, neutrophils and macrophages, are involved in causing lung injury that can result in lung failure and death," said Richard Wright, PhD, associate professor at the University of Colorado School of Medicine and lead study researcher. "While these cells are very important for our natural ability to fight off infection, the circumstances that lead to ALI/ARDS can overwhelm this beneficial role. Study of the neutrophils and macrophages that are responsible for ALI/ARDS has led to important ideas which offer hope for new concepts and options for treatment. For example, it is now known that the macrophage itself can exist in both an aggressive inflammatory state and in a more reparative state that can even help the lung to heal."

The researchers now have several drugs that work to achieve the same effect. Ideally, the researchers would like to see that by switching the state of the macrophages to the more reparative state, the ongoing inflammation will be stopped and the capacity of the lung to repair itself will improve.

"This could provide us with a vital new approach to treating this still devastating disease and reduce the persistent mortality of ALI/ARDS," said Wright.

"The results from this study clearly show how an essential enzyme involved in a vital metabolic pathway in our body can control the inflammatory state of key immune cells responsible for acute inflammatory diseases," said Mehdi Fini, MD, a research instructor at the University of Colorado School of Medicine and one of the authors of the paper. "The data from this study will also help us understand and dissect the molecular pathway involved in differential behavior of these cells in the pathogenesis of other diseases of the lung including chronic obstructive pulmonary disease (COPD), lung fibrosis and lung cancer."

Other University of Colorado School of Medicine researchers who collaborated on the study include Jenifer Monks, PhD, and Sean Colgan, PhD.

More Intensive Methods Needed to Identify TB in HIV-Prone Populations

ScienceDaily (Jan. 14, 2011) — Identifying tuberculosis patients in Africa using passive methods is leaving many cases undiagnosed, according to researchers from the Netherlands, Kenya and the United States, who studied case detection methods in HIV-prone western Kenya. Tuberculosis (TB) occurs commonly in men and women with HIV, but in these patients TB can be more difficult to detect.

The findings were published online ahead of the print edition of the American Thoracic Society'sAmerican Journal of Respiratory and Critical Care Medicine.

"Limited information exists on the prevalence of tuberculosis and the best methods of identifying TB patients in African populations with high rates of HIV," said study author Anja van't Hoog, MD, MSc, physician-researcher and epidemiologist, Academic Medical Centre, University of Amsterdam. "In this study, our goals were to estimate how many individuals have TB confirmed by bacteriological testing and the number of cases which occur along with HIV, as well as to evaluate case detection."

In passive detection, which has been the method predominantly used in Kenya and globally since the 1970s, diagnoses are made only after patients present to health clinics and report a prolonged period of coughing. Dr. van't Hoog, who conducted the study while serving as an epidemiologist at the Kenya Medical Research Institute, said more aggressive, intensive methods of detection are needed to help identify more cases, and identify them earlier.

"Previous studies have suggested that passive case finding might be adequate for TB control," she noted. "However, TB epidemiology has changed dramatically as a result of the HIV epidemic, and there is little information available regarding the prevalence of tuberculosis and the effectiveness of case-finding in African populations with high rates of TB and HIV. "

The researchers recruited 20,566 adults from 40 randomly sampled village clusters in a rural area of western Kenya and collected two sputum samples from each adult. Samples were evaluated using a smear microcopy test. Participants also were given questionnaires about their exposure to TB and nearly all participants agreed to undergo a chest X-ray. Those with abnormal X-ray findings or symptoms suggesting TB each provided an additional sputum sample for examination by sputum culture, a testing method which is much more sensitive than smear microscopy.

Following evaluation, 123 participants were identified as having tuberculosis. TB prevalence was greater among men, those who had received prior TB treatment and those in the lowest socioeconomic level. HIV information was available for 101 of the 123 TB-positive participants, of whom 51 percent were identified as being infected with HIV. The researchers estimated 48 percent of the undiagnosed burden of TB in the population is due to HIV.

Diagnosing TB earlier and more accurately can help prevent severe illness and death from TB, and reduce transmission of TB to other community members, Dr. van't Hoog said. Men and women with HIV infection are at much greater risk of getting TB, but the presentation of TB is more often atypical in patients with HIV, making diagnosis more difficult, she added.

"Most of the identified TB cases in this study would not have been identified by the current case detection approach, which includes symptom recognition, sputum smear microscopy and chest X-ray," Dr. van't Hoog noted. "Culturing sputum samples offers more accurate results, but is a more complicated, costlier procedure, making it largely unavailable in resource-limited settings.

"This study identified a considerable prevalence of infectious and largely undiagnosed pulmonary tuberculosis in western Kenya, where rates of HIV infection are high," she said. "The goals for TB control are unlikely to be met without continued improvements in case detection. Intensified case finding is required to control TB in this resource-limited, high HIV-prevalence setting, and future research should focus on ensuring these goals are met."