TUBERCULOSIS: New Tuberculosis Medicine Urgently Needed

Medical researchers are concerned the lack of new medicines developed to treat tuberculosis will encourage drug-resistant strains. More than 200 researchers are meeting at a symposium in Cameroon this week to discuss future steps.
Head of the Novartis Institutions for Developing World Medical Research, Dr. Paul Herrling, said there are many reasons tuberculosis is an increasing problem in places like Sub-Saharan Africa.
"The first one is that the last medicines that we had for TB are about 40 years old," he explained. "And one thing that people did not know at that time, is that this is a very, very clever bacteria - like many others. And when they are treated with the same medicines for a long time, they learn to escape it."
The Novartis Institute is holding the symposium to address challenges and try to determine possible solutions to tuberculosis. Herrling added it that it was crucial to hold the conference in a country that is affected by tuberculosis, because too often the scientists developing the treatments do not understand the everyday realities of their patients.
"It is extremely important to understand not only the molecular biology of your patients, but their culture, their environment, their problems," said Herrling. "And so very often our scientists, they live in laboratories working on TB sitting in Harvard or in London, and they have no clue as to what the disease really is. And on the other hand, local doctors here have no access to the most modern science."
The institute notes that of the 9 million people diagnosed with tuberculosis last year, 30 percent live in Africa. The disease also is increasingly prevalent among people with HIV/AIDS and kills two million annually.
"So many people are infected with tuberculosis, but they are healthy and have no symptoms, because their immune system keeps it in check," Herrling said. "And of course, exactly what HIV does, it weakens your immune system and then those people who were healthy before now become actively sick and can infect others. So it is very much reinforcing or making the problem much worse."
Some patients in rural Africa have a problem completing treatment with an antibiotic called isoniazid. Many fail to complete the treatment that lasts from six to eight months, and even more in some cases.

http://www.voanews.com/english/news/health/Researchers-say-New-Tuberculosis-Medicine-Urgently-Needed-104773149.html

Tuberculosis: 5 page review article: Management of Active Tuberculosis

Management of Active Tuberculosis
BETH POTTER, M.D., KIRSTEN RINDFLEISCH, M.D., University of Wisconsin Medical School, Madison, Wisconsin
CONNIE K. KRAUS, PHARM.D., University of Wisconsin School of Pharmacy, Madison, Wisconsin
Nearly one third of the world’s population is infected with Mycobacterium tuberculosis.1 More than one half of all infections occur in China, Southeast Asia, and the Indian subcontinent; the highest per capita incidence occurs in sub-Saharan Africa.2 In the United States, the incidence of active tuberculosis has decreased steadily since 1992.3 However, the rate of decline has slowed in the past two years.4 Some states and urban centers still report increases in infections, and disparities in incidence and morbidity persist among certain high-risk groups.
Screening and Primary Prevention
The U.S. Preventive Services Task Force5 recommends routine screening for tuberculosis in high-risk populations (Table 1 5). The goal of his recommendation
is to identify persons at significant risk for progressing to active disease. A validated riskassessment questionnaire may be used to identify children
who are likely to benefit from screening (Table 2 6). Primary prevention efforts have focused on the bacille Calmette-Guérin (BCG) vaccine, a live vaccine derived from an attenuated strain of Mycobacterium bovis.
Although BCG vaccine is used commonly in many parts of the world, few data support its effectiveness in reducing tuberculosisrelated morbidity and mortality in the general population. However, vaccination does reduce the occurrence of severe (e.g., meningeal) and disseminated forms of tuberculosis in young children. In the United States, vaccination may be considered for children
with continuous and unavoidable exposure to adults with inadequately treated or multidrug-resistant active disease.7 The decision to vaccinate should be made in consultation with local tuberculosis control programs.
Diagnosis
The diagnosis of active tuberculosis begins with a high index of suspicion for disease. A positive acid-fast bacillus (AFB) smear or positive culture for M. tuberculosis confirms active disease. However, if the suspicion for active disease is high enough, treatment should begin without waiting for a final diagnosis.
Although the overall incidence of tuberculosis has been declining in the United States, it remains an important public health concern, particularly among immigrants, homeless persons, and persons infected with human immunodeficiency virus. Patients who present with symptoms of active tuberculosis (e.g., cough, weight loss, or malaise with known exposure to the disease) should be evaluated. Three induced sputum samples for acid-fast bacillus smear and culture should be obtained from patients with findings of tuberculosis or suspicion for active disease.
If the patient has manifestations of extrapulmonary tuberculosis, smears and cultures should be obtained from these sites. Most patients with active tuberculosis should be treated initially with isoniazid, rifampin, pyrazinamide, and ethambutol for eight weeks, followed by 18 weeks of treatment with isoniazid and rifampin if needed. Repeat cultures should be performed after the initial eight-week treatment.
(Am Fam Physician 2005;72:2225-32, 2235. Copyright © 2005 American
Academy of Family Physicians.)
http://www.aafp.org/afp/2005/1201/p2225.pdf

TUBERCULOSIS: Multidrug-resistant tuberculosis in Europe: Managed or mismanaged?

07.09.2010
The European Respiratory Society as well as researchers from the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) are warning against the dangers of multidrug-resistant TB.

Every year, over 9 million new cases of TB are reported worldwide, with almost 2 million deaths. To make matters worse, the threat of multidrug-resistant bacilli has emerged, making the disease more expensive and difficult to treat.
In 2010, the World Health Organization (WHO) reported an unexpectedly high prevalence of multidrug-resistant tuberculosis with peaks of 25% or more among new cases of TB in some settings. At present, an estimated 5% of the more than 9 million people who develop TB around the world every year are infected with an MDR-TB strain, i.e. a strain that is resistant to (at least) the two most powerful anti-TB drugs currently available, isoniazid and rifampicin. During a joint press conference at the 20th Annual Congress of the European Respiratory Society, experts in the field of tuberculosis will address current challenges in the management of the disease, such as TB/HIV co-infection and the rise of resistant TB strains as well as present an European TB research network, TBNET, aimed at advancing science, clinical research, training, policy development and public health.“TB is a global problem that needs to be dealt with by the international community,” urges Professor Giovanni Battista Migliori, ERS Assembly Head of Respiratory Infections and Director of the WHO Collaborating Centre for TB and Lung Disease, Tradate, Italy.TBNET is an ERS-supported Clinical Research Collaboration (CRC) in the area of tuberculosis research, working in close collaboration with WHO and ECDC. The main areas of focus are the development of improved diagnostic methods and new drugs as well as the prevention and control of drug-resistant TB.“One of the biggest problems in most European countries is that treatment success rates are far below the 85% target set by the WHO World Health Assembly, thereby promoting resistance to common anti-tuberculosis drugs” explains Dr Davide Manissero, Head of Section Respiratory Tract Infections and Tuberculosis Programme Coordinator at the ECDC, Stockholm, Sweden. “Part of the problem is that treatment for multidrug-resistant TB takes substantially longer than for uncomplicated TB; treatment of MDR requires up to 24 months` worth of treatment. The drugs needed are less effective than the first-line drugs for the treatment of drug-susceptible TB and cause more side effects,” says Dr Manissero. For multidrug-resistant TB, the treatment success rate is extremely low (31%). A further threat is extensively multidrug-resistant TB (XDR-TB), defined as MDR-TB that is additionally resistant to any of the fluoroquinolones and any of the three injectable second-line anti-TB drugs, amikacin, kanamycin, and capreomycin.The M/XDR-TB threat is further aggravated by the poor outcomes of this group of patients. In a cohort of 1,100 patients only 30.9% of those who started treatment in 2006 (2006 cohort) were successfully treated in the EU/EEA. A high percentage (13.2%) of these MDR-TB cases defaulted from treatment, increasing the risk for XDR-TB.The latest figures on multidrug-resistant tuberculosis show about 440,000 cases of MDR-TB, causing at least 150,000 deaths. XDR-TB has been reported officially from 58 countries as of March 2010, explains Professor Mario Raviglione, Director, Stop TB Department, WHO, Geneva. “Of all cases of TB, over a million occurred among people living with HIV/AIDS and nearly half a million were fatal.”It is unclear whether HIV infection is a risk factor for drug-resistant or MDR-TB. Known factors that can promote the development of resistance include malabsorption, drug intolerance, drug interactions, and noncompliance among intravenous drug abusers.Dr Raviglione concludes: “Proper TB control based on early and rapid detection and adequate treatment until cure must be in place everywhere to interrupt transmission, avert deaths, and prevent MDR-TB.”
http://www.innovations-report.de/html/berichte/medizin_gesundheit/multidrug_resistant_tuberculosis_europe_managed_161168.html?

TUBERCULOSIS: Washington State: Health Department detains tuberculosis patient

ALEX SILVERMANKIRO
The Seattle-King County Health Department has detained a tuberculosis patient who failed to take required medication.
According to Dr. Masa Narita, director of the department's Tuberculosis Control Program, it is only the second time since 1986 the department has sought a court order to hold a patient who resisted treatment.
The department paid for a motel room and groceries for the patient for a month in order to shield the public from potential exposure and encourage compliance, Narita said. However, the patient missed appointments and treatments due to drug and alcohol use.
The detention will expire Tuesday; the department may then ask King County Superior Court for an extension which would allow it to hold the patient for 45 days.
http://www.mynorthwest.com/category/local_news_articles/20100903/Health-Department-detains-tuberculosis-patient/

TUBERCULOSIS: Extensively Drug-Resistant Tuberculosis: A Sign of the Times and

20 July 2010
Mycobacterium tuberculosis is an extraordinarily successful human pathogen,
infecting one-third of the world’s population and causing nearly two million deaths each year.
In this article, current trends in worldwide tuberculosis (TB) incidence, prevalence, and mortality are discussed along with standard TB treatment regimens, characteristics of first-line and second-line anti-tuberculosis drugs, and mechanisms of antibiotic resistance. The global TB emergency has been further exacerbated by extensively drug-resistant (XDR) TB strains that are resistant to our best antibiotics and very difficult to treat. This review also focuses on the emergence of XDR-TB strains, the global health impact, and existing treatment options and outcomes for XDR-TB disease. Finally, this review briefly describes new antituberculosis drugs currently in Phase II clinical evaluations and the impetus for discovering new antibacterial compounds to target drug-resistant M. tuberculosis and improve tuberculosis therapy.
http://www.mdpi.com/1424-8247/3/7/2268/

TUBERCULOSIS: Rifapentine is granted Orphan Drug Status

July 1, 2010 – Shorter treatment duration with rifapentine expected to bring
significant benefits to patients -
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that the European Commission has granted Orphan Drug status for rifapentine for the treatment of tuberculosis (TB). Rifapentine is an antibiotic member of the rifamycin class, with a higher inhibitory activity against Mycobacterium tuberculosis and a longer half-life than rifampin, the cornerstone of current
TB treatment regimen. These combined are expected to improve the drug exposure of patients to the drug and potentially lead to better efficacy.
European Orphan Drug designation is granted to medicines intended for treatment of life-threatening or chronically debilitating pathologies that affect no more than 5 in 10,000 people in the European Community. The European Commission’s decision follows the positive opinion released by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) that a rifapentine-based combination regimen may be of significant clinical benefit for drug-susceptible TB patients by shortening their tuberculosis treatment.
“Rifapentine is currently one of the most promising drugs for the improvement of patient compliance, which is key to the success of tuberculosis treatment,” said Robert Sebbag, Vice President, Access to Medicines, sanofi-aventis. “To avoid as much as possible the emergence of resistant strains, it is of utmost importance to simplify the treatment of non-resistant TB.”
Sanofi-aventis is revisiting the development of rifapentine to be given daily, in combination with standard daily companion drugs, with the objective of significantly shortening the duration of drug-susceptible TB treatment. This should lead to less premature cessations of treatment, and thus to a reduction of
treatment failures, a lesser risk of development of drug-resistance, as well as a reduction of costs, all of which are expected to bring significant benefits to patients and public health systems.
Rifapentine is currently marketed in the United States for the treatment of pulmonary and drugsusceptible TB within a standard 6-month course combination regimen.

http://en.sanofi-aventis.com/binaries/20100701_RIFAPENTINE_en_tcm28-28921.pdf

MALARIA: Customs group to fight $200 bln bogus drug industry

Counterfeit drugs have become a $200-billion-a-year industry and the 176-nation World Customs Organization (WCO) will sign a declaration later this month to fight the scourge, an official said on Thursday.
Fake or substandard versions of medicines are often hidden in cargoes sent on circuitous routes to mask their country of origin.
"We have more fakes than real drugs in the market," said Christophe Zimmermann, the WCO's anti-counterfeiting and piracy coordinator. "In 2007-2008 alone, it rose 596 percent."
Pharmacies and back street merchants in Africa sell fake medicines at rock-bottom prices.
The World Trade Organization says fake anti-malaria drugs kill 100,000 Africans a year and the black market deprives governments of 2.5-5 percent of their revenue.
The Brussels-based WCO represents customs operations globally and has joined with former French president's Jacques Chirac's foundation to raise awareness at upper echelons to curtail the illicit industry.
Spurred by Chirac's foundation, 176 national customs chiefs will sign a declaration on June 24 to ban the making and marketing of counterfeit drugs, Zimmermann told Reuters.
Fake medicines often contain the wrong or toxic ingredients and pose a growing health threat worldwide, especially in poor countries where drugs are sold to treat conditions such as malaria, tuberculosis and HIV.
"If these subjects are not dealt with and strong action not taken, they will be a source of conflict," said Catherine Joubert, director general of the Fondation Chirac, adding that so far 30 groups had signed the declaration.
Getting the WCO's 176 members on board will lend legitimacy to proposals to revamp obsolete legislation and improve coordination between enforcement agencies, Zimmermann said.
Western Europeans spend an estimated 10.5 billion euros ($14.3 billion) a year on illicitly sourced medicines, according to a Pfizer-sponsored survey published in February.
In a sign Europe is taking the issue seriously too, justice ministers on the Council of Europe are set to ratify a convention on counterfeit medicines in Istanbul this November.
http://www.reuters.com/article/idUSTRE65961U20100610

MALARIA: drug resistance

The World Health Organisation, governments, and non-profit groups are not paying enough attention to the dangers of drug-resistant drugs, a report from the Centre for Global Development has warned.
According to the report, laudable efforts to increase access to drugs in the developing world are hardly accompanied by measures to protect the continued effectiveness of drug treatment.
It called on the distributing agency to “strenuously enforce quality standards throughout the supply chain, ensure that adequate knowledge is gathered about the effectiveness of the medicines they are providing, and use their purchasing power to drive drug quality standards throughout the supply chain.”
The report, which was released on Tuesday, added that children in the developing world die every year from drug-resistant strains of malaria, tuberculosis, AIDS, and other diseases.
It also revealed that more than 40 percent of children worldwide live in malaria endemic countries, while malaria kills almost 1 million children under the age of five in sub-Saharan Africa alone annually.
Many of the drug distribution programmes may be driving drug resistance and endangering the lives they are meant to save, according to the report from the Centre for Global Development.
“We are rapidly losing our ability to cure an alarming number of the most serious and common diseases of the developing world because of an invisible adversary: drug resistance. Resistance is inevitable - but careless practices in drug supply and use are hastening it unnecessarily.
“Without an immediate global effort to safeguard lasting treatment effectiveness, drug resistance will quickly become a widespread threat, claiming lives, raising the cost of curing patients, and making future generations increasingly vulnerable to deadly diseases that were easily cured in the past, ” said the Centre’s Rachel Nugent, who led the group that wrote the report.
High cost
Since 2006, donors have spent more than 1.5 billion dollars on specialised drugs to treat resistant bacteria and viruses, and this could worsen the report cautions.
The Centre’s report looks for even broader action, urging WHO to lead others, including pharmaceutical companies, governments, philanthropies that buy and distribute medicines, hospitals, healthcare providers, pharmacies and patients.
The report finds clear links between increased drug availability and resistance. For instance, in countries with the highest use of antibiotics, 75 to 90 percent of Streptococcus pneumoniae strains are drug-resistant, it found.
“Poor quality drugs, counterfeit drugs, incomplete use of drugs, and other factors all contribute to the problem, and this problem will worsen as drug access programs succeed,” it cautions.
“The number of people being treated for HIV/AIDS, for example, increased 10-fold between 2002 and 2007; there was an 8-fold rise in deliveries of (drugs) for malaria treatment between 2005 and 2006.
“And the Stop TB Partnership’s Global Drug Facility has expanded access to drugs for TB patients, offering nearly 14 million patient treatments in 93 countries since 2001,” it added.
Child’s health impact
The long-term effects of malaria on a child’s health and development are often insufficiently recognised and poorly managed, the report identifies.
“A severe form of the disease, cerebral malaria, kills 10-20 percent of those children it affects, while an additional 7 percent are left with permanent neurological problems, including blindness, epilepsy, and speech and learning difficulties.
“Chloroquine was an effective first-line malaria treatment for more than 50 years, but when resistance rates became unacceptably high in the mid-1990s, SP became the only affordable, effective alternative with limited side effects,” it stated.
Mrs. Nugent, who is also the deputy director of global health, while commenting on drug resistance and the administering of bad malaria pills in some Africa countries, told journalists in February 2010, that, “there are many cases of malaria that are being only partially treated, and that just guarantees acceleration of artemisinin drug resistance.”
The result of a study conducted in Africa then revealed that high rates of the most effective type of malaria-fighting drugs sold in three African countries are poor quality - including nearly half the pills sampled in Senegal.
The group, however, highlighted the need for governments to “have a responsibility to provide regulation and oversight of drug licensing, manufacturing distribution, and use, as well as to properly support laboratory facilities and surveillance systems, in order to detect and monitor drug efficacy.”
Patients, prescribers, and dispensers were all advised to gain greater awareness of the personal and social costs of drug resistance, and employ far greater diligence in appropriately using drugs.
http://234next.com/csp/cms/sites/Next/Home/5581274-146/global_drug_resistance_raises_fear_says.csp

TUBERCULOSIS: Paediatric cases difficult to diagnose

DURBAN, 2 June 2010 (PLUSNEWS) - The fight against tuberculosis (TB) has failed children: the share of paediatric TB is increasing, and children have not escaped the rising tide of drug-resistant strains, according to new research presented at the South African TB Conference. Dr Ntombi Mhlongo-Sigwebela, TB programme director at the University Research Company, a public health consultancy, told the conference in the port city of Durban that TB in children under four years of age now accounted for about nine percent of all national TB cases annually. Dr Kalpesh Rahevar, a World Health Organization (WHO) medical officer, said inconclusive conventional TB skin tests (to determine whether a patient has a latent TB infection) and the inability to get sputum samples from young children made paediatric TB more difficult to diagnose and treat than in adults. "This highlights the challenge of diagnosing children, especially at the primary care level ... there are differing abilities to accurately diagnose TB; where there is a paediatrician who takes an interest in TB, you see a higher number of cases diagnosed," Mhlongo-Sigwebela told IRIN/PlusNews. To make things worse, paediatric drug formulations and international treatment guidance for children were also inadequate, said Dr Ben Marais of University of Stellenbosch, in Western Cape Province. "The WHO only produced guidelines this year on optimal isoniazid [a drug used to treat TB] dosing for children," he told IRIN/PlusNews. "I think this speaks to how poorly we've served children ... [it has been] more than 60 years since the discovery of the drugs [and only now do] we have an optimal [paediatric] dosing." WHO has listed South Africa's TB epidemic among the world's worst, and research has indicated that about 70 percent of adult TB patients are co-infected with HIV [http://www.aidsmap.com/en/news/BEF8C8CE-BC45-4DD4-B859-00E42D5F9459.asp]. Marais said the key to preventing paediatric TB infections was halting adult TB, improving infection control, and access to isoniazid preventive TB therapy.