TUBERCULOSIS: WHO: New action plan lays the foundation for tuberculosis elimination

13 OCTOBER 2010
New action plan lays the foundation for tuberculosis elimination. Targets are realistic, but a projected shortfall of US$ 4.2 billion per year for TB care and crucial research must be filled
The world could be on its way towards eliminating tuberculosis (TB) if governments and donors fully invest in a plan released today by the Stop TB Partnership. The global plan to stop TB 2011-2015: transforming the fight towards elimination of tuberculosis for the first time identifies all the research gaps that need to be filled to bring rapid TB tests, faster treatment regimens and a fully effective vaccine to market. It also shows public health programmes how to drive universal access to TB care, including how to modernize diagnostic laboratories and adopt revolutionary TB tests that have recently become available.
Action needed against TB
"There is an urgent need to scale up action against TB - 10 million people, including 4 million women and children, will lose their lives unnecessarily between now and 2015 if we fail," says Dr Margaret Chan, Director-General of WHO, which hosts the Stop TB Partnership. "TB control works, with global incidence of the disease declining since 2004, although much too slowly."
Twenty-two countries, including South Africa, bear 80% of the burden of TB worldwide. Some 9 million people become ill with active TB and nearly 2 million die each year. The new Global Plan sets out to provide diagnosis and treatment approaches recommended by the World Health Organization (WHO) for 32 million people over the next five years.
Blueprint to cut global TB deaths by half
"The Global Plan to Stop TB provides an urgently needed blueprint to cut global TB deaths by half," says Dr Aaron Motsoaledi, Minister of Health of South Africa. "In South Africa we have embarked on an ambitious agenda for reducing the toll of TB on our people, and we are committed to meeting the Global Plan's targets. We call on world leaders to invest in the plan, which can help move us towards ridding the world of TB."
Although TB is curable, the treatment requires taking a combination of drugs for at least six months. Laboratories in most countries are still using a century-old diagnostic method that involves searching for TB bacteria derived from a person's sputum under a microscope. And there is still no vaccine able to prevent pulmonary TB, the most common form of the disease.
"While-you-wait" rapid TB tests
In addition to helping public health programmes adopt already existing modern diagnostic tests, the Global Plan sets a research agenda aimed at engendering two new "while-you-wait" rapid tests that trained staff at even the most basic health outposts can use to diagnose TB accurately. By 2015, the aim is for three new drug regimens - one for drug-sensitive TB and two for drug-resistant TB - to be going through Phase III clinical trials, the final step before drugs are released to market. Four vaccine candidates should be at the same stage of testing.
Addressing drug-resistant TB
The Global Plan provides a clear roadmap for addressing drug-resistant TB. It calls for 7 million people to be tested for multidrug-resistant TB (MDR-TB) and one million confirmed cases treated according to international standards over the next five years.
Half a million people die each year from HIV-associated TB. Provided the plan's targets are met, by the end of 2015, all TB patients will be tested for HIV and, if the test is positive, receive anti-retroviral drugs and other appropriate HIV care. In HIV treatment settings, all patients will be screened for TB and receive appropriate preventive therapy or treatment as needed.
Financing
On financing, the Global Plan calls for US$ 37 billion for implementation of TB care between 2011 and 2015. A funding gap of about US$ 14 billion - approximately US$ 2.8 billion per year - will remain and needs to be filled by international donors.
The plan includes a separate calculation of the funding required to meet targets for research and development: a total of US$ 10 billion, or US$ 2 billion per year. High-income countries and those with growing economies will need to increase their investment in research and development to fill an estimated gap of about US$ 7 billion, or US$ 1.4 billion per year
In 2006 the Stop TB Partnership launched the Global Plan to Stop TB 2006-2015. The new roadmap for 2011-2015 follows on that earlier plan while setting new and more ambitious targets for the next five years.
For more information, please contact:
Judith Mandelbaum-Schmid, Mobile: +41 79 254 68 35, E-mail: schmidj@who.int

http://www.who.int/mediacentre/news/releases/2010/tb_20101013/en/index.html

MALARIA: Buffer substitution in malaria rapid diagnostic tests causes false-positive results

22 July 2010
Abstract (provisional)
Background
Malaria rapid diagnostic tests (RDTs) are kits that generally include 20 to 25 test strips or cassettes, but only a single buffer vial. In field settings, laboratory staff occasionally uses saline, distilled water (liquids for parenteral drugs dilution) or tap water as substitutes for the RDT kit's buffer to compensate for the loss of a diluent bottle. The present study assessed the effect of buffer substitution on the RDT results.
Methods
Twenty-seven RDT brands were run with EDTA-blood samples of five malaria-free subjects, who were negative for rheumatoid factor and antinuclear antibodies. Saline, distilled water and tap water were used as substitute liquids. RDTs were also run with distilled water, without adding blood. Results were compared to those obtained with the RDT kit's buffer and Plasmodium positive samples.
Results
Only eight cassettes (in four RDT brands) showed no control line and were considered invalid. Visible test lines occurred for at least one malaria-free sample and one of the substitutes in 20/27 (74%) RDT brands (saline: n = 16; distilled water: n = 17; and tap water: n = 20), and in 15 RDTs which were run with distilled water only. They occurred for all Plasmodium antigens and RDT formats (two-, three- and four-band RDTs). Clearance of the background of the strip was excellent except for saline. The aspects (colour, intensity and crispness) of the control and the false-positive test lines were similar to those obtained with the RDT kits' buffer and Plasmodium positive samples.
Conclusion
Replacement of the RDT kit's dedicated buffer by saline, distilled water and tap water can cause false-positive test results.
http://www.malariajournal.com/content/9/1/215

MALARIA: Reliability of Rapid Diagnostic Testing (RDT)

Malaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs) are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern.
Methods
Cross-sectional study. Subjects: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. Exclusion criteria: severe clinical condition needing urgent care.
Results
In the dry season, 186/852 patients with fever (22%) and 213/1,382 patients without fever (15%) had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64%) and 623/1,669 (37%), respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV) was 9% and the negative predictive value (NPV) was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for adults to 82% for infants, while the NPV ranged from 84% for infants to over 99% for adults.
Conclusions
In the dry season the RDT has a low positive predictive value, but a very high negative predictive value for malaria-attributable fever. In the rainy season the negative test safely excludes malaria in adults but not in children.
http://www.malariajournal.com/content/9/1/192

UN approval of rapid tests for malaria

The United Nations health body assessed 29 rapid tests from a range of different manufacturers and found that 16 of them met minimum performance criteria.
Around 40 percent of the world's population is at risk of malaria, a potentially deadly disease transmitted via mosquito bites. It kills around 860,000 people a year worldwide, most of them children in Africa. There are also cases in Asia, Latin America, the Middle East and parts of Europe.
"These rapid tests have been a major breakthrough in malaria control," Robert Newman, director of WHO's Global Malaria Program, said in a statement. "They allow us to test people who cannot access diagnosis based on microscopy in remote, rural areas where the majority of malaria occurs."
WHO malaria guidelines call for diagnosis using either microscopy or rapid tests before treatment in all suspected malaria cases, but in 2008, only 22 percent of suspected cases were tested in 18 of 35 African countries that reported data.
The Geneva-based WHO said wider diagnosis would allow health workers to identify which patients with fever have malaria and need drugs, and which have other causes of illness and need other treatment. It would also improve overall childhood survival, a key U.N. development goal.
"With 38 tests that now meet minimum performance criteria, malaria-endemic countries... have a wider choice of tests which have been assessed for quality and reliability," the WHO said.
The best treatments for malaria are artemisinin combination therapy (ACT) drugs made by firms like France's Sanofi-Aventis, but they can also be expensive.
Resistance to chloroquine and sulfadoxine-pyrimethamine, the cheapest malaria drugs, is becoming more common.
http://www.reuters.com/article/idUSTRE63M3T420100423

Rapid Diagnostic Tests (RDT) to prevent overuse of medication

Rapid diagnostic tests (RDTs) for malaria are at the early stages of introduction across malaria endemic countries. This is central to efforts to decrease malaria overdiagnosis and the consequent overuse of valuable anti-malarials and underdiagnosis of alternative causes of fever. Evidence of the effect of introducing RDTs on the overprescription of anti-malarials is mixed. A recent trial in rural health facilities in Ghana reduced overprescription of anti-malarials, but found that 45.5% patients who tested negative with RDTs were still prescribed an anti-malarial.
Methods
A qualitative study of this trial was conducted, using in-depth interviews with a purposive sample of health workers involved in the trial, ranging from those who continued to prescribe anti-malarials to most patients with negative RDT results to those who largely restricted anti-malarials to patients with positive RDT results. Interviews explored the experiences of using RDTs and their results amongst trial participants.
Results
Meanings of RDTs were constructed by health workers through participation with the tests themselves as well as through interactions with colleagues, patients and the research team. These different modes of participation with the tests and their results led to a change in practice for some health workers, and reinforced existing practice for others. Many of the characteristics of RDTs were found to be inherently conducive to change, but the limited support from purveyors, lack of system antecedents for change and limited system readiness for change were apparent in the analysis.
Conclusions
When introduced with a limited supporting package, RDTs were variously interpreted and used, reflecting how health workers had learnt how to use RDT results through participation. To build confidence of health workers in the face of negative RDT results, a supporting package should include local preparation for the innovation; unambiguous guidelines; training in alternative causes of disease; regular support for health workers to meet as communities of practice; interventions that address negotiation of health worker-patient relationships and encourage self-reflection of practice; feedback systems for results of quality control of RDTs; feedback systems of the results of their practice with RDTs; and RDT augmentation such as a technical and/or clinical troubleshooting resource.
http://www.malariajournal.com/content/9/1/95