MALARIA: in pregnancy

The intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) has been a key component of the focused antenatal care package for nearly a decade, reducing the burden of low birthweight attributable to malaria in sub-Saharan Africa. However, SP has lost parasite sensitivity in many sub-Saharan locations during the same period, rendering its beneficial effect in IPTp debatable. Malaria transmission has also declined in some epidemiological settings. There is no evidence to suggest, however, that the risk of malaria in pregnancy without preventive measures has declined in the same locations. Thus, the urgency to identify efficacious drugs and/or new strategies to prevent malaria in pregnancy remains as great as ever. We summarise the results of recently published SP-IPTp studies from areas of high drug resistance and/or low malaria transmission. We also present the evidence for mefloquine and azithromycin-based combinations (ABCs), two leading drug options to replace SP in IPTp. We discuss optimal dosing for ABCs and their likely protection against several sexually transmitted and reproductive tract infections. We also summarise data from a diagnosis-based alternative to IPTp known as the intermittent screening and treatment (IST) for malaria. Clinical and operational research is urgently needed to compare birth outcomes achieved by IPTp with ABCs vs. IST using an efficacious antimalarial therapy



http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2011.02765.x/abstract

MA:ARIA: Resistance - a barrier to malaria elimination

Bill Brieger : 07 Apr 2011

The World Health Organization reminds us today that, “Antimicrobial resistance is not a new problem but one that is becoming more dangerous; urgent and consolidated efforts are needed to avoid regressing to the pre-antibiotic era.” It is not just antibiotics that are in trouble, but other microbial agents including malaria drugs.
In the malaria community we are also worried about insecticide resistance. Growing resistance to DDT was one of the reasons that earlier efforts to eradicate the disease were not globally successful.
WHO explains clearly that human behavior (patients, providers, health service managers and drug manufacturers) plays a big role in developing antimicrobial resistance:
Antimicrobial resistance is facilitated by the inappropriate use of medicines, for example, when taking substandard doses or not finishing a prescribed course of treatment. Low-quality medicines, wrong prescriptions and poor infection control also encourage the development and spread of drug resistance. Lack of government commitment to address these issues, poor surveillance and a diminishing arsenal of tools to diagnose, treat and prevent also hinder the control of drug resistance.
Scientific American this month has two timely articles on antibiotic resistance that also highlight how human behavior exacerbates the problem. Agricultural use of antibiotics is one major problem. Another revolves around infection prevention procedures (or the lack thereof) in hospitals.
The use of combination drug treatments was expected to slow or prevent the emergence of resistance to another class of anti-malaria drugs, but prior and continued use of monotherapy artesunate drugs in Southeast Asia has raised the specter of resistance developing there and spreading throughout the world following the patterns of chloroquine and sulphadoxine-pyrimethamine. The following steps are designed to help:
Treatment only with combination therapies where there is no demonstrable resistance for either component of the combination
Treatment based only on positive results of parasitological tests thus avoiding indiscriminant use of malaria drugs
Regular/frequent drug efficacy testing using WHO protocols
Pharmacovigilence/Surveillance
Donors and National Malaria Control Programs must recognize and fund surveillance activities as one of the central interventions in efforts to eliminate malaria. As this year’s World Health Day theme clearly states: no action today, no cure tomorrow.
http://www.malariafreefuture.org/blog/?p=1188

TUBERCULOSIS: Canada: TB deaths in homeless not improving: study

Nathan Denette/Canadian Press Feb 21, 2011

Inadequate housing complicates TB treatment. About 20 per cent of homeless people with tuberculosis die within a year of diagnosis, a new Toronto study finds.
The 10-year study published in Wednesday's issue of the journal Emerging Infectious Diseases also found some key recommendations made by a provincial coroner's inquest in 2001 have not been implemented.
"Ten years ago we had a lot of problems with TB in our shelters with roughly about 20 per cent of patients dying [within] one year of diagnosis," said Dr. Michael Gardam, medical director of the tuberculosis clinic at Toronto Western Hospital and one of the study's authors.
A decade later, that figure hasn't changed, the researchers found.
The inquest into the death of Joseph Teigesser, a homeless man who died of tuberculosis in Toronto in 2001, made 13 formal recommendations. These included provincial funding for a centralized clinic system to provide specialized care for people with TB and improvements to shelter ventilation — two recommendations that have fallen short, the study's authors said.
Despite several reports on how to fight the treatable, airborne disease, timing is often a problem, said Dr. Elizabeth Rea, a study co-author and associate medical officer of health with Toronto Public Health.
"If someone is diagnosed relatively early with TB, even if they're homeless,even if they have a slew of other problems we can get them safely through treatment. But there are still a lot of people who are diagnosed late," said Rea.
Inadequate housing, substance dependence, language barriers, mental health problems and stigma complicate TB treatment, the researchers noted.
The team also found tuberculosis among homeless persons born outside of Canada is on the rise — nearly 40 per cent of homeless tuberculosis cases were in immigrants.
That change in patients increases the risk of introducing a drug-resistant strain of TB into the shelter system, Gardam said. If so, it could set off an outbreak that could possibly spread to the general population, he added.


Worldwide, TB claimed the lives of 1.7 million people in 2009, according to the World Health Organization.
http://www.cbc.ca/news/canada/toronto/story/2011/02/16/tuberculosis-homeless-toronto.html

TUBERCULOSIS: Nigeria: Multi-Drug Resistant TB Epidemic Imminent in Country

Chiomaobinna : 1 February 2011
An escalating number of Multi-Drug Resistant Tuberculosis (MDR-TB) cases in Nigeria is currently constituting a major source of worry.
Medical experts have warned that the trend should be quickly checked in order to forestall what they describe as "imminent and total collapse of the efficacy of the available first-line drugs for TB treatment."
Findings by Good Health Weekly show that the spectre of resistance is fast overwhelming important anti-TB drugs such as Isoniazid and Rifampicin.
Worse still, a number of the infectious diseases hospitals responsible for providing TB treatment nationwide are functioning below optimal capacity.
This development, which may lead to the country settling for the more expensive second-line drugs that not only less efficient but more toxic.
Specifically, when MDR-TB occurs, unlike the normal TB that requires six months to treat, a patient diagnosed of MDR-TB would be on treatment for at least 18 to 24 months. In the first phase of treatment, the patient must be hospitalised for six months, followed by ambulatory care for the next 18 months.
"TB is very much with us and we must all put all hands on deck to contain it before it gets out of control," says Dr. Oni Idigbe, Director of Research, and former Director-General of the Nigeria Institute of Medical Research (NIMR).
"A TB patient is said to have developed MDR -TB when the patient becomes resistant to the two most important and potent anti - TB drugs. The bottom line of TB control is to detect active cases of TB and render them non-infectious with adequate treatment," he remarked.
Statistics from the National Tuberculosis and Leprosy Control Programme have shown that currently, there are more than 7,000 MDR-TB cases in the country. Globally, there are about 500,000 cases of MDR-TB, of which only 3 per cent get proper treatment.
Idigbe who expressed concern on the poor management of TB in private facilities said: "We are beginning to see cases of multi-drug resistant (MDR) TB. These are cases that are now getting resistant to the normal drugs we use to treat TB. If these cases are allowed to continue to develop and transmit infections, we are going to run into the problem of losing all the drugs that we have for TB and start going for second line drugs".
Pointing out that most of the cases of MDR-TB develop as a result of wrong clinical management, he said drug-resistant TB is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period or health workers prescribe the wrong treatment regimens, or because the drug supply is unreliable.
Lamenting the development, Idigbe said most TB treatment programmes have not been succeeding because the nation is just operating at the level of secondary and tertiary healthcare forgetting the primary health care and the communities.
"This is where knowledge, attitudes and behavioural practices are very low. They need to be enhanced. The drive now is the public-private mix (PPM) so that the public and the private sector will work together. We need to go to communities and educate them on the signs and symptoms of TB because the earlier you detect a case and break the chain of transmission, the better."
He said using the recommendations of the WHO, efforts will now be geared towards using the Advocacy Communication and Social Mobilisation (ACSM) Strategies to detect existing active cases.
Nigeria ranks 4th out of the 22 countries that have 75 per cent of the global burden of TB. An estimated 450,000 new TB cases occur annually. Just 94,000 were detected last year.
To tackle TB effectively, the World Health Organisation (WHO) recommends that countries must detect at least 75 per cent of active case and attain 85 per cent treatment. In Nigeria only 36 per cent are detected and over 60 per cent cases are not being treated. The implication of this, according to experts, is that anybody can be infected with TB.
Close contact with a TB patient over a period, increases chances of infection even as one active TB case in a community has potential of infecting 10 people. Most cases are usually detected late with very few getting effective treatment. The patients die or develop MDR-TB.
However, a ray of hope may be on the way as the country is set to host the 18th Conference of The Union African Region of the International Union Against Tuberculosis and Lung Disease in Abuja, March 2-5, 2011.
The conference, with the theme: TB, TB/HIV and other Lung Diseases: Challenges to the attainment of MDGs in Africa, has been designed to address problematic areas of TB and lung diseases, particularly, MDR-TB cases and how to delist Nigeria and other African countries from the list of TB high-burden countries.
Participants are expected to deliberate on problems and solutions of lung disorders as well as new preventive, diagnostic and curative methods to fight TB, among others.
http://allafrica.com/stories/201102020428.html

TUBERCULOSIS: Viet Nam: More patients resistant to tuberculosis drugs

HCM CITY — Doctors warn that the number of tuberculosis patients resistant to drugs is on the increase in HCM City.
Director of the Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases Nguyen Huy Dung said the number of TB patients in the city had doubled from 8,000 to 15,000 in the past 10 years.
On average, the number of patients increases by about 2 per cent a year. Most patients are between 25-54 years old.
Hospital statistics show that TB patients and thousands more with lung and bronchial diseases are making life a burden for the medical sector.
Dung said that every year, about 14,000-15,000 more patients attended TB control programmes in the city. About 8,000 were new patients.
Last year, more than half of the 100,000 people – or nearly 1 per cent of the city's population – who went to the TB hospital for health checks were found to have various levels of the disease. About 1,100 of them were resistant to drugs, including about 200 patients who cannot be treated with them.
There are a total of about 700 chronic tuberculosis patients who are resistant to most drugs. Only about 50 per cent can be cured.
Phan Thuong Dat, a doctor of the hospital, said that treating these patients was as difficult as treating patients 50 years ago when there were few antibiotics.
Dung said the main reason for the increased number of TB patients resistant to drugs was the low awareness.
After treatment for two months many patients refused to take more drugs because they were feeling healthier, but the correct treatment period is about eight months.
Another reason for the increase in TB patients was the cost of treatment was nearly VND10 million (US$500) in eight months, so many patients could not afford a complete course.
"Patients joining the national tuberculosis control and prevention programme are exempted from paying for the five main drugs, but they still have to buy a number of restorative and other drugs," said Dung.
"Besides, doctors at private hospitals write prescriptions for tuberculosis patients although they do not specialise in the disease," he said.
Dung said that this year the medical sector would join hands with municipal police to supervise the work of private hospitals.
http://vietnamnews.vnagency.com.vn/Social-Isssues/208120/More-patients-resistant-to-tuberculosis-drugs-.html

TUBERCULOSIS: Rates of Anti-Tuberculosis Drug Resistance in Kampala-Uganda Are Low and Not Associated with HIV Infection

January 12, 2011
Drug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda.

Methods/Principal Findings
Among 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3–2.5) and resistance to any drug in 57 (12.1%, 9.3–15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8–22.6) and 17 (28.3%; 17.5–41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9–36.1) tested positive. Neither multidrug (adjusted odds ratio (ORadj) 0.7; 95% CI 0.19–2.6) nor any resistance (ORadj 0.7; 0.43–1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (ORadj 3.5; 1.0–12.0).

Conclusion/Significance
Anti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health care.

http://elitestv.com/pub/2011/01/rates-of-anti-tuberculosis-drug-resistance-in-kampala-uganda-are-low-and-not-associated-with-hiv-infection

TUBERCULOSIS: London: The Tuberculosis Capital Of Europe

sara: December 18, 2010

The UK is the only country in Western Europe with rising rates of tuberculosis (TB), and cases in London have increased more than 50% since 1999. Nationwide, there are now more than 9,000 cases of TB diagnosed per year (9,040 in 2009). The problem is becoming particularly acute in London, where 40% of all UK TB cases are diagnosed. In a Comment published Online First in The Lancet, Global TB expert Professor Alimuddin Zumla, University College London, UK, calls for recommendations from a recent UK TB review to be implemented urgently to keep this re-emerging problem under control. A World Report in this week’s Lancet also discusses TB in homeless people in London.
The death toll from TB (often called the ‘white plague’ in Victorian times) in the UK began to fall in London at the start of the 20th century as living standards (better housing, nutrition and economic status) improved and subsequent TB control was achieved by the introduction in the early 1960s of anti-TB drugs, improved health services and BCG vaccination. By the early 1980s TB was considered to be conquered in the UK and National Health Service (NHS) TB services were scaled down considerably.
Alarmingly, TB has returned to London with a vengeance with an increase in the number of TB cases by nearly 50% since 1999, from 2,309 cases in 1999 to 3,450 cases in 2009 accounting for nearly 40% of all TB cases in the UK. Since current detection methods (sputum microscopy and culture) only detect up to 70% of active cases, and UK doctors generally need to strongly suspect TB as a possibility before diagnosing it, it is likely the number of cases reported is underestimated.
The increase in the number of TB cases seen in the UK has largely been in non-UK born groups; in 2009 these were black African (28%), Indian (27%) and White (10%)3. Interestingly most of these were not in new migrants; 85% of cases born overseas had lived in the UK for two or more years and about half had lived here for five or more years (indicating that the TB was not imported into the UK) and TB was shown to be common in London boroughs experiencing relative deprivation. Cases of drug resistant TB are also increasing in London.
Professor Zumla says: “Poor housing, inadequate ventilation, and overcrowding – conditions prevalent in Victorian Britain – are causes of the higher TB incidence rates in certain London boroughs. In all European countries, the disease is mainly concentrated in high-risk groups, such as migrants, refugees, homeless people, drug users, prisoners, and HIV-infected groups.”
He highlights the issue of spread within prisons, and from prisoners and prison staff to the community. A retrospective 4 year (2004-2007) study of 205 prisoners with newly diagnosed TB showed that prisoners were more likely to be UK born (47% versus 25%), to be white (33% versus 22%) and to have pulmonary TB (75% versus 56%) compared to all other TB patients seen in the UK during that period (29,340 cases in those aged 16 years or older).
The situation in London is, says Professor Zumla, reminiscent of the multi-drug resistant TB outbreaks in prisons in the USA in the 1990s, that required a large financial investment to be brought under control. Professor Zumla refers to the recent London TB Service Review Assessment, written by the Public Health Assessment Support Team (a social enterprise organisation in London) that recommends:

- An urgent and radical re-think on delivery of NHS TB Services
- The urgent need to establish a multi-agency Board including service users for TB Control for London which will closely monitor the performance these services and achieve a year on year reduction in the incidence of TB.
- Greater integration across the full range of bodies involved in TB control, including NHS services, port health, health protection units, Directors of Public Health, local authorities, the third sector, and the office of the London Mayor
- Standardised pathways of care for TB in London, through the use of a Manual of Clinical Policies and Protocols, to be based on the New York model. ie, a community based model of care, moving away from the more traditional clinic model found in the UK.
- Improvements to the accessibility and responsiveness of TB NHS services in line with the needs of local people.
Professor Zumla concludes: “This review, if implemented by the UK NHS, would allow standardisation of TB clinical policy and practice and improve responsiveness of London’s TB services needs.
An immediate and serious long-term political and financial commitment is needed from the UK Government through the NHS if the tide is to be turned against the return of the white plague in London, and if tuberculosis is to be controlled. Such measures will erase London’s reputation as the tuberculosis capital of Europe.”
http://biomedme.com/general/the-tuberculosis-capital-of-europe_26172.html

MALARIA: Drug-resistant malaria feared in Southeast Asia

By Stephanie Nebehay

11/18/2010
A form of malaria resistant to the most powerful drugs available may have emerged along the Thai-Myanmar border as well as Vietnam, and containment measures are planned, the World Health Organization said.
Clinical trials are due to begin soon in Myanmar and if they confirm artemisinin-resistant malaria in some patients, it means millions living in the border area could be potentially exposed to the longer-to-treat form, a WHO official told Reuters.
Artemisinin-resistant malaria first broke out in the Mekong region along the Thai-Cambodian border by early 2007, raising fears that a dangerous new form of the mosquito-borne disease could be spreading across the globe.
"We have some early warning signals that apart from the border of Thailand and Cambodia, we could have some problems emerging at the border between Myanmar and Thailand and also in one province of Vietnam," Dr. Pascal Ringwald of the WHO's global malaria program told a news briefing.
Malaria infects about 243 million people a year and causes an estimated 863,000 deaths, making it a major killer, especially among African children.
http://www.msnbc.msn.com/id/40261549/ns/health-infectious_diseases/

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

TUBERCULOSIS: Possible Persistence Switch for Tuberculosis

September 21st, 2010
 Possible Persistence Switch for Tuberculosis Found: Computer Model Finds Probable Genetic Mechanism for TB Dormancy
The bacteria that cause tuberculosis (TB), Mycobacterium tuberculosis, can transition into a dormant state to ward off attacks from antibiotics and the immune system. A new report from Igoshin and Tiwari in this month's issue of Physical Biology examines a network of genes that may make this possible. A computer model of the network showed it can act as a "persistence" switch that toggles the organism from a fast-growing to a slow-growing state.
"The molecular mechanisms that allow Mycobacterium tuberculosis to switch into this slow-growing, persistent state have been associated with genes that are activated when the microorganism is under stress," said Igoshin, senior author of the study and an assistant professor in bioengineering at Rice.
Tiwari, lead author of the study and a graduate student in Igoshin's lab, said, "We examined a stress-response network of genes that are found in both the TB bacterium and other closely related mycobacteria. We analyzed the role of multiple feedback loops in this network, and were eventually able to identify an ultrasensitive mechanism that works in combination with the feedback loops to form a switch. This switch can possibly activate transition to the persistent state."
The study was a collaborative effort between Igoshin's laboratory at Rice's BioScience Research Collaborative and the research groups of Gabor Balazsi at the University of Texas M.D. Anderson Cancer Center and Maria Laura Gennaro at the Public Health Research Institute of the New Jersey Medical School.
Scientists have long known that the TB bacterium has the ability to "hunker down" and go dormant under stressful conditions. Previous studies have confirmed that both the slow-growing and fast-growing forms of the bacteria have identical genes.
"The fact that the same organism can exist in two states at the same time in the same environment raises many questions," Igoshin said. "What is the basis for this bistability? What are the environmental cues that activate the switch?"
Other bacteria can switch between stable states as well, but Mycobacterium tuberculosis' ability to make this transition is one reason TB is such a widespread disease. As much as 30 percent of the world's population is believed to be infected with TB, which causes about 2 million deaths every year.
http://www.sciencemagnews.com/possible-persistence-switch-for-tuberculosis-found-computer-model-finds-probable-genetic-mechanism-for-tb-dormancy.html

MALARIA: India: Persistent transmission of malaria in Garo hills of Meghalaya bordering Bangladesh, north-east India

Malaria Journal 2010, 9:263doi:10.1186/1475-2875-9-263
Published: 22 September 2010

Abstract (provisional)
Background
Malaria is endemic in Garo hills of Meghalaya, and death cases are reported annually. Plasmodium falciparum is the major parasite, and is solely responsible for each malaria-attributable death case. Garo hills are categorized high-risk for drug-resistant malaria; however, there exists no data on malaria transmitting mosquitoes prevalent in the region. Included in this report are entomological observations with particular reference to vector biology characteristics for devising situation specific intervention strategies for disease transmission reduction.

Methods
The epidemiological data of the West Garo hills have been reviewed retrospectively for 2001-2009 to ascertain the disease transmission profile given the existing interventions. Point prevalence study was conducted in Dalu Community Health Centre that lies in close proximity to international border with Bangladesh to ascertain the true prevalence of malaria, and parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination, and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT.

Results
Investigations revealed that the West Garo hill district is co-endemic for Plasmodium falciparum and Plasmodium vivax, but P. falciparum was the predominant infection (>82%). Malaria transmission was perennial and persistent with seasonal peak during May-July corresponding to months of high rainfall. Entomological collections revealed that Anopheles minimus was the predominant species that was incriminated by detection of sporozoites in salivary glands (infection rate 2.27%), and was ascertained to be fully susceptible to DDT.

Conclusion
For the control of malaria, improved diagnosis and sustained supply of drugs for artemisinin-based combination therapy are strongly advocated, which should be enforced for treatment of every single case of P. falciparum. Greater political commitment is called for organized vector control operations along border/ high-risk areas to contain the spread of drug-resistant malaria, and averting impending disease outbreaks.


http://www.malariajournal.com/content/9/1/263

TUBERCULOSIS: A new molecular test for tuberculosis made by Cepheid

By Kate Kelland
Sep 1, 2010 5:02pm EDT
A new molecular test for tuberculosis made by Cepheid can diagnose TB and detect a drug-resistant form of it far more easily and rapidly than other tests currently available, scientists said on Wednesday.
In a study in the New England Journal of Medicine (NEJM), researchers said that when used on 1,730 patients with suspected TB and suspected drug-resistant TB, the Xpert MTB/RIF test successfully identified 98 percent of all cases.
It also identified 98 percent of patients with a form of TB resistant to rifampin, or rifampicin -- one of the most powerful TB drugs -- and achieved these results in less than two hours.
Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases described the test findings as "impressive" in terms of speed, accuracy and sensitivity.
"Within two hours, you can not only have a diagnosis, but you can also have a good idea of the range of drugs you can use," he told Reuters, adding that such capabilities were "unheard of" with current testing methods.
Doctors say current diagnostic testing for TB -- which involves microscopy in labs with trained experts and can take weeks -- has barely been improved in the last 125 years.
Tests for drug-resistant TB can take months and are notoriously insensitive, so new, more accurate tools to rapidly diagnose TB and its drug-resistant forms are urgently needed.
"We're very pleased with the outcome," said Mark Perkins, chief scientific officer at the Geneva-based non-profit organization the Foundation for Innovative New Diagnostics (FIND), which worked on the study.
TB afflicts mostly the poor in developing regions such as sub-Saharan Africa, India and China, but also occurs in poor regions of developed nations and is common in patients with the HIV virus that causes AIDS. It is among the world's top 10 leading causes of death and killed 1.8 million people worldwide in 2008, or one person every 20 seconds.
COSTS
Perkins said his team had since followed up on this initial study and carried out further "demonstration trials" in six countries to see how the test works in real-life settings.
He said initial signs from these trials, which involved nearly 7,000 patients but have yet to be published or peer-reviewed, suggest the test is just as effective at detecting TB in real patients on the ground.
In a commentary about the NEJM study, Peter Small, who runs the TB program at the Bill & Melinda Gates Foundation global aid group, said he was encouraged by the results but concerned that the potential high cost of such a sophisticated test might limit its use around the world.
"Critical to a rapid scale-up of the test will be...whether its use improves outcomes for patients in a cost-effective manner," he wrote.
Perkins said FIND had already negotiated concessionary prices with Cepheid which would apply in developing countries which decide they want to use the test.
The machine and computer to analyze the tests cost around $17,500, and the negotiated price of the test kits for poorer countries will be based on the cost of manufacture plus a small margin, he said. He was not able to give a precise figure.
"Our goal is to make...tests as inexpensive as possible, This one happens to be quite sophisticated and quite difficult to make inexpensive. But it is like any other public good -- it will obviously have a big impact, and it obviously costs money."
http://www.reuters.com/article/idUSTRE68071A20100901

MALARIA: Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia

02 September 2010
Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P. vivax resistance to chloroquine and chloroquine plus primaquine treatment although these drugs have been used as the first line treatment for over 50 years. We assessed the efficacy of standard chloroquine and chloroquine plus primaquine treatment for P. vivax infections in a randomized open-label comparative study in Debre Zeit and Nazareth in East Shoa, Ethiopia.A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient settings of the two laboratory centers were enrolled: 145 patients were randomized to receive CQ and 145 to receive CQ+ PQ treatment. Participants were followed-up for 28–157 days according to the WHO procedures. There were 12 (6.5%) lost to follow-up patients and 9 (3.1%) withdrawals. In all, 96% (277/290) of patients were analysed at day 28. Baseline characteristics were similar in all treatment groups. In all, 98.6% (275/277) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens (48.34±17.68, 50.67±15.70 h for the CQ and CQ+ PQ group, respectively, P = 0.25). The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76% (95% CI: 2.2–14.61) and 0.75% (95% CI: 0.11–5.2%) in the CQ and CQ+ PQ group, respectively (P = 0.19). The relapse rate was 8% (9/108) for the CQ group and 3% (4/132) for the comparison group (P = 0.07). The cumulative risk of relapse at day 157 by a life-table method was 61.8% (95% CI: 20.1–98.4%) in the CQ group, compared with 26.3% (95% CI: 7.5–29.4%) in the CQ+ PQ group (P = 0.0038).

The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia. Although treatment failures were detected, they were similar between the treatment groups. We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematically selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes.
http://www.malarianexus.com/articles/read/47/therapeutic-efficacy-of-chloroquine-and-chloroquine-plus-primaquine-for-the-treatment-of-plasmodium-vivax-in-ethiopia/

MALARIA: Epidemiology of drug-resistant malaria

Since the first reports of chloroquine-resistant falciparum malaria in southeast Asia and South America almost half a century ago, drug-resistant malaria has posed a major problem in malaria control. By the late 1980s, resistance to sulfadoxine-pyrimethamine and to mefloquine was also prevalent on the Thai-Cambodian and Thai-Myanmar (Thai-Burmese) borders, rendering them established multidrug-resistant (MDR) areas. Chloroquine resistance spread across Africa during the 1980s, and severe resistance is especially found in east Africa. As a result, more than ten African countries have switched their first-line drug to sulfadoxine- pyrimethamine. Of great concern is the fact that the efficacy of this drug in Africa is progressively deteriorating, especially in foci in east Africa, which are classified as emerging MDR areas. Urgent efforts are needed to lengthen the lifespan of sulfadoxine-pyrimethamine and to identify effective, affordable, alternative antimalarial regimens. Molecular markers for antimalarial resistance have been identified, including pfcrt polymorphisms associated with chloroquine resistance and dhtr and drips CIhPS polymorphisms associated with sulfadoxine-pyrimethamine resistance. Polymorphisms in pfmdr1 may also be associated with resistance to chloroquine, mefloquine, quinine, and artemisinin. Use of such genetic information for the early detection of resistance foci and future monitoring of drug-resistant malaria is a potentially useful epidemiological tool, in conjunction with the conventional in-vivo and in-vitro drug-sensitivity assessments. This review describes the various features of drug resistance in Plasmodium falciparum, including its determinants, current status in diverse geographical areas, molecular markers, and their implications.

http://www.scopus.com/record/display.url?eid=2-s2.0-0036242351&origin=inward&txGid=570t1pj4m6HLiuI3ulhvnph%3a2

MALARIA: video on drug resistance

http://www.youtube.com/watch?v=omtd1rgofes

TUBERCULOSIS: AFRICA: Straight talk with MSF medical coordinator

JOHANNESBURG, 22 June 2010 (PLUSNEWS) - Dr Eric Goemaere is the medical coordinator of Médecins Sans Frontières (MSF) in South Africa. His career in HIV and AIDS has spanned decades, moving from an era in which antiretroviral (ARV) drugs were beyond the reach of most, to a time where millions are living with HIV and on treatment. IRIN/PlusNews sat down with Goemaere to ask him about the future of funding, drugs and the fight against HIV.
QUESTION: Has MSF experienced cuts in international funding and, if so, how is this affecting its programmes?
ANSWER: Indirectly. In some of our programmes in Uganda and in Kenya we have seen patients coming to us - and sometimes from far away - and saying, 'Where I used to get access to my drugs, I've been told, No'. By default, they come to an MSF programme where there are still treatment slots available. For the moment these numbers are limited, but in the future they might grow to the tens of thousands, and that would definitely put a strain on the programme. MSF is a very small fish in the pond ... we choose to be privately funded and we are extremely restricted in our funding. We are not in a position to absorb the withdrawal of funding, and we do not want in any way to pretend [to do] so. Q. Second- and third-line drugs are out of reach to many living with HIV and TB; as HIV/AIDS becomes increasingly less "exceptional", what is that likely to mean in the development of these drugs? A. MSF are supporting patent pools ... to avoid going back to those battles we had in the beginning of the 2000s against pharmaceutical companies. A patent pool is a sort of win-win agreement where [pharmaceutical companies] give up their patent to a pool; in exchange they get royalties for that, as part of a totally negotiated agreement. In the United States, someone diagnosed HIV-positive at 20 years old has a life expectancy of 69 years. Why so? There are an almost unlimited number of regimens, or different drugs that you can combine, to ensure that once resistance comes up you have an alternative. Here [in Africa], we don't have that luxury - we have two bullets; two regimens - so we estimate that we can offer [someone diagnosed with HIV] 10 years [or so] ... at this stage.
Q. How serious is the threat of drug resistance?
A. Drug resistance is a problem, [but] this is a natural phenomenon and we will have to deal with it, although I would say it has accelerated [because] people are not adherent. Twenty percent, or one-fifth, of our patients have drug resistance after one year, [which] compares very favourably with some European cohorts. So it's not more of a problem, but it is an alarming problem for the good reason that we need to shift to second-line regimens, [which] ... are about five times more expensive than first-line regimens - so [drug resistance] will increase cost.
Q. Why isn't tuberculosis (TB) declining in South Africa?
A. The answer is very simple: the TB epidemic is fuelled by the HIV epidemic. To tackle the TB epidemic, you need to tackle the HIV epidemic ... 70 percent of TB patients are HIV-positive, so they are co-infected. In Khayelitsha township [outside Cape Town], where I work, the TB incidence rate has reached astronomical levels, with more than 6,000 new notifications per year - that is more than the whole of the United Kingdom in one township - and this was fuelled only by the high HIV prevalence. The good news is that when you get a good coverage with the ARVs, you immediately see the TB notification rate going down, and that's what we've been seeing for the last two years.
Q. What is the single biggest obstacle to tackling HIV in southern Africa?
A. It's combined factors, and the importance of these factors changes with time. In the beginning the biggest obstacle was drug prices; we managed to tackle that problem. Then the problem became about healthcare facilities, because HIV was treated mostly at central level [large hospitals in urban centres, which] required lots of doctors, and not many doctors were available. Slowly, surely, by increasing coverage we managed to decentralise care to primary healthcare level [clinics]. Today, unfortunately, the biggest problem might become funding. If not enough funding is available we [will] go back in time ... back to centralised care, with patients [coming for treatment when they are] sicker, and [case management] becoming more complicated.

MALARIA: Drug-Resistant Malaria Spreading Beyond Western Cambodia

Resistance to artemisinin-based malaria medications seems to be spreading beyond western Cambodia, where it was first detected.
First spotted in western Cambodia in 2007, there are now signs of artemisinin-resistance noted in southern Myanmar and potentially emerging resistance along the Chinese-Myanmar border and in southern Vietnam near Cambodia.
Still, the total number of malaria cases had fallen, Ziemer told the conference. "In Vietnam, for example, they were down from about 190,000 in 1991 to 15,000 by 2008, he said. 'But it is essential that national governments remain focused to contain and eventually eliminate these multi-drug resistant strains,' he told the conference on international cooperation against infectious diseases," AFP writes. Ziemer noted the importance of getting rid of counterfeit and substandard drugs, which increase resistance.The WHO "warned early last year that parasites resistant to the drug artemisinin had emerged along the border between Cambodia and Thailand," according to the news service (6/18).
http://globalhealth.kff.org/Daily-Reports/2010/June/18/GH-061810-Drug-Resistant-Malaria.aspx

MALARIA: Malaria's Drug Miracle in Danger

Along the border between Thailand and Cambodia, Plasmodium falciparum, the most dangerous of malaria parasites, is showing unmistakable signs of becoming resistant to artemisinin derivatives, the group of powerful drugs that—as part of so-called artemisinin-based combination therapies—have become the cornerstone of malaria treatment worldwide. For the moment, the drugs still work in the area; they just take more time to do the job. But that is alarming enough, scientists say. If resistance gets worse and starts spreading out from here, the results could be catastrophic. There are few other drugs in the pipeline, and those that are closest to the market may not work against the resistant strain
http://www.sciencemag.org/cgi/content/summary/328/5980/844

TUBERCULOSIS: New anti-TB drugs could target host proteins

Indian scientists have shown that new anti-tuberculosis drugs can be developed by targeting human cell proteins that the tuberculosis (TB) bacterium depends on for its survival during infection.
The findings by a research team led by Kanury Rao, head of immunology at the International Centre for Genetic Engineering and Biotechnology, New Delhi, were reported last month (15 April) in PLoS Pathogens.
TB, caused by the bacterium Mycobacterium tuberculosis, is a global public health threat that accounted for 9.4 million new cases and 1.8 million deaths worldwide in 2008, according to the WHO.
Poor compliance with treatment schedules, lasting six to nine months, using three standard anti-TB drugs has led to increasing drug resistance that calls for more expensive second-line drugs.
Globally there are about half a million new cases of multi-drug resistant TB (MDR-TB), half of them in China and India. An emerging worry is extremely drug-resistant TB (XDR –TB) in which patients no longer respond to even second-line drugs.
An ideal new anti-TB drug would treat both MDR-TB and XDR-TB, as well as 'latent' cases where symptoms are not evident, Rao told SciDev.Net. It should also significantly reduce the duration of treatment to combat increasing drug resistance, he said.
Rao said the human cell or 'host' factors are important for survival of drug resistant strains of the TB bacterium
The team had earlier identified all the 275 human host cell proteins being used by M. tuberculosis. Of these, 74 were critical for the bacterium's survival, it reported in March in the journal Cell.
The next step is to identify chemicals that inhibit the critical proteins in human cells and develop them as drugs for TB. Rao's strategy is to simultaneously target the proteins with multiple inhibitors and to quickly eliminate the TB bacterium with minimum damage to the host cell.
Eventually the aim is to use chemicals whose inhibitory effect can be reversed after the elimination of the TB bacterium, thereby allowing the human cells to get back to normal functioning.
The new research is significant as it looks at an aspect of TB that has not been studied before, observes Zakir Thomas, project director of the Open Source Drug Discovery Foundation, an initiative launched by India's Council of Scientific and Industrial Research.
http://www.scidev.net/en/news/new-anti-tb-drugs-could-target-host-proteins.html

MALARIA: Haiti

Recent calls to eliminate malaria from Hispaniola — the last Caribbean island with endemic transmission of Plasmodium falciparum — are timely and important, write Joseph Keating, Donald Krogstad and Thomas Eisel from Tulane University in the United States in The Lancet Infectious Diseases.
It would provide proof of principle that malaria elimination is possible in complex environments. But elimination is also needed because there is now evidence of chloroquine resistance in Haiti and fast action is needed before the country is forced to switch to a more expensive combination therapy.
Lessons learnt in Haiti will be critical for informing other countries seeking malaria elimination. If elimination cannot be achieved on this small Caribbean island, there is little hope that it can be achieved in Sub-Saharan Africa where the malaria burden is higher and its control more complicated, say the authors.
But they add that elimination strategies used on the island should not be oversimplistic adaptation of control measures used in Africa or other endemic areas.
The key to eliminating malaria in Hispaniola lies in using a combination of methods to eliminate the parasite reservoir in human beings, prevent transmission and mobilise the community to seek out diagnosis and treatment.
All this requires unshakeable political will.
The cost of eliminating malaria in Hispaniola may be high — but it would set a precedent for health diplomacy and is a prerequisite to any global malaria elimination campaign.
http://www.scidev.net/en/opinions/why-we-must-eliminate-malaria-from-hispaniola.html