The vaccine against tuberculosis that is routinely given to 75 percent of the world’s infants is too risky to give to those born infected with the AIDS virus, says a new study published by the World Health Organization. It recommended that vaccination be delayed until babies can be tested. The Bacille Calmette-Guérin vaccine, known as BCG, protects children well against deadly tuberculous meningitis, though it does less well against the lung form. It has been in use since 1921, and children in many countries — though not the United States, which never adopted it — bear its characteristic round scar. But because it is a live vaccine, a weakened strain of bovine tuberculosis, it can cause its own problem — “disseminated BCG disease,” a type of bacterial infection that can rage through the body. It is fatal in more than 70 percent of cases.

British scientists have appealed to the World Health Organisation to publicly condemn homeopathy as a treatment for serious diseases, such as HIV, TB and malaria. The researchers, many of whom have worked in developing countries, called on the WHO to act amid fears that vulnerable patients are dying after turning to homeopathic preparations instead of effective medicines. The WHO works with national organisations that promote homeopathy and other alternative medicines in their public health programmes. Homeopathy practitioners have opened clinics throughout Asian and sub-Saharan Africa and offer to treat patients with HIV, malaria, influenza and childhood diarrhoea, none of which have been shown to respond to homeopathy. Many patients are told that conventional drugs work only temporarily and that homeopathic preparations are cheap and effective alternatives with fewer side effects. "Those of us working with the most rural and impoverished people of the world already struggle to deliver the medical help that is needed. When homeopathy stands in place of effective treatment, lives are lost," the scientists write in an open letter to the organisation. Homeopathic medicines are made by repeatedly diluting preparations with water until there is no trace left of the original compound. The overwhelming medical opinion is that homeopathic treatments are no more effective than placebos.

You have probably had your fill by now of swine flu, bird flu, flu of all descriptions; you have turned off your television, tossed the front section of this newspaper into the trash, and called for not one more word about the flu or any of the other dire infections breaking news around the globe. Sad news: you are out of luck. There will unquestionably be more words — many more — and you will probably wind up reading them. An insatiable fascination with contagious illness is hard-wired into all of us, as two new books make clear. From Philip Alcabes, an epidemiologist and a professor at Hunter College in New York, comes “Dread,” a sober analysis of why exactly this should be so. What is it that distinguishes epidemic infection from all other diseases, the ones that fail to generate breathless headlines and have failed to inspire the gigantic body of literature and commentary that trail behind history’s epidemics? The answer is logical enough: epidemics hit us right at the nexus of self-interest and altruism, that exquisitely uncomfortable spot where our brother’s misfortune nudges us just enough that we need to examine it and distance ourselves from it (and, in more highly evolved civilizations, take care of it before it takes care of us) ... For living color, turn to “The Lassa Ward,” which effortlessly transmits both the facts and the fascination of a bad infectious outbreak. Dr. Ross Donaldson spent two months in Sierra Leone as a medical student in 2003. Malaria, tuberculosis, yellow fever and AIDS were rampant, but Dr. Donaldson, for reasons clear perhaps only to the invulnerable post-adolescent he was at the time, decided to spend his time with Lassa fever patients. This rat-borne illness is one of Africa’s dire viral hemorrhagic fevers; like Ebola, it can reduce a human body to a bruised, bloated corpse in days. It is terrifying — the secretions of infected patients easily spread the disease — but it is also treatable, and in the best cases patients get well and go home. Dr. Donaldson had trailed the elderly Lassa specialist Dr. Conteh for only a few weeks when, to his horror, he was left alone in charge of the Lassa isolation ward. “No matter how low a cotton tree falls, it is still taller than grass,” the old doctor said as he left to teach in another town. In other words, the inexperienced Dr. Donaldson, with three years of medical school, had more formal education than anyone else around ...

The side effects associated with tuberculosis therapy bring with them the risk of noncompliance and subsequent drug resistance. Increasing the therapeutic index of antituberculosis drugs should thus improve treatment effectiveness. Several antituberculosis compounds require in situ metabolic activation to become inhibitory. Various thiocarbamide-containing drugs, including ethionamide, are activated by the mycobacterial monooxygenase EthA, the production of which is controlled by the transcriptional repressor EthR. Here we identify drug-like inhibitors of EthR that boost the bioactivation of ethionamide. Compounds designed and screened for their capacity to inhibit EthR-DNA interaction were co-crystallized with EthR. We exploited the three-dimensional structures of the complexes for the synthesis of improved analogs that boosted the ethionamide potency in culture more than tenfold. In Mycobacterium tuberculosis–infected mice, one of these analogs, BDM31343, enabled a substantially reduced dose of ethionamide to lessen the mycobacterial load as efficiently as the conventional higher-dose treatment. This provides proof of concept that inhibiting EthR improves the therapeutic index of thiocarbamide derivatives, which should prompt reconsideration of their use as first-line drugs.

High doses of the drug ethionamide cause side effects that limit its use against tuberculosis. Now, Alain Baulard of the Pasteur Institute in Lille, France, and his colleagues report that blocking the regulatory protein EthR in Mycobacterium tuberculosis boosts ethionamide's activity, markedly reducing the necessary dose of the drug. EthR controls production of the bacterial enzyme EthA, which activates ethionamide. Baulard's team designed and screened a drug library for compounds likely to block EthR (one example pictured) and thereby release its control on EthA. One such compound, BDM31343, bound to EthR and rendered ethionamide three times more potent against tuberculosis in mice.

Drug-resistant tuberculosis is rampant in Karachi's dense slums. And health dedicated to solving the crisis are challenged by a series of cultural barriers.

At a time when the dangers of HIV and tuberculosis (TB) co-infection are increasingly apparent, the Howard Hughes Medical Institute (HHMI) has teamed up with the University of KwaZulu-Natal in South Africa, to create a new international research facility dedicated entirely to studying these two diseases, as well as how they interact. The KwaZulu-Natal Research Institute for Tuberculosis and HIV will be housed within the grounds of the Nelson Mandela School of Medicine in Durban. "There is no place in the world where there is a dedicated integrated TB-HIV research center, so this is really the first one of those. And what I think is so exciting about this is that it is right in the middle of the worst parts of those epidemics," says Bruce Walker, an HHMI investigator who will lead immunology research within the HIV program at the new KwaZulu-Natal Research Institute. The region is ravaged by one of the world's most devastating TB-HIV co-epidemics, with about half of the local population suffering from HIV/AIDS. It is in the province's rural area of Tugela Ferry, where a severe outbreak of extremely drug-resistant TB was reported in 2006. Construction of the new institute, a six-story building that will contain high-security labs for TB research, is scheduled to begin in September. In addition to providing a platform for testing new vaccines and drugs, it is designed to serve as a global resource to attract top talent and train the next generation of African scientists. "There are vanishingly few opportunities for foreign-trained African researchers to come back and do research in their country," says Walker. HHMI has promised funding worth $60 million over the next ten years to secure the long-term vision of the key HHMI scientists involved.

New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-β-D-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB.

Mycobacterium tuberculosis infection induces complex CD4 T cell responses that include T helper type 1 (Th1) cells and regulatory T cells. Although Th1 cells control infection, they are unable to fully eliminate M. tuberculosis , suggesting that Th1-mediated immunity is restrained from its full sterilizing potential. Investigation into T cell – mediated defense is hindered by diffi culties in expanding M. tuberculosis – specifi c T cells. To circumvent this problem, we cloned CD4 + T cells from M. tuberculosis – infected B6 mice and generated transgenic mice expressing a T cell receptor specific for the immunodominant antigen early secreted antigenic target 6 (ESAT-6). Adoptively transferred naive ESAT-6 – specific CD4 + T cells are activated in pulmonary lymph nodes between 7 and 10 d after aerosol infection and undergo robust expansion before trafficking to the lung. Adoptive transfer of activated ESAT-6 – specifi c Th1 cells into naive recipients before aerosol M. tuberculosis infection dramatically enhances resistance, resulting in 100-fold fewer bacteria in infected lungs. However, despite large numbers of Th1 cells in the lungs of mice at the time of M. tuberculosis challenge, protection was not manifested until after 7 d following infection. Our results demonstrate that pathogen-specifi c Th1 cells can provide protection against inhaled M. tuberculosis , but only after the first week of infection.