TUBERCULOSIS: Some facts on drug-resistant "superbugs"

Reporting by Julie Steenhuysen in Chicago; Editing by Laura MacInnis: Apr 7 2011
LONDON (Reuters) - Some of the world's most powerful medicines are losing the war against drug-resistant strains of HIV, gonorrhea, tuberculosis and other microbes, global health experts said on Thursday.
"People assume that antibiotics will always be there to fight the worst infections, but antimicrobial resistance is robbing us of that certainty and new drug-resistant pathogens are emerging," Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention, said on Thursday.
"It's not enough to hope that we'll have effective drugs to combat these infections. We must all act now to safeguard this important resource," Frieden said in a statement released to coincide with World Health Day.

Here are some facts from the CDC about antimicrobial resistance and what people can do to prevent it.
* Scope of the problem: Antimicrobial resistance occurs when germs change in a way that reduces or eliminates the effectiveness of drugs to treat them. This happens when antibiotics, antivirals, antifungals and other medications are used too liberally. About half of antimicrobial drugs -- antibiotics in particular -- are used unnecessarily or inappropriately prescribed in U.S. hospitals and in doctors' offices, the CDC says. The best approach to preserving those drugs is to use them only when needed.
* Cost: The United States spends more than $1.1 billion a year on unnecessary antibiotics for respiratory infections in adults. Antibiotic-resistant infections are responsible for $20 billion in excess healthcare costs and $35 billion in costs to society, such as lost wages, plus 8 million additional hospital days.
* HIV: Studies suggest 4 to 20 percent of newly diagnosed HIV patients have transmitted a drug-resistant infection. A 2007 study of HIV patients in the United States found one of every six newly diagnosed infections was drug-resistant. Doctors can help by testing for resistance before prescribing drugs, and patients can help by taking their drugs as prescribed and practicing safe sex.
* Malaria: Worldwide, there were an estimated 225 million malaria infections and 780,000 deaths in 2009. Most deaths were of children in Africa. Plasmodium falciparum, the most dangerous of the malaria parasites, has developed resistance in nearly all areas of the world where it is transmitted.
* Gonorrhea: More than 700,000 people in the United States become infected with gonorrhea each year, and the infection is showing increasing signs of antibiotic resistance. In 2009, 23.5 percent of gonorrhea strains showed resistance to penicillin, tetracycline, fluoroquinolones, or a combination of those antibiotics. Cephalosporins are the only class of antibiotics left, and preliminary data suggest resistant strains may be emerging. To fight this, the CDC is working with the National Institutes of Health to find other drugs to treat gonorrhea.
* Tuberculosis: About 1.3 percent of all U.S. TB cases reported in 2009 were multiple drug-resistant, or MDR, TB, and there has been one reported case of extensively drug-resistant (XDR) TB. With MDR or XDR-TB, the standard cocktail of antibiotics does not work and stronger medicines must be used, often for a longer time. Surgery may also be required to remove pockets of infection. To prevent the spread of drug-resistant TB, patients need to take all of their medications exactly as prescribed.

Source: U.S. Centers for Disease Control and Prevention
http://www.reuters.com/article/2011/04/07/us-antibiotics-factbox-idUSTRE7366WT20110407

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

30 July 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