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Tips from the journals of the American Society for Microbiology

American Society for Microbiology

Preventative Treatment Against Malaria May be Less Effective in Malnourished Children

The effectiveness of an intermittent preventative treatment against malaria in infants across Africa may be inhibited by high incidences of malnutrition say researchers from Charite University Medicine, Berlin, Germany; the University of Tuebingen, Germany; the University of Munich, Germany; and the Northern Region Malaria Project, Tamale, Ghana. They report their findings in the May 2009 issue of the journal Antimicrobial Agents and Chemotherapy.

An initial trial in Tanzania of intermittent preventative treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), a promising tool for controlling malaria in young children, showed an effective rate of 59% against uncomplicated malaria in infancy. Malnutrition is rampant in some regions of Africa, such as Ghana where approximately 50% of preschool children suffer from poor nutritional status. Previous studies associate greater malaria morbidity and mortality with protein-energy malnutrition suggesting that treatment strategies may fail when not coinciding with proper nutritional programs.

In the study researchers analyzed the impact of malnutrition on the protective efficacy of IPTi in 1,200 children in Northern Ghana where malaria is hyperendemic. The children were administered IPTi-SP or a placebo at 3, 9, and 15 months of age (of which malnutrition was present in 32, 40, and 50% respectively) and monitored until 24 months old. Significant findings showed the protective efficacies of IPTi in malnourished children were about half or even less of those in nonmalnourished children. IPTi was much less effective at reducing the incidence of malaria in malnourished children receiving two doses in the first year of life than in nonmalnourished children. Finally, the rate of severe malaria appeared to increase in malnourished children who took IPTi.

"In conclusion, in northern Ghana, IPTi in malnourished children achieved only roughly half the protective efficacy attainable under normal nutritional conditions," say the researchers. "Moreover, malnourished children did not benefit from IPTi in terms of weight gain or growth and, possibly bear the risk of rare but severe adverse events."

(I. Danquah, E. Dietz, P. Zanger, K. Reither, P. Ziniel, U. Bienzle, F.P. Mockenhaupt. 2009. Reduced efficacy of intermittent preventative treatment of malaria in malnourished children. Antimicrobial Agents and Chemotherapy, 53. 5: 1753-1759.)

New Study Reports First Evidence of SHIV Resistance to Vaginal Microbicide

A new study reports the first evidence of simian-human immunodeficiency virus (SHIV) resistance to the protective vaginal microbicide, PSC-RANTES, in rhesus macaques. The researchers from Case Western Reserve University, Cleveland, Ohio; Tulane National Primate Research Center and Tulane University Health Sciences Center, Covington, Louisiana detail their findings in the May 2009 issue of the Journal of Virology.

Many recent failed attempts at developing a safe and effective vaccine against HIV-1 have led researchers to reexamine the potential of microbicides at preventing HIV-1 transmission. Along with cost and effectiveness, experts are now focusing on incorporating HIV-1 inhibitors, promising microbicide candidates capable of blocking virus replication. PSC-RANTES is one of the most potent entry inhibitors and a proven vaginal microbicide against SHIV in macaques when administered at high doses. However, further studies of PSC-RANTES suggest a dose-dependent decrease in protection in which case drug-resistant variants may emerge from the infecting SHIV or SIV population.

In this study researchers analyzed gene sequences from SHIV-infected rhesus macaques treated with varying doses of PSC-RANTES for drug-resistant variants. Results identified two distinct gene mutations present in the SHIV population, beginning at the earliest sample time and lasting throughout the 77 days of infection, in at least one macaque treated with a partially protective dose of PSC-RANTES.

"In conclusion, this PSC-RANTES-resistant variant in rhesus macaques is the first evidence for selection/infection by HIV or SHIV resistant to a vaginally applied microbiocide," say the researchers. "Due to the nature of microbicides, it is highly conceivable that after application, there will be a window of time when the drug is potent followed by a period when suboptimal doses of the drugs may provide the necessary conditions for emergence of drug resistance."

(D.M. Dudley, J.L. Wentzel, M.S. Lalonde, R.S. Veazey, E.J. Arts. 2009. Selection of a simian-human immunodeficiency virus strain resistant to a vaginal microbicide in macaques. Journal of Virology, 83. 10: 5067-5076.)

Historical Anecdote of Jordan's Red Soils May Offer New Antibiotic

Historical anecdotes of the red soils from the Hashemite Kingdom of Jordan tell of people using the soils to treat skin infections and diaper rash. A multinational group of researchers suggest the healing power may be due to antibiotic-producing bacteria they have found living in the soil. This discovery may ultimately lead to new antibiotic treatments against harmful pathogens such as Staphylococcus aureus. The researchers report their findings in the May 2008 issue of the journal Applied and Environmental Microbiology.

The increasing incidence of antibiotic-resistant bacteria, especially the methicillin-resistant S. aureus in communities and hospitals, has placed great emphasis on the need for new antimicrobial agents to treat infectious diseases. In an attempt to uncover such resources researchers are exploring some historically recognized natural remedies which are still being used in some communities as an alternative to expensive pharmaceutical drugs.

In the study researchers collected samples of red soils from various geographic locations throughout the Hashemite Kingdom of Jordan and inoculated them with Micrococcus luteus and S. aureus. Results showed the bacteria were rapidly killed. Additionally, over a three-week incubation period, researchers found that the number of antibiotic-producing bacteria (specifically actinomycetes, Lysobacter spp. and Bacillus spp.) increased and high antimicrobial activity was observed. Further, no myxobacteria or lytic bacteriophages with activity against M. luteus or S. aureus were detected in the soils before or after inoculation and incubation.

"These data provide a rationale for the traditional use of Jordan's red soils for the treatment of skin infections, including diaper rash," say the researchers. "We hypothesize that the application of red soils to an infected area of skin (i.e. inoculation) leads to the proliferation of bacteria that produce antibiotic compounds, killing the infecting skin microbiota."

(J.O. Falkinham III, T.E. Wall, J.R. Tanner, K. Tawaha, F.Q. Alali, C. Li, N.H. Oberlies. 2009. Proliferation of antibiotic-producing bacteria and concomitant antibiotic production as the basis for the antibiotic activity of Jordan's red soils. Applied and Environmental Microbiology, 75. 9: 2735-2741.)


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