More severe bone infections, health complications in children linked to MRSA, researchers find

DALLAS – June 30, 2008 – The emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a major pathogen has led to more complications and longer hospital stays for children with acute bone infections, UT Southwestern Medical Center researchers report.

Acute osteomyelitis, a bone infection that predominantly occurs in children, is usually caused by the staph bacteria. Treatment has traditionally been straightforward because most S. aureus bacteria can be killed with existing antibiotics.

Recently, however, more children with osteomyelitis have been developing the more severe, antibiotic-resistant, community-associated MRSA, resulting in more complications and prolonged antibiotic therapy and hospital stays.

"This study shows the transition from the normal S. aureus to the methicillin-resistant one that everybody calls the superbug," said Dr. Octavio Ramilo, professor of pediatrics at UT Southwestern and senior author of a study available online and in the July/August issue of the Journal of Pediatric Orthopaedics. "What's important about this is not only that MRSA infections are harder to treat because they are more resistant to the traditional antibiotics, but they are also more aggressive and cause more severe disease manifestations. This is reflected very clearly in this study."

Dr. Asunción Mejías, assistant professor of pediatrics and co-lead author, said MRSA isn't a new problem among children.

"But the MRSA that we used to see was acquired in the hospital," she said. "This is a different strain that patients acquire in the community. Now, we see kids with osteomyelitis who have bone abscesses in the legs and who get blood clots that lead to pulmonary embolisms.

"We don't want to alarm parents, but kids who limp or have backaches and fever after an otherwise minor trauma need to be evaluated by a physician," Dr. Mejías said.

Dr. Ramilo said osteomyelitis might be more common in children because kids tend to be more accident-prone. Most commonly, the bones get infected when bacteria reach the bone through the blood supply. It is thought that minor trauma to the bone facilitates the start of the infection.

For the study, researchers culled the medical records of 290 children admitted to Children's Medical Center Dallas between January 1999 and December 2003 with acute osteomyelitis. The median age of those surveyed was 6 years and most children were white or Hispanic. Sixty percent were male. Symptoms such as localized pain, fever, tenderness, swelling and limping were observed in more than half the patients.

The researchers divided the patient population into two groups (January 1999 to June 2001 and July 2001 to December 2003) to verify whether MRSA infections were becoming more common and more severe.

They then compared patients with MRSA osteomyelitis to children with non-MRSA osteomyelitis, which included those with methicillin-sensitive S. aureus (MSSA) infections. They also reviewed outcomes, including duration of fever, the type and length of antibiotic therapy, and the frequency of complications, such as muscle inflammation, bone abscesses, disseminated disease and the need to drain the bone surgically.

Though the clinical characteristics of the participants didn't change significantly between the first and second study periods, children who were treated in the latter period for osteomyelitis fared far worse, possibly because MRSA infections were more common, Dr. Ramilo said.

For example, in the second study period, bone abscesses were observed in 69 percent of the patients with MRSA osteomyelitis versus 26 percent among those with MSSA infections. Children admitted with MRSA osteomyelitis during the second study period also spent an average of 42 days on antibiotics, almost two weeks longer than those diagnosed with MSSA.

Dr. Ramilo said the number of children who needed surgery was also striking. Seventy-eight percent of the patients with MRSA required surgery, compared with 49 percent of those with MSSA.

He said the findings underscore the need for multicenter studies to identify the best antibiotic regimens as well as the best surgical approaches for complications.

"For now, the key is to treat the infection as early as possible with appropriate antibiotics and if needed, surgical drainage of the bone," Dr. Ramilo said.

Higher temperatures helped new strain of West Nile virus spread

Findings help explain spread of virus strain responsible for largest US epidemics

SANTA CRUZ, CA--Higher temperatures helped a new strain of West Nile virus invade and spread across North America, according to a study published in the June 27 issue of the journal PLoS Pathogens.

"The study shows that the warmer the temperature, the greater the advantage of the new strain. It also indicates that increases in temperatures due to global climate change would have major effects on transmission of the virus," said A. Marm Kilpatrick, first author of the paper and a senior research scientist for the Consortium for Conservation Medicine.

Kilpatrick, now an assistant professor of ecology and evolutionary biology at the University of California, Santa Cruz, joined with Laura Kramer and others at the New York State Department of Health's Wadsworth Center to conduct the study, which examined the effects of different temperatures on the transmission of two strains of West Nile virus.

The first occurrence of West Nile virus in North America was in New York City in 1999, when it caused a die-off of crows and other birds and 62 reported cases of human infections, including 7 deaths. In the two years after the introduction of the virus, the rate of transmission was relatively low. As it spread along the Atlantic seaboard, there were only 21 reported human cases in 2000 and 66 in 2001.

In 2002, however, a new strain of the virus emerged and rapidly spread throughout North America, completely displacing the old strain by 2005. Coincident with the spread of this new strain were two of the largest epidemics of West Nile virus recorded to date in North America, with 4,582 cases reported in 2002, 11,356 cases in 2003, and more than 270 deaths in both years. Since then, the number of reported cases per year has ranged from 2,500 to nearly 6,000, with more than 100 deaths each year.

Kilpatrick and Kramer set out to determine how the new strain of West Nile virus had displaced the first strain, and what effect temperature had on transmission by mosquitoes. They used laboratory tests to determine how soon mosquitoes are capable of transmitting the virus after feeding on infected blood. The results showed that the new strain is more efficiently transmitted than the older strain, and the advantage of the new strain increases with higher temperatures.

For both strains, increases in temperature greatly accelerated transmission by increasing the efficiency of viral replication in the mosquitoes. As a result, temperature increases of just a few degrees due to global warming could sharply accelerate transmission of the virus and possibly lead to more severe epidemics of West Nile virus in some cooler regions, Kilpatrick said. The researchers used the results to develop a model to predict the impact of increasing temperatures on West Nile virus transmission by mosquitoes.

"A previous study in our lab demonstrated that the new strain of the virus was more efficient at replicating in mosquitoes, which may have increased the intensity of epidemics in the field," Kramer said. "We wanted to examine whether temperature might have played a role in the invasion of the new strain, and whether its success may have been related to increasing temperatures."

Kramer's lab performed a series of studies that involved infecting one group of mosquitoes with the introduced 1999 strain of West Nile virus and siblings with the recently evolved strain. After holding the mosquitoes at different temperatures and for different lengths of time, researchers determined what fraction could transmit the virus. They found that the new strain was more efficient than the introduced strain at nearly all temperatures and time points after infection.

Kilpatrick, who analyzed the data and developed models to predict the impact of temperature on transmission, said the results provide a striking example of how climate and evolution can interact to increase the transmission of this virus. "These results also suggest that relatively small increases in temperature can have large impacts, due to the nonlinear acceleration of transmission with temperature," he said.

"This study shows how direct the impacts of climate change could be for us all," said Peter Daszak, executive director of the Consortium for Conservation Medicine, based at Wildlife Trust in New York. "It isn't just about a rise in sea level or the melting of a glacier in Alaska--it's about our health and our welfare."

Infant play drives chimpanzee respiratory disease cycles

The signature boom-bust cycling of childhood respiratory diseases was long attributed to environmental cycling. However, the effect of school holidays on rates of social contact amongst children is increasingly seen as another major driver. New research on chimpanzees suggests that this effect of social connectivity on disease cycling may long predate attendance of children at schools, with chimpanzee infant mortality rates cycling in phase with rates of social play amongst infants.

Published in the journal PLoS ONE, the new study examined more than two decades of infant mortality data from two chimpanzee communities in the Taï National Park, Côte d'Ivoire. Previous work by the authors, from the Max Planck Institute for Evolutionary Anthropology in Leipzig Germany, had shown that chimpanzees at the site were killed by respiratory viruses repeatedly introduced from humans. The new study found evidence for mortality cycling at two distinct intervals. On an annual scale, outbreak deaths peaked during the period of high food availability, when chimpanzees are most gregarious. However, infant mortality also cycled on a roughly three year period.

"What is fascinating about this three year cycle is that it appeared to be self-organized," said Hjalmar Kuehl, the lead author on the paper. "That is, the cycles were not forced by some extrinsic environmental cycle but emerged naturally from the demography, developmental ontogeny, and social behavior of chimpanzees." Climate cycles such as those caused by the El Nino Southern Oscillation were not good predictors of infant mortality patterns.

The key to the three year cycle was the ontogeny of playfulness in chimpanzee infants. Chimpanzee newborns are not very social but infants become increasingly playful with age, reaching a peak in social play at about two years old. Thus, each cycle started when an outbreak killed a group of infants, thereby synchronizing the reproductive cycles of their mothers. One year later, a large cohort of infants was born which, another two years further on, matured to peak play age. These highly playful infants produced a social bridge between community members who might otherwise engage in little direct interaction: ideal conditions for community-wide propagation of a new outbreak. The study provides a nice link between population dynamics and the behavioral issues traditionally studied by primatologists", said Yasmin Moebius, who did the analysis of play ontogeny.

It also has important implications for the conservation of chimpanzees, which are classed as Endangered by the World Conservation Union (IUCN), as well as Critically Endangered gorillas. Ape tourism has been heralded as a means of providing monetary value to governments and local communities. However, close approach to habituated gorillas and chimpanzees by tourists poses a serious disease transmission threat. "Our analyses not only tell us that disease transmission from tourists and researchers is a major problem", said Peter Walsh, another coauthor. "They tell us when the risk is greatest and, consequently, when measures such as vaccination would be most effective."

"We need to be more proactive about taking steps to minimize the disease transmission risk posed by both tourism and research," added Christophe Boesch, a coauthor who initiated the Tai Chimpanzee project in 1979. "We also need to expand our vision to include disease management measures such as vaccination as important parts of the ape conservation puzzle."

Skin colour and skin cancer

The team from Iceland's deCODE Genetics that identified sequence variations influencing hair, eye and skin pigmentation have found two more genetic determinants and two variants that confer an increased risk of melanoma.

The studies were published today in Nature Genetics, along with an Australian study identifying a new melanoma risk locus.

In October last year, deCODE reported novel single nucleotide polymorphisms (SNPs) influencing skin, eye and hair colour in Europeans.

They found that a SNP on chromosome 14 in the SLC24A4 gene is associated with an increased likelihood of blond rather than brown hair, and blue rather than green eyes. Blonde hair is also associated with a variant near the KITLG gene on chromosome 12.

A SNP on chromosome 6 is associated with freckles, as is a SNP in the tyrosinase (TYR) gene.

The team also confirmed previous studies associating red hair, freckles and sun sensitivity with the MC1R gene, and other variants near the OCA2 gene with eye and hair colour.

In the new studies, the team found a variant in the ASIP (encoding agouti signalling protein) gene, which has a well-documented role in pigmentation, which was very similar to those observed in MC1R. They also found two coding variants in TPCN2 that are associated with blond versus brown hair.

Importantly for skin cancer research, the team has found a haplotype near ASIP confers a significant risk of cutaneous melanoma, the highly aggressive cancer that causes the majority of deaths, and a risk of basal cell carcinoma, the more common but less deadly cancer.

A variant on TYR also conferred a risk of cutaneous melanoma and basal cell carcinoma.

In an independent study, Stuart McGregor, from the Queensland Institute of Medical Research, and colleagues found two SNPs on chromosome 20 conferred a risk of cutaneous melanoma. The SNPs are located in the region of ASIP but the team believes there are several other candidate loci.

deCODE papers: DOI: 10.1038/ng.160 and DOI: 10.1038/ng.161 MacGregor paper: DOI: 10.1038/ng.163

South Korea reports new case of suspected bird flu

SEOUL, April 29 (Reuters) - South Korea on Tuesday reported a suspected bird flu outbreak at a chicken farm in Ulsan City, which if confirmed would be the first in the southeast, as the country grapples with its worst outbreak of avian influenza।

South Korea previously confirmed 20 cases of the H5N1 strain in poultry in less than one month, despite having killed more than 5 million chickens and ducks, as the virus spreads at its fastest rate since the country reported its first case in 2003।

No human deaths from the disease have been reported in the country।On Tuesday, the Agriculture Ministry said a chicken farm in Ulsan, some 390 km (242 miles) southeast of Seoul, reported deaths of more than 100 chickens in a week and initial tests gave positive readings for the avian virus.

Seoul has stepped up the culling of birds in affected areas and launched an investigation into all of the country's 260 duck farms in a bid to prevent the spread of the virus.South Korea had to kill 5.29 million birds during the first outbreak between late 2003 and early 2004. The second outbreak in 2006-2007 saw about half that number culled.

(Reporting by Miyoung Kim; Editing by Ken Wills and Sanjeev Miglani)

Two cases of coinfection with HIV and simian foamy virus (SFV) are reported

Two cases of coinfection with HIV and simian foamy virus (SFV) are reported in the May 1st edition of the Journal of Infectious Diseases. Although the exact clinical significance of infection with SFV is unknown for HIV-positive individuals, there is some laboratory evidence that SFV may alter the natural history of SIV, which is similar to HIV, and that SFV-infected cells are more vulnerable to infection with HIV.

The investigators recommend that measures should be introduced to protect the blood supply from SFV, and that strategies to reduce human contact with mandrills and other primates should be developed to prevent transmission of SFV and other simian infections to humans. People in contact with nonhuman primates have a risk of infection with the parasites, viruses and bacteria with which these creatures can be infected. HIV originated as a simian virus and was subsequently spread by person-to-person contact showing the potential public health consequences of infections harboured by nonhuman primates.

SFV is a retrovirus that is common in nonhuman primates that are caught from the wild or held in captivity. It can be spread easily between nonhuman primates by contact with infected bodily fluids, usually through grooming, biting, and possibly sexual contact. Although laboratory studies have shown that SFV can damage the cells of nonhuman primates, it does not appear to cause disease in these species. There is a growing body of evidence suggesting transmission of SFV from nonhuman primates to humans is possible.

Transmission of SFV from a wide range of ape and monkey species, including chimpanzee, gorilla, macaque, African green monkey, baboon and mandrill to humans have been suggested. The ability of SFV to cause illness in humans, or be transmitted between humans is not yet fully understood, but no cases of disease in humans or sexual transmission between humans has been recorded so far. Little is known about the geographical distribution of SFV among humans, including those infected with HIV in west central Africa.

Investigators therefore conducted an analysis of blood samples obtained from 139 sex workers, 41 patients with sexually transmitted infection, and 179 blood donors . The commercial sex workers and individuals with sexually transmitted infections were located in the Democratic Republic of the Congo, and the blood donors in the Cameroon. Samples were obtained between 1985 and 2000. Of the 139 samples obtained from commercial sex workers, one (0.72%) was found to be infected with SFV. This sample was also infected with HIV and was obtained in 1985. In addition, one sample (0.56%) from the 179 blood donors in the Cameroon was also SFV-infected, and once again this sample came from an HIV-positive individual. Genetic analysis was performed on the sample from the blood donor and this showed that infection with SFV originated in a mandrill. “Our identification of what are, to our knowledge, the first reported cases of coinfection with SFV and HIV heightens the importance of defining the clinical and public health consequences of zoonotic SFV infection, especially in the context of AIDS”, write the investigators.

Although it is unclear if infection with SFV will cause illness in HIV-positive individuals, they point to laboratory evidence that suggests that this may be possible. For example, SFV may alter the course of SIV-associated disease in the gut of macaques that have SIV-associated immunosuppression. Laboratory studies also suggest that SFV-infected human cells are more “permissive” of infection with HIV. As SFV infection was found in both a sex worker and a blood donor, this suggests to the investigators that both sexual and bloodborne transmission of SFV may be possible.

They note that blood donations are not screened for SFV and propose that their findings may indicate that such precautions need to be introduced. Canada, for example, recently banned blood donations from individuals who had had contact with nonhuman primates “to prevent the introduction of SFV and other primate microbes into the blood supply.” Other studies in the Cameroon show that transmission of SFV, SIV and HTLV-1 from mandrills to humans has occurred, probably because of hunting and butchering. The investigators conclude, “these results suggest that frequent contact with mandrills in this region may explain the widespread zoonotic transmission of mandrill retroviruses.

Effective strategies to reduce hunting of mandrills and other nonhuman primates are needed to help preserve these endangered species and to prevent their viruses from being transmitted to humans.” Reference Switzer WM et al. Coinfection with HIV-1 and simian foamy virus in West Central Africans. J Infect Dis 197: 1 – 5, 2008.