Import and spread of Panton-Valentine Leukocidin-positive Staphylococcus aureus through nasal carriage and skin infections in travelers returning from the tropics and subtropics.

BACKGROUND: Antibiotic-resistant Staphylococcus aureus is a globally emerging pathogen. Exchangeable virulence factors, such as Panton-Valentine leukocidin (PVL), have been proposed to drive this epidemic. We investigated whether skin infections and nasal colonization in travelers contribute to the global spread of such strains. METHODS: We conducted a case-control study of 38 returnees from the tropics and subtropics with S. aureus-positive skin and soft tissue infections (SSTIs) and 124 control patients with other travel-associated disorders. We collected information on travel characteristics, clinical outcomes of SSTIs, antibiotic sensitivity patterns, and genotypes of S. aureus strains isolated from skin lesions and the nares. RESULTS: S. aureus-positive SSTIs were associated with travel duration and purpose and were most common in returnees from Africa (odds ratio, 4.2; P = .005). PVL-positive (PVL(+)) S. aureus was frequent in the lesional and nasal isolates from travelers with SSTIs but could not be found in the nares of the control patients. The presence of PVL in S. aureus in travelers was associated with complicated disease, reduced antibiotic susceptibility, and secondary spread. The genotypes of PVL(+) S. aureus in returnees were reported to be endemic to the visited destination but rarely observed in Europe. CONCLUSIONS: Geographic variation in the risk of SSTIs in travelers supports a globally heterogeneous distribution of virulent S. aureus. Complicated SSTIs in returnees from nontemperate climates are associated with PVL(+) S. aureus and promote the emergence and spread of virulent and antibiotic-resistant strains. We propose a network for the surveillance of imported S. aureus (www.staphtrav.eu).

Severity of Staphylococcus aureus infection of the skin is associated with inducibility of human beta-defensin 3 but not human beta-defensin 2.

Gram-positive bacteria are the predominant cause of skin infections. Antimicrobial peptides (AMPs) are believed to be of major importance in skin's innate defense against these pathogens. This study aimed at providing clinical evidence for the contribution of AMP inducibility to determining the severity of Gram-positive skin infection. Using real-time PCR, we determined the induction of human beta-defensin 2 (HBD-2), HBD-3, and RNase 7 by comparing healthy and lesional mRNA levels in 32 patients with Gram-positive skin infection. We then examined whether AMP induction differed by disease severity, as measured by number of recurrences and need for surgical drainage in patients with Staphylococcus aureus-positive lesions. We found that HBD-2 and -3, but not RNase 7, mRNA expression was highly induced by Gram-positive bacterial infection in otherwise healthy skin. Less induction of HBD-3, but not HBD-2, was associated with more-severe S. aureus skin infection: HBD-3 mRNA levels were 11.4 times lower in patients with more than 6 recurrences (P = 0.01) and 8.8 times lower in patients reporting surgical drainage (P = 0.01) than in the respective baseline groups. This suggests that inducibility of HBD-3 influences the severity of Gram-positive skin infection in vivo. The physiological function of HBD-2 induction in this context remains unclear.

Constitutive expression of the antimicrobial peptide RNase 7 is associated with Staphylococcus aureus infection of the skin.

BACKGROUND: Staphylococcus aureus infections of the skin are a public health problem of growing importance. Antimicrobial peptides in human skin are believed to play an important role in innate defense against intruding pathogens. This study aimed to clarify whether their baseline expression influences the propensity of healthy individuals to develop S. aureus-positive skin infections. METHODS: Using real-time polymerase chain reaction technique and a prospective case-control design, we determined the expression of messenger RNA coding for human beta-defensin 2 and 3 as well as RNase 7 in unaffected skin of 20 travelers returning with Staphylococcus aureus-positive skin infection (case patients) relative to levels in 40 matched control subjects. RESULTS: Expression of RNase 7 was found to be 64% higher in unaffected skin of control subjects, compared with unaffected skin of case patients (95% confidence interval, 17%-131%; P = .007). This association remained stable after controlling for S. aureus nasal carriage, smoking, level of accommodation, and history of allergy. No such association was present for human beta-defensin 2 or 3. CONCLUSIONS: In conjunction with the existing evidence from in vitro studies, these findings suggest that antimicrobial peptides found at high baseline levels in healthy skin, such as RNase 7, confer protection against S. aureus infection of the skin.

Evaluation of Mycobacterium tuberculosis drug susceptibility in clinical specimens from Nigeria using genotype MTBDRplus and MTBDRsl assays.

The incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR) continues to increase alarmingly worldwide, and reliable and fast diagnosis of MDR is essential for the adequate treatment of patients. In contrast to the standard culture methods, nucleid acid amplification tests (NAATs) provide information about presence of Mycobacterium tuberculosis complex (MTBC) DNA and a potential resistance pattern within hours. We analyzed specimens of 110 patients from Nigeria comparing culture-based drug susceptibility testing (DST) to NAAT assays detecting isoniazid (INH), rifampicin (RMP) (GenoType MTBDRplus), and ethambutol (EMB) (GenoType MTBDRsl) resistance. Compared to DST, the GenoType MTBDRplus and MTBDRsl showed a specificity of 100% (86.3-100) and a sensitivity of 86% (42.1-99.6%) for detection of INH and a specificity of 100% (86.3-100) and a sensitivity of 83% (35.9-99.6%) for detection of RMP, and a sensitivity 100% (47.8-100%) for EMB resistance. However, in two strains, the NAAT assays provided false susceptible results as the mutations causing resistance were in genomic regions not covered by the probes of the GenoType MTBDRplus assay. We show that, in combination to DST, application of the GenoType MTBDRplus and GenoType MTBDRsl assays might be a useful additional tool to allow a rapid and safe diagnosis of MDR and extensively drug-resistant (XDR) MTBC.

Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate.

Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily. Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi-immune individuals. Ten, 30 and 100 microg of GMZ2 were well tolerated in 30 healthy malaria-naïve German volunteers when given three times in monthly intervals. Antigen-specific antibodies as well as memory B-cells were induced and detectable throughout the one year follow-up of the study. We conclude that GMZ2 is a safe and immunogenic malaria vaccine candidate suitable for further clinical development.

Panton-Valentine leukocidin-producing methicillin-Sensitive Staphylococcus aureus as a cause for recurrent, contagious skin infections in young, healthy travelers returned from a tropical country: a new worldwide public health problem?

Skin infections associated with visits to tropical countries are well known. In most of the cases, the infection is caused by Staphylococcus aureus. After a sufficient antibiotic treatment, the skin infections resolve without any sequelae. But several patients suffer from recurrent skin infections. Panton-Valentine leukocidin (PVL) is a cytotoxin produced by S aureus, which is associated with severe necrotic skin lesions and with a high contagiosity.

Successful diagnosis and treatment 50 years after exposure: is mucocutaneous leishmaniasis still a neglected differential diagnosis?

We present a case of a long-term history of imported mucocutaneous leishmaniasis, illustrating the importance of this differential diagnosis even decades after exposure. Diagnostic pitfalls and the role of primary subspecies differentiation are demonstrated. Chemotherapy avoiding antimonials was successful and remarkably well tolerated by an elderly patient.