High Carrier Rate Research Articles

Characteristics of major virulence of Group A β-hemolytic streptococcus isolated from children

Objective To study the prevalence of superantigens, deoxy ribonuclease(DNase) genes and fibronectin-binding protein encoding (FBP) genes of Group A Streptococci(GAS) isolated from children, and to analyze its relationship with clinical infections and predominant emm type. Methods A total of 112 strains of GAS were collected from three Children's Hospitals during the period from 2008 to 2012, including 72 strains from patients and 40 strains from asymptomatic carriers.Emm, superantigens(speA, speC, speH, speI, speG, speJ, ssa, smeZ, speL, speM, speK and speF), DNase genes (sda, sdn, spd1, spd3 and spd4), phospholipase A2 gene and FBP genes (prtFl、prtF2、fba) were amplified by PCR, and emm was further typed by DNA sequencing. Results A total 7 types were identified, including emm1, emm12, emm22, emm4, emm77, emm86, and stG485.The most common emm type was emm12, which accounted for 68.8% of all isolates in this study.The emm type distribution of the pathogens was accorded with the carrier strains.The prevalence of 12 superantigens, including speA, speC, speF, speG, speH, speI, speJ, speK, speL, speM, ssa, smeZ were 13.4%, 95.5%, 85.7%, 74.1%, 63.4%, 63.4%, 14.3%, 0.9%, 0.9%, 0.9%, 74.1% and 93.8%, respectively.The prevalence of 5 DNase genes, including sda, sdn, spd1, spd3, spd4, was 66.96%, 12.5%, 94.64%, 27.68%, 0.89%, respectively.No sla gene was detected.The prevalence of fibronectin-binding protein, including prtF1, prtF2, fba, was 69.6%, 79.5%, 30.4%, respectively.The carriage rate of speJ, spd3 from invasive or noninvasive infections was higher than that from asymptomatic carriers, however, the positive rate of ssa, speF, speG, prtF1, prtF2 and prtF1/prtF2 was lower than that of asymptomatic carriers.The prevalence of speH, speI, speG, sda, spd1, prtF1, prtF2, prtF1/prtF2 from the emm12 isolates was higher than that from non-emm12 isolates, whereas speA, speJ, sdn, spd3 and fba were more common in non-emm12 isolates. Conclusions Emm12 is the prevalent genotype among S. pyogenes strains isolated from children, followed by emm1 and emm12, which is irrelevant to resources; Strains isolated from infected children and from asymptomatic carriers have different distribution characteristics of virulence genes; The prevalence of emm12 may be associated with the high carrier rate of the certain virulence gene. Key words: Streptococcus pyogenes; Virulence factors; Emm typing

An assessment of risk posed by a Campylobacter-positive puppy living in an Australian residential aged-care facility.

In April and June 2012, two outbreaks of Campylobacter gastroenteritis were investigated in an Australian aged-care facility (ACF); a Campylobacter-positive puppy was identified as a potential source of infection. An expert panel was convened to assess transmission risk from the puppy to elderly residents and to guide further public health action. Criteria considered as part of the panel's assessment included the puppy's infectivity, the bacterium's transmissibility, puppy-resident contact, infection control and cleaning practices and animal management at the facility. A literature review was used to assist the panel, with a final risk being determined using a likelihood and consequence matrix. The panel determined that the setting and low infective dose made transmission likely despite varying degrees of contact between the puppy and cases. While infection control practices were generally appropriate, the facility's animal policy did not adequately address potential zoonotic risk. In summary, puppies should not be considered as companion animals in ACFs due to high rates of Campylobacter carriage and the underlying susceptibility of the elderly. Infection control and animal policies in ACFs should reflect an awareness of zoonotic disease potential.

Rickettsia felisInfections and Comorbid Conditions, Laos, 2003–2011

<i>Rickettsia felis</i>Infections and Comorbid Conditions, Laos, 2003–2011

Leptospira spp. in rodents and shrews in Germany.

Leptospirosis is an acute, febrile disease occurring in humans and animals worldwide. Leptospira spp. are usually transmitted through direct or indirect contact with the urine of infected reservoir animals. Among wildlife species, rodents act as the most important reservoir for both human and animal infection. To gain a better understanding of the occurrence and distribution of pathogenic leptospires in rodent and shrew populations in Germany, kidney specimens of 2973 animals from 11 of the 16 federal states were examined by PCR. Rodent species captured included five murine species (family Muridae), six vole species (family Cricetidae) and six shrew species (family Soricidae). The most abundantly trapped animals were representatives of the rodent species Apodemus flavicollis, Clethrionomys glareolus and Microtus agrestis. Leptospiral DNA was amplified in 10% of all animals originating from eight of the 11 federal states. The highest carrier rate was found in Microtus spp. (13%), followed by Apodemus spp. (11%) and Clethrionomys spp. (6%). The most common Leptospira genomospecies determined by duplex PCR was L. kirschneri, followed by L. interrogans and L. borgpetersenii; all identified by single locus sequence typing (SLST). Representatives of the shrew species were also carriers of Leptospira spp. In 20% of Crocidura spp. and 6% of the Sorex spp. leptospiral DNA was detected. Here, only the pathogenic genomospecies L. kirschneri was identified.

Streptococcus pneumoniae in saliva of Dutch primary school children.

While nasopharyngeal sampling is the gold standard for the detection of Streptococcus pneumoniae carriage, historically seen, saliva sampling also seems highly sensitive for pneumococcal detection. We investigated S. pneumoniae carriage in saliva from fifty schoolchildren by conventional and molecular methods. Saliva was first culture-enriched for pneumococci, after which, DNA was extracted from all bacterial growth and tested by quantitative-PCR (qPCR) for pneumococcus-specific genes lytA and piaA. Next, serotype composition of the samples was determined by serotype-specific qPCRs, conventional-PCRs (cPCR) and sequencing of cPCR amplicons. Although only 2 (4%) of 50 samples were positive by conventional diagnostic culture, 44 (88%) were positive for pneumococci by qPCR. In total, we detected the presence of at least 81 pneumococcal strains representing 20 serotypes in samples from 44 carriers with 23 carriers (52%) positive for multiple (up to 6) serotypes. The number of serotypes detected per sample correlated with pneumococcal abundance. This study shows that saliva could be used as a tool for future pneumococcal surveillance studies. Furthermore, high rates of pneumococcal carriage and co-carriage of multiple pneumococcal strains together with a large number of serotypes in circulation suggests a ubiquitous presence of S. pneumoniae in saliva of school-aged children. Our results also suggest that factors promoting pneumococcal carriage within individual hosts may weaken competitive interactions between S. pneumoniae strains.

Patients with cystic fibrosis have a high carriage rate of non-toxigenic Clostridium difficile

Thirty-year-old observations report frequent asymptomatic Clostridium difficile carriage among cystic fibrosis (CF) patients. In this case-control study, we found more carriers among CF patients than controls (47% versus 11%), but most strains carried by CF patients were non-toxigenic (77% versus 17%). Among CF patients, carriers were younger, with more severe pulmonary disease than non-carriers. Strains belonged to multiple PCR-ribotypes, suggesting that these CF patients did not acquire strains from each other.

Livestock-associated MRSA carriage in patients without direct contact with livestock.

BackgroundLivestock-associated MRSA (MC398) has emerged and is related to an extensive reservoir in pigs and veal calves. Individuals with direct contact with these animals and their family members are known to have high MC398 carriage rates. Until now it was assumed that MC398 does not spread to individuals in the community without pig or veal calf exposure. To test this, we identified the proportion of MC398 in MRSA positive individuals without contact with pigs/veal calves or other known risk factors (MRSA of unknown origin; MUO).MethodsIn 17 participating hospitals, we determined during two years the occurrence of MC398 in individuals without direct contact with livestock and no other known risk factor (n = 271) and tested in a post analysis the hypothesis whether hospitals in pig-dense areas have higher proportions of MC398 of all MUO.ResultsFifty-six individuals (20.7%) without animal contact carried MC398. In hospitals with high pig-densities in the adherence area, the proportion of MC398 of all MUO was higher than this proportion in hospitals without pigs in the surroundings.ConclusionsOne fifth of the individuals carrying MUO carried MC398. So, MC398 is found in individuals without contact to pigs or veal calves. The way of transmission from the animal reservoir to these individuals is unclear, probably by human-to-human transmission or by exposure to the surroundings of the stables. Further research is needed to investigate the way of transmission.

Application of Genetic Deafness Gene Chip for Detection of Gene Mutation of Deafness in Pregnant Women

ObjectiveThe study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. MethodsThe pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genomic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 (35delG, 176del16bp, 235delC, 299delAT), GJB3 (C538T) ,SLC26A4 ( IVS72A>G, A2168G) and mitochondrial DNA 12S rRNA (A1555G, C1494T) . Further genetic testing were provided to the spouses and newborns of the screened carriers. ResultsPeripheral blood of 430 pregnant women were detected, detection of deafness gene mutation carriers in 24 cases(4.2%), including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took further genetic tests, and 6 newborns inherited the mutation from their mother. ConclusionThe common deafness genes mutation has a high carrier rate in pregnant women group, 235delC and IVS7-2A>G heterozygous mutations are common.

Managing Clostridium difficile in inflammatory bowel disease (IBD).

Clostridium difficile (C. difficile) infection has emerged as a significant clinical challenge for patients suffering from inflammatory bowel disease (IBD). C. difficile can both precipitate and worsen flares of IBD, contributing to emergent colectomies and mortality. Advances in the management of C. difficile infection in IBD include recommendations for testing for this infection in the setting of clinical flare and hospitalization, improved diagnostic testing, identification of high rates of carriage and infection in pediatric IBD, and new data associating patterns of IBD genetic risk alleles with the development of this infection. Therapeutically, oral vancomycin has emerged as a superior treatment for IBD patients with moderate to severe disease compared with metronidazole. Although highly effective in the general population, fecal microbiome transplantation for recurrent C. difficile infection in IBD patients has been associated with colitis flare in the majority of patients who have received this treatment.

Antimicrobial susceptibility pattern of nasal Staphylococcus aureus among Dessie Referral Hospital health care workers, Dessie, Northeast Ethiopia

Staphylococcus aureus is a major pathogen in skin and soft tissue infections. Methicillin-resistant S. aureus (MRSA) is prevalent in most of the countries in which it is sought. MRSA is one of the important pathogens implicated in hospital-acquired infections. The main objectives of this study were to determine the antimicrobial susceptibility pattern of S. aureus isolates, the prevalence of MRSA, and the nasal carriage rate in healthy hospital staff members. A total of 118 health care workers (HCWs) were enrolled using a cross-sectional study design. Nasal swabs were collected and cultured on mannitol salt agar (MSA). The slide coagulase test was performed. Susceptibility testing was carried out on Mueller-Hinton agar using the modified Kirby-Bauer disk diffusion method with 10 antibiotics. Of the 118 HCWs, 34 had S. aureus and 15 had MRSA, with overall positivity rates of 28.8% and 12.7%, respectively. None of the S. aureus isolates were sensitive to penicillin. MRSA isolates were resistant to commonly available antibiotics. Only two (13.3%) of the nasal isolates were vancomycin-resistant. A high rate of nasal carriage and multidrug-resistant S. aureus was found in this study, indicating the need for standard infection control to prevent transmission in our health care setting.

Construction and Evaluation of Fe3O4-Based PLGA Nanoparticles Carrying rtPA Used in the Detection of Thrombosis and in Targeted Thrombolysis

Thrombotic disease is extremely harmful to human health, but early detection and treatment can help improve prognoses and reduce mortality. To date, few studies have used MR molecular imaging in the early detection of thrombi and in the dynamic monitoring of the thrombolytic efficiency. In this article, we construct Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles to use in the detection of thrombi and in targeted thrombolysis using MRI monitoring. Cyclic arginine-glycine-aspartic peptide (cRGD) was grafted onto the chitosan (CS) surface to synthesize a CS-cRGD film using carbodiimide-mediated amide bond formation. A double emulsion solvent evaporation method (water in oil in water [W/O/W]) was used to construct Fe3O4-based PLGA nanoparticles carrying recombinant tissue plasminogen activator (rtPA) (Fe3O4-PLGA-rtPA/CS-cRGD). Fe3O4-PLGA, Fe3O4-PLGA-rtPA, and Fe3O4-PLGA-rtPA/CS nanoparticles were constructed using the same W/O/W method. The results showed that the Fe3O4-based nanoparticles were constructed successfully and have a regular shape, a relatively uniform size, a high carrier rate of Fe3O4 and encapsulation efficiency of rtPA, and a relatively high activity of released rtPA. Transmission electron microscope (TEM) images revealed that the iron oxide particles were relatively uniformly distributed in the nano-spherical shell. The Fe3O4-based nanoparticles could be imaged using a clinical MRI scanner, and there were no significant differences in the transverse relaxation rate (R2*) or in the signal-to-noise ratio (SNR) values between the Fe3O4-based nanoparticles and an Fe3O4 solution with the same concentration of Fe3O4. In vitro and in vivo experiments confirmed that the Fe3O4-PLGA-rtPA/CS-cRGD nanoparticles specifically accumulated on the edge of the thrombus and that they had a significant effect on the thrombolysis compared with the Fe3O4-PLGA, Fe3O4-PLGA-rtPA, and Fe3O4-PLGA-rtPA/CS nanoparticles and with free rtPA solution. These results suggest the potential of the Fe3O4-PLGA-rtPA/CS-cRGD nanoparticles as a dual-function tool in the early detection of a thrombus and in the dynamic monitoring of the thrombolytic efficiency using MRI.

Extended-Spectrumβ-Lactamase–Producing Enterobacteriaceae in French Nursing Homes: An Association between High Carriage Rate among Residents, Environmental Contamination, Poor Conformity with Good Hygiene Practice, and Putative Resident-to-Resident Transmission

We evaluated the spread of multidrug-resistant Enterobacteriaceae in 38 nursing homes (NHs) in the Centre region of France. We conducted a multicenter prevalence study and evaluated extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae (ESBLE and CPE, respectively) colonization of 1,155 residents. The colonizing isolates were studied by randomly amplified polymorphic DNA typing. We observed hygiene practices and studied the contamination of the environment in 8 NHs. A total of 114 residents were ESBLE carriers (9.9%); none were CPE carriers. A total of 82.6% of the ESBLE were Escherichia coli. ESBLE colonization was associated with poor health status (P = .002), malignancy (P = .006), urinary incontinence (P = .007), fecal incontinence (P = .002), previous hospitalization (P = .033), and carbapenem treatment (P = .040). The clonal relationship between isolates within NHs suggested resident-to-resident ESBLE transmission in 15 NHs. ESBLE isolates were recovered from 6 of 232 bedrooms studied. A total of 1,533 observations revealed low rates of conformity for hand hygiene (25.7%), the use of gloves (45.9%) and protective clothing (13.3%), and waste management (46.7%). Conformity rates correlated inversely with ESBLE carriage rates. In most of the participating NHs, improved application of standard precautions during incontinence care is needed, and greater efforts to clean the environment of residents are required.

High rate of faecal carriage of extended-spectrum β-lactamase and OXA-48 carbapenemase-producing Enterobacteriaceae at a University hospital in Morocco

Carbapenemase-producing Enterobacteriaceae isolates are being increasingly reported, particularly from countries surrounding the Mediterranean area. We aimed to quantify the prevalence of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in rectal swabs from hospitalized patients in a University hospital in Morocco, and to compare the performance of three screening media: ChromID ESBL (bioMérieux), Brilliance CRE (OXOID, Thermofisher) and SUPERCARBA (home made). Genetic detection and plasmid analysis were performed by PCR and sequencing. Strain comparison was performed by multi-locus sequence typing and the Diversilab technique (bioMérieux). The prevalence of multidrug-resistant Enterobacteriaceae was high, with 33 ESBL producers (42.85%, mainly CTX-M-15) and 10 OXA-48 producers (13%), corresponding to two major clones of K. pneumoniae (70%) and a clone of Enterobacter cloacae (30%). The three screening media showed the same sensitivity for detection of carbapenemase-producing Enterobacteriaceae, whereas the SUPERCARBA medium was more specific than the two other media. The average faecal carriage of ESBL or carbapenemase-producing Enterobacteriaceae varied from 1 × 102 to >1 × 108 CFU/g of stools. This study shows a high prevalence of multidrug-resistant Enterobacteriaceae, and particularly of OXA-48 producers. The new carbapenem-containing medium, SUPERCARBA, was as sensitive as Brilliance CRE and ChromID ESBL, and more specific for the detection of Enterobacteriaceae expressing those carbapenemases.

High MRSA Carriage Rate among Nursing Microbiology Students

Staphylococcus aureus is a common cause of disease, particularly in colonized persons. Although methicillin-resistant S. aureus (MRSA) infections have become increasingly reported, population- based studies of students preparing for the health professions having S. aureus and MRSA colonization are lacking. We have found that students in microbiology classes having more contact with individuals in a healthcare setting are more likely to carry MRSA in their nares and axilla. The classes who had the highest rate of MRSA carriage during the school year, 2013-2014, were those with nursing students, who had a greater exposure to clinical settings and nursing homes. The class which had the highest rate of S. aureus carriage, had nearly 50% of the infected students had been involved a clinical setting. Since the majority of the students in the nursing and biology courses are looking to pursue a career in medicine, this sampling was very beneficial to inform them and others if they were a carrier of S. aureus and MRSA and the preventative measures to reduce the risk of infection.

Clostridium difficile in Children: To Treat or Not to Treat?

Clostridium difficile infection has been increasing since 2000 in children and in adults. Frequent antibiotics use, comorbidity, and the development of hypervirulent strains have increased the risk of infection. Despite the high carriage rates of C. difficile, infants rarely develop clinical infection. Discontinuing antibiotics and supportive management usually leads to resolution of disease. Antibiotics use should be stratified depending on the patient's age and severity of the disease.

Correlations of integrons and resistance gene cassettes in Gram-negative bacteria with multi-drug resistance

To explore the correlations of integrons, gene cassettes and drug resistance phenotypes in 90 multi-drug resistant Gram-negative bacteria. Class I/II/III integron and variable region of positive strains of 90 Gram-negative bacteria were amplified by PCR and types of integron variable region gene cassettes analyzed by DNA sequence. And the resistant rates of integron positive and negative strains were tested by drug susceptibility. The detection rate of integron was 81.1% (73/90) in 90 Gram-negative bacteria. The integron types were class I (n = 70), class II (n = 3) and class III (n = 0). Based on the BLAST analysis by GenBank database, in the amplified fragments of Class I integron positive strains variable region gene ranging from 730 to 3300 bp, 8 types of integron structure were identified. And there were aadB (n = 11), aac (6')-II (n = 7), aadA5 (n = 10), dfrA17-aadA5 (n = 14), dfrA12-OrfF-aadA2(n = 1), aacA4-catB8-aadA1(n = 24), aacC1-OrfA-OrfB-aadA1 (n = 3), catB3-aadB-dhfrV-aacA4-nit1-nit2 (n = 1), in which catB3-aadB-dhfrV-aacA4-nit1-nit2 was a new resistance gene cassette; the variable region fragment of class II integron positive strain was 1600 bp, with 3 carrier strains of sat2-aadA1 gene cassette.Susceptibility testing showed that the antimicrobial resistance rate of integron positive strains to aminoglycosides and sulfa were significantly higher than those of integron negative strains and accorded with the results of integration variable region gene cassettes; the positive strains were more sensitive to amikacin with a resistance rate of 32.9% (24/73); and the drug resistance rates of all beta-lactam strains were ≥ 80%. There is a higher carrier rates of classI integron in Gram-negative bacteria. And the resistant phenotype is related with the types of resistance gene cassettes of integron variable region.

PW01-032 – FMF-like state: genetic factors unrelated to MEFV

FMF is considered an autosomal recessive autoinflammatory syndrome caused by single gene (MEFV) mutations. Recently, it has been known that also heterozygous mutation carriers can suffer from a mild or incomplete form of FMF, named FMF-like disease. Among Armenians, who have relatively high carrier rate of MEFV mutations, single mutation has been detected in about 1/5 of symptomatic cases. Thus, one cannot exclude the influence of other modifier genes and/or environmental factors which can contribute to the variable penetrance and to the phenotypic variability of FMF-like disease.

Antibiotics for preventing meningococcal infections

Meningococcal disease is a contagious bacterial infection caused by Neisseria meningitidis (N. meningitidis). Household contacts have the highest risk of contracting the disease during the first week of a case being detected. Prophylaxis is considered for close contacts of people with a meningococcal infection and populations with known high carriage rates. To study the effectiveness, adverse events and development of drug resistance of different antibiotics as prophylactic treatment regimens for meningococcal infection. We searched CENTRAL 2013, Issue 6, MEDLINE (January 1966 to June week 1, 2013), EMBASE (1980 to June 2013) and LILACS (1982 to June 2013). Randomised controlled trials (RCTs) or quasi-RCTs addressing the effectiveness of different antibiotics for: (a) prophylaxis against meningococcal disease; (b) eradication of N. meningitidis. Two review authors independently appraised the quality and extracted data from the included trials. We analysed dichotomous data by calculating the risk ratio (RR) and 95% confidence interval (CI) for each trial. No new trials were found for inclusion in this update. We included 24 studies; 19 including 2531 randomised participants and five including 4354 cluster-randomised participants. There were no cases of meningococcal disease during follow-up in the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed.Mortality that was reported in one study was not related to meningococcal disease or treatment. Ciprofloxacin (RR 0.04; 95% CI 0.01 to 0.12), rifampin (rifampicin) (RR 0.17; 95% CI 0.13 to 0.24), minocycline (RR 0.28; 95% CI 0.21 to 0.37) and penicillin (RR 0.47; 95% CI 0.24 to 0.94) proved effective at eradicating N. meningitidis one week after treatment when compared with placebo. Rifampin (RR 0.20; 95% CI 0.14 to 0.29), ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) and penicillin (RR 0.63; 95% CI 0.51 to 0.79) still proved effective at one to two weeks. Rifampin was effective compared to placebo up to four weeks after treatment but resistant isolates were seen following prophylactic treatment. No trials evaluated ceftriaxone against placebo but rifampin was less effective than ceftriaxone after one to two weeks of follow-up (RR 5.93; 95% CI 1.22 to 28.68). Mild adverse events associated with treatment were observed. Using rifampin during an outbreak may lead to the circulation of resistant isolates. Use of ciprofloxacin, ceftriaxone or penicillin should be considered. All four agents were effective for up to two weeks follow-up, though more trials comparing the effectiveness of these agents for eradicating N. meningitidis would provide important insights.

Human genetics in Johannesburg, South Africa: Past, present and future

Genetic services were set up in Johannesburg, South Africa, in the late 1960s, but only became widespread and formalised after the first Professor of Human Genetics, Trefor Jenkins, was installed at the University of the Witwatersrand in 1974. The first services involved chromosome studies, and these developed into genetic counselling services. Prenatal diagnosis began to be offered, particularly for older women at risk for chromosome abnormalities in the fetus, and those at risk for neural tube defects. Genetic screening was then initiated for the Jewish community because of their high carrier rate for Tay-Sachs disease. Educational courses in human genetics were offered at Wits Medical School, and medical as well as other health professionals began to be trained. Research, supported by national and international bodies, was integral in the activities of the Department (now Division) of Human Genetics and focused on genetic conditions affecting the generally understudied black community. In the late 1980s the first training programme for genetic counsellors was started at MSc level, and postgraduate scientists at MSc and PhD levels studied in and qualified through the Department. At the same time molecular genetic laboratories were set up. In the late 1990s training for medical geneticists was initiated. Extensive high-quality genetic services developed over the four decades were comparable to those of most other departments in developed countries.

GJB2-associated hearing loss: Systematic review of worldwide prevalence, genotype, and auditory phenotype

To perform a systematic review of GJB2-associated hearing loss to describe genotype distributions and auditory phenotype. 230 primary studies identified from Pubmed. Pubmed was searched systematically to screen broadly for any study reporting on genotype and carrier frequencies for biallelic GJB2-associated hearing loss in defined populations around the world. Genotype and audiometric data were extracted and subjected to meta-analysis to determine genotype distributions, carrier frequencies, rates of asymmetric or progressive hearing loss, and imaging abnormalities. A total of 216 articles comprising over 43,000 hearing-loss probands were included. The prevalence of biallelic GJB2-associated hearing loss was consistent across most of the 63 countries examined, with different mutations being predominant in different countries. Common mutations were found in greater than 3% of the general population worldwide. Meta-analysis of 48 case-control studies demonstrated a two-fold higher carrier frequency among hearing-impaired individuals compared to normal-hearing controls for truncating alleles, but not V37I. Progression, asymmetry, and imaging abnormalities were present in 14% to 19% of individuals with GJB2-associated hearing loss. GJB2 mutations are highly prevalent around the world. The multiple predominant mutations present in different populations attest to the importance of this gene for normal cochlear function and suggests an evolutionary heterozygote advantage. The unusually high carrier rate for truncating mutations among hearing-impaired individuals is consistent with either the presence of complementary mutations or a carrier phenotype. The significant rate of asymmetry and progression highlights the importance of diagnostic workup and close follow-up for this highly variable condition.