We reflect on remarkable accomplishments in global tuberculosis (TB) control and identify persistent obstacles to the successful elimination of TB from the United States and globally. One hundred and twenty nine years after Koch’s discovery of the etiologic agent of TB, this health scourge continues to account for 9.4 million cases and 1.7 million deaths annually worldwide. Implementation of the Directly Observed Treatment Short-course strategy from 1995 through 2009 has saved 6 million lives. TB control is increasingly being achieved in countries with high-income economies, yet TB continues to plague persons living in countries with low-income and lower-middle–income economies. To accelerate progress against the global effects of disease caused by TB and achieve its elimination, we must bridge 3 key gaps in implementation, knowledge, and ambition.

To characterize the distribution of nontuberculous mycobacteria (NTM) species isolated from pulmonary samples from persons in Asia and their association with pulmonary infections, we reviewed the literature. Mycobacterium avium complex bacteria were most frequently isolated (13%–81%) and were the most common cause of pulmonary NTM disease (43%–81%). Also pathogenic were rapidly growing mycobacteria (M. chelonae, M. fortuitum, M. abscessus). Among all NTM isolated from pulmonary samples, 31% (582/1,744) were considered clinically relevant according to American Thoracic Society diagnostic criteria. Most patients were male (79%) and had a history of tuberculosis (37%). In Asia, high prevalence of rapidly growing mycobacteria and a history of tuberculosis are distinct characteristics of pulmonary NTM disease. This geographic variation is not well reflected in the American Thoracic Society criteria for NTM infections and could be incorporated in future guidelines.

To assess Q fever in France, we analyzed data for 1985–2009 from the French National Reference Center. A total of 179,794 serum samples were analyzed; 3,723 patients (one third female patients) had acute Q fever. Yearly distribution of acute Q fever showed a continuous increase. Periodic variations were observed in monthly distribution during January 2000–December 2009; cases peaked during April–September. Q fever was diagnosed more often in patients in southeastern France, where our laboratory is situated, than in other areas. Reevaluation of the current positive predictive value of serologic analysis for endocarditis was performed. We propose a change in the phase I (virulent bacteria) immunoglobulin G cutoff titer to >1,600. Annual incidences of acute Q fever and endocarditis were 2.5/100,000 persons and 0.1/100,000 persons, respectively. Cases and outbreaks of Q fever have increased in France.

While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998–2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The proportion of homeless persons who were foreign-born increased from 24% in 1998–2002 to 39% in 2003–2007. Among foreign-born homeless persons with TB, 56% of infections were caused by strains not known to circulate among homeless persons in Toronto. Only 2% of infections were resistant to first-line TB medications. The rise in foreign-born homeless persons with TB strains likely acquired overseas suggests that the risk for drug-resistant strains entering the homeless shelter system may be escalating.

In 2009, the Tennessee Department of Health received reports of 5 tuberculin skin test (TST) conversions among employees of an elephant refuge and isolation of Mycobacterium tuberculosis from a resident elephant. To determine the extent of the outbreak and identify risk factors for TST conversion, we conducted a cohort study and onsite assessment. Risk for conversion was increased for elephant caregivers and administrative employees working in the barn housing the M. tuberculosis–infected elephant or in offices connected to the barn (risk ratio 20.3, 95% confidence interval 2.8–146.7). Indirect exposure to aerosolized M. tuberculosis and delayed or inadequate infection control practices likely contributed to transmission. The following factors are needed to reduce risk for M. tuberculosis transmission in the captive elephant industry: increased knowledge about M. tuberculosis infection in elephants, improved infection control practices, and specific occupational health programs.

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003–2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.

Recently, the number of human Q fever cases in the Netherlands increased dramatically. In response to this increase, dairy goats and dairy sheep were vaccinated against Coxiella burnetii. All pregnant dairy goats and dairy sheep in herds positive for Q fever were culled. We identified the effect of vaccination on bacterial shedding by small ruminants. On the day of culling, samples of uterine fluid, vaginal mucus, and milk were obtained from 957 pregnant animals in 13 herds. Prevalence and bacterial load were reduced in vaccinated animals compared with unvaccinated animals. These effects were most pronounced in animals during their first pregnancy. Results indicate that vaccination may reduce bacterial load in the environment and human exposure to C. burnetii.

Bacillus anthracis, the bacterium that causes anthrax, is responsible for varying death rates among animal species. Difficulties in case detection, hazardous or inaccessible carcasses, and misdiagnosis hinder surveillance. Using case reports and a new serologic assay that enables multispecies comparisons, we examined exposure to and illness caused by B. anthracis in different species in the Serengeti ecosystem in Tanzania during 1996–2009 and the utility of serosurveillance. High seroprevalence among carnivores suggested regular nonfatal exposure. Seropositive wildebeest and buffalo showed that infection was not invariably fatal among herbivores, whereas absence of seropositivity in zebras and frequent detection of fatal cases indicated high susceptibility. Exposure patterns in dogs reflected known patterns of endemicity and provided new information about anthrax in the ecosystem, which indicated the potential of dogs as indicator species. Serosurveillance is a valuable tool for monitoring and detecting anthrax and may shed light on mechanisms responsible for species-specific variability in exposure, susceptibility, and mortality rates.

Mycobacterium lentiflavum, a slow-growing nontuberculous mycobacterium, is a rare cause of human disease. It has been isolated from environmental samples worldwide. To assess the clinical significance of M. lentiflavum isolates reported to the Queensland Tuberculosis Control Centre, Australia, during 2001–2008, we explored the genotypic similarity and geographic relationship between isolates from humans and potable water in the Brisbane metropolitan area. A total of 47 isolates from 36 patients were reported; 4 patients had clinically significant disease. M. lentiflavum was cultured from 13 of 206 drinking water sites. These sites overlapped geographically with home addresses of the patients who had clinically significant disease. Automated repetitive sequence–based PCR genotyping showed a dominant environmental clone closely related to clinical strains. This finding suggests potable water as a possible source of M. lentiflavum infection in humans.

Serologic studies for swine influenza viruses (SIVs) in humans with occupational exposure to swine have been reported from the Americas but not from Europe. We compared levels of neutralizing antibodies against 3 influenza viruses—pandemic (H1N1) 2009, an avian-like enzootic subtype H1N1 SIV, and a 2007–08 seasonal subtype H1N1—in 211 persons with swine contact and 224 matched controls in Luxembourg. Persons whose profession involved contact with swine had more neutralizing antibodies against SIV and pandemic (H1N1) 2009 virus than did the controls. Controls also had antibodies against these viruses although exposure to them was unlikely. Antibodies against SIV and pandemic (H1N1) 2009 virus correlated with each other but not with seasonal subtype H1N1 virus. Sequential exposure to variants of seasonal influenza (H1N1) viruses may have increased chances for serologic cross-reactivity with antigenically distinct viruses. Further studies are needed to determine the extent to which serologic responses correlate with infection.

International foodborne norovirus outbreaks can be difficult to recognize when using standard outbreak investigation methods. In a novel approach, we provide step-wise selection criteria to identify clusters of outbreaks that may involve an internationally distributed common foodborne source. After computerized linking of epidemiologic data to aligned sequences, we retrospectively identified 100 individually reported outbreaks that potentially represented 14 international common source events in Europe during 1999–2008. Analysis of capsid sequences of outbreak strains (n = 1,456), showed that ≈7% of outbreaks reported to the Foodborne Viruses in Europe database were part of an international event (range 2%–9%), compared with 0.4% identified through standard epidemiologic investigations. Our findings point to a critical gap in surveillance and suggest that international collaboration could have increased the number of recognized international foodborne outbreaks. Real-time exchange of combined epidemiologic and molecular data is needed to validate our findings through timely trace-backs of clustered outbreaks.

To determine whether plumbing could be a source of nontuberculous mycobacteria (NTM) infection, during 2007–2009 I isolated NTM from samples from household water systems of NTM patients. Samples from 22/37 (59%) households and 109/394 (28%) total samples yielded NTM. Seventeen (46%) of the 37 households yielded >1 Mycobacterium spp. isolate of the same species as that found in the patient; in 7 of those households, the patient isolate and 1 plumbing isolate exhibited the same repetitive sequence-based PCR DNA fingerprint. Households with water heater temperatures <125°C (<50°C) were significantly more likely to harbor NTM compared with households with hot water temperatures >130°F (>55°C) (p = 0.0107). Although households with water from public or private water systems serving multiple households were more likely to have NTM (19/27, 70%) compared with households with a well providing water to only 1 household (5/12, 42%), that difference was not significant (p = 0.1532).

To understand circumstances of tuberculosis transmission that strain public health resources, we systematically reviewed Centers for Disease Control and Prevention (CDC) staff reports of US outbreaks in which CDC participated during 2002–2008 that involved >3 culture-confirmed tuberculosis cases linked by genotype and epidemiology. Twenty-seven outbreaks, representing 398 patients, were reviewed. Twenty-four of the 27 outbreaks involved primarily US-born patients; substance abuse was another predominant feature of outbreaks. Prolonged infectiousness because of provider- and patient-related factors was common. In 17 outbreaks, a drug house was a notable contributing factor. The most frequently documented intervention to control the outbreak was prioritizing contacts according to risk for infection and disease progression to ensure that the highest risk contacts were completely evaluated. US-born persons with reported substance abuse most strongly characterized the tuberculosis outbreaks in this review. Substance abuse remains one of the greatest challenges to controlling tuberculosis transmission in the United States.

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005–November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST.

Bats host noteworthy viral pathogens, including coronaviruses, astroviruses, and adenoviruses. Knowledge on the ecology of reservoir-borne viruses is critical for preventive approaches against zoonotic epidemics. We studied a maternity colony of Myotis myotis bats in the attic of a private house in a suburban neighborhood in Rhineland-Palatinate, Germany, during 2008, 2009, and 2010. One coronavirus, 6 astroviruses, and 1 novel adenovirus were identified and monitored quantitatively. Strong and specific amplification of RNA viruses, but not of DNA viruses, occurred during colony formation and after parturition. The breeding success of the colony was significantly better in 2010 than in 2008, in spite of stronger amplification of coronaviruses and astroviruses in 2010, suggesting that these viruses had little pathogenic influence on bats. However, the general correlation of virus and bat population dynamics suggests that bats control infections similar to other mammals and that they may well experience epidemics of viruses under certain circumstances.

In the Netherlands, 1.4% of tuberculosis (TB) cases are caused by Mycobacterium bovis. After we admitted 3 patients with M. bovis infections to our reference hospital, we conducted a retrospective analysis of all M. bovis disease in the Netherlands during 1993–2007. We analyzed data from 231 patients for clinical, demographic, treatment, and outcome characteristics and for risk factors. Most patients were native Dutch (n = 138; 59.7%) or Moroccan (n = 54; 23.4%). Disease was mainly extrapulmonary (n = 136; 58.9%). Although 95 patients had pulmonary disease, person-to-person transmission did not occur, as shown by structural DNA fingerprinting analysis. Lymph node TB was more likely to develop in women (p<0.0001), whereas pulmonary M. bovis disease developed more frequently in men (p<0.0001). Diagnosis was accurate but delayed and led to inadequate treatment in 26% of the cases. Proportion of deaths from M. bovis disease was higher than that for M. tuberculosis disease.

To assess population diversities among 81 strains of fungi in the genus Fonsecaea that had been identified down to species level, we applied amplified fragment-length polymorphism (AFLP) technology and sequenced the internal transcribed spacer regions and the partial cell division cycle, β-tubulin, and actin genes. Many species of the genus Fonsecaea cause human chromoblastomycosis. Strains originated from a global sampling of clinical and environmental sources in the Western Hemisphere, Asia, Africa, and Europe. According to AFLP fingerprinting, Fonsecaea isolates clustered in 5 groups corresponding with F. pedrosoi, F. monophora, and F. nubica: the latter 2 species each comprised 2 groups, and F. pedrosoi appeared to be of monophyletic origin. F. pedrosoi was found nearly exclusively in Central and South America. F. monophora and F. nubica were distributed worldwide, but both showed substantial geographic structuring. Clinical cases outside areas where Fonsecaea is endemic were probably distributed by human migration.

To monitor and characterize oseltamivir-resistant (OR) pandemic (H1N1) 2009 virus with the H275Y mutation, we analyzed 4,307 clinical specimens from Japan by neuraminidase (NA) sequencing or inhibition assay; 61 OR pandemic (H1N1) 2009 viruses were detected. NA inhibition assay and M2 sequencing indicated that OR pandemic (H1N1) 2009 virus was resistant to M2 inhibitors, but sensitive to zanamivir. Full-genome sequencing showed OR and oseltamivir-sensitive (OS) viruses had high sequence similarity, indicating that domestic OR virus was derived from OS pandemic (H1N1) 2009 virus. Hemagglutination inhibition test demonstrated that OR and OS pandemic (H1N1) 2009 viruses were antigenically similar to the A/California/7/2009 vaccine strain. Of 61 case-patients with OR viruses, 45 received oseltamivir as treatment, and 10 received it as prophylaxis, which suggests that most cases emerged sporadically from OS pandemic (H1N1) 2009, due to selective pressure. No evidence of sustained spread of OR pandemic (H1N1) 2009 was found in Japan; however, 2 suspected incidents of human-to-human transmission were reported.

To identify a candidate etiologic agent for turkey viral hepatitis, we analyzed samples from diseased turkey poults from 8 commercial flocks in California, USA, that were collected during 2008–2010. High-throughput pyrosequencing of RNA from livers of poults with turkey viral hepatitis (TVH) revealed picornavirus sequences. Subsequent cloning of the ≈9-kb genome showed an organization similar to that of picornaviruses with conservation of motifs within the P1, P2, and P3 genome regions, but also unique features, including a 1.2-kb sequence of unknown function at the junction of P1 and P2 regions. Real-time PCR confirmed viral RNA in liver, bile, intestine, serum, and cloacal swab specimens from diseased poults. Analysis of liver by in situ hybridization with viral probes and immunohistochemical testing of serum demonstrated viral nucleic acid and protein in livers of diseased poults. Molecular, anatomic, and immunologic evidence suggests that TVH is caused by a novel picornavirus, tentatively named turkey hepatitis virus.

Trends in Staphylococcus aureus infections are not well described. To calculate incidence in overall S. aureus infection and invasive and noninvasive infections according to methicillin susceptibility and location, we conducted a 10-year population-based retrospective cohort study (1999–2008) using patient-level data in the Veterans Affairs Maryland Health Care System. We found 3,674 S. aureus infections: 2,816 (77%) were noninvasive; 2,256 (61%) were methicillin-resistant S. aureus (MRSA); 2,517 (69%) were community onset, and 1,157 (31%) were hospital onset. Sixty-one percent of noninvasive infections were skin and soft tissue infections; 1,112 (65%) of these were MRSA. Ten-year averaged incidence per 100,000 veterans was 749 (± 132 SD, range 549–954) overall, 178 (± 41 SD, range 114–259) invasive, and 571 (± 152 SD, range 364–801) noninvasive S. aureus infections. Incidence of all S. aureus infections significantly increased (p<0.001), driven by noninvasive, MRSA, and community-onset infections (p<0.001); incidence of invasive S. aureus infection significantly decreased (p<0.001).

To assess the annual risk for latent tuberculosis infection (LTBI) among health care workers (HCWs), the incidence rate ratio for tuberculosis (TB) among HCWs worldwide, and the population-attributable fraction of TB to exposure of HCWs in their work settings, we reviewed the literature. Stratified pooled estimates for the LTBI rate for countries with low (<50 cases/100,000 population), intermediate (50–100/100,000 population), and high (>100/100,000 population) TB incidence were 3.8% (95% confidence interval [CI] 3.0%–4.6%), 6.9% (95% CI 3.4%–10.3%), and 8.4% (95% CI 2.7%–14.0%), respectively. For TB, estimated incident rate ratios were 2.4 (95% CI 1.2–3.6), 2.4 (95% CI 1.0–3.8), and 3.7 (95% CI 2.9–4.5), respectively. Median estimated population-attributable fraction for TB was as high as 0.4%. HCWs are at higher than average risk for TB. Sound TB infection control measures should be implemented in all health care facilities with patients suspected of having infectious TB.

To estimate the prevalence of extensively drug-resistant tuberculosis (XDR TB) in China, we retrospectively analyzed drug-resistance profiles of 989 clinical Mycobacterium tuberculosis isolates. We found 319 (32.3%) isolates resistant to >1 first-line drugs; 107 (10.8%) isolates were multidrug resistant, of which 20 (18.7%) were XDR. XDR TB is of major concern in China.

We performed a molecular epidemiologic survey of mutations associated with drug-resistance genes in Plasmodium falciparum in northeastern Myanmar. In this region, 3 highly mutated drug-resistance haplotypes and 1 associated with decreased quinine susceptibility were prevalent, which suggests that parasites may be resistant to multiple commonly used antimalarial drugs.

To estimate the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from humans that were sequence type (ST) 398, we surveyed 24 laboratories in 17 countries in Europe in 2007. Livestock-associated MRSA ST398 accounted for only a small proportion of MRSA isolates from humans; most were from the Netherlands, Belgium, Denmark, and Austria.

To determine whether tuberculosis (TB) and nontuberculous mycobacteria (NTM) infection patients could be distinguished from one another with limited information, we compared pulmonary TB and NTM patients during 2005–2006. Our finding that age, birthplace, and presence of chronic obstructive pulmonary disease could differentiate TB and NTM disease could assist tuberculosis control efforts.

We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008–April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa.

An outbreak of tuberculosis (TB) in Italy involved 19 schoolchildren with active TB and 43 with latent infection. The source of the outbreak was a school assistant born in Italy who had a family history of TB. This outbreak highlights the need for maintaining clinical and public health expertise in countries with low TB incidence.

We determined the proportion of foreign-born persons with tuberculosis (TB) in Singapore. This proportion increased from 25.5% in 2004 to 37.6% in 2009. Unskilled workers from countries with high incidences of TB accounted for the highest number of and greatest increase in foreign-born TB case-patients.

To better understand the epidemiology of European bat lyssavirus 1 (EBLV-1) in Europe, we phylogenetically characterized Lyssavirus from Eptesicus isabellinus bats in Spain. An independent cluster of EBLV-1 possibly resulted from geographic isolation and association with a different reservoir from other European strains. EBLV-1 phylogeny is complex and probably associated with host evolutionary history.

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome.

To analyze the molecular epidemiology of Mycobacterium tuberculosis strains at a hospital in Buenos Aires, Argentina, and mutations related to multidrug-resistant and extensively drug-resistant tuberculosis, we conducted a prospective case–control study. Our findings reinforce the value of incorporating already standardized molecular methods for rapidly detecting resistance.

Mycobacterium caprae is a pathogen that can infect animals and humans. To better understand the epidemiology of M. caprae, we spoligotyped 791 animal isolates. Results suggest infection is widespread in Spain, affecting 6 domestic and wild animal species. The epidemiology is driven by infections in caprids, although the organism has emerged in cattle.

To investigate sporadic human cryptosporidiosis trends in the United Kingdom, we tested 3,030 Cryptosporidium spp.–positive fecal samples, submitted for routine typing in 2007–2008, for C. cuniculus. C. cuniculus prevalence was 1.2%; cases were mostly indigenous and occurred across all age groups. Most occurred during August–October and may be linked to exposure opportunities.

We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005–2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable.

To determine patient characteristics associated with isoniazid resistance in cases of tuberculous meningitis, we conducted a cross-sectional study by using data from the US National Tuberculosis Surveillance System during 1993–2005. Foreign-born patients were more likely to be infected with an isoniazid-resistant strain.