Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

Ahead of Print / In Press

Disclaimer: Ahead of print articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 22, Number 3—March 2016

Perspective

  • Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease R. M. Raju et al.
    View Summary

    Recent advances in TB diagnosis and treatment must be considered in the basic scientific research of other mycobacterial diseases.

    View Abstract

    The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses.

Synopses

  • Methylotroph Infections and Chronic Granulomatous Disease E. Falcone et al.
    View Summary

    Disease caused by these environmental bacteria is almost exclusively limited to patients with this condition.

    View Abstract

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

  • Tuberculosis Caused by Mycobacterium africanum, United States, 2004–2013
    A. Sharma et al.
    View Summary

    Routine reporting of TB caused by this organism does not appear warranted at this time.

  • Avian Influenza A(H5N1) Virus in Egypt G. Kayali et al.
    View Summary

    An aggressive plan to curb these infections in poultry is urgently needed.

    View Abstract

    In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

Research

  • Improved Detection of Tuberculosis and Multidrug-Resistant Tuberculosis among Tibetan Refugees, India K. L. Dierberg et al.
    View Summary

    The prevalence of TB is extremely high in this population and requires urgent attention.

    View Abstract

    The incidence of tuberculosis (TB) among Tibetan refugees in India is 431 cases/100,000 persons, compared with 181 cases/100,000 persons overall in India in 2010. More than half of TB cases in these refugees occur among students, monks, and nuns in congregate settings. We sought to increase TB case detection rates for this population through active case finding and rapid molecular diagnostics. We screened 27,714 persons for symptoms of TB and tested 3,830 symptomatic persons by using an algorithm incorporating chest radiography, sputum smear microscopy, culture, and a rapid diagnostic test; 96 (2.5%) cases of TB were detected (prevalence 346 cases/100,000 persons). Of these cases, 5% were multidrug-resistant TB. Use of the rapid diagnostic test and active case finding enabled rapid detection of undiagnosed TB cases in congregate living settings, which would not have otherwise been identified. The burden of TB in the Tibetan exile population in India is extremely high and requires urgent attention.

  • Mortality Rates during Cholera Epidemic, Haiti, 2010–2011 F. J. Luquero et al.
    View Summary

    Actual rates were higher than rates calculated from healthcare facility reports.

    View Abstract

    The 2010 cholera epidemic in Haiti was one of the largest cholera epidemics ever recorded. To estimate the magnitude of the death toll during the first wave of the epidemic, we retrospectively conducted surveys at 4 sites in the northern part of Haiti. Overall, 70,903 participants were included; at all sites, the crude mortality rates (19.1–35.4 deaths/1,000 person-years) were higher than the expected baseline mortality rate for Haiti (9 deaths/1,000 person-years). This finding represents an excess of 3,406 deaths (2.9-fold increase) for the 4.4% of the Haiti population covered by these surveys, suggesting a substantially higher cholera mortality rate than previously reported.

  • Decreased Time for Initiation of Treatment for Pulmonary Multidrug-Resistant Tuberculosis Detected by Xpert MTB/RIF, Latvia
    H. R. Stagg et al.
    View Summary

    Patients with MDR TB detected by this test had an 84% reduction in time to treatment initiation.

  • Factors Associated with Loss to Follow-up during Treatment for Multidrug-Resistant Tuberculosis, the Philippines, 2012–2014 T. E. Tupasi et al.
    View Summary

    Most commonly reported was medication side effects or fear of side effects.

    View Abstract

    To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case–control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1–December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients’ higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB.

  • Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections
    K. A. Etienne et al.
    View Summary

    Next-generation technologies and bioinformatics enabled source attribution and implementation of effective control strategies.

  • Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication
    I. M. Blake et al.
    View Summary

    Identification of spatiotemporal clustering of acute flaccid paralysis cases can accelerate outbreak detection and thereby support rapid response activities.

  • Encephalitis, Ontario, Canada, 2002–2013 A. S. Parpia et al.
    View Summary

    The epidemiology of encephalitis in Ontario is remarkably similar to that in England.

    View Abstract

    Encephalitis, a brain inflammation leading to severe illness and often death, is caused by >100 pathogens. To assess the incidence and trends of encephalitis in Ontario, Canada, we obtained data on 6,463 Ontario encephalitis hospitalizations from the hospital Discharge Abstract Database for April 2002–December 2013 and analyzed these data using multiple negative binomial regression. The estimated crude incidence of all-cause encephalitis in Ontario was ≈4.3 cases/100,000 persons/year. Incidence rates for infants <1 year of age and adults >65 years were 3.9 and 3.0 times that of adults 20–44 years of age, respectively. Incidence peaks during August–September in 2002 and 2012 resulted primarily from encephalitis of unknown cause and viral encephalitis. Encephalitis occurred more frequently in older age groups and less frequently in women in Ontario when compared to England, but despite differences in population, vector-borne diseases, climate, and geography, the epidemiology was overall remarkably similar in the two regions.

  • Use of Transnational Services to Prevent Treatment Interruption in Tuberculosis-Infected Persons Who Leave the United States C. A. Tschampl et al.
    View Summary

    Scale up of such services is possible and encouraged because of potential health gains and reduced healthcare costs.

    View Abstract

    A major problem resulting from interrupted tuberculosis (TB) treatment is the development of drug-resistant TB, including multidrug-resistant TB (MDR TB), a more deadly and costly-to-treat form of the disease. Global health systems are not equipped to diagnose and treat the current burden of MDR TB. TB-infected foreign visitors and temporary US residents who leave the country during treatment can experience treatment interruption and, thus, are at greater risk for drug-resistant TB. Using epidemiologic and demographic data, we estimated TB incidence among this group, as well as the proportion of patients referred to transnational care–continuity and management services during relocation; each year, ≈2,827 visitors and temporary residents are at risk for TB treatment interruption, 222 (8%) of whom are referred for transnational services. Scale up of transnational services for persons at high risk for treatment interruption is possible and encouraged because of potential health gains and reductions in healthcare costs for the United States and receiving countries.

  • Identification of Novel Zoonotic Activity of Bartonella spp., France M. Vayssier-Taussat et al.
    View Summary

    These bacteria may cause paucisymptomatic bacteremia and endocarditis in humans.

    View Abstract

    Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans. We identified potentially zoonotic strains from 6 Bartonella species in samples from patients who had chronic, subjective symptoms and who reported tick bites. Three strains were B. henselae and 3 were from other animal-associated Bartonella spp. (B. doshiae, B. schoenbuchensis, and B. tribocorum). Genomic analysis of the isolated strains revealed differences from previously sequenced Bartonella strains. Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks.

  • Underestimation of Invasive Meningococcal Disease in Italy C. Azzari et al.
    View Summary

    Underestimation is attributable to misdiagnosis, especially in fatal cases, and use of insufficiently sensitive laboratory methods.

    View Abstract

    Knowing the incidence of invasive meningococcal disease (IMD) is essential for planning appropriate vaccination policies. However, IMD may be underestimated because of misdiagnosis or insufficiently sensitive laboratory methods. Using a national molecular surveillance register, we assessed the number of cases misdiagnosed and diagnoses obtained postmortem with real-time PCR (rPCR), and we compared sensitivity of rPCR versus culture-based testing. A total of 222 IMD cases were identified: 11 (42%) of 26 fatal cases had been misdiagnosed or undiagnosed and were reclassified as IMD after rPCR showed meningococcal DNA in all available specimens taken postmortem. Of the samples tested with both rPCR and culture, 58% were diagnosed by using rPCR alone. The underestimation factor associated with the use of culture alone was 3.28. In countries such as Italy, where rPCR is in limited use, IMD incidence may be largely underestimated; thus, assessments of benefits of meningococcal vaccination may be prone to error.

  • Changes in Predominance of Pulsed-Field Gel Electrophoresis Profiles of Bordetella pertussis Isolates, United States, 2000–2012 P. K. Cassiday et al.
    View Summary

    These changes are concurrrent with other recent molecular changes and may be contributing to US pertussis reemergence.

    View Abstract

    To clarify the characteristics of circulating Bordetella pertussis isolates, we used pulsed-field gel electrophoresis (PFGE) to analyze 5,262 isolates collected in the United States during 2000–2012. We found 199 PFGE profiles; 5 profiles accounted for 72% of isolates. The most common profile, CDC013, accounted for 35%–46% of isolates tested from 2000–2009; however, the proportion of isolates of this profile rapidly decreased in 2010. Profile CDC237, first seen in 2009, increased rapidly and accounted for 29% of 2012 isolates. No location bias was observed among profiles during 2000–2010, but differences were observed among isolates from different states during 2012. Predominant profiles match those observed in recent European PFGE studies. PFGE profile changes are concurrent with other recent molecular changes in B. pertussis and may be contributing to the reemergence of pertussis in the United States. Continued PFGE monitoring is critical for understanding the changing epidemiology of pertussis.

  • Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia H. R. Stagg et al.
    View Summary

    This test decreased time to treatment initiation by 66%–84%.

    View Abstract

    Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009–2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin-resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB.

  • Effects of Response to 2014–2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa
    A. S. Parpia et al.
    View Summary

    Reduced access to healthcare during the outbreak substantially increased mortality rates from other diseases.

Dispatches

Letters

Etymologia

Online Reports

  • Global Progress and Challenges in Implementing New Medications for Treating Multidrug-Resistant Tuberculosis J. Furin et al.
    View Abstract

    Two new drugs—bedaquiline and delamanid—have recently been approved by stringent regulatory authorities to treat multidrug-resistant tuberculosis (TB) and recommended by the World Health Organization for use under defined programmatic conditions. Introducing the medications in TB programs worldwide has not kept pace with the need for these drugs. In response, the DR-TB STAT (Drug-Resistant TB Scale-up Treatment Action Team) task force was formed in April 2015 to monitor progress and help overcome challenges. Information was collected from multiple sources and assessed monthly. Some progress has been made in introducing bedaquiline: as of October 2015, a total of 1,258 persons were on the medication under programmatic conditions. For delamanid, >100 patients, but few under programmatic conditions, have received the medication. Coordinated global action might help assist making these medications accessible for persons who need them most.

  • Global Introduction of New Multidrug-Resistant Tuberculosis Drugs—Balancing Regulation with Urgent Patient Needs T. Sullivan and Y. Ben Amor
    View Abstract

    New treatments for multidrug-resistant tuberculosis (MDR TB) are urgently needed. Two new drugs, bedaquiline and delamanid, have recently been released, and several new drugs and treatment regimens are in the pipeline. Misuse of TB drugs is a principal cause of drug resistance. As new drugs and regimens reach the market, the need to make them available to patients must be balanced with regulation of their use so that resistance to the new drugs can be prevented. To foster the rational use of new drugs, we propose 1) expanding/strengthening the capacity for drug susceptibility testing, beginning with countries with a high TB burden; 2) regulating prescribing practices by banning over-the-counter sale of TB drugs and enacting an accreditation system whereby providers must be certified to prescribe new drugs; and 3) decentralizing MDR TB care in rural communities by employing trained community health workers, using promising mobile technologies, and enlisting the aid of civil society organizations.

Volume 22, Number 4—April 2016

Perspective

  • Determinants and Drivers of Infectious Disease Threat Events in Europe
    J. C. Semenza et al.
    View Summary

    Top influences were travel and tourism, food and water quality, natural environment, global trade, and climate.

Synopsis

  • Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders H. Chen et al.
    View Summary

    Transmission of these viruses was limited to 2 immunocompromised patients in the same ward.

    View Abstract

    A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another.

Research

  • Dissemination of Extended-Spectrum β-Lactamase– and Plasmid-Encoded AmpC–producing Escherichia coli by Food, Sweden
  • Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings
  • Viremia Frequencies of a Novel Human Pegivirus Evaluated by using Bioinformatic Screening and PCR D. Bonsall et al.
    View Summary

    Bioinformatic screening and PCR-based approaches detected active infection with human hepegivirus-1 in exposed populations.

    View Abstract

    Next-generation sequencing has critical applications in virus discovery, diagnostics, and environmental surveillance. We used metagenomic sequence libraries for retrospective screening of plasma samples for the recently discovered human hepegivirus 1 (HHpgV-1). From a cohort of 150 hepatitis C virus (HCV)–positive case-patients, we identified 2 persons with HHpgV-1 viremia and a high frequency of human pegivirus (HPgV) viremia (14%). Detection of HHpgV-1 and HPgV was concordant with parallel PCR-based screening using conserved primers matching groups 1 (HPgV) and 2 (HHPgV-1) nonstructural 3 region sequences. PCR identified 1 HHPgV-1–positive person with viremia from a group of 195 persons with hemophilia who had been exposed to nonvirally inactivated factor VII/IX; 18 (9%) were HPgV-positive. Relative to HCV and HPgV, active infections with HHpgV-1 were infrequently detected in blood, even in groups that had substantial parenteral exposure. Our findings are consistent with lower transmissibility or higher rates of virus clearance for HHpgV-1 than for other bloodborne human flaviviruses.

  • Microevolution of Monophasic Salmonella Typhimurium during Epidemic, United Kingdom
    L. Petrovska et al.
    View Summary

    The clone arose recently, and subsequent microevolution resulted in considerable genotypic variation.

  • Domestically Transmitted Shiga Toxin 1–producing Shigella sonnei, California, United States, 2014–2015
    K. Lamba et al.
    View Summary

    Initially transmitted among persons traveling to the US from Mexico, the bacteria was domestically transmitted to 42 of 56 case-patients.

  • Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi
    J. C. Hunter et al.
    View Summary

    Early detection and adherence to infection prevention recommendations are necessary to avoid transmission.

  • Molecular Typing and Epidemiology of Human Listeriosis Cases, Denmark, 2002–2012
    A. Jensen et al.
    View Summary

    A clone of Listeria monocytogenes CC8 caused bacteremia in the elderly and a high incidence of listeriosis.

Dispatches

  • Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East C. Carias et al.
    View Abstract

    In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.

  • Definitive Hosts of Versteria Species (Cestoda: Taeniidae) Causing Fatal Infection in North America
    L. M. Lee et al.
  • Severe Infections with Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014
    A. E. Kajon and M. G. Ison
  • Deletion Variants of Middle East Respiratory Syndrome Coronavirus from Humans, Jordan, 2015 M. M. Lamers et al.
    View Abstract

    We characterized Middle East respiratory syndrome coronaviruses from a hospital outbreak in Jordan in 2015. The viruses from Jordan were highly similar to isolates from Riyadh, Saudi Arabia, except for deletions in open reading frames 4a and 3. Transmissibility and pathogenicity of this strain remains to be determined.

  • Arenavirus Diversity among Phylogroups of Mastomys natalensis Rodents, Nigeria
    A. Olayemi et al.
  • Neisseria meningitidis serogroup X in sub-Saharan Africa
    A. Agnememel et al.
  • Hypervirulent emm59 Clone Identified in Invasive Group A Streptococcus Outbreak, Southwestern United States
    D. M. Engelthaler et al.
  • Effectiveness of a Mobile Short-Message-Service–Based Disease Outbreak Alert System in Kenya
    M. Toda et al.

Letters

Books and Media

  • Immunity

Conference Summary

  • Enteric Fever and Invasive Nontyphoidal Salmonellosis—9th International Conference on Typhoid and Invasive NTS Disease, Bali, Indonesia, April 30–May 3, 2015
    M. Khan et al.

Volume 22, Number 5—May 2016

Research

  • Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains, Europe and United States
    T. Cerar et al.
    View Summary

    Strains from the United States are more virulent and have greater inflammatory potential.

  • Spectrum of Viral Pathogens in Blood of Returned, Malaria-Free, Ill Travelers from Canada
    R. Kariyawasam et al.
    View Summary

    Over a 2-year period, common and emerging viruses were documented in >20% of these travelers.

Dispatches

  • Q Fever, Scrub Typhus, and Rickettsial Diseases as Common Causes of Febrile Illness in Children, Western Kenya
    A. N. Maina et al.
  • Clinical, Virologic, and Epidemiologic Characteristics of Dengue Outbreak, Dar es Salaam, Tanzania, 2014

Letters

Volume 22, Number 6—June 2016

Synopsis

  • Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes
    V. J. Chalker et al.
    View Summary

    Genomic surveillance can effectively detect such outbreaks, providing increased intelligence to support infection control.

Research

  • Transmission of Mycobacterium chimaera from Heater–Cooler Units during Cardiac Surgery despite an Ultraclean Air Ventilation System
    R. Sommerstein et al.
    View Summary

    All units should be separated from air that can gain access to sterile areas.

TOP