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Volume 18, Number 11—November 2012

Volume 18, Number 11—November 2012   PDF Version [PDF - 8.55 MB - 219 pages]

Perspective

  • Investigation of Outbreaks Complicated by Universal Exposure PDF Version [PDF - 238 KB - 6 pages]
    A. Tostmann et al.
    View Summary

    Maximizing the information collected about aspects of the exposure can support investigations of disease outbreaks complicated by universal exposure.

       View Abstract

    Outbreaks in which most or all persons were exposed to the same suspected source of infection, so-called universal exposure, are common. They represent a challenge for public health specialists because conducting analytical studies in such investigations is complicated by the absence of a nonexposed group. We describe different strategies that can support investigations of outbreaks with universal exposure. The value of descriptive epidemiology, extensive environmental investigation, and the hypothesis-generation phase cannot be overemphasized. An exposure that seems universal may in fact not be universal when additional aspects of the exposure are taken into account. Each exposure has unique characteristics that may not be captured when investigators rely on the tools readily at hand, such as standard questionnaires. We therefore encourage field epidemiologists to be creative and consider the use of alternative data sources or original techniques in their investigations of outbreaks with universal exposure.

Research

  • Medscape CME Activity
    Coccidioidomycosis-associated Deaths, United States, 1990–2008 PDF Version [PDF - 234 KB - 6 pages]
    J. Y. Huang et al.
    View Summary

    Coccidioidomycosis is a fungal disease that occurs throughout the Americas. It is contracted by inhaling spores, which are carried in dust. Therefore, it occurs most commonly in dry areas and in persons who work in dusty conditions (such as agricultural workers, construction workers, military personnel, and archeological site workers). A substantial number of people die of this disease each year, so researchers examined what other factors increase the risk for death. They found that risk for death was highest among men, elderly persons (>65 years), Hispanics, Native Americans, residents of California and Arizona, and those who also had HIV or other immune-suppressive conditions. Physicians should be aware of which patients are at increased risk and should ask patients about their travel history or occupation to determine possible sources of exposure.

       View Abstract

    Coccidioidomycosis is endemic to the Americas; however, data on deaths caused by this disease are limited. To determine the rate of coccidioidomycosis-associated deaths in the United States, we examined multiple cause–coded death records for 1990–2008 for demographics, secular trends, and geographic distribution. Deaths were identified by International Classification of Diseases, 9th and 10th Revision, codes, and mortality rates were calculated. Associations of deaths among persons with selected concurrent conditions were examined and compared with deaths among a control group who did not have coccidioidomycosis. During the 18-year period, 3,089 coccidioidomycosis-associated deaths occurred among US residents. The overall age-adjusted mortality rate was 0.59 per 1 million person-years; 55,264 potential life-years were lost. Those at highest risk for death were men, persons >65 years, Hispanics, Native Americans, and residents of California or Arizona. Common concurrent conditions were HIV and other immunosuppressive conditions. The number of deaths from coccidioidomycosis might be greater than currently appreciated.

  • Medscape CME Activity
    Invasive Pneumococcal Disease and 7-Valent Pneumococcal Conjugate Vaccine, the Netherlands PDF Version [PDF - 229 KB - 9 pages]
    A. van Deursen et al.
    View Summary

    Disease incidence and case fatality rates declined 4 years after introduction of the vaccine.

       View Abstract

    In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004–June 2006) with those after PCV7 introduction (June 2008–June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ≈25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non–PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50–64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non–PCV7 serotype IPD.

  • Medscape CME Activity
    Nasopharyngeal Bacterial Interactions in Children PDF Version [PDF - 193 KB - 8 pages]
    Q. Xu et al.
    View Summary

    Pathogen prevalence differs during periods of health and at onset of acute otitis media.

       View Abstract

    Antimicrobial treatments and vaccines can alter bacterial interactions in the nasopharynx, thereby altering disease processes. To better understand these interactions, we examined colonization rates of 3 respiratory bacterial pathogens among 320 children when healthy and at onset of acute otitis media (AOM). Bacterial interactions were analyzed with a repeated measures logistic regression model. Among healthy children, Streptococcus pneumoniae and Moraxella catarrhalis were synergistically (positively) associated. Colonization with S. pneumoniae when healthy, but not at onset of AOM, was competitively (negatively) associated with Staphylococcus aureus. Among children with AOM, competitive associations were found between Haemophilus influenzae and S. pneumoniae and between H. influenzae and M. catarrhalis; rates of colonization with H. influenzae were higher. Bacterial interactions result in differing pathogen prevalence during periods of health and at onset of AOM. H. influenzae might become a more common cause of AOM among children who receive pneumococcal conjugate vaccine.

  • Lack of Evidence for Zoonotic Transmission of Schmallenberg Virus PDF Version [PDF - 319 KB - 9 pages]
    C. Reusken et al.
    View Summary

    The risk to public health is absent or extremely low.

       View Abstract

    The emergence of Schmallenberg virus (SBV), a novel orthobunyavirus, in ruminants in Europe triggered a joint veterinary and public health response to address the possible consequences to human health. Use of a risk profiling algorithm enabled the conclusion that the risk for zoonotic transmission of SBV could not be excluded completely. Self-reported health problems were monitored, and a serologic study was initiated among persons living and/or working on SBV-affected farms. In the study set-up, we addressed the vector and direct transmission routes for putative zoonotic transfer. In total, 69 sheep farms, 4 goat farms, and 50 cattle farms were included. No evidence for SBV-neutralizing antibodies was found in serum of 301 participants. The lack of evidence for zoonotic transmission from either syndromic illness monitoring or serologic testing of presumably highly exposed persons suggests that the public health risk for SBV, given the current situation, is absent or extremely low.

  • Unchanged Severity of Influenza A(H1N1)pdm09 Infection in Children during First Postpandemic Season PDF Version [PDF - 215 KB - 8 pages]
    M. Altmann et al.
    View Summary

    Improvement is needed in preventing severe disease and nosocomial transmission in children beyond pandemic situations.

       View Abstract

    We conducted a nationwide hospital-based prospective study in Germany of influenza A(H1N1)pdm09 cases among children <15 years of age admitted to pediatric intensive care units and related deaths during the 2009–10 pandemic and the 2010–11 postpandemic influenza seasons. We identified 156 eligible patients: 112 in 2009–10 and 44 in 2010–11. Although a shift to younger patients occurred in 2010–11 (median age 3.2 vs. 5.3 years), infants <1 year of age remained the most affected. Underlying immunosuppression was a risk factor for hospital-acquired infections (p = 0.013), which accounted for 14% of cases. Myocarditis was predictive of death (p = 0.006). Of the 156 case-patients, 17% died; the difference between seasons was not significant (p = 0.473). Our findings stress the challenge of preventing severe postpandemic influenza infection in children and the need to prevent nosocomial transmission of influenza virus, especially in immunosuppressed children.

  • Mycoplasmosis in Ferrets PDF Version [PDF - 504 KB - 8 pages]
    M. Kiupel et al.
    View Summary

    A newly recognized respiratory disease of domestic ferrets is associated with a novel Mycoplasma species.

       View Abstract

    We report an outbreak of severe respiratory disease associated with a novel Mycoplasma species in ferrets. During 2009–2012, a respiratory disease characterized by nonproductive coughing affected ≈8,000 ferrets, 6–8 weeks of age, which had been imported from a breeding facility in Canada. Almost 95% became ill, but almost none died. Treatments temporarily decreased all clinical signs except cough. Postmortem examinations of euthanized ferrets revealed bronchointerstitial pneumonia with prominent hyperplasia of bronchiole-associated lymphoid tissue. Immunohistochemical analysis with polyclonal antibody against Mycoplasma bovis demonstrated intense staining along the bronchiolar brush border. Bronchoalveolar lavage samples from 12 affected ferrets yielded fast-growing, glucose-fermenting mycoplasmas. Nucleic acid sequence analysis of PCR-derived amplicons from portions of the 16S rDNA and RNA polymerase B genes failed to identify the mycoplasmas but showed that they were most similar to M. molare and M. lagogenitalium. These findings indicate a causal association between the novel Mycoplasma species and the newly recognized pulmonary disease.

  • Lack of Cross-protection against Bordetella holmesii after Pertussis Vaccination PDF Version [PDF - 486 KB - 9 pages]
    X. Zhang et al.
    View Summary

    Vaccines for B. pertussis do not protect against circulating strains of a closely related respiratory pathogen.

       View Abstract

    Bordetella holmesii, a species closely related to B. pertussis, has been reported sporadically as a cause of whooping cough–like symptoms. To investigate whether B. pertussis–induced immunity is protective against infection with B. holmesii, we conducted an analysis using 11 human respiratory B. holmesii isolates collected during 2005–2009 from a highly B. pertussis–vaccinated population in Massachusetts. Neither whole-cell (wP) nor acellular (aP) B. pertussis vaccination conferred protection against these B. holmesii isolates in mice. Although T-cell responses induced by wP or aP cross-reacted with B. holmesii, vaccine-induced antibodies failed to efficiently bind B. holmesii. B. holmesii–specific antibodies provided in addition to wP were sufficient to rapidly reduce B. holmesii numbers in mouse lungs. Our findings suggest the established presence of B. holmesii in Massachusetts and that failure to induce cross-reactive antibodies may explain poor vaccine-induced cross-protection.

  • Seroprevalence of Antibodies against Chikungunya, Dengue, and Rift Valley Fever Viruses after Febrile Illness Outbreak, Madagascar PDF Version [PDF - 658 KB - 7 pages]
    N. G. Schwarz et al.
    View Summary

    The outbreak was an isolated chikungunya epidemic without relevant dengue virus co-transmission.

       View Abstract

    In October 2009, two–3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450–1,300 m high, IgG seroprevalence against CHIKV was 0%–3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission.

  • Epidemic Myalgia in Adults Associated with Human Parechovirus Type 3 Infection, Yamagata, Japan, 2008 PDF Version [PDF - 236 KB - 7 pages]
    K. Mizuta et al.
    View Summary

    This virus typically causes illness in young children but was found to be associated with illness in adults.

       View Abstract

    Human parechovirus has rarely been shown to cause clinical disease in adults. During June–August 2008, a total of 22 adults sought treatment at Yonezawa City Hospital in Yamagata, Japan, for muscle pain and weakness of all limbs; most also had fever and sore throat. All patients received a clinical diagnosis of epidemic myalgia; clinical laboratory findings suggested an acute inflammatory process. Laboratory confirmation of infection with human parechovirus type 3 (HPeV3) was made for 14 patients; we isolated HPeV3 from 7 patients, detected HPeV3 genome in 11, and observed serologic confirmation of infection in 11. Although HPeV3 is typically associated with disease in young children, our results suggest that this outbreak of myalgia among adults was associated with HPeV3 infection. Clinical consideration should be given to HPeV3 not only in young children but also in adults when an outbreak occurs in the community.

  • Infectious Disease Mortality Rates, Thailand, 1958–2009 PDF Version [PDF - 407 KB - 8 pages]
    S. Aungkulanon et al.
    View Summary

    Reliable, relevant, and timely data guide public health policies that protect and promote health.

       View Abstract

    To better define infectious diseases of concern in Thailand, trends in the mortality rate during 1958–2009 were analyzed by using data from public health statistics reports. From 1958 to the mid-1990s, the rate of infectious disease–associated deaths declined 5-fold (from 163.4 deaths/100,000 population in 1958 to 29.5/100,000 in 1997). This average annual reduction of 3.2 deaths/100,000 population was largely attributed to declines in deaths related to malaria, tuberculosis, pneumonia, and gastrointestinal infections. However, during 1998–2003, the mortality rate increased (peak of 70.0 deaths/100,000 population in 2003), coinciding with increases in mortality rate from AIDS, tuberculosis, and pneumonia. During 2004–2009, the rate declined to 41.0 deaths/100,000 population, coinciding with a decrease in AIDS-related deaths. The emergence of AIDS and the increase in tuberculosis- and pneumonia-related deaths in the late twentieth century emphasize the need to direct resources and efforts to the control of emerging and re-emerging infectious diseases.

  • HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina PDF Version [PDF - 321 KB - 9 pages]
    V. Ritacco et al.
    View Summary

    Disease trends are driven by HIV co-infection and transmission of a few strains within narrow geographic niches.

       View Abstract

    During 2003–2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs.

  • Risk for Travel-associated Legionnaires’ Disease, Europe, 2009 PDF Version [PDF - 178 KB - 6 pages]
    J. Beauté et al.
    View Summary

    Infections increased in a southeastern direction, with highest risk in Greece.

       View Abstract

    Legionnaires’ disease is underreported in Europe; notification rates differ substantially among countries. Approximately 20% of reported cases are travel-associated. To assess the risk for travel-associated Legionnaires’ disease (TALD) associated with travel patterns in European countries, we retrieved TALD surveillance data for 2009 from the European Surveillance System, and tourism denominator data from the Statistical Office of the European Union. Risk (number cases reported/number nights spent) was calculated by travel country. In 2009, the network reported 607 cases among European travelers, possibly associated with 825 accommodation sites in European Union countries. The overall risk associated with travel abroad was 0.3 cases/million nights. We observed an increasing trend in risk from northwestern to southeastern Europe; Greece had the highest risk (1.7). Our findings underscore the need for countries with high TALD risks to improve prevention and control of legionellosis; and for countries with high TALD risks, but low notification rates of Legionnaires’ disease to improve diagnostics and reporting.

  • Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009 PDF Version [PDF - 300 KB - 8 pages]
    J. Paireau et al.
    View Summary

    Outbreaks are spatiotemporally associated with litchi harvest, but the causative agent remains unknown.

       View Abstract

    Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May–July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004–2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90–2.57), 2.94 (95% CI 1.88–4.60), and 2.76 (95% CI 1.76–4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.

  • Community Outbreak of Adenovirus, Taiwan, 2011 PDF Version [PDF - 319 KB - 8 pages]
    T. Tsou et al.
    View Summary

    Adenovirus type 7 caused a high proportion of severe infections.

       View Abstract

    In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14–October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008–2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People’s Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.

  • Antigenic Diversity of Enteroviruses Associated with Nonpolio Acute Flaccid Paralysis, India, 2007–2009 PDF Version [PDF - 503 KB - 8 pages]
    C. Rao et al.
    View Summary

    Three new enterovirus 71 genogroups are geographically widely disbursed.

       View Abstract

    Because of the broadened acute flacid paralysis (AFP) definition and enhanced surveillance, many nonpolio AFP (NP-AFP) cases have been reported in India since 2005. To determine the spectrum of nonpolio enterovirus (NPEV) serotypes associated with NP-AFP from polio-endemic and -free regions, we studied antigenic diversity of AFP-associated NPEVs. Of fecal specimens from 2,786 children with NP-AFP in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for NPEVs in RD cells, of which 532 (64.6%) were positive by viral protein 1 reverse transcription PCR. We identified 66 serotypes among 581 isolates, with enterovirus 71 most frequently (8.43%) detected, followed by enterovirus 13 (7.1%) and coxsackievirus B5 (5.0%). Most strains within a serotype represented new genogropups or subgenogroups. Agents for ≈35.0% and 70.0% of culture-positive and -negative cases, respectively, need to be identified. Association of human enterovirus with NP-AFP requires better assessment and understanding of health risks of NPEV infections after polio elimination.

  • Livestock Density as Risk Factor for Livestock-associated Methicillin-Resistant Staphylococcus aureus, the Netherlands PDF Version [PDF - 964 KB - 9 pages]
    B. J. Feingold et al.
    View Summary

    The risk for livestock-associated MRSA increases with increasing density of pigs and calves.

       View Abstract

    To determine whether persons living in areas of high animal density are at increased risk for carrying livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), we used an existing dataset of persons in the Netherlands with LA-MRSA carriage and controls who carried other types of MRSA. Results of running univariate and multivariate logistic regression models indicated that living in livestock-dense areas increases the odds of nasal carriage of LA-MRSA. We found that doubling pig, cattle, and veal calf densities per municipality increased the odds of LA-MRSA carriage over carriage of other types of MRSA by 24.7% (95% CI 0.9%–54.2%), 76.9% (95% CI 11.3%–81.3%), and 24.1% (95% CI 5.5%–45.9%), respectively, after adjusting for direct animal contact, living in a rural area, and the probable source of MRSA carriage. Controlling the spread of LA-MRSA thus requires giving attention to community members in animal-dense regions who are unaffiliated with livestock farming.

  • Sources of Dengue Viruses Imported into Queensland, Australia, 2002–2010 PDF Version [PDF - 470 KB - 8 pages]
    D. Warrilow et al.
    View Summary

    Molecular epidemiologic analysis shows that travelers returning from Asia are the greatest source of risk.

       View Abstract

    To assess risk for importation of dengue virus (DENV) into Queensland, Australia, and sources of imported viruses, we sequenced the envelope region of DENV isolates from symptomatic patients with a history of travel during 2002–2010. The number of imported dengue cases greatly increased over the surveillance period, some of which were associated with domestic outbreaks. Patients reported traveling to (in order) Asia, Papua New Guinea, Pacific Island countries, and non–Asia-Pacific countries. By using phylogenetic methods, we assigned DENV isolates from returning residents and overseas visitors with viremia to a specific genotypic group. Genotypes circulating in Asia were extremely diverse. Genotyping and molecular clock analysis supported Asian origination of a strain that caused an outbreak of DENV-4 in Pacific Island countries during 2007–2009, and subsequently, in Innisfail, Australia, in 2009. Our findings indicate that Asia is a major source of DENVs that are imported into Australia, causing a risk for epidemics.

  • Phylogeography of Dengue Virus Serotype 4, Brazil, 2010–2011 PDF Version [PDF - 367 KB - 7 pages]
    M. Nunes et al.
    View Summary

    Multiple origins indicate this serotype was introduced in several episodes.

       View Abstract

    Dengue virus serotype 4 (DENV-4) reemerged in Roraima State, Brazil, 28 years after it was last detected in the country in 1982. To study the origin and evolution of this reemergence, full-length sequences were obtained for 16 DENV-4 isolates from northern (Roraima, Amazonas, Pará States) and northeastern (Bahia State) Brazil during the 2010 and 2011 dengue virus seasons and for an isolate from the 1982 epidemic in Roraima. Spatiotemporal dynamics of DENV-4 introductions in Brazil were applied to envelope genes and full genomes by using Bayesian phylogeographic analyses. An introduction of genotype I into Brazil from Southeast Asia was confirmed, and full genome phylogeographic analyses revealed multiple introductions of DENV-4 genotype II in Brazil, providing evidence for >3 introductions of this genotype within the last decade: 2 from Venezuela to Roraima and 1 from Colombia to Amazonas. The phylogeographic analysis of full genome data has demonstrated the origins of DENV-4 throughout Brazil.

Dispatches

Commentaries

Another Dimension

Letters

About the Cover

Etymologia

Online Reports

  • Peer Reviewed Report Available Online Only
    Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response
    F. M. Aarestrup et al.
       View Abstract

    The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.

  • Peer Reviewed Report Available Online Only
    Challenges and Controversies in Defining Totally Drug-Resistant Tuberculosis
    P. Cegielski et al.
       View Abstract

    In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB. Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB. Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

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