**11. Drug resistant TB infection (tansmission) in the community and hospitals**

In 1998, the Centers for Disease Control and Prevention (CDC) and the Institute of Medicine of the National Academy of Sciences conducted a study to determine if TB eradication in the United State was feasible. The resulting report "*Ending Neglect: The Elimination of Tuberculosis in the United States*" concluded that TB elimination would require "aggressive and decisive action beyond what was in effect." One of the top objectives of the new CDC plan is to ensure that patient-centered case management and monitoring of treatment outcomes are the standard of care for all TB patients [108]. In particular, the CDC guidelines recommend all patients with active TB must be tested for HIV infection and that all patients double infected with Mtb and HIV infection must be appropriately and adequately treated. To ensure adher‐ ence to treatment, the CDC recommend the inclusion of multiple enablers (e.g., transportation vouchers and housing for the homeless) and incentives that will motivate the patient (e.g., food coupons), and other treatment enhancers such as alternative treatment delivery sites, and

Addressing social and economic barriers definitely increases patient access to adequate TB care. However, health education would also strengthen patient-centered approaches. Under‐ standing an illness and how it affects ones life, as well as available treatment options, are necessary for a patient and community to take an active role in TB management. With input from community health professionals from several countries, a literacy tool kit "Within Our Reach: A TB Literacy Toolkit" was developed in 2009 for health educators, outreach workers,

counselors, and supervisors who provide services to TB patients [109] and (Box 5).

Increasing knowledge about TB, the link between TB and HIV, TB treatment, and TB

The tools are designed to educate TB and HIV patients, their caregivers, and their communities about TB and what it takes to complete a full course of TB treatment. The kit developers suggest that individual sessions should be conducted with flipcharts between the health provider and patient, and videos should be played in a waiting area or during community education events.

Patient-centeredness has become a central approach towards realizing universal access for all patients to efficient TB care. However scaling up this approach is progressing slowly in high TB-burden countries and is mainly challenged by the socio-economic determinants of knowl‐ edge and attitudes about TB among health care providers and the general population. Therefore optimal patient-centeredness approach requires collaborative efforts between all organizations serving TB patients to ensure that health care providers, policy makers, com‐

Giving patients confidence that they can complete TB treatment and be cured

Educating caregivers and families about how to support TB patients

munity leaders and the public are knowledgeable about TB disease.

Raising awareness that TB is a serious but treatable disease

Reducing stigma attached to TB and HIV

**Box 5.** Supporting objectives of the TB Literacy Toolkit

strategies to overcome social and cultural barriers.

222 Tuberculosis - Current Issues in Diagnosis and Management

transmission

TB is a highly contagious disease, acquired mainly through inhalation of airborne aerosols. Infection can occur by inhaling as few as 5-10 living bacteria. People with active TB infection spread the bacterium not only by coughing and sneezing but also by spitting, speaking, singing or laughing. The infectiousness of a TB patient is directly related to the number of droplet nuclei carrying Mtb that are expelled into the air. These droplets rapidly evaporated to form tiny particle nuclei, which could remain airborne for several days [110]. Given this mode of propagation, a person with active TB can spread the germs to up to 15 people in a year, if left untreated [4]. Therefore the process of TB spread also needs to be controlled in order to successfully combat the TB epidemic. In this regards, Nardell recommend the term "trans‐ mission control of TB" instead of "infection control of TB", since a third of the world's population is already infected with TB, a situation that appear to be stationary [111].

Because MDR strains carry mutations in major metabolic activities, in particular INH resistant strains lacking catalase activity [112], some researchers have suggested that they may be less virulent and less transmissible [113]. Contrasting with this hypothesis, the epidemic that occurred in New York City in the 1990s [114,115], which affected mainly HIV-infected persons, proved that MDR strains are highly virulent and transmissible. Current data on MDR TB prevalence in Africa, Eastern Europe and Asia [116] provides further evidence of this phe‐ nomenon. Drug resistant TB can be transmitted in virtually any setting but healthcare settings, correctional institutions and homeless shelters have an increased risk of transmission. The level of drug resistance TB in hospital settings varies according to local TB prevalence. For instance an university hospitals in Paris (France), reported MDR rates of respectively 1.2% among TB cases [117], while in university hospitals in Manila (Philippine), this figure was an alarming 53.5% [118].

It is generally thought that the emergence of drug-resistant TB (usually termed acquired) occurs in settings where patients fail to adhere to proper treatment regimens or receive inadequate treatment. It is difficult to assign the current magnitude of the epidemic to acquired resistance alone. Another mechanism for the perpetuation of resistance, which has largely been neglected in the development of TB control programmes, is the direct transmission of drugresistant strains (called primary or transmitted resistance) [119]. In the 2006 XDR-TB outbreak in KwaZulu-Natal (South Africa), 52 of 53 people who contracted the disease (all of them HIV infected) died within weeks [120]. This outbreak received international attention because 85 percent of infected patients had genetically similar XDR strain, indicating that resistance was likely transmitted rather than acquired. Consistent with these findings, a study conducted in Tomsk (Siberia) –a setting where HIV infection is not widespread and effective TB treatment is available– to identify factors leading to increases in MDR-TB cases [121], revealed that a patient was six times more likely to develop MDR-TB if hospitalized for drug-susceptible TB than if not hospitalized. These results strongly suggest that nosocomial transmission of TB rather than resistance (acquired predominantly by nonadherence) is increasingly responsible for the rising MDR TB case rates in Russia and probably in many other places.

Worthy of note is that nosocomial transmission of TB is a risk not only to inpatients but also health care workers (HCWs). In fact, early studies revealed transmission of MDR-TB from patient to patient and from patient to HCWs [122]. A systematic review by Joshi and colleagues [123] demonstrated that TB is a significant occupational problem among HCWs in many low- and middle-income countries and that most health care facilities in these sittings lack resources to prevent nosocomial transmission of TB. HIV-infected HCWs have a particularly high risk of TB, which may be fatal if the disease is caused by a drug-resistant strain [124]. Indeed, dramatic nosocomial outbreaks of MDR TB occurred the late 1980s, largely in HIV infected HCWs, and caused many deaths [110]. This situation increased the concern of HCWs about the safety of working in institutions with a large numbers of admissions for active TB. Indeed, it is estimated that 1% to 10% of HCWs are infected annually in hospitals with more than 200 admissions per year for TB [110]. The risk of TB transmis‐ sion to HCWs is particularly high in certain areas of the hospital, such as emergency rooms and units that admit patients with active TB [125].

A review of several reports of TB outbreaks with transmission to HCWs in industrialized countries revealed that many factors contribute to nosocomial transmission, such as delayed diagnosis, poor ventilation with positive pressure in isolation rooms, aerosolization of bacilli through mechanical ventilation, bronchoscopy and dressing change [110]. There was also strong evidence that technicians involved in cough-inducing procedures, histologic prepara‐ tions and autopsies are at high risk, even in institutions caring for few patients with TB [126]. These outbreaks revealed many deficiencies in the knowledge of TB and its transmission as well as strategies used to control the disease. Therefore, various health authorities have implemented effective control programmes based on the early detection of TB and the prompt isolation and treatment of persons with TB in addition to introducing strong measures to prevent nosocomial transmissions of TB. For instance, the US Centers for Disease Control (CDC) [127] recommended the following levels of controls: **1. Administrative controls,** which reduce risk of exposure. **2. Environmental controls,** which prevent spread and reduce concentration of droplet nuclei. **3. Respiratory-protection controls,** which further reduce risk of exposure in special areas and circumstances. (Box 6).

Implementation of a full hierarchy of these measures lead to a significant reduction in nosocomial transmission of TB in the United States [128]. Whereas the extent of the epidemics in low and middle income countries is still attributed, in large part, to ineffective transmission control strategies. In these countries, double infection with TB and HIV has further accelerated the transmission of drug resistant TB and increased the spread of HIV. Such a dramatic situation blocks the efforts of both the Stop TB Partnership and anti-retroviral therapy programmes. It is regrettable that many health care institutions continue to house HIV positive individuals with patients who have drug-resistant TB, thus leading to nosocomial transmission with subsequent community transmission. In this regards, health authorities in Haiti imple‐ mented an effective community-based transmission control programme with a baseline triage and separation strategy [111]. Patients are admitted to either the general medical ward, a TB pavilion, or very basic isolation rooms based on smear results and HIV status (Fig. 2).

**Figure 2. Community-based TB treatment triage strategy in Haiti.** The general medical ward has natural ventila‐ tion and UV air disinfection. The TB ward has natural ventilation with fenestrated brick and more UV fixtures to disin‐ fect the air than the general ward has. The six isolation rooms are off a common corridor, and each has a large exhaust fan built into the wall that draws air into the room from the corridor, as well as a UV fixture. Reprinted from Ref. 111

Administrative Controls

Management of Drug-Resistant TB http://dx.doi.org/10.5772/55531 225

Environmental Controls

• Ventilation technologies (Natural ventilation and Mechanical ventilation) • High efficiency particulate air filtration •

Respiratory Protection Controls • Implement a respiratory-protection programme • Train health-care workers on respiratory protection • Educate patients on respiratory hygiene and the importance of covering their cough • Test HCWs for mask fit and functionality

• Assign responsibility for TB infection control • Conduct TB risk assessment • Develop and institute a written TB infection-control plan • Ensure the timely availability of recommended laboratory processing, testing, and reporting of

• Implement effective work practices for the management of patients with suspected or confirmed TB disease • Ensure proper cleaning and sterilization or disinfection of potentially contaminated equipment • Train and educate health-care workers • Test and evaluate health-care workers for TB infection and disease • Apply epidemiology-based prevention principles • Use posters and signs demonstrating and advising respiratory hygiene and cough etiquette •

Coordinate efforts with the local or state health department.

**Box 6.** TB Infection-Control Programme: Level of Controls

Ultraviolet germicidal irradiation

Reduce concentration of infectious droplet nuclei through the following technologies:

Although this simple baseline strategy is not sufficient, Nardell considers that its implement‐ ing in other resource-poor settings would contribute significantly to reduce the burden of TB

with permission of the International Union Against Tuberculosis and Lung Disease. Copyright © The Union

epidemic [111].

results

Administrative Controls

• Assign responsibility for TB infection control • Conduct TB risk assessment • Develop and institute a written TB infection-control plan • Ensure the timely availability of recommended laboratory processing, testing, and reporting of results

• Implement effective work practices for the management of patients with suspected or confirmed TB disease • Ensure proper cleaning and sterilization or disinfection of potentially contaminated equipment • Train and educate health-care workers • Test and evaluate health-care workers for TB infection and disease • Apply epidemiology-based prevention principles • Use posters and signs demonstrating and advising respiratory hygiene and cough etiquette • Coordinate efforts with the local or state health department.

Environmental Controls

Reduce concentration of infectious droplet nuclei through the following technologies:

• Ventilation technologies (Natural ventilation and Mechanical ventilation) • High efficiency particulate air filtration • Ultraviolet germicidal irradiation

Respiratory Protection Controls

• Implement a respiratory-protection programme • Train health-care workers on respiratory protection • Educate patients on respiratory hygiene and the importance of covering their cough • Test HCWs for mask fit and functionality

Worthy of note is that nosocomial transmission of TB is a risk not only to inpatients but also health care workers (HCWs). In fact, early studies revealed transmission of MDR-TB from patient to patient and from patient to HCWs [122]. A systematic review by Joshi and colleagues [123] demonstrated that TB is a significant occupational problem among HCWs in many low- and middle-income countries and that most health care facilities in these sittings lack resources to prevent nosocomial transmission of TB. HIV-infected HCWs have a particularly high risk of TB, which may be fatal if the disease is caused by a drug-resistant strain [124]. Indeed, dramatic nosocomial outbreaks of MDR TB occurred the late 1980s, largely in HIV infected HCWs, and caused many deaths [110]. This situation increased the concern of HCWs about the safety of working in institutions with a large numbers of admissions for active TB. Indeed, it is estimated that 1% to 10% of HCWs are infected annually in hospitals with more than 200 admissions per year for TB [110]. The risk of TB transmis‐ sion to HCWs is particularly high in certain areas of the hospital, such as emergency rooms

A review of several reports of TB outbreaks with transmission to HCWs in industrialized countries revealed that many factors contribute to nosocomial transmission, such as delayed diagnosis, poor ventilation with positive pressure in isolation rooms, aerosolization of bacilli through mechanical ventilation, bronchoscopy and dressing change [110]. There was also strong evidence that technicians involved in cough-inducing procedures, histologic prepara‐ tions and autopsies are at high risk, even in institutions caring for few patients with TB [126]. These outbreaks revealed many deficiencies in the knowledge of TB and its transmission as well as strategies used to control the disease. Therefore, various health authorities have implemented effective control programmes based on the early detection of TB and the prompt isolation and treatment of persons with TB in addition to introducing strong measures to prevent nosocomial transmissions of TB. For instance, the US Centers for Disease Control (CDC) [127] recommended the following levels of controls: **1. Administrative controls,** which reduce risk of exposure. **2. Environmental controls,** which prevent spread and reduce concentration of droplet nuclei. **3. Respiratory-protection controls,** which further reduce risk

Implementation of a full hierarchy of these measures lead to a significant reduction in nosocomial transmission of TB in the United States [128]. Whereas the extent of the epidemics in low and middle income countries is still attributed, in large part, to ineffective transmission control strategies. In these countries, double infection with TB and HIV has further accelerated the transmission of drug resistant TB and increased the spread of HIV. Such a dramatic situation blocks the efforts of both the Stop TB Partnership and anti-retroviral therapy programmes. It is regrettable that many health care institutions continue to house HIV positive individuals with patients who have drug-resistant TB, thus leading to nosocomial transmission with subsequent community transmission. In this regards, health authorities in Haiti imple‐ mented an effective community-based transmission control programme with a baseline triage and separation strategy [111]. Patients are admitted to either the general medical ward, a TB

pavilion, or very basic isolation rooms based on smear results and HIV status (Fig. 2).

and units that admit patients with active TB [125].

224 Tuberculosis - Current Issues in Diagnosis and Management

of exposure in special areas and circumstances. (Box 6).

**Figure 2. Community-based TB treatment triage strategy in Haiti.** The general medical ward has natural ventila‐ tion and UV air disinfection. The TB ward has natural ventilation with fenestrated brick and more UV fixtures to disin‐ fect the air than the general ward has. The six isolation rooms are off a common corridor, and each has a large exhaust fan built into the wall that draws air into the room from the corridor, as well as a UV fixture. Reprinted from Ref. 111 with permission of the International Union Against Tuberculosis and Lung Disease. Copyright © The Union

Although this simple baseline strategy is not sufficient, Nardell considers that its implement‐ ing in other resource-poor settings would contribute significantly to reduce the burden of TB epidemic [111].
