Professor Andrew Whitelaw, Infection Control Society of Southern Africa
Case scenario 1:
A medical student was asked to clerk a patient with MDR-TB who was being admitted for a partial pneumonectomy. He had been on treatment with standard MDR therapy for 12 months with no resolution of symptoms, and was still smear positive 2 months prior to admission. On chest X-Ray he had severe disease in the right middle and upper lobes. Approximately one month later the medical student started complaining of non-specific symptoms of tiredness and lethargy, and occasional fevers. A chest X-Ray showed a left pleural effusion. The pleural effusion was tapped. Microscopy of the effusion showed no acid fast bacilli, however a GeneXpert MTB/Rif assay was performed which was positive for M. tuberculosis, resistant to rifampicin. A line probe assay was also performed on the effusion and this was negative. The GeneXpert was repeated and was negative. Culture of the pleural fluid was requested.
Case scenario 2:
A medical student was diagnosed with rifampicin susceptible pulmonary tuberculosis using the GeneXpert. Subsequent microscopy showed that he was smear-positive. He used to work in a study group with 5 other students, and these students were now concerned about their risk of acquiring TB. They wanted to know whether they should be tested, how they should be tested, and whether they should take prophylaxis.
Question 1: Was sinusitis an appropriate diagnosis in the first instance?
Answer to Q1
The GeneXpert MTB/Rif assay is an automated real time PCR assay able to detect M. tuberculosis in clinical samples, as well as detect the presence or absence of rifampicin resistance. It works by amplifying a portion of the rpoB gene using primers specific for M. tuberculosis complex, and by determining whether there are any mutations within the gene. The rpoB gene encodes RNA polymerase, which is the target of rifampicin. If there are mutations within the gene, this implies resistance to rifampicin.
Most work to date has focused on the performance of the assay on sputum samples. The sensitivity (i.e. the ability to detect TB) is overall about 90% (i.e. it detects 90% of TB patients). However this does depend very much on whether the patient is sputum smear-positive or sputum smear-negative (and in turn this is influenced by HIV status – HIV-infected patients often have smear negative TB). The GeneXpert detects about 65-70% of TB in patients who have negative microscopy. This still represents a substantial improvement over smear microscopy. In South Africa the GeneXpert MTB/Rif test is being rolled out nationally, and ultimately all TB suspects should have a GeneXpert MTB/if test performed (instead of microscopy). If the GeneXpert MTB/Rif is negative, then follow up samples can be sent for culture if necessary (eg in HIV infected patients).
False positive GeneXpert MTB/Rif results are very uncommon – in practice a sample with a positive GeneXpert MTB/Rif result means the patient has TB, and treatment should be initiated. The performance for detection of rifampicin resistance is slightly more concerning. A result that indicates that the isolate is sensitive to rifampicin is generally reliable; however there have been a number of reports of GeneXpert MTB/Rif results showing rifampicin resistance that turn out to be incorrect – the patient still has TB, but it is sensitive to rifampicin. Approximately 80-90% of GeneXpert MTB/Rif rifampicin resistant results correlate with true resistance, but 10-20% of the rifampicin resistant results are incorrect – the patients have rifampicin susceptible TB. This percentage does vary according to how common rifampicin resistance is – the more common rifampicin resistance, the more reliable the GeneXpert MTB/Rif rifampicin result. However, in South Africa where rifampicin resistance occurs in < 10% of tb cases, the above figures apply. thus the current recommendation is that all patients who have rifampicin resistance detected using the genexpert mtb />Rif must have a second sample sent in order to confirm rifampicin resistance using an alternative method. However, the patient should still be commenced on therapy for MDR-TB.
Question 2: What infection control precautions are recommended for HCWs exposed to patients with TB (drug sensitive and drug resistant TB)?
Answer to Q2
Numerous organisations, such as the Centres for Disease Control (CDC) and the World Health Organisation (WHO) have published recommendations for prevention of nosocomial TB. These comprehensive recommendations are often adapted for use in many countries, including South Africa. All agree that prevention of nosocomial spread of TB requires administrative controls, engineering controls and personal protective equipment (summarized in Box 1).
Effective TB infection control requires all three elements to be in place. The decision of how exactly to implement the various measures, and which measures to implement, is another of the major difficulties facing TB infection control, especially in resource limited settings. There is unfortunately little data to indicate which individual measures are the most effective, as most programmes implement a combined approach.
Administrative controls are often regarded as the most effective, but are also often the most challenging to put in place, as well as to sustain and enforce. Administrative controls usually require a co-ordinated effort among multiple levels of the health care facility, and incorporate:
Administrative controls would also be those that govern the use of engineering controls, use of personal protective equipment, decisions about who should use PPE, when it should be used, which patients should be placed into isolation, etc. Thus without adequate administrative controls, it is hard to envisage any health care facility being able to have an effective TB infection control programme.
Engineering controls Engineering controls refer to those measures taken to reduce the number of infectious particles circulating in the environment, and usually take the form of either ventilation or ultra-violet germicidal irradiation. Some of these can be accomplished quite simply – improving natural ventilation by opening windows, for example, can result in up to 28 air changes per hour (far more than the 12 air changes per hour recommended in most guidelines). However, the reliability of this approach is affected by the outside weather (rain and wind especially), and by the design of the facility. Many hospitals have not been designed with the need for adequate airborne ventilation in mind – and have lower ceilings and smaller windows. However, given that good mechanical ventilation is a luxury available to few facilities in the state sector, use of natural ventilation should be encouraged wherever possible – both at the hospital as well as at the clinic level. Basu et al used modelling to describe the potential impact of different administrative measures and engineering controls in the transmission of XDR-TB in Tugela Ferry. Although there may be limitations involved in interpreting modelling data, it is interesting that they found that improvement in natural ventilation was one of the most effective single measures in reducing transmission of XDR-TB – and the same would presumably hold for transmission of drug susceptible TB. However, they also found that a combination of multiple interventions reduced the possible transmission of XDR-TB by nearly 50% - again highlighting the need for an integrated approach to nosocomial TB prevention. Sputum collection and sputum induction procedures should be conducted in well ventilated areas (preferably outside) or in sputum induction booths. Even with supposedly adequately ventilated booths, there is an increase in airborne bacteria after sputum induction, and HCWs should either not be in the same room when sputum induction occurs, or should wear personal protective equipment. The other commonly described engineering control is ultra-violet germicidal irradiation. This is a more contentious area of TB infection control. While there is evidence that it is effective, it can be a costly intervention as UV lamps need regular maintenance and replacement. Lamps need to be well positioned to avoid unnecessary exposure of patients and staff, and it is important to ensure that the airflow in the room allows the air (and thus the airborne bacilli) to be exposed to the UV light.
Personal respiratory protection
Ordinary surgical masks are not designed to filter out the small droplet nuclei that may carry tubercle bacilli. For adequate respiratory protection, particulate respirators are recommended, such as the N95 masks. The WHO guidelines recommend that patients wear surgical masks if they need to move within the hospital, and that particulate respirators (N95 masks) be worn by health care workers; these recommendations have been adopted by South Africa. The major challenges faced by health services with respect to mask use relate to the cost of the masks, the discomfort, and the need for proper fit testing. Fit testing should be performed for all HCs who are going to be wearing these masks, although there is a problem with lack of availability of the appropriate equipment and expertise to do ft testing. However, some of the manufacturers of the masks are able to assist with fit testing. Although the masks are expensive, they do not need to be disposed of after only one use. As long as the mask remains unsoiled, dry and undamaged, it can be reused.
Question 3: What is the appropriate follow up for a HCW known to have been exposed to someone (patient or colleague) with TB?
Answer to Q3
There is likely to be some disagreement about this! For all exposed HCWs (and actually all HCWs in general), symptom screening and education about likely symptoms of TB is crucial, and many would recommend a baseline chest X-Ray. This is not done so much to look for TB, but to serve as a baseline for comparison if a follow up X-Ray is mandated by development of symptoms. The value of routine annual chest X-Rays is less clear, and the decision of whether or not to offer this to HCWs must be based on the available resources both to do the X-rays, as well as availability of radiologists to report on them, and the ability to monitor adherence to the schedule.
In HIV-infected HCWs with exposure, provision of INH prophylaxis may be valuable. Tuberculin skin testing (TST) is recommended for all people living with HIV. However it is important to exclude active TB before starting prophylaxis. Patients with a positive TST do benefit more from IPT (INH preventive therapy) than those with a negative skin test, and IPT is recommended for those patients with a positive TST. However if the TST cannot be done for any reason, then IPT should be provided (i.e. absence of a TST result is not a contra-indication to providing IPT). Some have argued that an interferon-gamma release assay may be useful to guide the decision of whether or not to provide INH prophylaxis. However, in an endemic setting (such as South Africa), this is unlikely to be helpful. There is no evidence to support the use of IGRAs to decide who will benefit from IPT in high TB prevalence setting.
Case 1 – the student was started on MDR therapy, and the result of the TB culture of pleural fluid is awaited.
Case 2 – the exposed students were offered baseline CXRs, 3-monthly symptom screens are being performed, and counseling and testing for HIV infection is being offered.
Prevention is better than cure. Only HCWs who absolutely need to should attend to patients with known MDR-TB, and appropriate infection control precautions MUST be in place. Unfortunately sometimes exposure is unavoidable – but if it does occur, the circumstances around the exposure need to be investigated, and if necessary, additional administrative controls put into place.
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