JAIDS Journal of Acquired Immune Deficiency Syndromes:
Infection Control Best Practices in Clinical Research in Resource-Limited Settings
Godfrey, Catherine MD, FRACP*; Schouten, Jeffrey T. MD, JD†
*Division of AIDS, National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD; and
†Office of HIV/AIDS Network Coordination, Fred Hutchinson Cancer Research Center, Seattle, WA.
Correspondence to: Catherine Godfrey, MD, FRACP, National Institutes of Health, National Institute of Allergy and Infectious Diseases, 6700B Rockledge Dr, Bethesda, MD 20892 (e-mail: email@example.com).
The Office of HIV/AIDS Network Coordination has been funded in whole or in part with Federal funds from the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, grant number UM01 AI068614, entitled Leadership Group for a Global HIV Vaccine Clinical Trials (Office of HIV/AIDS Network Coordination) with additional support from the National Institute of Mental Health.
This article was written by C.G. in her capacity as NIH employee, but the views expressed in this paper do not necessarily represent those of the NIH.
The authors have no conflicts of interest to disclose.
Abstract: Infection control activities in the international research setting include the development of meaningful and effective policies on specific topics such as hand and respiratory hygiene. Prevention of infection in health care workers and management of occupational exposure to transmissible agents are important aspects of the role of an infection control practitioner. Hand hygiene reduces health care associated infections and practices may be implemented in the research setting.
Well-conceived and carefully implemented infection control (IC) programs reduce illness, prevent death, and save money.1–3 Yet, proven interventions have not been widely adopted in resource-limited settings (RLS) and standards of IC vary widely. A recent survey of international research sites conducting HIV therapeutic clinical trials suggested that there were significant differences between clinical sites. Sites that did not have dedicated resources to IC organization were unlikely to have established policies and procedures for isolation, hand hygiene, respiratory hygiene, and injection safety.4 Monitoring activities, prevention of infection in health care workers (HCWs), specific policies regarding hand and respiratory hygiene, safe injection practices, and ongoing education of IC practitioners have all been shown to be important in reducing health care–associated infections.5–7 In the international RLS, well-established IC committees with regulatory oversight are uncommon and few resources are deployed in this area. Educational opportunities for IC practitioners are limited, and regulatory bodies that assess and monitor IC outcomes are uncommon.8 This article describes best practices for IC in the RLS and makes specific recommendations about selected practices in the research setting.
Arguably, the most important feature of a successful IC program is a supportive organizational structure emphasizing a commitment to a culture of safety that allows for successful monitoring of the appropriate components of IC.9–13 In the acute care setting, good evidence demonstrates that nosocomial infections are significantly reduced by IC programs that include trained personnel.14 Historically, incipient programs have focused on structure: the careful development of meaningful and effective policies, procedures, and tight administrative controls. Growing programs focus on process: the implementation and adherence to those policies, procedures, and administrative controls and advanced programs have focused directly on outcomes associated with the implementation of the policies procedures and administrative controls (ie, measurable reductions in health care–associated infections associated with the structural and process interventions). In the research setting, preemployment screening, management of workplace exposures to infectious agents, policies concerning respiratory and hand hygiene, surveillance and outbreak management, where appropriate, and the development of guidelines for best practice are appropriate tasks for an IC practitioner (Table 1). Most importantly though, implementation plans for each protocol considered for a site should explicitly consider infection risk reduction and should be fully integrated into the planning for each protocol.15–19 An identified person who has IC expertise should be tasked with the implementation of IC policies at the research site and should liaise with local IC organizations and laboratories to develop and monitor the implementation of appropriate policies and procedures and provide feedback to practitioners on a regular basis. The research community has the opportunity to model best practice, but IC practice in research cannot happen in isolation from the clinical setting. A culture of considering infection risk reduction in all aspects of protocol development and implementation embraced by staff, research participants, and the community is likely to produce meaningful results.
HCWs are at risk for acquiring infections from patients and put patients at risk if they have a transmissible infection. HCW acquisition and transmission of tuberculosis are well described in RLS. The estimated tuberculin skin test conversion rate among nursing students in Harare is triple that of students who are not training in health care.20 Newer methodologies for screening, such as interferon-γ–release assays21–23 may facilitate screening in a Bacillus Calmette–Guérin (BCG)-exposed population and may be cost effective.24 Preemployment screening followed by repeated testing at defined intervals and after exposure facilitates management of inadvertent exposures and treatment of early disease; all may reduce transmission in the research setting. Vaccine-preventable illnesses in HCW are an important focus of occupational health strategies.25 Hepatitis B virus (HBV) is a potentially fatal illness and nonimmune HCWs are at risk for acquisition. There are strong recommendations in the United States to exclude nonvaricella immune–exposed HCWs from patient care to minimize respiratory transmission to patients.26–29 Disseminated varicella infection with fulminant pneumonitis is a well-recognized and potentially lethal complication of primary varicella infection in pregnant women.30 Staff working in obstetrics and researching aspects of the prevention of maternal to child transmission of HIV might be targeted for intensive surveillance. Occupationally acquired rubella is an important consideration for female HCWs with reproductive potential and measles and mumps are important sources of morbidity.31 Strategies for preemployment screening of vaccine-preventable illnesses include a questionnaire, targeted serological testing, and either mass vaccination without testing or targeted vaccination.25,32,33 Influenza vaccination in HCWs has been shown to reduce mortality in the hospital environment and skilled nursing facilities. HIV-infected patients are at greater risk for complications of influenza,34 and vaccination of their care givers has been recommended yearly,35 a practice that could be recommended in the research setting. Automated systems for tracking the health status of employees have been developed for resource-rich settings and are easily adapted for RLS.
Attention to hand hygiene prevents many health care–associated infections. A recent review documented more than 20 studies in the acute care setting in which improved hand hygiene was associated with measurable reductions in carefully defined hospital-associated infections.36 Hand hygiene is an important component of the IC “bundles,” which have proven efficacy for the prevention of catheter-related infections, ventilator-associated pneumonias, and urinary catheter sepsis. Although the best efficacy measurements have occurred in the hospital setting where endpoints such as bacteremia are more easily detected and measured, improved hand hygiene is also associated with significant reductions in diarrheal and respiratory illnesses in the outpatient setting.37 Alcohol and chlorhexidine-based products are more effective than soap and water for removing bacteria from hands, but soap and clean water remain important interventions.38 The World Health Organization has developed an inexpensive method for local manufacture of antiseptic hand rub and has shown this to be acceptable and feasible in RLS.39,40 Despite proven efficacy, adherence to hand hygiene recommendations is generally low with rates of adherence to best practice between 40% and 60%.41,42 Removing the barriers to hand hygiene may be the single most important intervention to improve compliance with recommendations. Products should be accessible and available without cost and hand washing supplies such as soap and single-use towels should be readily available. The use of hand basins with standing water should be actively discouraged. Several tools and methodologies are available that measure hand hygiene practices and regular surveys may improve practice.43,44
Inappropriate and outdated injection practices, such as the reuse of needles and syringes, and the use of multidose vials have been implicated in the transmission of HBV, hepatitis C virus (HCV), and HIV in RLS.45 Despite the availability of needle safe systems and disposal sharp containers, needle-stick injuries are still common even in resource-rich settings.46 The global impact of outdated needle practices combined with high prevalence rates of HIV, HBV, and HCV means that the absolute risk of exposure to a blood-borne pathogen for a HCW in RLS is significant.47 A large multicenter survey of HCWs in West Africa estimated an incidence of percutaneous injuries of 0.33/HCW/yr, a value that the authors note is triple that of a prospective European study.48 Modeling data from the World Health Organization suggest that up to 5% of HIV infections and nearly half of HCV and HBV infections in HCWs in Africa may be attributable to occupational exposure.49 Recapping needles after use has been shown to be an important risk factor for occupational exposure; a strict recapping policy and easy availability of sharps containers reduce the risk of percutaneous exposures and are low-cost interventions that can be systematically adopted.50,51 Reprocessing and reuse of single-use medical devices especially injection equipment are practices to be discouraged, the use of needle safe systems may add further value.52 Unnecessary injections should be avoided and the preferential use of oral agents when appropriate may reduce needle stick injuries. Finally, preemployment vaccination for HBV and secondary prevention with postexposure prophylaxis for both HIV and HBV may also be important in preventing disease when injuries occur.53
Most IC data are generated from inpatient settings where endpoints, such as nosocomial bacteremia and ventilator-associated pneumonia, can be collected and the effect of an intervention or interventions (“multimodal” or “bundled” interventions) can be assessed using these endpoints. In the outpatient setting where most HIV clinical research is performed, assessing the impact of an IC intervention is more difficult because endpoints are rare, and when they do occur, the patient may no longer be in the health care environment. Good data on the impact of IC interventions in the outpatient setting are therefore limited. Process measures, such as opportunities for hand hygiene, have sometimes been used as surrogate markers for “hard” endpoints in IC, but these have not been rigorously validated and the approach is still in development. Finally, IC standards for outpatient care have been developed for the North American context, but these standards may not always be achievable in the international research RLS. Importantly, there are no regulatory requirements that mandate participation in these activities. The international research community has the opportunity to add to this discussion by designing trials with an infection prevention package to define the appropriate “bundle” of interventions and test their effectiveness. Such a strategy can be initiated in the context of assessing program quality and can be a powerful tool for improving patient outcomes.
The authors would like to thank D. Henderson and T. Palmore for their careful and thoughtful review.
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infection control; resource-limited setting; hand hygiene; occupational health
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