Post-exposure prophylaxis against blood-borne viral infections among health care workers: A bibliometric analysis

Abstract

BACKGROUND:

Health care workers face a wide range of chemical, physical, and biological occupational hazards in their jobs.

OBJECTIVE:

The present study aimed to investigate research trends on post-exposure prophylaxis (PEP) against blood-borne viral infections among health care workers.

METHOD:

Keywords related to health care workers, PEP, and blood-borne viruses were entered in the Scopus database for the period from 1950 to 27 January 2022.

RESULTS:

The search query returned 271 papers. The earliest publication was in 1984. The Pan African Medical Journal ranked first (n = 8, 3.0%), followed by the Infection Control and Hospital Epidemiology and Journal of Hospital Infection with 6 (2.2%) papers for each. One hundred ninety-one journals took part in publishing the retrieved papers. Authors from 63 different countries took part in publishing the retrieved papers. The United States (US) ranked first (n = 53, 19.6%) followed by India (n = 26, 9.6%). The United States Centers for Disease Control and Prevention contributed the most (n = 9, 3.3%) and ranked first in the top active institutions. The mean number of authors per paper was 4.4 and the mean number of citations per paper was 17.0. The most frequent author keywords focused on PEP, health care workers, occupational exposure, HIV, hepatitis B, anti-retroviral and needle-stick injuries. Research themes in the retrieved papers focused on knowledge/attitude/practice and management and epidemiology of occupational exposure and PEP. There was a limited number of research publications in this field.

CONCLUSION:

Research activity in this field needs to be strengthened in low- and middle-income countries through reporting and training of HCWs.

Keywords

Post-exposure prophylaxis health care workers HIV bibliometric occupational exposure

1. Background

Blood-borne pathogens such as hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) are commonly encountered in health care settings. Occupational exposure of healthcare workers (HCWs) to blood-borne pathogens occurs through percutaneous injuries such as needle stick injuries (NSIs) or contact with the mucus membranes or non-intact skin of an infected person. Over twenty pathogens have been transmitted to health care workers due to a needle stick injury, most importantly HIV, HBV, and HCV [1]. Occupational exposure to blood or other body fluids constitutes a major health risk [2]. A systematic review and meta-analysis from 21 African countries reported a high prevalence of occupational exposure to HIV from body fluids [3]. It is estimated that up to three million percutaneous exposures occur among HCWs worldwide; the vast majority occur in the least developed countries [4]. Because of these occupational exposures, up to 1000 cases of HIV infections are transmitted annually to HCWs. A World Health Organization (WHO) report estimated that 2.5% of HIV- positive and 40% of HBV- and HCV- positive cases in 2002 were due to occupational exposure among HCWs [5]. The United States Centers for Disease Control and Prevention (US CDC) estimates that approximately half of the percutaneous-related injuries among HCWs go unreported [6].

In 1984, a case of an HCW has developed HIV infection was documented after occupational exposure [7]. This incident was followed by many confirmed cases of occupationally acquired HIV infection among HCWs. Since that incident, concerns about the transmission of deadly blood-borne pathogens to HCWs became a central issue in the safety of HCWs. Occupational injury or exposure of HCWs to deadly blood-borne pathogens threatens the functionalities of health care delivery systems, especially in countries with limited medical human resources. Furthermore, occupational exposure to deadly blood-borne pathogens causes a lot of psychological stress and fear among HCWs [8]. Therefore, it is extremely important to train and educate HCWs on how to practice post-exposure prophylaxis (PEP) when accidentally exposed to blood-borne pathogens to minimize their risk of deadly infections. Primary prevention is the most effective strategy to avoid occupational infection with blood-borne pathogens. However, when exposures do occur, secondary prevention with exposure-specific PEP should be offered to HCWs based on scientific evidence. A well-known example of PEP is the use of antiretroviral therapy (ART) immediately after accidental occupational exposure to prevent HIV infection [9]. According to the US CDC, the mainstay HBV PEP is the hepatitis B vaccine [10]. No currently proven vaccine or anti-viral therapy is proven effective for HCV PEP [11].

Analysis of global research publications on PEP against blood-borne pathogens is a step in the right direction to minimize the risk of occupational exposure to deadly viruses among HCWs. Analysis of research publications and shedding light on research gaps is an important initial step for health policymakers to adopt and implement measures to protect HCWs against such deadly hazards. The results obtained from the analysis of scientific research can be used as an indicator of national commitment to enhancing the safety of HCWs and strengthening the health system. Furthermore, identifying research hotspots and research trends on PEP among HCWs is important for researchers and academics in planning future research agendas. The tool most commonly used to analyzed and assess research trends is “bibliometrics” defined as “the application of mathematical and statistical methods to books and other media of communication [12]. Bibliometric studies on various aspects of HIV and hepatitis have been published [13–15]. Similarly, bibliometric studies on the occupational health of HCWs have been carried out [16,17]. Searching Google Scholar for bibliometric studies on PEP returned one Chinese article that focused on HIV with emphasis on China [18]. The article was non-occupational PEP.

Based on the aforementioned background, the current study was undertaken to investigate and analyze research publications on PEP against blood-borne pathogens among HVWs.

2. Methods

The current study was a descriptive cross-sectional study of research publications on PEP against blood-borne pathogens among HCWs. Scopus database, owned by Elsevier, was used in the present study for the advantages it has over other databases [19].

2.1. Search query

The terms used in the current study to retrieve documents relevant to PEP were: “post-exposure prophylaxis”, “post-exposure prophylaxis”, “post-exposure prevention”, and “post-exposure management”. These terms were entered in the titles/abstract search to retrieve the maximum relevant documents. The terms used for HCWs were: physician*, nurse, “healthcare worker*”, “healthcare professional*”, “healthcare provider”, dentist, occupation*, “health worker*”, “health care worker*”, doctor, “medical service personnel”, “medical staff”, “occupational exposure”, “health care profess*”, “hospital staff”, “medical personnel”, “health care personnel”, “health-care worker*”, “health-care provider*”, “health-care profession*”, “occupation* exposure”, “health care profess*”, “hospital staff”, “medical personnel”, “health care personnel”, “health-care worker*”, “health-care provider*”, “health-care profession*”, “clinic worker*”, “nursing staff”, “hospital worker*”, “hospital employ*”, “labo* employee”, “lab* employee”, “lab* personnel”, “lab* worker”, “lab* staff”, and “clinic worker*”. These keywords were also entered in the titles/abstracts search. The keywords used to retrieve documents relevant to blood-borne viral infections included hepatitis, HIV, “AIDS”, “HBV”, “HCV”, “human immunodef*”, “blood borne”, and “antiretrovir*”. The quotation marks were used to retrieve the exact phrase, while the asterisk was used as a wild card. The search results for three terms (PEP, HCWs, and blood-borne viral infection”) were combined to return the relevant documents.

2.2. Inclusion and exclusion criteria

Since the focus of the study was on post-exposure prophylaxis, documents on needlestick injuries that did not discuss post-exposure prophylaxis/management were not included. Only journal documents were considered without any language limitation. Therefore, books and book chapters were excluded. Furthermore, research articles on PEP in non-occupational exposures or sexual assault were excluded. The time limits were from 1970 to 27 January 2022.

2.3. Validation

The retrieved documents were reviewed to confirm the absence of false-positive results. The validation process was carried out by colleagues in the medical field. The retrieved documents were sent to the colleagues as an endnote file and were asked to review the title and abstract to confirm that the retrieved papers were in the field of occupational PEP. The search query was modified based on the response of the reviewers. For example, few papers were found on non-occupational PEP and sexual assault, and the search query was modified to exclude such papers.

The validity for the absence of missing data (false-negative) was tested by using the Pan African Medical Journal as a reference test. The number of research articles in the reference journal (n = 8 papers) was compared with the number of papers retrieved through the search query (n = 8 papers). The result was identical, suggesting that the search query was capable of retrieving all relevant research articles.

2.4. Data export

The retrieved data was exported as a .csv file to the Microsoft Excel program for further analysis. The exported data included the annual number of publications, publishing journals, countries contributing to the retrieved documents, citations, authors, institutions, and titles/abstracts of the papers.

2.5. Bibliometric indicators

The annual growth of publications was presented as a linear graph. Most frequent author keywords and terms were presented using the VOSviewer program [20]. In VOSviewer maps, the circle’s size is proportional to the word’s frequency of occurrence representing the circle. The VOSviewer maps can assess research collaboration among authors. The thickness of connecting lines and distance between authors are indicators of the extent of research collaboration between any two authors. Finally, the Hirsch index (h-index) was used to assess the quality of retrieved papers.

Fig. 1.

Annual growth of publications on post-exposure prophylaxis against blood-borne pathogens among health care workers.

3. Results

The search query returned 271 papers. One hundred ninety-eight (73.1%) papers were research articles and forty-six (17.0%) were review articles. The remaining (n = 27, 9.9%) were editorials, letters, and notes. The majority (n = 237, 87.5%) of the retrieved papers were published in English. The earliest publication appeared in 1984 and was about the cost of post-exposure prevention of hepatitis B among hospital employees [21]. The annual number of publications showed a lot of fluctuations after the mid-1990s. The number of publications showed the highest peak in 2004 (n = 17) (Fig. 1).

The retrieved research articles were published in 191 different journals. The Pan African Medical Journal ranked first (n = 8, 3.0%), followed by the Infection Control And Hospital Epidemiology and Journal Of Hospital Infection (n = 6, 2.2%). Table 1 shows the names of journals with a minimum publication of three papers. Two journals in the list are published from the African region and two journals are specialized in HIV/AIDS. Of the 191 journals, eight (4.2%) journals were in the field of occupational medicine and published 14 (5.2%) papers.

Table 1
List of journals with a minimum contribution of three papers on post-exposure prophylaxis against blood-borne pathogens among health care workers

Journal Number of publications % (N = 271)

Pan African Medical Journal 8 3.0

Infection Control and Hospital Epidemiology 6 2.2

Journal of Hospital Infection 6 2.2

Medycyna Pracy 5 1.8

PLoS One 5 1.8

BMC Research Notes 4 1.5

Clinical Infectious Diseases 4 1.5

International Journal of STD and AIDS 4 1.5

Occupational Medicine 4 1.5

AIDS Care Psychological and Socio Medical Aspects of AIDS HIV 3 1.1

Current Opinion in Infectious Diseases 3 1.1

Journal of Clinical and Diagnostic Research 3 1.1

MMWR Recommendations and Reports Morbidity and Mortality Weekly Report Recommendations and Reports Centers for Disease Control 3 1.1

Nigerian Journal of Clinical Practice 3 1.1

Journal	Number of publications	% (N = 271)
Pan African Medical Journal	8	3.0
Infection Control and Hospital Epidemiology	6	2.2
Journal of Hospital Infection	6	2.2
Medycyna Pracy	5	1.8
PLoS One	5	1.8
BMC Research Notes	4	1.5
Clinical Infectious Diseases	4	1.5
International Journal of STD and AIDS	4	1.5
Occupational Medicine	4	1.5
AIDS Care Psychological and Socio Medical Aspects of AIDS HIV	3	1.1
Current Opinion in Infectious Diseases	3	1.1
Journal of Clinical and Diagnostic Research	3	1.1
MMWR Recommendations and Reports Morbidity and Mortality Weekly Report Recommendations and Reports Centers for Disease Control	3	1.1
Nigerian Journal of Clinical Practice	3	1.1

Authors from 63 different countries participated in publishing the retrieved papers. The United States (US) ranked first (n = 53, 19.6%) followed by India (n = 26, 9.6%). Table 2 shows 29 countries with a minimum contribution of three papers. Six countries in the list are in the African region and two are in the Eastern Mediterranean region.

Table 2

List of countries with a minimum contribution of three papers on post-exposure prophylaxis against blood-borne pathogens among health care workers

Country	Number of publications	% (N = 271)
United States	53	19.6
India	26	9.6
United Kingdom	22	8.1
Germany	14	5.2
Italy	13	4.8
South Africa	12	4.4
Poland	10	3.7
France	9	3.3
Nigeria	9	3.3
Brazil	8	3.0
Switzerland	8	3.0
Cameroon	6	2.2
Ethiopia	6	2.2
Tanzania	6	2.2
Canada	5	1.8
Spain	5	1.8
Thailand	5	1.8
Australia	4	1.5
Croatia	4	1.5
Iran	4	1.5
The Netherlands	4	1.5
Turkey	4	1.5
Denmark	3	1.1
Japan	3	1.1
Kenya	3	1.1
Nepal	3	1.1
Saudi Arabia	3	1.1
South Korea	3	1.1
Sweden	3	1.1

A total of 1201 authors participated in publishing the retrieved articles, an average of 4.4 authors per article. Forty papers (14.8%) were single-authored, 44 (16.2%) two-authored, 50 (18.5%) three-authored, 44 (16.2%) four-authored, and the remaining (n = 93, 34.3%) had ≥5 authors. Henderson, D.K. at National Institutes of Health (NIH/USA) and Ippolito, G. at IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani (Rome, Italy) appeared to be the most active authors in this field. Figure 2 shows the top 15 active authors. The map shows three separate research clusters, the largest cluster included eight researchers. The remaining seven authors were split into two small research clusters.

Fig. 2.

Mapping author research collaboration for top 15 active authors. The thickness of the connecting lines between authors is a measure of the strength of collaboration. Authors with the same color share similar research interests.

At the institutional level, The US CDC was the most active (n = 9, 3.3%), followed by University Hospital Frankfurt (n = 6, 2.2%), University Of Saarland (n = 5, 1.8%), and the University of California, San Francisco (n = 5, 1.8).

The retrieved research articles received 4620 citations, an average of 17.0 citations per paper, and an h-index of 26. The top-cited articles focused on the US guidelines for PEP due to occupational exposure (Table 3).

Table 3

Top ten cited papers on post-exposure prophylaxis against blood-borne pathogens among health care workers [24–27,45–50]

Title	Year	Source title	Number of citations
Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.	2001	MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports/Centers for Disease Control	900
Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis.	2005	MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports/Centers for Disease Control	314
Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. Centers for Disease Control and Prevention.	1998	MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports/Centers for Disease Control	283
Updated US Public Health service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis	2013	Infection Control and Hospital Epidemiology	218
Preventing needlestick injuries among healthcare workers: A WHO-ICN collaboration	2004	International Journal of Occupational and Environmental Health	160
CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management	2013	MMWR Recommendations and Reports	155
Prophylaxis for occupational exposure to HIV	1996	Annals of Internal Medicine	108
Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: Findings of the HIV postexposure prophylaxis registry	2000	Infection Control and Hospital Epidemiology	89
European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus.	2005	Euro surveillance: bulletin européen sur les maladies transmissibles = European communicable disease bulletin	86
Study of prevalence and response to needle stick injuries among health care workers in a tertiary care hospital in Delhi, India	2010	Indian Journal of Community Medicine	73

Mapping the top 40 author keywords showed that keywords related to PEP, occupational exposure, health care workers, NSIs, had the largest circle size indicating the highest occurrences in the retrieved papers (Fig. 3). Mapping the 100 most frequent terms in the titles and abstracts of the retrieved papers showed two clusters of terms representing two major research themes in the retrieved papers (Fig. 4). The research themes included one focusing on knowledge/practice/awareness (KAP) studies using a questionnaire. The second cluster focused on management and treatment used in PEP against blood-borne pathogens among health care providers.

Fig. 3.

The most frequent author keywords mapped using co-occurrence analysis. Of the 321 author keywords present in the retrieved papers, the most frequent 40 keywords were mapped. The circle size in the map is proportional to the number of occurrences in the retrieved articles.

Fig. 4.

Research themes were obtained by mapping the most frequent terms in the titles/abstracts of the retrieved papers. Of the 4578 terms, the most frequent 100 terms were mapped. The circles in the map represent the number of occurrences of each term in the titles/abstracts. The most frequent terms existed in two clusters.

4. Discussion

The present study aimed to investigate and assess worldwide research publications on PEP against blood-borne pathogens among HCWs. The study showed that the research volume on this topic was relatively limited and the pattern of growth was unpredictable.

The limited volume of publications could be attributed to several reasons. The poor reporting of incidents that require PEP especially in low- and middle-income countries. The poor research capabilities of several low- and middle-income countries where NSIs took place. A third potential reason is the lack of major success in the field of PEP against HCV and limited advancement in PEP against HIV since its introduction more than two decades ago. The limited research publications in this field mean limited information about the epidemiology of accidents requiring PEP, the guidelines and treatment protocols implemented in such accidents, and the degree of knowledge and awareness of HCWs about this topic.

The current study showed that the earliest publications on PEP appeared in the early 1980s. The early publications were about the potential role of the HBV vaccine in PEP. For HIV, the Ziduvodine (AZT or ZDV) was approved in 1987 and showed efficacy in PEP and in preventing the vertical transmission of the virus. Currently, combination anti-retroviral agents are used for prophylactic purposes. In 2005, the US Department of Health and Human Services (DHHS) released the first recommendations for non-occupational PEP followed by updated guidelines in 2016 [22,23]. Guidelines for occupational PEP were also published and received the highest citations [24–26]. According to updated guidelines, PEP should be initiated immediately (within 2–72 hrs) after potential HIV exposure with a basic 4-week regimen of two anti-retroviral drugs. If properly used, PEP can reduce the risk of occupational risk of HIV by 81% [27]. Reviewing the annual growth of publications showed that numerous peaks were present that could be due to the release of guidelines for occupational and non-occupational PEP.

The current study showed that a large number of journals participated in publishing the retrieved papers. No specific journal(s) showed dominance in this topic. Furthermore, most journals publishing papers on this topic were in general medicine, infection control/prevention, and public health. Specialized journals in the field of occupational medicine contributed to 14 papers, approximately 5% of the retrieved papers. The finding that two journals of the active ones were issued from the African region was not surprising given the large burden of HIV and other blood-borne viral infections in Africa [28,29]. The higher the prevalence of blood-borne pathogens in the population, the higher risk of occupational HIV transmission [30]. It should be emphasized that in developing countries, handling and management of needles and contaminated specimens might be less than optimum which increases the risk of occupation transmission of blood-borne pathogens [31]. One of the active journals was the Nigerian Journal of Clinical Practice . Nigeria ranked one of the top 10 countries in the number of people living with HIV[32]. The large number of HIV people living in Africa, unsafe needle handling in developing countries in general, and the presence of several specialized medical journals issued from countries in the region of Africa explain, in part, the presence of South Africa and Nigeria among the top active journals. The presence of specialized journals in the active list was justifiable given that HIV is one of the deadly blood-borne pathogens and HCWs have the potential to be exposed to this virus mainly through needle stick injuries. Furthermore, evidence for effective management of occupational exposure to HIV started three decades ago and has proven to be effective.

The current study showed that the US ranked first followed by India. The leading role of the US is attributed to the presence of many academic and research institutions including the US CDC. The health system in the US is well-developed and reporting occupational exposure and incidents allows for better documentation and subsequent follow-up and research. India has the third-largest HIV epidemic in the world with more than 2.1 million people living with HIV[33].

Mapping the most frequent author keywords returned keywords related to PEP, occupational exposure, nurses, HCWs, HIV, HBC, antiretroviral, Zidovudine, and others. The keyword needle stick injury/injuries were prominent. The Incidence of NSIs has fallen gradually due to safety guidelines and precautions. Nevertheless, NSIs still occur frequently among HCWs [34]. Needle-stick injuries are encountered most commonly by nurses, lab workers, and cleaners [35]. According to the US CDC, the annual number of sharp injuries in the US among the HCWs is 385,000 [36]. In Europe, there is an average of 0.64 NSIs for every health worker per year, as estimated on injuries that occurred in 2000 [4]. A recently published review study estimated the rates of NSIs vary between 14.9 and 69.4% in HCWs, depending on settings, countries, and methodologies [37]. Most needle-stick injuries occur due to needle recapping [38], and most go unreported [39]. A global research analysis of needle-stick injuries concluded that research on NSIs is generally increasing but the growth is asymmetrical [34]. Future research in this field should focus on non-industrialized areas.

Mapping the most frequent terms in titles and abstracts of the retrieved papers returned two clusters suggesting that research in this field is limited to two major themes. The first theme is knowledge/attitude/practice (KAP) about PEP while the second theme is management approaches as well as incidence and prevalence of PEP. There were a lot of variations in the results of KAP studies based on the group of targeted HCWs as well as the country of the study. A recent study in Bhutan found a positive attitude of nurses toward PEP but their knowledge about PEP was very low demanding formal training and education about PEP [40]. A recently published review paper on PEP in the African context found a strong need to increase awareness and implement training for HCWs [41]. Similar conclusions were found in Nepal and other countries [42]. Most KAP studies were carried out in developing countries and most recommended training and introducing the PEP concept in medical curricula [43].

The current study gave a snapshot analysis of research publications on PEP against deadly blood-borne viruses among HCWs. The WHO recommended investing in HCWs from aspects of manpower and safety [44]. Therefore, this study will shed light on the biological occupational hazards facing HCWs to attract the attention of academics, policymakers, and funders to this issue especially in low- and middle-income countries. The current study has a few technical limitations that are inherent to the nature of bibliometric studies. The use of Scopus means that publications in un-indexed journals were not retrieved and not analyzed. Most un-indexed journals are those in Africa, the Middle East, and Asia. Therefore, countries in these areas were under-represented. The second limitation is the search query which was built to retrieve the maximum results. However, the presence of false-positive or negative results remains a slight possibility.

5. Conclusion

The PEP against deadly blood-borne viruses is an old topic but has not received a large volume of research publications. The growth of research on PEP showed a lot of fluctuations since the mid-1990s. The overall growth of research publications from the mid-1990s to 2000 was generally constant. Research activity on PEP was skewed toward the US with slight contribution from other European countries, India, and South Africa. Training on PEP against blood-borne pathogens is needed especially in low- and middle-income countries where knowledge/awareness among certain HCWs is limited. Health policies about reporting occupational exposure to NSIs and other sources of infections should be strengthened. Introducing the concept of PEP into medical curricula and training is also encouraged. Finally, research in the field of occupational exposure of HCWs should be supported to build policies and guidelines that ultimately protect HCWs.

Footnotes

Availability of data and materials

All data present in this article can be retrieved from Scopus using the keywords listed in the methodology.

Conflict of interest

The author declares that there are no financial or non-financial competing interests.

Ethical approval and consent to participate

Not applicable.

Funding

None to report.

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