Bibliometric analysis of pathogenic organisms

Abstract

Infectious diseases remain as an important public health threat to humans. Research into pathogens can be useful for planning an organized response to infectious diseases. Bibliometric analysis is an important method for scientific research and assessing capability. In this study, 100 pathogens of public health importance were selected, and the distributions of annual, national, institutional, and journal publications on Science Citation Index (SCI) journals were statistically analyzed. The United States of America ranked the first in terms of the number of relevant studies published. China attaches great importance to the prevention and control of infectious diseases, but still needs to improve in the following areas: for example, insufficient SCI reports on particular pathogens, institutions SCI reports on pathogens lower than world top pathogen research institutions, and lack of influential international pathogen-related journals. Scientific literature databases are important tools for science-of-science analysis. The findings of this study shed light on the hot spots and the ignored spots in pathogen researches, and thus would be useful for drawing a national and institutional research plan.

Highlights

• •Scientific question
• •Scientific literature databases are important tools for science-of-science analysis, which can be referred as Science of the Science of biosafety/biosecurity (SSBS) in the field of biosafety and biosecurity.
• •Evidence before this study
• •In this study, we conducted a comprehensive literature analysis of pathogens, including health-threatening pathogens (HTPs) and biodefense-associated pathogens (BDAPs).
• •New findings
• •Our new findings indicated that some literature on pathogens, particularly BDAPs, showed a decrease followed by an increase. The total number of Science Citation Index reports on pathogens in China is the second highest in the world, but it is significantly behind the number of published studies in the United States. Particularly, SCI reports on BDAPs in China is insufficient, specifically at the university level.
• •Significance of this study
• •The findings of this study highlight the hot spots and ignored spots in pathogen research; therefore, can be helpful on drawing a national and institutional research plan.

1. Introduction

Living standards have continuously been improving on account of the rapid developments in science and technology. Although infectious diseases, in general, have become less common than other diseases such as cancer, cardiovascular disease, metabolic diseases, etc., the frequent genetic transformation of pathogens and the existence of antimicrobial-resistant pathogens are still issues that we have to face today.

During the last few decades, there have been significant advances in the treatment and prevention of infectious diseases, such as HIV, viral hepatitis, and tuberculosis. However, many new infectious diseases have emerged since the SARS epidemic in 2003, such as H5N1 and H7N9 avian influenza, Middle East Respiratory Syndrome, Ebola virus disease, Zika virus disease, Chikungunya virus disease, and the current Coronavirus Disease 2019 (COVID-19). Consequently, human beings are constantly facing the threat of new and re-emerging infectious diseases [1]. In addition to naturally occurring infectious diseases, another danger posed by pathogens is their potential use as biological weapons or in bioterrorism. Large-scale research and development of biological weapons were once carried out in some countries [2]. In 2001, the anthrax mail attack in the United States resulted in significant public panic. Therefore, in recent years, both the United States and United Kingdom have released biosecurity or biodefense national strategies for responding to such threats [3].

Pathogens are defined as microorganisms and parasites that cause infectious and parasitic diseases. At present, there are still many infectious diseases that do not have effective treatments. The development of diagnostic test kits, drugs, vaccines and other countermeasures needs to be based on the full understanding of the biological characteristics and pathogenic mechanisms of these infectious diseases.

Bibliometric analysis is an important method of scientific research assessment. Science-of-science analysis in the field of biosafety and biosecurity can be called Science of Science of biosafety/biosecurity (SSBS). Based on the statistical data of published studies on pathogens, it is possible to gain overall understanding of the worldwide pictures, such as the number of studies on pathogens, the research capability of different countries, the key research institutions, the major journals reporting studies on pathogens, and other parameters of research capability. It is then possible to know the research status, dominant areas, and major gaps, which are important for making strategic plans for scientific research. In the present bibliometric analysis, 100 species of pathogens of public health importance were selected, and the related published literatures were retrieved and statistically analyzed. The findings shed light on the hot spots and ignored spots in pathogen research and can be useful for drawing a national and institutional research plan.

2. Methods

An SCI literature search was performed in November 2018 by using Web of Science and the search scope of SCI-EXPANDED. We examined the titles and screened for article types. The names of pathogens, but not the names of the corresponding disease, were used for the search (Tables 1 –3). Use of the title as the search target can avoid those non-essential studies, but in the same time some studies may have been missed, when compared with the search results using abstracts as the search target. The main purpose of the study is to compare the studies from different years, countries, institutions, and journals, under the same search conditions.

Table 1.

Query key words and comparison by the number of published pathogen studies between China and the United States (bacterial pathogens only).

Order	Pathogens	Abbreviation	Group*	Disease	Query	Article	Country-wise distribution	United States		China
								Sort	Quantity	Sort	Quantity
1	Bacillus anthracis	B. anthracis	A	Anthrax	TI = “Bacillus anthracis”	1,722	68	1	1,104	6	59
2	Yersinia pestis	Y. pestis	A	Plague	TI = “Yersinia pestis”	1,216	59	1	715	2	137
3	Clostridium botulinum	C. botulinum	A	Botulinum	TI = “Clostridium botulinum”	794	56	1	238	12	13
4	Francisella tularensis	F. tularensis	A	Tularemia	TI = “Francisellatularensis”	1,039	42	1	634	11	17
5	Brucella spp.	Brucella	A	Brucellosis	TI=Brucella	3,132	106	1	713	5	234
6	Burkholderia mallei	B.mallei	A	Glanders	TI = “Burkholderia mallei”	141	29	1	97	27	1
7	Burkholderia pseudomallei	B. pseudomallei	A	Melioidosis	TI = “Burkholderiapseudomallei”	1,041	54	2	285	11	31
8	Clostridium perfringens	C.perfringens	A	Gas gangrene	TI = “Clostridium perfringens”	1,952	69	1	635	8	90
9	Salmonella spp.	Salmonella	A	Food poisoning	TI=Salmonella	21,476	160	1	7,306	4	1,282
10	Escherichia coli O157:H7	O157:H7	A	Enteric disease	TI=O157 AND TI=H7	4,261	93	1	2,226	3	329
11	Shigella	Shigella	A	Enteric disease	TI=Shigella	2,283	115	1	692	3	253
12	Staphylococcus	Staphylococcus	A	Skin infections	TI=Staphylococcus	27,944	157	1	8,383	3	1,847
13	Vibrio cholerae	V. cholerae	A	Cholera	TI = “Vibrio cholerae”	3,151	102	1	1,361	5	156
14	Helicobacter pylori	H. pylori	B	peptic ulcers	TI = “Helicobacter pylori”	17,677	153	1	3,386	4	1,433
15	Mycobacterium tuberculosis	M. tuberculosis	B	Tuberculosis	TI = “Mycobacterium tuberculosis”	13,511	155	1	4,634	4	1,220
16	Mycobacterium leprae	M. leprae	B	Human leprosy	TI = “Mycobacterium leprae”	632	66	1	212	13	14
17	Haemophilus influenzae	H. influenzae	B	Respiratory tract infections	TI = “Haemophilus influenzae”	3,116	115	1	1,261	17	54
18	Corynebacterium diphtheriae	C. diphtheriae	A	Diphtheria	TI = “Corynebacterium diphtheriae”	230	45	1	79
19	Clostridium tetani	C. tetani	B	Tetanus	TI = “Clostridium tetani”	51	27	2	8	9	3
20	Streptococcus pyogenes	S. pyogenes	B	Tonsilitis	TI = “Streptococcus pyogenes”	1,597	72	1	490	14	34
21	Streptococcus pneumoniae	S. pneumoniae	B	Respiratory disease	TI = “Streptococcus pneumoniae” OR TI = pneumococcus	6,439	127	1	2,350	8	284
22	Streptococcus suis	S. suis	B	meningitis, endocarditis, and arthritis in swine	TI = “Streptococcus suis”	920	42	6	67	1	348
23	Neisseria meningitidis	N. meningitidis	B	Septicemia and meningitis	TI = “Neisseria meningitidis” OR TI = Meningococcus OR TI = Meningococci	2,206	97	1	562	14	48
24	Neisseria gonorrhoeae	N.gonorrhoeae	B	Gonorrhea	TI = “Neisseria gonorrhoeae” OR TI = Gonococcus OR TI = Gonococci	2,029	109	1	887	8	88
25	Bordetella pertussis	B. pertussis	B	Whooping cough	TI = “Bordetella pertussis”	1,205	63	1	345	16	29
26	Legionella pneumophila	L.pneumophila	A	Legionnaire's disease	TI = “Legionella pneumophila”	1,604	63	1	554	9	61
27	Campylobacter jejuni	C. jejuni	B	Food poisoning	TI = “Campylobacter jejuni”	2,958	92	1	850	9	113
28	Borreliella burgdorferi	B. burgdorferi	B	Lyme disease	TI = “Borrelia burgdorferi” OR TI = “Lyme disease spirochete”	2,731	72	1	1,640	12	57
29	Treponema pallidum	T. pallidum	B	Pathogenic spirochete	TI = “Treponema pallidum”	494	59	1	232	2	78
30	Leptospira	Leptospira	B	Leptospirosis	TI = Leptospira	1,555	97	1	392	6	101
31	Listeria monocytogenes	L.monocytogenes	B	Meningitis and sepsis	TI = “Listeria monocytogenes”	7,493	95	1	2,525	5	354

* A = Biodefense-associated pathogens (BDAPs), B = Health-threatening pathogens (HTPs).

The selection of the 100 pathogens was based on their historical importance in infectious diseases or their potential impact on humans, in the case of newer pathogens. Several parasitic pathogens, such as those caused malaria and schistosomiasis, were also included. The pathogens were selected from the laboratory biosafety pathogen lists of the National Institutes of Health of the United States, the European Union, and China; the bioterrorism response pathogen lists of the Centers for Disease Control and Prevention of the United States, the European Union, and Russia; and select agent program pathogens listed by the United States [4]. Additionally, the World Health Organization's list of key emerging pathogens for preparedness and response [5], the list of pathogens released by Law of the PRC on the Prevention and Treatment of Infectious Diseases [6], and the pathogens listed in some Chinese textbooks were also referred to [[7], [8], [9], [10]]. The pathogenicity and epidemiologic potential of the pathogens were considered in the selection process.

The selected 100 pathogens were divided into two categories (50 each): biodefense-associated pathogens (BDAPs) and health-threatening pathogens (HTPs)(Table 1, Table 2, Table 3 ). HTPs mainly affect people's health, while BDAPs, which are characterized by rapid and widespread infection, have a serious impact on social stability. We retrieved the relevant literature on the pathogens published from 1995 to retrieval time in 2018. For the annual analysis, we retrieved the literatures published from 1995 to 2017, and used all the literatures for the country-, institution-, and journal-wise analysis based on Web of Science online statistics. The Web of Science literature statistics does not distinguish the first author from the other authors for country-wise and institution-wise analysis, so the cumulative number of studies for each country or institution may higher than the total number of studies.

Table 2.

Query key words and comparison by the number of published pathogen studies between China and the United States (viral pathogens only).

Order	Pathogens	Abbreviation	Group*	Disease	Query	Article	Country-wise distribution	United States		China
								Sort	Quantity	Sort	Quantity
1	Variola virus	Variola	A	Smallpox	TI = “Smallpox virus” OR TI = “Variola virus”	72	16	1	35
2	Ebola virus	Ebola	A	Ebola virus disease	TI = “Ebola virus” OR TI = ebolavirus	1,641	97	1	996	6	123
3	Marburg virus	Marburg	A	Marburg virus disease	TI = “Marburg virus” OR TI = marburgvirus	211	30	1	129	6	12
4	Lassa virus	Lassa	A	Lassa fever	TI = “Lassa virus”	156	26	1	82	16	3
5	Venezuelan equine encephalitis virus	VEE	A	Venezuelan equine encephalitis	TI = “Venezuelan equine encephalitis virus”	237	25	1	191	23	1
6	Eastern equine encephalitis virus	EEE	A	Eastern equine encephalitis	TI = “Eastern Equine Encephalitis virus”	85	10	1	77	2	5
7	Western equine encephalitis virus	WEE	A	Western equine encephalitis	TI = “Western equine encephalitis virus”	41	9	1	25	9	1
8	Nipah virus	Nipah	A	Nipah virus infection	TI = “Nipah virus”	307	27	1	170	13	6
9	Hendra virus	Hendra	A	Hendra virus disease	TI = “Hendra virus”	141	15	2	70	9	4
10	Hantavirus	Hantavirus	A	Hemorrhagic feverpulmonary syndrome	TI = “Hantavirus”	1,181	82	1	426	8	64
11	Hantaan virus	Hantaan	A	Hantavirus hemorrhagic fever with renal syndrome (HFRS)	TI = “Hantaan virus”	168	19	2	44	1	77
12	Sin Nombre virus	SNV	A	Hantavirus pulmonary syndrome (HPS)	TI = “Sin nombre virus”	84	7	1	82
13	Crimean-Congo hemorrhagic fever virus	CCHFV	A	Crimean-Congo hemorrhagic fever	TI = “Crimean Congo hemorrhagic fever virus”	245	56	1	66	6	22
14	Rift Valley fever virus	RVFV	A	Rift Valley fever	TI = “Rift Valley fever virus”	390	58	1	198	15	8
15	Junin virus	Junin	A	Argentine hemorrhagic fever	TI = “Junin virus”	102	14	2	38	6	2
16	Yellow fever virus	YFV	A	Yellow fever	TI = “Yellow fever virus”	259	43	1	130	10	8
17	Dengue virus	Dengue	B	Dengue fever	TI = “Dengue virus”	3,131	111	1	1,045	6	236
18	Japanese encephalitis virus	JEV	A	Japanese encephalitis	TI = “Japanese encephalitis virus”	932	44	5	132	1	202
19	Tick-borne encephalitis virus	TBEV	A	Tick-borne encephalitis	TI = “Tick-borne encephalitis virus” OR TI = TBEV	459	49	8	31	20	6
20	West Nile virus	WNV	A	West Nile fever	TI = “West Nile virus”	2,802	104	1	1,778	8	70
21	Zika virus	Zika	B	Zika fever	TI = “Zika Virus”	1,486	102	1	788	3	144
22	Chikungunya virus	Chikungunya	B	Chikungunya fever	TI = “Chikungunya virus” OR TI=CHIKV	849	90	1	260	17	16
23	Severe fever with thrombocytopenia syndrome virus	SFTSV	B	Severe fever with thrombocytopenia syndrome	TI = “Severe fever with thrombocytopenia syndrome virus” OR TI = “SFTS virus”	113	14	4	19	1	67
24	Influenza virus	Influenza	A	Influenza	TI = “Influenza virus”	6,869	116	1	2,642	2	1,199
25	H5N1 influenza virus	H5N1	A	Influenza	TI=H5N1 AND TI = “Influenza virus”	742	69	1	241	2	223
26	H1N1 influenza virus	H1N1	A	Influenza	TI=H1N1 AND TI = “Influenza virus”	635	60	1	198	2	138
27	H7N9 influenza virus	H7N9	A	Influenza	TI=H7N9 AND TI = “Influenza virus”	89	16	2	29	1	57
28	Measles virus	Measles	B	Measles	TI = “Measles virus”	1,317	84	1	480	6	61
29	Rubella virus	Rubella	B	Rubella	TI = “Rubella virus”	317	51	1	107	5	25
30	Mumps virus	Mumps	B	Mumps	TI = “Mumps virus”	259	37	1	63	5	17
31	Adenovirus	Adenovirus	B	upper respiratory tract infection	TI = Adenovirus	9,706	104	1	4,390	2	1,416
32	Respiratory syncytial virus	RSV	B	Upper respiratory tract infection	TI = “Human respiratory syncytial virus” OR TI=HRSV	428	63	1	131	4	35
33	Severe acute respiratory syndrome coronavirus	SARS	A	Severe acute respiratory syndrome	TI = “SARS Coronavirus” OR TI = “Severe acute respiratory syndrome Coronavirus” OR TI=SARS-CoV	1,394	50	2	481	1	551
34	Middle East respiratory syndrome coronavirus	MERS	A	Middle-East respiratory syndrome	TI = “Middle East Respiratory Syndrome Coronavirus” OR TI = “MERS coronavirus” OR TI = MERS-CoV	610	51	1	251	3	138
35	Human immunodeficiency virus	HIV	B	Acquired immunodeficiency syndrome (AIDS)	TI = “Human immunodeficiency virus”	17,846	147	1	10,019	11	450
36	Human T-lymphotropic virus	HTLV	B	T-cell leukemia	TI = “Human T-lymphotropic virus” OR TI=HTLV	2,680	99	2	814	11	52
37	Hepatitis A virus	HAV	B	Hepatitis A	TI = “Hepatitis A virus”	1,088	81	1	221	2	94
38	Hepatitis B virus	HBV	B	Hepatitis B	TI = “Hepatitis B virus”	10,712	147	2	2,017	1	3,099
39	Hepatitis C virus	HCV	B	Hepatitis C	TI = “Hepatitis C virus”	16,791	151	1	5,335	6	1,077
40	Coxsackievirus	Coxsackievirus	B	Viral myocarditis	TI=Coxsackievirus OR TI = “Coxsackie virus”	1,489	61	1	409	2	376
41	Rotavirus	Rotavirus	B	Severe diarrhea	TI = Rotavirus	4,723	149	1	1,677	6	257
42	Enterovirus 71	EV71	B	Hand-foot-and-mouth disease	TI = “Enterovirus 71” OR TI = EV71	1,111	43	3	115	1	569
43	Norwalk virus	Norwalk	B	Gastroenteritis	TI=Norovirus OR TI = “Norwalk virus”	2,444	95	1	892	3	201
44	Poliovirus	Poliovirus	B	Polio	TI=Poliovirus	1,577	114	1	843	7	62
45	Herpes simplex virus	HSV	B	Gingival stomatitis and neonatal infection, etc.	TI = “Herpes simplex virus”	7,544	114	1	3,959	6	336
46	Varicella-zoster virus	VZV	B	Varicella and herpes zoster	TI = “Varicella zoster virus”	1,611	78	1	667	14	36
47	Human cytomegalovirus	HCMV	B	Congenital malformation	TI=Cytomegalovirus	10,832	113	1	4,170	7	492
48	Epstein-Barr virus	EBV	B	Infectious mononucleosis	TI = “Epstein barr virus”	7,497	107	1	2,295	3	746
49	Monkeypox virus	Monkeypox	A	Monkey pox	TI = “Monkeypox virus”	82	16	1	70	14	1
50	Rabies virus	Rabies	B	Rabies	TI = “Rabies virus”	1,129	92	1	321	2	179
51	Human papillomavirus	HPV	B	Squamous epithelial proliferation of human skin and mucosa	TI = “Human papillomavirus”	10,975	147	1	4,383	2	899
52	Human parvovirus B19	B19	B	Fetal severe anemia, abortion or death	TI = “Human Parvovirus B19” OR TI = “Erythrovirus B19”	423	64	2	73	5	23
53	Foot-and-mouth disease virus	FMDV	A	Foot-and-mouth disease	TI = “Foot-and-mouth disease virus”	1,487	86	3	273	2	290
54	African swine fever virus	ASFV	A	African swine fever	TI = “African swine fever virus”	416	53	3	73	13	9
55	Newcastle disease virus	NDV	A	Newcastle disease	TI = “Newcastle disease virus”	1,317	96	1	371	2	324
56	Vesicular stomatitis virus	VSV	B	Bubbles and erosion of the epithelium of the tongue, lip, oral mucosa	TI = “Vesicular Stomatitis” AND TI = Virus	932	46	1	640	3	58

* A = BDAPs; B = HTPs.

Table 3.

Query key words and comparison by the number of published pathogen studies between China and the United States (Rickettsia, Mycoplasma, Chlamydia, fungi, and protozoa).

Order	Pathogens	Abbreviation	Group*	Disease	Query	Article	Country-wise distribution	United States		China
								Sort	Quantity	Sort	Quantity
1	Coxiella burnetii	C. burnetii	A	Q-fever	TI = “Coxiella burnetii”	1,055	87	1	292	16	18
2	Rickettsia prowazekii	R. prowazekii	A	Typhus	TI = “Rickettsia prowazekii”	95	15	1	69	11	1
3	Rickettsia rickettsii	R. rickettsii	A	Rocky Mountain Spotted Fever	TI = “Rickettsia rickettsii”	132	15	1	78	3	6
4	Orientia tsutsugamushi	O.tsutsugamushi	B	Scrub typhus	TI = “Rickettsia tsutsugamushi” OR TI = “Orientia tsutsugamushi”	294	28	3	69	6	19
5	Bartonella	Bartonella	B	Trench fever	TI=Bartonella	1,504	94	1	706	12	35
6	Mycoplasma pneumoniae	M. pneumoniae	B	Respiratory tract infections	TI = “Mycoplasma pneumoniae”	1,289	63	1	287	2	188
7	Chlamydia psittaci	C. psittaci	A	Psittacosis in birds	TI = “Chlamydophila psittaci” OR TI = “Chlamydia psittaci”	436	49	1	83	5	35
8	Chlamydia pneumoniae	C. pneumoniae	B	Respiratory infections in people	TI = “Chlamydophila pneumoniae” OR TI = “Chlamydia pneumoniae”	1,891	71	1	476	10	66
9	Chlamydia trachomatis	C. trachomatis	B	Disease in either the eye or the urogenital tract	TI = “Chlamydia trachomatis”	3,366	119	1	1,316	8	143
10	Coccidioides immitis	C. immitis	A	Coccidioidomycosis	TI = “Coccidioides immitis”	134	15	1	124
11	Plasmodium spp.	Plasmodium	B	Human malaria	TI=Plasmodium OR TI = “malaria parasite”	16,098	162	1	5,451	15	482
12	Cryptosporidium	Cryptosporidium	A	Diarrhea	TI=Cryptosporidium	3,862	114	1	1,602	3	259
13	Schistosome	Schistosome	B	Schistosomiasis	TI=Schistosome OR TI = “Blood flukes”	704	78	1	292	3	58

* A = BDAPs; B = HTPs.

3. Results

3.1. Annual number of publications

In this study, a total of 309,624 articles were retrieved. Of these, 295,866 were published in the period 1995–2017, and the highest number of articles (n = 16,658) was published in the year 2006. Based on the trends in the published literatures, three stages were identified: from 1995 to 2002, the increase in the number of published articles was not very remarkable; during 2002 to 2011, the increase was rapid; and during 2011–2017, the increase tended to slow down (Fig. 1 ).

Fig. 1.

Annual number of published studies on all the pathogens.

We noted that the number of studies for some pathogens showed (1) continuous growth, such as Mycobacterium tuberculosis, Dengue virus, Hepatitis B virus, Norwalk virus, and Plasmodium spp.; (2) a rapid increase followed by a gradual decrease, such as Bacillus anthracis, Yersinia pestis, Ebola virus, H5N1 Influenza virus, H1N1 Influenza virus, H7N9 Influenza virus, SARS coronavirus, and Chlamydia pneumoniae (Fig. 2 ); and (3) a generally decreasing trend. For example, there were 1109 reports on human immunodeficiency virus in 1995, but the number decreased to 471 in 2017.

Fig. 2.

Annual number of published studies on different pathogens (increase followed by a decrease).

In addition to the above three trends, the reports on other pathogens showed (4) a plateau followed by an increase, such as Zika virus; (5) an increase followed by a plateau, such as Escherichia coli O157:H7; (6) a decrease followed by an increase, such as Vibrio cholerae; (7) a consistent plateau, such as Epstein-Barr virus; (8) a plateau followed by a decrease, such as measles virus; (9) a decrease followed by a plateau, such as poliovirus; and (10) an irregular pattern, mainly for pathogens with a small number of reports (Table 4 , Supplementary Table 1).

Table 4.

Trends by the annual number of published pathogen studies.

Order	Trend	Pathogens
A	Sustained growth	Brucella; B. pseudomallei; Salmonella; M. tuberculosis; L.monocytogenes; Hendra; Dengue; SFTSV; HBV; HCV; Norwalk; Rabies; M. pneumoniae; Plasmodium
B	Plateau followed by increase	S. suis; N.gonorrhoeae; Leptospira; Marburg; Lassa; CCHFV; RVFV; YFV; JEV; TBEV; Zika; Chikungunya; RSV; Coxsackievirus; Rotavirus; EV71; HPV; FMDV; ASFV; NDV; C. burnetii; O. sutsugamushi; C. trachomatis
C	Increase followed by plateau	F. tularensis; B.mallei; O157:H7; Staphylococcus; S. pneumoniae; L.pneumophila; C. jejuni; WNV; MERS; Cryptosporidium
D	Increase followed by decrease	B. anthracis; Y. pestis; H. pylori; Ebola; Influenza; H5N1; H1N1; H7N9; SARS; Bartonella; C. pneumoniae
E	Decrease followed by increase	V. cholerae; T. pallidum
F	Plateau	C. botulinum; Shigella; M. leprae; H. influenzae; C. diphtheriae; C. tetani; N. meningitidis; B. pertussis; B. burgdorferi; Variola; EEE; WEE; Hantavirus; Rubella; Adenovirus; HAV; VZV; HCMV; EBV; B19; VSV; Schistosome
G	Plateau followed by decrease	Measles; Mumpsvirus; C. immitis
H	Decrease followed by steady	HTLV; Poliovirus
I	Continued reduction	HIV; HSV
G	Irregular	C.perfringens; S. pyogenes; VEE; Nipah; Hantaan; SNV; Junin; Monkeypox; R. prowazekii; R. rickettsii; C. psittaci

In the case of some pathogens, particularly BDAPs, the literature showed a decrease followed by a rapid increase. For example, after the outbreak of SARS, many studies were focused on vaccine researches and productions [[11], [12], [13]], which were discontinued thereafter. Had the research been continued, the world would have been better prepared for the current COVID-19 pandemic.

3.2. Country and region distributions of pathogen studies

The pathogens with the highest number of published studies were Staphylococcus (27,944), Salmonella (21,476), human immunodeficiency virus (17,846), Helicobacter pylori (17,677), and Hepatitis C virus (16,791). The most common pathogens across countries were Plasmodium (162), Salmonella (160), Staphylococcus (157), Mycobacterium tuberculosis (155), and Helicobacter pylori (153) (Table 1, Table 2, Table 3, Fig. 3 ).

Fig. 3.

Number of published studies and country/region distribution for each type of pathogen.

The countries/regions with the largest number of published studies on pathogens included the United States of America, China, Japan, England, Germany, France, Canada, Italy, Spain, and India. The United States of America led the highest number of publications on most of the pathogens (82 of the 100 pathogens selected), and also had the second highest number of publications on the following pathogens: Hepatitis B virus, Human T-lymphotropic virus, severe acute respiratory syndrome coronavirus, Burkholderia pseudomallei, Human parvovirus B19, Hendra virus, Hanta Virus, Junin virus, H7N9 Influenza virus, and Clostridium tetani. It had the third and after highest number of publications on the following pathogens: Foot-and-mouth disease virus, Enterovirus 71, African swine fever virus, Orientia tsutsugamushi, severe fever with thrombocytopenia syndrome virus, Japanese encephalitis virus, Streptococcus suis, and tick-borne encephalitis virus.

China had the highest number of published studies on the following pathogens: Hepatitis B virus, Enterovirus 71, severe acute respiratory syndrome coronavirus, Streptococcus suis, Japanese encephalitis virus, Hanta virus, severe fever with thrombocytopenia syndrome virus, and H7N9 Influenza virus. It had also the second highest number of publications on the following pathogens: Adenovirus, Influenza virus, human papillomavirus, Coxsackievirus, Newcastle disease virus, foot-and-mouth disease virus, H5N1 Influenza virus, Mycoplasma pneumoniae, rabies virus, H1N1 Influenza virus, Yersinia pestis, hepatitis A virus, Treponema pallidum, and Eastern equine encephalitis virus. In addition, it had the third highest number of publications on the following pathogens: Staphylococcus, Epstein-Barr virus, Escherichia coli O157:H7, Cryptosporidium, Shigella, Norwalk virus, Zika virus, Middle East respiratory syndrome coronavirus, vesicular stomatitis virus, Schistosoma, and Rickettsia rickettsii.

Japan had the highest number of studies on human T-lymphotropic virus and human parvovirus B19, while England had the highest number of studies on foot-and-mouth disease virus. Further, France had the highest number of studies on Clostridium tetani, while Spain had the highest number of studies on African swine fever virus. For Australia, it was Hendra virus; for Korea, Orientia tsutsugamushi; for Russia, tick-borne encephalitis virus; for Thailand, Burkholderia pseudomallei; and for Argentina, Junin virus (Table 5 ).

Table 5.

Top ranked Countries/regions by number of published studies on various pathogens.

Countries/regions	Top-ranked
United States	Except: HBV, HTLV, SARS, B. pseudomallei, B19, Hantaan, Junin, H7N9, C. tetani, Hendra (Rank 2); FMDV, EV71, ASFV, O. sutsugamushi (Rank 3); SFTSV; JEV; S. suis; TBEV (Rank after 3)
China	S. suis; Hantaan; JEV; SFTSV; H7N9; SARS; HBV; EV71
Japan	HTLV; B19
England	FMDV
France	C. tetani
Spain	ASFV
Australia	Hendra
Russia	TBEV
South Korea	O. sutsugamushi
Thailand	B. pseudomallei
Argentina	Junin

The number of studies exploring various pathogens in the selected 15 countries and regions is shown in Supplementary Table 2. The countries have been selected mainly based on the total number of published studies.

3.3. Top-ranked institutes on published pathogen studies

With regard to the distribution of studies across institutions, the following institutions had the highest number of publications: Pasteur Institute (4,688), Harvard University (4,330), Unites States National Institute of Allergy and Infectious Diseases (NIAID) (3,808), Johns Hopkins University (3,188), University of Washington (3,140), University of Oxford (2,753), University of California San Francisco (2,658), Emory University (2,314), University of Maryland (2,220), and University of Tokyo (2,178). Furthermore, some institutions had the highest number of studies for specific pathogens, such as: Baylor College of Medicine on Helicobacter pylori; Harvard University on human immunodeficiency virus; Chinese Academy of Sciences on severe acute respiratory syndrome coronavirus (Table 6 ).

Table 6.

Institutions with the highest number of published studies on select pathogens.

Countries/regions	Institutes	Pathogens
United States	ARS	O157:H7
	Baylor Coll Med	H. pylori
	Colorado State Univ	M. leprae
	Ctr Dis Control Prevent	S. pneumoniae; Variola; EEE; Nipah; CCHFV; WNV; Influenza; Rotavirus; Norwalk; Poliovirus; Monkeypox; Bartonella; Cryptosporidium
	Georgia State Univ	Rubella
	Harvard Univ	Staphylococcus; HIV; HSV
	Mayo Clin	Measles
	NCI	HPV
	NIAID	Ebola; C. trachomatis
	Northwestern Univ	L. pneumophila
	Oregon Hlth Sci Univ	HCMV
	Thomas Jefferson Univ	Rabies
	Univ Arizona	C. immitis
	Univ Colorado	VZV
	Univ Georgia	M. pneumoniae
	Univ Kentucky	Y. pestis
	Univ New Mexico	SNV
	Univ Pittsburgh	C. perfringens
	Univ S Alabama	R. prowazekii
	Univ Texas	Adenovirus; Zika
	Univ Washington	T. pallidum
	US FDA	Mumps
	USA (US Army)	B. anthracis; B. mallei; VEE
	USDA ARS	Salmonella
	Yale Univ	B. burgdorferi; VSV
China	Chinese Acad Agr Sci	FMDV; NDV
	Chinese Acad Sci	SARS
	Chung Shan Med Univ	B19
	Fourth Mil Med Univ	Hantaan
	Fudan Univ	HBV
	Univ Hong Kong	H1N1; H7N9; MERS
	Chang Gung Univ (Taiwan of China)	EV71
	Natl Def Med Ctr (Taiwan of China)	JEV
Japan	Hokkaido Univ	H5N1
	Kagoshima Univ	HTLV
	Natl Inst Infect Dis	SFTSV
England	Inst Food Res	C. botulinum
	Univ Birmingham	EBV
	Univ Oxford	H. influenzae; N. meningitidis
	Univ York	Schistosome
Germany	Bernhard Nocht Inst Trop Med	Lassa
	Univ Marburg	Marburg
France	INRA	Brucella
	INSERM	HCV
	Inst Pasteur	Shigella; M. tuberculosis; C. tetani; B. pertussis; L.monocytogenes; RVFV; YFV; Chikungunya
Canada	Def Res Dev Canada Suffield	WEE
	Natl Res Council Canada	C. jejuni
	Univ British Columbia	Coxsackievirus
	Univ Montreal	S. suis
Spain	Inst Salud Carlos III	RSV
	Univ Autonoma Madrid	ASFV
	Univ Barcelona	HAV
India	Natl Inst Cholera Enter Dis	V. cholerae
Australia	CSIRO	Hendra
Sweden	Lund Univ	S. pyogenes
	Orebro Univ Hosp	N.gonorrhoeae
	Umea Univ	F. tularensis
Russia	Russian Acad Sci	TBEV
Belgium	Univ Ghent	C. psittaci
Slovakia	Slovak Acad Sci	C. burnetii
Finland	Univ Helsinki	Hantavirus
Brazil	Univ Estado Rio De Janeiro	C. diphtheriae
	Univ Sao Paulo	Leptospira; R. rickettsii
Argentina	Univ Buenos Aires	Junin
South Korea	Seoul Natl Univ	O. sutsugamushi
Thailand	Mahidol Univ	B. pseudomallei; Dengue; Plasmodium

The number of studies exploring various pathogens by the selected 20 institutions is shown in Supplementary Table 3. The institutions were mainly selected based on the total number of published studies. The list also included some institutions and universities in China, such as the Chinese Academy of Sciences, University of Hong Kong, Fudan University, Chinese Academy of Medical Sciences, Chinese Center for Disease Control and Prevention, and Peking University. “CTR DIS CONTROL PREVENT” ranked the first for its number of published studies. However, as “CTR DIS CONTROL PREVENT” represents the Centers for Disease Control and Prevention of the United States, its published number of studies may come from more than one institution, therefore, it was not selected. The next institution was Pasteur Institute, but studies on influenza virus, severe acute respiratory syndrome coronavirus, and Francisella tularensis were relatively rare. Harvard University was listed next to Pasteur Institute, but studies on Japanese encephalitis virus, Influenza virus, Middle East respiratory syndrome coronavirus, and foot-and-mouth disease virus were relatively rare. The Chinese Academy of Sciences had a relatively high number of studies on Yersinia pestis, Escherichia coli O157:H7, Zika virus, Influenza virus, and severe acute respiratory syndrome coronavirus, and the University of Hong Kong also had a relatively high number of studies on Burkholderia pseudomallei, Helicobacter pylori, influenza virus, severe acute respiratory syndrome coronavirus, and hepatitis B virus. Some universities and institutions in China, such as Fudan University and the Chinese Academy of Medical Sciences, had a small number of studies on BDAPs, such as Bacillus anthracis and Francisella tularensis, in comparison with some universities and institutions in the United States, such as University of Maryland or National Institute of Allergy and Infectious Diseases (NIAID) (Supplementary Table 3).

3.4. Journal distribution of the published studies

With regard to the total number of studies on various pathogens, the following journals had published the highest number of studies: Journal of Virology (14,586), Journal of Clinical Microbiology (7,273), Infection and Immunity (6,885), Journal of Infectious Diseases (5,643), and Vaccine (4,151) (Supplementary Table 4). Some journals had the highest number of studies on some particular pathogens: For example, Emerging Infectious Disease had the highest number of studies on Ebola virus, Infection and Immunity had the highest number of studies on Yersinia pestis, and Vaccine had the highest number of studies on Rotavirus (Table 7 ).

Table 7.

Journals with the highest number of published studies on select pathogens.

Journal country/regions	Journals	Impact Factor (2018)	Pathogens
United States	Emerg Infect Dis	7.2	Hantavirus; SNV; MERS
	J Virol	4.3	Ebola; Marburg; Lassa; VEE; WEE; Nipah; Hendra; Hantaan; CCHFV; RVFV; Junin; YFV; Dengue; JEV; TBEV; SFTSV; Influenza; H5N1; H1N1; H7N9; Measles; Rubella; Mumps; Adenovirus; RSV; SARS; HIV; HAV; HBV; HCV; Coxsackievirus; Norwalk; Poliovirus; HSV; VZV; HCMV; EBV; Monkeypox; Rabies; HPV; FMDV; ASFV; NDV; VSV
	PLoS Negl Trop Dis	4.5	Leptospira; Chikungunya
	Antimicrob Agents Chemother	4.7	Staphylococcus; S. pneumoniae
	Helicobacter	3.4	H. pylori
	J Clin Microbiol	5.0	M. tuberculosis; C. diphtheriae; T. pallidum; Variola; Bartonella; M. pneumoniae
	Appl Environ Microbiol	4.1	C. botulinum; C. jejuni
	Infect Immun	3.2	Y. pestis; F. tularensis; Brucella; B.mallei; B. pseudomallei; Shigella; H. influenzae; S. pyogenes; N. meningitidis; B. pertussis; L.pneumophila; B. burgdorferi; C. burnetii; R. rickettsii; C. pneumoniae; C. immitis
	J Bacteriol	3.2	B. anthracis; V. cholerae; R. prowazekii
	PLoS One	2.8	EV71
	Am J Trop Med Hyg	2.3	C. tetani; EEE; O. sutsugamushi
	Vector Borne Zoonotic Dis	1.9	WNV
	J Med Virol	2.0	B19
	Sex Transm Dis	2.3	N. gonorrhoeae; C. trachomatis
	AIDS Res Hum Retroviruses	1.8	HTLV
	J Food Prot	1.6	Salmonella; O157:H7; L.monocytogenes
England	Vaccine	4.8	Rotavirus
	Sci Rep	4.0	Zika
	Malar J	2.8	Plasmodium
	Anaerobe	2.7	C. perfringens
	Parasitology	2.5	Schistosome
	Lepr Rev	0.5	M. leprae
Netherlands	Vet Microbiol	2.8	S. suis; C. psittaci
	Vet Parasitol	2.0	Cryptosporidium

The number of studies exploring various pathogens for the selected 20 journals is shown in Supplementary Table 4. The journals were selected mainly based on their impact factor and the total number of pathogens studies published. Infection and Immunity and Molecular Microbiology had the highest number of publications on bacterial pathogens; Vaccine had publications on almost all kinds of pathogens; PNAS mainly had reports on viruses; and Emerging Infectious Diseases had more virus-related literature. Some top journals published a number of related studies on particular pathogens: pathogens studies published on Science rank first and second are Plasmodium spp. and Salmonella spp., Nature are Plasmodium spp. and influenza virus; Cell are Plasmodium spp. and Zika virus; New England Journal of Medicine are human immunodeficiency virus and human cytomegalovirus; Lancet are Helicobacter pylori and Hepatitis C virus. (Supplementary Table 4).

4. Discussion

4.1. Characteristics of the retrieved studies

From the quantitative analysis of studies on the selected pathogens, the following characteristics were evidenced:

• (1)The number of studies is closely related to disease epidemics. Some pathogens, such as SARS coronavirus, H1N1 influenza virus, and Ebola virus, have resulted in a rapid increase in the number of studies published after the disease outbreaks. However, once the epidemic has been controlled, the number of studies declined.
• (2)The number of studies was closely related to disease distribution. The number of studies related to pathogens tended to be related to the geographical distribution of the corresponding diseases. For example, the literatures on H7N9 avian influenza is predominate in China, while the most relevant literatures on Burkholderia pseudomallei is in Thailand. In studies assessing Junin virus, it was Argentina which published the most studies.
• (3)Core research institutions play significant roles on pathogen studies. Such as the Pasteur Institute in France, Harvard University, the National Institute of Allergy and Infectious Diseases in the United States, and the Chinese Academy of Sciences.

4.2. Research studies on pathogens in China

China attaches great importance to the prevention and control of infectious diseases; thus has made significant progress in relevant research and biosafety management since the SARS outbreak in 2002–2003 [14]^. Although the great advance and progress have been made, improvement in the following areas are still needed:

• (1)Pathogens studied are unbalanced. Relatively large number of published studies is on health-threatening pathogens, such as hepatitis B virus and Japanese encephalitis, while relatively small number of published studies is on biodefense-associated pathogens such as Bacillus anthracis and Ebola virus, specifically at the university level.
• (2)Institutions SCI reports on pathogens lower than world top pathogen research institutions. In the field of pathogen research, national institutions such as the Chinese Academy of Sciences, Chinese Academy of Medical Sciences, and Chinese Center for Disease Control and Prevention play an important role. However, in comparison with the world's top pathogen research institutions such as the Pasteur Institute in France and the National Institute of Allergy and Infectious Diseases in the United States of America, there are still some gap on pathogen research SCI reports.
• (3)The level of Chinese pathogen-related journals needs to be enhanced. It can be seen from the data that the pathogen-related SCI journal are mainly from the United States and Europe. Although the total number of Chinese SCI reports on pathogens is the second largest in the world, there are still not many influential international journals in China in this field.

4.3. Pathogen research is closely related to biosafety and biosecurity

Pathogen researches can protect human health, but it can also create potential biosafety and biosecurity issues that threaten human health.

• (1)The level of research on pathogens is an important index for the ability to deal with infectious diseases. Pathogen research is based on historic infectious diseases, emerging infections, and control of new biological threats. In addition, it is also an important aspect of national biodefense capacity. By strengthening investment in science and technology, China's ability to prevent and control infectious diseases has increased significantly [15]. Consequently, the number of related SCI reports has grown significantly [16], although there is still gaps between China and the United States [17].
• (2)Pathogen research can result in biosafety and biosecurity risks. With the rapid development of life sciences and biotechnology, biosafety and biosecurity issues are receiving increasing attention [[18], [19], [20], [21]]. Pathogen-related researches may lead to an increased likelihood of pathogen laboratory errors, and there is also the possibility of deliberate use by humans [22].
• (3)Towards reducing the biosafety and biosecurity risk, it is necessary to ameliorate the supervision and support for pathogenic researches, including improvement on biosafety management monitoring and risk assessment systems [23]. Furthermore, researches on molecular biocontainment and other methods should also be strengthened [[24], [25]].

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Appendix A. Supplementary data

Supplementary material