Journal of Tropical Medicine
Volume 2018 (2018), Article ID 7875482, 15 pages
https://doi.org/10.1155/2018/7875482

Review Article

Prevalence of Human Bocavirus in Africa and Other Developing Countries between 2005 and 2016: A Potential Emerging Viral Pathogen for Diarrhea

Mpumelelo Casper Rikhotso,¹ Jean Pierre Kabue,¹ Solanka Ellen Ledwaba,¹ Afsatou Ndama Traoré,¹ and Natasha Potgieter1,2

¹Department of Microbiology, School of Mathematical and Natural Science, University of Venda, Thohoyandou, South Africa
²School of Mathematical Sciences, University of Venda, Thohoyandou, South Africa

Correspondence should be addressed to Natasha Potgieter; natasha.potgieter@univen.ac.za

Received 21 December 2017; Revised 20 June 2018; Accepted 16 July 2018; Published 12 September 2018

Academic Editor: Shyam Sundar

Copyright © 2018 Mpumelelo Casper Rikhotso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Background. Human Bocavirus (HBoV) is an emerging virus discovered in 2005 from individuals suffering gastroenteritis and respiratory tract infections. Numerous studies related to the epidemiology and pathogenesis of HBoV have been conducted worldwide. This review reports on HBoV studies in individuals with acute gastroenteritis, with and without respiratory tract infections in Africa between 2005 and 2016. Material and Method. The search engines of PubMed, Google Scholar, and Embase database for published articles of HBoV were used to obtain data between 2005 and 2016. The search words included were as follows: studies performed in Africa or/other developing countries or/worldwide; studies for the detection of HBoV in patients with/without diarrhea and respiratory tract infection; studies using standardized laboratory techniques for detection. Results. The search yielded a total of 756 publications with 70 studies meeting the inclusion criteria. Studies included children and individuals of all age groups. HBoV prevalence in Africa was 13% in individuals suffering gastroenteritis with/without respiratory tract infection. Conclusion. Reports suggest that HBoV infections are increasingly being recognized worldwide. Therefore, surveillance of individuals suffering from infections in Africa is required to monitor the prevalence of HBoV and help understand the role of HBoV in individuals suffering from gastroenteritis with/without respiratory tract infection.

1. Introduction

Diarrhea is a leading cause of morbidity and mortality in children worldwide [1, 2]. Diarrhea is the third major cause of childhood mortality in children less than 5 years of age especially in Africa and developing countries [3–5]. The modes of transmission include ingestion of contaminated food or water (e.g., via flies, inadequate sanitation facilities, sewage and water treatment systems, and cleaning food with contaminated water), direct contact with infected feces (fecal-oral route), person-to-person contact, and poor personal hygiene [6, 7].

According to WHO [1], approximately 90% of the estimated 2.2 million of deaths caused by diarrheal infections in children less than 5 years of age are related to poor sanitation and hygiene behaviors worldwide. While the mortality due to diarrheal diseases has declined significantly in children over the past twenty years in developed countries [8, 9], the incidence of childhood diarrhea in developing countries has not decreased [1, 2]. Those who survive these illnesses have repeated infections by enteric pathogens which remains a critical factor leading to serious lifelong health consequences [10] and eventually result in death [11]. Viruses are recognized as major cause of gastroenteritis, particularly in children, and the number of viral agents associated with diarrheal disease in humans has increased progressively. Viruses such as rotavirus, norovirus, astrovirus, and adenovirus that cause diarrhea have been reported worldwide [11].

The Human Bocavirus (HBoV) is a viral agent that has been reported worldwide in various studies as a potential cause of diarrhea outbreaks [5, 12–18]. The HBoV is a member of the Parvoviridae family, Parvovirinae subfamily, and the genus of Bocavirus [19–21]. The family Parvoviridae includes small, nonenveloped, icosahedral viruses with 5.3 kb single stranded DNA genome containing three open reading frames (ORFs); the first ORF, at the 5′ end, encodes NS1, a nonstructural protein [22]. The second ORF encodes NP1, a second nonstructural protein. The third ORF, at the 3′ end, encodes the two structural capsid viral proteins (VPs), VP1 and VP2 [23, 24]. There are currently four Bocavirus species identified worldwide, namely, HBoV1, HBoV2, HboV3, and HBoV4 [5, 25–28]. HBoV was first discovered in 2005 in children with acute respiratory tract infection [28]. In 2007, HBoV was detected in children suffering from gastroenteritis with and without symptoms of respiratory tract infections [14, 29–31]. Primary infection with HBoV occurs early in life in children between 6–24 months of age [32–34]; however, older children and adults can also be infected [28, 35]. Currently there is no specific approved treatment or vaccine for HBoV infection [25, 36, 37]. Since its discovery, the virus was mainly associated with respiratory tract infections, but recent studies have revealed the involvement of the virus in gastroenteritis. These studies indicate that only HBoV2, HBoV3, and HBoV4 strains of the virus are mainly involved in gastroenteritis [37–39]. Currently, there is limited data on ELISA method for the detection of the virus. HBoV detection has been done by conventional PCR [17, 28, 40, 41] and real-time PCR [42–45]. While HBoV epidemiological studies have shown evidence for widespread exposure to the virus, the causative role of HBoV in respiratory tract disease and gastroenteritis is still under investigation [46]. Proven evidence is difficult to obtain without an in vitro culture system and animal model [28, 47–49].

The prevalence of HBoV has been reported in Europe [50, 51], America [17, 41], Asia [34, 52], Australia [40, 53], Africa [54], and the Middle East [18], ranging from 1.5% to 19.3% [17, 55]. This review is a summary of reported HBoV studies in individuals with acute gastroenteritis, with and without respiratory tract infections looking specifically to studies in Africa to determine the role of HBoV in diarrheal outbreaks.

2. Materials and Methods

2.1. Search Strategy

A literature search of selected studies that investigated HBoV in Africa, in other developing countries and worldwide was performed using the following terms: Human + Bocavirus + Africa + Developing countries + Worldwide on PubMed, Google scholar and Embase. This search yielded 756 publications (Figure 1). The first search was performed for HBoV + Africa, the second search was HBoV + other developing countries, and the third search was HBoV + worldwide. Keywords used included Human Bocavirus, Bocavirus, and Human parvovirus combined for each (Africa; Developing country; Worldwide). To avoid leaving out any studies not found in major scientific databases, Google search was also used. After reviewing each article, studies were selected if they met the following inclusion criteria:

(i)Studies performed in Africa/other developing countries/worldwide between 2005 and 2016. (ii)Studies for the detection of HBoV in patients with or without diarrhea and respiratory tract symptoms. Diarrhea defined as the passage of loose or watery stools, at least three times in a 24-h period [56]. (iii)Studies using standardized laboratory techniques for detection of HBoV including PCR, real-time-PCR, and Multiplex PCR (m-PCR).

Figure 1: Schematic presentation of search engine used.

3. Data Extraction

Information extracted from the inclusion studies included country where study was done, time period of study, age range of participants, study setting (rural/urban/periurban), sampled population (number of included samples), method used for detection, clinical symptoms, sample type, and HBoV subtype.

4. Statistical Analysis

All analysis were conducted using R programming environment for data analysis and graphics Version 3.5.0 [57] to calculate random and fixed effects. Function “rma” from the package Metafor [58] was used to calculate heterogeneity between studies and generate a forest plot. Heterogeneity was assessed by Cochran’s Q test.

5. Results and Discussion

Between 2005 and 2016 a total of 756 studies were published in Africa, other developing countries and worldwide. From these studies, 70 studies met the inclusion criteria of which 11 studies were from African countries and 59 studies combined were for other developing countries and worldwide. None of the studies reported on outbreaks (Tables 1, 2, and 3).

Table 1: Human Bocavirus globally, studies published between 2005 and 2016.

Country
Study period
Setting
Age range
Sampled population
Tested samples
Positive samples ()
Hospitalized
Outpatient
Sample type
Symptoms
Detection method
HBoV type
Reference

Australia
2001
-
-
children
197
125 (63.5%)
197
-
Stool
Diarrhea
Nested PCR
1,2,3
[25]

2003-2004
Urban
≤ 5 years
children
700
41 (6%)
604
96
Nasal–throat, stool, whole blood
Respiratory infection/diarrhea
Real-time PCR
1
[26]

America
2004
Urban
< 2 years
children
1271
22 (1.7%)
1271
-
Nasal
Respiratory tract infection
PCR
1
[41]

-
Peri-urban
All
children
641
101 (16%)
-
-
Stool
Diarrhea
PCR
1,2,3,4
[74]

2007-2008

2-11 years
children
149
7 (5%)
-
149
Throat, Nasal
Respiratory tract infection
Real-time PCR
1
[66]

Argentina
2011
Peri-urban
≤ 2 years
children
222
15 (7%)
222
-
Nasal
Respiratory tract infection
PCR
1
[76]

Argentina, Nicaragua, Peru
-
-
< 6 years
children
568
61 (11%)
568
-
Nasal
Respiratory tract infection
Real time PCR
1
[77]

Brazil
2004-2007
Peri-urban
≤ 2 years
children
397
3 (0.76%)
-
397
Nasal, throat
Respiratory tract infection
PCR
1
[62]

2003-2005
Peri-urban
<15 years
children
705
14 (2%)
285
420
Stool
Diarrhea
PCR
1
[15]

1998-2004
Urban
< 5 years
children
762
44 (5.8%)
762
-
Stool
Diarrhea
PCR
1,3
[78]

2008
Urban
<2 years
children
511
55 (11%)
511
-
Nasal
Respiratory tract infection
PCR
1,2,3
[79]

2010-2012
Urban/rural
≤18
children
200
67 (33.9%)
200
-
Nasal
Respiratory tract infection
Real-time (RT-PCR)
1
[80]

2010-2011
Urban/rural
1-14 years
children
121
36 (29.8%)
121
-
Nasal
Respiratory tract infection
Real-time PCR
1
[81]

2005-2007
Urban/rural
All
Children/adults
1015
49 (4.8%)
1015
-
Nasal
Respiratory tract infection
PCR
1
[82]

2008-2009
Urban
< 5 years
children
407
77 (19%)
407
-
Nasal
Respiratory tract infection
PCR
1
[83]

2006-2007
Urban/rural
All
Children/adults
90
2 (2%)
90
-
Stool
Diarrhea
PCR
1
[84]

Cambodia
2009-2010
Urban
All
Children/adults
292
162 (55%)
292
-
Nasal, throat
Respiratory tract infection
Multiplex PCR
1
[85]

Cameroon
2011-2013
Urban
≤15 years
children
347
37 (11%)
347
-
Throat
Respiratory tract infection
Multiplex PCR
1
[86]

China
2009-2013
Urban/rural
All
Children/adults
29248
551 (2%)
29 248
-
Nasal
Respiratory tract infection
Real-time PCR
1
[87]

2004-2005
Urban
< 18 years
children
203
83 (40%)
203
-
Stool, Nasal
Respiratory infection/diarrhea
PCR
1
[88]

2007-2008
Urban
≤15 years
children
235
21 (9%)
235
-
Nasal
Respiratory tract infection
PCR
1,2
[89]

2009-2012
Urban/rural
All
Children/adults
14237
180 (1.26%)
14237
-
Nasal
Respiratory tract infection
PCR
1
[23]

2012-2013
Urban/rural
<14 years
children
4130
(16.7%)
4130
-
Throat
Respiratory tract infection
Real-time PCR
1
[90]

2012
Peri-urban
≤ 5 years
children
122
-
-
122
Stool
Diarrhea
Multiplex real-time PCR
1
[91]

2009-2014
-
All
Children/adults
12502
225 (2%)
12502
-
Nasal
Respiratory tract infection
PCR
1
[92]

2009-2014
Urban
<14 years
children
4242
125(3%)
4242
-
Nasal
Respiratory tract infection
Real time PCR
1
[93]

2012-2013
Urban
< 6 years
children
346
60 (17.34%)
346
-
Stool
Diarrhea
PCR
1,2
[94]

Egypt
2013-2014
Urban
≤ 36 months
children
95
54 (56.8%)
95
-
Nasal
Respiratory tract infection
Real-time PCR
1
[8]

2013-2015
Urban
1 month-2 years
children
100
2(2%)
100
-
Stool
Diarrhea
PCR
1
[95]

Finland
2000-2002
Urban
3 months-15 years
children
117
24 (49%)
117
-
Nasal, serum
Respiratory tract infection
Qualitative PCR
1
[96]

2010
Urban
All
Children/adults
250
4 (1.6%)
250
-
Stool
Diarrhea
Multiplex real-time quantitative PCR
1,2,3,4
[27]

France
2003-2004
-
< 5 years
children
589
9 (1.5%)
589
-
Nasal
Respiratory tract infection
PCR
1
[51]

2010-2011
Urban
All
Children/adults
1465
5 (0.3%)
1465
-
Nasal
Respiratory tract infection
Multiplex PCR
1
[97]

Germany
2007
Urban
-
children
834
115 (14%)
834
-
Stool, nasal, serum
Respiratory tract infection
Real-time PCR
1
[98]

Hong Kong
2004-2005
Periurban
-
children
1178
12 (1%)
1178
-
Nasal
Respiratory tract infection
Real time PCR; PCR
1
[99]

2004-2005
Urban
<18 years
children
3035
103 (3.4%)
3035
-
Nasal
Respiratory tract infection
PCR
1
[88]

Iran
2009-2011
Peri-urban
2-108 months old
children
80
6(8%)
80
-
Stool
Diarrhea
Real-time PCR
1
[100]

2010-2011
Urban
<4 years
children
200
16 (8%)
200
-
Stool
Diarrhea
Real-time PCR
1
[101]

Istanbul
2014-2015
Urban/rural
All
Children/adults
845
91 (11%)
845
-
Nasal
Respiratory tract infection
Real time PCR
1
[102]

Italy
2005-2006
Urban
-
Children/adults
426
42 (9.9%)
426
-
Nasal
Respiratory tract infection
PCR
1
[103]

2000-2006
Urban
All
Children/adults
355
4.5%,
355
-
Nasal
Respiratory tract infection
PCR
1
[30]

2004-2007
Urban/rural
<14 years
children
415
34 (8.2%)
415
-
Nasal
Respiratory tract infection
PCR
1
[104]

2011-2012
Urban
All
Children/adults
689
14 (2%)
689
-
Stool
Diarrhea
Real time PCR
1
[105]

India
2010-2011
Rural/Peri-urban
0–6 years
children
300
2 (0.67%)
300
-
Throat
Respiratory tract infection
PCR
1
[106]

Jordan
2003-2006
Peri-urban
< 5years
children
326
57 (17%)
326
-
Nasal
Respiratory tract infection
PCR
1
[18]

2007
Peri-urban
≤13 years
children
220
20 (9%)
220
-
Nasal
Respiratory tract infection
PCR/ real-time PCR
1
[107]

2003-2004
Urban
≤ 5 years
children
326
57 (17%)
326
-
Nasal
Respiratory tract infection
Real time PCR
1
[108]

Japan
2005-2011
Peri-urban
0-136 months
children
850
132 (15.5%)
850
-
Nasal
Respiratory tract infection
Nested PCR
1,2,3,4
[73]

2007–2009
Urban/rural
<2 years
children
402
34 (8.5%)
402
-
Nasal
Respiratory tract infection
PCR
1
[109]

Kenya
2013
Rural
≤5 years.
children
125
21 (17%)
125
-
Throat
Respiratory tract infection
PCR
1
[59]

2007-2009
Urban
All age group
Children/adults
384
7 (1.8%)
-
384
Nasal
Respiratory tract infection
PCR
1,2,3,4
[3]

United Kingdom
1993–1996
Urban/rural
All
Children/adults
4380
324 (7.4%)
4380
-
Stool
Diarrhea
Real time PCR
1,2,3
[110]

Malaysia
2012
Urban/rural
Children
children
1
1 (99%)
1
-
Nasal
Respiratory tract infection
PCR
1
[111]

Netherland
2005-2006
Peri-urban
3 months-6 years
children
257
4 (1.6%)
-
257
Nasal
Respiratory infection/diarrhea
Real time PCR
1
[112]

Pakistan
2008
Rural
-
Children/adults
98
-
-
-
Stool
Diarrhea
PCR
1,2
[113]

Philippines
2008-2009
Urban
8 days to 13 years
children
1242
2 (0.16%)
1242
-
Nasal
Respiratory tract infection
PCR
1
[114]

Senegal
2009-2011
Urban
All age group
Children/adults
232
1 (0.4%)
232
-
Nasal
Respiratory tract infection
Real-Time PCR
1
[115]

2007
Rural
≤5
children
82
1 (1.2%)
82
-
Nasal
Respiratory tract infection
PCR
1
[4]

South Africa
1998-2000
Urban
<2
children
1460
332 (22.8%)
1460
-
Nasal
Respiratory tract infection
RT-PCR
1
[116]

2004
Urban
2 days–12 years
children
341
13 (37%)
341
-
Nasal
Respiratory tract infection
PCR
1
[54]

2004-2005
Urban
2 months to 6 years
children
242
18 (7.4%)
242
-
Nasal
Respiratory tract infection
Nested PCR
1
[117]

2009-2010
Rural
3 months to <5 years
children
260
30 (11.5%)
-
260
Nasal
Respiratory tract infection
PCR
1
[118]

Shanghai
2009-2012
Peri-urban
≤ 5 years
children
554
39 (7.0%)
554
-
Nasal, stool, whole blood
Respiratory tract infection
Real time PCR/ PCR
1
[29]

Spain
2005-2006
Urban
<3 years
children
527
48 (9.1%)
527
-
Stool, Nasal
Respiratory tract infection/diarrhea
PCR
1
[14]

Sweden
2000-2002
Urban
3 months to 15 years
children
259
49 (19%)
259
-
Nasal, serum
Respiratory tract infection
Real-time PCR
1
[42]

Taiwan
2008-2009
Peri-urban
5 months-9 years
children
705
35 (5%)
-
705
Throat
Respiratory tract infection
PCR
1
[119]

Thailand
2006
Urban
1 month-9 years
children
252
18 (7%)
252
-
Nasal
Respiratory tract infection
PCR
1
[20]

2005-2007
Peri-urban
2 months-5 years
children
427
2 (0.4%)
225
202
Stool
Diarrhea
PCR
1
[33]

Turkey
2015
Urban
Five months
children
1
1 (99%)
1
-
Nasal, stool
Respiratory tract infection/diarrhea
Multiplex PCR
1,2,3,4
[120]

Table 2: Human Bocavirus studies in other developing countries between 20005 and 2016.

Country
Study period
Setting
Age range
Sampled population
Tested samples
Positive samples ()
Hospitalized
Outpatient
Sample type
Symptoms
Detection method
HBoV type
Reference

Argentina, Nicaragua and Peru
-
-
< 6 years
children
568
132 (23%)
568
-
Nasal
Respiratory tract infection
Real time PCR
1
[77]

Brazil
2007
Rural
<3 years
children
260
27 (10.4)
260
-
Nasal
Respiratory tract infection
Real-time PCR
1
[121]

Cambodia
2009-2010
-
All
Children/adults
292
9 (3%)
292
-
Throat swabs, nasal
Respiratory tract infection
Multiplex real-time PCR
1
[85]

China
2012
Peri-urban
≤ 5 years
children
122
-
-
-
Stool
Diarrhea
Multiplex real-time PCR
1
[91]

2009-2014
-
All
Children/adults
12502
225 (2%)
12502
-
Nasal
Respiratory tract infection
PCR
1
[92]

2009-2014
Urban
<14 years
children
4242
125 (3%)
4242
-
Nasal
Respiratory tract infection
Real time PCR
1
[98]

2012-2013
Urban
< 6 years
children
346
60 (17.34%)
346
-
Stool
Diarrhea
PCR
1,2
[94]

India
2010-2011
Rural/Peri-urban
0–6 years
children
300
2 (0.6 %)
300
-
Throat swabs
Respiratory tract infection
PCR
1
[106]

Jordan
2003-2004
Urban
≤ 5 years
children
326
57 (17%)
326
-
Nasal
Respiratory tract infection
Real time PCR
1
[108]

Philippines
2008-2009
Urban
8 days to 13 years
children
1242
2 (0.16)
1242
-
Nasal
Respiratory tract infection
PCR
1
[114]

Table 3: Human Bocavirus studies in Africa between 2005 and 2016.

Country
Study period
Setting
Age range
Sampled population
Tested samples
Positive Samples ()
Hospitalized
Outpatient
Sample type
Symptoms
Detection method
HBoV type
Reference

Cameroon
2011-2013
Urban
Children aged ≤15 years
children
347
37 (10.6%)
347
-
Throat
Respiratory tract infection
Multiplex PCR
1
[86]

Egypt
2013-2015
Urban
1 month-2 years
children
100
2 (2%)
40 (40%)
60 (60%)
Stool
Diarrhea
PCR
1
[95]

2013-2014
Urban
≤ 36 months
children
95
54 (56%)
11 (40%)
43 (63%)
Nasal
Respiratory tract infection
Real-time PCR
1
[8]

Kenya
2013
Urban
≤5
children
125
21 (16.8%)
125
-
Throat
Respiratory tract infection
PCR
1
[59]

2007-2009
Urban
All age group
Children/adults
384
7 (1.8%)
-
384
Nasal
Respiratory tract infection
PCR
1,2,3,4
[3]

Senegal
2007
Rural
≤5
children
82
1 (1.2%)
-
82
Nasal
Respiratory tract infection
PCR
1
[4]

2009-2011
Urban
All age group
Children/adults
232
1 (0.43%)
-
232
Nasal
Respiratory tract infection
Real-Time PCR
1
[115]

South Africa
1998-2000
Urban
<2
children
1460
174 (22.8%)
1460
-
Nasal
Respiratory tract infection
RT-PCR
1
[116]

2004
Urban
2 days–12 years
children
341
38 (11%)
341
-
Nasal
Respiratory tract infection
PCR
1
[54]

2004-2005
Urban
2 months to 6 years
children
242
18 (7.4%)
242
-
Nasal
Respiratory tract infection
Nested PCR
1
[117]

2009-2010
Rural
3 months to <5 years
children
260
30 (11.5%)
-
260
Nasal
Respiratory tract infection
PCR
1
[118]

All 70 studies were reports on children ≤5 years of age (33%; 23/70) and children and individuals of all ages, ≥5 years (67%; 47/70). The majority of the studies (78%; 55/70) were reports on patients suffering from respiratory tract infection and 21.4% (15/70) were reports on patients suffering from diarrheal disease. Fifty-four studies (77%; 54/70) were done in urban settings and 23% (16/70) were done in rural settings (Table 1). The most reported HBoV subtype was HBoV1 (100%; 70/70), followed by HBoV2 (16%; 11/70), HBoV3 (13%; 9/70), and HBoV4 (7%; 5/70) (Table 1). A total of 54% (36/67) studies were done on samples collected from nasal swabs, 7% (5/67) were done on samples collected from throat swabs, 22% (15/67) were done on stool samples, 4% (3/67) were combined nasal/throat samples, 3% (2/67) were combined stool/nasal samples, 6% (4/67) were combination of nasal/stool/serum samples, and 3% (3/67) were a combination of nasal/serum samples.

Meta-analysis was done to provide transparent, objective, and replicable summaries of the study findings. From all the 70 studies, 66 had sufficient information to enable statistical analysis. As shown in Figure 2 with the dispersion in study prevalence, there was a low heterogeneity among the studies (Cochran Q = 12.2800 [df = 65] P-Val = 1). Apart from the observed increase in the prevalence of HBoV, none of the other drivers (including age, setting, symptoms, method of detection, and hospitalization) achieved statistical significance. The test for overall effect was Z = 13.29 (P<0.0001) which was highly significant in the findings.

Figure 2: Forest plot for prevalence studies in detection of Human Bocavirus.

Ten studies were from other developing countries of which eight studies (80%) reported on patients suffering from respiratory tract infection and two studies (20%) reported on patients suffering from diarrheal disease. All ten of the studies focused only on children (100%; 10/10) (Table 2). All studies in other developing countries worked on hospitalized patients (Table 2). A total of 70% (7/10) of the studies collected nasal swabs, 20% collected throat swabs, and 20% of the studies collected stool samples. The most sampled population was children ≤ 6 years of age (Table 2). Majority 60% (6/10) were done in urban setting in other developing countries while 40% (4/10) were done in rural settings. Eight (80%) of the studies reported on patients suffering from respiratory tract infections (Table 2). In other developing countries, HBoV was reported in Argentina 10% (1/10), Cambodia 10% (1/10), China 40% (4/10), India 10% (1/10), Jordan 10%(1/10), and the Philippines 10%(1/10).

In Africa, the majority of studies (82%; 9/11) were done in urban settings while 18% (2/11) were done in rural settings. Ten (91%) of the studies reported on patients suffering from respiratory tract infections and one study (9%) reported on patients suffering from gastroenteritis. In these studies, a total of 383 (10.4%) samples tested positive for HBoV (Table 3). More studies reported HBoV in children less than five years of age (54%; 6/11) compared to children above the age of 5 and adults 45% (5/11) (Table 3).

Countries that reported on HBoV in Africa included Kenya 18% (2/11), South Africa 36% (4/11), Egypt 18% (2/11), Cameroon 9% (1/11), and Senegal 18% (2/11). Five of the 11 studies in Africa focused on hospitalized patients and 36% (4/11) studies focused on outpatients, while 18% (2/11) studies focused on both hospitalized and outpatients. Eight (73%; 8/11) of the studies in Africa collected nasal swabs, two studies 18% (2/11) collected throat swabs, and one (9%; 1/11) study collected stool samples.

The prevalence of HBoV in Africa was 13% in individuals suffering from gastroenteritis with and without respiratory tract symptoms. The high detection rate of HBoV in Africa was consistent with the global increase of HBoV in children less than 5 years of age [4, 59]. Children of all age group are most likely to experience HBoV infection as a result of poor sanitation and hygiene practices [59]. The most predominant HBoV subtype identified in Africa was HBoV1, which was detected in all the studies. Only one study (9%), from Kenya detected all subtypes (HBoV1-4) from children of all age group (Table 3). Not all the studies tested for all HBoV subtypes; this may be due to the fact that other HBoV subtypes have just been recently discovered compared to HBoV1 [37]. The most predominant HBoV subtype identified in other developing countries was HBoV1, which was isolated in all the studies. Only 10% (1/10) of the studies from china detected HBoV2 in the study population (Table 2).

The results in Africa indicated that HBoV in children less than five years of age was high, 54% (6/11) compared to children above 5 years of age and adults 45% (5/11) (Table 3). Schildgen and colleagues [60] showed that all age groups can be affected by HBoV, although severe infections requiring hospitalization occur primarily in patients with an underlying disease and children under 5 years of age [61–64]. Severe clinical cases (such as destruction of the epithelium of the respiratory system) have been described in children [61, 64–66] and adults with immunodeficiency [64] and other risk groups [67]. Studies in Africa (13%; 9/70) were mostly done in urban setting compared to other developing countries/worldwide (87%; 61/70) (Tables 1, 2, and 3). This could be due to the lack of laboratory resource capacity and technology for the detection of HBoV in rural settings.

The methods used for detecting HBoV have been conventional PCR [17, 28, 40, 41, 45, 53, 64] and real-time PCR [42–45, 54, 68], due to the limited success of serological and viral culture techniques. Real-time PCR is more sensitive and offers greater sensitivity, increased specificity with the addition of oligoprobes, and the added benefit of a closed detection system, reducing the likelihood of false positive results due to contamination with amplicon [33]. In Africa, 63% (7/11) of studies used conventional PCR for detection, 27% (3/11) used real-time PCR, and 9% (1/11) used Multiplex PCR which is also conventional PCR (Table 3).

In all eleven African studies, HBoV1 was detected (Table 3), similarly in other developing countries HBoV1 was detected in all the studies. HBoV Subtype 1 is mainly associated with respiratory diseases but can also be found in stool samples from patients suffering from diarrhea. Previous studies have reported prevalence of HBoV in symptomatic patients 1.5–16% worldwide [69, 70]. Several studies have isolated HBoV from children with respiratory tract infection worldwide, and the prevalence of HBoV in these children was 1.5%–19% [32, 33, 35].

The reports on HBoV in Africa, other developing countries, and worldwide in individuals suffering from respiratory tract infection 78% (55/70) were higher compared to those suffering from gastroenteritis 21% (15/70) (Tables 1, 2, and 3). This could be due to the fact that most studies focused on HBoV in respiratory tract infection since its discovery in 2005 [28, 33, 36, 71]. However recent studies are increasingly detecting HBoV in individuals suffering from diarrheal diseases due to the presence of the virus in stool samples of individuals suffering from gastroenteritis [37, 72–74].

Although the number of studies in Africa is limited, the HBoV prevalence rate of 13% indicates that this virus is one of the emerging viral agents in those suffering from diarrhea with and without respiratory tract infections. Currently there is no available reporting system for HBoV infection in the primary healthcare systems in Africa, suggesting that diarrheal cases with and without respiratory tract infection are likely to be underreported [47]. The high frequency of HBoV in children raises a potential health risk as these children may act as reservoir for other emerging epidemic HBoV strains [27, 37, 75].

6. Conclusion

More studies are required in Africa, especially in rural settings to monitor the prevalence of HBoV and help understand the role of HBoV in individuals suffering from gastroenteritis with/without respiratory tract infection. HBoV infections are likely to be underreported in Africa considering the costs of testing for the virus. This review was done to shed light on HBoV and its possible role in diarrheal incidence.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

The authors would like to express their gratitude to the library staff members of the University of Venda who provided assistance for this review. This study was done through funding from the Director of Research and Innovation, University of Venda, Project no. SMNS/17/MBY/03.

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