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

Authors: Mpumelelo Casper Rikhotso; Jean Pierre Kabue; Solanka Ellen Ledwaba; Afsatou Ndama Traoré; Natasha Potgieter
Journal: Journal of Tropical Medicine
 (2018)

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## 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.


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## Body

## 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 ofBocavirus [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 anin 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 (Figure1). 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.


## 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 (Figure1). 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 (Tables1, 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 (Table1). 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 Figure2 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) (Table2). 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 (Table3). 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) (Table3). 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 (Table3), 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) (Tables1, 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.



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