Introduction

The Camelidae family comprises two genera comprising the genus Camelus and the genus of lama (also named Camelids). The old-world genus of Camelus is divided into two species of Camelus dromedarius (the one-humped camel) and the Camelus bactrianus (the two-humped camel). Dromedary camels occupy the West Central and Near East Asia, North Africa, and Ethiopia (Wardeh, 2004). The habitat of the Camelus bactrianus is the cold deserts of China, East-Central Asia, and Mongolia (Jasra and Mirza, 2004). It is estimated that the world population of camels is 25.89 million, composed of 11% two-humped and 89% of one-humped dromedary camels (Kula and Tegegne, 2016). More than 60% of the dromedary camel population is habited in the countries of North-East Africa, such as Sudan, Kenya, Ethiopia, and Somalia (Gizachew et al., 2014). As a vital source of subsistence and income, the camel has socioeconomic effects on the survival of the populations of the arid and semi-dry areas living in Asia and Africa (Ahmad et al., 2010; Aujla et al., 1998). As camels are still an important part of the nomadic and pastoral livelihoods and because of the lack of mandatory vaccination programs for camels, the precise size of their population worldwide is difficult to determine. Like other livestock species, Camels are susceptible to brucellosis (Abbas and Agab, 2002; Gwida et al., 2012).

Exposure to pathogenic bacteria and fungi can endanger human and animal health (Chinakwe et al., 2019; Lu et al., 2021; Sabrina Mahyuddin et al., 2020). Brucellosis is a zoonotic bacterial infection caused by gram-negative bacteria from the Brucella genus, classified as a risk group III pathogen by the WHO. The control of this widespread disease is of high economic importance in different camel-rearing countries (Abbas and Agab, 2002; Chinakwe et al., 2019; Gwida et al., 2012; Lu et al., 2021; Mahyuddin et al., 2020). Brucellosis in a camel through the B. abortus and B. melitensis has been documented in all camel-keeping countries except Australia (Alamian and Dadar, 2019; Wernery, 2014). Camel brucellosis can induce significant productivity loss by long calving interval time, low herd fertility, comparatively low milk production, and late first calving age. Other studies also reported that brucellosis is responsible for abortion, stillbirth, and decreased appetite in the camel population (Abdel Hafez et al., 2015; Warsame et al., 2020).

The disease also can play an important role in the import and export of animals constraining livestock trade. It has been estimated that the seroprevalence of brucellosis is low (2–5%) in camels reared under extensively or nomadic husbandry systems and relatively high (8–15%) in semi-intensively or intensively rearing husbandry systems (Abbas and Agab, 2002). However, despite the developments of surveillance and control programs for camel herds, the prevalence of brucellosis showed an increasing trend in different developing countries because of numerous socioeconomic, sanitary, and political risk factors (Corbel, 2006; Pappas, 2010). Therefore, the zoonotic threat of camel brucellosis should be considered a severe public health problem, particularly in camel- rearing areas (Sprague et al., 2012). Infected camels and their derived products could be a source of human brucellosis, leading to severe arthritis, fever, infertility, and in some cases, chronic infections following misdiagnosis (Corbel, 2006; Gutema Wegi, 2020).

For this reason, serological surveillance of camel brucellosis; isolation of infected camel; proper disposal of placental tissues, aborted fetus, and uterine discharge; and disinfecting of contaminated areas are of overwhelming importance for the successful prevention and control of camel brucellosis (Abbas and Agab, 2002; Sprague et al., 2012). However, no meta-analysis is available on the prevalence of camel brucellosis worldwide. The present meta- epidemiological study is aimed to evaluate the global prevalence of camel brucellosis and the associated risk factors impacting the transmission of Brucella infection.

Material and methods

Search strategy

The meta-analysis of published data on camel brucellosis was performed following the Cochrane protocol (Higgins and Green, 2011). The data were extracted and selected according to the PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analyses) method (Figure 1) (Liberati et al., 2009). Available databases were screened for all publications on camel brucellosis, including CABI, PubMed, Embase, Cochrane, Scielo, Scopus, Web of Science, and Science Direct to retrieve related papers on brucellosis in the camel population from 1 January 1980 to 1 April 2021. The Medical Subject Headings (MeSH) terms used in this study were “Malta Fever,” “Brucella infection,” “prevalence,” OR “camel,” OR “Brucella spp.” OR “B. melitensis” OR “B. abortus” OR “B. ovis” OR “brucellosis” OR “seroprevalence” OR “Camelus bactrianus” OR “Camelus dromedaries.” The selected articles were checked and cleaned in Endnote X7.8 for duplicates.

Figure 1. Flow chart of search processing based on Prisma.

Inclusion and exclusion criteria

The inclusion criteria in this study were considered as follows: (1) full-text article in English; (2) related subjects to camel brucellosis like infertility, for example, (3) original and descriptive investigations by qualitative or quantitative data, as case-control, cohort, cross-sectional, case reports, and case series studies; (4) research study on camel brucelloses like positive results and total sample sizes. In addition, clinical trials, thesis, books, workshops, and hosts other than camel and review article were excluded (Dadar et al., 2020; De Souza et al., 2021; Mokhtarian et al., 2020).

Data extraction

The data associated with camel brucellosis were extrac ted from all related articles that comprised the first author, geographic location, study period, type of sample, positive samples, diagnostic tests, isolated Brucella species, biovars, gender, and symptoms (if any). Articles were sorted according to detection method classification (direct (D) and indirect (ID)). Indirect methods such as serological tests could detect anti-Brucella antibodies in serum and milk, such as the Rose Bengal Test (RBT), Rivanol Test, Serum Agglutination Test (SAT), Milk Ring Test (MRT), 2-Mercaptoethanol Test (2-ME), Complement Fixation Test (CFT), the Fluorescence Polari zation Assay (FPA), Buffered Acidified Plate Antigen Test (BAPAT), Brucellosis Skin Test (BST), competitive Enzyme-Linked Immunosorbent Assay (c-ELISA), and indirect Enzyme-Linked Immunosorbent Assay (i-ELISA). The direct brucellosis diagnosis methods can be performed by bacterial culture and nucleic acid detection by molecular appro aches such as Real-Time or Quantitative Polymerase Chain Reaction (RT- or QPCR) and Polymerase Chain Reaction (PCR).

Meta-epidemiological analysis of camel brucellosis

The prevalence of camel brucellosis was calculated as a ratio of positive Brucella specimens to the total sample size. Meta-analysis of prevalence was conducted by metaprop command. The I-squared test (I² index) evaluated the heterogeneity among different studies, and it was verified if the I² > 50% (Higgins and Thompson, 2002). Furthermore, a random-effects model (REM) calculated the pooled odds ratio (OR) in the studies to investigate the pooled prevalence of camel brucellosi s in exanimated subgroups. Moreover, meta-regression analysis calculated the prevalence of camel brucellosis over time (Jackson et al., 2015; Stanley and Jarrell, 1989). Version 12.0 of the STATA software (STATA Corp, College Station, TX, USA) was used to evaluate the statistical analyses. The findings were investigated as significant when P-values were less than 0.05.

Results

Search results

Our results included 2426 studies dealing with camel brucellosis from different databases of CABI (n = 143), PubMed (n = 504), Web of Science (n = 311), Cochrane (n = 209), Scielo (n = 148), Embase (n = 297), Scopus (n = 621) and Science Direct (n = 193) (Figure 1). We analyzed 56 articles with 205 data reports based on the exclusion and inclusion rules. Articles published between 1 January 1980 and 1 April 2021 were included in the analysis (Figure 2). A total of 56 articles were acceptable and complied with the selection criteria. All eligible data listed in the “data extraction” section are available in Supplementary file 1.

Figure 2. Distribution of the number of studies on the prevalence of Brucella spp. in camels over time.

Geographical distribution of relevant studies in camel

The results of 56 articles (205 studies with a sample size of 134,949) (Figure 1) revealed that the number of studies investigating the occurrence of camel brucellosis in different regions varied from 46 studies in Egypt to one study in Niger (Table 1). In addition, the highest number of studies (n = 22) on camel brucellosis was observed in 2015 (Figure 2). However, no studies have focused on camel brucellosis in some countries such as Mauritania, Chad, Djibouti (countries with a high camel population), and Qatar and South Morocco (countries with an extremely high population of camels). The lowest and highest prevalence of camel brucellosis were observed in Oman (0.34%, 95%CI: 0.18–0.55) and Sudan (37.41%, 95%CI: 25.27–50.31), respectively (Table 1 and Figures 3 and 4).

Figure 3. Spatial distribution of the number of studies on the prevalence of Brucella spp. in camels.

Figure 4. Spatial distribution of the prevalence of Brucella spp. in camels.

Diagnostic methods

Table 2 showed that RBT (n = 50) and CFT (n = 43) were the most used tests for the diagnosis of camel brucellosis, followed by c-ELISA (n = 22), bacterial culture (n = 20), SAT (n = 19), PCR-based methods (n = 25), MRT (n = 5), 2-ME (n = 2), and i-ELISA (n = 2). The lowest and highest prevalence rates were reported by the MRT (3.46%) and the FPA (79.33%), respectively (Table 2). However, our results showed remarkable differences between the prevalence of camel brucellosis obtained through direct methods (15.08%) and indirect methods (8.49%) (Table 2).

Prevalence rates based on sample types and sampling methods

The biological specimens used for Brucella investigation in camels were, in the vast majority of cases, blood samples (n = 165 studies), followed by milk (n = 18 studies), lymph node (n = 13 studies), aborted fetus (n = 4 studies), vaginal swab (n = 3 studies), and semen (n = 1 study), while other samples, including abomasum contents (fetuses), and testes were not investigated (Table 2). Of note, testes were analyzed after experimental infection with B. abortus wild-type (n = 1) and B. abortus S19) vaccine (n = 5) but no Brucella strain has been isolated from these samples (Damir et al., 1989). Not surprisingly, aborted fetuses showed a higher prevalence of Brucella spp. with 29.23% when compared to those reported in lymph nodes (21.45%), vaginal swabs (9.54%), blood samples (8.60%), milk (8.30%), and semen (2.13%). In most studies, sampling was done among apparently healthy camels (in 155 out of 195 studies). Coherently, the prevalence of camel brucellosis was higher in animals with apparent symptoms such as wry neck syndrome (50%), knee hygroma (37.17%), arthritis (33.33%), abortion (7.74%), and the lowest rates of brucellosis were showed among animals with infertility (1.54%) (Table 3).

Overall brucellosis prevalence according to the gender of camel

This meta-analysis reported remarkable differences between the prevalence of camel brucellosis in females (9.64% among 62 studies) and males (6.83% in 41 studies). The gender of exanimated camels was not reported in 102 studies (Table 2).

Most prevalent Brucella spp. infecting camel

Although the isolation of B. melitensis (n = 29), B. abortus (n = 22), and Brucella suis (n = 1) from camel was reported in different investigations, the species level of Brucella isolates was not reported in 153 studies. Among identified Brucella spp., B. abortus biovar 6 showed the highest prevalence rate (71.88%), followed by B. abortus biovar 3 (14.58%), B. melitensis biovar 3 (12.06%), B. melitensis biovar 2 (8.92%), B. melitensis biovar 1 (3.4%), and B. abortus biovar 5 (3.13%). In some studies (n = 27), the biovar of Brucella spp. was not reported (prevalence rate of 10.26%)

Risk factor analysis of camel brucellosis

The risk factors, including geographical location, sex, herd size, age, and mixed rearing with other animals, can be considered the main risk factors for brucellosis in camels (Figure 5). Among data reports investigating the association between location and the occurrence of camel brucellosis, 60 reported a positive (n = 33) or negative (n = 27) association, whereas others found no evidence of a significant association (n = 145). Thirty-three studies have reported the effects of sex as a significant risk for brucellosis. Although the results of studies investigating the association between herd size and camel brucellosis were discording, most studies found a significant association (29 significant vs. 10 nonsignificant reports). Eighteen studies evaluating the effects of age reported an increased risk of brucellosis with greater age. Furthermore, several studies reported a significant association of mix herding/rearing with other livestock species and camel brucellosis (n = 39), although other studies showed a nonsignificant association (n = 10). Abortion history was only evaluated in 10 studies of the evaluated risk factors. Significant and insignificant associations were found in four and six studies, respectively.

Figure 5. Effective risk factors of Brucellosis in camels that considered in research studies.

Discussion

Brucellosis is a severe zoonotic disease in camel-rearing countries with serious economic consequences (Abbas and Agab, 2002; Gwida et al., 2012). Considering the close relationship between camels and humans, camel brucellosis should be an important public health issue (Alamian and Dadar, 2019; Dadar and Alamian, 2020; Sprague et al., 2012). Nevertheless, brucellosis in camels remains a neglected disease with low attention from health authorities and scientists. Since the first report of camel brucellosis in 1931 (Solonitsuin, 1949), the disease has been reported in all camel-raising areas worldwide. Although mixed herding with other livestock species was reported as a significant risk factor for camel brucellosis in 39 studies, no such association was seen in 10 studies. In this regard, Musa and his colleagues showed that cattle were a possible source of camel brucellosis because of the negative brucellosis results of all small ruminants screened in their study (Musa et al., 2008). In another study, close contact with small ruminants and cattle climbed to over 2.3 and 3.6 times the seropositivity of Brucella spp (Hadush et al., 2013). Our findings showed that the prevalence of camel brucellosis varied for different camel-rising countries over time. There are also significant differences in diagnostic tests, regional breeding technology, agro-ecology of camel-rising countries, husbandry and management systems, absence of adequate veterinary service, large-scale animal grazing, sharing of grazing pasture with other livestock species, lack of awareness about camel brucellosis, continuous movement of infected animals into a susceptible herd, cohabitation with other ruminants, as well as sanitation conditions (Abdelgawad et al., 2017; Gwida et al., 2012; Mokhtar et al., 2007; Sprague et al., 2012). In addition, illegal animal movement, unreported outbreaks, communal clashes, and the absence of brucellosis control programs in different regions are often combined factors contributing to the maintenance and establishment of camel brucellosis.

In some developing countries, the proportion of camels infected by Brucella spp. is relatively large because camel herds suffer from a lack of appropriate surveillance programs. Furthermore, the control of camel brucellosis is severely hampered in camel-raising countries (Sprague et al., 2012). Therefore, several strategies should be used to improve the situation of camel brucellosis and significantly decrease the occurrence of the disease, including encouragement of animal keepers for closer interaction with the veterinary organization and awareness about camel brucellosis and sustainable control approaches. In some countries, no or only a few studies have been performed, thereby stressing the need for further investigation into camel populations.

Our analysis shows that geographical location, sex, herd size, age, and mixed rearing are important risk factors for brucellosis in camels. Several studies showed a higher prevalence of brucellosis among adult camels >4 years old compared to 6 months to 4-year-old animals (Dawood, 2008; Khan et al., 2020; Salisu et al., 2018). Among the risk factors evaluated in camel brucellosis in Ethiopia, body condition and abortion showed a statistically significant difference concerning the seropositivity of camel brucellosis (Waktole et al., 2022). The seroprevalence and associated risk factors for camel brucellosis in Algeria showed a higher seroprevalence in animals living in flocks with a history of abortion and females (P = 0.01) (Benfodil et al., 2022). Moreover, it has been shown that the seroprevalence of brucellosis obtained by i-ELISA was 22.9% in the age group lower than 8 years, 27.9% in animals aged 8–11 years, and 25.7% among camels aged 13–15 years (Khan et al., 2020). In another study, the seroprevalence of camel brucellosis using RBT was remarkably higher (29.4%) in the 5–9 year age group compared to 0–4 ones (8%) (Abebe et al., 2017). The seroprevalence in females (9.64%) was significantly higher than in males (6.83%). Previous data show that females with a history of abortion reported a higher prevalence of camel brucellosis followed by pregnant and nonpregnant females (Fatima et al., 2016). Other studies also showed the antibodies of Brucella as frequently detected in males (7%) compared to females (8.3%) (Kudi et al., 1997). Such high seropositive rates in males may be related to the fact that the main populations of imported camels for slaughter are males (Khan et al., 2020). Therefore, abattoir surveys may have an important selection bias, and inferences about the local population must be made with caution. It has been suggested that female camels can transmit the infection to other livestock species by vaginal mucous, aborted fetuses, and milk (Al-Majali et al., 2008; Dadar et al., 2020). Limited data on aborted fetuses showed a high prevalence (29.23%), suggesting high prevalence and transmission rates in pregnant animals during the last 4 months of pregnancy (Al-Majali et al., 2008). Another study also highlighted that rearing camels with other ruminants were significantly associated with camel brucellosis (Fatima et al., 2016). Moreover, camel herds with more than 30 animals were more sustainable for brucellosis seropositivity (Ghanem et al., 2009). Mixed husbandry systems were associated with seropositive brucellosis camel herds (Ghanem et al., 2009). However, some reported risk factors, such as age, sex, breed, mixed herds, and locality, were unrelated in some studies (Khan et al., 2020; Ullah et al., 2015). Therefore, there is high demand for enrolment in control programs and increasing public health knowledge to prevent camel brucellosis. The RBT is a cost-effective and easy-to-use test that shows specific specificity and sensibility values, especially in endemic areas for camel brucellosis (Gwida et al., 2011). However, some nonspecific agglutination could occur due to the interference with nonspecific antibodies reported in other livestock species (OIE) and humans in endemic areas (Díaz et al., 2011). The CFT was used in different studies and compared favorably with other serological tests like the SAT that the OIE approves for the serological identification of brucellosis in livestock (Gwida et al., 2011; Sprague et al., 2012). The c-ELISA and i-ELISA have also been applied to detect anti-Brucella antibodies in camels. According to Gwida et al. (2011), the c-ELISA detected the lowest number of positive cases (68.8%) compared to the RBT (70.7%), the SAT (70.6%), the CFT (71.4%), and the FPA (79.3%). Another study also showed seroprevalence of camel brucellosis in south Algeria as 5.3 and 1.4% through the ELISA test and RBPT, respectively (Benfodil et al., 2022). The tests of RBT and CFT were also used as screening and confirmatory methods of camel brucellosis seroepidemiology in Ethiopia (Waktole et al., 2022). Tests that are not widely used are the FPA and the BST, both reported in one study. Our results suggest fewer clinical signs in Brucella-infected camels than in other ruminant animals. Indeed, 155 studies reported camel brucellosis in apparently healthy animals, and only 32 studies reported an abortion history in the herd. Other signs such as wry neck syndrome, knee hygroma, arthritis, orchitis, and infertility were also reported in some studies (Gutema and Tesfaye, 2019; Hussein, 2021; Musa et al., 2008). However, Musa and his colleagues showed no significant link between the wry neck syndrome in camels with brucellosis, although repeated abortion, hygroma, and arthritis were associated with the disease occurrence (Musa et al., 2008). Raising public awareness and education about the zoonotic importance of camel brucellosis, proper hygienic practices, control of risk factors, and multidisciplinary work between health and veterinary personnel should be improved (Admasu and Kaynata, 2017). Our research has limitations, such as a few studies on camel brucellosis in African countries such as Mauritania, Chad, and Djibouti (countries with a high population of camel livestock), Qatar, and South Morocco. The small sample size of camels in some studies made it difficult to determine the true prevalence of camel brucellosis in any specific locality.

Data related to the epidemiology of brucellosis in Bactrian camels have been reported infrequently in the international literature (Bayasgalan et al., 2018; Kim et al., 2016). Both studies were performed in Mongolia and suggested that Bactrian camels are secondary hosts for Brucella spp. A relevance between the seropositivity of cattle and camel, but not small ruminants, was described in different studies. The fact that Brucella isolates in camels were B. abortus further support an association between brucellosis in camels and cattle in Mongolia (Bayasgalan et al., 2018; Damir et al., 1989). Finally, it should be highlighted that there is an important knowledge gap related to anti-brucellosis vaccination in camels. Field data are sparse and often lack validation, while vaccine safety and efficacy have not been studied experimentally. Currently, there is no vaccine registered for use in camels, and thus vaccination is not recommended by the OIE.

Conclusion

Our knowledge of brucellosis in camels has increased over the last decade through comprehensive laboratory diagnosis, field analysis, and experimental infection trials. Infection with B. abortus and B. melitensis is frequent in different countries. The overall prevalence of camel brucellosis worldwide was 9.23%. The lack of prevention and control programs could make it a public health threat for the pastoral community. The highest incidence is when camels are kept together with infected small ruminants and bovines. A combination of direct methods and indirect methods can detect all positive reactors. However, isolation of the bacteria is still the golden test, although several molecular-based methods have been improved. Currently, no anti-brucellosis vaccine is recommended for use in camels by the OIE. Questions about the implementation of vaccination and the safety and efficacy of anti-Brucella vaccines in camels remain entirely open in endemic areas.