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. 2026 Sep 7;15(5):e70388. doi: 10.1002/mbo3.70388

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta‐Analysis

Aliasghar Fakhri‐Demeshghieh 1, Elnaz Rostamzaman 2, Fatemeh Sayareh 3, Amir Nikoukar 4, Faranak Farahani 5, Farniya Bakhtiary nia 5, Helia Sepahvand 5, Maryam Khaleghi 5, Mohammadsaeed Azamian 6, Mohammad Reza Shirzadi 7, Hesameddin Akbarein 6, Vahid Rahmanian 8,✉
PMCID: PMC13548425  PMID: 42703925

ABSTRACT

Background

Brucellosis is a multi‐systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta‐analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region.

Methods

PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta‐analysis was performed using a random‐effects model with Freeman–Tukey double arcsine transformation. Where applicable small‐study effects was assessed using funnel plots and Egger's test. Separate by‐country, by‐age, and by‐publication‐decade subgroup analyses were performed if feasible.

Results

Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n = 177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%–61%, I 2 = 96.63%). The evidences is up‐to‐date until March 4, 2024.

Conclusions

Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Keywords: brucellosis, meta‐analysis, Middle East, systematic review, West Asia

In 51.66% of the included studies in West Asia, the sample size was inadequate for at least half of the complications measured.

graphic file with name MBO3-15-e70388-g001.webp

1. Introduction

Brucellosis is a zoonotic infection caused by the species of Brucella particularly Brucella melitensis (Zhao et al. 2025). The transmission of brucellosis to humans generally occurs via the consumption of unpasteurized dairy products or contact with infected animals (Getachew et al. 2025). However, its airborne transmission has also been documented (Abd El‐Wahab 2025).

In humans, brucellosis infection is multi‐systemic (Safdari 2025). Brucellosis is able to cause complications such as osteo‐articular involvement, cardiovascular complications, hematologic complications, genitourinary complications, gastrointestinal involvement, respiratory involvement, nervous system involvement, cutaneous involvement, and ocular involvement (Pang et al. 2025; Khan et al. 2025). Brucellosis also has a low case fatality rate in humans with endocarditis being considered as the main cause of mortality (Bhat et al. 2024; Ragmoun et al. 2025; Wei et al. 2025). Moreover, for human brucellosis, it has been estimated that treatment costs per patient can range from 340 to 4095 dollars in severe cases (Oreiby et al. 2025). Early and accurate diagnosis of brucellosis is vital for its effective management and treatment (Shi et al. 2024).

The West Asia/Middle East region is an important global hotspot for brucellosis (Holloway et al. 2025) where brucellosis causes a significant public health challenge (Kaki et al. 2025). The pooled prevalence of Brucella spp in milk and other dairy products in the West Asia/Middle East region has been estimated to be 36% (95% confidence interval [CI]: 28%–54%) in raw cow milk, 13% (95%CI: −22% to 48%) in raw buffalo milk, 9% (95%CI: −16% to 35%) in cheese with the overall prevalence of Brucella spp. across all products being estimated to be 29% (95%CI: 23%–35%) (Abedi et al. 2020). The pooled prevalence of brucellosis in the West Asia/Middle East region has been estimated to be 20.45% (95% CI: 17.85%–23.19%) with the pooled prevalence being higher in Oman, Lebanon, Palestine, Jordan, and Kuwait (Dadar et al. 2024). However, the relative frequency of the complications of brucellosis in the West Asia/Middle East region is unknown.

Moreover, further research is required to better characterize the clinical course of brucellosis (Di Bari et al. 2022). Therefore, this systematic review and meta‐analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region.

2. Methods

This systematic review and meta‐analysis was designed and conducted according to the instructions of JBI Manual for Evidence Synthesis (Aromataris and Munn 2020) and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 (PRISMA 2020) statement (Page et al. 2021). The study protocol obtained official approval from the Ethics Committee of Torbat Jam Faculty of Medical Sciences [IR.TRJUMS.REC.1403.003].

2.1. Inclusion and Exclusion Criteria

The inclusion criteria were studies investigating the relative frequency of any of the complications of brucellosis in adults and children diagnosed with human brucellosis, confirmed through laboratory tests such as serology or Polymerase chain reaction (PCR), in countries within the West Asia region. We defined brucellosis complications as the involvement of any organs due to brucellosis. We accepted the clinical‐ and laboratory‐based definitions of the complications used by the authors of the included studies. The exclusion criteria consisted of studies written in languages other than English or Persian, studies without clear diagnostic confirmation of brucellosis, case reports, and studies on non‐human brucellosis cases.

2.2. Search Strategy

PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched using two blocks of keywords: “Brucella” OR “Brucellosis” OR “Malta Fever” and the list of countries. The search strategy was translated for each database. No restrictions based on date, language, study design, publication type, or the availability of data were made. This search strategy was a revision to the strategy that was stated in the protocol and it was revised to maximize the comprehensiveness of the search. The search was performed on March 4, 2024 except for Google Scholar for which the search was performed from March 2 to 4, 2024. The search strategy algorithms used for each database are presented in Supporting Information: Table S1. The references retrieved by the search were stored in an EndNote file. Duplicate results were omitted using the EndNote 20 software.

2.3. Title and Abstract Screening

ER, FS, AN, FF, FB, HS, MK, and MA independently screened the titles and abstracts of the results from each database. AFD resolved the conflicts risen on the inclusion of studies.

2.4. Data Extraction

AFD, AN, HS, MK, and MA independently extracted the data into Google Sheets. The data of each study was extracted independently by two review authors. Due to the limitation in the labor force, we only extracted data for 254 outcomes chosen based on their clinical importance and their frequency of being reported in the included studies. Inconsistencies on the extracted data were resolved by re‐checking the full‐text of the studies (by AFD) and reaching consensus. AFD emailed the corresponding authors of studies with incomplete outcome (numerator or denominator) data requesting the missing information. None of the corresponding authors of studies with incomplete outcome data provided the requested data. Therefore, the missing outcome data of those studies was not included. For studies that reported the percentage of a complication without reporting the numerators, we imputed the numerators according to the reported total number of brucellosis patients in the studies. For studies with two or more reports, we combined the data of the reports.

2.5. Risk of Bias Assessment

AFD, MA, and VR independently assessed the risk of bias of the included studies using JBI Critical Appraisal Checklist for Studies Reporting Prevalence data (Munn et al. 2015). The judgements for each item were stored in Google Sheets. Then, the judgements of the two review authors were compared. Conflicts risen on the risk of bias of the included studies were resolved with consensus.

2.6. Small‐Study Effects

For outcomes reported in 10 or more number of studies, funnel plots were drawn and Egger's test was performed to assess the small‐study effects. A p‐value of 0.05 was considered statistically significant.

2.7. Data Synthesis

We used the total number of patients with brucellosis as the denominator for the complications except sex‐specific complications for which we used the total number of brucellosis patients of that sex as the denominator and pregnancy‐related complications for which we used the number of pregnant women with brucellosis as the denominator. We used a random‐effects model for pooled estimation. We applied a Freeman‐Tukey double arcsine transformation before the synthesis in order to stabilize the variance. We used I‐squared and Q statistics to assess the heterogeneity. AFD performed the analyses using STATA 17.0.

2.8. Subgroup Analysis

Where feasible, we performed separate subgroup analyses for country, the age of participants (studies conducted on children vs studies conducted on adults), and publication period (2020–2024 vs. 2010–2019 vs. 2001–2009 vs. 1990–1999 vs. 1980–1989 vs. 1970–1979 vs. 1960–1969 vs. 1950–1959).

2.9. Sensitivity Analysis

For outcomes for which meta‐analysis was deemed feasible and contained at least three included studies, we performed sensitivity analysis with leave‐one‐out method.

2.10. Quality of Evidence

AFD and VR independently assessed the quality of evidence of for each outcome by adopting the applicable components (risk of bias, inconsistency, and imprecision) of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Disagreements on the certainty of evidence of the outcomes were resolved by discussion.

3. Results

3.1. Results of the Search

Initially, 9518 results were retrieved by the search. After the removal of 3163 duplicate results, the remaining 6355 results entered the stage of title‐and‐abstract screening of which 6086 results were omitted. In full text screening, nine studies were excluded. Finally, 240 studies belonging to 260 references were included (Figure 1).

Figure 1.

Figure 1

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Flow chart of the included studies.

3.2. Included Studies

Most of the included studies were conducted in Turkey (n = 117), Iran (n = 57), and Saudi Arabia (n = 34). There were 12 studies conducted in Occupied Palestine. Six studies were conducted in Kuwait. Three studies were conducted in Iraq, Jordan, and Oman each. Two studies were performed in Qatar while from Lebanon, United Arab Emirates, and Yemen only one study was included each. The majority of studies included participants of both sexes (n = 220) while 10 and seven studies only included males and females respectively. The sex of the participants was not given (NG) in three studies. 68 studies included brucellosis patients of all ages while 81 studies only contained adults and adolescence (adults‐only) and 61 studies only contained children participants (children‐only). The age of the participant was not reported in 30 studies (Table 1).

Table 1.

Characteristics of the included studies.

Study ID Publication year Country Type age Age average Sex Sample period
1 Abbasi 2020 (Abbasi 2020)  2020 Iran Mixed 34.17 ± 17.10 years Mixed 2011–2015
2 Abd Alrheam 2015 (Abd Alrheam 2015)  2015 Saudi Arabia Adults only NG Mixed 2010– 2014
3 Abdi‐Liae 2007 (Abdi‐Liae 2007)  2007 Iran Mixed Median: 38 years Mixed 1997–2002
4 Afify 2013 (Afify 2013) 2013 Saudi Arabia Children only 7.6 ± 1.8 years Mixed 2010–2011
5 Akbayram 2011 (Akbayram 2011a)  2011 Turkey Children only NG Mixed 2004–2010
6 Akbayram 2015 (Akbayram 2015, Karaman 2016)  2015 Turkey Children only 11.06 ± 4.3 years Mixed 2009–2015
7 Akcali 2007 (Akcali 2007) 2007 Turkey Mixed 45.81 ± 15.62 years Mixed 2000–2002
8 Akdeniz 1998 (Akdeniz 1998)  1998 Turkey NG NG Mixed 1994–1997
9 Akinci 2006 (Akinci 2006) 2006 Turkey NG NG Male 2001–2004
10 Akkoc 2023 (Akkoc 2023)  2023 Turkey Children only 136 ± 51.6 months Mixed 2017–2018
11 Al Hashan 2017 (Al Hashan 2017) 2017 Saudi Arabia Children only 6.1 ± 2.2 years Mixed 2013–2017
12 Al Nokhatha 2021 (Al Nokhatha 2021) 2021 United Arab Emirates Adults only 44 years Mixed 2009–2016
13 Al Sawafi 2023 (Al Sawafi 2023)  2023 Oman Children only 6.0 ± 3.8 years Mixed 2006–2020
14 Al Shamahy 2001 (Al Shamahy 2001) 2001 Yemen Mixed 25.6 years Mixed 1992–1993
15 Al‐Dubooni 1986 (Al‐Dubooni 1986) 1986 Iraq Children only NG Mixed 1983–1984
16 Al‐Eissa 1993 (Al‐Eissa 1993, Al‐Eissa 1993) 1993 Saudi Arabia Children only 7.8 years Mixed 1985–1991
17 Al‐Eissa1990 (Al‐Eissa 1990a, Al‐Eissa 1990b) 1990 Saudi Arabia Children only 8.2 years Mixed 1984–1987
18 Al‐Freihi 1986 (Al‐Freihi 1986) 1986 Saudi Arabia Mixed Median: 35 years Mixed 1981–1985
19 Al‐Koubaisy 2011 (Al‐Koubaisy 2011) 2011 Iraq Adults only NG Mixed 2009–2010
20 AlRashidi 2022 (AlRashidi 2022) 2022 Saudi Arabia Children only 8.2 ± 4.6 years Mixed 2021
21 Artuk 2019 (Artuk 2019) 2019 Turkey Mixed 25.62 ± 5.46 years Mixed 2001–2012
22 Aygen 2002 (Aygen 2002) 2002 Turkey Adults only 44.1 ± 16.4 years Mixed 1989–1998
23 Aypak 2012 (Aypak 2012) 2012 Turkey Mixed 25 ± 18.6 years Mixed 2010
24 Magableh 2007 (Magableh 2007) 2007 Jordan Mixed NG Mixed 1996–2006
25 Baykan 2019 (Baykan 2019) 2019 Turkey Mixed Median: 33 years Male 2014–2018
26 Bayram 1997 (Bayram 1997) 1997 Turkey Adults only NG Male 1992–1996
27 Beheshti 2001 (Beheshti 2001) 2001 Iran Mixed 30 Mixed NG
28 Behzadnia 2018 (Behzadnia 2018) 2018 Iran Children only 12.5 years Mixed 2010–2016
29 Benbir 2013 (Benbir 2013) 2013 Turkey Mixed 42.35 ± 16.46 years Mixed NG
30 Benjamin 1992 (Benjamin 1992, Benjamin 1992) 1992 Saudi Arabia Children only NG Mixed 1985–1990
31 Besharat 2010 (Besharat 2010) 2010 Iran Adults only NG Mixed NG
32 Bodur 2003 (Bodur 2003, Bodur 2004) 2003 Turkey Adults only 44.2 ± 17.7 years Mixed 2001–2002
33 Bozdemir 2017 (Bozdemir 2017) 2017 Turkey Children only Median: 130 months Mixed 2013–2016
34 Bozgeyik 2014 (Bozgeyik 2014) 2014 Turkey Mixed 50.2 years Mixed NG
35 Bozgeyik 2008 (Bozgeyik 2008) 2008 Turkey Mixed 52.8 years Mixed 2002–2007
36 Bukharie 2009 (Bukharie 2009) 2009 Saudi Arabia Adults only Median: 32 ± 9 years Mixed 1998–2007
37 Bulut 2011 (Bulut 2011) 2011 Turkey Adults only 44.0 ± 18.3 years Mixed 1999–2005
38 Caksen 2002 (Caksen 2002, Çaksen 2001) 2002 Turkey Children only 8.31 ± 3.58 years Mixed 1994–1998
39 Celen 2010 (Celen 2010) 2010 Turkey Adults only NG Male 1998–2006
40 Celik 2023 (Celik 2023) 2023 Turkey Adults only NG Male 2012–2022
41 Çelik 2023 (Çelik 2023) 2023 Turkey Adults only 41.79 ± 11.31 years Mixed 2018
42 Çiftdogan 2020 (Çiftdogan 2020) 2020 Turkey Children only 7.37 ± 4.14 years Mixed 2012–2013
43 Çirakli 2015 (Çirakli 2015) 2015 Turkey Children only 11 years Mixed 2008–2013
44 Conkar 2018 (Conkar 2018) 2018 Turkey Children only 12.7 ± 2.97 years Mixed 2013–2014
45 Coskun 2004 (Coskun 2004) 2004 Turkey NG NG NG NG
46 Coskun 2009 (Coskun 2009) 2009 Turkey Adults only Median: 26 years Male 1997–2008
47 Dabaja‐Younis 2023 (Dabaja‐Younis 2023) 2023 Occupied Palestine Mixed NG Mixed 2000–2021
48 Dal 2013 (Dal 2013) 2013 Turkey Adults only 33 years Mixed 2005–2009
49 Demir 2014 (Demir 2014) 2014 Turkey Adults only 40.9 ± 15.4 years Mixed 2012–2013
50 Demirtuerk 2008 (Demirtuerk 2008) 2008 Turkey NG NG Mixed 2002–2006
51 Ebrahimpour 2017 (Ebrahimpour 2017) 2017 Iran Mixed NG Mixed 2005–2015
52 Eini 2012 (Eini 2012a, Eini 2012b) 2012 Iran Mixed 40.84 ± 20.29 years Mixed 2005–2010
53 El Bayoumy 2014 (El Bayoumy 2014) 2014 Kuwait Mixed 42 years Mixed 2008–2012
54 Çiğdem 2019 (Çiğdem 2019) 2019 Turkey Children only 7.4 years Mixed 2016–2018
55 El‐Amin 2001 (El‐Amin 2001) 2001 Oman Children only 5.6 years±3.343 Mixed 1995–1998
56 El‐Koumi 2013 (El‐Koumi 2013) 2013 Saudi Arabia Children only 7.6 ± 1.8 years Mixed 2011–2012
57 Elhassanien 2014 (Elhassanien 2014) 2014 Kuwait Children only 9.5 ± 3.2 years Mixed 2008–2013
58 Elshamy 2008 (Elshamy 2008) 2008 Saudi Arabia Adults only 27 ± 6 years Female 2005–2007
59 Erat 2023 (Erat 2023) 2023 Turkey Children only 10.45 ± 4.36 years Mixed 2019–2021
60 Eroglu 2020 (Eroglu 2020) 2020 Turkey Adults only 38 years Mixed 2018
61 Ertek 2006 (Ertek 2006) 2006 Turkey Adults only NG Mixed 1985–2002
62 Esmailpour 2010 (Esmailpour 2010) 2010 Iran Mixed NG Mixed 1998–2006
63 Fallah 2005 (Fallah 2005) 2005 Saudi Arabia Mixed NG Mixed 1995–2001
64 Fruchtman 2020 (Fruchtman 2020, Fruchtman 2015) 2020 Occupied Palestine Children only 8.48 ± 4.81 year Mixed 2005–2012
65 Geyik 2002 (Geyik 2002) 2002 Turkey Mixed 33.14 ± 15.03 years Mixed 1992–2000
66 Golsha 2011 (Golsha 2011) 2011 Iran Adults only NG Mixed 2004–2008
67 Gonen 2014 (Gonen 2014) 2014 Turkey Adults only Median: 47.4 ± 17.1 years Mixed 2004–2012
68 Gottesman 1996 (Gottesman 1996) 1996 Occupied Palestine Children only NG Mixed 1987–1992
69 Gozdaz 2020 (Gozdas 2020) 2020 Turkey Adults only NG Male 2010–2018
70 Gul 2014 (Gul 2014) 2014 Turkey Adults only 25.62 ± 5.46 years Mixed 1997–2011
71 Guler 2014 (Guler 2014) 2014 Turkey Mixed 39.6 ± 18.2 years Mixed 2006–2012
72 Güngör 2002 (Güngör 2002) 2002 Turkey NG NG Mixed 1996–2000
73 Gür 2003 (Gür 2003) 2003 Turkey Mixed 32.69 ± 14.39 years Mixed 1992–2000
74 Hadadi 2009 (Hadadi 2009) 2009 Iran Mixed 35.5 ± 11.3 years Mixed 1998–2005
75 Hamid Hashemi 2016 (Hamid Hashemi 2016) 2016 Iran NG NG NG 2013–2014
76 Hasanjani Roushan 2016a (Hasanjani Roushan 2016a) 2016 Iran Mixed 34 ± 16.9 years Mixed NG
77 Hasanjani Roushan 2004 (Hasanjani Roushan 2004, Hasanjani Roushan 2006, Hasanjani Roushan 2004) 2004 Iran Adults only 36.97 ± 15 years Mixed 1997–2003
78 Hasanjani Roushan 2016b (Hasanjani Roushan 2016b) 2016 Iran Children only NG Mixed 2005–2015
79 Hashemi 2007 (Hashemi 2007) 2007 Iran Mixed 26.9 ± 19.2 years Mixed 2004–2005
80 Hassan 2021 (Hassan 2021) 2021 Oman Adults only Median: 31.5 years Mixed 2015–2018
81 Hatipoglu 2005 (Hatipoglu 2005) 2005 Turkey NG NG Mixed 2001–2003
82 Heidari 2011 (Heidari 2011) 2011 Iran NG 35 ± 19 years Mixed NG
83 Hizel 2007 (Hizel 2007) 2007 Turkey Adults only 43 years Mixed 1997–2003
84 Inan 2019 (Inan 2019) 2019 Turkey Adults only 28.8 ± 6.28 years Female 2002–2015
85 Issa 1999 (Issa 1999) 1999 Jordan Children only NG Mixed NG
86 Kaptan 2013 (Kaptan 2013) 2013 Turkey Adults only 49 years Mixed 2005–2008
87 Karaoglan 2008 (Karaoglan 2008) 2008 Turkey NG NG Mixed 2003–2006
88 Karli 2015 (Karli 2015) 2015 Turkey Children only NG Mixed 2008–2013
89 Kayaaslan 2016 (Kayaaslan 2016) 2016 Turkey Adults only 41.5 ± 17.0 years Mixed 2002–2014
90 Kazak 2016 (Kazak 2016) 2016 Turkey Adults only NG Mixed 1986–2012
91 Keyvanfar 2021 (Keyvanfar 2021) 2021 Iran Mixed 43.07 ± 18.521 years Mixed 2015–2020
92 Khateeb 1990 (Khateeb 1990, Khateeb 1988) 1990 Kuwait Mixed 33 years Mixed 1985–1986
93 Kokoglu 2006 (Kokoglu 2006) 2006 Turkey Adults only 32.2 ± 14.1 years Mixed 2000–2002
94 Kursun 2013 (Kursun 2013) 2013 Turkey Adults only 48 ± 17 years Mixed 2004–2011
95 Kurtaran 2012 (Kurtaran 2012) 2012 Turkey Adults only 40 ± 17 years Mixed 1997–2010
96 Kutlu 2018 (Kutlu 2018) 2018 Turkey Adults only 48.5 ± 15.9 year Mixed 2007–2016
97 Lazutkin 2018 (Lazutkin 2018) 2018 Occupied Palestine Mixed 36 years Mixed 2007–2016
98 Madkour 1988 (Madkour 1988) 1988 Saudi Arabia Mixed NG Mixed 1986–1987
99 Majzoobi 2023 (Majzoobi 2023) 2023 Iran Adults only 27.84 ± 6.13 years Female 2018–2020
100 Malik 1997 (Malik 1997) 1997 Saudi Arabia Adults only 32 years Mixed 1986–1989
101 McLean 1992 (McLean 1992) 1992 Saudi Arabia NG NG Mixed 1983–1991
102 Megged 2016 (Megged 2016) 2016 Occupied Palestine Mixed NG Mixed 2014
103 Ulug 2011 (Ulug 2011) 2011 Turkey Adults only 36.4 ± 14.2 years Mixed 2007–2008
104 Mermut 2011 (Mermut 2011) 2011 Turkey Adults only NG Mixed 1996–2008
105 Mohamed 1986 (Mohamed 1986) 1986 Saudi Arabia Mixed NG Mixed 1981–1982
106 Mohammad Saeed 2012 (Mohammad Saeed 2012) 2012 Iran Children only 8.02 years Mixed 2003–2006
107 Mousa 1988 (Mousa 1988a, Mousa 1988b, Mousa 1987) 1988 Kuwait Mixed NG Mixed 1983–1986
108 Mugahi 2014 (Mugahi 2014) 2014 Iran Mixed 38.1 years Mixed 1998–2007
109 Nabavi 2019 (Nabavi 2019) 2019 Iran Mixed 39.59 ± 17.28 years Mixed 2009–2015
110 Najari 2018 (Najari 2018) 2018 Iran Adults only 42.5 ± 18.3 years Mixed 2012–2015
111 Namiduru 2003 (Namiduru 2003, Namiduru 2004) 2003 Turkey Adults only NG Mixed 1995–2000
112 Norton 1984 (Norton 1984) 1984 Saudi Arabia Mixed NG Mixed 1977‐1984
113 Okur 2012 (Okur 2012) 2012 Turkey Children only 9.14 ± 3.4 years Mixed 2009–2010
114 Özdem 2022 (Özdem 2022) 2022 Turkey Children only Median: 10.4 years Mixed 2005–2021
115 Özen 2022 (Özen 2022) 2022 Turkey Children only Median: 11.3 years Mixed 2018–2021
116 Parlak 2015 (Parlak 2015) 2015 Turkey Children only 10.0 ± 3.95 years Mixed 2009–2013
117 Rajapakse 1987 (Rajapakse 1987) 1987 Saudi Arabia NG NG Mixed 1982–1985
118 Rashad 2019 (Rashad 2019) 2019 Saudi Arabia Children only NG NG 2016–2017
119 Roushan 2005 (Roushan 2005) 2005 Iran Children only 10.49 ± 3.49 years Mixed 1999–2003
120 Roushan 2011 (Roushan 2011) 2011 Iran Adults only 25.0 ± 4.62 years Female 2000–2010
121 Salman 2022 (Salman 2022) 2022 Turkey Children only 10.7 ± 4.5 years Mixed 2011–2021
122 Sanivar 2017 (Sanivar 2017) 2017 Turkey Adults only 37.90 ± 13.64 years Mixed 2013–2014
123 Savas 2007 (Savas 2007) 2007 Turkey Mixed 45.81 ± 15.62 years Mixed 2000–2002
124 Savion 2023 (Savion 2023) 2023 Occupied Palestine Children only 11.01 ± 4.914 years Mixed 2010–2020
125 Sayad 2019 (Sayad 2019) 2019 Iran NG NG Mixed 2011–2016
126 Shahnaz 2007 (Shahnaz 2007) 2007 Iran Children only 7.3 years Mixed 1996–2005
127 Shalev 1994 (Shalev 1994) 1994 Occupied Palestine Children only NG Mixed 1989
128 Zia Sheikholeslami 2007 (Zia Sheikholeslami 2007) 2007 Iran NG NG Mixed 2006
129 Simsek 2011 (Simsek 2011) 2011 Turkey NG NG Mixed 1998–2008
130 Somily 2017 (Somily 2017) 2017 Saudi Arabia Mixed 29 ± 8 years Mixed 2003–2013
131 Sungur 2009 (Sungur 2009) 2009 Turkey Mixed NG Mixed 1992–2006
132 Tanir 2009 (Tanir 2009) 2009 Turkey Children only 9.02 ± 3.59 years Mixed 1997–2006
133 Tasbakan 2003 (Tasbakan 2003) 2003 Turkey Adults only 40.2 years Mixed 1996–2001
134 Tasova 1999 (Tasova 1999) 1999 Turkey Adults only 32.3 ± 14 years Mixed 1990–1997
135 Teke 2015 (Teke 2015) 2015 Turkey Children only NG Mixed 2005–2011
136 Tekin 2012 (Tekin 2012) 2012 Turkey Adults only 32.8 ± 15.3 Mixed 2007–2009
137 Tohmé 2004 (Tohmé 2004, Tohme 2004, Tohmé 2001) 2004 Lebanon Mixed 38 ± 21 years Mixed 1994–2003
138 Turan 2011 (Turan 2011) 2011 Turkey Adults only 46.7 ± 18 years Mixed 2003–2009
139 Ulu‐Kilic 2013 (Ulu‐Kilic 2013) 2012 Turkey NG NG Mixed 2008–2011
140 Varikkodan 2024 (Varikkodan 2024) 2024 Qatar Adults only 39.6 ± 15.05 years Mixed 2015–2020
141 Yetkin 2005 (Yetkin 2005, Yetkin 2006a, Yetkin 2006b) 2006 Turkey Adults only NG Mixed 1999–2004
142 Yilmaz 2004 (Yilmaz 2004) 2004 Turkey NG NG Mixed 1986–2001
143 Zaks 1995 (Zaks 1995) 1995 Occupied Palestine Mixed 25 years Mixed 1972–1990
144 Zamani 2011 (Zamani 2011) 2011 Iran Children only NG Mixed 1997–2005
145 Abbasi 2012 (Abbasi 2012, Asadipooya 2011) 2012 Iran NG NG Mixed NG
146 Alsubaie 2005 (Alsubaie 2005) 2005 Saudi Arabia Mixed NG Mixed 2001–2002
147 Kayaaslan 2013 (Kayaaslan 2013) 2013 Turkey Adults only 47 ± 17 years Mixed 2005–2008
148 Kiel 1987 (Kiel 1987) 1987 Saudi Arabia NG 32 years Mixed 1983–1986
149 Akbayram 2011 (Akbayram 2011b) 2011 Turkey Children only NG Mixed 2004‐2010
150 Kisacik 2011 (Kisacik 2011) 2011 Turkey NG 32.2 ± 10.1 years Mixed NG
151 Sagi 2017 (Sagi 2017) 2017 Occupied Palestine Adults only 39.2 ± 16.1 years Mixed 2015–2016
152 Mousa 1986 (Mousa 1986) 1986 Kuwait NG NG Mixed 1985
153 Kutlu 2009 (Kutlu 2009) 2009 Turkey Adults only 43.08 ± 15.3 years Mixed 2003–2004
154 Hasanjani Roushan 2009 (Hasanjani Roushan 2009) 2009 Iran NG NG Male 1998–2008
155 Samra 1983 (Samra 1983) 1983 Occupied Palestine Mixed NG Mixed 1955–1977
156 Feiz 1978 (Feiz 1978) 1978 Iran Children only Median: 9.7 years Mixed NG
157 Turunç 2008 (Turunç 2008) 2008 Turkey Adults only NG Mixed 2001–2006
158 Naz 2009 (Naz 2009) 2009 Turkey Adults only 46.93 ± 17.65 years Mixed 2001–2006
159 Opawoye 1994 (Opawoye 1994) 1994 Saudi Arabia Children only NG Mixed 1992–1993
160 Al Shaalan 2002 (Al Shaalan 2002) 2002 Saudi Arabia Children only 5.8 years Mixed 1984–1995
161 Memish 2001 (Memish 2001) 2001 Saudi Arabia Adults only NG Mixed 1991–2000
162 Nabi 1992 (Nabi 1992) 1992 Saudi Arabia Children only NG Mixed NG
163 Gulsun 2011 (Gulsun 2011) 2011 Turkey Adults only 28.07 years Female 2003–2010
164 Kurdoglu 2010 (Kurdoglu 2010) 2010 Turkey Adults only 26.79 ± 5.07 years Female 2003–2008
165 Khan 2001 (Khan 2001) 2001 Saudi Arabia Adults only 26.9 years Female 1983–1995
166 Rahil 2014 (Rahil 2014) 2014 Qatar Adults only NG Mixed 2000–2006
167 Qasim 2020 (Qasim 2020) 2020 Saudi Arabia Children only 7.75 ± 3.28 years Mixed 2015–2019
168 Suvak 2016 (Suvak 2016) 2016 Turkey Adults only 33.6 years Mixed 2013–2014
169 Türker 2014 (Türker 2014) 2014 Turkey Adults only NG Mixed 1997–2012
170 Patel 1988 (Patel 1988) 1988 Saudi Arabia Mixed NG Mixed NG
171 Ertekin 2004 (Ertekin 2004) 2004 Turkey Children only 7.1 ± 4.2 years Mixed 1996–2001
172 Torkaman 2017 (Torkaman 2017) 2017 Iran Mixed 41.1 ± 17.2 years Mixed 2013–2014
173 Naz 2016 (Naz 2016) 2016 Turkey Adults only NG Male 2001–2013
174 Uluğ 2011 (Uluğ 2011) 2011 Turkey Children only 8.9 ± 2.8 years Mixed 2007–2008
175 Yoldas 2015 (Yoldas 2015) 2015 Turkey Children only 10 ± 3.8 years Mixed 2000–2010
176 Buzgan 2010 (Buzgan 2010) 2010 Turkey Mixed 33.7 ± 16.34 years Mixed 1998–2007
177 Edathodu 2021 (Edathodu 2021) 2021 Saudi Arabia Adults only Median: 50 years Mixed 2003–2018
178 Köse 2014 (Köse 2014) 2014 Turkey Adults only 44.8 ± 18 years Mixed 2004–2010
179 Fanni 2013 (Fanni 2013) 2013 Iran Children only 6.88 years Mixed 2002–2010
180 Kaman 2022 (Kaman 2022) 2022 Turkey Children only 9.4 ± 4.7 years Mixed 2005–2018
181 Keramat 2009 (Keramat 2009) 2009 Iran Adults only 40.69 years Mixed 2002–2006
182 Keramat 2018 (Keramat 2018) 2018 Iran Adults only NG Mixed 2016–2017
183 Metin 2001 (Metin 2001) 2001 Turkey Mixed 30.45 ± 15.08 years Mixed NG
184 Kaya 2018 (Kaya 2018) 2018 Turkey Adults only 33.88 ± 14.96 years Mixed 2009–2013
185 Shehabi 1990 (Shehabi 1990) 1990 Jordan Mixed 27±17years Mixed 1987
186 Aktug‐Demir 2014 (Aktug‐Demir 2014) 2014 Turkey Adults only 43.1 ± 15.2 years Mixed 2010–2012
187 Najafi 2018 (Najafi 2018, Najafi 2014) 2014 Iran Mixed 41.6 ± 16.9 years Mixed 2009–2014
188 Rahmanpour 2019 (Rahmanpour 2019)  2019 Iran NG 39.89 ± 16.11 years Mixed 2017–2018
189 Majzoobi 2018 (Majzoobi 2018) 2018 Iran Adults only NG Mixed 2015–2016
190 Saltoglu 2002 (Saltoglu 2002) 2002 Turkey Adults only 36.8 ± 11.3 years Mixed 1997–2001
191 Pourbagher 2006 (Pourbagher 2006) 2006 Turkey Mixed NG Mixed 2000–2004
192 Pourakbari 2019 (Pourakbari 2019) 2019 Iran Children only 7.02 ± 3.5 years Mixed 2011–2016
193 Firouzeh 2019 (Firouzeh 2019) 2019 Iran Mixed NG Mixed 2013–2018
194 El‐Kafas 1999 (El‐Kafas 1999) 1999 Saudi Arabia Children only NG Mixed 1996–1998
195 Mohammadbeigi 2021 (Mohammadbeigi 2021) 2021 Iran Mixed 39.87 ± 19.93 years Mixed 2015–2019
196 Hatami 2019 (Hatami 2019) 2019 Iran Mixed 35.05 ± 17.35 years Mixed 2012–2016
197 Hatami 2010 (Hatami 2010) 2010 Iran Mixed NG Mixed 1988–2005
198 Ayatollahi 2004 (Ayatollahi 2004) 2004 Iran Mixed NG Mixed 1995–2001
199 Sabbaghian 1974 (Sabbaghian 1974) 1974 Iran Mixed NG Mixed 1967–1972
200 Vafaei 2019 (Vafaei 2019) 2019 Iran Children only 80.5 months Mixed 2007–2016
201 Biglarzadeh 2020 (Biglarzadeh 2020)  2020 Iran NG NG Mixed 2013–2017
202 Kuruoglu 2023 (Kuruoglu 2023) 2023 Turkey Adults only 46.4 ± 15.8 years Mixed 2010–2022
203 Demir 2021 (Demir 2021) 2021 Turkey Children only 122 ± 54 months Mixed 2017–2019
204 Zilberman 2022 (Zilberman 2022) 2022 Occupied Palestine Mixed NG Mixed 2017–2019
205 Bayazit 2002 (Bayazit 2002) 2002 Turkey Adults only 40.5 years Mixed NG
206 Citak 2010 (Citak 2010) 2010 Turkey Children only NG Mixed 2004–2009
207 Aypak 2015 (Aypak 2015) 2015 Turkey Mixed 14.5 ± 3.3 years Mixed 2010–2011
208 Gholami 2012 (Gholami 2012) 2012 Iran NG NG Mixed 2009–2011
209 Shimol 2012 (Shimol 2012) 2012 Occupied Palestine Mixed NG Mixed 2011
210 Mohamed 2018 (Mohamed 2018) 2018 Iraq Adults only NG Mixed 2017–2018
211 Ibrahim 2021 (Ibrahim 2021) 2021 Saudi Arabia Mixed 35.1 ± 21.2 years Mixed 2015–2019
212 Hashemi 2018 (Hashemi 2018) 2018 Iran NG 42.2 ± 18.1 years Mixed 2016
213 Eskandari‐Nasab 2014 (Eskandari‐Nasab 2014) 2014 Iran Mixed 31.24 ± 16.6 years Mixed NG
214 Kaygusuz 2005 (Kaygusuz 2005) 2005 Turkey Mixed 31.62 ± 13.97 years Mixed 1999–2002
215 Sayin‐Kutlu 2012 (Sayin‐Kutlu 2012) 2012 Turkey Adults only 32 ± 6 years Mixed 2010–2011
216 Sari 2008 (Sari 2008) 2008 Turkey Adults only NG Mixed 1999–2005
217 Demiraslan 2009 (Demiraslan 2009) 2009 Turkey Adults only NG Mixed 1997–2006
218 Guven 2013 (Guven 2013) 2013 Turkey Adults only NG Mixed 2002–2005
219 Ranjbar 2009 (Ranjbar 2009) 2009 Iran NG NG Mixed 2001–2005
220 Karabay 2004 (Karabay 2004) 2004 Turkey Adults only NG Mixed 1999–2001
221 Karakurt 2023 (Karakurt 2023) 2023 Turkey NG NG Mixed 2016–2018
222 Ertem 2004 (Ertem 2004) 2004 Turkey Adults only 43 years Mixed 1999–2002
223 Paul 2017 (Paul 2017) 2017 Saudi Arabia Mixed 28.50 ± 13.65 years Mixed 2014–2016
224 Karakukcu 2004 (Karakukcu 2004) 2004 Turkey Children only NG Mixed 1996–2003
225 Olt 2015 (Olt 2015) 2015 Turkey NG 41.7 ± 16.1 years Mixed NG
226 Sen 2019 (Sen 2019) 2019 Turkey Adults only 45.4 ± 17.4 years Mixed 2010–2016
227 Kara 2019 (Kara 2019) 2019 Turkey Children only 10.9 ± 3.9 years Mixed 2015
228 Aghaali 2015 (Aghaali 2015) 2015 Iran Children only NG Mixed 2013
229 Ahmadinejad 2016 (Ahmadinejad 2016) 2016 Iran Mixed 27.6 ± 20.6 years Mixed 2012
230 Lubani 1989 (Lubani 1989) 1989 Kuwait Mixed NG Mixed NG
231 Salari 2003 (Salari 2003) 2003 Iran Mixed NG Mixed 1993–1998
232 Cuzdan 2022 (Cuzdan 2022) 2022 Turkey Adults only 46.58 ± 15.43 years Mixed 2017–2020
233 Alim 2015 (Alim 2015) 2015 Turkey Mixed NG Mixed 2011
234 Kahbazi 2012 (Kahbazi 2012) 2012 Iran Children only NG Mixed 2011
235 Lifeso 1985 (Lifeso 1985) 1985 Saudi Arabia NG NG Mixed 1976–1983
236 Kadanali 2005 (Kadanali 2005) 2005 Turkey Adults only 33.7 ± 15.8 years Mixed 2001–2004
237 Rezazadeh 2006 (Rezazadeh 2006) 2006 Iran Mixed 40.8 ± 19 years Mixed 2004–2005
238 Çiftdoğan 2017 (Çiftdoğan 2017) 2017 Turkey Mixed NG Mixed 2012–2013
239 Najafi 2011 (Najafi 2011) 2011 Iran NG NG Male 1997–2009
240 Ergun 2008 (Ergun 2008) 2008 Turkey Adults only NG Mixed 2004–2005
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Abbreviation: NG, not given.

Overall, the data of 61,171 individuals with brucellosis were synthesized in this systematic review. Among the studies that reported the sex of the individuals, 29,481 individuals were male while 15,671 of the individuals were female. The majority of individuals were studied only in hospital settings either as inpatients or outpatients (N = 185) while in nine additional studies, the subjects were from hospitals combined with another source including medical school (N = 1), health station (N = 1), patient family members (N = 3), and clinic (N = 4). Four studies were conducted solely in community settings. Among the studies that reported the method of diagnosis of Brucellosis, the majority used a combination of diagnostic methods such as bacterial cultures and/or clinical findings combined with serology techniques such as 2‐mercaptoethanol (2‐ME). Serology techniques were the predominant methods of diagnosis and were used in the eligibility criteria in 220 studies while bacterial isolation/culture procedures were used as an inclusion criterion in 173 studies. PCR was only used in two studies (Supporting Information: Table S2–1).

Among the included studies, the reported complications varied and different categorizations were detected. Some studies had used system‐level outcomes such as osteoarticular involvement, musculoskeletal involvement, and nervous system involvement while some studies measured organ‐level involvement such as orchitis, kidney involvement, and lung involvement while other studies studied more specific outcomes such as nephrotic syndrome, hydrocephalus, optic neuritis, and endocarditis. Some studies used vague outcomes such as “spondylitis or sacroillitis”, “paravertebral or psoas abscess”, “permanent aspermia or oligospermia”, “pneumonitis or bronchiolitis”, “focal involvement”, and “local abscess”. The full list of the 254 included outcomes is reported in Supporting Information: Table S3–1.

3.3. Excluded Studies

We excluded nine studies due to Non‐representativeness and high non‐response in full‐text screening (Table 2).

Table 2.

Characteristics of excluded studies.

Study ID Reason for exclusion
1 Aydin 2005 (Aydin 2005) Not representative
2 Rahmanian 2019 (Rahmanian 2019) Not representative
3 Young 2014 (Young 2014) High non‐response
4 Rathi 1993 (Rathi 1993) Not representative
5 Dokuzoğuz 2005 (Dokuzoğuz 2005) Not representative
6 Erdem 2016 (Erdem 2016) Not representative
7 Eren 2006 (Eren 2006) Not representative
8 Guenlue 2022 (Guenlue 2022) Not representative
9 Mousa 1990 (Mousa 1990) Not representative
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3.4. Risk of Bias in Included Studies

Overall, the highest risk of bias in the included studies was related to inappropriateness of the sample frame (studies limiting their inclusion criteria to children or adults) and the inadequacy of their sample sizes in relation to the complications whose relative frequency they were to measure. In 51.66% of the included studies, the sample size was inadequate for at least half of the complications measured in the study. The risk of bias was summarized in Supporting Information: Table S4–1 per study while the overall risk of bias for each outcome was reported in Supporting Information: Tables S4–2 to S4‐255.

3.5. Effect Sizes

We were able to perform meta‐analysis for 152 outcomes while for the rest, only one study was included for each of them and meta‐analysis was not feasible. For those outcomes, we reported the point estimates of the single studies instead. In the main‐text, we focused on the outcomes with more clinical importance or with interesting findings. The pooled estimates of all meta‐analyses are reported in Supporting Information: Table S3–1. The funnel plots of the complications with at least 10 number of included studies are presented in Supporting Information: Figures S5–1 to S5‐40. The findings of sensitivity analysis are presented in Supporting Information: Figures S6–1 to S6‐105. The findings of subgroup analyses by country, age group, and publication year are reported in Supporting Information: S7 (Figures S7–1 to S7‐152), S8 (Figures S8–1 to S8‐126), and S9 (Figures S9–1 to S9‐152). The quality of evidence for each outcome is reported in Supporting Information: Table S10–1. The PRISMA checklist is reported in Supporting Information: S11. The pooled estimates of 10 selected complications are presented in Figure 2.

Figure 2.

Figure 2

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Pooled estimates of 10 selected complications of brucellosis in West Asia.

3.6. Complications of the Bones, Joints, Tendons, and Paravertebral or Periarticular Soft Tissue

The pooled estimates for arthritis or peripheral arthritis, spondylodiscitis, and sacroilitis were 20% (95%CI: 17%–23%, I 2 = 97.70%; very low certainty of evidence), 14% (95%CI: 11%–18%, I 2 = 92.05%; very low certainty of evidence), and 13% (95%CI: 11%–16%, I 2 = 96.56%; very low certainty of evidence), respectively. The funnel plots of musculoskeletal involvement, osteoarticular involvement, spondylitis, spondylodiscitis, spinal brucellosis, arthritis or peripheral arthritis, and osteomyelitis showed signs of small‐study effects. Egger's test was statistically significant for Arthritis or peripheral arthritis (p < 0.001). For the rest of the outcomes in this category, Egger's test was not statistically significant (p > 0.05). In sensitivity analysis with leave‐one‐out method, the pooled estimates for skeletal involvement and arthropathy were found to be not robust. The pooled estimates for the rest of the outcomes in this category were deemed to be robust.

In subgroup analysis by country, the pooled estimate of sacroilitis was higher in Turkey (15%, 95%CI: 11%–19%) and Iran (14%, 95%CI: 8%–21%). The highest pooled estimates of spondylitis (9%, 95%CI: 6%–13%) and spondylodiscitis (15%, 95%CI: 12%–18%) were observed in Turkey. The pooled estimate of spinal brucellosis was the highest in Saudi Arabia (14%, 95%CI: 3%–32%). The pooled estimate for arthritis or peripheral arthritis was the highest in Kuwait (41%, 95%CI: 26%–58%). The pooled estimate of Occupied Palestine for osteomyelitis (8%, 95%CI: 3%–16%) was the highest. The pooled estimate for bursitis in Turkey (2%, 95%CI: 1%–3%) was the highest.

In subgroup analysis by age, the pooled estimate of sacroilitis was 15% (95%CI: 11%–20%) in adults‐only studies vs 4% (95%CI: 2%–6%) in children‐only studies. The pooled estimate of Spondylitis in adults‐only studies was 11% (95%CI: 7%–14%) while in children‐only studies, the pooled estimate was 1% (95%CI: 0%–2%). However, the pooled relative frequency of Arthritis or peripheral arthritis was higher in children‐only studies (33%, 95%CI: 28%–39%) compared to adults‐only studies (11%, 95%CI: 8%–14%).

3.7. Complications of the Genito‐Urinary System

Among the sex‐specific complications of genito‐urinary system, the pooled estimates for epididymoorchitis was 7% (95%CI: 6%–9%, I 2 = 90.94%; very low certainty of evidence). The pooled estimates for urinary system complications (nephritis, nephrotic syndrome, renal failure, renal abscess, and kidney involvement) were less than 1% and they were rated as very low quality of evidence. The funnel plots of genito‐urinary system involvement, orchitis, and epididymoorchitis depicted signs of small‐study effects. Egger's test was statistically significant for orchitis (p = 0.004) and epididymoorchitis (p < 0.001). For the rest of the outcomes in this category, Egger's test was not statistically significant (p > 0.05). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes in this category were deemed to be robust.

In subgroup analysis by country, the pooled estimates of orchitis in male patients (very low certainty of evidence) in Iran (7%, 95%CI: 3%–11%) and Occupied Palestine (7%, 95%CI: 1%–16%) were higher compared to Turkey (4%, 95%CI: 2%–7%) while the pooled estimate of epididymoorchitis was the highest in Iran (9%, 95%CI: 7%–12%) and Kuwait (9%, 95%CI: 7%–12%). Prostatitis (very low certainty of evidence) was only reported in Turkey.

In subgroup analysis by age, the pooled estimate of orchitis in male patients was higher in adults‐only studies (5%, 95%CI: 2%–8%) compared to children‐only studies (1%, 95%CI: 0%–3%). Similarly, epididymoorchitis was more common in adults‐only studies (7%, 95%CI: 5%–9%) compared to children‐only studies (3%, 95%CI: 0%–7%).

In subgroup analysis based on publication year, for orchitis and epididymoorchitis, the pooled estimates for studies published between 2020 and 2024 were 0% (95%CI: 0%–1%, I 2 = 55.15%) and 3% (95%CI: 2%–5%, I 2 = 84.65%) and were lower than studies published between 2010 and 2019 (7%, 95%CI: 5%–9%, I 2 = 58.72% and 8%, 95%CI: 7%–10%, I 2 = 69.98%).

3.8. Complications of the Lymphatic System

In this category, the pooled estimate for lymphadenopathy was the highest (9%, 95%CI: 7%–10%, I 2 = 91.89%; very low certainty of evidence). The funnel plot of lymphadenopathy showed signs of small‐study effects. However, Egger's test was not statistically significant (p = 0.07). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes in this category were deemed robust.

In subgroup analysis by country, the highest pooled estimate for lymphadenopathy was reported in Occupied Palestine (16%, 95%CI: 11%–22%) while a single study in Yemen in 2001 reported the point estimate of 34% (95%CI: 28%–40%).

In subgroup analysis by age, the pooled estimate of lymphadenopathy was higher in children‐only studies (14%, 95%CI: 10%–19%) compared to adults‐only studies (6%, 95%CI: 5%–8%).

3.9. Complications of the Nervous System and Psychologic Disorders

In this category, the pooled estimates for meningitis, brain abscess, and cranial nerve involvement were 3% (95%CI: 2%–3%, I 2 = 80.26%; very low certainty of evidence), 1% (95%CI: 1%–3%, I 2 = 71.06%; very low certainty of evidence), and 2% (95%CI: 1%–3%, I 2 = 44.26%; very low certainty of evidence). Except for one outcome (deep sensory loss) for which meta‐analysis was not feasible, all the outcomes in this category were rated as very low certainty of evidence. The funnel plots of nervous system involvement, central nervous system involvement, neurobrucellosis, neuropsychiatric involvement, meningitis, cranial nerve involvement, hearing loss, and depression showed signs of small‐study effects. Egger's test was not statistically significant for any of the outcomes in this category (p > 0.05). In sensitivity analysis with leave‐one‐out method, the pooled estimate for psychiatric involvement was not robust. For the rest of the outcomes, the pooled estimates were deemed to be robust in this category.

In subgroup analysis by country, the pooled estimate for neurobrucellosis was higher in Turkey (4%, 95%CI: 3%–6%) and Iran (4%, 95%CI: 2%–6%) while in Occupied Palestine, its pooled estimate was less than 1% (95%CI: 0%–1%). Cranial nerve involvement was only reported in Turkey (2%, 95%CI: 1%–4%) and a single study in Kuwait (2%, 95%CI: 1%–4%). The pooled estimate for hearing loss in Turkey (2%, 95%CI: 0%–6%) was higher than Saudi Arabia (1%, 95%CI: 0%–3%). The pooled estimate for depression was the highest in Iran (8%, 95%CI: 0%–36%).

In subgroup analysis by age, the pooled estimate of central nervous system involvement was higher in adults‐only studies (5%, 95%CI: 2%–9%) compared to children‐only studies (less than 1%, 95%CI: 0%–2%). The pooled estimate of neurobrucellosis was higher in adults‐only studies (4%, 95%CI: 3%–6%) compared to children‐only studies (2%, 95%CI: 1%–3%) The pooled estimate of meningitis was higher in adults‐only studies (4%, 95%CI: 2%–5%) compared to children‐only studies (1%, 95%CI: 0%–4%).

In subgroup analysis based on publication year for meningitis, the pooled estimate of the subgroup of studies published between 2020 and 2024 (1%, 95%CI: 0%–2%, I 2 = 0%) was lower compared to studies published between 2010 and 2019 (3%, 95%CI: 2%–4%, I 2 = 72.73%). For cranial nerve involvement, the pooled estimate of the subgroup of studies published between 2010 and 2019 (4%, 95%CI: 2%–7%, I 2 not calculable) was higher compared to studies published between 2000 and 2009 (1%, 95%CI: 0%–2%, I 2 = 11.91%).

3.10. Complications of the Cardiovascular System

In this category, except for “perimyocarditis” and “aortitis and aortic rupture” for which meta‐analysis was not feasible, the outcomes were rated as very low certainty of evidence. The pooled estimate for anemia was 35% (95%CI: 31%–39%, I 2 = 96.39%; very low certainty of evidence) and the pooled estimate for endocarditis was 1% (95%CI: 0%–1%, I 2 = 39.61%; very low certainty of evidence). The funnel plots of endocarditis, hematologic involvement, leukopenia, leukocytosis, neutropenia, anemia, thrombocytopenia, thrombocytosis, and pancytopenia showed signs of small‐study effects. Egger's test was statistically significant for leukopenia (p = 0.01) and neutropenia (p = 0.02). For the rest of the outcomes in this category, Egger's test was not statistically significant (p > 0.05). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes in this category were deemed to be robust.

Capillary leak syndrome was only reported in Turkey (less than 1%, 95%CI: 0%–1%; very low certainty of evidence). In subgroup analysis by country, the pooled estimate for leukopenia was the highest in Saudi Arabia (23%, 95%CI: 14%–34%). However, the pooled estimate for leucocytosis was the highest in Iran (12%, 95%CI: 10%–15%) and Saudi Arabia (12%, 95%CI: 7%–18%). The pooled estimate for anemia was the highest in Saudi Arabia (41%, 95%CI: 33%–49%). The pooled estimates for thrombocytopenia (13%, 95%CI: 9%–16%) and thrombocytosis (6%, 95%CI: 5%–8%) were the highest in Turkey. The pooled estimate for pancytopenia in Occupied Palestine (12%, 95%CI: 1%–32%) was the highest. Hemophagocytosis was only reported in Turkey (2%, 95%CI: 1%–2%).

In subgroup analysis by age, the pooled estimate for endocarditis was higher in adults‐only studies (1%, 95%CI: 1%–1%) compared to children‐only studies (less than 1%, 95%CI: 0%–1%). The pooled estimates of leukopenia (19%, 95%CI: 14%–24% vs. 12%, 95%CI: 10%–15%), leucocytosis (12%, 95%CI: 9%–15% vs. 7%, 95%CI: 5%–9%), thrombocytosis (6%, 95%CI: 3%–9% vs. 5%, 95%CI: 2%–10%), and pancytopenia (7%, 95%CI: 5%–10% vs. 5%, 95%CI: 3%–6%) were higher in children‐only studies compared to adults‐only studies. However, the pooled estimates of lymphocytosis (54%, 95%CI: 40%–68% vs. 18%, 95%CI: 3%–41%) and thrombocytopenia (13%, 95%CI: 8%–19% vs. 9%, 95%CI: 7%–11%) were higher in adults‐only studies compared to children‐only studies.

3.11. Complications of the Skin

In this category, the highest pooled estimate was observed for cutaneous involvement (4%, 95%CI: 3%–6%, I 2 = 91.90%; very low certainty of evidence). The funnel plot of cutaneous involvement was deemed to be affected by small‐study effects. However, Egger's test was not statistically significant (p = 0.77). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes classified in this category were deemed to be robust.

In subgroup analysis by country, the pooled estimate for cutaneous involvement in Occupied Palestine (8%, 95%CI: 5%–11%) was the highest. The pooled estimate for petechiae and purpura (very low certainty of evidence) in Saudi Arabia (5%, 95%CI: 2%–10%) was higher compared to Turkey (2%, 95%CI: 0%–7%).

In subgroup analysis by age, the pooled estimate of cutaneous involvement was higher in children‐only studies (4%, 95%CI: 2%–8%) compared to adults‐only studies (3%, 95%CI: 1%–5%).

3.12. Complications of the Gastrointestinal and Hepatobiliary Systems

In this category, all the outcomes were rated as very low certainty of evidence. The pooled estimate for “gastrointestinal involvement” was 12% (95%CI: 6%–18%, I 2 = 96.58%; very low certainty of evidence). The funnel plots of “gastrointestinal involvement” and hepatitis showed signs of small‐study effects. However, Egger's test for “gastrointestinal involvement” (p = 0.77) and hepatitis (p = 0.75) was not statistically significant. In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes classified in this category were deemed robust.

In subgroup analysis by country, the pooled estimate for “gastrointestinal involvement” was the highest in Kuwait (25%, 95%CI: 21%–39%). The pooled estimate for hepatitis was higher in Turkey (5%, 95%CI: 2%–9%) compared to Iran (less than 1%, 95%CI: 0%–2%).

In subgroup analysis by age, the pooled estimate of “gastrointestinal involvement” was higher in children‐only studies (13%, 95%CI: 2%–31%) compared to adults‐only studies (9%, 95%CI: 1%–22%). However, the pooled estimate of hepatitis was higher in adults‐only studies (5%, 95%CI: 2%–10%) compared to children‐only studies (1%, 95%CI: 0%–3%).

3.13. Complications of the Respiratory System

In this category, all the outcomes were rated as very low certainty of evidence. The pooled estimate for pulmonary involvement (5%, 95%CI: 2%–9%, I 2 = 87.56%; very low certainty of evidence) was the highest. The funnel plots of respiratory system involvement, pneumonia, and pleural effusion depicted signs of small‐study effects. However, Egger's test was not statistically significant for any of the outcomes in this category (p > 0.05). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes classified in this category were considered to be robust.

In subgroup analysis by country, the pooled estimate for pneumonia was the highest in Saudi Arabia (2%, 95%CI: 1%–4%). Bronchitis (1%, 95%CI: 0%–3%) and pleurisy (2%, 95%CI: 0%–4%) were only reported in Turkey.

In subgroup analysis by age, the pooled estimate of respiratory system involvement was higher in adults‐only studies (2%, 95%CI: 1%–5%) compared to children‐only studies (0%, 95%CI: 0%–2%). However, for pneumonia, the pooled estimate was higher in children‐only studies (2%, 95%CI: 1%–3%) compared to adults‐only studies (1%, 95%CI: 0%–3%).

3.14. Complication of the Eye

“Ocular involvement” (very low certainty of evidence) showed evidence of small‐studies effects and Egger's test was statistically significant (p = 0.003). In this category, the highest pooled estimates were observed for conjunctivitis (10%, 95%CI: 4%–18%, I 2 not calculable; very low certainty of evidence) and anterior uveitis (8%, 95%CI: 5%–12%, I 2 not calculable; very low certainty of evidence). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes classified in this category were deemed to be robust. Except for two studies in Kuwait in 1988 and in Saudi Arabia in 2005 that reported “ocular involvement”, all the included studies for the specific complications of the eye were conducted in Turkey and subgroup analysis by country was not feasible. Subgroup analysis to compare the pooled estimates of adults‐only and children‐only studies was not feasible for any of the complications of the eye.

3.15. Complications Related to Pregnancy

In this category, all the outcomes except for threatened abortion for which meta‐analysis was not feasible, were rated as very low certainty of evidence. The highest pooled estimate was observed for abortion (20%, 95%CI: 9%–34%, I 2 = 91.57%; very low certainty of evidence). The funnel plot of abortion showed signs of small‐study effects. However, Egger's test was not statistically significant (p = 0.24). In sensitivity analysis with leave‐one‐out method, the pooled estimates for all the outcomes classified in this category were deemed as robust.

In subgroup analysis by country, the pooled estimate for abortion (37%, 95%CI: 30%–45%) and Intrauterine fetal demise (5%, 95%CI: 2%–10%) were the highest in Saudi Arabia. The pooled estimate for preterm labor was the highest in Turkey (7%, 95%CI: 0%–22%).

Subgroup analysis to compare the pooled estimates of adults‐only and children‐only was not feasible for pregnancy complications.

3.16. Complications of the Soft Tissue Except Periarticular or Paravertebral Soft Tissue

Only one study reported “soft tissue involvement” (very low certainty of evidence). Meta‐analysis, sensitivity analysis, and subgroup analysis were not feasible for this outcome.

3.17. Complications of the Endocrine System Except Genital Glands

We included thyroiditis and thyroid abscess in this category. However, meta‐analysis, sensitivity analysis, and subgroup analysis were not feasible for these outcomes. The certainty of evidence for both of the outcomes were very low.

4. Discussion

This systematic review and meta‐analysis aimed to aggregate and synthesize all the available evidence for the relative frequency of the complications of brucellosis in West Asia/Middle East region.

To our knowledge, this is the most comprehensive study on the relative frequency of the complications of brucellosis particularly due to the high number of included studies and the variety of the included complications.

Based on our findings, the pooled estimate of the relative frequency of avascular necrosis of femoral head was less than 1%. Evidence suggests Brucella may act as an under‐recognized ischemic trigger causing osteonecrosis while its diagnosis is often delayed resulting in irreversible joint damage (Konarski et al. 2026).

Based on our findings, the pooled estimate for neurobrucellosis in the West Asia/Middle East region was 3%. However, we noticed that the definition of neurobrucellosis differed among the included studies. For instance, Buzgan defined neurobrucellosis as the central nervous system involvement (Buzgan et al. 2010). This is not recommended as we have shown that brucellosis can also involve the peripheral nervous system. In China, the pooled estimate for central nervous system dysfunction was 5% (95% CI: 3%–10%) (Zheng et al. 2018). This was higher than our pooled estimate for central nervous system involvement (3%). The pooled estimate for hearing loss in the West Asia/Middle East region was 2%. Hearing loss has been associated with a greater risk of relapse or sequalae in patients with neurobrucellosis (Fusetti et al. 2024).

Based on our findings, the pooled estimate of endocarditis was higher in adults‐only studies. This is consistent with the findings of Başaran et al. that reported endocarditis due to brucellosis was more common among younger male patients (Başaran et al. 2025).

We identified three types of infarctions: Putamen infarction, myocardial infarction, and splenic infarction. However, meta‐analysis was not possible due to the fact that only one study assessing each of the aforementioned outcomes was included. Due to the potential severity and fatality of tissue infarction, early diagnosis and prompt treatment are vital for these cases (Keyvanfar et al. 2025).

It is unknown how much of these complications are caused by B. melitensis and other Brucella species and whether the incidence rates of these complications differ based on the causative Brucella species. Therefore, it is suggested to study if the relative frequency of the complications caused by Brucella species is different.

Based on our findings, except for two studies in Kuwait in 1988 and in Saudi Arabia in 2005 reporting “ocular involvement”, all the included studies for the specific complications of the eye were conducted in Turkey. Therefore, we suggest that other countries in the region should also determine the ocular complications among their patient populations. Among ocular complications, conjunctivitis and anterior uveitis were the most common. This finding is consistent with the findings of Evlice et al. where it was reported that among the ocular involvement outcomes, the most common types were uveitis (52.2%) and conjunctivitis (17.6%) (Evlice et al. 2023).

In some complications, the pooled estimate for Kuwait and Saudi Arabia was higher. However, the studies of those subgroups were from the 20th century and early 2000s. Moreover, the findings of subgroup analysis by publication year suggest that orchitis, epididymoorchitis, and meningitis may have decreased over time and that time might influence the relative frequency of these complications. An alternative hypothesis could be the changes in the surveillance systems, diagnostic tools, and the extent of awareness of the complications of brucellosis among patient populations and healthcare workers in the region might have played a role in the influence of time.

Based on our findings, the relative frequency of different complications of brucellosis is different. Therefore, primary studies should take into account these differences in their sample size determination to reach the desired precision. Moreover, the investigators should report their diagnostic criteria for the complications of brucellosis. It is recommended that the criteria used for the determination of the presence of the brucellosis complications be explained in the primary studies.

We limited the number of included outcomes to 254. In future updates of this systematic review, we will increase this number to cover all complications of brucellosis. We performed analyses for all the codes keeping overlapping codes such as “orchitis” and “epididymoorchitis” so that the clinicians using any coding systems could use the findings of this review. However, we advocate the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Based on the differences of the definitions of neurobrucellosis among the included studies including the restriction of neurobrucellosis to the complications of the central nervous system, it is suspected that the complications of brucellosis are being missed and misclassified when using system‐ and organ‐level outcomes. Moreover, based on our findings, the relative frequencies of the complications of brucellosis are different. Therefore, it is recommended to not document the complications in system‐ or organ‐level formats.

Overall, the certainty of evidence for the majority of the outcomes was rated as very low mostly due the high risk of bias of the included studies. Therefore, these values should be interpreted cautiously as approximate summaries, not exact prevalence rates for all West Asian settings.

4.1. Limitations

We were unable to perform other subgroup analyses. We were able to include articles written in English or Persian which could result in missing eligible studies written in other languages. The generalizability of the findings could be affected by the lack of reporting of the complications in all of the countries, risk of bias, and low to very low certainty of evidence.

5. Conclusion

In summary, the pooled estimate for endocarditis was higher in adults‐only studies. With the exception of two studies in Kuwait in 1988 and in Saudi Arabia in 2005 reporting “ocular involvement”, all the included studies for the specific complications of the eye were conducted in Turkey. Future studies should take into account the difference in the relative frequency of different complications of brucellosis in their sample size determination and report the diagnostic criteria used for the determination of the complications of brucellosis. The definitions of the complications of brucellosis should be standardized in order to achieve comparability.

Author Contributions

Aliasghar Fakhri‐Demeshghieh: conceptualization, methodology, investigation, formal analysis, writing – original draft. Elnaz Rostamzaman: investigation, writing – original draft. Fatemeh Sayareh: investigation, writing – original draft. Amir Nikoukar: investigation, writing – original draft. Faranak Farahani: investigation, writing – original draft. Farniya Bakhtiary nia: investigation, writing – original draft. Helia Sepahvand: investigation, writing – original draft. Maryam Khaleghi: investigation, writing – original draft. Mohammadsaeed Azamian: investigation, writing – original draft. Mohammad Reza Shirzadi: conceptualization, methodology, writing – review and editing. Hesameddin Akbarein: conceptualization, methodology, writing – review and editing. Vahid Rahmanian: conceptualization, methodology, investigation, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The protocol of this systematic review was prospectively registered in International prospective register of systematic reviews (PROSPERO) with PROSPERO ID: CRD420251044071. The objectives, inclusion criteria, search strategy, and the number of included outcomes were amended. We used the applicable components of GRADE approach (risk of bias, inconsistency, and imprecision) to assess the certainty of evidence.

Conflicts of Interest

The authors declare no conflict of interest.

Supporting information

Supporting File 1

MBO3-15-e70388-s001.docx (13.8KB, docx)

Supporting File 2

MBO3-15-e70388-s005.docx (15.6KB, docx)

Supporting File 3

MBO3-15-e70388-s008.docx (28.9KB, docx)

Supporting File 4

MBO3-15-e70388-s010.docx (89.6KB, docx)

Supporting File 5

MBO3-15-e70388-s009.docx (352.4KB, docx)

Supporting File 6

MBO3-15-e70388-s006.docx (876KB, docx)

Supporting File 7

MBO3-15-e70388-s007.docx (1.4MB, docx)

Supporting File 8

MBO3-15-e70388-s003.docx (1.3MB, docx)

Supporting File 9

MBO3-15-e70388-s011.docx (1.4MB, docx)

Supporting File 10

MBO3-15-e70388-s004.docx (24KB, docx)

Supporting File 11

MBO3-15-e70388-s002.docx (268.6KB, docx)

Data Availability Statement

The data and statistical codes used in this systematic review and meta‐analysis are available from the corresponding author upon request.

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MBO3-15-e70388-s006.docx (876KB, docx)

Supporting File 7

MBO3-15-e70388-s007.docx (1.4MB, docx)

Supporting File 8

MBO3-15-e70388-s003.docx (1.3MB, docx)

Supporting File 9

MBO3-15-e70388-s011.docx (1.4MB, docx)

Supporting File 10

MBO3-15-e70388-s004.docx (24KB, docx)

Supporting File 11

MBO3-15-e70388-s002.docx (268.6KB, docx)

Data Availability Statement

The data and statistical codes used in this systematic review and meta‐analysis are available from the corresponding author upon request.

Articles from MicrobiologyOpen are provided here courtesy of Wiley

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