2.1. Protocol and registration

The current study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (S1 Table) [19]. Additionally, the research protocol was registered with the Prospective International Registry of Systematic Reviews (PROSPERO) under the identification number CRD42024582854. The protocol originally registered in PROSPERO underwent some minor changes. These changes included specifying a detailed descriptive extraction for the reports and case series and assigning a greater number of investigators to various study processes, such as evaluation, article selection, and data analysis, all with the aim of strengthening the research.

2.2. Eligibility criteria

Studies that met the following criteria were included: a) observational studies (cohort, case-control, cross-sectional), case reports, and case series; b) investigations that provide information on the epidemiological and clinical characteristics of Peruvian patients with mpox; and c) patients diagnosed with mpox through clinical criteria or by RT-PCR (reverse transcriptase polymerase chain reaction). Studies that met the following criteria were excluded: editorials, letters to the editor, randomized clinical trials, conference abstracts, and narrative or systematic reviews.

2.3. Information sources and search strategy

Comprehensive searches were conducted in ten databases or search tools: PubMed, Scopus, Web of Sciences, Embase, ScienceDirect, Google Scholar, Virtual Health Library, Scielo, Dimensions, and Epistemonikos, until August 22, 2024, without applying language or time restrictions. The MeSH (Medical Subject Headings) terms used in the search were “mpox” and “Peru,” combined using the logical operators AND and OR. The search strategy, independently validated by two authors (RCN and AECI), is detailed in S2 Table. In addition, complementary methods were used, such as manual searches in national journals and review of the reference lists of the selected studies. However, the potential studies identified were found to be within the scope of the main strategy applied.

2.4. Study selection

The search results were stored using EndNote version X9 software (Thomas Reuters, New York, NY, USA). Duplicate entries, along with repeated titles and abstracts, were subsequently removed. Following this, the remaining titles and abstracts were independently screened to evaluate their alignment with the inclusion criteria. Full-text articles were then meticulously reviewed to confirm compliance with these criteria. Any discrepancies that arose during the process were resolved through consensus.

2.5. Outcomes

The primary outcome is to assess the prevalence of epidemiological and clinical characteristics among Peruvian patients diagnosed with mpox.

2.6. Quality assessment

The quality and potential bias of the studies included in the meta-analysis were evaluated using the JBI-MAStARI (Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument) tool. The assessment considered several factors, such as the research setting, outcome measures, explanatory variables, defined inclusion criteria, measurement methods, clarity in problem definition, and the rigor of statistical analysis. Based on their scores, the studies were classified as high quality (≥ 7 points), moderate quality (4–6 points), or low quality (< 4 points) (S3 Table) [20].

2.7. Data collection process and data items

The article data was organized in an Excel spreadsheet during the months of September and October 2024. Two authors (DALF and MDT) independently and manually extracted a comprehensive dataset. For the meta-analysis, the following variables were collected: author, year, study type, region, sample size, sex (male/female), age, mpox diagnostic method, HIV (human immunodeficiency virus) status, sexual orientation (heterosexual, homosexual, bisexual), history of syphilis, hospitalization, HIV-infected individuals receiving antiretroviral therapy, sexual risk behaviors, data collection methods, fever, headache, fatigue or asthenia, local lymphadenopathy, generalized lymphadenopathy, any type of lymphadenopathy, rash or skin lesions (local and general), anogenital rash, proctitis, lesion location, lesion morphology, and other symptoms.

For the descriptive analysis of case series and reports, the following data were extracted: author, year, study type, region, sample size, sex (male/female), age (in years), disease duration, HIV status, history of syphilis, antiretroviral therapy, sexual orientation, clinical manifestations, lesion types, lesion distribution, diagnostic method, and disease progression.

During a meeting, the data extractions conducted by the two independent authors (EAM and MJVG) were compared, and any discrepancies were resolved through mutual agreement. Following this, a thorough review and verification process was performed by a third independent investigator (VEFR) to ensure the accuracy and quality of the extracted data.

2.8. Data analysis

A prevalence meta-analysis (proportions) was conducted using R software version 4.2.3 (https://www.r-project.org/) (S5 Table and S6 Table). To estimate the combined prevalence of epidemiological and clinical characteristics in Peruvian patients with mpox, a variance-weighted inverse random effects model was applied. Between-study variability was assessed using the Cochrane Q statistic, while heterogeneity was quantified with the Inconsistency Index (I²). Heterogeneity levels were categorized as low (<25%), moderate (25% to 50%), and high (>75%) [21].

To assess the potential presence of publication bias, two methods were employed: visual examination of the funnel plot and Egger’s test. These approaches were utilized only when the meta-analysis included a minimum of 10 studies, as fewer studies reduce the test’s ability to detect true asymmetry. Publication bias was considered significant if the p-value was below 0.05 [22].

The findings of the study were presented through tables and descriptive graphs. A forest plot was used to visually represent the combined prevalence of epidemiological and clinical characteristics among Peruvian patients with mpox, incorporating 95% confidence intervals to ensure a more precise depiction of the data.

3.1. Study selection

The search strategy initially produced 150 results. After removing duplicates, 47 articles were screened by comparing their titles and abstracts against the inclusion criteria. Following this, 25 full-text articles were thoroughly evaluated, leading to the final inclusion of 9 studies in the review (S4 Table). The selection process is visually summarized in Fig 1 using a PRISMA flow chart [23–31].

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Fig 1. Study selection process based on the PRISMA flowchart.

https://doi.org/10.1371/journal.pone.0327097.g001

3.2. Characteristics of the included studie

The review included four retrospective observational studies, four case series, and one case report, encompassing a total of 3,960 Peruvian patients diagnosed with mpox, aged between 20 and 50 years [23–31]. Mpox assessments were conducted using clinical evaluation and PCR testing. The studies were primarily based in the regions of Lima and La Libertad (Table 1 and 2) [23–31].

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Table 1. Summary of the epidemiological characteristics of the studies included in the meta-analysis.

https://doi.org/10.1371/journal.pone.0327097.t001

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Table 2. Summary of the clinical characteristics of the studies included in the meta-analysis.

https://doi.org/10.1371/journal.pone.0327097.t002

In the five case series studies and reports developed in Lima during 2022–2024, 22 Peruvian patients diagnosed with mpox were included. Of these, 90.9% (n = 20) were men and 9.1% (n = 2) were women, with a mean age of 35.8 years [27–30]. Eleven patients with HIV infection were identified, of whom two were receiving antiretroviral therapy and two had a history of syphilis. In terms of sexual orientation, seven patients identified as homosexual, five as bisexual, and seven as heterosexual. 95.5% (n = 21) of mpox cases were confirmed by PCR testing. Most patients experienced complete recovery, with a total of five deaths reported. The most common clinical manifestations included fever, lymphadenopathy, headache, and myalgia, while lesions observed consisted of vesicles, papules, ulcers, and scabs (Table 3) [27–31].

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Table 3. Summary of the epidemiological and clinical characteristics of the reports and case series included in the systematic review.

https://doi.org/10.1371/journal.pone.0327097.t003

3.3. Quality of the included studies and publication bias

The quality of the studies included in the analysis was rated as moderate, as indicated in S3 Table [23–31]. Due to the meta-analysis comprising fewer than 10 studies, publication bias could not be evaluated using visual inspection of the funnel plot or Egger’s test.

3.4. Prevalence of epidemiological and clinical characteristics of Peruvian patients with mpox

The overall sex distribution showed a prevalence of 97% (95% CI: 96–98%) in males and 3% (95% CI: 2–4%) in females [23–26]. Regarding medical history, syphilis was reported in 17% (95% CI: 9–26%) of cases, HIV in 63% (95% CI: 57–68%), and 91% (95% CI: 83–97%) of individuals with HIV were receiving antiretroviral therapy [23–26]. Additionally, 5% (95% CI: 3–9%) of patients required hospitalization [23–26]. Based on sexual orientation, 21% (95% CI: 11–33%) identified as heterosexual, 61% (95% CI: 46–75%) as homosexual, and 16% (95% CI: 14–17%) as bisexual [23–26]. The most common clinical manifestations included a rash or skin lesions at consultation (general), present in 88% (95% CI: 79–94%) of patients [23–26], lymphadenopathy any type in 83% (95% CI: 25–100%) [23,24], anogenital rash in 72% (95% CI: 65–79%) [23–25], fever in 67% (95% CI: 59–76%) [23–26], and headache in 52% (95% CI: 47–57%) [23,24,26] (Table 4 and Fig 2).

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Table 4. Pooled prevalence of epidemiological and clinical characteristics of Peruvian patients with mpox.

https://doi.org/10.1371/journal.pone.0327097.t004

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Fig 2. Most prevalent clinical manifestations in Peruvian patients with mpox.

https://doi.org/10.1371/journal.pone.0327097.g002

Epidemiological trends

The present study provides a comprehensive overview of the epidemiological and clinical characteristics of Peruvian patients with mpox, providing relevant evidence in the Latin American context. In terms of epidemiology, we found that males accounted for 97% of cases, a finding consistent with recent global literature on mpox outbreaks that reports a marked male predominance, particularly among MSM [32,33]. This pattern has been consistent in outbreaks in Colombia [34] and regions such as Europe [35] and North America [36], suggesting that factors such as sexual contact networks and risk practices may be driving transmission in these specific populations. On the other hand, transgender women may have a higher risk of sexual transmission compared to cisgender women, coexisting with HIV infection and lesions similar to those found in men, such as lesions in the anogenital region [37]. This increased risk in transgender women is influenced by various factors, including societal stigma, discrimination, limited access to healthcare, and higher rates of HIV infection, which together contribute to their vulnerability to mpox [37,38].

The Table 5 presents a detailed analysis of the clinical characteristics and epidemiological background of Peruvian patients diagnosed with mpox between 2022 and 2024, based on data from the National Center for Epidemiology, Disease Prevention, and Control of Peru. It is observed that the majority of cases are concentrated in young adults (18–59 years), with a notably higher prevalence in men (96.1%). The predominant sexual orientation among patients is homosexual (56.2%), followed by bisexual (15.5%) and heterosexual (24.3%). A significant percentage of patients live with HIV (55.6%), most of whom are undergoing antiretroviral treatment (87.9%). The most common clinical manifestations include fever, generalized rash, headache, and myalgia. In terms of background, a considerable percentage report previous infections such as syphilis (16.1%) and other infections (7.7%) [39].

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Table 5. Characteristics and epidemiological background of Peruvian patients with mpox from 2022 to 2024, according to the Peruvian National Center for Epidemiology, Prevention, and Disease Control.

https://doi.org/10.1371/journal.pone.0327097.t005

These data are consistent with that reported by León-Figueroa DA et al., who identified that 98.72% of 4537 confirmed cases involved men, with 95.72% linked to MSM [6], and by WHO, which reported that 97.1% of cases during the 2022 outbreak involved young men with a median age of 35 years [40]. This epidemiological pattern is also reflected in the work of Du M. et al., who reported that 79.8% of cases involved MSM [41], underscoring that close contact and risky sexual practices are determinant factors in the transmission of the virus [13,14].

Although current data indicate a higher prevalence of mpox among men, particularly among MSM, this trend should not be interpreted as evidence of lower impact among women. A meta-analysis by Satapathy et al. revealed a notable decline in the proportion of female cases—from 44.09% in studies conducted prior to 2022 to just 2.40% in those published thereafter [42]. This proportion varies significantly depending on geographic region, endemic status of the country, and the reporting period. Such disparities point to the possibility of diagnostic biases and underreporting in women, rather than a true difference in disease burden. Therefore, strengthening epidemiological surveillance systems with an inclusive approach that considers all populations—regardless of gender—is essential. Doing so will not only provide a more accurate picture of mpox transmission dynamics but also help address the specific health needs of women and other vulnerable groups [38].

Impact of HIV coinfection in patients with mpox

In relation to comorbidities, coinfection with HIV was observed in 63% of the cases, highlighting the high vulnerability of this population to mpox. This percentage exceeds those reported in previous studies, which documented coinfection rates between 36% and 41% [32,43,44]. According to a systematic review by Ortiz-Saavedra B. et al., 40.32% of 6345 confirmed cases of mpox were coinfected with HIV [45]. Similarly, Liu BM et al. reported that more than 35% of cases had coinfection with HIV, in addition to 40% with sexually transmitted infections (STIs), such as Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus [46]. Likewise, another systematic review proposed by Chenchula S. et al. reported that 36.1% of 18,275 cases of mpox had coinfection with HIV, reinforcing the relevance of this comorbidity in the clinical course of the disease [47].

However, it is important to differentiate between individuals living with HIV who have well-controlled infections, characterized by undetectable viral loads and preserved immune function, and those with advanced HIV or AIDS, who may have significant immunosuppression, characterized by low CD4 + cell counts and high viral loads [48,49]. On the other hand, the fact that 91% of coinfected patients were receiving antiretroviral therapy suggests that, although access to treatment is adequate, these individuals remain susceptible to mpox infection, raising questions about the impact of relative immunosuppression due to higher viral loads and lower CD4 counts on the clinical course of the disease [50]. Individuals with well-controlled HIV, who have undetectable viral loads and CD4 + counts above 500 cells/mm3, may experience a less severe course of mpox compared to those with advanced HIV or AIDS, who are at higher risk for severe disease due to significant immunosuppression [50,51]. A global case series that included only HIV patients with CD4 + cell counts less than 350 cells/mm3 reported severe mpox necrotizing disease and more severe complications in HIV patients who had CD4 + cell counts less than 200 cells/mm3; on the other hand, in 21 of 85 patients who initiated or restarted ART, an inflammatory syndrome of immune reconstitution to mpox was suspected [50].

These findings could be explained by the fact that HIV causes immunosuppression, which makes it difficult for the body to mount an effective immune response against pathogens such as mpox. People who are coinfected are at increased risk of severe illness and death; it is critical to prioritize interventions and improve treatment strategies designed specifically for people living with HIV, distinguishing between those with well-controlled infections and those with advanced immunosuppression [52,53].

Clinical manifestations of mpox patients

Our study documented a high prevalence of skin lesions (88%), lymphadenopathy (83%), anogenital rash (72%), fever (67%), and headache (52%), findings that coincide with those described in the scientific literature. Jaiswal V. et al. reported that the most significant symptoms in patients with mpox were rash (100%) and fever (99%), in addition to upper respiratory symptoms (55%), headache (78%), vomiting (25%), oral ulcers (56%), conjunctivitis (21%), and lymphadenopathy (85%) [54].

Similarly, the meta-analysis by Benites-Zapata VA. et al. noted that among 1958 patients, the most prevalent manifestations were rash (93%), fever (72%), pruritus (65%), and lymphadenopathy (62%) [55]. A meta-analysis by Satapathy P. et al. identified a broad spectrum of clinical manifestations of mpox, encompassing cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related symptoms. Cutaneous manifestations, present in up to 100% of cases, were the most prevalent, highlighting characteristic lesions and rashes. Constitutional symptoms associated with viral diseases were reported in 60% to more than 85% of cases, while significant respiratory symptoms affected approximately 50%. Among neurological symptoms, headaches were the most common, present in more than 30% of patients. Gastrointestinal manifestations included oral lesions in 39% of cases, with less frequent diarrhea (~5%) and proctitis, especially in adolescents and young adults. Finally, ophthalmic manifestations were less common (6%), although with notable variability among the studies analyzed [7].

Other studies have reported a high prevalence of systemic symptoms in countries where mpox is endemic, indicating a prevalence between 85 and 90% for fever, 80% for headache, and between 70 and 100% for lymphadenopathy, which is higher than that reported in our country [56–58]. Regarding cutaneous and anogenital rash, they have had an important consideration in our country. An anogenital, oral, and perioral pattern has been reported, which raised the hypothesis that the lesions appear at the site of inoculation [37,58]. However, a distribution of lesions on the face, trunk, and extremity areas has also been reported [43,44,59]. These results could be explained by variations in clinical manifestations according to the severity of mpox (from mild to severe), demographic and epidemiological differences in the populations studied, the stage of the disease at the time of evaluation, as well as possible changes in the virulence of the virus or in the immune response of the patients [60,61]. It is important to consider the limitations of the cited studies, such as sample heterogeneity due to variations in patient populations, regions, and clinical settings, which can affect the generalizability of the results. Additionally, publication bias should be taken into account, as studies with positive results may be overrepresented, influencing the overall conclusions.

Hospitalization rates and disease severity in mpox patients

Regarding disease severity and hospitalization, only 5% of patients in our review required hospitalization, a relatively low figure compared to a study in Brazil where the hospitalization rate was 10.5%, with people with HIV having more proctitis and requiring invasive support, and mpox severity was associated with low CD4 + cell counts and discontinuation of HIV treatment [62]. It is important to note that the healthcare infrastructure and diagnostic practices in Peru and Brazil may vary, with differences in the availability of resources, healthcare access, and hospitalization criteria potentially influencing the reported rates. Another study in 2022 that evaluated a cohort of patients hospitalized for mpox found that there were no clinical, laboratory, or complication differences in patients with and without HIV coinfection; however, no HIV patients had advanced disease [63]. Additionally, some complications of mpox disease have been reported, such as ocular manifestations, coalescing lesions resulting in large plaques, encephalitis, and encephalomyelitis, among others. Also, in patients with advanced HIV infection, a necrotizing form of mpox has been reported [64,65].

A meta-analysis proposed by Benites-Zapata VA, et al., reported that among patients with mpox, 35% were hospitalized, and about 4% of hospitalized patients had fatal outcomes [55]. These results could be explained by variations in the characteristics of the populations studied, such as the prevalence of severe comorbidities (e.g., immunosuppression or advanced HIV), the level of access to health services, and the application of early diagnosis and timely management strategies in various epidemiological contexts [10,66]. The low rates observed in our population could be due to the fact that most HIV patients were receiving antiretroviral therapy, which could have mitigated the severity of infection. However, these findings should be interpreted with caution, as the small number of studies included in the analysis limits the ability to make robust comparisons.

Strengths and limitations of the study

This study has several strengths. First, a significant sample of 3960 Peruvian patients with mpox was included, which allows us to provide a representative view of the epidemiology and clinical characteristics of the disease in the national context. This is particularly relevant at a time when information on mpox in Latin America remains limited. In addition, our analysis provides important data on HIV coinfection, a critical factor in understanding the vulnerability and clinical evolution of this specific population. Another key strength is the methodological rigor applied at all stages of the study, following PRISMA guidelines for systematic reviews and meta-analyses, which guarantees the reproducibility of the results. Likewise, the use of multiple databases, both international and regional, allowed for an exhaustive search, which reduces the risk of omitting relevant studies.

However, the study also has some limitations that should be considered when interpreting the results. First, the limited number of included studies (n = 9) restricts the generalizability of the findings and may have influenced the precision of the estimates derived from the meta-analysis. Second, the inability to assess publication bias due to the small number of studies is another important limitation, as this could have introduced undetected bias in the results. Third, most of the included studies were retrospective in nature, which may be associated with an increased possibility of bias, particularly in data collection. The retrospective nature of these studies could have led to recall bias, missing data, and unmeasured confounding variables, all of which could have influenced the reported trends. Finally, heterogeneity among the investigations, both in terms of design and patient characteristics, could have influenced the findings, making it difficult to identify consistent patterns across the populations analyzed. The wide confidence intervals in some estimates suggest a high degree of uncertainty in the aggregated results, requiring caution when interpreting them. The implications of this variability indicate that care should be taken when considering estimates with high variability. Additionally, it is recognized that more studies with larger sample sizes and more precise measurements are needed to reduce uncertainty and provide more reliable estimates.

To address some of the limitations identified in this study, future research should aim to include a larger number of prospective studies, which would reduce the risk of bias and improve the generalizability of the findings. In addition, implementing more rigorous methods to assess and control for potential confounders and conducting sensitivity analyses to evaluate the impact of missing data would enhance the reliability of the conclusions drawn. Expanding the study sample and standardizing patient characteristics across studies could help minimize heterogeneity and provide clearer insights into the epidemiological trends.

Clinical implications

The results of this study have important clinical implications, especially in the management of patients with mpox in populations with high HIV prevalence. The high percentage of HIV coinfection among Peruvian patients addresses the need for a comprehensive approach to the diagnosis and treatment of mpox in immunocompromised individuals [46]. Recognizing the most prevalent clinical features, such as skin lesions, fever, and lymphadenopathy, is critical to improving early diagnosis and avoiding serious complications [67]. In addition, specialized care should focus on this high-risk population, not only for the management of acute mpox symptoms but also for co-infection surveillance and long-term monitoring of their immune status. Early detection and appropriate treatment of these features can help reduce the rate of hospitalization and improve clinical outcomes [68].

Public health interventions should be a key component of the response to mpox, particularly in the context of populations with high HIV prevalence. Vaccination efforts should prioritize high-risk groups, including individuals living with HIV, as part of a comprehensive prevention strategy [17,69]. Contact tracing and active surveillance are also crucial for identifying and isolating cases early, preventing further spread. Engaging with communities, particularly through education and outreach programs, will be essential to increasing awareness of mpox, its symptoms, and the importance of timely treatment [70]. Such strategies are especially relevant in regions like Peru, where diverse populations may face varying levels of access to healthcare and public health infrastructure [70,71].

Longitudinal studies are recommended to evaluate the long-term progression of mpox in people with HIV, as well as their response to therapeutic interventions. It is also crucial to expand research to other regions of Peru, given that most of the studies included in this review focused on urban areas such as Lima and La Libertad. Research in more remote and diverse regions could provide a broader understanding of the epidemiology of mpox throughout the country. Additionally, greater inclusion of women and heterosexuals in future studies is needed, given that this review reflects an overrepresentation of homosexual and bisexual males. This will allow for a more complete and equitable view of the different population groups affected by the disease. Finally, intervention studies focused on prevention and treatment in HIV co-infected patients could also offer key strategies to mitigate the effects of future outbreaks. These studies could focus on the development of novel therapeutic approaches, as well as preventive measures tailored to the unique needs of co-infected individuals. This could include exploring the role of antiretroviral therapy in reducing the susceptibility to mpox, understanding the impact of immunocompromised states on disease progression, and evaluating the effectiveness of vaccines in this specific population. In addition, identifying biomarkers or other indicators of early infection in co-infected patients may help improve early detection and response strategies, which are essential for controlling future outbreaks.