A retrospective study on 198 mpox cases in South Florida: Clinical characteristics and outcomes with focus on human immunodeficiency virus status

Abstract

Background

Men who have sex with men (MSM) and persons living with human immunodeficiency virus (PLWH) were disproportionately affected by global mpox outbreak in 2022. In this retrospective review, we describe epidemiology and clinical characteristics of mpox infection in South Florida with a focus on human immunodeficiency virus (HIV) status.

Methods

This was a retrospective observational study of 198 adult patients with confirmed diagnosis of mpox between 01 January 2020, and 10 September 2022, in two large health systems in South Florida. A descriptive analysis was performed to summarize demographic, clinical and laboratory characteristics, and outcomes of the patients.

Results

Young male patients and PLWH were disproportionately represented among patients with mpox. HIV positive patients were less likely to have adenopathy and myalgia and were more likely to have oral or facial lesions. 22.7% of studied patients were diagnosed with one or more concurrent STI at the time of mpox diagnosis.

Conclusions

We suggest screening for sexually transmitted infections and HIV for patients diagnosed with mpox. We suggest prompt consultation or referral to infectious disease specialist if needed for the patients who are diagnosed with mpox especially in the severely immunocompromised host.

Keywords

Human immunodeficiency virus homosexual location North America other viral disease

Background

Mpox is a zoonotic infection caused by mpox virus, an enveloped double-stranded DNA virus and a member of the Orthopoxvirus genus in the family Poxviridae, transmitted from person to person by close contact, body fluids, or respiratory droplets. Two distinct genetic clades have been identified: the central African clade (Congo Basin, clade 1) and the West African clade (clade 2a). Historically, it has been endemic only in West and Central Africa, however in May 2022 an outbreak of mpox clade 2b was confirmed in more than 20 non-endemic countries.¹

Mpox is usually a self-limited disease and symptoms last approximately from 2 to 4 weeks, although severe cases have been reported and there have been 38 mpox-associated deaths (1.3 per 1000 mpox cases) reported to CDC during 10 May 2022, to 7 March 2023.² There is a strong relationship between mpox severity and advanced human immunodeficiency virus (HIV) infection, as well as a high prevalence of other sexually transmitted infections (STIs) such as syphilis. The most affected population are men who have sex with men (MSM), and these have shown to have worse outcomes in the setting of uncontrolled HIV infection.³

An mpox outbreak in 2017 in Nigeria reported a case fatality rate of 6% (7/118), of which four cases had uncontrolled HIV with features of AIDS, low CD4 count (below 200 cells/mm³), or a recent HIV-related illness.⁴ Data from the 2022 multinational outbreak showed a high HIV prevalence (38%) in mpox infected patients as well as high prevalence of one or more other reportable STIs in the preceding year (41%).⁵ A case series conducted in 19 countries analyzed 392 mpox cases in persons living with HIV (PLWH) who has CD4 cell count less than 350 cells/mm³.⁶ In this group of patients with advanced HIV disease, the study reported hospitalization rate of 28%, and among hospitalized patients, 25% died.⁶ Significantly, all death occurred in people with CD4 cell count less than 200 cells/mm³.⁶

We conducted a retrospective review on 198 patients who were diagnosed with mpox virus infection in South Florida, where the incidence and prevalence of the HIV infection was reported to be the highest of any other states in the U.S.^7,8 Herein we describe the clinical characteristics and outcomes of mpox virus infection.

Methods

Study design and participants

This was a retrospective observational study of all consecutive adult (>18 years) patients with confirmed diagnosis of mpox between 01 January 2020, and 10 September 2022, in Memorial Healthcare System in Broward County (2020 total licensed beds across six hospitals) and Jackson Health System (1500 total licensed beds). Confirmed cases were defined as those who had a positive polymerase chain reaction (PCR) test for human monkeypox virus (hMPXV) from a swab of any pertinent anatomical site, either seen as outpatients, emergency department visits and/or hospitalizations across our health systems. The study protocol was reviewed and approved by the Institutional Review Boards of the Memorial Healthcare System (MHS.2022.087) and the University of Miami/Jackson Health System. Written informed consent was waived as this was a secondary data analysis of existing data. Separate image-specific consent was obtained for the use of images included in this report.

Data collection

Data was manually extracted from patients’ electronic health records (EHRs) and entered in an anonymized database containing no personally identifiable information. Data of interest included demographics (age, gender identity, race, sexual orientation), comorbidities, smoking status, smallpox vaccination history, HIV, hepatitis B, hepatitis C, pre-exposure prophylaxis (PrEP), concomitant STIs, and COVID-19 status, risk of exposure, and days from onset of illness to diagnosis. The following clinical features were collected: fever, chills, and/or documented fever ≥38°C; headache; malaise/fatigue; lymphadenopathy; presence or absence of a rash; distribution of rash lesions and numbers of concurrent lesions, antiviral treatment and duration of treatment, the need for hospitalization or intensive care, and in-hospital death. For PLWH, the most recent CD4 cell count, within 6 months from the point of data collection, was recorded.

Statistical analysis

A descriptive analysis was performed to summarize demographic, clinical and laboratory characteristics, and outcomes of the patients. The Shapiro-Wilk test was used to assess the normality of continuous variables. Mean and standard deviation or median and interquartile range (IQR) were calculated for continuous variables, as appropriate. Frequencies and percentages were calculated for categorical variables. Patients were stratified by HIV status and their clinical characteristics were compared using Mann-Whitney U tests or t-tests for continuous variables, and Fisher’s exact tests or chi-squared tests for categorical variables, as appropriate. A two-tailed, p value of <.05 was considered statistically significant. The analyses were performed using GraphPad Prism 9.0 (San Diego, CA, USA) software.

Results

A total of 198 cases of confirmed mpox virus infection were analyzed in the study. Demographic characteristics are presented in Table 1. Median age was 35 years (IQR, 29.8–43) and 189 (95.5%) individuals were men. Only 8 (4%) individuals were female and there was one transgender patient in the study. One-hundred and thirty-two (66.7%) of 198 individuals were White, 58 (29.3%) were Black, 2 (1%) were Asian and 6 (3%) were of other race. In terms of ethnicity, 99 (50%) were Hispanic, 87 (43.9%) were not Hispanic, and 12 (6.1%) did not have documented ethnicity. One hundred (50.5%) had a previous diagnosis of HIV. Among PLWH, 43 had recent CD4 cell count documented which was at median of 606 cells/mm³ (IQR 396–865). Total of 47 (23.7%) patients, which is 47.9% of HIV negative patients, were receiving HIV PrEP. Forty-five (22.7%) were diagnosed with one or more concurrent STI such as gonorrhea, chlamydia, syphilis, genital herpes, Trichomonas vaginalis, at the time of mpox diagnosis. In addition, 2 (1.0%) were HBV-positive, 17 (8.6%) were HCV-positive, and 21 (10.6%) had a concurrent COVID-19 infection.

Table 1.

Demographics of patients with confirmed mpox infection.

	Total (N = 198)
Age, years
Median (IQR)	35 (29.8–43)
Mean (SD)	36.3 (9.9)
Gender, n (%)
Male	189 (95.5%)
Female	8 (4%)
Transgender	1 (0.5%)
Ethnicity
Hispanic	99 (50%)
Not hispanic	87 (43.9%)
Not documented	12 (6.1%)
Race, n (%)
White	132 (66.7%)
Black	58 (29.3%)
Asian	2 (1.0%)
Other	6 (3.0%)
Comorbidities
Hypertension	11 (5.6%)
Diabetes	6 (3.0%)
Smoking	13 (6.6%)
HBV-positive	2 (1.0%)
HCV-positive	17 (8.6%)
HIV-positive	100 (50.5%)
CD4⁺ cells/mm³	606 (396–865)
Missing	57/100 (57%)
HIV PrEP	47 (23.7%)
Concurrent STIs	45 (22.7%)
COVID-19	21 (10.6%)

Data given as the median (interquartile range), n (%), or n/N (%), where N is the total number of patients with available data.

The clinical characteristics of patients are presented in Table 2. Sixteen (8.1%) individuals had history of receiving vaccination against smallpox virus. 29 (14.6%) individuals had documented history of exposure to other individuals with confirmed or suspected mpox virus infections. All patients presented with skin lesions. Associated symptoms were fever or chill (34.8%), adenopathy (14.1%), fatigue, malaise, or lethargy (10.6%), myalgia (11.6%), and headaches (6.6%). To further describe the distribution of skin lesions, 48.5% had anogenital lesions, 23.7% had lesions on the trunk or extremities, 18.7% had oral or facial lesions. 48.9% had lesions involving more than two anatomical sites. The median interval from symptom onset to diagnosis were 4 days (IQR, 3−7). Sixty-three (31.8%) of 198 individuals received antiviral treatment for mpox; of those 54 (81.6%) patients were given tecovirimat. Twenty-eight (14.1%) individuals required admission to the hospital, mainly due to localized bacterial cellulitis requiring antibiotic treatment. No patients died due to mpox virus infection during their hospitalization.

Table 2.

Clinical characteristics of patients with confirmed mpox infection.

	Total (N = 198)
Smallpox vaccination history	16 (8.1%)
Recent exposure history	29 (14.6%)
Systemic symptoms
Rash	198 (100.0%)
Fever or chill	69 (34.8%)
Adenopathy	28 (14.1%)
Fatigue, malaise, or lethargy	21 (10.6%)
Myalgia	22 (11.1%)
Headache	13 (6.6%)
Localization of skin lesion
Anogenital	96 (48.5%)
Trunk, arms, or legs	47 (23.7%)
Oral or face	37 (18.7%)
Multiple lesions (≥2)	95 (47.9%)
Days from symptoms to diagnosis
Median (IQR)	4 (3–7)
Missing data	19/198 (9.6%)
Antiviral treatment
Tecovirimat	54 (27.3%)
Other	9 (4.5%)
Outcomes
Hospitalization	28 (14.1%)
ICU admission	0 (0%)
Death	0 (0%)

Data given as the median (interquartile range), n (%), or n/N (%), where N is the total number of patients with available data.

The demographic and clinical characteristics according to HIV status are presented in Table 3. There was no statistically significant difference in age, sex, and racial distribution. Nine (9%) of 100 HIV positive individuals and 6 (6.1%) of 98 non-HIV positive individuals had received smallpox virus vaccination in the past. Regarding differences in symptoms, PLWH had less incidence of adenopathy (4% vs. 27.3%, p < .001) and myalgia (4% vs. 18.4%, p = .001). PLWH had more incidence of extra-anogenital skin lesions, especially oral or facial lesions (28% vs. 9.2%, p = .001). There was no statistically significant difference in days from symptom onset to diagnosis between the two groups. PLWH were more likely to receive tecovirimat (36% vs. 18.4%, p = .005). PLWH were more likely to be admitted to hospital but did not reach statistical significance compared to non-HIV-positive individuals (16% vs. 12.2%, p = .542).

Table 3.

Clinical characteristics of patients stratified by HIV status.

	HIV+ (n = 100)	HIV- (n = 98)	p-value
Age, years	36 (30–44)	33 (28–42)	.211
Male	100 (100%)	89 (90.8%)	.002
Race			.235
White	63 (63%)	68 (69.4%)
Black	34 (34%)	24 (24.5%)
Other	3 (3%)	6 (6.1%)
Ethnicity			.781
Non-hispanic white	16/63 (35.4%)	19/69 (27.5%)
Hispanic white	47/63 (74.6%)	50/69 (72.5%)
Smallpox vaccination history	9 (9%)	6 (6.1%)	.444
Systemic symptoms
Fever or chill	36 (36%)	33 (33.7%)	.731
Adenopathy	4 (4%)	24 (27.3%)	<.001
Fatigue, malaise, or lethargy	8 (8%)	13 (13.3%)	.229
Myalgia	4 (4%)	18 (18.4%)	.001
Headache	10 (10%)	3 (3.1%)	.049
Localization of skin lesion
Anogenital	38 (38%)	58 (59.2%)	.003
Trunk, arms, or legs	26 (26%)	21 (21.4%)	.449
Oral or face	28 (28%)	9 (9.2%)	.001
Multiple lesions (≥2)	42 (42%)	53 (54.1%)	.089
Days from symptoms to Dx
Median (IQR)	4 (2–7)	4 (3–7)	.644
Missing data	11/100 (11%)	8/98 (8.2%)	.644
Antiviral treatment
Tecovirimat	36 (36%)	18 (18.4%)	.005
Outcomes
Hospitalization	16 (16%)	12 (12.2%)	.448
ICU admission	0 (0%)	0 (0%)	>.999
Death	0 (0%)	0 (0%)	>.999

Data given as the median (interquartile range), n (%), or n/N (%), where N is the total number of patients with available data.

Discussion

We present the demographic data and clinical characteristics of the global mpox outbreak in a population with one of the highest burden of HIV infection in the United States.⁷ In 2021, the prevalence of HIV infection was 971.2 and 1079.4 per 100,000 population in Miami Dade and Broward County respectively.⁸ Our data demonstrated that 50.5% of patients with mpox infection were HIV positive, which was consistent with the report from the Centers for Disease Control and Prevention (CDC) in which 57% had HIV infection.⁹ Per CDC, Florida had the fourth highest number of mpox infection cases (total 2875) as of March 1^st among 50 states.¹⁰ These data demonstrate how PLWH are disproportionately represented among those with mpox infection.

The clinical presentation of mpox virus infection in our study was similar to other published reports.^4,9 All patients presented with skin lesions, of which the majority being anogenital. In both groups, time from symptom onset to diagnosis was similar (median of 4 days). When comparing clinical presentation between HIV positive and HIV negative patients, the former were less likely to have adenopathy and myalgia and were more likely to have oral or facial lesions. Earlier reports of the U.S. mpox outbreak showed higher prevalence of rectal signs and symptoms among PLWH, possibly related to differences in site of exposure. However, we observed a comparable rate of anogenital lesions between HIV positive and negative patients.⁴ Given this data, we suggest clinicians to have low threshold to suspect mpox virus infection in HIV positive patients who present with extra-anogenital lesions such as lesions on the face, mouth, trunk, or extremities.

Regarding the severity of illness, studies from previous mpox outbreaks in Nigeria during 2017-2018 reported a case fatality rate of 6%, from which 4 among 7 deaths involved patients with HIV/AIDS.³ Studies on recent outbreaks showed the disease is mild and self-limited.¹¹ Patients who required hospitalization were more likely to be HIV positive and the most common cause of hospitalization was pain control and bacterial superinfection.¹² In our study we observed no significant difference in hospitalization rate between HIV positive and negative patients. Also, there were no reported intensive care unit (ICU) admissions or deaths. In a study by Miller et al. regarding patients with severe mpox who required hospitalization, 82% had HIV infection, 30% were admitted to ICU and 21% died.¹³ We believe that due to low fatality rate and limited sample size of our study, we were not able to detect a severe case. The fact that the median time from symptom onset to diagnosis was relatively short at 4 days might have contributed to the low fatality rate in our study. This imposes a limitation on our study that we could not elucidate the risk factors for severe mpox virus infection. In addition, only 43% of PLWH had recent CD4 count documented, because most encounters with the healthcare systems at the point of mpox diagnosis were based on the emergency department visits, in which situation the patient’s HIV care was often provided from a different healthcare facility. For the same reason, we were not able to collect sufficient data on anti-retroviral therapy (ART) status and viral load. Among our 43% of HIV positive patients who had a CD4 count documented, most did not have advanced HIV disease. This contrasts to the data from the study by Miller et al., where 72.1% of patient had CD4 cell count less than 50 cells/mm³, 20.9% had between 50 to 200 cells/mm³, and only 7.0% had higher than 200 cells/mm³.¹³ This difference might explain why fatality rate was not increased in HIV positive patients in our study.

Our study showed 22.7% of patients were diagnosed with one or more concomitant STIs at the time of mpox diagnosis. Similarly, the study by Miller et al. described that over 41% of persons with mpox had been diagnosed with another STI in the preceding year.⁵ Given high proportion of PLWH and their risk of STI, we recommend that all patients diagnosed with mpox infection have on-site HIV and STI screening. CDC recommends patient with newly diagnosed HIV infection at the time of mpox diagnosis should be started on ART immediately.¹⁴ If HIV test is negative, we suggest that PrEP should be considered in patients with mpox.

In our study, HIV positive patients were more likely to receive mpox-specific therapy, tecovirimat, as it was the first-line medication recommended by CDC for treatment of mpox including PLWH at the time of the study.¹² During the retrospective chart review, we noticed that PLWH are more likely to have established care with an infectious disease specialist, thus were more likely to be provided the option of receiving tecovirimat. Knowing the importance of the role of infectious disease specialists or outpatient providers who have experience in treating HIV and other STIs, we suggest a care transition model for patients who are diagnosed with mpox in an urgent care or an emergency department. We suggest creating a “mpox order set” in the electronic health record (EHR) which includes screening for HIV, STIs, and referral to infectious disease clinic. In the specialist clinic, the patients can be offered more comprehensive care including mpox-directed treatment options, ART or PrEP, prevention of transmission, and adequate follow-up. For resource-poor or rural areas with no access to local infectious disease clinic, consultation with an infectious disease expert would be highly recommended. These approaches would potentially lead to better and sooner treatment and improved outcomes. Finally, patients who are already being followed for HIV infection should be prioritized for mpox vaccination considering higher risk of mpox infection.

Conclusion

In this retrospective study involving 198 patients diagnosed with mpox virus infection in South Florida during the 2022-2023 mpox epidemic, most patients were young (median age of 35) males. HIV positive patients were disproportionately represented among the patients diagnosed with mpox virus infection. A significant portion of patients diagnosed with mpox had concomitant STIs and/or were on PrEP. Hospitalization rate was not significantly different between HIV positive and HIV negative groups, and there was no ICU admission or death. PLWH were less likely to have adenopathy and myalgia and were more likely to have oral or facial lesions. We recommend the development and clinical use of a structured order sets in EHR where it is applicable to provide HIV and STI screening and referral to infectious disease specialist for patients diagnosed with mpox to improve the quality of care.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The study protocol was reviewed and approved by the Institutional Review Board of the Memorial Healthcare System (MHS.2022.087).

ORCID iDs

Myeongji Kim

Nathalie P Suárez Moscoso

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