Clinical, Virological, Immunological, Psychosocial and Epidemiological Consequences of Human Monkeypox Virus (ProMPX) (ProMPX)

Clinical, Virological, Serological and Psychosocial Outcomes in Human Monkeypox Virus Infectious Disease - a PROspective Observational Cohort Study for Epidemiology and Outcomes of MPXVID

MonkeyPox Virus Infectious Disease (MPXVID) is a viral infection caused by the monkeypox virus (MPXV) which is an orthopoxvirus that is endemic in countries in West and Central Africa. The clinical course of the MPXVID is similar to smallpox (variola) but usually milder - with less severe disease symptoms seen in the West African subtype. Historically, the case fatality ratio of MPXVID ranged from 0 to 11% and fatality occurs more commonly among children. In Europe, human MPXVID only occurred as an imported disease with limited onward transmission. However, since May 2022 over 19.000 cases of MPXVID - mostly with the West African subtype - have been reported in Europe without a travel history to the endemic areas in Africa. The far large majority of patients with MPXVID in the current outbreak are gay, bisexual and other men who have sex with men (GBMSM). There is an urgent need to address essential knowledge gaps for optimal clinical care and public health management.

The aim of this study is to improve our understanding of clinical, virological, and psychosocial outcomes in patients with MPXVID. To get a better understanding of associated risk factors for MPXV infection, and to measure quality of life and stigma, the investigators will also include a control population of men without proctitis and MPXVID-related symptoms at day 0. In addition, the investigators want to assess the vaccine effectiveness against MPXVID of infant smallpox vaccination given before 1974, as well as vaccine effectiveness of the modified vaccinia Ankara (MVA) smallpox vaccine, when administered as pre- or post-exposure prophylaxis in high risk contacts of MPXVD patients.

Study Overview

• Status: Recruiting
• Conditions: Monkeypox; Monkey Pox
• Intervention / Treatment: Other: Natural course of disease

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Henry J.C. de Vries, Prof. dr.; Phone Number: + 315555665; Email: h.j.devries@amsterdamumc.nl
• Study Contact Backup: Name: Buhari Teker, MD; Phone Number: +315555665; Email: bteker@ggd.amsterdam.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1054cs
      • Recruiting
      • Public Health Service
      • Contact: Henry JC de Vries; Phone Number: +315555665; Email: h.j.devries@amsterdamumc.nl
      • Contact: Buhari Teker; Phone Number: +315555665; Email: bteker@ggd.amsterdam.nl
      • Principal Investigator: Henry JC de Vries, MD PhD
      • Sub-Investigator: Buhari Teker, MD
      • Principal Investigator: Else Hoornenborg, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The target population are all individuals visiting the STI-clinic of the Public Health Services of Amsterdam, irrespective of their gender, aged 16 years or older with a laboratory confirmed MPXV infection, or are suspected of MPXV while laboratory confirmation is pending. MPXV infection is diagnosed according to a routinely performed PCR test on lesion, anal-, pharyngeal and vaginal swabs in patients suspect of having MPXVID. The controls will be clients of the STI clinic who are individuals without proctitis and without MPXVID-related symptoms; they will only be matched on date of inclusion.

Description

Inclusion Criteria

Case:

- Individuals, with: I. Laboratory confirmed MPXVID, or II. A presumptive MPXVID case with pending laboratory confirmation

- Be able to provide informed consent by means of: I. Verbal or deferred informed consent, which will be complemented with a written informed consent during the subsequent outpatient study visit; II. Written informed consent during the baseline visit for presumptive cases

- Sufficient understanding of the Dutch or English language.

Control:

- Individuals without proctitis and MPXVID-related symptoms

Exclusion Criteria

Case:

• Presumptive cases with subsequent negative test for MPXV (can be included as control);
• Being under the age of 16 years old;
• Unlikely to comply with the study procedures, as deemed by the recruiting research doctor/nurse;
• Mental disorder that in the view of the investigator would interfere with adherence to the study procedures, or the decision to participate in the study;
• Investigators or otherwise dependent persons;
• Living in long term care facility.

Control:

• Positive test result for MPXV at baseline (day 0)
• Being under the age of 16 years old;
• Unlikely to comply with the study procedures, as deemed by the recruiting research doctor/nurse;
• Mental disorder that in the view of the investigator would interfere with adherence to the study procedures, or the decision to participate in the study;
• Investigators or otherwise dependent persons;
• Living in long term care facility.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; Individuals with laboratory confirmed MPXVID	Other: Natural course of disease; Sample and questionnaire collection
Control; Individuals without proctitis and without MPXVID-related symptoms	Other: Natural course of disease; Sample and questionnaire collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
What is the time to resolution of symptoms among patients with symptomatic MPXVID?	The time between appearance of the first lesions and the day on which all skin lesions are epithelialized and crusts fall off, and all systemic symptoms (incl. proctitis) have resolved.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe and analyse demographic characteristics in patients with MPXVID.	Demographic characteristics at enrolment visit.	180 days
To describe and analyse sexual characteristics in patients with MPXVID.	Sexual characteristics at enrolment visit.	180 days
To describe and analyse clinical characteristics in patients with MPXVID.	Clinical status of MPXVID at baseline and days 4, 8, 14, 21, 60 and 180: According to a 4 pt ordinal scale.; Location(s) of lesion(s): peri-genital, peri-anal, peri-oral, romp, arms, legs, head.; Number of lesions: 1, 2-5, >5.; Presence of proctitis related symptoms.	180 days
To describe and analyse other clinical characteristics in patients with MPXVID.	Other clinical outcomes on days 4, 8, 14, 21, 60 and 180, as follows: Proportion of patients with systemic symptoms.; Proportion of patients with proctitis.; Proportion of patients with oral lesions, pharyngitis and/or oesophagitis; Proportion of patients requiring pain medication.; Proportion of patients requiring additional medical consultations; Proportion of patients with a significant reduction of their quality of live (measured with Dermatology Life Quality Index (DLQI) with outcome above 10 points).; Proportion of patients with secondary bacterial infection of MPXVID lesions.	180 days
To describe the presence of MPXV DNA and cycle threshold (Ct) values in patients with MPXVID.	The presence of MPXV DNA and cycle threshold (Ct) values in lesion swabs on baseline and days 4, 8, 14, 21 and 28.	180 days
To describe other virological outcomes in patients with MPXVID.	Change from baseline in MPXV DNA levels in anal-, pharyngeal and vaginal swabs, semen and blood (also the development of antibody levels) on days 4, 8, 14, 21, 28, 60 and 180.	180 days
To describe changes in sexual behaviour in patients with MPXVID in comparison to controls.	Sexual behaviour measurement at baseline and change at days 14, 28, 60 and 180 (only baseline, day 60 and day 180 for controls).	180 days
To describe changes in quality of life in patients with MPXVID in comparison to controls.	DLQI questionnaire measurement of the quality of live change at baseline and change at days 14, 28, 60 and 180 (only baseline, day 60 and day 180 for controls).	180 days
To describe changes in the experience of (internalized) stigma in patients with MPXVID in comparison to controls.	Questionnaires of the experience of (internalized) stigma at baseline and change at days 28 and 180 (only baseline and day 180 for controls).	180 days
To describe changes in the experience of fatigue in patients with MPXVID in comparison to controls.	Sexual Function Questionnaire (SFQ) questionnaire measurement of fatigue at baseline and change at days 14, 28, and 60 (only baseline and day 60 for controls).	60 days
To describe changes in the physical and psychological health in patients with MPXVID in comparison to controls.	PATIENT HEALTH QUESTIONNAIRE - Schedule for Affective Disorders and Schizophrenia (PHQ-SADS) questionnaire measurement of anxiety, depression, somatic complaints at baseline and change at days 28 and 180 (only baseline and day 180 for controls).	180 days
To estimate the effectiveness against MPXVID of infant smallpox vaccine given before 1974.	Measuring the proportion of patients with a laboratory confirmed MPXVID and of controls without MPXVID who are vaccinated with the infant smallpox vaccine before 1974, and estimate vaccine effectiveness (i.e. disease severity outcome).	through study completion, an average of 1 year
To estimate the effectiveness against MPXVID of modified vaccinia Ankara (MVA) smallpox vaccine.	Measuring the proportion of patients with a laboratory confirmed MPXVID and of controls without MPXVID who are vaccinated with the modified vaccinia Ankara (MVA) smallpox vaccine, either as pre- or as post-exposure prophylaxis against MPX after June 2022.	through study completion, an average of 1 year
To describe the use of antiviral medication and/or immunoglobulins.	Proportion of patients treated with antiviral and/or immunoglobulins.	180 days

Collaborators and Investigators

• Sponsor: Public Health Service of Amsterdam

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Anticipated): September 19, 2023
• Study Completion (Anticipated): December 19, 2023

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Monkeypox
• Other Study ID Numbers: ProMPX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No