Clinical trial NCT06652646: Mpox Biology, Outcome, Transmission and Epidemiology
Official title: MBOTE-Kamituga / Mpox Biology, Outcome, Transmission and Epidemiology - Protocole De Caractérisation Clinique Et Virologique Des Infections À Virus De Monkeypox À Kamituga (MBOTE-Kamituga)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Mpox (Monkeypox)
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Ministry of Public Health, Democratic Republic of the Congo
name: Research Foundation Flanders
name: National Institutes of Health (NIH)
First posted: 2024-10-22
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All persons applying to be tested for VMPX at HGR or another test center.

Brief summary: The MBOTE-Kamituga clinical and virological characterization protocol is a prospective observational cohort study with clinical and virological description of suspected mpox cases and longitudinal follow-up of confirmed mpox cases. Research activities will be aligned as far as possible with the response to the epidemic.

Detailed description: For several decades, the Democratic Republic of Congo (DRC) has been the country most affected by monkeypox. While the global monkeypox epidemic (commonly known as mpox) of 2022-2023 was caused by clade II monkeypox virus (VMPX), outbreaks in the DRC are caused by the more virulent clade I variant. In recent years, and particularly in 2023, the country has seen a sharp increase in the number of cases, as well as a geographical expansion of the disease, with previously unaffected regions now reporting cases. Until recently, VMPX infections in the DRC were thought to be primarily the result of zoonotic transmission, with rather limited secondary human-to-human transmission. However, in recent months, an increasing number of cases linked to sexual transmission of clade I have been reported.

The Kamituga health zone is a densely populated mining region in South Kivu. The region reported no cases of smallpox in recent decades until, in October 2023, the disease was detected for the first time and began to affect mainly adolescents and young adults. To date, nearly 200 cases have been reported to health authorities, although the actual number of cases may be much higher due to significant under-reporting. Preliminary data show that the epidemic is mainly due to heterosexual transmission, and that up to 30% of cases are reported by sex workers, many of whom come from Burundi, Rwanda, Uganda and Tanzania. The ongoing transmission poses a significant risk of cross-border spread and could therefore lead to a new global smallpox epidemic, this time caused by the more virulent clade I.

The study will be carried out in collaboration with the Direction Provincial de la Santé/Kamituga and the Programme National de Lutte contre le Monkeypox et les Fièvres Virales Hémorragiques (PNLMPX/FVH) in the Kamituga Health Zone. Participants will be recruited at the Kamituga general referral hospital (HGR) or at health centers that provide mpox screening and treatment.

The MBOTE (Monkeypox Biology, Outcome, Transmission and Epidemiology) project is a multidisciplinary research collaboration between the National Institute for Biomedical Research (INRB), the Antwerp Institute of Tropical Medicine (ITM Antwerp) and the University of Antwerp.

This research protocol aims to better understand the mpox epidemic currently raging in the Kamituga SZ, as well as to provide more general information on the disease. The protocol describes the research activities that will be integrated into the ongoing epidemic investigation and control activities. Research activities will be aligned as far as possible with the ongoing epidemic response and should not hinder the response, but rather support it.

Similarly, sample collection will be aligned with the sampling carried out by the national program, and some samples will undergo additional analysis to answer the research objectives and questions.

Participation in this epidemic investigation protocol will in no way prevent patients from taking part in any other research study.

The study will be aligned as far as possible with the investigation and management of the epidemic by the national program. The study will therefore run for up to 2 months after the end of the epidemic (for convalescent patients who can be followed up for up to 2 months (day 59) after confirmation of infection), or could run for 2 years whether or not the epidemic is over. The shorter duration will be chosen, so as not to delay the reporting of results to the competent authorities, which will be essential for informing control and research activities in subsequent epidemics.

There is no fixed sample size defined for this protocol. On the contrary, as far as possible, all patients with suspected mpox will be included in the study.

Eligibility criteria: Inclusion Criteria:

* To be tested for VMPX at the HGR or another testing center. Patients of all ages and sexes
* Minors (≤ 17 years) are excluded from genital, anal and semen sampling and follow-up blood sampling.

Patient or culturally acceptable representative is willing and able to give informed consent for study participation.

Exclusion Criteria:

* NA

Primary outcomes:
measure: Characterize the clinical presentation of suspected mpox cases
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Characterize the longitudinal clinical course of PCR-confirmed cases
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Identification of viral shedding sites and appropriate sampling strategy
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Characterize the virological evolution of confirmed cases
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Determine the seroconversion rate among confirmed cases of mpox
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Assess risk factors for mpox disease.
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: To assess the protective effect of previous smallpox vaccination on symptomatic mpox disease.
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
Secondary outcomes:
measure: Assess genomic differences between VMPX strains isolated from confirmed cases of mpox due to sexual transmission and other modes of transmission
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
measure: Support General Referral Hospital (GRH) Kamituga
timeFrame: Up to 2 months after the end of the epidemic, with a maximum of 2 years
Other outcomes:
Locations:
city: Kamituga
country: Congo, The Democratic Republic of the
facility: Kamituga General Hospital
Study officials:
affiliation: Institute of Tropical Medicine
name: Laurens Liesenborghs
role: STUDY_DIRECTOR
References:
citation: Vakaniaki EH, Kacita C, Kinganda-Lusamaki E, O'Toole A, Wawina-Bokalanga T, Mukadi-Bamuleka D, Amuri-Aziza A, Malyamungu-Bubala N, Mweshi-Kumbana F, Mutimbwa-Mambo L, Belesi-Siangoli F, Mujula Y, Parker E, Muswamba-Kayembe PC, Nundu SS, Lushima RS, Makangara-Cigolo JC, Mulopo-Mukanya N, Pukuta-Simbu E, Akil-Bandali P, Kavunga H, Abdramane O, Brosius I, Bangwen E, Vercauteren K, Sam-Agudu NA, Mills EJ, Tshiani-Mbaya O, Hoff NA, Rimoin AW, Hensley LE, Kindrachuk J, Baxter C, de Oliveira T, Ayouba A, Peeters M, Delaporte E, Ahuka-Mundeke S, Mohr EL, Sullivan NJ, Muyembe-Tamfum JJ, Nachega JB, Rambaut A, Liesenborghs L, Mbala-Kingebeni P. Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo. Nat Med. 2024 Oct;30(10):2791-2795. doi: 10.1038/s41591-024-03130-3. Epub 2024 Jun 13.