---
title: "Cocirculation of Monkeypox Virus Clade 1b and Varicella Zoster Virus in Uganda"
id: "cdc-emerging-infectious-diseases-journal-7-cocirculation-of-human-monkeypox-virus-clade-1b-with-varicella-zoster-virus"
canonical_url: "https://medichelpline.com/clinical-feed/cdc-emerging-infectious-diseases-journal-7-cocirculation-of-human-monkeypox-virus-clade-1b-with-varicella-zoster-virus"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "CDC Emerging Infectious Diseases Journal"
source_url: "https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article"
published_at: "2026-09-21T04:00:00.000Z"
evidence_level: "Agency Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Cocirculation of Monkeypox Virus Clade 1b and Varicella Zoster Virus in Uganda
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** CDC Emerging Infectious Diseases Journal
- **Source URL:** [Original Journal Publication](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article)
- **Published At:** 2026-09-21T04:00:00.000Z
- **Evidence Rating:** Agency Feed
## Executive GIST (TL;DR)
- In July–December 2024, Uganda collected 1,072 specimens from patients with clinically suspected mpox; 193 (18%) were PCR-positive for **monkeypox virus (MPXV)** and 879 (82%) were MPXV-PCR negative. - Confirmed mpox patients were 48.7% male and 51.3% female; 47.8% were aged 16–30 years. Approximately 65% of samples originated from central Uganda. - Researchers sequenced 115 MPXV-positive samples (target enrichment NGS) and a randomly selected subset of 127 MPXV-negative samples (metagenomic and target enrichment NGS). - All new MPXV genomes clustered within **clade 1b**, closely related to previously reported Uganda and Democratic Republic of Congo sequences, though mutational profiles showed limited overlap with earlier Uganda strains. - Phylogenetic and mutational reconstruction identified 284 mutation events in Uganda MPXV sequences; 118 (41.4%) were consistent with **APOBEC3**-mediated TC->TT or GA->AA dinucleotide substitutions. - Functional annotation of nonsynonymous changes in recent strains implicated proteins involved in immune evasion, inhibition of host responses (inflammasome, T-cell activation), transcription and RNA metabolism, virion morphogenesis, and viral entry/egress. - Of 127 MPXV-PCR–negative samples sequenced, **varicella zoster virus (VZV)** was detected with >80% genome coverage in 106 (83%); most VZV sequences formed a single Uganda clade related to sequences from Nigeria, Ghana, and Guinea-Bissau. - Other pathogens identified in MPXV-negative samples included coxsackievirus A6, measles virus genotype B3, polyomaviruses, and several bacterial species. - MPXV sequences (n = 115) were submitted to GISAID; VZV genomes were deposited in GenBank (BioProject PRJNA1281018). The study underscores the need to refine differential diagnosis by molecular testing and strengthen surveillance for co-circulating rash illnesses.
## Clinical Analysis & Structured Key Points
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[EID Journal](https://wwwnc.cdc.gov/eid/) 2. [Volume 32](https://wwwnc.cdc.gov/eid/early-release) 3. [Early Release](https://wwwnc.cdc.gov/eid/early-release#issue-1346) 4. [Main Article](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article) * [Facebook](https://www.facebook.com/sharer/sharer.php?u=%2Feid%2Farticle%2F32%2F10%2F25-1264_article "Share to Facebook") * [Twitter](http://twitter.com/share?url=%2Feid%2Farticle%2F32%2F10%2F25-1264_article&text= "Share to Twitter") * [LinkedIn](https://www.linkedin.com/shareArticle?url=%2Feid%2Farticle%2F32%2F10%2F25-1264_article&title= "Share to LinkedIn") * [Syndicate](https://tools.cdc.gov/medialibrary/index.aspx#/sharecontent//eid/article/32/10/25-1264_article "Embed this Page") [ Emerging Infectious Disease journal ISSN: 1080-6059 ](https://wwwnc.cdc.gov/eid/) _Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released._ #### Volume 32, Number 10—October 2026 ##### _Research Letter_ ### Cocirculation of Human Monkeypox Virus Clade 1b with Varicella Zoster Virus, Uganda On This Page [Research Letter](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article) * * * [Suggested Citation](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article) Figures [Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f1) * * * [Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f2) Downloads [Appendix 1 ](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app1.pdf) * * * [Appendix 2 ](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app2.xlsx) * * * [RIS [TXT - 2 KB] ](https://wwwnc.cdc.gov/eid/article/32/10/25-1264.ris) Article Metrics [Metric Details](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article) Related Articles [Meta-analysis of Asymptomatic MPXV Prevalence](https://wwwnc.cdc.gov/eid/article/32/10/26-0305_article) * * * [Monkeypox Virus, Sierra Leone, June 2025](https://wwwnc.cdc.gov/eid/article/32/10/25-1697_article) * * * [Monkeypox Virus Surveillance in Wastewater](https://wwwnc.cdc.gov/eid/article/32/13/26-0414_article) * * * [More articles on monkeypox, mpox](https://wwwnc.cdc.gov/eid/spotlight/mpox) Nicholas Bbosa[![Comments to Author](https://wwwnc.cdc.gov/eid/content/images/icon/email.gif)](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#comment) , Alfred Ssekagiri, Hamidah S. Namagembe, Stella E. Nabirye, Ronald Kiiza, Danstan Kabuuka, Stephen Balinandi, Tom Lutalo, John Kayiwa, Henry Kyobe Bosa, Robert Downing, Michael G. Berg, Mary A. Rodgers, Gavin A. Cloherty, Pontiano Kaleebu, and Deogratius Ssemwanga Author affiliation: Uganda Virus Research Institute, Entebbe, Uganda (N. Bbosa, A. Ssekagiri, S.E. Nabirye, D. Kabuuka, S. Balinandi, T. Lutalo, J. Kayiwa, R. Downing, P. Kaleebu, D. Ssemwanga); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe (N. Bbosa, H.S. Namagembe, R. Kiiza, P. Kaleebu, D. Ssemwanga); Abbott Pandemic Defense Coalition, Abbott Park, Illinois, USA (N. Bbosa, M.G. Berg, M.A. Rodgers, G.A. Cloherty); Uganda Ministry of Health, Kampala, Uganda (H.K. Bosa); Uganda People’s Defence Forces, Kampala (H.K. Bosa); Makerere University Lung Institute, Kampala (H.K. Bosa); Abbott Diagnostics, Abbott Park (M.G. Berg, M.A. Rodgers, G.A. Cloherty) [Suggested citation for this article](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#suggestedcitation) ### Abstract In July 2024, we reported information on the initial human mpox cases in Uganda. Genomic characterization of clinically suspected cases (July–December 2024) revealed cocirculation of several monkeypox virus clade 1b clusters and varicella zoster virus. Our findings highlight the need to refine differential diagnoses by molecular techniques and strengthen surveillance. In July 2024, human mpox cases were initially reported in Uganda ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r1 "1")). As of May 28, 2025, up to 6,479 confirmed mpox cases, including 44 deaths, have been reported ([_2_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r2 "2")). However, several clinically suspected mpox case-patients tested negative for monkeypox virus (MPXV) by real-time PCR. Mpox can be misdiagnosed as other infections that manifest in rash, especially during the early macule and papule stages of the infection ([_3_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r3 "3")). Patients with mpox and chickenpox co-infections have been reported in the Democratic Republic of Congo (DRC) ([_4_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r4 "4")), Burundi ([_5_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r5 "5")), and Nigeria ([_6_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r6 "6")). Mpox case-patients frequently experience a febrile prodrome with a high fever 1–4 days before the onset of rash, whereas a low-grade fever is more common in chickenpox patients ([_4_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r4 "4")). Furthermore, lymphadenopathy is a distinguishing symptom characteristic of mpox infection ([_6_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r6 "6")) but not chickenpox infection. Here, we describe phylogenetic characterization and mutational analysis of circulating MPXV and other viruses from clinically suspected mpox cases in Uganda. We conducted real-time PCR on 1,072 samples from patients with clinically suspected MPXV during July–December 2024. A total of 193 persons tested positive for MPXV. Confirmed mpox case-patients were 48.7% male, 51.3% female; cases primarily occurred in persons 16–30 years of age (47.8%) ([Appendix 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app1.pdf) Table 1). We obtained 65% of samples from central Uganda. Of the 879 (82%) samples that tested negative for MPXV by PCR, we sequenced a randomly selected subset (127 [14%]) to identify other potential pathogens. Figure 1 ![Phylogenetic and mutational characterization of Uganda monkeypox virus \(MPXV\) strains in study of cocirculation of human MPXV clade 1b with varicella-zoster virus, Uganda. A\) Maximum-likelihood phylogenetic tree of MPXV sequences generated with 1,000 bootstrap resampling. Tree includes 115 new sequences from Uganda \(highlighted with a gray rectangular background\) and 37 clade 1B reference sequences retrieved from GenBank and GISAID \(https://www.gisaid.org\) \(accession numbers provided\). Highly similar sequences have been collapsed \(denoted by triangle\). Scale bar indicates number of nucleotide substitutions per site. B\) New \(n = 115; red squares\) and previously reported \(n = 22; blue squares\) Uganda sequences were aligned, and Squirrel software was used to infer the maximum-likelihood phylogeny and map APOBEC \(brown circle\) and non-APOBEC \(yellow circle\) mutation events. The number of unique mutations from this study and shared mutations distinct from the DQ011155.1 clade I archetype are listed.](https://wwwnc.cdc.gov/eid/images/25-1264-F1-tn.jpg) [Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f1 "Figure 1"). Phylogenetic and mutational characterization of Uganda monkeypox virus (MPXV) strains in study of cocirculation of human MPXV clade 1b with varicella-zoster virus, Uganda. A) Maximum-likelihood phylogenetic tree of MPXV sequences... We genotyped 115 MPXV PCR–positive samples using target enrichment NGS (Illumina, [External Link](https://www.illumina.com); Twist Biosciences, [External Link](https://www.twistbioscience.com)) and the 127 MPXV PCR–negative samples using metagenomic NGS and target enrichment NGS, followed by sequencing on a MiSeq ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r1 "1")). We analyzed FASTQ files using UVRI’s in-house metagenomic NGS ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r1 "1")) and Abbott’s DiVir pipelines ([_7_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r7 "7")) and One Codex software (S.S. Minot et al., unpub. data, [External Link](https://www.biorxiv.org/content/10.1101/027607v2)). We performed phylogenetic tree reconstructions using IQ-TREE ([_8_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r8 "8")), which showed new Uganda MPXV sequences were clade 1b and genetically close to previous sequences from Uganda and DRC ([Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f1), panel A). We performed a mutational analysis on Uganda strains (n = 137) using Squirrel software (https://artic.network/software/squirrel), comparing new sequences (n = 115) to previous sequences (n = 22) relative to reference strain Zaire-1979-DQ011155.1 from GenBank. Squirrel infers a maximum-likelihood phylogeny with IQ-TREE2 and performs ancestral state reconstruction to map APOBEC and non-APOBEC mutation events onto individual branches ([Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f1), panel B). TC->TT or GA->AA dinucleotide substitutions were consistent with APOBEC3-mediated cytosine deamination. The reconstructed phylogeny identified 284 mutation events (synonymous, nonsynonymous, intergenic) in Uganda sequences; of those, 118 (41.4%) mutations were APOBEC3-mediated ([Appendix 1 ](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app1.pdf)Table 2). We observed distinct profiles of affected genes among sequences from this study compared with previously reported Uganda sequences ([Appendix 2](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app1.pdf)). Focusing on nonsynonymous changes, functional annotations of affected genes acquiring APOBEC and non-APOBEC mutations were similar between cohorts. For previous strains, fewer functional annotations were identified related to apoptosis inhibition, viral maturation, and mRNA (de)capping. For strains sequenced in this study, amino acid changes affected proteins involved in inhibition of host responses (inflammasome, T-cell activation) and immune evasion, transcription and RNA metabolism (poly-A polymerase, DNA-dependent RNA polymerase), virion morphogenesis, and viral entry/egress pathways. Figure 2 ![Distribution of viral pathogens and phylogenetic analysis in study of cocirculation of human monkeypox virus clade 1b with varicella-zoster virus, Uganda. A\) Viral pathogens detected in monkeypox virus–negative samples by metagenomic next-generation sequencing. Bar plot shows the number of samples in which viruses were identified with a genome coverage >80%. B\) Maximum-likelihood phylogenetic tree of varicella-zoster virus sequences. The tree includes 106 high-coverage genome sequences \(>80% genome coverage\) generated in this study and other publicly available complete genomes from NCBI \(accession numbers provided\). Most sequences have been collapsed into the triangle at the top, which contains 98 varicella zoster virus sequences generated in this study and 16 publicly available Uganda genomes, together forming a single well-supported clade. Sequences shown individually are those resolving outside that clade: 8 study sequences from Uganda \(red\), which form 2 distinct lineages, and the 6 publicly available genomes from Ghana, Nigeria and Guinea-Bissau \(blue\) that are their closest relatives. NCBI, National Center for Biotechnology Information. ](https://wwwnc.cdc.gov/eid/images/25-1264-F2-tn.jpg) [Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f2 "Figure 2"). Distribution of viral pathogens and phylogenetic analysis in study of cocirculation of human monkeypox virus clade 1b with varicella-zoster virus, Uganda. A) Viral pathogens detected in monkeypox virus–negative samples by... We detected varicella zoster virus (VZV) in 106 (83%) of 127 specimens with genome coverage >80% ([Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f2), panel A). VZV sequences were genetically similar to those identified in Nigeria, Ghana, and Guinea-Bissau ([Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-f2), panel B). Other pathogens identified included coxsackievirus A6 (9 [7%]), measles virus genotype B3 (7 [6%]), polyomaviruses (5 [4%]), _Cutibacterium acnes_ , _Staphylococcus aureus_ , _Streptococcus pyogenes,_ and _Corynebacterium diphtheriae._ We submitted MPXV sequences (n = 115) to GISAID ( [External Link](https://www.gisaid.org), under EpiPox) in nonsequential installments ([Appendix 1](https://wwwnc.cdc.gov/eid/article/32/10/25-1264-app1.pdf)) and VZV data (National Center for Biotechnology Information BioProject no. PRJNA1281018) to GenBank (accession nos. PV845252–301). Genotypic characterization of confirmed mpox cases determined that MPXV sequences belonged to clade Ib and were highly related to previously reported Uganda sequences ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/25-1264_article#r1 "1")), although mutational profiles displayed minimal overlap. Gene ontology suggests recent strains are under selective pressure to evade host responses and increase transmission through improved replicative and transc
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