Can investigating viral causes of vesicular rash reduce misclassification of mpox cases in South Africa?
Mpox is a viral zoonotic disease caused by the monkeypox virus (MPXV) and remains a public health concern globally. Prior to 2022, human mpox was reported sporadically from a limited number of countries in West and Central Africa. Since 2022, sustained human-to-human transmission has driven a multi-country outbreak, with more than 130 000 laboratory-confirmed cases reported from over 100 countries. These trends reflect a shift in the epidemiology of mpox and have highlighted limitations in existing detection and response systems.
Multiple MPXV clades have contributed to recent transmission. A large proportion of cases reported between 2022 and 2025 were associated with the Clade IIb sublineage B.1, which emerged following prolonged human transmission. More recently, Clade Ib MPXV, first identified in the Democratic Republic of the Congo, has continued to evolve and has been detected outside the region since 2024, indicating ongoing international spread.
Mpox transmission occurs primarily through close contact with infectious skin lesions, lesion fluid, or scabs, with additional spread via contaminated fomites and respiratory droplets. Clinical presentation is variable and may include a non-specific febrile illness followed by a vesicular rash.
The clinical diagnosis of mpox is complicated by a broad differential diagnosis, as several infectious and non-infectious conditions may present with similar rash manifestations. Laboratory confirmation using polymerase chain reaction testing of lesion samples is therefore essential. In South Africa, mpox has been reported since 2022 and is a Category 1 notifiable medical condition, with testing coordinated through the National Institute for Communicable Diseases.
The following report describes the epidemiology of mpox in South Africa and examines the differential diagnosis of suspected mpox cases to support improved surveillance and case detection.
Materials and Methods
A retrospective analysis of samples submitted for diagnostic investigation of mpox to the Special Viral Pathogens Laboratory (SVPL) of the Centre for Emerging Zoonotic and Parasitic Diseases (CEZPD), held within the NICD was performed.
The study used a Microsoft® Excel database, curated at the CEZPD, containing data pertaining to suspected mpox cases. The database was developed from data extracted from test requests and case investigation forms submitted with samples for mpox investigations.
A new spreadsheet was created with variables extracted from the mpox Microsoft® Excel database and included patient number, MPXV test result, date of test, and age and sex. The results of the multiplex PCR test for each virus target were additionally captured for the analysis. The results were summarised in frequency tables containing tallies and percentages.
Results
A total of 52% (n=193/372) of MPXV DNA-negative cases tested PCR positive for other causes of viral vesicular rash when using the multiplex approach. PCR positivity for two targets was detected in 18 cases.
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