Figure 1

Figure 1. Geographic distribution of recorded human cases of tanapox. A) Locations of previous tanapox cases reported in the literature. Red dots indicate cases acquired locally; red outlines indicate regions of countries...

We obtained written consent from the patient in this study and received ethics clearance from the Faculty of Health Sciences of University of the Witwatersrand, Johannesburg (approval no. M210752). During February 2–6, 2022, a 61-year old woman served as a volunteer in Kruger National Park (KNP), South Africa. She stayed in a tented bush camp along the banks of the Sand River, ≈20 km from the town of Skukuza (24°59′43′′ S, 31°35′34′′E) (Figure 1; Appendix Figure 1). The woman noted large numbers of arthropods (e.g., spiders, insects, and ticks) around the camp site and reported being bitten on several occasions on various body parts (especially on her hands, shoulders, arms, and back). Because of heavy rains, trails were overgrown, so bushwalks resulted in scratches on her arms, and many ticks were found on her clothing. During February 7–9, she continued her visit to KNP as a guest in air-conditioned accommodation and had no further direct contact with vegetation. She reported no direct contact with primates, although vervet monkeys (Chlorocebus pygerythrus) are seen near the camps.

Two days after her return to urban Johannesburg, she experienced pruritus at the base of her thumb on the dorsal side of her right hand and noticed a pale blister forming there, followed 2 days later by another blister on the side of her left hand. Initially, both papules were round and white with erythematous edges (Appendix Figure 2, panel A), but they became dome-shaped, firm, smooth, umbilicated nodules 12–15 mm in size (Appendix Figure 2, panels B, C). A third lesion formed on the woman’s mid-upper back but was perforated through chafing from clothing. About 3 days after the appearance of the first lesion, the woman reported feeling unwell, fatigued, and feverish and had severe headaches. No lymphadenopathy was recorded. The lesions were persistently painful and hypersensitive, but none were cystic or became pustular. Instead, they became ulcerated, open, and dry (Appendix Figure 2, panel D), and all 3 resolved over a period of 6 weeks, leaving slight discoloration. After discovering the third lesion, the woman sought medical attention. Differential diagnoses included allergies, cellulitis, erysipelas, pyoderma gangrenosum, or granulomas caused by foreign bodies or insect bites (e.g., mango fly bites).

Figure 2

Figure 2. Diagnostic light and electron microscopy of tanapox lesion biopsies from a case-patient, South Africa, 2022. A) High-power photomicrograph of initial skin biopsy, showing prominent vacuolation of epidermal keratinocytes, granular intracytoplasmic...

Histopathologic examination of a lesion biopsy indicated a possible pox infection, given the presence of acidophilic intracytoplasmic inclusion bodies and cellular vacuolation (Figure 2, panel A). The lesion was confined to the epithelial layers with many cells that had vacuolated nuclei, and we observed ballooning cells in the deeper epithelial layer (Figure 2, panel B). Subsequently, we took an additional biopsy for electron microscopy and 2 lesion swab specimens for molecular characterization. After routine processing (Appendix), we observed numerous brick-shaped virions 287 nm x 221 nm with distinct surface tubules and generally an outer membrane layer (capsular form) (Figure 2, panel C). We used 1 dry swab sample for PCR analysis (Appendix), and partial sequence analysis indicated clustering with available TANV sequences (Appendix Figure 3). Attempts at full genomic sequencing and virus isolation (from the second swab specimen) were unsuccessful, possibly because of the limited clinical material available.

Recent surveys of the mosquito distribution in southern Africa have found that 2 culicine genera (Culex and Mansonia) comprise 91% of the mosquito population in the town of Skukuza (11). Weather conditions at the time of the case exposure were conducive to vector replication; recent rainfall was up to 147% higher than the average annual cumulative total (12), and ambient temperatures were 100°F–104°F (38°C–40°C) (13). In terms of virus reservoirs, a limitation of Monroe et al.’s model (9) was that the restricted range of recorded human cases determined the exclusion of many other primates with extensive geographic ranges. Our report extends this range beyond the most southerly predictions of the model, which increases the pool of potential reservoir hosts.

The clinical findings for this reported case were in keeping with previous clinical reports of tanapox, and the diagnosis was supported by histopathology, electron microscopy, and molecular analyses. The importance and continuing relevance of histopathology and microscopy to the diagnosis and investigation of zoonotic disease were clearly illustrated. Given that tanapox is a vectorborne disease, many drivers, including anthropogenic destruction of wildlife habitats, environmental instability, and global climate change, may influence its emergence (14). Improved surveillance, including studies relating to the ecology and epidemiology of TANV in vectors, hosts, and humans, is warranted.