Challenges Associated with Management of Buruli Ulcer/Human Immunodeficiency Virus Coinfection in a Treatment Center in Ghana: A Case Series Study

Abstract

The synergy between Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome is well established but not so in Buruli ulcer (BU). We screened confirmed BU cases for HIV infection and followed seven BU/HIV-coinfected patients. Management of BU/HIV was based on the World Health Organization guidelines and patient condition. The HIV positivity among BU patients (8.2%; 11/134) was higher compared with that of general patients attending the facility (4.8%; 718/14,863; P = 0.07) and that of pregnant women alone (2.5%; 279/11,125; P = 0.001). All seven BU/HIV-coinfected cases enrolled in the study presented with very large (category III) lesions with four having multiple lesions compared with 54.5% of category III lesions among HIV-negative BU patients. During the recommended BU treatment with streptomycin and rifampicin (SR) all patients developed immune infiltrates including CD4 T cells in their lesions. However, one patient who received antiretroviral therapy (ART) 1 week after beginning SR treatment developed four additional lesions during antibiotic treatment, while two out of the four who did not receive ART died. Further evidence is required to ascertain the most appropriate time to commence ART in relation to SR treatment to minimize paradoxical reactions.

Figure 1.

Emergence of new lesions during streptomycin (SR) treatment in one of the enrolled coinfected patients (case 2). (A) Features of the first lesion before the start of SR treatment, (B) appearance of a new lesion after 2 weeks of antibiotic treatment, (C) appearance of a third lesion after 4 weeks of SR treatment, (D) appearance of a fourth lesion after 6 weeks of SR treatment, and (E) increase in wound sizes after surgical excision and appearance of a fifth lesion after start of the SR treatment.

Figure 2.

Emergence of immune infiltrates in the Buruli ulcer (BU) lesion during SR treatment in a representative patient (case 7). Histological sections were stained either with hematoxylin–eosin (A–E), or with antibodies against CD20 (F), CD3 (G), CD8 (H), or CD4 (I) (counterstain hematoxylin). (A) cross section through a BU lesion presenting with epidermal hyperplasia, an intact dermis, healthy fat cells as well as fat cell ghosts, a layer of numerous well-defined granulomas, and a necrotic area. Fat cell ghosts (B), granulomas (C), giant cells (D), and necrosis (E) are shown at higher magnification. Immunohistochemical analysis of the granulomas showed the presence of B-cell clusters (F) as well as the presence of large numbers of CD3, CD4, and CD8 positive T cells (G, H, and I).