Molecular investigations of Mycobacterium tuberculosis genotypes among baseline and follow-up strains circulating in four regions of Eswatini.

BACKGROUND: The tuberculosis (TB) epidemic remains a major global health problem and Eswatini is not excluded. Our study investigated the circulating genotypes in Eswatini and compared them at baseline (start of treatment) and follow-up during TB treatment. METHODS: Three hundred and ninety (n = 390) participants were prospectively enrolled from referral clinics and patients who met the inclusion criteria, were included in the study. A total of 103 participants provided specimens at baseline and follow-up within six months. Mycobacterium tuberculosis (M.tb) strains were detected by GeneXpert® MTB/RIF assay (Cephied, USA) and Ziehl -Neelsen (ZN) microscopy respectively at baseline and follow-up time-points respectively. The 206 collected specimens were decontaminated and cultured on BACTEC™ MGIT™ 960 Mycobacteria Culture System (Becton Dickinson, USA). Drug sensitivity testing was performed at both baseline and follow-up time points. Spoligotyping was performed on both baseline and follow-up strains after DNA extraction. RESULTS: Resistance to at least one first line drug was detected higher at baseline compared to follow-up specimens with most of them developing into multidrug-resistant (MDR)-TB. A total of four lineages and twenty genotypes were detected. The distribution of the lineages varied among the different regions in Eswatini. The Euro-American lineage was the most prevalent with 46.12% (95/206) followed by the East Asian with 24.27% (50/206); Indo-Oceanic at 9.71% (20/206) and Central Asian at 1.94% (4/206). Furthermore, a high proportion of the Beijing genotype at 24.27% (50/206) and S genotype at 16.50% (34/206) were detected. The Beijing genotype was predominant in follow-up specimens collected from the Manzini region with 48.9% (23/47) (p = 0.001). A significant proportion of follow-up specimens developed MDR-TB (p = 0.001) with Beijing being the major genotype in most follow-up specimens (p < 0.000). CONCLUSION: Eswatini has a high M.tb genotypic diversity. A significant proportion of the TB infected participants had the Beijing genotype associated with MDR-TB in follow-up specimens and thus indicate community wide transmission.

Extra-uterine myoid tumours in patients with acquired immunodeficiency syndrome: a clinicopathological reappraisal.

AIMS: AIDS-associated myoid tumours (AIDS-MTs), often Epstein-Barr virus (EBV)-associated (EBV-positive MTs), include smooth muscle tumors (SMTs) and the relatively recently recognized myopericytomas (MPCTs). The myoid immunophenotype of AIDS-MTs has been documented inconsistently. The aim of this study was to reappraise the phenotypic and immunophenotypic features of extra-uterine AIDS-MTs and the clinical profile of afflicted patients. METHODS AND RESULTS: EBV early RNA in-situ hybridization testing on 27 AIDS-MTs from 25 patients identified 19 of 27 (70.4%) EBV-positive MTs and eight of 27 (29.6%) EBV-negative MTs. EBV-positive MTs comprised 12 of 19 EBV-positive SMTs [six leiomyomas, one smooth muscle tumour of uncertain malignant potential (STUMP), five leiomyosarcomas] and seven of 19 EBV-positive MPCTs [benign (five), malignant (two)]. The EBV-negative MTs, made up exclusively of EBV-negative SMTs, included angioleiomyoma (one), leiomyoma (one), STUMP (one) and leiomyosarcomas (five). Malignant AIDS-MTs demonstrated hypercellularity, pleomorphism, increased mitoses and necrosis. EBV-positive leiomyosarcomas retained a conspicuous fascicular architecture. Four of five EBV-negative leiomyosarcomas demonstrated marked pleomorphism. All EBV-positive MPCTs and two EBV-positive leiomyosarcomas contained aggregates of desmin-negative round and oval cells. Seventeen of 25 patients died, mainly from comorbid diseases. CONCLUSION: While the reappraised spectrum of AIDS-MTs does not demonstrate divergent subtype-determined clinical behaviour, heightened awareness/recognition of this expanded spectrum will not only promote improved diagnosis of pleomorphic and myopericytic variants, which may be the sentinel clue to AIDS and its comorbidity, but will also facilitate distinction from histopathological mimics in specific anatomic locations.

Granulomas in acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.

BACKGROUND: Co-lesional acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma (AIDS-KS) and Mycobacterium tuberculosis-associated granulomatous inflammation are undocumented. METHOD: Retrospective appraisal of skin biopsies with co-lesional AIDS-KS and microscopic tuberculosis (TB). RESULTS: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non-necrotizing and a combination of necrotizing and non-necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl-Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co-lesional TB in 15/16 biopsies. Co-lesional AIDS-KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. CONCLUSION: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co-lesional occurrence of AIDS-KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB.

Tuberculids as sentinel lesions of tuberculous epididymo-orchitis.

BACKGROUND: Tuberculids are rarely associated with male genital tract tuberculosis (TB). Tuberculous epididymo-orchitis (TBEO) has been associated rarely with papulonecrotic tuberculid (PNT) but not with erythema induratum (EI) or the simultaneous occurrence of different tuberculids. METHODS: A retrospective assessment of tuberculids that occurred with underlying TBEO was carried out. RESULTS: Five patients, four with one and one with two skin biopsies, with clinical diagnoses of PNT (two), EI (one), impetigo (two) and calf ulcer (one), formed the study cohort. Histopathological evaluation confirmed PNT and EI in four and two skin biopsies, respectively. Two patients who returned for follow-up were commenced on anti-tuberculous therapy. All patients sought medical attention 3-34 months later for tender right-sided (two) and left-sided (three) testicular masses. Orchidectomy was undertaken following a poor clinical response to empirical treatment with trimethoprim sulfamethoxazole. Pathological examination of the testis and epididymis confirmed TBEO. The patients were initiated on anti-tuberculous therapy. There was dramatic healing of the skin lesions. CONCLUSION: Tuberculids are a sentinel cutaneous manifestation of visceral TB and a valuable external audit of treatment compliance and response. Heightened recognition of and more rigorous genitourinary tract investigation are necessary to identify occult or asymptomatic TBEO as the underlying cause of tuberculids.

Amebiasis cutis revisited.

BACKGROUND: Amebiasis cutis (AC) is reported infrequently. This study assesses the clinicopathological spectrum, co-existent visceral involvement and impact of human immunodeficiency virus (HIV) co-infection on AC. METHODS: An 8-year prospective clinicopathological evaluation of patients with AC. RESULTS: Thirty-one biopsies of ulcers, fistulae, fissures, abscesses, polypoid and warty lesions in perianal, penile, scrotal, vulval, buttock, chest and abdominal wall sites were evaluated. Of these, 11 had a 'superficial' (superficial AC) and 20 a 'deep' (deep AC), histopathological pattern. Superficial AC showed predominant epidermal spongiosis, liquefactive necrosis, ulceration and fissures with hematophagous amebic trophozoites (HATs). Deep AC had confluent deep dermal and subcutaneous liquefactive, coagulative or suppurative necrosis and HATs. Seven biopsies showed vasculitis or thrombosis with luminal HATs. OUTCOME: Fourteen patients died; 9 had concomitant visceral amebiasis, 5 had other co-infections. Six who died were HIV seropositive, three were seronegative; all had deep AC. Of the 17 survivors, 11 (8 HIV positive) had superficial AC that healed with metronidazole treatment; the remaining 6 (one HIV seropositive) required additional surgical intervention. CONCLUSION: Deep AC is predictive of co-existent, contiguous visceral disease. The effective management, histopathological mimickers and diagnostic pitfalls of superficial and deep AC differ. The outcome in HIV-infected patients is dependent on co-existent systemic diseases.

Cytomegalovirus neuritis in perineal ulcers.

BACKGROUND: Although a range of cytomegalovirus (CMV)-induced cutaneous manifestations is described in AIDS patients, skin involvement in immunocompromised patients is rare, and intraneural CMV inclusions or CMV neuritis has not been documented in skin biopsies. METHODS AND RESULTS: Cutaneous biopsies of CMV lesions were collected prospectively for 12 months. The morphology, sites and symptomatology of the individual lesions, associated systemic illnesses, treatment schedules and disease outcome were recorded. A total of nine biopsies were obtained from three females who presented with extensive painful perineal ulceration and disseminated cutaneous ulcers, nodules and plaques. Clinically, herpes simplex virus (HSV) ulceration was diagnosed and treatment with acyclovir was initiated after biopsies from the natal cleft, perineum and neck were obtained. All were superficial and demonstrated HSV infection. Only the natal cleft biopsy demonstrated coexistent CMV inclusions. Suboptimal healing necessitated two further biopsies from each patient, none of which demonstrated HSV inclusions. Three of four deep perineal biopsies demonstrated CMV inclusions within nerves attended by a lymphocytic infiltrate and architectural disturbances. Two deep cutaneous biopsies of the trunk and abdominal wall confirmed CMV in extraneural locations only. One superficial perineal biopsy did not demonstrate any viral inclusion. CONCLUSIONS: In documenting CMV neuritis in painful perineal ulcers, the histopathological spectrum of perineal CMV ulcers is expanded, a cutaneous neurotropic characteristic of CMV is presented and a direct role for CMV in the pathogenesis of pain is suggested. CMV latency within perineal nerves is also revisited as another potential site of CMV reactivation in immunocompromised patients, and another potential site for possible venereal transmission of CMV infection. The exclusive presence of HSV in initial superficial biopsies highlights the need for optimally biopsied tissue to confirm the coexistence of CMV infection.