OBJECTIVES:Kiribati has one of the highest rates of leprosy worldwide. A nationwide screening and chemoprophylaxis program for household leprosy contacts was introduced in 2018. In 2022, population-wide screening and rifamycin-based treatment or chemoprophylaxis for leprosy and tuberculosis was introduced as part of the PEARL and COMBINE studies. Largescale rifamycin use theoretically risks selection of resistant Mycobacterium leprae strains. This study aimed to elucidate the baseline antimicrobial resistance (AMR) profile of M. leprae isolates in Kiribati using a novel molecular method. METHODS:Mycobacterium leprae genomes from skin biopsies of patients clinically diagnosed with leprosy in Kiribati between 2017 and 2024 were analysed. We used an M. leprae specific repetitive element (RLEP) PCR to confirm the presence of M. leprae DNA. Samples with sufficient DNA (cycle threshold (CT) value < 30) proceeded for resistance testing. A combination of nested and heminested PCR assays was used to amplify the drug resistance determining regions (DRDR's) for dapsone (folP1), rifampicin (rpoB) and fluoroquinolones (gyrA) followed by DNA Sanger sequencing. RESULTS:216 skin biopsies (multibacillary [MB], n = 155, paucibacillary [PB], n = 61) underwent confirmatory testing. 192/216 (89%) samples were PCR positive (median Ct value 24.5 [range 12.0-44.4]), including 145 MB cases (median CT 21.1 [range 12.0-42.0]) and 47 PB cases (median CT 34.0 [range 14.8-37.0]). Twenty-four (11%) samples were PCR negative and 21 of these underwent histopathological testing, with 12 (57%) showing changes consistent with leprosy. 116 (60%) positive samples proceeded to AMR testing (MB, n = 106; PB, n = 10). In 10 cases (9%), dapsone resistance-conferring mutations were identified in the folP1 region. No mutations were identified in the rpoB or gyrA genes. CONCLUSION:Molecular analysis of skin biopsies revealed moderate-level dapsone resistance but no rifampicin resistance in Kiribati. Establishing this baseline AMR profile will enable a before-versus-after intervention analysis of antimicrobial resistance in M. leprae isolates in Kiribati.
Fumarate hydratase-deficient renal cell carcinoma is a rare type of renal cell carcinoma often associated with hereditary leiomyomatosis and renal cell carcinoma syndrome. These tumors tend to exhibit an aggressive behavior and metastasize at an early stage. We describe the case of a 41-year-old woman of Chinese ethnicity who presented with progressive left flank pain and macroscopic hematuria. Computed tomography (CT) scan of the abdomen showed a large renal mass occupying the entire left kidney, left renal vein and inferior vena cava (IVC) tumor thrombus extension, left renal hilar lymphadenopathy, and indeterminate iliac bony and multiple large uterine fibroids. The patient underwent radical nephrectomy, caval thrombectomy and IVC reconstruction, total abdominal hysterectomy, and bilateral salpingo-oophorectomies. Histopathological examination revealed metastatic fumarate hydratase-deficient renal cell carcinoma associated with uterine leiomyomatosis with R1 resection margin at IVC. Owing to the lack of uniformly agreed guidelines for the management of this tumor, close surgical surveillance was advised. The patient subsequently developed postoperative liver metastases and sought self-funded medical care abroad. She subsequently received bevacizumab and erlotinib and achieved a favorable response. However, the patient experienced renal impairment with proteinuria following treatment, and the next cycle of systemic therapy was delayed. During this pause, we proceeded with stereotactic body radiation therapy (SBRT) to the remaining solitary liver metastasis. This case illustrates the practical challenges faced in treating fumarate hydratase-deficient renal cell carcinoma, including the lack of established systemic treatment guidelines and management of treatment-related adverse events. It highlights the value of integrating radiotherapy during interruptions in systemic therapy and the importance of multidisciplinary collaboration in this rare tumor.
Strict homoeostatic control of potassium is necessary for normal muscle and neural function, and as a result, hyperkalaemia can be life-threatening and requires timely management. Prior to treating the patient, however, it is important to determine if hyperkalaemic blood test results are authentic and not due to pre-analytical factors as treatment in this context may provoke potentially dangerous hypokalaemia. We present the case of a 47-year-old female referred for further investigation following 2 years of otherwise unexplained intermittent hyperkalaemia. Her highest recorded potassium was 8.9 mmol/L (reference interval: 3.5-5.2 mmol/L). She was otherwise healthy, not on regular medications, and asymptomatic during these episodes. There was no evidence of associated electrocardiogram (ECG) changes. She had been referred to the Emergency Department twice in 6 months due to hyperkalaemia, but these episodes resolved on repeat testing without any intervention. Further investigation revealed a significant time- and temperature-dependent increase in potassium concentration in whole blood samples, compared to a control. ABCB6 single gene testing revealed a heterozygous variant, c.1123 C>T, p. (Arg375Trp), consistent with a diagnosis of familial pseudohyperkalaemia (FP). This is an autosomal dominant condition, which results in increased efflux of potassium from red blood cells at sub-physiological temperatures. Whilst this is an ex vivo phenomenon, unless recognised it poses a clinical risk to patients as they may be treated erroneously.
