Cytomegalovirus (CMV) is a significant cause of morbidity, mortality and graft loss in solid organ transplantation (SOT). Treatment options for ganciclovir‐resistant CMV are limited. We describe a case of ganciclovir‐resistant CMV disease in a renal transplant recipient manifested by thrombotic microangiopathy‐associated glomerulopathy. Adoptive T cell immunotherapy using CMV‐specific T cells from a donor bank was used as salvage therapy. This report is a proof‐of‐concept of the clinical and logistical feasibility of this therapy in SOT recipients.
An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012–2015 revealed that 95 belonged to a single modern Beijing sub-lineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation. The Beijing sub-lineage strain demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2 %) attributed to an inhA promoter mutation combined with inhA and ndh coding mutations. Multi-drug resistance, observed in 78/95 samples, emerged with the acquisition of a typical rpoB mutation together with a compensatory rpoC mutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance, and evidence of local transmission of extensively drug resistant (XDR) strains from 2009. These findings underline the importance of whole genome sequencing in informing an effective public health response to MDR/XDR TB.
6 April 2016 in The American Journal of Tropical Medicine and Hygiene
Chromobacterium violaceum is a bacterium associated with soil and water exposure in tropical regions and causes rare and serious clinical infections that are often fatal. We reviewed the demographic and clinical details of 28 patients with C. violaceum detected over 15 years from 2000 to 2015, from the Top End of the Northern Territory. Of these patients, 18 had infections attributable to C. violaceum. Patients with infections were more commonly male (55.6%), and in the 16- to 60-year (61.1%) age group. Skin and soft tissue infections (50%), predominantly involving the limbs, were the major clinical manifestation. Water, mud exposure, and trauma were all noted as precipitating circumstances and comorbidities were present in 61.1% of the patients with infections. Of the 28 patients, 10 (35.8%) had C. violaceum isolated as an incidental finding or as asymptomatic colonization; these 10 patients did not require or receive therapy for C. violaceum bacterial infections. There were no relapsing infections in this group. Chromobacterium violaceum remains a serious infection, with seven patients (25%) in our series requiring intensive care management. However, the mortality rate (7.1%) in our series was far lower than previously described. This case series of C. violaceum infections from a single geographic area provides additional information of the characteristics of infection with this pathogen.
Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining ‘missed’ TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test. This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care. A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%. Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are required before national scale-up.
Tuberculosis (TB) is a major public health issue in Papua New Guinea, with incidence rates particularly high in the South Fly District of Western Province. We present three case studies, along with additional vignettes, that were derived from interviews and focus groups carried out between July 2019 and July 2020 of people living in rural areas of the remote South Fly District depicting their challenges accessing timely TB diagnosis and care; most services within the district are only offered offshore on Daru Island. The findings detail that rather than ‘patient delay’ attributed to poor health seeking behaviours and inadequate knowledge of TB symptoms, many people were actively trying to navigate structural barriers hindering access to and utilisation of limited local TB services. The findings highlight a fragile and fragmented health system, a lack of attention given to primary health services, and undue financial burdens placed on people living in rural and remote areas associated with costly transportation to access functioning health services. We conclude that a person-centred and effective decentralised model of TB care as outlined in health policies is imperative for equitable access to essential health care services in Papua New Guinea.