Treatment of Rifampicin-Resistant Tuberculosis Disease and Infection in Children: Key Updates, Challenges and Opportunities.

Children affected by rifampicin-resistant tuberculosis (RR-TB; TB resistant to at least rifampicin) are a neglected group. Each year an estimated 25,000-30,000 children develop RR-TB disease globally. Improving case detection and treatment initiation is a priority since RR-TB disease is underdiagnosed and undertreated. Untreated paediatric TB has particularly high morbidity and mortality. However, children receiving TB treatment, including for RR-TB, respond well. RR-TB treatment remains a challenge for children, their caregivers and TB programmes, requiring treatment regimens of up to 18 months in duration, often associated with severe and long-term adverse effects. Shorter, safer, effective child-friendly regimens for RR-TB are needed. Preventing progression to disease following Mycobacterium tuberculosis infection is another key component of TB control. The last few years have seen exciting advances. In this article, we highlight key elements of paediatric RR-TB case detection and recent updates, ongoing challenges and forthcoming advances in the treatment of RR-TB disease and infection in children and adolescents. The global TB community must continue to advocate for more and faster research in children on novel and repurposed TB drugs and regimens and increase investments in scaling-up effective approaches, to ensure an equitable response that prioritises the needs of this vulnerable population.

Telemedicine in Resource-Limited Settings to Optimize Care for Multidrug-Resistant Tuberculosis.

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) poses a major threat to the global targets for TB control. In recent years, an evolving science and evidence base for MDR-TB has led to much needed changes in international guidelines promoting the use of newer TB drugs and regimens for MDR-TB, however, there remains a significant implementation gap. Due to the complexity of treating MDR-TB, management of cases is often supported by an expert multidisciplinary team, or clinical expert group. This service is often centralized, and may be delivered through a telemedicine platform. We have implemented a Web-based "store-and-forward" telemedicine service to optimize MDR-TB patient care in Daru, a remote and resource limited setting in Papua New Guinea (PNG). From April 2016 to February 2019, 237 cases were discussed using the service. This encompassed diagnostic (presumptive) and treatment cases, and more recently, support to the scale up of preventative therapy for latent TB infection. There were 75 cases in which the use of Bedaquiline was discussed or mentioned, with a high frequency of discussions occurring in the initial period (26 cases in the first 12 months), which has appeared to decrease as clinicians gained familiarity with use of the drug (15 cases in the last 12 months). This service has supported high quality clinical care and fostered collaboration between clinicians and technical experts in a shared learning environment.

Prolonged Detection of Japanese Encephalitis Virus in Urine and Whole Blood in a Returned Short-term Traveler.

We describe a fatal case of Japanese encephalitis virus infection following short-term travel to Thailand. Viral RNA was detected in urine and whole blood out to 26 and 28 days, respectively, after the onset of symptoms. Live virus was isolated from a urine specimen from day 14.

Staphylococcus aureus Prostatic abscess: a clinical case report and a review of the literature.

BACKGROUND: Prostatic abscess is a rare complication of acute bacterial prostatitis and is most commonly caused by Enterobacteriaceae. We report on a case of prostatic abscess caused by Staphylococcus aureus and conduct a review of the literature. CASE PRESENTATIVE: We present a case of S. aureus prostatic abscess that was successfully treated with a combination of antibiotic and surgical therapy. The isolate was non­multidrug-resistant, methicillin-resistant Staphylococcus aureus and was genotyped as clonal complex 5, an emerging regional clone that is trimethoprim resistant and Panton-Valentine leukocidin positive. This current case report is the first to describe the use of clindamycin step-down therapy. A literature review identified a further 39 cases of S. aureus prostatic abscesses, of which 26 were methicillin resistant. CONCLUSION: S. aureus is an uncommon cause of prostatic abscess. Optimal management includes both antibiotic therapy and surgical drainage. Our use of clindamycin as step-down therapy was guided by its excellent prostatic penetration.

Genomic Characterization of Recrudescent Plasmodium malariae after Treatment with Artemether/Lumefantrine.

Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.

Management of dengue in Australian travellers: a retrospective multicentre analysis.

OBJECTIVES: To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. DESIGN, SETTING AND PARTICIPANTS: Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. MAIN OUTCOME MEASURES: Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. RESULTS: 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.