pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom.

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended.

Molecular epidemiology and antimicrobial resistance pattern of extended-spectrum-ß-lactamase-producing Enterobacteriaceae in Glasgow, Scotland.

OBJECTIVES: To establish the molecular epidemiology and antimicrobial resistance pattern of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae harbouring bla(CTX-M) in Glasgow, Scotland. METHODS: During a 12 week period, Enterobacteriaceae isolates obtained from urine samples were collected and susceptibility testing performed. Isolates were screened for the presence of bla(CTX-M) by multiplex PCR and selected Escherichia coli genes were subsequently sequenced. PFGE analysis was performed on selected E. coli isolates in order to identify clonal relationships. RESULTS: There were 155 phenotypically confirmed non-duplicate Enterobacteriaceae isolates obtained from urine samples. bla(CTX-M) was identified in 131/155 (84.5%) of the ESBL-producing isolates, with CTX-M group 1 enzymes accounting for 103/131 (78.6%) of these. The remaining 24 isolates carried other bla(CTX-M) types, including CTX-M group 2, CTX-M group 9 and an unidentifiable combination designated CTX-M group G2/Gx. A sample of 46/97 (47.4%) CTX-M-positive E. coli isolates was chosen for PFGE and demographic information regarding the source of the isolates was collated. Eight E. coli clusters were identified by PFGE; however, they did not achieve the 85% cut-off to demonstrate clonality. Nitrofurantoin resistance was significantly greater in the E. coli isolates expressing a non-CTX-M group 1 ESBL when compared with the E. coli isolates expressing a CTX-M group 1 ESBL. CONCLUSIONS: As seen in other British studies, bla(CTX-M) has become the predominant ESBL type in Glasgow, Scotland. The PFGE results show that four different CTX-M groups appear to be circulating in the community and within all four hospitals in the locality. There is little correlation between strain genotype and CTX-M group, thus it is unlikely that cross-infection alone is the driver. It is possible that plasmid migration of CTX-M genes within the E. coli population is occurring.

Delayed Onset of Symptoms and Atovaquone-Proguanil Chemoprophylaxis Breakthrough by Plasmodium malariae in the Absence of Mutation at Codon 268 of pmcytb.

Plasmodium malariae is widely distributed across the tropics, causing symptomatic malaria in humans with a 72-hour fever periodicity, and may present after latency periods lasting up to many decades. Delayed occurrence of symptoms is observed in humans using chemoprophylaxis, or patients having received therapies targeting P. falciparum intraerythrocytic asexual stages, but few investigators have addressed the biological basis of the ability of P. malariae to persist in the human host. To investigate these interesting features of P. malariae epidemiology, we assembled, here, an extensive case series of P. malariae malaria patients presenting in non-endemic China, Sweden, and the UK who returned from travel in endemic countries, mainly in Africa. Out of 378 evaluable P. malariae cases, 100 (26.2%) reported using at least partial chemoprophylaxis, resembling the pattern seen with the relapsing parasites P. ovale spp. and P. vivax. In contrast, for only 7.5% of imported UK cases of non-relapsing P. falciparum was any chemoprophylaxis use reported. Genotyping of parasites from six patients reporting use of atovaquone-proguanil chemoprophylaxis did not reveal mutations at codon 268 of the cytb locus of the P. malariae mitochondrial genome. While travellers with P. malariae malaria are significantly more likely to report prophylaxis use during endemic country travel than are those with P. falciparum infections, atovaquone-proguanil prophylaxis breakthrough was not associated with pmcytb mutations. These preliminary studies, together with consistent observations of the remarkable longevity of P. malariae, lead us to propose re-examination of the dogma that this species is not a relapsing parasite. Further studies are needed to investigate our favoured hypothesis, namely that P. malariae can initiate a latent hypnozoite developmental programme in the human hepatocyte: if validated this will explain the consistent observations of remarkable longevity of parasitism, even in the presence of antimalarial prophylaxis or treatment.