In vitro efficacy of imipenem-relebactam and cefepime-AAI101 against a global collection of ESBL-positive and carbapenemase-producing Enterobacteriaceae.

OBJECTIVES: To evaluate the potential clinical in vitro efficacy of novel ß-lactam/ß-lactamase-inhibitor combinations - including imipenem-relebactam (IPM-REL) and cefepime-AAI101 (enmetazobactam) (FEP-AAI) - against contemporary multidrug-resistant (MDR) Enterobacteriaceae. METHODS: Agar-based MIC screening against MDR Enterobacteriaceae (n = 264) was used to evaluate the in vitro efficacy of IPM-REL and FEP-AAI, to compare the results with established combinations, and to investigate alternative ß-lactam partners for relebactam (REL) and enmetazobactam (AAI). The inhibition activities of REL, AAI and the comparators avibactam (AVI) and tazobactam, against isolated recombinant ß-lactamases covering representatives from all four Ambler classes of ß-lactamases, were tested using a fluorescence-based assay. RESULTS: Using recombinant proteins, all four inhibitors were highly active against the tested class A serine ß-lactamases (SBLs). REL and AVI showed moderate activity against the Class C AmpC from Pseudomonas aeruginosa and the Class D OXA-10/-48 SBLs, but outperformed tazobactam and AAI. All tested inhibitors lacked activity against Class B metallo-ß-lactamases (MBLs). In the presence of REL and IPM, but not AAI, susceptibility increased against Klebsiella pnuemoniae carbapenemase (KPC)-positive and OXA-48-positive isolates. Both aztreonam-AVI and ceftolozane-tazobactam were more effective than IPM-REL. In all the tested combinations, AAI was a more effective inhibitor of class A ß-lactamases (ESBLs) than the established inhibitors. CONCLUSION: The results lead to the proposal of alternative combination therapies involving REL and AAI to potentiate the use of ß-lactams against clinical Gram-negative isolates expressing a variety of lactamases. They highlight the potential of novel combinations for combating strains not covered by existing therapies.

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication.

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function.

The future of Chagas disease control.

In the past 15 years, there have been major advances in the control of Chagas disease in most of the countries endemic for this infection. Attention now turns to the future continuity of surveillance and control interventions - especially in regions where control has been so successful that the epidemiological significance of Chagas disease is in steep decline. The effort and expenditure of the recent past cannot continue indefinitely, but a degree of surveillance and selective intervention will be required because of the risk of new infestations and infections resulting from adventitious silvatic vectors accidentally entering houses. In this review, we summarize the progress of multinational control initiatives against Chagas disease. In addition, we suggest that the most sustainable approach to future surveillance involves both the primary healthcare system and university-based teams, with progressively greater attention given to case detection and treatment. Such an idea is not new, but we believe that it merits extensive discussion because of the different ways that research and health interventions are financed and because of the need to establish clearer reporting links between the research communities and the national health authorities.

21 years of parasitology.

Every parasitologist must have seen the first issue of Parasitology Today in July 1985. More than 13 000 copies were sent to those on society and World Health Organization mailing lists. Modelled on the hugely successful Immunology Today, the new journal aimed to provide well-written digests covering all aspects of parasitology, spiced with smaller items of general interest--including the elegant cartoons of Len Goodwin and occasional acerbic comments on style and semantics. The format seemed well appreciated, and subscriptions quickly climbed to commercially sustainable figures, reflected in the increasing willingness of the publisher, Elsevier, to finance colour printing. Within the first year, the journal went "glossy", and under its later title--Trends in Parasitology--it is now ranked highest of all similar organs, with an impact factor of 6.788. As the journal celebrates its "coming of age", I was asked--as founder Editor--to reflect on key changes during these eventful 21 years.

Epidemiological status of kissing-bugs in South East Asia: A preliminary assessment.

Kissing-bugs (Triatominae) are being increasingly reported as a biting nuisance in SE Asia, with severe bite reactions sometimes leading to anaphylactic shock. In addition, they pose a risk for vector-borne transmission of trypanosomiasis, with potential diagnostic difficulties due to the range of trypanosome species in the region. Here, we review available information about Triatominae in Asia, and present additional comparisons using morphometry, cytogenetics, and new DNA sequence data, to clarify their relationship with each other and with the better known American species. We deduce that all Asian Triatominae have probably derived from forms originally spread during the 15-18th centuries on sailing ships, from the area that now forms the southern USA.

Progress towards the eradication of Tsetse from the Loos islands, Guinea.

BACKGROUND: The tsetse fly Glossina palpalis gambiensis is the main vector of sleeping sickness (Human African Trypanosomiasis - HAT) in West Africa, in particular in littoral Guinea where this disease is currently very active. The Loos islands constitute a small archipelago some 5 km from mainland Guinea, where G. p. gambiensis is well known as a nuisance and potential disease vector by inhabitants of the three main islands, Fotoba, Room, and Kassa. The National Control Program against HAT of Guinea has decided to eradicate tsetse in Loos islands in order to sustainably protect humans and economic activities. After baseline data collection, tsetse control began on the islands in 2006. On each of the three islands a specific combination of control methods was implemented according to the entomological situation found. RESULTS: Starting densities before control operations were 10, 3 and 1 tsetse/trap/day in Kassa, Room and Fotoba respectively, but by July 2010, tsetse were no longer caught in any of the sentinel traps used for monitoring. The reduction rate was faster where several control methods were implemented as a combination (impregnated traps and targets ITT, selective groundspraying, epicutaneous insecticide treatment of pigs, and impregnated fences around pig pens), whereas it was slower when ITT were used as the only control method. CONCLUSIONS: This 100% suppression is a promising step in the eradication process, but G. p. gambiensis may still occur at very low, undetectable, densities on the archipelago. Next step will consist in assessing a 0.05 probability of tsetse absence to ascertain a provisional eradication status. Throughout these operations, a key factor has been the involvement of local teams and local communities without whom such results would be impossible to obtain. Work will continue thanks to the partners involved until total eradication of the tsetse on Loos islands can be declared.

Trypanosomiasis vector control in Africa and Latin America.

Vectors of trypanosomiasis - tsetse (Glossinidae) in Africa, kissing-bugs (Triatominae) in Latin America - are very different insects but share demographic characteristics that render them highly vulnerable to available control methods. For both, the main operational problems relate to re-invasion of treated areas, and the solution seems to be in very large-scale interventions covering biologically-relevant areas rather than adhering to administrative boundaries. In this review we present the underlying rationale, operational background and progress of the various trypanosomiasis vector control initiatives active in both continents.

Estimación de las tasas de incidencia de infecciones y parasitosis crónicas a partir de la prevalencia: La enfermedad de Chagas en América Latina / Estimating incidence rates on chronic infections from prevalence data: Chagas' disease in Latin America

Estimating incidence rates of chronic infections from prevalence data: Chagas' disease in Latin America

Population biology of Rhodnius domesticus Neiva & Pinto, 1923 (Hemiptera: Reduviidae) under laboratory conditions

The entire life cicle of Rhodnius domesticus, fed weekly on mice, was studied under controlled conditions. Aspects related to hatching, life time, mortality, feeding behaviour and fecundity for each stage of the insect life-cycle were evaluated. The hatching rate observed in 100 eggs was 57 per cent and the mean time of hatching was 15.6 days. Forth-six nymphs (80.7 per cent) completed the cycle and the mean time from NI to adult was 93.8 days. The average span in days for each stage was 12.4 for NI, 9.8 for NII, 14.2 for NIII, 16.8 for NIV and 25.0 for NV. The number of bloodmeals in each nymphal stage varied from 1 to 3. The mortality rate was 12.3 per cent for NI, 3.5 per cent for NII and 1.7 per cent for NIII and NIV nymphs. The mean number of eggs laid per female in a 9-month period was 333.1. Average adult survival rates were 287.6 + 133 and 328 + 73 days for males and females respectively.