SummaryBackgroundGram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK.MethodsEnterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene blaNDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan.FindingsWe identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries.InterpretationThe potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.FundingEuropean Union, Wellcome Trust, and Wyeth.

Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain–affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent a...

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CitationHepatitis C seroprevalence and HIV co-infection in subSaharan Africa: a systematic review and meta-analysis. SummaryBackground An estimated 150 million people worldwide are infected with hepatitis C virus (HCV). HIV co-infection accelerates the progression of HCV and represents a major public health challenge. We aimed to determine the epidemiology of HCV and the prevalence of HIV co-infection in sub-Saharan Africa.

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BackgroundAs international funding for malaria programmes plateaus, limited resources must be rationally managed for malaria and non-malarial febrile illnesses (NMFI). Given widespread unnecessary treatment of NMFI with first-line antimalarial Artemisinin Combination Therapies (ACTs), our aim was to estimate the effect of health-systems factors on rates of appropriate treatment for fever and on use of ACTs.MethodsA decision-tree tool was developed to investigate the impact of improving aspects of the fever care-pathway and also evaluate the impact in Tanzania of the revised WHO malaria guidelines advocating diagnostic-led managementResultsModel outputs using baseline parameters suggest 49% malaria cases attending a clinic would receive ACTs (95% Uncertainty Interval:40.6–59.2%) but that 44% (95% UI:35–54.8%) NMFI cases would also receive ACTs. Provision of 100% ACT stock predicted a 28.9% increase in malaria cases treated with ACT, but also an increase in overtreatment of NMFI, with 70% NMFI cases (95% UI:56.4–79.2%) projected to receive ACTs, and thus an overall 13% reduction (95% UI:5–21.6%) in correct management of febrile cases. Modelling increased availability or use of diagnostics had little effect on malaria management outputs, but may significantly reduce NMFI overtreatment. The model predicts the early rollout of revised WHO guidelines in Tanzania may have led to a 35% decrease (95% UI:31.2–39.8%) in NMFI overtreatment, but also a 19.5% reduction (95% UI:11–27.2%), in malaria cases receiving ACTs, due to a potential fourfold decrease in cases that were untested or tested false-negative (42.5% vs.8.9%) and so untreated.DiscussionModelling multi-pronged intervention strategies proved most effective to improve malaria treatment without increasing NMFI overtreatment. As malaria transmission declines, health system interventions must be guided by whether the management priority is an increase in malaria cases receiving ACTs (reducing the treatment gap), reducing ACT waste through unnecessary treatment of NMFI or expanding appropriate treatment of all febrile illness.

In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sitescaused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis.