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The ability of Plasmodium falciparum parasites to develop resistance to widely used anti-malarials threatens malaria control and elimination efforts. Regular drug efficacy monitoring is essential for ensuring effective treatment policies. In low transmission settings where therapeutic efficacy studies are often not feasible, routine surveillance for molecular markers associated with anti-malarial resistance provides an alternative for the early detection of emerging resistance. Such a longitudinal survey of changes in the prevalence of selected molecular markers of resistance was conducted in the malaria-endemic regions of Mpumalanga Province, South Africa, where malaria elimination at a district-level is being pursued.
Molecular analyses to determine the prevalence of alleles associated with resistance to lumefantrine (mdr86N, crt76K and mdr1 copy number variation) and sulfadoxine–pyrimethamine (dhfr triple, dhps double, SP quintuple) were conducted between 2001 and 2018, while artemisinin resistance markers (kelch13 mutations) were assessed only in 2018.
Parasite DNA was successfully amplified from 1667/2393 (70%) of malaria-positive rapid diagnostic tests routinely collected at primary health care facilities. No artemisinin resistance-associated kelch13 mutations nor amplification of the mdr1 gene copy number associated with lumefantrine resistance were observed. However, prevalence of both the mdr86N and crt76K alleles increased markedly over the study period, with all isolates collected in 2018 carrying these markers. SP quintuple mutation prevalence increased steadily from 14% in 2001 to 96% in 2018. Mixed alleles at any of the codons assessed were rare by 2018.
No kelch13 mutations confirmed or suspected to be associated with artemisinin resistance were identified in 2018. Although parasites carrying the mdr86N and crt76K alleles associated with reduced lumefantrine susceptibility were strongly selected for over the study period, nearing fixation by 2018, the marker for lumefantrine resistance, namely increased mdr1 copy number, was not observed in this study. The increase in mdr86N and crt76K allele prevalence together with intense regional artemether–lumefantrine drug pressure, raises concern regarding the sustained artemether–lumefantrine efficacy. Regular, rigorous anti-malarial resistance marker surveillance across all three South African malaria-endemic provinces to inform case management is recommended.
Migraines are the most common disabling type of headache among children and adolescents. Globally, of all non-communicable diseases in children aged 5–14 years, migraine ranks third for disease burden after conduct disorder and anxiety disorder. On Aug 14, the American Academy of Neurology (AAN) and the American Headache Society released new guidelines on the pharmacological prevention and acute treatment of migraine in children and adolescents. These are the first updates to AAN guidance in this area in 15 years, and outline that although there are now more evidence-based treatments for acute migraine attacks, finding the right approach for preventing migraines remains a challenge.
As the 20th century drew to a close, there was an air of optimism among psychiatrists. Long gone were the days when mental disorder and distress were attributed to childhood trauma or “refrigerator mothers” to be treated—if the patient could afford it—by psychoanalysis. Rather, they were manifestations of a biological disease, a malfunctioning of brain processes, either genetically or developmentally caused. The psychiatrists' bible was the monumental US Diagnostic and Statistical Manual of Mental Disorders (DSM) or WHO's equivalent, the International Classification of Diseases.
Clara K Chow, Rajeev Gupta
Raised blood pressure is the most important risk factor in the global burden of disease.1 Although there is robust evidence to show that lowering blood pressure can substantially reduce cardiovascular morbidity and mortality,2 the global burden of hypertension is increasing.3,4 To achieve a reduction in the burden of disease related to hypertension, health systems must ensure that high blood pressure treatment and control rates are achieved. The status of controlled blood pressure is being promoted as a measure of universal health coverage, especially in the context of non-communicable diseases.
Daniel Munday, Kirsty Boyd, Jenifer Jeba, Kellen Kimani, Sebastien Moine, Liz Grant, Scott Murray
Much has been achieved in advancing palliative care on the global health agenda, but there is more to do. The 2014 World Health Assembly (WHA) committed countries to integrating palliative care into their health systems and WHO was tasked with monitoring progress.1 By 2017, WHO had updated the definition of universal health coverage (UHC)—Sustainable Development Goal 3.8—to include palliation along with promotion, prevention, treatment, and rehabilitation.2 A Lancet Commission in 2017 highlighted the global need to take action when 61 million people are living with serious health-related suffering due to uncontrolled pain and without access to an affordable essential package for palliative care.
David Sanders, Sulakshana Nandi, Ronald Labonté, Carina Vance, Wim Van Damme
Primary health care (PHC), codified at the historic 1978 Alma Ata Conference, was advocated as the means to achieve health for all by the year 2000.1 The principles of PHC included universal access and equitable coverage; comprehensive care emphasising disease prevention and health promotion; community and individual participation in health policy, planning, and provision; intersectoral action on health determinants; and appropriate technology and cost-effective use of available resources.2 These principles were to inform health-care provision at all levels of the health system and the programmatic elements of PHC that focused primarily on maternal and child health, communicable diseases, and local social and environmental issues.
Almost 1% of Canadians are hepatitis C (HCV)-infected. The liver-specific complications of HCV are established but the extra-hepatic comorbidity, multimorbidity, and its relationship with HCV treatment, is less well known. We describe the morbidity burden for people with HCV and the relationship between multimorbidity and HCV treatment uptake and cure in the pre- and post-direct acting antiviral (DAA) era.
We linked adults with HCV at The Ottawa Hospital Viral Hepatitis Program as of April 1, 2017 to provincial health administrative data and matched on age and sex to 5 Ottawa-area residents for comparison. We used validated algorithms to identify the prevalence of mental and physical health comorbidities, as well as multimorbidity (2+ comorbidities). We calculated direct age- and sex-standardized rates of comorbidity and comparisons were made by interferon-based and interferon-free, DAA HCV treatments.
The mean age of the study population was 54.5 years (SD 11.4), 65% were male. Among those with HCV, 4% were HIV co-infected, 26% had liver cirrhosis, 47% received DAA treatment, and 57% were cured of HCV. After accounting for age and sex differences, the HCV group had greater multimorbidity (prevalence ratio (PR) 1.38, 95% confidence interval (CI) 1.20 to 1.58) and physical-mental health multimorbidity (PR 2.71, 95% CI 2.29–3.20) compared to the general population. Specifically, prevalence ratios for people with HCV were significantly higher for diabetes, renal failure, cancer, asthma, chronic obstructive pulmonary disease, substance use disorder, mood and anxiety disorders and liver failure. HCV treatment and cure were not associated with multimorbidity, but treatment prevalence was significantly lower among middle-aged individuals with substance use disorders despite no differences in prevalence of cure among those treated.
People with HCV have a higher prevalence of comorbidity and multimorbidity compared to the general population. While HCV treatment was not associated with multimorbidity, people with substance use disorder were less likely to be treated. Our results point to the need for integrated, comprehensive models of care delivery for people with HCV.
Alexander C Fanaroff, Robert M Califf, Renato D Lopes
One of the basic tenets of evidence-based medicine is that randomisation is crucial to understanding treatment effects. Observational studies are subject to confounding and selection bias. Researchers can adjust for measured differences between treatment groups, but unmeasured or unmeasurable differences might exist between groups that obscure true treatment effects and cannot be accounted for by any statistical method.1 The published medical literature is filled with examples of associations between treatment and outcome identified in observational studies that were subsequently disproven by well conducted randomised controlled trials (RCTs).
Ahead of the annual conference of the European Society of Cardiology together with the World Congress of Cardiology held in Paris, France (Aug 31–Sept 4), this issue's research section is devoted to Articles on hypertension. These Articles paint an interesting picture of the global state of, and discussions about, this important risk factor for cardiovascular diseases and other non-communicable diseases (NCDs). The NCD Risk Factor Collaboration authors show increases in awareness and control in 12 selected high-income countries over the past four decades.
Housing mapping and household enumeration are essential for the planning, implementation, targeting, and monitoring of malaria control interventions. In many malaria endemic countries, control efforts are hindered by incomplete or non-existent housing cartography and household enumeration. This paper describes the development of a comprehensive mapping and enumeration system to support the Bioko Island Malaria Control Project (BIMCP).
A highly detailed database was developed to include every housing unit on Bioko Island and uniquely enumerate the associated households residing in these houses. First, the island was divided into a virtual, geo-dereferenced grid of 1 × 1 km sequentially numbered map-areas, each of which was in turn subdivided into one hundred, 100 × 100 m sequentially numbered map-sectors. Second, high-resolution satellite imagery was used to sequentially and uniquely identify all housing units within each map-sector. Third, where satellite imagery was not available, global positioning systems (GPS) were used as the basis for uniquely identifying and mapping housing units in a sequential manner. A total of 97,048 housing units were mapped by 2018, 56% of which were concentrated in just 5.2% of Bioko Island’s total mapped area. Of these housing units, 70.7% were occupied, thus representing uniquely identified households.
The housing unit mapping and household enumeration system developed for Bioko Island enabled the BIMCP to more effectively plan, implement, target, and monitor malaria control interventions. Since 2014, the BIMCP has used the unique household identifiers to monitor all household-level interventions, including indoor residual spraying, long-lasting insecticide-treated nets distribution, and annual malaria indicator surveys. The coding system used to create the unique housing unit and household identifiers is highly intuitive and allows quick location of any house within the grid without a GPS. Its flexibility has permitted the BIMCP to easily take into account the rapid and substantial changes in housing infrastructure. Importantly, by utilizing this coding system, an unprecedented quantity and diversity of detailed, geo-referenced demographic and health data have been assembled that have proved highly relevant for informing decision-making both for malaria control and potentially for the wider public health agenda on Bioko Island.
Paediatrician who used digital technologies to improve global health. Born on Sept 1, 1948, in Newton, MA, USA, he died while hiking in Alaska, USA, on June 25, 2019, aged 70 years.
Gruenberg M, Hofmann N, Nate E, et al.
AbstractBackgroundAccurate quantification of female and male gametocytes and sex-ratios in low-density malaria infections are important for assessing the transmission potential of asymptomatic infections. Gametocytes often escape detection even by molecular methods, therefore ultra-low gametocyte densities were quantified in large blood volumes.MethodsFemale and male gametocytes were quantified in 161 PCR-positive Plasmodium falciparum (Pf) infections from a cross-sectional survey in Papua New Guinea. Ten-fold concentrated RNA from 800µL blood was analysed using female-specific pfs25 and male-specific pfmget or mssp qRT-PCR. Gametocyte sex-ratios by qRT-PCR were compared with those obtained from immunofluorescence assays (IFA).ResultsGametocytes were identified in 58% (93/161) Pf-positive individuals. Mean gametocyte densities were frequently below 1 female and 1 male gametocyte/µL by qRT-PCR. The mean proportion of males was 0.39 [95%CI: 0.33; 0.44] by pfs25/pfmget. The proportion of males correlated well between IFA and qRT-PCR (Pearsons r2=0.91; p
Rachel Nugent, Edward Fottrell
In the annual University College London–Lancet Global Health Lecture in April, 2019, we called for non-communicable diseases (NCDs) to be regarded as a global emergency and we compared the spread of NCDs to climate change, a global emergency of unprecedented proportion. This is not hyperbole—there is ample reason for that claim. NCDs present an overwhelming and widespread threat to populations globally and cause more than 70% of global deaths.1 Worldwide, there are more than 1·1 billion people who have high blood pressure, almost 800 000 people die from suicide annually, 425 million adults have diabetes, and about 40% of adults are overweight or obese.
Provision of palliative care in Tajikistan is growing rapidly, after being non-existent just 15 years ago, despite political sensitivities over opioids for medical use. Jacqui Thornton reports.
Melissa Depypere, Mario Morgenstern, Richard Kuehl, Eric Senneville, T. Fintan Moriarty, William T. Obremskey, Werner Zimmerli, Andrej Trampuz, Katrien Lagrou, Willem-Jan Metsemakers
Both fracture-related infections (FRI) and periprosthetic joint infections (PJI) include orthopaedic implant-associated infections. However, key aspects of management differ due to the bone-and soft tissue damage in FRI and the option of removing the implant after fracture healing. In contrast to PJI, research and guidelines for diagnosis and treatment in FRI are scarce.
Political dictatorship, racism, slavery, abortion, and gender-based violence are all themes that feature in Paula Rego: Obedience and Defiance. This remarkable retrospective of Rego's work, ranging from the 1960s to the 21st century, at MK Gallery in Milton Keynes, UK, showcases what the curator, Catherine Lampert, describes as the “moral challenges to humanity, particularly in the face of violence, gender discrimination and political tyranny”. Rego grew up under Portuguese dictator António de Oliveira Salazar and attended the UK's Slade School of Art in the 1950s, where she met painter Victor Willing who became her husband.
Anushka A Patel, Mark D Huffman
In 2001, combined use of blood pressure-lowering drugs, a statin, and aspirin was proposed as a new approach to prevent cardiovascular disease.1 Reconceptualised soon thereafter as a population-level, so-called polypill strategy for all individuals aged 55 years and older, regardless of pretreatment risk factors, a modelling paper2 predicted that this approach would reduce cardiovascular disease by more than 80%. However, to date, empirical data have been scarce. A 2017 Cochrane review update3 identified 13 randomised controlled trials of polypills (defined as fixed-dose combinations of blood pressure-lowering and cholesterol-lowering drugs, with or without aspirin, in a single pill), including 9059 predominantly male participants with age ranging from 53 to 64 years.
On Aug 13, the US Preventive Services Task Force (USPSTF) published a draft recommendation on screening for illicit drugs, including the non-medical use of prescription drugs. The announcement comes amid the opioid crisis in the USA and is motivated by the need for early identification of people at risk for drug use. The task force draws on data from a 2017 national survey in which 11·5% of Americans reported illicit drug use with more than 700 000 overdoses. In contrast to the 2008 recommendation against drug screening in both adults and adolescents because of insufficient evidence, for the first time, USPSTF is now advising physicians to screen all adult patients for illicit drug use without biological drug testing.
Elevated blood pressure is the major risk factor for disease and premature death globally, and the association between blood pressure and fatal cardiovascular complications is strong.1,2 Antihypertensive treatment can reduce cardiovascular morbidity and all-cause mortality and, supported by evidence summarised in 2018,3 lower target blood pressure values have been introduced into existing recommendations on the management of hypertension.4,5 However, the absolute benefit of antihypertensive treatment in reducing cardiovascular events is determined by the overall cardiovascular risk of the individual.
Andreas Rieckmann, Christine S Benn
We thank Hertzel Gerstein and colleagues1 for reminding us of the importance of randomised controlled trials (RCTs). However, RCTs require uncertainty about the benefits of an intervention, and once an intervention has already become health policy, ethical issues with doing an RCT arise.
Hertzel C Gerstein, John McMurray, Rury R Holman
We thank the correspondents for their responses to our Comment.1
“Things have a life of their own…It's simply a matter of waking up their souls.”Gabriel García Márquez, One Hundred Years of Solitude
Thomas A Fox, Gillian A Horne, Charles Craddock, Gordon Cook, Stephen O'Brien, Sonia Fox, Anna Hockaday, Graham Silk, Peter Hillmen
Clinical trials play a pivotal role in improving patient outcomes and are a crucial factor in the National Institute of Clinical Excellence's assessment of novel therapies.1 From 2016–17 670 000 people were recruited into over 4700 trials across the National Health Service (NHS),2 thanks to more than £200 million of annual investment in the National Institute for Health Research's (NIHR) Clinical Research Network.3 UK cancer trials are developed by the National Cancer Research Institute (NCRI) and delivered by the NIHR.
Effective malaria surveillance requires detailed assessments of mosquitoes biting indoors, where interventions such as insecticide-treated nets work best, and outdoors, where other interventions may be required. Such assessments often involve volunteers exposing their legs to attract mosquitoes [i.e., human landing catches (HLC)], a procedure with significant safety and ethical concerns. Here, an exposure-free, miniaturized, double-net trap (DN-Mini) is used to assess relationships between indoor–outdoor biting preferences of malaria vectors, Anopheles arabiensis and Anopheles funestus, and their physiological ages (approximated by parity and insemination states).
The DN-Mini is made of UV-resistant netting on a wooden frame and PVC base. At 100 cm × 60 cm × 180 cm, it fits indoors and outdoors. It has a protective inner chamber where a volunteer sits and collects host-seeking mosquitoes entrapped in an outer chamber. Experiments were conducted in eight Tanzanian villages using DN-Mini to: (a) estimate nightly biting and hourly biting proportions of mosquitoes indoors and outdoors; (b) compare these proportions to previous estimates by HLC in same villages; and, (c) compare distribution of parous (proxy for potentially infectious) and inseminated mosquitoes indoors and outdoors.
More than twice as many An. arabiensis were caught outdoors as indoors (p
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Lumbalpunktur af patienter i blodfortyndende behandling (2019)
False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers
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Reply to Krahn and Sebastiani
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Hvad synes Professor Thomas Benfield om"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor synes Professor Niels Obel, at du bør læse"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
Hvorfor anbefaler Professor Thomas Benfield artiklen"Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial."?
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Hvorfor synes Professor Niels Obel, at du bør læse"Use of statins and risk of AIDS-defining and non-AIDS-defining malignancies among HIV-1 infected patients on antiretroviral therapy."?
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