Nyt fra tidsskrifterne

Tropical Medicine & International Health, Accepted Article.

Abstract Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6–59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.…

Journal of Medical Virology, Accepted Article.

Mobility is a necessary part of human being life (Saha et al., 2020). Community moves for diverse reasons, viz. going to workplaces, retail, and recreation, parks, learning institutions, etc (Saha et al., 2020). Various cities in Asian countries offer different means of commuting: walking, cycling, motorcycles, public and mass transport, micro-mobility, para-transit, private cars, public taxis, and ride-hailing systems (United Nations, 2020). Residential Mobility in the direction of places of residence where a person or community lived (Google, 2020; Saha et al., 2020).

Different species of leishmania cause leishmaniasis in Brazil but L. braziliensis and L. guyanensis are responsible for the majority of cases of tegumentary leishmaniasis (TL), that may affect skin and mucosal, being the most common in the latter group the nasal mucosa (Amato et al. 2007). TL is composed by distinct clinical forms as cutaneous leishmaniasis (CL), mucosal leishmaniasis (ML), disseminated leishmaniasis (DL) and diffuse cutaneous leishmaniasis (DCL). In the Amazon region L. guyanensis is the main causal agent of TL, while L.

Scrub typhus is a potentially severe tropical rickettsiosis, which is known for centuries in the Asia Pacific region, where it threatens >1 billion people, causing significant morbidity and mortality [1]. In recent years, however, scrub typhus caused by a distinct Orientia species has been discovered in various regions of Chile [2,3]. Here we report a scrub typhus case from the extreme south of Chile, where the infection has never been detected before.

Gram staining of the sputum specimen from a 33-year-old male with cystic fibrosis (CF) showed Gram-positive cocci. At presentation, the patient’s complaint was a dry cough that worsened upon his return from a camping trip in incremental weather the previous week. He was taking part in clinical trial medication for CF, azithromycin 500mg once daily, together with inhalation antibiotics colistin and aztreonam. (Figs. 1–3)…

A female was admitted to our hospital with a penetrating abdominal lesion. A foreign body was removed surgically from the abdominal cavity. She developed severe sepsis necessitating repeated surgical explorations of the abdomen. Despite these surgical interventions and initiation of broad-spectrum antibacterial therapy septic shock developed. A blood culture became positive, showing a yeast-like cell with a germ tube in the Gram stain (Fig 1a). The same day stool cultures became positive with the mould Lomentospora prolificans.

Introduction Mental health disorders are common during pregnancy and the postnatal period and can have serious adverse effects on women and their children. The consequences for global mental health due to COVID-19 are likely to be significant and may have a long-term impact on the global burden of disease. Besides physical vulnerability, pregnant women are at increased risk of mental health problems such as anxiety, depression and post-traumatic stress disorder due to the consequences of social distancing. It can result in altered healthcare routines, less support from the family and friends, and in some cases, partners not being allowed to be present during prenatal visits, labour and delivery. Higher than expected, rates of perinatal anxiety and depression have been already reported during the pandemic. Pregnant women may also feel insecure and worried about the effects of COVID-19 on their unborn child if they get infected during pregnancy. Today, young urban women are used to using internet services frequently and efficiently. Therefore, providing mental health support to pregnant women via internet may be effective in ameliorating their anxiety/depression, reducing the risk of serious mental health disorders, and lead to improved maternal and perinatal outcomes. Overarching aim Our aim is to explore the effectiveness of a web-based psychosocial peer-to-peer support intervention in reducing the risk and severity of perinatal mental health disorders and preventing adverse pregnancy outcomes among pregnant women living in metropolitan urban settings. Methods and analysis We plan to conduct a multicentre prospective randomised controlled trial, Mental health of Urban Mothers trial. Pregnant women living in large metropolitan cities will be recruited using internet-based application through non-profit organisations’ websites. The women who consent will be randomised to receive a web-based peer-to-peer support intervention or usual care. Data will be analysed to identify the effects of intervention on Edinburgh Postnatal Depression Score and Generalised Anxiety Disorder 7 scores as well as pregnancy outcomes. The impact of COVID-19 pandemic on maternal stress will be assesed using Impact Event Scale-R. Any differences in outcomes between cities will be addressed in subgroup analyses. Ethics and dissemination The study will be conducted according to the principles of Good Clinical Practice and will follow the ethical principles of the Declaration of Helsinki. The study protocol has been approved by the ethical review board of Chinese University of Hong Kong (IRB number 2019-8170) and Shanghai Center for Women’s and Children’s Health (international review board (IRB) number 2020-F001-12). The results will be disseminated at national and international scientific conferences, published in peer-reviewed medical journals and spread to the public through social media, news outlets and podcasts. Trial registration number NCT04363177; Trial sponsor Karolinska Institute, CLINTEC, Stockholm, Sweden.…

Objective To characterise published evidence regarding preclinical and clinical interventions to overcome mask shortages during epidemics and pandemics. Design Systematic scoping review. Settings All healthcare settings relevant to epidemics and pandemics. Search strategy English peer-reviewed studies published from January 1995 to June 2020 were included. Literature was identified using four databases (Medline-OVID, EMBASE, CINAHL, Cochrane Library), forwards-and-backwards searching through Scopus and an extensive grey literature search. Assessment of study eligibility, data extraction and evidence appraisal were performed in duplicate by two independent reviewers. Results Of the 11 220 database citations, a total of 47 articles were included. These studies encompassed six broad categories of conservation strategies: decontamination, reusability of disposable masks and/or extended wear, layering, reusable respirators, non-traditional replacements or modifications and stockpiled masks. Promising strategies for mask conservation in the context of pandemics and epidemics include use of stockpiled masks, extended wear of disposable masks and decontamination. Conclusion There are promising strategies for overcoming face mask shortages during epidemics and pandemics. Further research specific to practical considerations is required before implementation during the COVID-19 pandemic.…

Objective The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. Design Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. Setting All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. Participants Participants over the age of 18 years were included. Primary outcomes We investigated in-hospital mortality during the study period. Results A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 μg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 μg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. Conclusions In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.…

Introduction Low-cost digital adherence technologies (DATs) such as 99DOTS have emerged as an alternative to directly observed therapy (DOT), the current standard for tuberculosis (TB) treatment supervision. However, there are limited data to support DAT scale-up. The ‘DOT to DAT’ trial aims to evaluate the effectiveness and implementation of a 99DOTS-based TB treatment supervision strategy. Methods and analysis This is a pragmatic, stepped-wedge cluster randomised trial, with hybrid type 2 effectiveness-implementation design. The trial will include all adults (estimated N=1890) treated for drug-susceptible pulmonary TB over an 8-month period at 18 TB treatment units in Uganda. Three sites per month will switch from routine care (DOT) to the intervention (99DOTS-based treatment supervision) beginning in month 2, with the order determined randomly. 99DOTS enables patients to be monitored while self-administering TB medicines. Patients receive daily automated short message service (SMS) dosing reminders and confirm dosing by calling toll-free numbers. The primary effectiveness outcome is the proportion of patients completing TB treatment. With 18 clusters randomised into six steps and an average cluster size of 15 patients per month, the study will have 89% power to detect a 10% or greater increase in treatment completion between the routine care and intervention periods. Secondary outcomes include more proximal effectiveness measures as well as quantitative and qualitative assessments of the reach, adoption and implementation of the intervention. Ethics and dissemination Ethics approval was granted by institutional review boards at Makerere University School of Public Health and the University of California San Francisco. Findings will be disseminated through peer-reviewed publications, presentations at scientific conferences and presentations to key stakeholders. Trial registration number PACTR201808609844917.…

Abstract Background Plasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART. Methods Four-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016. After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0. Results Out of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. Conclusion Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.…

Abstract Background Belgium was among the first countries in Europe with confirmed coronavirus disease 2019 (COVID-19) cases. Since the first diagnosis on February 3rd, the epidemic has quickly evolved, with Belgium at the crossroads of Europe, being one of the hardest hit countries. Although risk factors for severe disease in COVID-19 patients have been described in Chinese and United States (US) cohorts, good quality studies reporting on clinical characteristics, risk factors and outcome of European COVID-19 patients are still scarce. Methods This study describes the clinical characteristics, complications and outcomes of 319 hospitalized COVID-19 patients, admitted to a tertiary care center at the start of the pandemic in Belgium, and aims to identify the main risk factors for in-hospital mortality in a European context using univariate and multivariate logistic regression analysis. Results Most patients were male (60%), the median age was 74 (IQR 61–83) and 20% of patients were admitted to the intensive care unit, of whom 63% needed invasive mechanical ventilation. The overall case fatality rate was 25%. The best predictors of in-hospital mortality in multivariate analysis were older age, and renal insufficiency, higher lactate dehydrogenase and thrombocytopenia. Patients admitted early in the epidemic had a higher mortality compared to patients admitted later in the epidemic. In univariate analysis, patients with obesity did have an overall increased risk of death, while overweight on the other hand showed a trend towards lower mortality. Conclusions Most patients hospitalized with COVID-19 during the first weeks of the epidemic in Belgium were admitted with severe disease and the overall case fatality rate was high. The identified risk factors for mortality are not easily amenable at short term, underscoring the lasting need of effective therapeutic and preventative measures.…

Human malaria parasites are transmitted by more than 70 species of mosquitoes in the genus Anopheles across many ecological settings [1]. An important challenge for planning malaria control is to understand how mosquito populations would respond to vector control based on measurable differences in their behavior and ecology. A common starting point for understanding these differences has been the Ross–Macdonald model, which describes transmission using a small set of entomological parameters (Box 1) [2,3].

Inflammasomes function as intracellular sensors of pathogen infection or cellular perturbation and thereby play a central role in numerous diseases. Given the high abundance of NLRP1 in epithelial barrier tissues, we screened a diverse panel of viruses for inflammasome activation in keratinocytes. We identified Semliki Forest virus (SFV), a positive-strand RNA virus, as a potent activator of human, but not murine NLRP1. SFV replication and the associated formation of double-stranded (ds) RNA was required to engage the NLRP1 inflammasome. Moreover, delivery of long dsRNA was sufficient to trigger activation. Biochemical studies revealed that NLRP1 binds dsRNA via its LRR, resulting in its NACHT domain gaining ATPase activity. Altogether, these results establish human NLRP1 as a direct sensor for dsRNA and thus RNA virus infection.…

New England Journal of Medicine, Volume 383, Issue 22, November 2020. …

Finding antivirals that reduce mortality from severe respiratory viral infections has proven challenging. Phase 3 trials of baloxavir and pimodivir for severe influenza were unsuccessful (NCT03684044 and NCT03376321). Lopinavir–ritonavir and hydroxychloroquine are not efficacious in treating COVID-19.1,2 Interim results from the WHO-led, open-label, randomised SOLIDARITY trial3 of patients with COVID-19 report that 301 (11·0%) of 2743 patients analysed who received remdesivir and 303 (11·2%) of 2708 patients analysed who received standard care died by day 28 (Kaplan-Meier rate ratio [RR] 0·95, 95% CI 0·81–1·11; p=0·50).

Although global attention is dominated by COVID-19, the HIV/AIDS pandemic, as it enters its fifth decade, is far from over. Since the early 1980s, 75·7 million people have become infected with HIV. 32·7 million people have died from AIDS-related illnesses. HIV/AIDS remains a major public health crisis and only a few countries will meet the 90–90–90 treatment target for 2020. Much has been made of how information systems and service models in the HIV response have helped the COVID-19 response, but the COVID-19 pandemic could have knock-on effects on the HIV response and be devastating for communities.

With the sulfonylurea gliclazide and insulin, metformin is part of the triad of antihyperglycaemic agents on the 2019 WHO list of essential medications. In most international guidelines on the management of hyperglycaemia, metformin is the recommended first-line glucose-lowering agent in patients with type 2 diabetes. The evidence that underpins these recommendations is partly based on the efficacy results in a small subgroup of the UK Prospective Diabetes Study participants, which showed a reduction in macrovascular and microvascular complications in overweight people with newly diagnosed type 2 diabetes randomised to metformin or non-pharmacological (diet) intervention.

The Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, USA, publishes weekly reports on progress to control the COVID-19 pandemic in Europe. They make grim reading. The latest iteration, dated Nov 19, predicts that daily deaths from COVID-19 will continue to rise in the coming weeks, reaching a peak of over 7000 deaths per day around mid-January. Hospitals will be stretched to breaking point from December through to the end of February. COVID-19 is currently the second leading cause of death in the region—29 858 weekly deaths (ischaemic heart disease killed 44 253 people across Europe during the same period).

UN Relief and Works Agency for Palestine Refugees in the Near East says that a $300 million shortfall is threatening health services. Sharmila Devi reports.

The One Health Global Leaders Group on Antimicrobial Resistance aims to raise awareness and political advocacy on antimicrobial resistance. John Zarocostas reports from Geneva.

Afghan health workers predict a second wave of COVID-19 infections, but is the health system ready? Sophie Cousins reports from Afghanistan.

This year has been one of tremendous uncertainty for medical students, especially those entering their final year. The dynamics of selecting a specialty, preparing to apply for it, and entering the application process have been disrupted. Many rotations were cancelled or changed so the opportunities to fully explore a specialty were curtailed. Other research and extracurricular activities in support of such training were also constrained. Students entered application season with only the small comfort of knowing that everyone was pretty much in the same boat.

“It is curious how awareness of consciousness science is so low in the medical and scientific arenas. We need to inspire more neurologists and doctors to be interested in consciousness—and what it means for the thousands of people who experience traumatic brain injury and disorders of consciousness every year”, Steven Laureys says. He's spent much of his career trying to do just that. As Research Director for the Belgian National Fund for Scientific Research, Laureys founded the GIGA Consciousness and Coma Science Group at the University of Liège, Belgium, comprising around 60 staff focused on contrasting areas of consciousness research, ranging from anaesthesia to dreaming, and the important clinical question of consciousness in patients after traumatic brain injury.

The global COVID-19 death toll stands at more than 1·3 million. Among the lives lost have been those of health-care workers, who have had crucial roles throughout the response and continue to serve at the front lines. At the outset of the pandemic, doctors warned of the potential implications of the virus. As the virus spread, many doctors provided treatment for a disease they little understood, while others contributed to accelerated research on potential treatments and vaccines. And as the COVID-19 pandemic worsened worldwide, health professionals worked tirelessly to provide care for patients—some even emerged from retirement to provide assistance.

The WHO–UNICEF–Lancet Commission1 identified an important threat to children's health and futures by stating that children across the globe are exposed to exploitative advertising and marketing by the private sector. Fast food and sugar-sweetened beverages, alcohol, tobacco, e-cigarettes, breastmilk substitutes, and gambling, were positioned as the key products that children are increasingly exposed to and harmed by. However, by focusing on the marketing of particular so-called unhealthy products, the Commission has made a critical oversight.

We thank Darren Powell for his insightful feedback. Members of the WHO–UNICEF–Lancet Commission1 agree with Powell that marketing of any products to children might encourage potentially harmful consumption for the child, the planet, and children's futures, and that more work in both academic and political spheres is needed to highlight the risks.1 Our Commission's analysis of children's wellbeing and rights extends to the dangers of the commercialisation of childhood.

We read with interest the study by David Rosmarin and colleagues,1 which investigated the safety and efficacy of ruxolitinib cream in vitiligo. The study concluded that ruxolitinib cream is safe and effective as monotherapy in treating patients with vitiligo.1 We believe that this generalised statement cannot be concluded based on major study limitations.

We thank Shelley Uppal and colleagues for their comments on the randomised phase 2 trial of ruxolitinib cream for the treatment of vitiligo,1 in which concerns over the generalisability of the study population were raised. As a phase 2 study, the goal was to evaluate the efficacy and safety of different concentrations and dosing regimens of ruxolitinib cream in patients with non-segmental vitiligo before progressing to phase 3 studies, in which generalisability would be assessed. As such, our study1 does not state that ruxolitinib cream is a safe and effective treatment for vitiligo or conclude that the study's findings should extend to clinical practice.

This clinical report of the first documented human facial retransplantation is proof-of-concept that the loss of a facial transplant after CAMR can be mitigated successfully by retransplantation combined with an aggressive desensitisation process.

A 24-year-old woman was referred to our specialist unit with a 3-month history of 15·8 kg weight loss, increasing abdominal pain and bloating, fatigue, night sweats, difficulty passing urine, amenorrhoea, and trouble walking. She was nulligravida and had a copper intrauterine device (IUD) in situ for the past 4 years. She was a non-smoker, drank alcohol socially, and had no history of recent travel. She stated she was allergic to penicillin.

Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding.

The authors regret that the Methods section has error in the formula. Corrections follow.

Antibiotic stewardship in the emergency department (ED) must be a priority of any antibiotic stewardship program (ASP), since initiation of antibiotics has shifted largely to the ED and prescribing in the ED deeply influences antibiotic prescribing practices both among inpatients and outpatients. In this theme issue, we would like to point to the importance of systematically targeting the ED in any ASP and of conducting high-quality research to address the unmet needs identified in the reviews published in this Clinical Microbiology and Infection Theme issue.

This Commentary discusses the finding of a study recently published in CMI (Langford B, Daneman N, Diong C, Marchand-Austin A, Adomako K, Saedi A, et al. Antibiotic Susceptibility Reporting and Association with Antibiotic Prescribing: A Cohort Study).It also discusses the available evidence on selective reporting of antibiotic susceptibility testing results, especially on the following topics: What is selective reporting and its forms ? What are the aims we want to achieve with selective reporting ? What is the evidence that it can achieve these aims ? Is there potential harm to the patient, and what is the evidence that this occurs or not ? Potential role of ESCMID and EUCAST ?…

Enterococcal bloodstream infection (BSI) is associated with high morbidity and mortality. Interestingly, enterococcal BSI associated with central-line (i.e., CLABSI) or intravascular devices (i.e., CRBSI) showed increasing incidence or proportion [1,2]. We read with great interest the review of Rosselli Del Turco E et al. in which the authors recommended (Table 1) 2-4 weeks of treatment for endovascular device-related (i.e., central venous catheter [CVC] including haemodialysis catheters, peripherally inserted central venous catheter [PICC] or midline catheters) enterococcal BSI [3].

Abstract Background Larval source management is recommended as a supplementary vector control measure for the prevention of malaria. Among the concerns related to larviciding is the feasibility of implementation in tropical areas with large numbers of habitats and the need for frequent application. Formulated products of spinosad that are designed to be effective for several weeks may mitigate some of these concerns. Methods In a semi-field study, three formulations of spinosad (emulsifiable concentrate, extended release granules and tablet formulations) were tested in naturalistic habitats in comparison to an untreated control. Cohorts of third instar Anopheles gambiae (Diptera: Culicidae) were introduced into the habitats in screened cages every week up to four weeks after application and monitored for survivorship over three days. A small-scale field trial was then conducted in two villages. Two of the spinosad formulations were applied in one village over the course of 18 months. Immature mosquito populations were monitored with standard dippers in sentinel sites and adult populations were monitored by pyrethrum spray catches. Results In the semi-field study, the efficacy of the emulsifiable concentrate of spinosad waned 1 week after treatment. Mortality in habitats treated with the extended release granular formulation of spinosad was initially high but declined gradually over 4 weeks while mortality in habitats treated with the dispersable tablet formulation was low immediately after treatment but rose to 100% through four weeks. In the field study, immature and adult Anopheles mosquito populations were significantly lower in the intervention village compared to the control village during the larviciding period. Numbers of collected mosquitoes were lower in the intervention village compared to the control village during the post-intervention period but the difference was not statistically significant. Conclusions The extended release granular formulation and the dispersible tablet formulations of spinosad are effective against larval Anopheles mosquitoes for up to four weeks and may be an effective tool as part of larval source management programmes for reducing adult mosquito density and malaria transmission.…

Abstract Background Haptoglobin (Hp) is an acute phase protein that takes part in systemic regulation of haem during Plasmodium falciparum infections. Numerous genotypes of haptoglobin have been reported in malaria endemic populations. In this study, the relationship between haptoglobin genotypes and incidence of uncomplicated malaria in a cohort of children living in a malaria-endemic area of Uganda was determined. Methods This is an extension of a longitudinal study comprising of 423 children aged between six months and nine years, who were actively followed up for one year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Haptoglobin genotypes were determined by an allele-specific PCR method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of haptoglobin genotypes on incidence of uncomplicated malaria in the children’s cohort. In all statistical tests, a P–value of 

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Respiratory syncytial virus (RSV) is an enveloped, single stranded RNA virus, of the pneumoviridae family, which causes yearly outbreaks throughout the community between late fall to early spring, along with other respiratory viruses as influenza. RSV is no longer considered as an infecting pathogen of infants and children alone. RSV infection in adults has been reported since the 1970s (Hall et al., 1976) and was studied thereafter. Most infections were of the upper respiratory tract with mild severity.

During an infectious disease outbreak, the reported number of deaths may underestimate the true mortality caused by the disease. Both changing case definitions (Tsang et al., 2020), and a lack of access to testing can bias reported cause-specific mortality counts, as repeatedly noted during the COVID-19 pandemic crisis (Kiang et al., 2020). One approach to evaluating the magnitude of the bias in such burden estimates is by estimating the deviation of total number of deaths from the expected baseline levels of mortality from previous years, a measure called “excess deaths”.

Human seasonal influenza is a vaccine-preventable disease with a global burden of 300,000-650,000 deaths annually (Iuliano et al., 2018). However, coinciding with the global pandemic of COVID-19, there has also been a global reduction in influenza virus circulation in 2020 (WHO, 2020e). One hypothesized reason for this reduction is increased social distancing, and other community mitigation interventions employed to control COVID-19 worldwide (Olsen et al., 2020).

Coronavirus disease 2019 (COVID-19) represents a mild course in the majority of cases, but about one-fifth of the patients develop clinical complications, such as acute respiratory distress syndrome (ARDS), severe thrombocytopenia, venous thromboembolism and a systemic hyperinflammatory response (Huang et al. 2020, Martincic et al. 2020). The latter disorder is accompanied by lymphopenia, decreased interferon-γ expression in CD4 + T cells and upregulated cytokine levels (e.g. interleukin-6, IL-6) that may lead to the development of a ‘cytokine storm’ in severe COVID-19 (Pedersen and Ho 2020).

The oxygen concentration between 20-21% is definitory for normoxia. On the contrary, hypoxic conditions are reached at low oxygen levels in organs, tissues and cells. The cellular response to hypoxia is mediated by the hypoxia-inducible factor-1 (HIF-1) transcription factor, which represents the key regulator of oxygen homeostasis, promoting cellular adaptation to reduced oxygen availability (Semenza, 2006; Wenger et al., 2005).

In spite of global efforts towards combatting malaria, this disease is still one of the major health issues in the world, especially in tropical countries. The World Health Organization (WHO) estimated that 219 million cases of malaria occurred worldwide in 2017, which claimed around 435,000 lives (WHO 2018). Indonesia, as a tropical country, suffers from malaria. The most common Plasmodium species in Indonesia were Plasmodium falciparum and Plasmodium vivax with around 63% and 37% in 2017 respectively (WHO 2017).

Bernardes et al. explore COVID-19 disease trajectories by performing longitudinal multi-omics analyses in peripheral blood samples from hospitalized patients. The analyses identify increased numbers of plasmablasts, interferon-activated megakaryocytes and erythroid cells as hallmarks of severe disease, and define molecular signatures linked to a fatal COVID-19 disease outcome.

Bacher et al. identify excessive but low avidity T cell responses to SARS-CoV-2 as a hallmark of severe but not mild COVID-19. Pre-existing memory to SARS-CoV-2 in unexposed donors also displayed low avidity and harbored multiple, highly variable cross-reactivities that were not restricted to common cold coronaviruses.