Optimising systemic insecticide use to improve malaria control.

BACKGROUND: Long-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy's sustainability. METHODS: Here, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation. RESULTS: The review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations. CONCLUSIONS: These findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway

Putting surveillance data into context: The role of health care utilization surveys in understanding population burden of pneumonia in developing countries

AbstractBackgroundSurveillance is essential to estimating the global burden of pneumonia, yet differences in surveillance methodology and health care-seeking behaviors limit inter-country comparisons.MethodsResults were compared from community surveys measuring health care-seeking for pneumonia defined as: (1) cough and difficulty breathing for ⩾2days; or, (2) provider-diagnosed pneumonia. Surveys were conducted in six sites in Guatemala, Kenya and Thailand; these sites also conduct, active, hospital- and population-based disease surveillance for pneumonia.ResultsFrequency of self-reported pneumonia during the preceding year ranged from 1.1% (Thailand) to 6.3% (Guatemala) and was highest in children aged <5years and in urban sites. The proportion of persons with pneumonia who sought hospital-based medical services ranged from 12% (Guatemala, Kenya) to 80% (Thailand) and was highest in children <5years of age. Hospitals and private provider offices were the most common places where persons with pneumonia sought health care. The most commonly cited reasons for not seeking health care were: (a) mild illness; (b) already recovering; and (3) cost of treatment.ConclusionsHealth care-seeking patterns varied widely across countries. Using results from standardized health care utilization surveys to adjust facility-based surveillance estimates of pneumonia allows for more accurate and comparable estimates

Assessing a potential non-invasive method for viral diagnostic purposes in European squirrels.

Viral infections globally threaten wild and captive mammal populations, with surveillance options limited by a lack of non-invasive diagnostics; especially when infection is asymptomatic in nature. We explored the potential for hair samples collected from red (Sciurus vulgaris) and grey (Sciurus carolinensis) squirrels to provide a means of screening for adenovirus (ADV) and squirrelpox virus (SQPV) using evolving polymerase chain reaction (PCR) assays. An initial pilot study phase utilised samples opportunistically harvested from grey squirrels controlled in Gwynedd, United Kingdom (UK). The screening of 319 grey squirrel carcasses revealed 58% spleen ADV DNA qPCR and 69% SQPV antibody enzyme linked immunosorbent assay (ELISA) positives. We developed new nested ADV and SQPV qPCRs and examined tail hair samples from a sub-set of 80 of these 319 sampled squirrels and these assays amplified ADV and SQPV DNA in a higher proportion of animals than the original qPCR (94% and 21% respectively). Tail hair samples obtained from six Cumbrian red squirrels which had died from squirrelpox disease also revealed 100% SQPV and 50% ADV DNA positive by the nested qPCR assays. These findings indicate enhanced sensitivity for the new platform. The integration of this non-invasive approach in assessing viral infection has wide application in epidemiological studies of wild mammal populations, in particular, during conservation translocations, where asymptomatic infections are of concern

Plasmodium falciparum importation does not sustain malaria transmission in a semi-arid region of Kenya

Human movement impacts the spread and transmission of infectious diseases. Recently, a large reservoir of Plasmodium falciparum malaria was identified in a semi-arid region of northwestern Kenya historically considered unsuitable for malaria transmission. Understanding the sources and patterns of transmission attributable to human movement would aid in designing and targeting interventions to decrease the unexpectedly high malaria burden in the region. Toward this goal, polymorphic parasite genes (ama1, csp) in residents and passengers traveling to Central Turkana were genotyped by amplicon deep sequencing. Genotyping and epidemiological data were combined to assess parasite importation. The contribution of travel to malaria transmission was estimated by modelling case reproductive numbers inclusive and exclusive of travelers. P. falciparum was detected in 6.7% (127/1891) of inbound passengers, including new haplotypes which were later detected in locally-transmitted infections. Case reproductive numbers approximated 1 and did not change when travelers were removed from transmission networks, suggesting that transmission is not fueled by travel to the region but locally endemic. Thus, malaria is not only prevalent in Central Turkana but also sustained by local transmission. As such, interrupting importation is unlikely to be an effective malaria control strategy on its own, but targeting interventions locally has the potential to drive down transmission

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL

Theory and description in African Linguistics: Selected papers from the 47th Annual Conference on African Linguistics

The papers in this volume were presented at the 47th Annual Conference on African Linguistics at UC Berkeley in 2016. The papers offer new descriptions of African languages and propose novel theoretical analyses of them. The contributions span topics in phonetics, phonology, syntax, semantics, and pragmatics and reflect the typological and genetic diversity of languages in Africa. Four papers in the volume examine Areal Features and Linguistic Reconstruction in Africa, and were presented at a special workshop on this topic held alongside the general session of ACAL