The prevalence of antibodies to Brucella abortus in marketed milk in Kenya and its public health implications

The risk of infection by milk-borne brucellosis is one reason for public health regulations which discourage informal milk markets that sell unpasteurized milk. However, these regulations are not generally implemented in many developing countries. Kenya is a typical example, with over 85% of milk sales passing through informal channels. Consumer practices to reduce or eliminate potential infection by milk-borne health hazards under these circumstances have rarely been studied. Seasonal survey data were collected between January 1999 and January 2000 from informal milk market agents of various cadres and from households consuming unpasteurized milk in rural and urban locations in central Kenya. Respondents were randomly selected within production system (extensive and intensive) and human population density (urban, peri-urban and rural) strata. In addition, pasteurized and packaged milk samples from five processors were collected. Samples were screened for antibodies to Brucella abortus using the milk ring test (MRT) (unpasteurized milk) and indirect antibody ELISA (both unpasteurized and pasteurized milk). Milk samples originating from farms in the extensive production system and those containing milk from many sources were associated with higher antibody detection proportions. Five percent of all raw milk samples collected from consumer households and 4% of samples collected from various levels of bulking of market samples were positive to the ELISA. There was poor to no agreement between the two antibody detection tests. All urban consumers and 96% of rural consumers of unpasteurized milk indicated that they boil the milk (in tea or otherwise) before consumption. The implications of these results on milk marketing in Kenya are discussed

CULTURAL MANAGEMENT OF RUSSIAN WHEAT APHID INFESTATION OF BREAD WHEAT VARIETIES IN KENYA

Wheat ( Triticum aestivum L.) is ecologically suited to East African countries and is the second important cereal after maize in Kenya. It is an important source of food, livestock feeds and income. However, its production (442,000 MT) does not meet annual domestic demand (1,750,000 MT), due to cereal aphids infestation. The most serious cereal aphid in Kenya is the Russian wheat aphid (RWA) ( Diuraphis noxia Kurdjumov), causing yield losses of >90% when not controlled. The objective of this study was to develop low cost cultural, sustainable and environmentally safe practices for the management of the RWA in East Africa. Treatments included nine varieties, three seeding rates and three rates of nitrogen application. Nine commercial wheat varieties, K. Tai, K. Kingbird, K Wren, K. Korongo, K. Hawk, K. Sunbird, Robin, K. Eagle, and NBWII were sown. Main plots were assigned to wheat varieties, sown at three seeding rates 75, 100 and 125 kg ha-1. Sub-plots were assigned to three rates of nitrogen, 75, 100 and 130 kg N ha-1, applied at tillering stage (GS 22). Variety K. Korongo supported the lowest aphid count of 3.6 per 5 plants; followed by K. Hawk (3.8) and Robin (2.9 aphids). Robin gave the highest grain yield (2.9 t ha-1), followed by K. Korongo (2.7 t ha-1) and K. Hawk (2.5 t ha-1). Application of 100 kg N ha-1 and seeding at 100 kg ha-1 were the best rates.Le bl\ue9 ( Triticum aestivum L.) convient \ue9cologiquement aux pays de l\u2019Afrique de l\u2019est et est la deuxi\ue8me c\ue9r\ue9ale importante apr\ue8s le ma\uefs au Kenya. C\u2019est une source importante de nourriture, nourritures de b\ue9tail et revenu. Pourtant, sa production (442,000 MT) ne satisfait pas de demande domestique annuelle (1,750,000 MT), en raison de l\u2019infestation de pucerons de c\ue9r\ue9ale. Le puceron de c\ue9r\ue9ale le plus s\ue9rieux au Kenya est le puceron de bl\ue9 russe (RWA) ( Diuraphis noxia Kurdjumov), en provoquant des pertes de production de> 90 % sinon contr\uf4l\ue9s. L\u2019objectif de cette \ue9tude \ue9tait de d\ue9velopper bas le prix les pratiques culturelles, durables et environnementalement s\ufbres pour l\u2019administration du RWA \ue0 Afrique de l\u2019est. Les traitements ont inclus neuf vari\ue9t\ue9s, trois taux seeding et trois taux d\u2019application d\u2019azote. Neuf vari\ue9t\ue9s de bl\ue9 commerciales, K. Tai, K. Kingbird, K le Troglodyte, K. Korongo, K. Faucon, K. Sunbird, Robin, K. L\u2019aigle et NBWII ont \ue9t\ue9 sem\ue9s. Les complots principaux ont \ue9t\ue9 allou\ue9s aux vari\ue9t\ue9s de bl\ue9, sem\ue9es \ue0 trois taux seeding 75, 100 et \ue0 125 kg ha 1. Les sous-complots ont \ue9t\ue9 allou\ue9s \ue0 trois taux d\u2019azote, 75, 100 et de 130 kg N ha-1, appliqu\ue9 au stade tillering (GS 22). Vari\ue9t\ue9 K. Korongo a soutenu le compte de puceron le plus bas de 3.6 par 5 usines; suivi par K. Le faucon (3.8) et Robin (2.9 pucerons). Robin a donn\ue9 la plus haute production de grain (2.9 t ha-1), suivi par K. Korongo (2.7 t ha-1) et K. Le faucon (2.5 t ha-1). L\u2019application de 100 kg N ha-1 et de seeding \ue0 100 kg ha-1 \ue9tait les meilleurs taux

Identification of stingless bees (Hymenoptera: Apidae) in Kenya using Morphometrics and DNA barcoding

Stingless bees are important pollinators of wild plants and crops. The identity of stingless bee species in Africa has not been fully documented. The present study explored the utility of morphometrics and DNA barcoding for identification of African stingless bee populations, and to further employ these tools to identify potential cryptic variation within species. Stingless bee samples were collected from three ecological zones, namely Kakamega Forest, Mwingi and Arabuko-Sokoke Forest, which are geographically distant and cover high, medium and low altitudes, respectively. Forewing and hind leg morphometric characters were measured to determine the extent of morphological variation between the populations. DNA barcodes were generated from the mitochondrial cytochrome c-oxidase I (COI) gene. Principal Component Analysis (PCA) on the morphometric measurements separated the bee samples into three clusters: (1) Meliponula bocandei; (2) Meliponula lendliana + Plebeina hildebrandti; (3) Dactylurina schmidti + Meliponula ferruginea black + Meliponula ferruginea reddish brown, but Canonical Variate Analysis (CVA) separated all the species except the two morphospecies (M. ferruginea reddish brown and black). The analysis of the COI sequences showed that DNA barcoding can be used to identify all the species studied and revealed remarkable genetic distance (7.3%) between the two M. ferruginea morphs. This is the first genetic evidence that M. ferruginea black and M. ferruginea reddish brown are separate species

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease