This study aims to understand the time-to-treatment initiation pre and post DAA access to inform strategies to improve HCV care. The data for our study were derived from the SuperMIX cohort study of people who inject drugs in Melbourne, Australia. Time-to-event analysis using Weibull accelerated failure time was performed for data collected between 2009 and 2021, among a cohort of HCV-positive participants. Among 223 participants who tested positive for active hepatitis C infection, 102 people (45.7%) reported treatment initiation, with a median time-to-treatment of 7 years. However, the median time-to-treatment reduced to 2.3 years for those tested positive after 2016. The study found that treatment with Opioid Agonist Therapy (TR 0.7, 95% CI 0.6–0.9), engagement with health or social services (TR 0.7, 95% CI 0.6–0.9), and having a first positive HCV RNA test after March 2016 (TR 0.3, 95% CI 0.2–0.3) were associated with a reduced time-to-treatment initiation. The study highlights the need for strategies to improve engagement with health services, including drug treatment services into routine HCV care to achieve timely treatment.

In torrid regions, thermal environment is of very great importance as regards comfort and certainly influences the health and efficiency of white men. The human race may have arisen under the influence of climates similar to those now prevailing in the Tropics where indigenous peoples sojourn in an almost natural state with little protection against either heat or cold. The European brings with him his native conventions as regards houses and clothing, developed, in the case of Britons, in quite northern regions, where the human race requires protection against cold. These may be more or less unsuitable for tropical heat but, being conventions, they cannot be lightly thrown aside. European clothes afford protection against disease-carrying insects, poisonous stings and bites, and the question arises as to the best way to modify them to suit the hot climate. In any case, the northern European in the Tropics is in an abnormal climatic environment and, though he may survive a long time, there can be little doubt that he rarely enjoys his natural robustness of health with the result that even trivial ailments assume serious aspects. It appears that there is a much narrower margin of health stability, and proportionately greater care is required if the system is to be kept within the limits. Mr Elsworth Huntingdon1 has adduced evidence suggesting that white races, even if they are able to survive within the torrid zone, undergo deterioration.

1. The mechanical effects of morphine, heroin, codeine, dilaudid, dicodid, and eukodol upon the alimentary tract are discussed and contrasted.

2. The results of these mechanical effects upon the passage of food along the alimentary canal are discussed.

3. The constipating action of morphine is explained upon an almost purely mechanical basis.

4. From experimental evidence it is concluded that dilaudid is probably a constipating drug although this effect may not be so marked as that produced by morphine.

5. There is no experimental evidence to suggest that the administration of dicodid would ever produce constipation.

6. It is suggested that small doses of eukodol are not constipating, whereas large doses, in certain circumstances which are discussed, may produce a mild degree of constipation.

A metabolic inhibition test based upon phosphatase production is described. This is of value for those Mycoplasma species which produce phosphatase but which cannot be examined by the previously published metabolic inhibition techniques.

To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011–2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs (n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0–17.0); PAF = 55.3% (95% CI 43.3–83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3–8.7); PAF = 38.0% (95% CI 18.3–93.6)) and anal STI (RR = 5.3 (95% CI 1.7–16.7); PAF = 22.0 (95% CI −16.8 to 100.0)) were significantly (P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6–2.4); PAF = 19.5 (95% CI 10.6–30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0–3.0); PAF = 28.0 (95% CI 21.0–36.4)) were also significantly associated with anal STI, as was younger age (16–34/≥35; RR = 1.7 (95% CI 1.4–2.1); PAF = 15.5 (95% CI 6.4–27.6)) and group sex (RR = 1.3 (95% CI 1.1–1.6); PAF = 9.0 (95% CI −2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.

Transmission of Staphylococcus aureus colonization in community-based populations is not well understood. We sought to describe the molecular epidemiology of S. aureus colonization in the Old Order Amish. The study was a prospective, observational study of healthy adults and their same-sex siblings who were cultured from the anterior nares twice. S. aureus isolates were characterized using spa typing. Overall, 40% (159/398) of the study population was colonized with S. aureus. There were 84 spa types with the most abundant spa types being t012 (13%) and t021 (7%). There was no clustering of spa types within sibling groups; however, there was clustering within households. There were 111 S. aureus-colonized participant pairs living within the same household. Of these, 47% had concordant spa types. The diversity of spa types across a relatively isolated, genetically homogenous population with a similar lifestyle is striking. Taken together this suggests that S. aureus transmission is a local phenomenon limited to very close contact.

The mechanisms whereby staphylococcal strains grown in plasma assume increased resistance to polymorph bactericidins were investigated. Observations reported here showed that cultural conditions could determine the path of conversion to resistance. Staphylococcal strains and mutants lacking either free coagulase or clumping factor or both all showed enhanced resistance after 10 h incubation in plasma proteins, thus giving no clear indication that these factors were involved in the interactions. In fact, prolonged incubation in bovine serum albumin (22 h) and ordinary broth medium (24 h) also resulted in increased resistance. A distinction between staphylococcal factors interacting specifically with plasma proteins and such non-specific conversions was obtained in two different ways. Stripping of a hypothetical surface protein by treatment with trypsin or 2 M potassium bromide rendered plasma- but not 24 h-broth organisms susceptible, indicating protein coating of plasma-grown organisms. Also free coagulase-positive strains and mutants incubated in plasma for 30 min were converted while those lacking both or possessing clumping factor alone were not. It therefore appears that one of the mechanisms of acquiring resistance involves a rapid interaction between staphylococcal-free coagulase and fibrinogen, resulting in the deposition of fibrin or fibrin derivatives on the bacterial surface.

Contact with livestock and consumption of unpasteurised dairy products are associated with an increased risk of zoonotic and foodborne infection, particularly among populations with close animal contact, including pastoralists and semi-pastoralists. However, there are limited data on disease risk factors among pastoralists and other populations where livestock herding, particularly of dromedary camels, is common. This cross-sectional study used a previously validated survey instrument to identify risk factors for self-reported symptoms. Adults (n = 304) were randomly selected from households (n = 171) in the Somali Region of Ethiopia, a region characterised by chronic food insecurity, population displacement, recurrent droughts and large semi-pastoralist and pastoralist populations. Multivariable logistic regression assessed associations between self-reported symptoms and type of milk consumed, controlling for demographics and human-animal interaction. Consumption of days-old unrefrigerated raw camel milk was significantly associated with symptoms in the 30 days prior to the survey (AOR = 5.07; 95% CI 2.41–10.66), after controlling for age, refugee status, sanitation, camel ownership and source of drinking water and accounting for clustering. Consumption of days-old unrefrigerated raw ruminant milk was significantly associated with symptoms (AOR = 4.00, 95% CI 1.27–12.58). Source of drinking water and camel ownership, a proxy for camel contact, were significantly associated with the outcome in each model. There were no significant associations between self-reported symptoms and fresh or soured animal milk consumption. Research is needed to identify pathogens and major routes of transmission. Tailored communication campaigns to encourage safe food preparation should also be considered.

An outbreak of suspected infectious hepatitis in a primary school was investigated using sensitive diagnostic methods for hepatitis A. A total of 116 sera from children were tested for the presence of both IgM and IgG antibodies to hepatitis A (HAV). The results were compared to those obtained for samples from a control school. IgG antibodies were present in 45 % and 10% of the children in the outbreak and control schools respectively.

Self-instigated isolation is heavily relied on to curb severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Accounting for uncertainty in the latent and prepatent periods, as well as the proportion of infections that remain asymptomatic, the limits of this intervention at different phases of infection resurgence are estimated. We show that by October 2020, SARS-CoV-2 transmission rates in England had already begun exceeding levels that could be interrupted using this intervention alone, lending support to the second national lockdown on 5th November 2020.

A strain of Proteus vulgaris, recovered from a case of cystitis, showed extreme pleomorphism in a primary culture on ordinary agar.

Pleomorphism was not found in sub-cultures on media free from added NaCl, but it appeared in the presence of a limited range of NaCl concentrations; with still higher concentrations it was not observed, although growth occurred. It was rarely found in cultures which grew with difficulty.

Pleomorphism, occurring under the conditions mentioned as to salt concentration, was most marked in young cultures which grew vigorously; it usually disappeared as the cultures aged; and it became less and less evident in serial sub-cultures on medium containing the same amount of salt.

The morphology of the organism differed on different media, e.g. filamentous on salt-free agar, short bacillary on MacConkey's agar, but it was practically constant in repeated sub-cultures on any one type of medium.

Pleomorphism could be re-induced on any of the media used by suitable alteration of its NaCl content (increase or decrease). Pleomorphism was not determined by variation of the H-ion concentration of salt-free media; nor by variation of the temperature of incubation of cultures; nor by growth in fluid media as opposed to solid media.

After nearly 4 years under laboratory conditions the organism is still sensitive to variation in the NaCl concentration of its environment, as evidenced by pleomorphism; but pleomorphism is now less extreme than it was originally.

Pleomorphism is still most marked in young sub-cultures on media with suitably altered salt concentration, but it is sometimes difficult now to induce pleomorphism unless a stock culture several weeks old is used as the inoculum.

The pleomorphism comprises aberrant forms similar to many of those which are regarded by certain observers as evidence of stages in a life cycle; but, in the case of the organism described, these forms can be induced by the simple expedient of altering the salt concentration of the medium on which it is grown. The occurrence of such forms is thus, of itself, no proof of a life cycle.

Congenital Zika is a devastating consequence of maternal Zika virus infections. Estimates of age-dependent seroprevalence profiles are central to our understanding of the force of Zika virus infections. We set out to calculate the age-dependent seroprevalence of Zika virus infections in Brazil. We analyzed serum samples stratified by age and geographic location, collected from 2016 to 2019, from about 16,000 volunteers enrolled in a Phase 3 dengue vaccine trial led by the Institute Butantan in Brazil. Our results show that Zika seroprevalence has a remarkable age-dependent and geographical distribution, with an average age of the first infection varying from region to region, ranging from 4.97 (3.03–5.41) to 7.24 (6.98–7.90) years. The calculated basic reproduction number, $ {R}_0 $, varied from region to region, ranging from 1.18 (1.04–1.41) to 2.33 (1.54–3.85). Such data are paramount to determine the optimal age to vaccinate against Zika, if and when such a vaccine becomes available.

1. Twenty-six passages from rat to rat have been effected without recourse to artificial media. The time taken was 89 days.

2. Our results furnish no evidence that the virulence of the bacillus used for the passages undergoes any alteration.

3. The experiment gives evidence of the varying susceptibility to plague of the Bombay rat.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2–5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

SARS-CoV-2 rapidly spreads among humans via social networks, with social mixing and network characteristics potentially facilitating transmission. However, limited data on topological structural features has hindered in-depth studies. Existing research is based on snapshot analyses, preventing temporal investigations of network changes. Comparing network characteristics over time offers additional insights into transmission dynamics. We examined confirmed COVID-19 patients from an eastern Chinese province, analyzing social mixing and network characteristics using transmission network topology before and after widespread interventions. Between the two time periods, the percentage of singleton networks increased from 38.9$ \% $ to 62.8$ \% $$ (p<0.001) $; the average shortest path length decreased from 1.53 to 1.14 $ (p<0.001) $; the average betweenness reduced from 0.65 to 0.11$ (p<0.001) $; the average cluster size dropped from 4.05 to 2.72 $ (p=0.004) $; and the out-degree had a slight but nonsignificant decline from 0.75 to 0.63 $ (p=0.099). $ Results show that nonpharmaceutical interventions effectively disrupted transmission networks, preventing further disease spread. Additionally, we found that the networks’ dynamic structure provided more information than solely examining infection curves after applying descriptive and agent-based modeling approaches. In summary, we investigated social mixing and network characteristics of COVID-19 patients during different pandemic stages, revealing transmission network heterogeneities.

There is limited research on whether inequalities exist among individuals from different ethnicities and deprivation status among enteric fever cases. The aim of the study was to investigate the association between the enteric fever incidence rates, ethnicity and deprivation for enteric fever cases in England. Additionally, it was assessed if ethnicity and deprivation were associated with symptom severity, hospital admission and absence from school/work using logistic regression models. Incidence rates were higher in the two most deprived index of multiple deprivation quintiles and those of Pakistani ethnicity (9.89, 95% CI 9.08–10.75) followed by Indian (7.81, 95% CI 7.18–8.49) and Bangladeshi (5.68, 95% CI 4.74–6.76) groups: the incidence rate in the White group was 0.07 (95% CI 0.06–0.08). Individuals representing Pakistani (3.00, 95% CI 1.66–5.43), Indian (2.05, 95% CI 1.18–3.54) and Other/Other Asian (3.51, 95% CI 1.52–8.14) ethnicities had significantly higher odds of hospital admission than individuals representing White (British/Other) ethnicity, although all three groups had statistically significantly lower symptom severity scores. Our results show that there are significant ethnic and socioeconomic inequalities in enteric fever incidence that should inform prevention and treatment strategies. Targeted, community-specific public health interventions are needed to impact on overall burden.

Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar. Diphtheria vaccination is delivered in combination with pertussis and tetanus antigens and coverage of this vaccine is often used as a core measure of health system functioning. However, coverage is challenging to estimate due to the difficulty in translating numbers of doses delivered into numbers of children effectively immunised. Serology provides an alternative lens onto immunisation, but is complicated by challenges in discriminating between natural and vaccine-derived seropositivity. Here, we leverage known features of the serological profile of diphtheria to bound expectations for vaccine coverage for diphtheria, and further refine these using serology for pertussis. We measured diphtheria antibody titres in 185 children aged 6–11 months and 362 children aged 8–15 years and analysed them with pertussis antibody titres previously measured for each individual. Levels of diphtheria seronegativity varied among age groups (18.9% of children aged 6–11 months old and 11.3% of children aged 8–15 years old were seronegative) and also among the districts. We also find surprisingly elevated levels of individuals seropositive to diphtheria but not pertussis in the 6–11 month old age group suggesting that vaccination coverage or efficacy of the pertussis component of the DTP vaccine remains low or that natural infection of diphtheria may be playing a significant role in seropositivity in Madagascar.

Ehrlichiosis is a zoonotic illness caused by Ehrlichia pathogens transmitted by ticks. Case data from 1999 to 2015, provided by the Missouri Department of Health and Senior Services (DHSS), were used to compare the seasonality and the change in incidence over time of ehrlichiosis infection in two Missouri ecoregions, Eastern Temperate Forest (ETF) and Great Plains (GP). Although the number of cases has increased over time in both ecoregions, the rate of change was significantly faster in ETF region. There was no significant difference in seasonality of ehrlichiosis between ecoregions. In Missouri, the estimated ehrlichiosis season begins, on average, in mid-March, peaks in June, and concludes in mid-October. Our results show that the exposure and risk season for ehrlichiosis in Missouri is at least 7 months long.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.