The Human-Baited Double Net Trap: An Alternative to Human Landing Catches for Collecting Outdoor Biting Mosquitoes in Lao PDR

Estimating the exposure of individuals to mosquito-borne diseases is a key measure used to evaluate the success of vector control operations. The gold standard is to use human landing catches where mosquitoes are collected off the exposed limbs of human collectors. This is however an unsatisfactory method since it potentially exposes individuals to a range of mosquito-borne diseases. In this study several sampling methods were compared to find a method that is representative of the human-biting rate outdoors, but which does not expose collectors to mosquito-borne infections. The sampling efficiency of four odour-baited traps were compared outdoors in rural Lao PDR; the human-baited double net (HDN) trap, CDC light trap, BG sentinel trap and Suna trap. Subsequently the HDN, the best performing trap, was compared directly with human landing catches (HLC), the ‘gold standard’, for estimating human-biting rates. HDNs collected 11–44 times more mosquitoes than the other traps, with the exception of the HLC. The HDN collected similar numbers of Anopheles (Rate Ratio, RR = 1.16, 95% Confidence Intervals, 95% CI = 0.61–2.20) and Culex mosquitoes (RR = 1.26, 95% CI = 0.74–2.17) as HLC, but under-estimated the numbers of Aedes albopictus (RR = 0.45, 95% CI = 0.27–0.77). Simpson’s index of diversity was 0.845 (95% CI 0.836–0.854) for the HDN trap and 0.778 (95% CI 0.769–0.787) for HLC, indicating that the HDN collected a greater diversity of mosquito species than HLC. Both HLC and HDN can distinguish between low and high biting rates and are crude ways to measure human-biting rate. The HDN is a simple and cheap method to estimate the human-biting rate outdoors without exposing collectors to mosquito bites.     

Killer whale (Orcinus orca) population dynamics in response to a period of rapid ecosystem change in the eastern North Atlantic

This study investigates survival and abundance of killer whales (Orcinus orca) in Norway in 1988–2019 using capture–recapture models of photo‐identification data. We merged two datasets collected in a restricted fjord system in 1988–2008 (Period 1) with a third, collected after their preferred herring prey shifted its wintering grounds to more exposed coastal waters in 2012–2019 (Period 2), and investigated any differences between these two periods. The resulting dataset, spanning 32 years, comprised 3284 captures of 1236 whales, including 148 individuals seen in both periods. The best‐supported models of survival included the effects of sex and time period, and the presence of transients (whales seen only once). Period 2 had a much larger percentage of transients compared to Period 1 (mean = 30% vs. 5%) and the identification of two groups of whales with different residency patterns revealed heterogeneity in recapture probabilities. This caused estimates of survival rates to be biased downward (females: 0.955 ± 0.027 SE, males: 0.864 ± 0.038 SE) compared to Period 1 (females: 0.998 ± 0.002 SE, males: 0.985 ± 0.009 SE). Accounting for this heterogeneity resulted in estimates of apparent survival close to unity for regularly seen whales in Period 2. A robust design model for Period 2 further supported random temporary emigration at an estimated annual probability of 0.148 (± 0.095 SE). This same model estimated a peak in annual abundance in 2015 at 1061 individuals (95% CI 999–1127), compared to a maximum of 731 (95% CI 505–1059) previously estimated in Period 1, and dropped to 513 (95% CI 488–540) in 2018. Our results indicate variations in the proportion of killer whales present of an undefined population (or populations) in a larger geographical region. Killer whales have adjusted their distribution to shifts in key prey resources, indicating potential to adapt to rapidly changing marine ecosystems.     

Preclinical Detection of Variant CJD and BSE Prions in Blood

The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later went on to develop the disease. As there is no validated assay for detection of vCJD/BSE infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q₁₇₁ PrP substrates provided the best amplification performances. These results indicate that the homology of PrP amino-acid sequence between the seed and the substrate is not the crucial determinant of the vCJD agent propagation in vitro. The ability of this method to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep and primate models of the disease, the assay enabled the identification of infected individuals in the early preclinical stage of the incubation period. Finally, sample panels that included buffy coat from vCJD affected patients and healthy controls were tested blind. The assay identified three out of the four tested vCJD affected patients and no false positive was observed in 141 healthy controls. The negative results observed in one of the tested vCJD cases concurs with results reported by others using a different vCJD agent blood detection assay and raises the question of the potential absence of prionemia in certain patients.     

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review

Background

The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries.

Methods

We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally.

Results

The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996.

Conclusions

Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.     

The Magnitude of Tobacco Smoking-Betel Quid Chewing-Alcohol Drinking Interaction Effect on Oral Cancer in South-East Asia. A Meta-Analysis of Observational Studies

Tobacco smoking, betel quid chewing and alcohol drinking are oral cancer risk factors. Observational studies unanimously report that oral cancer risk in smoking-drinking-chewing exposed subjects is exceptionally high. However, none of them assessed the fractions of this risk attributable to the three individual risk factors and to the smoking-drinking-chewing interaction. The present study sought to assess the magnitude of the smoking-drinking-chewing interaction effect on oral cancer. A meta-analysis of observational South-East Asian studies which reported oral cancer odds ratios (ORs) stratified for smoking-drinking-chewing exposures was performed. The pooled ORs were estimated and controlled for quality, heterogeneity, publication bias and inclusion criteria. The smoking-drinking-chewing interaction effect was estimated through the pooled Relative Excess Risk due to Interaction (RERI, excess risk in smoking-drinking-chewing exposed individuals with respect to the risk expected from the addition of the three individual risks of smoking, drinking and chewing). Fourteen studies were included with low between-study heterogeneity. The pooled ORs for smoking, drinking, chewing, smoking-drinking-chewing, respectively were 3.6 (95% confidence interval −95% CI, 1.9–7.0), 2.2 (95% CI, 1.6–3.0), 7.9 (95% CI, 6.7–9.3), 40.1 (95% CI, 35.1–45.8). The pooled RERI was 28.4 (95% CI, 22.9–33.7). Among smoking-drinking-chewing subjects, the individual effects accounted for 6.7% (smoking), 3.1% (drinking), 17.7% (chewing) of the risk, while the interaction effect accounted for the remaining 72.6%. These data suggest that 44,200 oral cancer cases in South-East Asia annually occur among smoking-drinking-chewing exposed subjects and 40,400 of these are exclusively associated with the interaction effect. Effective oral cancer control policies must consider concurrent tobacco smoking, alcohol drinking, betel quid chewing usages as a unique unhealthy lifestyle.     

Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes

Background

In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy.

Methods

We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents.

Results

We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results.

Interpretation

Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.     

Recurrence of Subdural Haematoma in a Population-Based Cohort – Risks and Predictive Factors

Objectives

To estimate the risks of and identify predictors for recurrent subdural haematoma in surgically and conservatively treated patients.

Methods

The cohort comprised all individuals diagnosed with a first-time subdural hematoma in Denmark 1996–2011. Information on potential predictors was retrieved from the Danish health registers. Cumulative recurrence risks were estimated using the Aalen-Johansen estimator. Rate ratios (RR) were estimated using Poisson regression.

Results

Among 10,158 individuals with a subdural hematoma, 1,555 had a recurrent event. The cumulative risk of recurrent subdural hematoma was 9% at 4 weeks after the primary bleeding, increasing to and stabilising at 14% after one year. Predictors associated with recurrence were: Male sex (RR 1.60, 95% CI:1.43–1.80), older age (>70 years compared to 20–49 years; RR 1.41, 95% CI: 1.21–1.65), alcohol addiction (RR 1.20, 95% CI:1.04–1.37), surgical treatment (RR 1.76, 95% CI:1.58–1.96), trauma diagnoses (RR 1.14, 95% CI:1.03–1.27), and diabetes mellitus (RR 1.40, 95% CI:1.11–1.74). Out of a selected combination of risk factors, the highest cumulative 1-year recurrence risks for subdural hematoma of 25% (compared to 14% for all patients) was found in surgically treated males with diabetes mellitus.

Conclusions

The recurrence risk of subdural hematoma is largely limited to the first year. Patient characteristics including co-morbidities greatly influence the recurrence risk of SDH, suggesting that individualized prognostic guidance and follow-up is needed.     

Screening for Decreased Glomerular Filtration Rate and Associated Risk Factors in a Cohort of HIV-Infected Patients in a Middle-Income Country

With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m²) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m², 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m² were as follows: age ≥50 years (PR = 3.4; 95% CI: 1.7–6.8), diabetes (PR = 2.0; 95% CI: 1.2–3.4), hypertension (PR = 2.0; 95% CI: 1.3–3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3–3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3–9.4) and past exposure to indinavir (PR = 1.7; 95% CI: 1.0–2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.     

Obstetric Outcomes of Mothers Previously Exposed to Sexual Violence

Background

There is a scarcity of data on the association of sexual violence and women''s subsequent obstetric outcomes. Our aim was to investigate whether women exposed to sexual violence as teenagers (12–19 years of age) or adults present with different obstetric outcomes than women with no record of such violence.

Methods

We linked detailed prospectively collected information on women attending a Rape Trauma Service (RTS) to the Icelandic Medical Birth Registry (IBR). Women who attended the RTS in 1993–2010 and delivered (on average 5.8 years later) at least one singleton infant in Iceland through 2012 formed our exposed cohort (n = 1068). For each exposed woman''s delivery, nine deliveries by women with no RTS attendance were randomly selected from the IBR (n = 9126) matched on age, parity, and year and season of delivery. Information on smoking and Body mass index (BMI) was available for a sub-sample (n = 792 exposed and n = 1416 non-exposed women). Poisson regression models were used to estimate Relative Risks (RR) with 95% confidence intervals (CI).

Results

Compared with non-exposed women, exposed women presented with increased risks of maternal distress during labor and delivery (RR 1.68, 95% CI 1.01–2.79), prolonged first stage of labor (RR 1.40, 95% CI 1.03–1.88), antepartum bleeding (RR 1.95, 95% CI 1.22–3.07) and emergency instrumental delivery (RR 1.16, 95% CI 1.00–1.34). Slightly higher risks were seen for women assaulted as teenagers. Overall, we did not observe differences between the groups regarding the risk of elective cesarean section (RR 0.86, 95% CI 0.61–1.21), except for a reduced risk among those assaulted as teenagers (RR 0.56, 95% CI 0.34–0.93). Adjusting for maternal smoking and BMI in a sub-sample did not substantially affect point estimates.

Conclusion

Our prospective data suggest that women with a history of sexual assault, particularly as teenagers, are at increased risks of some adverse obstetric outcomes.     

Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID₅₀) of 11,000 spores (95% confidence interval 7,200–17,000), ID₁₀ of 1,700 (1,100–2,600), and ID₁ of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID₅₀, 11.8 days (9.5–15.0) for ID₁₀, and 12.1 days (9.9–15.3) for ID₁. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses.     

Early Life Exposure to Famine and Colorectal Cancer Risk: A Role for Epigenetic Mechanisms

Background

Exposure to energy restriction during childhood and adolescence is associated with a lower risk of developing colorectal cancer (CRC). Epigenetic dysregulation during this critical period of growth and development may be a mechanism to explain such observations. Within the Netherlands Cohort Study on diet and cancer, we investigated the association between early life energy restriction and risk of subsequent CRC characterized by the (promoter) CpG island methylation phenotype (CIMP).

Methodology/Principal Findings

Information on diet and risk factors was collected by baseline questionnaire (n = 120,856). Three indicators of exposure were assessed: place of residence during the Hunger Winter (1944–45) and World War II years (1940–44), and father''s employment status during the Economic Depression (1932–40). Methylation specific PCR (MSP) on DNA from paraffin embedded tumor tissue was performed to determine CIMP status according to the Weisenberger markers. After 7.3 years of follow-up, 603 cases and 4631 sub-cohort members were available for analysis. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for CIMP+ (27.7%) and CIMP- (72.3%) tumors according to the three time periods of energy restriction, adjusted for age and gender. Individuals exposed to severe famine during the Hunger Winter had a decreased risk of developing a tumor characterized by CIMP compared to those not exposed (HR 0.65, 95%CI: 0.45–0.92). Further categorizing individuals by an index of ‘0–1’ ‘2–3’ or ‘4–7’ genes methylated in the promoter region suggested that exposure to the Hunger Winter was associated with the degree of promoter hypermethylation (‘0–1 genes methylated’ HR = 1.01, 95%CI:0.74–1.37; ‘2–3 genes methylated’ HR = 0.83, 95% CI:0.61–1.15; ‘4–7 genes methylated’ HR = 0.72, 95% CI:0.49–1.04). No associations were observed with respect to the Economic Depression and WWII years.

Conclusions

This is the first study indicating that exposure to a severe, transient environmental condition during adolescence and young adulthood may result in persistent epigenetic changes that later influence CRC development.     

Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight

Background

It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population–based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.

Methodology/Principal Findings

We followed 65,212 children born in Denmark from 1970–1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08–2.61) at 12 years of age and 1.63 (95% CI 1.00–2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71–6.42 at age 12, and OR 2.31, 95% CI 1.08–4.97 at age 13).

Conclusions/Significance

Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.     

Association between Blood Dioxin Level and Chronic Kidney Disease in an Endemic Area of Exposure

Background

Dioxin is an industrial pollutant related to various diseases, but epidemiological data on its effects on the kidney are limited. Therefore, we conducted a study to evaluate the association between dioxin exposure and chronic kidney disease (CKD) and identify the related factors.

Methods

We conducted a community-based cross-sectional study and recruited participants from an area where the residents were exposed to dioxin released from a factory. We defined a “high dioxin level” as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) ≥ 20 pg WHO₉₈-TEQ_DF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR) ≤ 60 mL/min/1.73m² or a diagnosis of CKD by a physician. The renal function was assessed between 2005 and 2010, and we excluded those who had had kidney diseases before the study started. Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD.

Results

Of the 2898 participants, 1427 had high dioxin levels, and 156 had CKD. In the univariate analyses, CKD was associated with high dioxin levels, age, gender, metabolic syndrome, diabetes mellitus, hypertension, and high insulin and uric acid levels. After adjusting for other factors, we found high dioxin levels (adjusted odds ratio [AOR] = 1.76, 95% confidence interval [CI]: 1.04–2.99), female gender (AOR = 1.74, 95%CI: 1.20–2.53), hypertension (AOR = 1.68, 95%CI: 1.17–2.42), high insulin levels (AOR = 2.14, 95% CI: 1.26–3.61), high uric acid levels (AOR = 4.25, 95% CI: 2.92–6.20), and older age (AOR = 4.66, 95% CI: 1.87–11.62 for 40–64 year and AOR = 26.66, 95% CI: 10.51–67.62 for age ≥ 65 year) were independent predictors of CKD.

Conclusion

A high dioxin level was associated with an increased prevalence of CKD. Therefore, the kidney function of populations with exposure to dioxin should be monitored.     

Assessment of the risk posed by bovine spongiform encephalopathy in cattle in Great Britain and the impact of potential changes to current control measures

We extended an existing back-calculation model to analyse data on reported clinical cases of bovine spongiform encephalopathy (BSE), data from random testing of healthy animals slaughtered in abattoirs and testing data from animals reported as sick or dying on the farm. Extensive analysis of demographic data was also undertaken. We estimated past and current BSE infection prevalences in the cattle population and the degree of case under-ascertainment resulting from excess mortality in cattle near to disease onset. Ongoing levels of human exposure to BSE infectivity were also estimated, together with the effect on these of a range of possible exposure-reduction strategies that might replace the current rule banning tissue from cattle over 30 months (OTM) of age from the human food supply. While any policy change that allows a wider age range of animals into the human food supply will increase levels of human exposure to infectivity, the risk posed by such increases is small by comparison with historical exposure levels. Making the pessimistic assumption that there will be 5000 deaths during the variant Creutzfeldt-Jakob disease (vCJD) epidemic in total, our analysis indicates that replacement of the OTM rule with testing would result in 0.04 additional vCJD deaths over the next 60 years. However, there is substantial (more than 40-fold) uncertainty surrounding this estimate, the sources of which are discussed.     

Prevalence of Latent and Active Tuberculosis among Dairy Farm Workers Exposed to Cattle Infected by Mycobacterium bovis

Background

Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW) exposed in settings with poor control of bovine tuberculosis.

Methodology/Principal Findings

Tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI) was 76.2% (95% CI, 71.4–80.9%) by TST and 58.5% (95% CI, 53.0–64.0%) by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31–5.64) and IGRA (OR 2.38; 95% CI, 1.31–4.30) adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines.

Conclusions

We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.     

Effect of Spatial Separation of Pigs on Spread of Streptococcus suis Serotype 9

The spread of an infectious agent in a population can be reduced by interfering in the infectiousness or susceptibility of individuals, and/or in their contact structure. The aim of this study was to quantify the effect of prevention of direct contact between infectious and susceptible pigs on the transmission of Streptococcus suis (S. suis). In three replicate experiments, S. suis-free pigs were housed in boxes either in pairs (25 pairs) or alone (15 pigs). The distance between the boxes was ±1 m. At 7 weeks of age, one pig of each pair was inoculated intranasally with S. suis serotype 9; the other pigs were exposed to S. suis by either direct (pairs) or indirect contact (individually housed pigs). Tonsillar brush and saliva swab samples from all pigs were collected regularly for 4 weeks post inoculation to monitor colonization with S. suis. All inoculated pigs became infected, and their pen mates became colonized within 2 days. Thirteen indirectly exposed pigs became positive within 7–25 days after exposure. The rate of direct transmission β_dir was estimated to be 3.58 per pig per day (95% CI: 2.29–5.60). The rate of indirect transmission increased in time, depending on the cumulative number of days pigs tested positive for the presence of S. suis. The estimate β’_ind was 0.001 (95% CI: 0.0006–0.0017) new infections per pig per day for each day that an infected pig was tested positive for S. suis. We conclude that prevention of direct contact reduces the rate at which susceptible pigs become colonized. Simulation studies using these parameters showed, however, that such intervention measure would not limit S. suis serotype 9 spread in a commercial pig farm to a relevant extent, implying that spatial separation of groups op pigs within a compartment would not be effective on a farm.     

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log₁₀) and cART-initiating cohorts (5.1–5.3 log₁₀) by about one log₁₀. The proportion of individuals with high (≥50,000 (4.7 log₁₀) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log₁₀) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.     

The COVID-19 outbreak in Sichuan,China: Epidemiology and impact of interventions

In January 2020, a COVID-19 outbreak was detected in Sichuan Province of China. Six weeks later, the outbreak was successfully contained. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of interventions in limiting SARS-CoV-2 transmission. We analyzed patient records for all laboratory-confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimated the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. We estimated R₀ at 2.4 (95% CI: 1.6–3.7). The epidemic was self-sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95% CI: 31–68 days), causing 9,216 more cases (95% CI: 1,317–25,545).