Summary Background Routine data from Malawi’s prevention of mother-to-child transmission (MTCT) option B+ programme suggest high uptake of antiretroviral therapy (ART) among pregnant women. Malawi’s Ministry of Health led the National Evaluation of Malawi’s PMTCT Program to obtain nationally representative data on maternal ART coverage and prevention of MTCT effectiveness. Here, we present the early transmission data for infants aged 4–12 weeks. Methods We used a multistage cluster design to recruit a nationally representative sample of HIV-exposed infants and their mothers in Malawi. Between October 16, 2014, and May 17, 2016, we screened for HIV in all mothers attending an under-5 vaccination or outpatient sick-child clinic with infants aged 4–26 weeks at 54 health facilities selected across ten districts and four regional sampling zones. Infants with mothers identified as HIV-infected were enrolled in the cohort. We calculated weighted MTCT rates for only the subset of infants aged 4–12 weeks at screening, thereby capturing MTCT from early pregnancy, to delivery, and early breastfeeding. We collected data on maternal and infant demographics and self-reported use of HIV services, ART, and antenatal clinics. We tested HIV-exposed infants for the virus and assessed associations of certain variables with infant HIV status. Findings We confirmed HIV exposure in 3542 (10.4%) of 33 980 mother (guardian)-infant pairs with infants aged 4–26 weeks. Of those, 2530 (2514 mothers and 16 guardians) had infants aged 4–12 weeks at the time of screening (2498 singlets and 32 twins). We excluded 25 infants from the analysis because no information was available about their HIV status. 91.3% (95% CI 85.6–96.9) of mothers were on ART during pregnancy. The MTCT rate was 3.7% (2.3–6.0) overall and ranged from 1–4% (0.4–4.4) in women who initiated ART before pregnancy to 19–9% (13.4–28.6) in women not on ART. In multivariable logistic regression analysis, the odds of early MTCT were higher in mothers starting ART post partum (adjusted odds ratio 16.7, 95% CI 1–6-171.5; p=0–022) and in those not on ART with an unknown HIV status during pregnancy (19.1, 8–5.43–0; p<0–0001) than in mothers on ART before pregnancy. Among HIV-exposed infants, 98–0% (95% CI 96.9–99-1) were reported by the mother to have received infant nevirapine prophylaxis, and only 45–6% (34.8–56.4) were already enrolled in an exposed infant HIV care clinic at the time of study screening. Interpretation These data suggest that Malawi’s decentralisation of ART services has resulted in higher ART coverage and lower early MTCT. However, the uptake of services for HIV-exposed infants remains suboptimal.

BackgroundKey populations, including people who inject drugs (PWID), men who have sex with men (MSM), and female sex workers (FSW), are disproportionately affected by the HIV epidemic. Understanding the magnitude of, and informing the public health response to, the HIV epidemic among these populations requires accurate size estimates. However, low social visibility poses challenges to these efforts.ObjectiveThe objective of this study was to derive population size estimates of PWID, MSM, and FSW in Kampala using capture-recapture.MethodsBetween June and October 2017, unique objects were distributed to the PWID, MSM, and FSW populations in Kampala. PWID, MSM, and FSW were each sampled during 3 independent captures; unique objects were offered in captures 1 and 2. PWID, MSM, and FSW sampled during captures 2 and 3 were asked if they had received either or both of the distributed objects. All captures were completed 1 week apart. The numbers of PWID, MSM, and FSW receiving one or both objects were determined. Population size estimates were derived using the Lincoln-Petersen method for 2-source capture-recapture (PWID) and Bayesian nonparametric latent-class model for 3-source capture-recapture (MSM and FSW).ResultsWe sampled 467 PWID in capture 1 and 450 in capture 2; a total of 54 PWID were captured in both. We sampled 542, 574, and 598 MSM in captures 1, 2, and 3, respectively. There were 70 recaptures between captures 1 and 2, 103 recaptures between captures 2 and 3, and 155 recaptures between captures 1 and 3. There were 57 MSM captured in all 3 captures. We sampled 962, 965, and 1417 FSW in captures 1, 2, and 3, respectively. There were 316 recaptures between captures 1 and 2, 214 recaptures between captures 2 and 3, and 235 recaptures between captures 1 and 3. There were 109 FSW captured in all 3 rounds. The estimated number of PWID was 3892 (3090-5126), the estimated number of MSM was 14,019 (95% credible interval (CI) 4995-40,949), and the estimated number of FSW was 8848 (95% CI 6337-17,470).ConclusionsOur population size estimates for PWID, MSM, and FSW in Kampala provide critical population denominator data to inform HIV prevention and treatment programs. The 3-source capture-recapture is a feasible method to advance key population size estimation.

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.

ObjectiveTo develop transparent and reproducible methods for imputing missing data on disease incidence at national-level for the year 2005.MethodsWe compared several models for imputing missing country-level incidence rates for two foodborne diseases – congenital toxoplasmosis and aflatoxin-related hepatocellular carcinoma. Missing values were assumed to be missing at random. Predictor variables were selected using least absolute shrinkage and selection operator regression. We compared the predictive performance of naive extrapolation approaches and Bayesian random and mixed-effects regression models. Leave-one-out cross-validation was used to evaluate model accuracy.FindingsThe predictive accuracy of the Bayesian mixed-effects models was significantly better than that of the naive extrapolation method for one of the two disease models. However, Bayesian mixed-effects models produced wider prediction intervals for both data sets.ConclusionSeveral approaches are available for imputing missing data at national level. Strengths of a hierarchical regression approach for this type of task are the ability to derive estimates from other similar countries, transparency, computational efficiency and ease of interpretation. The inclusion of informative covariates may improve model performance, but results should be appraised carefully.

Objectives and designThis trial evaluated the effect of bandaging of acute painful ulcerative bovine digital dermatitis (DD) lesion (stage M2) in dairy cows, tested using two different topical treatments.DesignRandomised clinical trial.SettingThis study was conducted using Holstein-Friesian cows ranging in age from heifers to fourth lactation in a single dairy herd and diagnosed with acute ulcerative DD lesions (stage M2) on the first examination (week 0). Cows were randomly assigned into either a non-bandaged or bandaged group across two treatment conditions: topical chlortetracycline spray (CTC) and Intra Hoof-Fit Gel (IHF). Lesions received standardised bandaging and treatment on a weekly basis. Unhealed lesions could receive up to five repeated treatments, at weekly intervals, within a four-week period. Both M-stage and locomotion were also evaluated and scored weekly. Cows with healthily formed skin (stage M0) were deemed healed and subsequently released from the study.ResultsIn total, 163 M2 lesions were diagnosed at week 0. Bandaged M2 lesions had a significantly higher probability of cure than non-bandaged lesions regardless of treatment type (HR: 4.1; P<0.001; 95 per cent CI: 2.5 to 6.8). Most healing occurred within the first three weeks of trial. Furthermore, bandaged lesions (group 2 and group 4) were significantly less likely to progress into the chronic hyperkeratotic or proliferative stage (M4) than non-bandaged lesions in group 1 and group 3 (HR: 0.10; P<0.001; 95 per cent CI: 0.04 to 0.22). Out of concern for the cow’s wellbeing, this study investigated the effects of bandaging on locomotion. Bandaging had no effect on locomotion for either cows treated with CTC (group 1: median Sprecher score, 2; IQR=1–2; group 2: median Sprecher score, 2; IQR=1–3; P=0.3) or IHF (group 3: median Sprecher score, 2; IQR=1–2; group 4: median Sprecher score, 2; IQR=1–3; P=0.3).

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Tibiotarsal fractures are a common presentation in small bird species and anecdotally have been reported to carry a good prognosis with proper treatment, such as external coaptation. For this retrospective study, the medical records of 5 institutions were reviewed for tibiotarsal fractures diagnosed in companion birds weighing less than 200 g. A total of 86 cases met the inclusion criteria. Cockatiels ( Nymphicus hollandicus) (24/86) and budgerigars ( Melopsittacus undulatus) (19/86) were the most frequently represented species. Median body weight of the birds included was 72 g (range, 16-182 g). Mid-diaphyseal (46/86) and closed (73/86) fractures with intact, deep pain sensation in the affected limb (69/76) were most frequent. A tape splint alone (79/86) or a tape splint in addition to an intramedullary pin (7/86) were applied in all cases. Median time to fracture stabilization based on palpation was 19 days (range, 7-49 days). In most cases (61/86), the initial splint applied was maintained until fracture healing was complete. A successful outcome was documented in 92% (79/86) of birds. Fractures caused by a dog or cat attack, birds presenting without deep pain sensation in the affected limb, and cases where the splint was removed before 14 days after fixation were associated with a significantly increased risk of complications, resulting in an unsuccessful outcome. The findings of this study indicated that a tape splint is an appropriate means for treatment of tibiotarsal fractures in birds weighing less than 200 g.

The purpose of this study was to apply a novel statistical method for variable selection and a model-based approach for filling data gaps in mortality rates associated with foodborne diseases using the WHO Vital Registration mortality dataset. Correlation analysis and elastic net regularization methods were applied to drop redundant variables and to select the most meaningful subset of predictors. Whenever predictor data were missing, multiple imputation was used to fill in plausible values. Cluster analysis was applied to identify similar groups of countries based on the values of the predictors. Finally, a Bayesian hierarchical regression model was fit to the final dataset for predicting mortality rates. From 113 potential predictors, 32 were retained after correlation analysis. Out of these 32 predictors, eight with non-zero coefficients were selected using the elastic net regularization method. Based on the values of these variables, four clusters of countries were identified. The uncertainty of predictions was large for countries within clusters lacking mortality rates, and it was low for a cluster that had mortality rate information. Our results demonstrated that, using Bayesian hierarchical regression models, a data-driven clustering of countries and a meaningful subset of predictors can be used to fill data gaps in foodborne disease mortality.