Wuchereria bancrofti infection is associated with progression to clinical visceral leishmaniasis in VL- endemic areas in Muzaffarpur, Bihar, India.

BACKGROUND: Co-endemicity of neglected tropical diseases (NTDs) necessitates that these diseases should be considered concomitantly to understand the relationship between pathology and to support disease management and control programs. The aims of the study were to assess the prevalence of filarial infection in asymptomatic Leishmania donovani infected individuals and the correlation of Wuchereria bancrofti infection with progression to clinical visceral leishmaniasis (VL) in Bihar, India. METHODOLOGY/PRINCIPAL FINDINGS: Within the Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) area, a cohort of Leishmania seropositive (n = 476) or seronegative individuals (n = 1130) were sampled annually for three years for filarial infection and followed for progression to clinical VL. To corroborate the results from the cohort study, we also used a retrospective case-control study of 36 VL cases and 71 controls selected from a subset of the HDSS population to investigate the relationship between progression to clinical VL and the prevalence of filarial infection at baseline. Our findings suggest a higher probability of progression to clinical VL in individuals with a history of filarial infection: in both the cohort and case-control studies, progression to clinical VL was higher among filaria infected individuals (RR = 2.57, p = 0.056, and OR = 2.52, p = 0.046 respectively). CONCLUSION: This study describes that progression to clinical VL disease is associated with serological evidence of prior infection with W. bancrofti. The integration of disease programs for Leishmania and lymphatic filariasis extend beyond the relationship of sequential or co-infection with disease burden. To ensure elimination targets can be reached and sustained, we suggest areas of co-endemicity would benefit from overlapping vector control activities, health system networks and surveillance infrastructure.

A cluster of nosocomial Lassa fever cases in a tertiary health facility in Nigeria: Description and lessons learned, 2018.

BACKGROUND: Lassa fever is an acute viral haemorrhagic disease endemic in Nigeria. The 2018 Lassa fever outbreak in Nigeria was unprecedented, with 8% of all cases occurring among healthcare workers (HCWs). A disproportionately high number of these infections occurred in HCWs working in a tertiary health facility in Nigeria. This paper describes the cluster of Lassa fever infections among HCWs in a treatment centre and the lessons learnt. METHODS: We analysed clinical, epidemiological and laboratory data from surveillance and laboratory records kept during the 2018 outbreak. Interviews were conducted with surviving HCWs using a questionnaire developed specifically for the investigation of Lassa fever infections in HCWs. Descriptive analysis of the data was performed in Microsoft excel. RESULTS: The index case was a 15-year-old male who presented at the health facility with fever and uncontrolled nasopharyngeal bleeding, following a recent uvulectomy by a traditional healer. Overall, 16 HCWs were affected (15 confirmed and 1 probable) with five deaths (CFR-31.6%). Of the 15 confirmed cases, five (33.3%) were asymptomatic. Nine HCWs were direct contacts of the index case; the remaining six HCWs had no direct contact with the index case. HCW interviews identified a low index of suspicion for Lassa fever leading to inadequate infection prevention and control (IPC) practices as possible contributing factors to nosocomial transmission. CONCLUSION: Maintaining a high index of suspicion for Lassa fever in all patients, especially in endemic areas, is essential in adhering to adequate IPC practices in health facilities in order to prevent nosocomial transmission of Lassa fever among HCWs. There is a need to continually train and sensitise HCWs on strict adherence to IPC measures while providing care, irrespective of a patient's provisional diagnosis.

Waterparks are high risk for cryptosporidiosis: A case-control study in Victoria, 2015.

BACKGROUND: An increase in notifications of cryptosporidiosis was observed in Victoria between March and April 2015. Cases mostly resided in one metropolitan region and hypothesis-generating interviews identified common exposures to aquatic facilities. We conducted a case-control study to determine exposure source(s) and facilitate control measures. METHODS: Laboratory-confirmed cases of cryptosporidiosis from the region of interest notified between 1 March and 23 April 2015 were included. Controls residing in the same region were recruited from participants in a population health survey and frequency matched (2 per case) by age group. Details of exposure to potential risk factors were collected using a standardised telephone questionnaire for the 14-days prior to illness for cases, and an analogous exposure period for controls. Univariable and multivariable logistic regression were used to determine risk factors associated with illness using STATA SE 13.1. RESULTS: Thirty cases and 66 controls were included in the study. Half the cases were less than 12 years of age and 62% were female. Illness was most strongly associated with recreational water exposure at any waterpark (adjusted odds ratio (aOR)=73.5; 95% confidence interval (CI):6.74-802), and specifically at Victorian waterparks (aOR=45.6; 95% CI:5.20-399). Cases were linked with attendance at either a waterpark in the region or an adjacent region. As a result of this investigation, hyperchlorination was completed at identified facilities and swim hygiene information distributed. CONCLUSION: This study reinforces the potential for recreational water facilities, particularly waterparks, to act as a transmission source of Cryptosporidium infections. Continued communication to patrons is required to ensure healthy swimming practice in Victorian aquatic facilities.

Probiotics to prevent or treat excessive infant crying: systematic review and meta-analysis.

IMPORTANCE Excessive infant crying is common, distressing, but without proven effective prevention or management options. Probiotics may be a promising solution. OBJECTIVE To examine whether probiotics are effective in the prevention/management of crying ("colic") in infants 3 months or younger. DATA SOURCES A systematic search of MEDLINE, EMBASE, and the Cochrane Library, supplemented by the metaRegister of Controlled Trials. STUDY SELECTION Studies that randomized infants 3 months or younger to oral probiotics vs placebo or no or standard treatment with the outcome of infant crying, measured as the duration or number of episodes of infant crying/distress or diagnosis of "infant colic." Twelve of the 1180 initially identified studies were selected. DATA EXTRACTION AND SYNTHESIS This review/meta-analysis was conducted according to guidelines from the Cochrane Handbook for Systematic Reviews of Interventions, with reporting following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were independently extracted by 3 of us. MAIN OUTCOME(S) AND MEASURE(S) Infant crying, measured as the duration or number of episodes of infant crying/distress, or diagnosis of "infant colic." RESULTS Of the 12 trials (1825 infants) reviewed, 6 suggested probiotics reduced crying, and 6 did not. Three of the 5 management trials concluded probiotics effectively treat colic in breastfed babies; 1 suggested possible effectiveness in formula-fed babies with colic, and 1 suggested ineffectiveness in breastfed babies with colic. Meta-analysis of 3 small trials of breastfed infants with colic found that Lactobacillus reuteri markedly reduced crying time at 21 days (median difference, -65 minutes/d; 95% CI, -86 to -44). However, all trials had potential biases. Meanwhile, of 7 prevention trials, 2 suggested possible benefits. Considerable variability in the study populations, study type, delivery mode/dose of probiotic supplementation, and outcomes precluded meta-analysis. CONCLUSIONS AND RELEVANCE Although L reuteri may be effective as treatment for crying in exclusively breastfed infants with colic, there is still insufficient evidence to support probiotic use to manage colic, especially in formula-fed infants, or to prevent infant crying. Results from larger rigorously designed studies applicable to all crying infants will help draw more definitive conclusions.

Blood lead levels in the adult Victorian population: results from the Victorian Health Monitor.

OBJECTIVE: To estimate blood lead levels (BLLs) in the adult Victorian population and compare the distribution of BLLs with the current national reference level to better inform public health prevention and management of lead toxicity. METHODS: Population-based cross-sectional health measurement survey of 50 randomly selected Census Collection Districts (CDs) throughout Victoria. The Victorian Health Monitor (VHM) was conducted over 12 months from May 2009 to April 2010. One eligible person (aged 18-75 years) from each household selected within each CD was randomly selected to participate. Persons with an intellectual disability and pregnant women were excluded from the sampling frame. BLLs were obtained from 3,622 of the 3,653 (99%) VHM participants. RESULTS: The geometric mean and median BLLs from the adult sample were 0.070 µmol/L (95%CI, 0.068-0.073) and 0.05 µmol/L (range: 0.05 to 1.22 µmol/L), respectively. Elevated BLLs (≥0.483 µmol/L or ≥10 µg/dL) were identified in 19 participants (0.7%; 95%CI, 0.3-1.6). Additionally, 86 participants (1.8%; 95%CI, 1.3-2.4) were identified with BLLs between 0.242 and <0.483 µmol/L (5 to <10 µg/dL). The geometric mean BLL was significantly higher for males, compared with females (0.077 µmol/L vs 0.064 µmol/L; p<0.001). BLLs increased significantly with age for both sexes. CONCLUSIONS: The first population estimates of BLLs in Victorian adults indicate the average adult BLL to be well below the current national reference level. However, some groups of the population have BLLs at which adverse effects may occur. Implications : The results provide baseline estimates for future population health surveillance and comparison with studies of at-risk groups.

Patient characteristics associated with hospitalisations for ambulatory care sensitive conditions in Victoria, Australia.

BACKGROUND: Ambulatory Care Sensitive Conditions (ACSCs) are those for which hospitalisation is thought to be avoidable with the application of preventive care and early disease management, usually delivered in a primary care setting. ACSCs are used extensively as indicators of accessibility and effectiveness of primary health care. We examined the association between patient characteristics and hospitalisation for ACSCs in the adult and paediatric population in Victoria, Australia, 2003/04. METHODS: Hospital admissions data were merged with two area-level socioeconomic indexes: Index of Socio-Economic Disadvantage (IRSED) and Accessibility/Remoteness Index of Australia (ARIA). Univariate and multiple logistic regressions were performed for both adult (age 18+ years) and paediatric (age <18 years) groups, reporting odds ratios (OR) and 95% confidence intervals (CI) for a number of predictors of ACSCs admissions compared to non-ACSCs admissions. RESULTS: Predictors were much more strongly associated with ACSCs admissions compared to non-ACSCs admissions in the adult group than for the paediatric group with the exception of rurality. Significant adjusted ORs in the adult group were 1.06, 1.15, 1.13, 1.06 and 1.11 for sex, rurality, age, IRSED and ARIA variables, and 1.34, 1.04 and 1.09 in the paediatric group for rurality, IRSED and ARIA, respectively. CONCLUSIONS: Disadvantaged paediatric and adult population experience more need of hospital care for ACSCs. Access barriers to primary care are plausible causes for the observed disparities. Understanding the characteristics of individuals experiencing access barriers to primary care will be useful for developing targeted interventions meeting the unique ambulatory needs of the population.

Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration.

PURPOSE: Diabetic patients who also have retinitis pigmentosa (RP) appear to have fewer and less severe retinal microvascular lesions. Diabetic retinopathy may be linked to increased inner retinal hypoxia, with the possibility that this is exacerbated by oxygen usage during the dark-adaptation response. Therefore, patients with RP with depleted rod photoreceptors may encounter proportionately less retinal hypoxia, and, when diabetes is also present, there may be fewer retinopathic lesions. This hypothesis was tested in rhodopsin knockout mice (Rho-/-) as an RP model in which the diabetic milieu is superimposed. The study was designed to investigate whether degeneration of the outer retina has any impact on hypoxia, to examine diabetes-related retinal gene expression responses, and to assess lesions of diabetic retinopathy. METHODS: Streptozotocin-induced diabetes was created in male C57Bl6 (wild-type; WT) and Rho-/- mice, and hyperglycemia was maintained for 5 months. The extent of diabetes was confirmed by measurement of glycated hemoglobin (%GHb) and accumulation of advanced glycation end products (AGEs). Retinal hypoxia was assessed using the bioreductive drug pimonidazole. The retinal microvasculature was studied in retinal flatmounts stained by the ADPase reaction, and the outer retina was evaluated histologically in paraffin-embedded sections. Retinal gene expression of VEGF-A, TNF-alpha, and mRNAs encoding basement membrane component proteins were quantified by real-time RT-PCR. RESULTS: The percentage GHb increased significantly in the presence of diabetes (P < 0.001) and was not different between WT or Rho-/- mice. Hypoxia increased in the retina of WT diabetic animals when compared with controls (P < 0.001) but this diabetes-induced change was absent in Rho-/- mice. Retinal gene expression of VEGF-A was significantly increased in WT mice with diabetes (P < 0.05), but was unchanged in Rho-/- mice. TNF-alpha gene expression significantly increased (4.9-fold) in WT mice with diabetes (P < 0.05) and also increased appreciably in Rho-/- mice but to a reduced extent (1.5 fold; P < 0.05). The outer nuclear layer in nondiabetic Rho-/- mice was reduced to a single layer after 6 months, but when diabetes was superimposed on this model, there was less degeneration of photoreceptors (P < 0.05). Vascular density was attenuated in diabetic WT mice compared with the nondiabetic control (P < 0.001); however, this diabetes-related disease was not observed in Rho-/- mice. CONCLUSIONS: Loss of the outer retina reduces the severity of diabetic retinopathy in a murine model. Oxygen usage by the photoreceptors during dark adaptation may contribute to retinal hypoxia and exacerbate the progression of diabetic retinopathy.

Rod photoreceptor loss in Rho-/- mice reduces retinal hypoxia and hypoxia-regulated gene expression.

PURPOSE: This study was conducted to evaluate whether regions of the retinal neuropile become hypoxic during periods of high oxygen consumption and whether depletion of the outer retina reduces hypoxia and related changes in gene expression. METHODS: Retinas from rhodopsin knockout (Rho-/-) mice were evaluated along with those of wild-type (WT) control animals. Retinas were also examined at the end of 12-hour dark or light periods, and a separate group was treated with l-cis-diltiazem at the beginning of a 12-hour dark period. Hypoxia was assessed by deposition of hypoxyprobe (HP) and HP-protein adducts were localized by immunohistochemistry and quantified using ELISA. Also, hypoxia-regulated gene expression and transcriptional activity were assessed alongside vascular density. RESULTS: Hypoxia was observed in the inner nuclear and ganglion cell layers in WT retina and was significantly reduced in Rho-/- mice (P < 0.05). Retinal hypoxia was significantly increased during dark adaptation in WT mice (P < 0.05), whereas no change was observed in Rho-/- or with l-cis-diltiazem-treated WT mice. Hypoxia-inducible factor (HIF)-1alpha DNA-binding and VEGF mRNA expression in Rho-/- retina was significantly reduced in unison with outer retinal depletion (P < 0.05). Retina from the Rho-/- mice displayed an extensive intraretinal vascular network after 6 months, although there was evidence that capillary density was depleted in comparison with that in WT retinas. CONCLUSIONS: Relative hypoxia occurs in the inner retina especially during dark adaptation. Photoreceptor loss reduces retinal oxygen usage and hypoxia which corresponds with attenuation of the retinal microvasculature. These studies suggest that in normal physiological conditions and diurnal cycles the adult retina exists in a state of borderline hypoxia, making this tissue particularly susceptible to even subtle reductions in perfusion.

Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy.

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNF-alpha-/- and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF-alpha significantly improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.

Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy.

We investigated whether inhibition of platelet-derived growth factor (PDGF) receptor tyrosine kinase activity would affect pericyte viability, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) expression and angiogenesis in a model of retinopathy of prematurity (ROP). ROP was induced in Sprague Dawley rats by exposure to 80% oxygen from postnatal (P) days 0 to 11 (with 3 hours/day in room air), and then room air from P12-18 (angiogenesis period). Shams were neonatal rats in room air from P0-18. STI571, a potent inhibitor of PDGF receptor tyrosine kinase, was administered from P12-18 at 50 or 100 mg/kg/day intraperitoneal (i.p.). Electron microscopy revealed that pericytes in the inner retina of both sham and ROP rats appeared normal; however STI571 induced a selective pericyte and vascular smooth muscle degeneration. Immunolabeling for caspase-3 and alpha-smooth muscle cell actin in consecutive paraffin sections of retinas confirmed that these degenerating cells were apoptotic pericytes. In all groups, VEGF and VEGFR-2 gene expression was located in ganglion cells, the inner nuclear layer, and retinal pigment epithelium. ROP was associated with an increase in both VEGF and VEGFR-2 gene expression and blood vessel profiles in the inner retina compared to sham rats. STI571 at both doses increased VEGF and VEGFR-2 mRNA and exacerbated angiogenesis in ROP rats, and in sham rats at 100 mg/kg/day. In conclusion, PDGF is required for pericyte viability and the subsequent prevention of VEGF/VEGFR-2 overexpression and angiogenesis in ROP.