Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling

We recently identified a new minor histocompatibility antigen, termed HA-8, which is presented by human leucocyte antigen (HLA)-A*0201 or HLA-A*0202 and expressed ubiquitously among tissues. A retrospective analysis of 577 Caucasian patients with HLA-A*0201 or A*0202 who had received a haematopoietic stem cell transplant from a human leucocyte antigen (HLA)-identical sibling was conducted to determine whether HA-8 disparity correlated with clinical outcome. HA-8 disparity was detected in 72 recipients, and grades II-IV graft-versus-host disease (GVHD) occurred in 46 (64%), compared with 251 (50%) of the 503 patients without HA-8 disparity. After adjusting for known risk factors for acute GVHD, this difference was statistically significant (odds ratio, 1.8; 95% confidence interval, 1.0-3.1; P = 0.04). However, the hazards of clinical extensive chronic GVHD, overall mortality and recurrent malignancy were not statistically significantly different between the two groups. These data suggest that the increased risk of acute GVHD associated with recipient HA-8 disparity was not sufficient to change other clinical outcomes.     

Proteolytic activity of cysteine protease in excretory-secretory product of Paragonimus westermani newly excysted metacercariae pivotally regulates IL-8 production of human eosinophils

This study investigated the effect of the excretory-secretory product (ESP) of Paragonimus westermani newly excysted metacercariae (PwNEM) on IL-8 production of human mature eosinophils. Treatment of eosinophils with lower concentrations (0.3 and 1 microg/ml) of the ESP significantly (P < 0.01) induced IL-8 production, whereas treatment of cells with higher concentrations (3 and 10 microg/ml) did not. This effect of the ESP was concentration-dependent. Interestingly, the amount of IL-8 production released into the culture supernatants was inversely correlated with the rate of eosinophil survival. When eosinophils were cultured with the same concentrations of the ESP for 24 h, the ESP resulted in eosinophil death in a dose-dependent manner. To investigate whether high proteolytic activity of proteases in the ESP could cause little production of IL-8, 10 microg/ml of ESP was pretreated with heat at 100 degrees C for 10 min or 56 degrees C for 30 min to reduce its proteolytic activity. IL-8 production of eosinophils incubated with heat-treated ESP was markedly increased comparable to that of cells treated with the lowest concentration used in this study. These findings suggest that the protease in the ESP of PwNEM pivotally regulates IL-8 production by controlling of eosinophil survival, depending on the amount of ESP released in vivo. Thus, the cysteine protease in the ESP of PwNEM could provide a novel role to control recruitment of inflammatory cells in larval-infected lesions in human paragonimiasis.     

Identification of Old World Leishmania species by PCR–RFLP of the 7 spliced leader RNA gene and reverse dot blot assay

The aim of the study was to assess the 7SL RNA PCR followed by restriction fragment length polymorphism (RFLP) and reverse dot blot (RDB) assays for use in identification of Old World Leishmania species. Species‐specific RFLP patterns were obtained for Leishmania major, Leishmania tropica and the Leishmania donovani complex when the 7SL RNA PCR product was digested with the restriction enzyme BsuRI, an isoschizomer of HaeIII. For the RDB assay, biotin‐labelled 7SL RNA amplicons were hybridized to Leishmania genus‐specific and species‐specific oligonucleotide probes immobilized onto a membrane. The Old World Leishmania species could be distinguished by using five probes: one that was a genus‐specific probe and hybridized to all Leishmania species (Lc), two that were specific for L. major (Lm1 and Lm2), one that was specific for L. tropica (Lt) and one that detected both L. major and L. tropica (Lmt). The PCR–RDB was 10 times more sensitive than 7SL PCR and can detect <1 parasite. In addition, the identification of species was easier and more reliable than with 7SL PCR–RFLP. 7SL PCR–RFLP detected parasites in 50 of 57 clinical samples, whereas PCR–RDB detected 53 and 55 were detected by amplification of kinetoplast (k) DNA. The 7SL RNA PCR has proven useful for direct diagnosis of Old World leishmaniasis, especially when combined with the RBD assay for species identification.     

Access to maternal and perinatal health services: lessons from successful and less successful examples of improving access to safe delivery and care of the newborn

The huge majority of the annual 6.3 million perinatal deaths and half a million maternal deaths take place in developing countries and are avoidable. However, most of the interventions aiming at reducing perinatal and maternal deaths need a health care system offering appropriate antenatal care and quality delivery care, including basic and comprehensive emergency obstetric care facilities. To promote the uptake of quality care, there are two possible approaches: influencing the demand and/or the supply of care. Five lessons emerged from experiences. First, it is difficult to obtain robust evidence of the effects of a particular intervention in a context, where they are always associated with other interventions. Second, the interventions tend to have relatively modest short‐term impacts, when they address only part of the health system. Third, the long‐term effects of an intervention on the whole health system are uncertain. Fourth, because newborn health is intimately linked with maternal health, it is of paramount importance to organise the continuum of care between mother and newborn. Finally, the transfer of experiences is delicate, and an intervention package that has proved to have a positive effect in one setting may have very different effects in other settings.     

Prevention of mother to child transmission of HIV (PMTCT) programme in KwaZulu‐Natal,South Africa: an evaluation of PMTCT implementation and integration into routine maternal,child and women’s health services

Objectives To evaluate prevention of mother to child transmission of HIV (PMTCT) implementation and integration of PMTCT with routine maternal and child health services in two districts of KwaZulu‐Natal; to report PMTCT coverage, to compare recorded and reported information, and to describe responsibilities of nurses and lay counsellors. Methods Interviews were conducted with mothers in post‐natal wards (PNW) and immunisation clinics; antenatal and child health records were reviewed. Interviews were conducted with nurses and lay counsellors in primary health care clinics. Results Eight hundred and eighty‐two interviews were conducted with mothers: 398 in PNWs and 484 immunisation clinics. During their recent pregnancy, 98.6% women attended antenatal care (ANC); 60.8% attended their first ANC in the third trimester, and 97.3% were tested for HIV. Of 312 mothers reporting themselves HIV positive during ANC, 91.3% received nevirapine, 78.2% had a CD4 count carried out, and 33.1% had a CD4 result recorded. In the immunisation clinic, 47.6% HIV‐exposed babies had a PCR test, and 47.0% received co‐trimoxazole. Of HIV‐positive mothers, 42.1% received follow‐up care, mainly from lay counsellors. In 12/26 clinics, there was a dedicated PMTCT nurse, PCR testing was not offered in 14/26 clinics, and co‐trimoxazole was unavailable in 13/26 immunisation clinics. Nurses and lay counsellors disagreed about their roles and responsibilities, particularly in the post‐natal period. Conclusions There is high coverage of PMTCT interventions during pregnancy and delivery, but follow‐up of mothers and infants is poor. Poor integration of PMTCT services into routine care, lack of clarity about health worker roles and poor record keeping create barriers to accessing services post‐delivery.     

Homocysteine and markers of inflammation in acute coronary syndrome

BACKGROUND:

An elevated level of homocysteine (Hcy) has been shown to be a cardiovascular risk factor in the majority of research studies. Recently, it was found to be associated with new risk factors such as inflammatory markers.

OBJECTIVES:

To investigate the distribution of plasma total Hcy (tHcy) and the levels of inflammatory markers in patients with acute coronary syndrome (ACS), and to evaluate the association between these parameters and the severity of the disease.

METHODS:

A total of 122 patients with ACS and 80 control subjects were recruited from the cardiac intensive care unit of the Military Hospital of Tunis, Tunisia. Lipid profile and the levels of tHcy, high-sensitivity C-reactive protein (HsCRP), interleukin (IL)-6, IL-8, IL-1β and tumour necrosis factor-alpha (TNFα) were determined for all participants. The distribution of these parameters were compared between groups and according to the number of diseased vessels in patients with ACS.

RESULTS:

ACS patients had significantly elevated levels of tHcy (P<0.01), HsCRP (P<0.001), IL-6 (P<0.001), TNFα (P<0.001), folates (P<0.05) and vitamin B₁₂ (P<0.001), but lower high-density lipoprotein cholesterol (P<0.05) levels. The analysis of the association between these parameters and the number of diseased vessels showed significant differences in tHcy, HsCRP, IL-6 and TNFα, with positive correlations. Significantly negative correlations were found between the number of diseased vessels and folate (r=−0.34; P<0.01), and vitamin B₁₂ (r=−0.22; P<0.01).

CONCLUSION:

Elevated levels of tHcy, IL-6, TNFα and HsCRP appear to be associated with a greater number of diseased arteries and, consequently, the severity of coronary artery disease.     

Evaluating the impact of individual alcohol licensing decisions on local health and crime: a natural experiment with synthetic controls

BackgroundLocal authorities in England can influence the local alcohol environment by contributing to the licensing process and controlling the enforcement of existing licenses. However, a gap remains in the availability of quantitative evidence of effectiveness and impact of these local interventions, including a shortage of public health evidence around individual premises. Natural experiments offer the opportunity to evaluate these interventions where formal randomisation is not possible. We aimed to assess whether it is possible to quantitatively evaluate three natural experiments of alcohol licensing decisions at small spatial scale.MethodsThree situations presenting a natural experiment were identified in different English Local Authority areas by public health or licensing practitioners: (i) the closure of a nightclub in 2013, (ii) the closure of a restaurant-nightclub following reviews in 2016, and (iii) the implementation of new local licensing guidance (LLG) in 2013/14. We obtained monthly numbers of reported incidents of emergency department admissions for alcohol-related reasons, ambulance call-outs, and various crimes at lower/middle-super-output-area level (from 2010–14 for case i, 2015–17 for case ii, and 2008–14 for case iii). Bayesian structural timeseries were used to compare trends to their counterfactuals, approximated by synthetic controls based on time series of the same outcomes in other, comparable, areas.FindingsClosure of the nightclub was associated with temporary reductions in antisocial behaviour (–18%; 95% Bayesian Credible Interval [BCI] –37 to –4); equivalent to 60 averted incidents in 4 months. Closure of the restaurant-nightclub was not associated with measurable changes in outcomes. There was some evidence that the LLG introduction was associated with a reduction in drunk and disorderly behaviour (–42%, 95% BCI –109 to 23), but this reduction equated to less than one incident per month. The unplanned end of the LLG might have contributed to an increase in domestic violence (11%, 95% BCI –10 to 35), corresponding to two additional incidents per month.InterpretationIt is possible to evaluate the impact of local alcohol policies, even at the level of individual premises, using this methodology. We provide quantitative evidence that local government actions to influence the local alcohol environment can have a positive impact on health and crime in the area but could also have unintended consequences.FundingThis work was funded by the National Institute for Health Research School for Public Health Research (NIHR SPHR), a partnership between the Universities of Sheffield, Bristol, Cambridge, Exeter, and University College London); the London School for Hygiene and Tropical Medicine; the LiLaC collaboration between the Universities of Liverpool and Lancaster and Fuse; and the Centre for Translational Research in Public Health, a collaboration between Newcastle, Durham, Northumbria, Sunderland and Teesside Universities. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health.