Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Maternal mortality in the rural Gambia, a qualitative study on access to emergency obstetric care

BACKGROUND: Maternal mortality is the vital indicator with the greatest disparity between developed and developing countries. The challenging nature of measuring maternal mortality has made it necessary to perform an action-oriented means of gathering information on where, how and why deaths are occurring; what kinds of action are needed and have been taken. A maternal death review is an in-depth investigation of the causes and circumstances surrounding maternal deaths. The objectives of the present study were to describe the socio-cultural and health service factors associated with maternal deaths in rural Gambia. METHODS: We reviewed the cases of 42 maternal deaths of women who actually tried to reach or have reached health care services. A verbal autopsy technique was applied for 32 of the cases. Key people who had witnessed any stage during the process leading to death were interviewed. Health care staff who participated in the provision of care to the deceased was also interviewed. All interviews were tape recorded and analyzed by using a grounded theory approach. The standard WHO definition of maternal deaths was used. RESULTS: The length of time in delay within each phase of the model was estimated from the moment the woman, her family or health care providers realized that there was a complication until the decision to seeking or implementing care was made. The following items evolved as important: underestimation of the severity of the complication, bad experience with the health care system, delay in reaching an appropriate medical facility, lack of transportation, prolonged transportation, seeking care at more than one medical facility and delay in receiving prompt and appropriate care after reaching the hospital. CONCLUSION: Women do seek access to care for obstetric emergencies, but because of a variety of problems encountered, appropriate care is often delayed. Disorganized health care with lack of prompt response to emergencies is a major factor contributing to a continued high mortality rate

Systematic review of effect of community-level interventions to reduce maternal mortality

<p>Abstract</p> <p>Background</p> <p>The objective was to provide a systematic review of the effectiveness of community-level interventions to reduce maternal mortality.</p> <p>Methods</p> <p>We searched published papers using Medline, Embase, Cochrane library, CINAHL, BNI, CAB ABSTRACTS, IBSS, Web of Science, LILACS and African Index Medicus from inception or at least 1982 to June 2006; searched unpublished works using National Research Register website, metaRegister and the WHO International Trial Registry portal. We hand searched major references.</p> <p>Selection criteria were maternity or childbearing age women, comparative study designs with concurrent controls, community-level interventions and maternal death as an outcome. We carried out study selection, data abstraction and quality assessment independently in duplicate.</p> <p>Results</p> <p>We found five cluster randomised controlled trials (RCT) and eight cohort studies of community-level interventions. We summarised results as odds ratios (OR) and confidence intervals (CI), combined using the Peto method for meta-analysis. Two high quality cluster RCTs, aimed at improving perinatal care practices, showed a reduction in maternal mortality reaching statistical significance (OR 0.62, 95% CI 0.39 to 0.98). Three equivalence RCTs of minimal goal-oriented versus usual antenatal care showed no difference in maternal mortality (1.09, 95% CI 0.53 to 2.25). The cohort studies were of low quality and did not contribute further evidence.</p> <p>Conclusion</p> <p>Community-level interventions of improved perinatal care practices can bring about a reduction in maternal mortality. This challenges the view that investment in such interventions is not worthwhile. Programmes to improve maternal mortality should be evaluated using randomised controlled techniques to generate further evidence.</p

Assessment of facility readiness and provider preparedness for dealing with postpartum haemorrhage and pre-eclampsia/eclampsia in public and private health facilities of northern Karnataka, India: a cross-sectional study

BACKGROUND: The maternal mortality ratio in India has been declining over the past decade, but remains unacceptably high at 212 per 100,000 live births. Postpartum haemorrhage (PPH) and pre- eclampsia/eclampsia contribute to 40% of all maternal deaths. We assessed facility readiness and provider preparedness to deal with these two maternal complications in public and private health facilities of northern Karnataka state, south India. METHODS: We undertook a cross-sectional study of 131 primary health centres (PHCs) and 148 higher referral facilities (74 public and 74 private) in eight districts of the region. Facility infrastructure and providers’ knowledge related to screening and management of complications were assessed using facility checklists and test cases, respectively. We also attempted an audit of case sheets to assess provider practice in the management of complications. Chi square tests were used for comparing proportions. RESULTS: 84.5% and 62.9% of all facilities had atleast one doctor and three nurses, respectively; only 13% of higher facilities had specialists. Magnesium sulphate, the drug of choice to control convulsions in eclampsia was available in 18% of PHCs, 48% of higher public facilities and 70% of private facilities. In response to the test case on eclampsia, 54.1% and 65.1% of providers would administer anti-hypertensives and magnesium sulphate, respectively; 24% would administer oxygen and only 18% would monitor for magnesium sulphate toxicity. For the test case on PPH, only 37.7% of the providers would assess for uterine tone, and 40% correctly defined early PPH. Specialists were better informed than the other cadres, and the differences were statistically significant. We experienced generally poor response rates for audits due to non-availability and non-maintenance of case sheets. CONCLUSIONS: Addressing gaps in facility readiness and provider competencies for emergency obstetric care, alongside improving coverage of institutional deliveries, is critical to improve maternal outcomes. It is necessary to strengthen providers’ clinical and problem solving skills through capacity building initiatives beyond pre-service training, such as through onsite mentoring and supportive supervision programs. This should be backed by a health systems response to streamline staffing and supply chains in order to improve the quality of emergency obstetric care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2393-14-304) contains supplementary material, which is available to authorized users

Availability and quality of emergency obstetric care in Gambia's main referral hospital: women-users' testimonies

<p>Abstract</p> <p>Background</p> <p>Reduction of maternal mortality ratio by two-thirds by 2015 is an international development goal with unrestricted access to high quality emergency obstetric care services promoted towards the attainment of that goal. The objective of this qualitative study was to assess the availability and quality of emergency obstetric care services in Gambia's main referral hospital.</p> <p>Methods</p> <p>From weekend admissions a group of 30 women treated for different acute obstetric conditions including five main diagnostic groups: hemorrhage, hypertensive disorders, dystocia, sepsis and anemia were purposively selected. In-depth interviews with the women were carried out at their homes within two weeks of discharge.</p> <p>Results</p> <p>Substantial difficulties in obtaining emergency obstetric care were uncovered. Health system inadequacies including lack of blood for transfusion, shortage of essential medicines especially antihypertensive drugs considerably hindered timely and adequate treatment for obstetric emergencies. Such inadequacies also inflated the treatment costs to between 5 and 18 times more than standard fees. Blood transfusion and hypertensive treatment were associated with the largest costs.</p> <p>Conclusion</p> <p>The deficiencies in the availability of life-saving interventions identified are manifestations of inadequate funding for maternal health services. Substantial increase in funding for maternal health services is therefore warranted towards effective implementation of emergency obstetric care package in The Gambia.</p

Does diet affect breast cancer risk?

The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol is the best established dietary risk factor, probably by increasing endogenous estrogen levels. Hypotheses relating diet during youth to risk decades later will be difficult to test. Nevertheless, available evidence is strong that breast cancer risk can be reduced by avoiding weight gain during adult years, and by limiting alcohol consumption

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches