Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia

BACKGROUND: Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. METHODS: The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR(+) and/or CD69(+) surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. RESULTS: Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69(+) and HLA-DR(+) T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). CONCLUSIONS: These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection

Reproductive tract infections in women seeking abortion in Vietnam

<p>Abstract</p> <p>Background</p> <p>Women requesting abortion are at increased risk of developing RTI complications. However, RTI control in many resource-poor countries including Vietnam have been faced with logistical and methodological problems due to lack of standardized definitions of RTIs, lack of well-validated diagnostic criteria, lack of accurate laboratory tests, and lack of diagnostic equipment and skills. This article investigates the prevalence of RTIs among Vietnamese abortion-seeking women, to evaluate the available diagnostic techniques, and to assess antibiotic resistance among aetiological agents of RTI.</p> <p>Method</p> <p>The study was conducted in Phu-San hospital (PSH) from December 2003 through April 2004 among 748 abortion clients. A structured questionnaire was used to collect data on socio-economic and reproductive characteristics. Specimens were collected for laboratory analyses of chlamydia, gonorrhoea, trichomoniasis, vaginal candidiasis (VC), bacterial vaginosis (BV) and syphilis. To assess the validity of the obtained results, the study was repeated among 100 women and the duplicate samples were analysed at PSH and Copenhagen University Hospital (CUH).</p> <p>Results</p> <p>In all 54% of the women were diagnosed as having an RTI, including 3.3% with sexually transmitted infections. Endogenous infections were most prevalent (VC 34% and BV 12%) followed by chlamydia (1.3%) and trichomoniasis (0.7%). The sensitivity of culture for VC and BV was 30% and 88%, respectively, when tests in PSH were measured against tests in CUH. Antibiotic resistance was common among bacterial isolates.</p> <p>Conclusion</p> <p>RTIs are common among women seeking abortion. The presence of RTIs is associated with an increased risk of developing iatrogenic infections, routine administration of prophylactic antibiotic to all women undergoing abortion should be considered. However, the choice of routine prophylactic antibiotics should be based on relevant surveillance data of antibiotic resistance. Moreover, since the accuracy of diagnosis is doubtful and to address the problem of under-diagnosed and treated RTIs new investment in diagnostic facilities with simple performed microscopy or improved rapid tests should also be taken into consideration.</p

Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

<p>Abstract</p> <p>Background</p> <p>Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has – besides of its well known haematopoietic properties – significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined.</p> <p>Methods</p> <p>Female C57BL/6j mice (4–6 weeks), infected with <it>Plasmodium berghei </it>ANKA, were treated with recombinant human Epo (rhEpo; 50–5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR.</p> <p>Results</p> <p>Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect.</p> <p>Conclusion</p> <p>These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.</p