结核病和结核病/艾滋病病毒双重感染的负担与挑战:尼日利亚的案例研究

目的: 了解尼日利亚结核病与结核病/艾滋病病毒(TB/HIV)双重感染的负担和结核病综合防治措施的落实情况,以确定尼日利亚结核病防控所面临的挑战,为尼日利亚消除结核病提供参考依据。方法: 利用2010—2020年世界卫生组织的全球结核病报告数据描述尼日利亚的结核病与TB/HIV双重感染负担趋势。结果: 尼日利亚是结核病与TB/HIV双重感染高负担国家,HIV感染者结核病发病率从2010年的54/10万下降至2020年的17/10万;2020年结核病确诊患者数为13.5万例,估计发病例数为45.2万,结核病治疗覆盖率仅为30%;TB/HIV双重感染患者抗逆转录病毒治疗覆盖率从2010年的6.9%增加至2020年的26.0%;结核病成功治疗率从2010年的81%提高至2019年的88%,TB/HIV双重感染患者成功治疗率从2012年的78.9%提高至2019年的81.1%;尼日利亚结核病资金总量增加,TB/HIV项目资金变化小,从2010年的450万美元增长至2020年的540万美元。结论: 尼日利亚与2020年“终止结核病战略”的目标有很大的差距。尼日利亚要减轻并消除结核病和TB/HIV双重感染负担,必须优先考虑落实结核病综合防治措施,增加必要的结核病防治资源和经费,提高结核病诊断能力。     

In vivo MRS markers of response to CHOP chemotherapy in the WSU-DLCL2 human diffuse large B-cell lymphoma xenograft

To identify 1H-MRS molecular biomarkers of early clinical therapeutic response in non-Hodgkin's lymphoma, an in vivo longitudinal study was performed on human non-Hodgkin's diffuse large B-cell lymphoma xenografts (WSU-DLCL2) grown in the flanks of female SCID mice. 31P-MRS measurements, which have been demonstrated to be prognostic clinical indices of response (Arias-Mendoza et al. Acad. Radiol. 2004; 11: 368-376) but which provide lower spatial resolution, were included for comparison. The animals received CHOP (cyclophosphamide, hydroxydoxorubicin, oncovin and prednisone) chemotherapy for three 1-week cycles, resulting in stable disease based on tumor volume. Localization of total choline and phosphorus metabolites in vivo was achieved with stimulated echo acquisition mode and image selected in vivo spectroscopy sequences, respectively. Significant decreases in lactate were detected by the selective multiple quantum coherence spectral editing technique after the first cycle of CHOP, whereas total choline and the phosphomonoester/nucleoside triphosphate ratio did not change until the third cycle. Ex vivo extract MRS of tumors corroborated the in vivo results. Histological staining with antibodies to Ki67 revealed a decrease in proliferation rate in CHOP-treated tumors that coincided with the decrease in lactate. This study demonstrates the utility of lactate as an early proliferation-sensitive indicator of therapeutic response in a mouse model of non-Hodgkin's lymphoma and serves as a basis for future clinical implementation of these methods.     

Cost of maternal near miss and potentially life-threatening conditions,Kenya

ObjectiveTo estimate the direct costs of treating women with maternal near misses and potentially life-threatening conditions in Kenya and the factors associated with catastrophic health expenditure for these women and their households.MethodsAs part of a prospective, nationally representative study of all women with near misses during pregnancy and childbirth or within 42 days of delivery or termination of pregnancy, we compared the cost of treating maternal near-miss cases admitted to referral facilities with that of women with potentially life-threatening conditions. We used logistic regression analysis to assess clinical, demographic and household factors associated with catastrophic health expenditure.FindingsOf 3025 women, 1180 (39.0%) had maternal near misses and 1845 (61.0%) had potentially life-threatening conditions. The median cost of treating maternal near misses was 7135 Kenyan shillings (71 United States dollars, US$) compared with 2690 Kenyan shillings (US$ 27) for potentially life-threatening conditions. Of the women who made out-of-pocket payments, 26.4% (122/462) experienced catastrophic expenditure. The highest median costs for treatment of near misses were in Nairobi and Central region (22 220 Kenyan shillings; US$ 222). Women with ectopic pregnancy complications and pregnancy-related infections had the highest median costs of treatment, at 7800 Kenyan shillings (US$ 78) and 3000 Kenyan shillings (US$ 30), respectively. Pregnancy-related infections, abortion, ectopic pregnancy, and treatment in secondary and tertiary facilities were significantly associated with catastrophic expenditure.ConclusionThe cost of treating maternal near misses is high and leads to catastrophic spending through out-of-pocket payments. Universal health coverage needs to be expanded to guarantee financial protection for vulnerable women.     

Incidence of individual organ dysfunction in fatal acute pancreatitis: analysis of 1024 death records

Background:

Extrapancreatic organ dysfunction is the key determinant of mortality in acute pancreatitis (AP). This study aimed to document the frequency and duration of individual organ dysfunction in all fatalities caused by AP in a large, population-based cohort.

Methods:

All deaths caused by AP in Scotland between 2000 and 2006 inclusive were analysed (n = 1024).

Results:

The median time lapse between the onset of AP and death was 6 days (interquartile range [IQR] 17 days); that between the onset of organ dysfunction and death was 3 days (IQR 7 days). There was no apparent bimodal distribution. The majority of patients had single- (384 patients) or two-system (242 patients) extrapancreatic organ dysfunction. Pulmonary dysfunction was most prevalent (30% of organ-specific entries, 198/660), followed by cardiovascular (18%, 117/660), renal (16%, 108/660), liver (11%, 71/660), gastrointestinal (9%, 59/660), haemorrhage (6%, 38/660), coagulopathy (5%, 31/660) and central nervous system (6%, 38/660) dysfunction.

Conclusions:

Death in AP occurs early in the disease course. The present findings support the primacy of pulmonary injury as the modal pattern of organ dysfunction in severe AP, with increased frequencies of cardiovascular and renal compromise in fatal AP.     

Effects of artesunate-cotrimoxazole and amodiaquine-artesunate against asexual and sexual stages of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> malaria in Nigerian children

The activities of artesunate-cotrimoxazole and artesunate-amodiaquine combinations against asexual-and sexual-stage parasites were evaluated in 182 Nigerian children with uncomplicated Plasmodium falciparum malaria. One hundred and twenty-one children received artesunate-cotrimoxazole and 61 received artesunate-amodiaquine and all were followed up for 28 days. Clinical recovery from illness occurred in all children. There was no significant difference in fever clearance time (P = 0.35). Both treatment groups achieved a parasite clearance time of less than 2 days (1.84 +/- 0.66 days and 1.31 +/- 0.48 days); gametocyte carriage rates were comparable in the two treatment groups prior to and following treatment; both treatments appeared to reduce gametocyte carriage. The pretreatment gametocyte sex ratio, which was female-biased, was maintained throughout the period of follow up in both treatment groups. Reduction of gametocyte carriage by these two treatment regimens may reduce transmissibility in P. falciparum malaria, and this reduction is presumed to be related to the accelerated clearance of the asexual forms of the parasite.     

Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure

The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.     

In vitro-reduced susceptibility to artemether in P. falciparum and its association with polymorphisms on transporter genes

Plasmodium falciparum with reduced sensitivity to artemisinin derivatives has been observed in endemic areas, but the molecular mechanisms for this reduced sensitivity remain unclear. We evaluated the association between in vitro susceptibility of P. falciparum isolates obtained from southwest Nigeria and polymorphisms in selected putative transporter genes (PFE0775C, PF13_0271, pfmrp1, pfcrt, and pfmdr1). Modified schizont inhibition assay was used to determine the in vitro parasite susceptibility to artemether (ATH). Polymorphisms in selected genes were detected by polymerase chain reaction followed by direct DNA sequencing. The half-maximal inhibitory concentration (IC(50)) geometric mean (GM) for all P. falciparum isolates was 1.78?nM (range, 0.03-10.43?nM). Polymorphisms at codons 241, 86, and 76 of PFE0775C, pfmdr1, and pfcrt genes, respectively, were associated with reduced susceptibility to ATH. A new S263P single-nucleotide polymorphism on the PFE0775C gene was also detected in 27% of the isolates. Patient isolates harboring V241L or S263P polymorphisms on the PFE0775C gene showed increased IC(50) (GM: 3.08?nM and 1.79?nM, respectively). Plasmodium falciparum isolates harboring mutant Y86 pfmdr1 and P263 PFE0775C alleles showed a 2.5-5.5-fold increase in ATH IC(50.) This study shows that polymorphisms on the PFE0775C and pfmdr1 genes are associated with reduced sensitivity to ATH in fresh isolates of P. falciparum from Nigeria.