Implementation of an outbreak response vaccination campaign with typhoid conjugate vaccine - Harare, Zimbabwe, 2019.

Introduction: Typhoid fever is a public-health problem in Harare, the capital city of Zimbabwe, with seasonal outbreaks occurring annually since 2010. In 2019, the Ministry of Health and Child Care (MOHCC) organized the first typhoid conjugate vaccination campaign in Africa in response to a recurring typhoid outbreak in a large urban setting. Method: As part of a larger public health response to a typhoid fever outbreak in Harare, Gavi approved in September 2018 a MOHCC request for 340,000 doses of recently prequalified Typbar-TCV to implement a mass vaccination campaign. To select areas for the campaign, typhoid fever surveillance data from January 2016 until June 2018 was reviewed. We collected and analyzed information from the MOHCC and its partners to describe the vaccination campaign planning, implementation, feasibility, administrative coverage and financial costs. Results: The campaign was conducted in nine high-density suburbs of Harare over eight days in February-March 2019 and targeted all children aged 6 months-15 years; however, the target age range was extended up to 45 years in one suburb due to the past high attack rate among adults. A total of 318,698 people were vaccinated, resulting in overall administrative coverage of 85.4 percent. More than 750 community volunteers and personnel from the MOHCC and the Ministry of Education were trained and involved in social mobilization and vaccination activities. The MOHCC used a combination of vaccination strategies (i.e., fixed and mobile immunization sites, a creche and school-based strategy, and door-to-door activities). Financial costs were estimated at US$ 2.39 per dose, including the vaccine and vaccination supplies (US$ 0.79 operational costs per dose excluding vaccine and vaccination supplies). Conclusion: A mass targeted campaign in densely populated urban areas in Harare, using the recently prequalified typhoid conjugate vaccine, was feasible and achieved a high overall coverage in a short period of time.

Tissue factor-bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer.

Cancer is associated with an increased risk of venous thromboembolism (VTE); the exact mechanisms for the induction of VTE remain to be fully elucidated, but it is widely acknowledged that tissue factor (TF)-bearing microparticles (TF-MPs) may play a significant role. However, TF-MPs have yet to be accepted as a genuine biomarker for cancer-associated VTE, as the presence of elevated TF-MP levels is not always accompanied by thrombosis; interestingly, in certain cases, particularly in pancreatic cancer, VTE seems to be more likely in the context of acute inflammation. Although several potential mechanisms for the development of VTE in cancer have been postulated, this review explores the homeostatic disruption of TF-MPs, as the main reservoir of bloodborne TF, in the context of cancer and inflammation, and considers the abrogated responses of the activated endothelium and mononuclear phagocyte system in mediating this disruption.

Real-time modelling used for outbreak management during a cholera epidemic, Haiti, 2010-2011.

The emergence of epidemic cholera in post-earthquake Haiti portended a public health disaster of uncertain magnitude. In order to coordinate relief efforts in an environment with limited healthcare infrastructure and stretched resources, timely and realistic projections of the extent of the cholera outbreak were crucial. Projections were shared with Government and partner organizations beginning 5 days after the first reported case and were updated using progressively more advanced methods as more surveillance data became available. The first projection estimated that 105 000 cholera cases would occur in the first year. Subsequent projections using different methods estimated up to 652 000 cases and 163 000-247 000 hospitalizations during the first year. Current surveillance data show these projections to have provided reasonable approximations of the observed epidemic. Providing the real-time projections allowed Haitian ministries and external aid organizations to better plan and implement response measures during the evolving epidemic.

[Coagulation and fibrinolysis system in pediatric cardiopulmonary bypass].

Coagulation and fibrinolysis system was evaluated during and after pediatric cardiopulmonary bypass (CPB. Twenty-two atrial septal defect (ASD) patients were surgically repaired under CPB and aortic cross-clamp through right thoracotomy. Drainage was established by gravity, CPB flow was kept 2.4 l/min/m2 and ACT was controlled over 400 seconds. HCT, PLT, fibrinogen, AT-III, D-dimer, thrombin-antithrombin complex (TAT), alpha2 plasmin inhibitor-plasmin complex (PIC), and plasminogen activator inhibitor (PAI-1) were measured at 6 points [after induction of anesthesia, 10 minutes after initiating CPB, end of CPB, on the entrance of intensive care unit (ICU), postoperative day (POD) 1, and at outpatient division]. Both fibrinogen and AT-III showed low values during CPB (121.9 +/- 22.0 mg/dl, 57.6 +/- 10.6%). D-dimer increased at 1 week postoperatively in all patients (5.57 +/- 3.45 microg/ml). There were significantly positive correlations between CPB duration and TAT value at the end of CPB (r = 0.88, p < 0.01), on the entrance of ICU (r = 0.71, p < 0.01). There was also a positive correlation between CPB duration and PIC value on the entrance of ICU (r = 0.53, p < 0.01). Five patients showed high PAI-1 value on the entrance of ICU, which remained high in 2 of them on POD 1. The outcomes from the current study suggest that there is a potential of coagulation-dominant disseminated intravascular coagulation (DIC) during pediatric CPB even in ASD patients who do not need long CPB. Longer CPB and severe hemodilution might become risk factors.

Evaluation of styrene oligomers eluted from polystyrene for estrogenicity in estrogen receptor binding assay, reporter gene assay, and uterotrophic assay.

Styrene dimers (SDs) and styrene trimers (STs) eluted a little from polystyrene have been suspected of having estrogenic activity in the Wingspread Declaration [Our Stolen Futures, 1996] despite the lack of scientific analysis. Therefore, we have studied and reported styrene oligomers to have no endocrine disrupting effects [J. Food Hygienic Soc. Japan 40 (1999) 36; 41 (2000) 109; Yuki Goseikagaka Kyokaishi 57 (1999) 58; Bunseki Kagaku 49 (2000) 493, 857; Food Chem. Toxicol. 39 (2001) 1233; 40 (2002) 129]. However, Ohyama et al. reported that certain styrene oligomers have estrogenic effects in E-SCREEN and estrogen receptor (ER) binding assay [Environ. Health Perspect. 109 (2001) 699]. Recently, several assay systems have been developed, and a few of them can show false positive reactions at the high concentrations to which test compounds are precipitated [J. Health Sci. 48 (2002) 83]. In order to assess the estrogenic effect of SDs and STs in more detail, we examined the accuracy of the binding assay system and tested SDs and STs by three types of ER binding assay. In one ER binding assay, the same method that Ohyama et al. performed, SDs and STs showed a little estrogenic activity at high concentration; they did not dissolve, but this assay system tended to detect false positive effects at high concentration. In contrast, in the other assay systems, SDs and STs did not show any binding affinity to ER. In addition, luciferase reporter gene assay in HeLa cells transfected with ER expression plasmid and reporter plasmid, as a newly developed standard assay, and immature rat uterotrophic assay were conducted. In these tests, styrene oligomers showed no estrogenic activity.

Endocrine-disrupting effects of styrene oligomers that migrated from polystyrene containers into food.

The endocrine-disrupting effects of styrene dimers (SD: NSD-01, -08 and -09) and styrene trimers (ST: NST -01, -03 and -12), which migrated from polystyrene (PS) containers into instant food, were investigated together with styrene monomer (SM) using in vitro and in vivo assays. In the estrogen (ER) and androgen receptor (AR) binding assay, SM, SD and ST showed no binding activity at concentration of 10(-10)-10(-5) mol/l. In order to evaluate the estrogenic activity in vivo, the uterotrophic assay was conducted. When prepubertal and ovariectomized adult rats were dosed with SM, SD and ST for 3 days by subcutaneous injection, these compounds did not induce significant increase in uterine weight. Additionally, to evaluate anti-androgen activity in vivo, the Hershberger assay for anti-androgenic activity in the presence of testosterone treatment was conducted. When castrated, testosterone-treated immature male rats were dosed SM, SD and ST for 7 days by oral gavage, these compounds did not induce a decrease in the seminal vesicle, ventral prostate and levator ani plus bulbocavernosus muscle weights. To evaluate the effects on hormones other than sex hormones, the thyroid hormone receptor (TR) binding assay and rat serum prolactin (PRL) was conducted. In the TR binding assay, SM, SD and ST showed no binding activity at a concentration of 10(-5) mol/l. When ovariectomized rats were dosed with SM, SD and ST for 3 days by sc injection, the results showed there was no change in rat serum PRL. From the above these results, we concluded that SM, SD and ST exhibit no apparent estrogenic, androgenic, anti-androgenic and thyroid activity.

Identification, determination, and biological evaluation of a novel styrene trimer contained in polystyrene food containers. 2.

An unidentified styrene trimer (ST) isolated from the acetonitrile extract of polystyrene (PS) food containers was characterized as (1S*,6R*,7S*,8S*,11R*)-6,11-diphenyltricyclo[6,2,2,0(2,7)]dodeca-2,9-diene. The content and migration of this compound in PS food containers were determined by GC-MS (SIM). Furthermore, an endocrine-disrupting effect was tested using in vitro and in vivo assays of the compound. In conclusion, it seems that the compound does not present the effect.

NTE-122, an acyl-coa:cholesterol acyltransferase inhibitor, prevents the progression of atherogenesis in cholesterol-fed rabbits.

The cholesterol-lowering and anti-atherosclerotic effects of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylaminophenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, were evaluated in 1% cholesterol diet-fed rabbits. NTE-122 (1, 3 and 10 mg/kg per day) lowered the total cholesterol levels in both plasma and liver dose-dependently (by 99% and 94% at 10 mg/kg per day, respectively). In the aortic wall of the rabbits given NTE-122, the atherosclerotic lesion area in both aortic arch and thoracic aorta were dose-dependently reduced (by 100% at 10 mg/kg per day), and the total cholesterol content in aortic arch was also lowered significantly at more than 3 mg/kg per day. These results suggest that NTE-122 is capable of exhibiting anti-atherosclerotic effects.

Establishment and characterization of a human B cell line from the lung tissue of a patient with scleroderma; extraordinary high level of IL-6 secretion by stimulated fibroblasts.

Progressive systemic sclerosis is a connective tissue disease of unknown aetiology. This is the first study to demonstrate induction by a human B cell line of IL-6 secretion from fibroblasts. The cell line was established from lesional lung tissue of a patient with progressive systemic sclerosis. These cells, referred to as kon-1 cells, showed characteristics of pro-B cell by flow cytometry. Although kon-1 cells alone secreted a small amount of IL-6, a co-culture of kon-1 cells with normal lung fibroblasts significantly increased IL-6 levels. Whereas IL-6 mRNA was weakly expressed in kon-1 cells alone, it was clearly expressed in cells from the co-culture. Immunocytochemical identification of IL-6 showed localization in the cytoplasm of fibroblasts. IL-6 is a pleiotropic cytokine, essential for B cell differentiation, which has been shown to stimulate the production of collagen and glycosaminoglycan. Thus, abnormally augmented B cell proliferation and the inflammatory response stimulated by these cells may cause the fibrotic changes in patients with progressive systemic sclerosis.

HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice.

We reported that NK4, composed of the N-terminal hairpin and subsequent four kringle domains of hepatocyte growth factor (HGF), acts as the competitive antagonist for HGF. We now provide the first evidence that NK4 inhibits tumor growth and metastasis as an angiogenesis inhibitor as well as an HGF antagonist. Administration of NK4 suppressed primary tumor growth and lung metastasis of Lewis lung carcinoma and Jyg-MC(A) mammary carcinoma s.c. implanted into mice, although neither HGF nor NK4 affected proliferation and survival of these tumor cells in vitro. NK4 treatment resulted in a remarkable decrease in microvessel density and an increase of apoptotic tumor cells in primary tumors, which suggests that the inhibition of primary tumor growth by NK4 may be achieved by suppression of tumor angiogenesis. In vivo, NK4 inhibited angiogenesis in chick chorioallantoic membranes and in rabbit corneal neovascularization induced by basic fibroblast growth factor (bFGF). In vitro, NK4 inhibited growth and migration of human microvascular endothelial cells induced by bFGF and vascular endothelial growth factor (VEGF) as well as by HGF. HGF and VEGF activated the Met/HGF receptor and the KDR/VEGF receptor, respectively, whereas NK4 inhibited HGF-induced Met tyrosine phosphorylation but not VEGF-induced KDR phosphorylation. NK4 inhibited HGF-induced ERK1/2 (p44/42 mitogen-activated protein kinase) activation, but allowed for bFGF- and VEGF-induced ERK1/2 activation. These results indicate that NK4 is an angiogenesis inhibitor as well as an HGF antagonist, and that the antiangiogenic action of NK4 is independent of its activity as HGF antagonist. The bifunctional properties of NK4 to act as an angiogenesis inhibitor and as an HGF antagonist raises the possibility that NK4 may prove therapeutic for cancer patients.

Asymptomatic adenomyoma of the common hepatic duct discovered during a medical checkup: report of a case.

Although adenomyoma of the gallbladder is not so rare, adenomyoma arising in the bile duct is extremely rare. We herein report a case of partial biliary obstruction due to adenomyoma of the common hepatic duct. A 64-year-old woman was referred to the 1st Department of Surgery, Niigata University School of Medicine for surgical intervention, in whom a biliary stricture in the common hepatic duct was discovered incidentally during a medical check-up for hyperamylasemia in an affiliated hospital. She was asymptomatic without jaundice. Based on her past history of abdominal contusion, the insidious presentation and the smooth biliary stricture on cholangiography, a diagnosis of benign biliary stricture secondary to blunt abdominal trauma was made. A suspicion of malignancy, however, could not be ruled out. Subsequently, she underwent a resection of the extrahepatic bile duct with lymph node dissection in the hepatoduodenal ligament. The patient's postoperative course was uneventful. She was discharged 18 days after the operation. Histology of the resected specimen confirmed the diagnosis of adenomyoma in the common hepatic duct. Clinicians should note to avoid overlooking or misdiagnosing that adenomyoma is a cause of biliary obstruction, although extremely rare.

[Continuous monitoring of hepatic venous oxygen saturation (SHVO2) as a new diagnostic indicator of abdominal malperfusion in acute aortic dissection].

A 73-year-old woman was admitted with sudden-onset back and abdominal pain. Computed tomography scanning revealed type B acute aortic dissection with narrowing of the true lumen. We inserted an oximetric catheter into the right hepatic vein and started continuous measurement of ShvO2. The initial value was 20%. Consecutive aortograms showed an intimal tear in the thoracic descending aorta. Endovascular stent graft placement was performed to close the entry, and ShvO2 rose to more than 60% immediately after the stent graft expansion. ShvO2 is an excellent indicator of abdominal blood flow, not only for early diagnosis but also for the evaluation of treatment.

Successful resection of metachronous liver metastasis from alpha-fetoprotein-producing gastric cancer: report of a case.

We present herein the case of a 68-year-old man in whom metachronous liver metastasis from an alpha-fetoprotein (AFP)-producing gastric cancer was successfully treated. The patient initially underwent a distal gastrectomy for an AFP-producing gastric cancer on January 30, 1997, following which the serum AFP level which had been 228 ng/ml prior to surgery decreased to 30 ng/ml. However, 7 months after surgery, follow-up examination revealed an abnormal elevation of the serum AFP level up to 301 ng/ml, and a liver tumor was subsequently detected at segment 8 (S8) by abdominal ultra-sonography. There was no evidence of hepatitis B or C virus infections. After various investigations, he was diagnosed to have liver metastases in S6 and S8, from the AFP-producing gastric cancer, and a partial hepatectomy of S6 and S8 was performed. His postoperative course was uneventful and he was discharged on postoperative day 26. Thereafter, his serum AFP levels decreased and have remained within normal limits for 12 months since his operation. To the best of our knowledge, this is the first case of successful resection of metachronous liver metastasis from an AFP-producing gastric cancer.

Histological and genetic changes in malignant transformation of gallbladder adenoma.

DESIGN: Elucidate the histological and genetic changes in malignant transformation of adenoma of the gallbladder. MATERIALS AND METHODS: Forty-three adenomas and 20 intramucosal tumors of carcinoma-in-adenomas were studied for histological and genetic changes (particularly K-ras mutation and p53 protein overexpression by immunohistochemistry) in malignant transformation. The genetic changes were compared with those of 164 carcinomas without anomalous union and 17 carcinomas with anomalous union of pancreatico-biliary duct. RESULTS: Atypical cell foci, i.e. spindle cell foci, were observed only in the adenoma area, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. 129 of 130 spindle cell foci examined were negative for Ki-67 staining and all the spindle cell foci were negative for p53 stain. K-ras mutation and p53 overexpression were not found in all adenomas, pure and with carcinoma i.s., and only one carcinoma (1/16, 6%) with adenoma showed p53 overexpression. K-ras mutation was low (10%, 4/40) in carcinomas without adenoma, but high in carcinomas with anomalous union of pancreatico-biliary duct. While, p53 overexpression was high and similar in carcinomas with and without anomalous union. CONCLUSIONS: These results suggest that there are three distinct pathways in gallbladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, de novo carcinoma with anomalous union from K-ras mutation and p53 mutation, and carcinoma-in-adenoma from K-ras-, p53-, and probably APC-gene-related, as yet unknown, alteration.

Major hepatectomy combined with pylorus-preserving pancreatoduodenectomy for middle bile duct cancer with multiple lymph node metastases: a case report of 5-year survival.

Hepatopancreatoduodenectomy has been well established as an aggressive surgical approach for advanced biliary tract malignancy. However, long-term survival of more than 5 years after this operation is rarely reported, especially with bile duct carcinoma. We report herein a 64 year-old man with middle bile duct cancer who underwent extended right hepatectomy combined with pylorus-preserving pancreatoduodenectomy because of widespread intramural extension of the tumor. Resection margin, which is considered the most significant prognostic parameter, was made clear only by additional hepatectomy in this case. In addition, although microscopic examination revealed multiple lymph node involvement up to the superior mesenteric node, the patient has survived 5 years and 6 months without tumor recurrence. It remains unclear whether aggressive lymph node dissection may improve surgical outcome; however, it is thought that surgical clearance of potentially involved nodes and tissue may be the only chance for long-term survival.

A model of port-site metastases of gallbladder cancer: the influence of peritoneal injury and its repair on abdominal wall metastases.

BACKGROUND: Recent surgical literature contains several reports of wound metastases of unexpected gallbladder cancer after laparoscopic cholecystectomy. We hypothesized that peritoneal injury caused by trocar insertion potentiates wound metastases. This study was designed to determine the effect of peritoneal injury on tumor implantation. METHODS: Cultured human gallbladder cancer cells were injected into the peritoneal cavity of mice immediately after surgical procedures. In a peritoneal injury group muscle and the peritoneum were perforated; in a peritoneal injury and repair group each muscle and peritoneal wound was sutured carefully; in a laparoscopic model group animals underwent peritoneal insufflation with carbon dioxide gas and tumor cell injection and then the abdominal wall was perforated. Some mice (controls) were not subjected to any surgical procedure. All mice (n = 178) were killed 2 weeks after tumor cell injection and were examined for tumor implantation. RESULTS: Although no control mice showed intraperitoneal tumor, all mice in the peritoneal injury group showed tumors at the injured sites. In the laparoscopic model group, 90% of injured sites had tumors. The traumatized site-specific implantation rate in the peritoneal injury and repair group was only 40%, whereas it was 100% in the peritoneal injury group (P < .001). CONCLUSIONS: Peritoneal injury enhances peritoneal implantation of carcinoma cells. Repair of injured peritoneum at trocar sites may reduce the frequency of wound metastases in laparoscopic surgery for unexpected gallbladder carcinoma.

Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization.

By means of comparative genomic hybridization (CGH), we screened 58 primary gastric cancers for changes in copy number of DNA sequences. We detected frequent losses on Ip32-33 (21%), 3p21-23 (22%), 5q14-22 (36%), 6q16 (26%), 9p21-24 (22%), 16q (21%), 17p13 (48%), 18q11-21(33%), and 19(40%). Gains were most often noted at I p36 (22%), 8p22-23 (24%), 8q23-24 (29%), 11q12-13 (24%), 16p(21%), 20p (38%), 20q (45%), Xp21-22(38%), and Xq21-23 (43%), with high-level amplifications at 6p21(2%),7q31(10%), 8p22-23(5%), 8q23-24 (7%), 11q13(4%), 12p12-13(4%), 17q21(2%), 19q12-13(2%), and 20q13(2%). High-level amplification at 8p22-23 has never been reported in any other cancer type and its frequency was as high as that reported for the MYC, MET, and KRAS genes. We narrowed down the smallest common amplicon to 8p23.1 by reverse-painting FISH to prophase chromosomes. Southern blot analysis using one EST marker (D38736) clearly demonstrated that amplification of this exon-like sequence had occurred in all three tumors in which amplifications at 8p22-23 had been detected by CGH. Our data provide evidence for several, previously undescribed, genomic aberrations that are characteristic of gastric cancers.

[Genetic alterations in gallbladder carcinoma: a review].

Earlier evidence suggests that gallbladder carcinoma (GBC) has three carcinogenic pathways; de novo development; adenoma-carcinoma sequence; and hyperplasia-carcinoma sequence associated with an anomalous arrangement of the pancreaticobiliary duct (AAPBD). We review gene abnormalities in GBC reported to date. p53 mutation and its protein overexpression are frequently observed in de novo carcinoma and GBC with AAPBD, but never found in carcinoma with adenoma. The incidence of K-ras codon 12 mutation in GBCs with AAPBD is significantly higher than that in the other types. Mutation of K-ras is never detected in carcinoma with adenoma. These findings suggest that diverse genetic pathways may exist in gallbladder carcinogenesis and reflect morphologic variations.