Adverse events following yellow fever preventive vaccination campaigns in eight African countries from 2007 to 2010.

BACKGROUND: Serious, but rare adverse events following immunization (AEFI) have been reported with yellow fever (YF) 17D vaccine, including severe allergic reactions, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). The frequency with which YEL-AND and YEL-AVD occur in YF endemic countries is mostly unknown. METHODS: From 2007 to 2010, eight African countries - Benin, Cameroon, Guinea, Liberia, Mali, Senegal, Sierra Leone, and Togo- implemented large-scale YF preventive vaccination campaigns. Each country established vaccine pharmacovigilance systems that included standard case definitions, procedures to collect and transport biological specimens, and National Expert Committees to review data and classify cases. Staff in all countries received training and laboratory capacity expanded. RESULTS: In total, just over 38 million people were vaccinated against YF and 3116 AEFIs were reported of which 164 (5%) were classified as serious. Of these, 22 (13%) were classified as YF vaccine reactions, including 11 (50%) hypersensitivity reactions, six (27%) suspected YEL-AND, and five (23%) suspected YEL-AVD. The incidence per 100,000 vaccine doses administered was 8.2 for all reported AEFIs, 0.43 for any serious AEFI, 0.058 for YF vaccine related AEFIs, 0.029 for hypersensitivity reactions, 0.016 for YEL-AND, and 0.013 for YEL-AVD. Our findings were limited by operational challenges, including difficulties in obtaining recommended biological specimens leading to incomplete laboratory evaluation, unknown case ascertainment, and variable levels of staff training and experience. CONCLUSIONS: Despite limitations, active case-finding in the eight different countries did not find an incidence of YF vaccine associated AEFIs that was higher than previous reports. These data reinforce the safety profile of YF vaccine and support the continued use of attenuated YF vaccine during preventive mass vaccination campaigns in YF endemic areas.

[Surveillance system for adverse events following immunization against yellow fever in Burkina Faso in 2008. Good practice recommendations]. / Dispositif de surveillance des effets indésirables graves lors de la campagne de vaccination preventive contre la fièvre jaune au Burkina Faso en 2008. Recommandations de bonnes pratiques.

Yellow fever (YF) remains a public health problem in Africa. In 2007 and 2008, Togo, Senegal, Mali and Burkina Faso became the first countries to implement mass YF immunization campaigns within the framework of the Yellow Fever Initiative. The goal of this initiative led by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) with the support of The Global Alliance for Vaccines and Immunization (GAVI) is to organize mass YF immunization campaigns in 12 African countries at high risk forYF transmission between 2006 and 2013. A total of 290 million USD have been allocated for vaccination of 180 million people with the highly effective attenuated 17DYF vaccine. Working in partnership with the WHO, the 12 member states are to identify and target high risk areas with the dual aim of preventing epidemics and increasing immunization coverage. Surveillance of adverse events following immunization (AEFI) is a mandatory component for organization of these campaigns. Purpose. The purpose of this article is to describe the AEFI surveillance system implemented in Burkina Faso in 2008. Methods. The strategy used in Burkina Faso was based on a combination of regular passive surveillance and active surveillance. General guidelines and related operational processes were established including reporting forms, investigation forms, and procedures for collection, storage and transport of biological specimens. Classification of cases was based on clearly defined criteria. Any patient meeting the defined criteria and requiring hospitalization was considered as a serious case. In addition to case definition criteria, serious cases were tracked according to presented signs and symptoms using a line-listing form at two university hospital centers in Ouagadougou and one regional hospital center. Emergency room admission records and patient charts were examined during the surveillance period (30 days after the end of the immunization campaign) and on-duty hospital staff were interviewed. The Ministry of Health appointed an 11-member National Expert Committee (NEC) to investigate and judge the status of reported cases. After eliminating coincidental events, program errors, and undetermined cases, vaccination was established as the suspected cause. Suspected cases were classified as viserotrophic or neurotrophic AEFI and recorded as probable cases pending confirmation by virologic studies. An AEFI center with a duly mandated coordinator was designated to coordinate the activities of the different teams involved and to serve as an interface for the expert committee. Detection and investigation teams were formed at each of the hospital locations. A national laboratory as well as an international virology laboratory were designated as reference centers for performance of further testing. Results. Between November 28, 2008, and December 9, 2008, a total 7,566,218 people (aged 9 months and older) excluding pregnant women, critically ill patients, and individuals allergic to eggs, were immunized in 37 of the 63 districts in Burkina Faso. Administrative vaccination coverage was 102.3%. Systematic line-listing at the 3 hospital centers accounted for most of the suspected serious AEFIs identified from reported cases. During the AEFI surveillance period, the NEC met once a week to discuss the suspected serious AEFI. Some cases were excluded and others were designated for further testing. At least one biological specimen was available for all retained cases. Each case benefited from laboratory testing to achieve differential clinical diagnosis as well as from virological testing (results pending). Conclusion. Experiences in Burkina Faso demonstrates the value of active surveillance and of systematic line listing. However, the duration of case investigation and data management was at least six months. To improve AEFI surveillance in future campaigns, several measures can be recommended. Planning should begin well in advance with appropriate funding. Training should be given to raise awareness at all levels of the health system. Mechanisms should be developed for systematic and timely collection and processing of biological samples and data at national level.

Photodynamic treatment of normal endothelial cells or glioma cells in vitro.

Photodynamic therapy is based on the interaction of a sensitizer (hematoporphyrin derivative) selectively retained by tumor cells, which becomes toxic after light exposure. We studied the influence of exogenous prostaglandins and indomethacin on photodynamic therapy of normal human endothelial cells and glioma cells. Although differing in origin and kinetic properties, endothelial cells exhibited photodynamic therapy sensitivity quite comparable to that of C6 cells. However, in contrast to studies performed using radiotherapy, exogenous prostaglandins decreased rather than protected the surviving fraction of both cell types treated by photodynamic therapy. Indomethacin, a potent inhibitor of endogenous prostaglandin synthesis, increased the surviving fraction of C6 glioma cells but not that of endothelial cells. Exogenous or endogenous prostaglandins seem to influence in vitro photodynamic therapy in a different way than does radiotherapy.

Photosensitization of L1210 leukaemic cells by argon laser irradiation after incubation with haematoporphyrin derivative and rhodamine 123.

The selectivity and efficacy of photodynamic therapy (PDT) may be improved by the combined use of photosensitizers in a similar manner to the combined use of drugs in cancer chemotherapy. Two photosensitizers (haematoporphyrin derivative (HPD) and rhodamine 123 (Rh-123) were analysed which can be irradiated at the same wavelength (514 nm), are preferentially taken up by tumour tissue and are not specific for the same target (membrane for HPD, mitochondria for Rh-123). The analysis of the phototoxic effects in surviving fractions showed a dependence on dose for both products and a dependence on incubation time for HPD but not Rh-123. The lethal dose for 50% cell death (LD50) for HPD increased from 25 to 56 J cm-2 when the HPD dose was reduced from 2.5 to 1 micrograms ml-1 for the same incubation time. When the incubation time was increased from 15 to 45 min, the surviving fraction decreased by 37% and 17% for doses of 1 and 2.5 micrograms ml-1 respectively. For low doses (0.5 and 1 microgram ml-1), the toxicity of the two photosensitizers added simultaneously was weaker than for Rh-123 alone, whereas for high doses (2.5 micrograms ml-1) the surviving fraction was less than that obtained with Rh-123 alone. These results were compared with the light energy absorbed, the quantum yield of singlet oxygen and Rh-123 uptake as determined by flow cytometry analysis.

[Effect of gastrin and enprostil, a PGE2 analog, on colonic cancerous cell growth]. / Influence de la gastrine et de l'enprostil, analogue de la PGE2, sur la croissance de cellules cancéreuses coliques.

The effects of gastrin (G-17), proglumide (a gastrin receptor antagonist), and enprostil (a synthetic analog of prostaglandin E2) used alone or in association were studied in colonic cancer Prob and Regb cell growth. The Prob (progressive in BD IX rats) and Regb (regressive) cell lines were cloned from a single chemically-induced rat colonic cancer. After a serum-free period corresponding to one doubling cell time, cells were incubated with 100 to 1,200 pM G-17, 40 or 80 mM proglumide, and 2.5 to 5 micrograms/ml enprostil for 8 h. Cell growth was measured 48 h later by colorimetric MTT assay. Two and four hundred pM G-17 gave a growth stimulation of 17.4 percent and 31 percent for Prob cells respectively or 35.5 percent and 49 percent for Regb cells. Growth stimulation was found to be statistically different (P less than 0.01) for Prob and Regb cells. Proglumide partially inhibited this growth stimulation whereas enprostil inhibited in totally. These results suggest that growth of some colonic cancer cell lines may be G-17 dependent. However the intensity of cell-growth stimulation depends on the level of cell malignancy or differentiation in a single tumor.

Endoscopic photodynamic therapy with haematoporphyrin derivative in gastroenterology.

Endoscopic photodynamic therapy (PDT) with haematoporphyrin derivative was used in the primary treatment of 69 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups: 31 with oesophageal squamous cell carcinoma, 17 with adenocarcinoma of the stomach or lower third of the oesophagus and 21 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg haematoporphyrin derivative per kilogram of body weight, lesions were irradiated using an argon dye laser (632 nm). During a follow-up period averaging 20 months (27.9 months for 35 surviving patients), complete local tumour destruction and negative histology were observed in 32 out of 69 cases. Flow-cytometric analysis of DNA content before and after PDT suggests that a clonal selection occurs in some cases of treatment failure. The results of this open pilot study suggest the potential efficacy of PDT as a curative treatment for selected cases of inoperable gastrointestinal cancers.

Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients.

Endoscopic photodynamic therapy with hematoporphyrin derivative was used in the primary treatment of 54 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups including 24 with esophageal squamous cell carcinoma, 14 with adenocarcinoma of the stomach or lower third of the esophagus, and 16 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg hematoporphyrin derivative/kg of body weight, lesions were photoradiated using an argon dye laser with power set at 300-400 mW for 5 min/site. During a follow-up period averaging 14.5 months (range 1-33 months), complete local tumor destruction and negative histology were observed in 24 of 54 cases. The mean recurrence-free period varied from 13.8 to 17.4 months according to groups. Fifteen patients remain alive and disease-free. The results of this open pilot study suggest the potential efficacy of photodynamic therapy as curative treatment for selected cases of inoperable gastrointestinal cancers, possibly in association with locoregional radiotherapy.