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.

Cost of screening and treatment of cervical dyskaryosis in Germany.

Human papillomavirus (HPV) infection is the principal cause of cervical cancer. Clinical trials with HPV vaccines have shown high efficacy against HPV-induced precancerous cervical lesions. Before implementing a vaccination programme, up-to-date data on cervical dyskaryosis, incidence and annual treatment costs are needed. We assessed resource use and costs for 12 months following diagnosis for women with abnormal Pap smears in Germany based on a sample of 138 women who had received abnormal results on Pap smears taken during March and April of 2004. Most women had a Pap IIID (57%) vs Pap III (20%) or Pap IV (23%). Women with a Pap IV consulted their gynaecologist more frequently than those with a Pap III or Pap IIID (5.6 visits vs 4.2 and 4.6 visits, respectively). Only 9% of patients underwent colposcopy plus biopsy; this may be due to the lack of histological assessment by coloposcopy and biopsy done currently in Germany. More women in the Pap IV group had a cold knife conisation, compared with those in the Pap IIID group, (84% vs 27%) hysterectomy (22% vs 4%) and laser coagulation (12.5% vs 4%). Median treatment duration was shorter for women with a Pap III than for those with Pap IIID and IV (3 vs 5 months, respectively). Overall, 28.3% of the women were hospitalised (median 5; range 1-33 days). The estimated average annual cost per patient was Euro 1,055, Euro 943 and Euro 3,174 for Pap III, IIID and IV, respectively. The cost of managing precancerous cervical lesions in Germany was shown to be high.

[Anogenital warts incidence, medical management and costs in women consulting gynaecologists in France]. / Incidence, prise en charge et coût des condylomes acuminés anogénitaux chez les femmes consultant leur gynécologue en France.

OBJECTIVES: The objectives of this study were to estimate the incidence of genital warts and treatment costs in women consulting gynaecologists in France in 2005. PATIENTS AND METHODS: A prospective observational study was performed through a representative sample of gynaecologists. Investigators enrolled all patients seen with genital warts during a 2-month period. A questionnaire detailing socio-demographic characteristics, case description, patient's clinical profile, past/ current management, and treatment of genital warts was completed by the investigators. RESULTS: 212 gynaecologists participated in the study. Questionnaires were completed for 263 patients including 198 (75.3%) new cases, 53 (20.2%) recurrent cases and 12 (4.5%) resistant cases. The overall incidence was estimated at 228.9/100,000 (female 15-65year old population) corresponding to 47,755 cases annually managed by gynaecologists in France. The average treatment cost was 482.70euro for society and 342.40 euro for third-party payers. The annual direct cost of genital warts management was estimated at 23,051,339euro, of which 16,351,312euro was funded by the French health care system. DISCUSSION AND CONCLUSION: The costs of treating genital warts are considerable. The introduction of a quadrivalent (type 6,11,16,18) Human Papillomavirus vaccine including types responsible for 90% of genital warts could potentially substantially reduce these costs.

[Cervical cancer screening and associated treatment costs in France]. / Coût du dépistage et de la prise en charge des lésions précancéreuses du col utérin en France.

OBJECTIVE: Oncogenic human papillomaviruses (HPV) cause cervical cancer (CC). Screening prevents CC by detecting and removing cervical intraepithelial neoplasia (CIN) lesions that are detected through abnormal Pap smears. This study assessed the costs of CC screening, management of abnormal Pap smears, and treatment of CIN in France. PATIENTS AND METHODS: Pap smears received by laboratory Pasteur-Cerba during a 7-month period were examined. Patients with abnormal Pap smears were identified and followed for 6 months after diagnosis. The management of abnormal Pap smears was documented. These data and other published studies were used to estimate the total number of pap smears, distribution of abnormal smears requiring further examinations, and number of CIN diagnosed. Economic analyses were performed to estimate total CC screening costs from the health care payer (HCP) and societal perspective. RESULTS: An estimated 6,111,787 Pap smears were performed in 2004, including 222,350 abnormal (3.9%) and 63,616 follow-up smears. In total, 58,920 cervical biopsies and 52,525 HPV tests were performed after an abnormal Pap smear. The cost associated with CC screening, including management of abnormal findings, was estimated at 174.2 million euro from the HCP perspective. Total treatment cost for all CIN was estimated at 22.3 million euro (HCP perspective). DISCUSSION AND CONCLUSION: Overall cost for screening, diagnosis and management of Pap smears was estimated at 335.7 million euro of which 196.5 million euro where funded by the HCP. An HPV vaccine that prevents pre-cancerous or cancerous lesions of the cervix will decrease the socio-economic burden associated with the screening of these lesions.

Costs of detection and treatment of cervical cancer, cervical dysplasia and genital warts in the UK.

OBJECTIVE: Infection with human Papillomavirus (HPV) is a necessary cause of cervical cancer (CC) and genital warts (GW). HPV vaccination studies have shown excellent efficacy against HPV-induced lesions. To assess the cost-effectiveness of a HPV quadrivalent (6, 11, 16 and 18) vaccine it is necessary to estimate the costs of managing current levels of HPV-related diseases. This study estimates the annual 2003 expenditures in the UK for CC screening, follow-up of abnormal findings, CC treatment and GW treatment. DESIGN AND METHODS: CC screening programmes provided the annual number of screening tests, their results and use of colposcopy procedures in women with abnormal findings. Incident CC cases and hospital admissions for CC in 2003 were used to estimate CC costs. Health Protection Agency data provided the annual number of new, recurrent or persistent cases of GW treated in Genitourinary Medicine (GUM) clinics. Treatment patterns for managing GW were estimated by GUM clinicians. The annual physician visits, tests, procedures, hospital admissions and topical genital wart medications were costed to estimate the total annual expenditures for CC and GW. RESULTS: There were 4.8 million screening tests and 230 303 colposcopy procedures. Estimated costs for screening, management of abnormal and inadequate findings were 138.5 million pounds sterlings. Annual management costs for incident and prevalent CC cases were 46.8 million pounds sterlings. There were an estimated 76 457 incident and 55 657 recurrent/persistent GW cases in 2003. The costs for managing these cases were approximately 22.4 million pounds sterlings. Total annual estimated costs for CC screening, management and treatment of GW were 208 million pounds sterlings and ranged from 186.9 pounds sterlings to 214 million pounds sterlings based upon sensitivity analyses. CONCLUSIONS: The direct medical costs for the NHS associated with detection and management of CC, cervical dysplasia and treatment of GW in the UK are substantial. These medical costs are invaluable for future cost-effectiveness analyses of a quadrivalent HPV vaccine programme.

Investigation of an unexplained skin disorder in a prison clinic in the Netherlands in 2002.

An unexplained outbreak of skin disorder with itching papules or pustules occurred among drugs body packers in a detention clinic in the Netherlands in October-November 2002. The descriptive cohort study suggests this outbreak could be associated with an expired batch of disposable linens, with an overall attack rate of 30% in the study population (n=118). No additionnal cases have been noted since this expired batch was replaced.

Developmental differences in endplate response to P-type calcium channel blockade in the rat diaphragm.

Endplate potentials (epps) were recorded intracellularly from single diaphragm fibers of newborn (7-10 days, n = 11) and older (24-30 days, n = 11) rats in the presence of 100 nM omega-agatoxin IVA, a P-type Ca2+ channel blocker. The muscle was stimulated via the phrenic nerve for 1 s at 40 Hz. In both age groups epp amplitude decreased with omega-agatoxin, however the decrease was greater in the older group (mean = 60% of control vs. 40% of control in the younger group). A larger number of fibers in the older group (84% vs. 54% in the young) showed a > or = 50% decrease in epp amplitude. These data suggest that although P-type Ca2+ channels are present in the immature presynaptic nerve terminals at the neuromuscular junction, functional maturation of these channels occurs with development. This may contribute to the susceptibility to neuromuscular transmission failure in the newborn diaphragm.