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Blaise Genton

Publications and source records attributed to Blaise Genton.

35 records · Page 2Linked to original sources

Prevalence rate and reasons for refusals of influenza vaccine in elderly.

More knowledge on the reasons for refusal of the influenza vaccine in elderly patients is essential to target groups for additional information, and hence improve coverage rate. The objective of the present study was to describe precisely the true motives for refusal. All patients aged over 64 who attended the Medical Outpatient Clinic, University of Lausanne, or their private practitioner's office during the 1999 and 2000 vaccination periods were included. Each patient was informed on influenza and its complications, as well as on the need for vaccination, its efficacy and adverse events. The vaccination was then proposed. In case of refusal, the reasons were investigated with an open question. Out of 1398 patients, 148 (12%) refused the vaccination. The main reasons for refusal were the perception of being in good health (16%), of not being susceptible to influenza (15%), of not having had the influenza vaccine in the past (15%), of having had a bad experience either personally or a relative (15%), and the uselessness of the vaccine (10%). Seventeen percent gave miscellaneous reasons and 12% no reason at all for refusal. Little epidemiological knowledge and resistance to change appear to be the major obstacles for wide acceptance of the vaccine by the elderly.

Age Factors↗

Molecular monitoring in malaria vaccine trials.

Molecular techniques offer new approaches for malaria field trials, particularly PCR techniques, which facilitate accurate diagnosis of Plasmodium infections and increase the power of estimates of vaccine effects on malaria prevalence or incidence. Molecular methods also help to assess selective effects of vaccines. Longitudinal genotyping data can be used to initiate novel analyses of parasite dynamics, including estimates of incidence of infection with individual parasite clones and duration of infections. In addition, high-throughput methods can be used to apply these techniques routinely in randomized controlled trials, as well as programme-based evaluations of malaria control.

Animals↗

The malaria vaccine development program in Papua New Guinea.

Through a collaborative project led by the Papua New Guinea Institute of Medical Research (PNGIMR), Papua New Guinea has a significant role in the global effort to develop a malaria vaccine, ensuring that the malaria patterns in Asia and the Pacific region are considered in vaccine development strategies. Some of the major perspectives and achievements of the program are discussed here, one of the most successful being the trial of Combination B, a vaccine comprising three asexual blood-stage proteins [merozoite surface protein (MSP)1, MSP2 and ring-infected erythrocyte surface antigen (RESA)], which led to a considerable reduction of parasite density in the immunized children.

Animals↗

Practice guidelines for evaluation of Fever in returning travelers and migrants.

BACKGROUND: Fever upon return from tropical or subtropical regions can be caused by diseases that are rapidly fatal if left untreated. The differential diagnosis is wide. Physicians often lack the necessary knowledge to appropriately take care of such patients. OBJECTIVE: To develop practice guidelines for the initial evaluation of patients presenting with fever upon return from a tropical or subtropical country in order to reduce delays and potential fatal outcomes and to improve knowledge of physicians. TARGET AUDIENCE: Medical personnel, usually physicians, who see the returning patients, primarily in an ambulatory setting or in an emergency department of a hospital and specialists in internal medicine, infectious diseases, and travel medicine. METHOD: A systematic review of the literature--mainly extracted from the National Library of Medicine database--was performed between May 2000 and April 2001, using the keywords fever and/or travel and/or migrant and/or guidelines. Eventually, 250 articles were reviewed. The relevant elements of evidence were used in combination with expert knowledge to construct an algorithm with arborescence flagging the level of specialization required to deal with each situation. The proposed diagnoses and treatment plans are restricted to tropical or subtropical diseases (nonautochthonous diseases). The decision chart is accompanied with a detailed document that provides for each level of the tree the degree of evidence and the grade of recommendation as well as the key points of debate. PARTICIPANTS AND CONSENSUS PROCESS: Besides the 4 authors (2 specialists in travel/tropical medicine, 1 clinical epidemiologist, and 1 resident physician), a panel of 11 European physicians with different levels of expertise on travel medicine reviewed the guidelines. Thereafter, each point of the proposed recommendations was discussed with 15 experts in travel/tropical medicine from various continents. A final version was produced and submitted for evaluation to all participants. CONCLUSION: Although the quality of evidence was limited by the paucity of clinical studies, these guidelines established with the support of a large and highly experienced panel should help physicians to deal with patients coming back from the Tropics with fever.

Algorithms↗

[Investigating fever after travel].

Two questions are crucial in the evaluation of fever in returning travellers, i.e. "Where have you been?" and "When did you go and when did you return from your trip?". Prior to establishing practice guidelines for fever in returning travellers and migrants, we did a systematic review of the geographical distribution of all infectious diseases in the tropical and subtropical countries. In the present paper, results are summarized by disease per continent. We also reviewed the extreme ranges for the incubation of the same diseases. Results are expressed graphically. Detailed information on space and time should help the practitioner to do an appropriate differential diagnosis, in particular to exclude diseases that are absent in the country visited or diseases with an incubation period that is incompatible with the travel history and symptoms occurrence dates.

Fever↗

Prospective study of a serogroup X Neisseria meningitidis outbreak in northern Ghana.

After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.

Adolescent↗

A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.

Animals↗

Malaria vaccines: from the laboratory to the field.

The demonstration of the i) acquired protective immunity in adults living in endemic areas, ii) cure of malaria patients with passive transfer of specific immunoglobulins, and iii) protection conferred by vaccination with sporozoites attenuated by radiation, justifies the search for a malaria vaccine. Given the improbability that a vaccine directed against a single antigen will be completely protective, the preferred option is to combine several antigens of different stages of the parasite in a multi-component multi-stage vaccine which is likely to protect both the travellers and the populations living in endemic areas. Potential manufacturing technologies include recombinant proteins, synthetic peptides and DNA vaccines, the relevant genes encoding malaria antigens being inserted into a plasmid or a live vector such as vaccinia or poxvirus. A number of human trials using different antigens and technologies have been carried out in the last ten years. Three vaccines have undergone safety and efficacy testing in the field. SPf66, comprising a linear polymerised synthetic peptide with several distinct epitopes, has been extensively evaluated in different epidemiological settings. The efficacy overall was 23%, but was only 2% in African infants, the most susceptible group. The circumsporozoite recombinant protein fused with the antigen S of the hepatitis B virus and formulated in a potent adjuvant (RTS,S) led to a high, but short-term, level of protection against infection and disease in Gambian adults. The first pure asexual blood-stage vaccine comprising three antigens of the merozoite stage (MSP1&2 and RESA, Combination B) had an efficacy of 62% in reducing parasite density in Papua New Guinean children. A malaria vaccine that can reduce the burden of disease in the most affected populations is thus an achievable goal, and each trial provides additional knowledge about mechanisms of protection as well as about new vaccine technology.

Animals↗

Clonal groupings in serogroup X Neisseria meningitidis.

The genetic diversity of 134 serogroup X Neisseria meningitis isolates from Africa, Europe, and North America was analyzed by multilocus sequence typing and pulsed-field gel electrophoresis. Although most European and American isolates were highly diverse, one clonal grouping was identified in sporadic disease and carrier strains isolated over the last 2 decades in the United Kingdom, the Netherlands, Germany, and the United States. In contrast to the diversity in the European and American isolates, most carrier and disease isolates recovered during the last 30 years in countries in the African meningitis belt belonged to a second clonal grouping. During the last decade, these bacteria have caused meningitis outbreaks in Niger and Ghana. These results support the development of a comprehensive conjugate vaccine that would include serogroup X polysaccharide.

Africa↗

Clinical and laboratory predictors of imported malaria in an outpatient setting: an aid to medical decision making in returning travelers with fever.

No evidence-based information exists to guide clinicians for giving presumptive treatment to returning travelers when malaria is strongly suspected on clinical grounds but laboratory confirmation is not immediately available or is negative. A prospective study was conducted in travelers or migrants who sought care for fever to identify clinical and laboratory predictors of Plasmodium parasitemia. A total of 336 questionnaires were collected (97 malaria case patients and 239 controls). Multivariate regression analysis showed inadequate prophylaxis, sweating, no abdominal pain, temperature > or = 38 degrees C, poor general health, enlarged spleen, leucocytes < or = 10 x 10(3)/L, platelets < 150 x 10(3)/L, hemoglobin < 12 g/dL, and eosinophils < or = 5% to be associated with parasitemia. Enlarged spleen had the highest positive likelihood ratio for a diagnosis of malaria (13.6), followed by thrombopenia (11.0). Posttest probabilities for malaria were 85% with enlarged spleen and 82% with thrombopenia. A rapid assessment can thus help to decide whether a presumptive treatment should be given or not, especially when the results of the parasitological examination are not immediately available or are uncertain.

Female↗

[Malaria.02: research for a world-wide exposition].

To reduce malaria-attributable mortality, there is a need to improve the diagnosis, to develop new drugs and vaccines, and to promote evidence-based case management. Following a case/control study aimed at identifying clinical and laboratory predictors of malaria, we made a systematic review on fever in returning travelers. We then developed evidence-based guidelines for these febrile patients. The next step is to assess the feasibility and safety of these web-based guidelines in the context of primary care. As far as the prevention is concerned, the Medical Outpatient Clinic (MOC) is collaborating to the pre-clinical and clinical development of several malaria vaccines: one of them (Combination B), including three proteins of the asexual blood stage (MSP1, MSP2, RESA), has already shown a remarkable efficacy to reduce parasite density in Papua New Guinean children: The MOC is thus heavily involved in research for the health of travelers, as well as the one of populations living in poor countries. Prevention and treatment of defavorised populations represents indeed one of the specific mission of the Medical Outpatient Clinic.

Case Management↗

[Vaccines against poverty].

In spite of major technological advances during the past ten years, the gap between rich and poor countries remains considerable. Among the 10.5 million children deaths in 1995, 99% occurred in developing countries and 1% in industrialised ones. Only 5 diseases (pneumonia, diarrhoea, measles, malaria and AIDS), as well as malnutrition, are responsible for more than 60% of the deaths. Most of them could be averted by an equitable access to health care and efficacious prevention programmes in the community. Every year, 3 million children are saved thanks to routine vaccinations, but also 4 millions die because they are not immunised, and this almost exclusively in developing countries. It is therefore urgent to develop strategies aimed at reaching the poorest of the poor, in order to reduce the burden of disease in these population and contribute thus to the well-being of families and to a sustainable economical development.

Acquired Immunodeficiency Syndrome↗

Improving influenza vaccination rates in the elderly.

BACKGROUND: Vaccination coverage for influenza in the elderly remains low when the physician is the only person responsible for immunization. Integration of other health care workers may improve the coverage rate of at-risk groups. OBJECTIVES: To estimate vaccination coverage rate by using a strategy based on the systematic intervention of a health care professional proposing vaccination before the doctor's consultation, to evaluate the changes in coverage rates before and after introduction of this strategy, and to assess the feasibility of this intervention and the achieved coverage rate in family physician offices. STUDY DESIGN: Prospective study in a medical outpatient clinic and 5 family physician practices in Switzerland. POPULATION: Participants consisted of all patients 65 years or older attending a medical outpatient clinic during the vaccination period in 1999 (n = 401), patients 65 years or older regularly followed at a medical outpatient clinic in 1998 and 1999 (n = 195), and patients 65 years or older presenting to 5 family physician offices in 1999 (n = 598). OUTCOME MEASURED: Rates of vaccination coverage. RESULTS: Among all participants, vaccination coverage rates in 1999 were 85% at the medical outpatient clinic and 83% in family physician offices. Among participants regularly followed at the medical outpatient clinic, vaccination coverage increased from 48% in 1998 to 76% in 1999. Rates of refusal were 9% at the medical outpatient clinic and 14% in the family physician offices. CONCLUSIONS: The systematic intervention of a health care professional to suggest vaccination before the doctor's visit is an effective measure to achieve high coverage rate. Such a strategy also improves outpatient clinic or private practice efficiency by reducing pressures on physicians.

Aged↗

Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in the elderly.

BACKGROUND: Protection against hepatitis A virus (HAV) in the elderly is becoming more important as more senior travelers visit areas of high HAV endemicity, and less have protective antibodies acquired after natural infection during childhood. This study assessed the immunogenicity and safety of hepatitis A vaccine in elderly compared to young adults. METHODS: In this open, uncontrolled study, subjects of 18 to 45 years or < or = 50 years of age received two doses of aluminum-free, virosomal HAV vaccine, Epaxal (Berna Biotech Ltd, formerly Swiss Serum and Vaccine Institute, Bern, Switzerland) 12 months apart. RESULTS: After both the basic and the booster doses, geometric mean titers (GMT) for anti-HAV antibodies were 1.7-fold higher in subjects younger than 45 years compared with those < or = 50 years of age. The proportional increase in GMT after the booster dose, however, was similar in younger and older subjects. Seroprotection (< or = 20 mIU/mL) rates in the younger and older subjects were 100 and 65%, respectively, after the first vaccination and 100 and 97%, respectively, after the booster dose. Systemic and local adverse events were mainly mild and short-lived. CONCLUSION: These data show that HAV virosomal vaccine (Epaxal) is well tolerated and immunogenic in elderly subjects. The clinical relevance of lower seroconversion rates after the primary dose is unknown in this population of travelers.

Adult↗

Do travelers really take their mefloquine malaria chemoprophylaxis? Estimation of adherence by an electronic pillbox.

BACKGROUND: Nonadherence to chemoprophylaxis could explain why some travelers get malaria. Adherence is notoriously difficult to assess, and most studies have been conducted using questionnaires. This study aims at assessing continuous adherence more accurately with the help of an electronic pillbox. METHODS: Adult travelers to sub-Saharan Africa had to fill a questionnaire on demographic and travel data, drug intake, and adverse events. They received oral and written information about malaria and mefloquine prophylaxis and a Medication Event Monitoring System (MEMS, Aardex, Zug, Switzerland), ie, a bottle closed with a cap containing a microprocessor recording date and time of all openings, filled with the exact number of mefloquine 250 mg tablets (Lariam, Roche Reinach, Switzerland). The MEMS) was returned with the questionnaire after completion of chemoprophylaxis. RESULTS: According to the MEMS, only 26 of 81 travelers (32.1%) took all the doses at the expected date, another 8 (9.9%) did so but starting late with the first dose, and 19 others (23.5%) took all the pills but with intervals of +/-1 day from the right date. Another eight (9.9%) took all the pills but in a random way. The remaining 20 travelers (24.7%) missed some doses, mainly after return. Strict adherence as assessed by electronic monitoring was therefore lower than adherence measured by questionnaire (32.1% vs 48% in taking all the tablets on the right day). There was no difference between the two methods when a broader definition of adherence was applied [taking all the tablets on the right day (+/-1 day); 53/81 (65.4%)], but the MEMS showed that some answers to the questionnaire were not reliable. CONCLUSION: The use of electronic pillboxes confirms the low adherence of travelers to mefloquine chemoprophylaxis in spite of extensive information about the disease and its prevention. Electronic assessment of pill taking, for the first time applied to malaria chemoprophylaxis, gives new insights into the real adherence of travelers.

Adult↗

Parasitological and clinical efficacy of standard treatment regimens against Plasmodium falciparum, P. vivax and P. malariae in Papua New Guinea.

Resistance of Plasmodium falciparum (Pf) and P. vivax (Pv) to standard antimalarials is widespread in Papua New Guinea (PNG). The objective of the study was to assess the rate of clinical treatment failure (TF) and parasite resistance to amodiaquine (AQ), chloroquine (CQ) and quinine+sulfadoxine/pyrimethamine (Q+SP) for malaria in a rural health centre of the East Sepik Province. 179 patients presenting with symptoms and signs of malaria and with Pf (144 patients), Pv (18 patients), P. malariae (Pm) (7 patients) or mixed infection (10 patients) were included. 86 were treated with AQ, 88 with CQ and 5 with Q+SP. 21/179 patients (12%) were not cured or had a recrudescence of symptoms associated with parasitaemia in the 28 days following treatment, 14% after AQ, 10% after CQ and 0% after Q+SP. The proportion of TF was higher (17%) when the analysis population included only the 108 subjects who had a complete follow-up, especially for failure with Pf following AQ treatment (26%). During the 28 days of follow-up, RII or RIII level of resistance in Pf was detected in 55% of the subjects treated with amodiaquine, 30% of those treated with chloroquine and 0% of those treated with quinine+SP. Of the Pv or Pm parasites only one Pv was found to be RII resistant to CQ in the 28-day test. In vitro resistance of Pf to CQ was higher than to AQ (50% versus 27% of 36 parasite samples that grew successfully). The level of TF and parasitological resistance to standard antimalarial drugs was lower in this area than in urban settings, where drugs are more easily available. AQ performed less well than CQ but the difference is likely to be due to the age of the users, ie, their level of immunity, AQ being the first-line drug for young children. These results provided support for the recent change in the policy for the standard treatment of uncomplicated malaria in PNG from AQ or CQ to the combination of AQ+SP or CQ+SP, a recommendation aimed at slowing down the spread of multidrug resistance.

Adolescent↗