Dieter Stürchler

Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting East Africa

There is much confusion over which malaria chemoprophylaxis should be used in areas such as East Africa. We did two consecutive studies between 1985 and 1991 to assess the efficacy and side-effects of malaria chemoprophylaxis in short-term travellers to East Africa. All passengers returning from Kenya to Europe received an in-flight questionnaire and a second one three months later. Any report of documented malaria or of admission to hospital for possible side-effects was verified with the physician. 145 003 travellers completed questionnaires. Among the 139 164 who stayed in East Africa for less than one year, 296 cases of confirmed malaria were reported (275 due to P falciparum). In people who used no chemoprophylaxis, the incidence of falciparum malaria was 1.2% per month. Prophylactic effectiveness was 91% (95% Cl 85 to 94) for mefloquine, 82% (71 to 89) for pyrimethamine and sulfadoxine, 72% (56 to 82) for chloroquine plus proguanil, and 10 to 42% for chloroquine at various doses. Rates of side-effects, which were usually mild, were 18.8% for mefloquine users, 17.1% and 18.6% for chloroquine 300 mg and 600 mg base per week, respectively, 30.1% for chloroquine plus proguanil, and 11.7% for sulfadoxine and pyrimethamine. Mefloquine is significantly more effective than chloroquine plus proguanil for malaria prophylaxis in short-term tourists visiting East Africa and has a tolerance similar to that of chloroquine used alone.

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

How Frequent are Notified Severe Cutaneous Adverse Reactions to Fansidar

SummaryAn attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar® (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar® or a related product, Bactrim® (cotrimoxazole; Sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar®: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar® users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984—1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons. With extreme assumptions (90% underreporting of cases and 500% overestimation of users) a risk of 54 (51 to 57) per million would result which, we conclude, is acceptable when compared with a 1% case fatality of severe falciparum malaria.

Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults

A Plasmodium falciparum sporozoite vaccine, composed of a synthetic dodecapeptide (NANP)3 coupled to tetanus toxoid (TT), was injected, at weeks 0 and 8, into non-immune volunteers in two randomized double-blind placebo-controlled trials. In the first trial, 37 volunteers received the vaccine simultaneously with placebo (group 1), 0.5 x 10(6-) (group 2), or 1.5 x 10(6) U (group 3) of recombinant human interferon-alpha (= IFN-alpha). In the second trial, 35 other volunteers received the vaccine with placebo (group 4), 0.25 x 10(6) (group 5), or 1.0 x 10(6) IU (group 6) of interferon-gamma (= IFN-gamma). Immunizations were well tolerated and resulted in seroconversion rates (greater than or equal to 4-fold increase of antibody titre in immunofluorescence or enzyme-linked immunosorbent assays) of 67-100% of volunteers. IFN-alpha significantly enhanced the IgG antibody titres in ELISA to malaria peptide.

National laboratory reports of Chlamydia trachomatis seriously underestimate the frequency of genital chlamydial infections among women in Switzerland

Background Public health authorities want to evaluate their sexually transmitted disease (STD) surveillance systems to promote the most effective use of health resources. Goal The goal of this study was to estimate the sensitivity of national laboratory reports of Chlamydia trachomatis in Switzerland (the proportion of cases detected by national laboratory reports). Study Design A cross sectional prevalence study was conducted by the Swiss Sentinel Surveillance Network of Gynecologists in 1998. Two groups of women aged less than 35 years were included in the study: those having a first consultation for pregnancy and those having a routine check-up. Results A total of 1589 women were tested for C trachomatis. The prevalence among pregnant women (n = 817) was 1.3%, and that among sexually active women (n = 772) was 2.8%. Using the prevalences observed among check-up women, we estimate that there were at least 24,400 C trachomatis infections in Switzerland among women aged 20 to 34 years in 1998 (95% CI: 14,300–34,300). The number of laboratory reports of C trachomatis in this age group was 1150 in 1998. Conclusion Our study suggests that the sensitivity of national laboratory reports of C trachomatis in 1998 was less than 5% for women aged 20 to 34 years.

[Malaria--chemoprophylaxis 2001].

An estimated 20,000 to 30,000 cases of imported malaria are annually diagnosed in industrialised countries. Some 700 of them concern Swiss travellers and foreign guests. Exposure prophylaxis and chemoprophylaxis for high risk destinations lower the risk of malarial disease. The latter is defined as regular intake of antimalarial drugs in subtherapeutic dosage in order to suppress the development of clinical disease. Drugs are usually taken from one week before travel until four weeks after return from an endemic area. Mefloquine, doxycycline, chloroquine plus proguanil, and presumably soon also atovaquone plus proguanil are available in Switzerland for chemoprophylaxis.

Massnahmen bei einer influenza-Pandemie in der Schweiz

As an influenza pandemic is to be expected, contingency plans are being developed in industrialized nations. During the interpandemic phase the responsibilities are clearly defined and no shortage occurs with respect to vaccines and drugs. In contrast, a lack of material and of infrastructure must be expected in a pandemic which will stress public health and disrupt social and business life. This plan illustrates how with the available means we should attempt to the best possible primarily to reduce premature mortality, secondarily to diminish morbidity and to maintain essential public services and security. Options are described, for instance how an increased production of vaccine already during the interpandemic phase would probably reduce the impact of a pandemic.