Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe.

Since its introduction to the market in 1985, mefloquine has been used for malaria chemoprophylaxis by more than 35 million travellers. In Europe, in 2014, the European Medicines Agency (EMA) issued recommendations on strengthened warnings, prescribing checklists and updates to the product information of mefloquine. Some malaria prevention advisors question the scientific basis for the restrictions and suggest that this cost-effective, anti-malarial drug will be displaced as a first-line anti-malaria medication with the result that vulnerable groups such as VFR and long-term travellers, pregnant travellers and young children are left without a suitable alternative chemoprophylaxis. This commentary looks at the current position of mefloquine prescribing and the rationale of the new EMA recommendations and restrictions. It also describes the new recommendations for malaria prophylaxis that have been adapted by Switzerland, Germany, Austria and Italy where chemoprophylaxis use is restricted to high-risk malaria-endemic areas.

Clinical aspects and management of cutaneous leishmaniasis in rheumatoid patients treated with TNF-α antagonists.

Patients under immunosuppressive therapy with tumor necrosis factor alpha (TNF-α) antagonists are vulnerable to various opportunistic infections including leishmaniasis. We present a case series of 8 travellers developing cutaneous leishmaniasis whilst on TNF-α antagonist treatment and review the literature on aspects of cutaneous leishmaniasis developing in patients treated with TNF-α antagonists. We make interim recommendations regarding the drug therapy used to maintain remission in travellers with rheumatoid disease travelling to leishmania prone areas. Despite having a medical condition requiring continued rheumatological review the interval to diagnosis appears not to be reduced compared to that described in non-rheumatoid patients. Rheumatologists and family doctors should be aware of the need for post-travel surveillance for leishmaniasis in rheumatoid patients on TNF-alpha antagonist treatment.

[Adventure travel]. / Abenteurer unterwegs.

Extreme travelling experiences appear to be a quite popular kick offered by tourist operators and sought by some travellers. But some travellers expose themselves to increased risk also during normal holidays, either voluntarily by booking hikes or tours leading them to adventurous locations or to unexpectedly encountering dangerous situations. In planned adventures, precise information in advance, good physical condition, careful planning, and profound medical preparation may contribute to a less hazardous adventure. Advising medical persons may need an expert consultation for specific topics in order to optimise the preparation. Based on three specific environmental situations (jungle, desert, and cave) the specific conditions, dangers and some medical aspects are outlined.

Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers.

There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.

Successful memory response following a booster dose with a virosome-formulated hepatitis a vaccine delayed up to 11 years.

Boosting adult travelers with the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal up to 128 months after a single primary dose confers full protection against hepatitis A, even in travelers aged 50 years and above. Delaying the booster dose did not influence the immune memory response to Epaxal.

Lepromatous leprosy with erythema nodosum leprosum as immune reconstitution inflammatory syndrome in an HIV-1 infected patient after initiation of antiretroviral therapy.

We present the case of an HIV infected male patient with erythema nodosum leprosum and function loss of the peroneus nerve as manifestations of lepromatous leprosy. Since symptoms occurred after initiation of antiretroviral therapy and recovery of the immune system, the clinical picture is suggestive of a rare form of an immune reconstitution inflammatory syndrome.

First case of ivermectin-induced severe hepatitis.

Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literature.

Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.

OBJECTIVE: To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. DESIGN: Randomised, double blind, study with placebo run-in phase. SETTING: Travel clinics in Switzerland, Germany, and Israel. MAIN OUTCOME MEASURE: Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. PARTICIPANTS: 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. RESULTS: A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013). CONCLUSIONS: Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.

Successful booster antibody response up to 54 months after single primary vaccination with virosome-formulated, aluminum-free hepatitis A vaccine.

This study demonstrates that a booster dose of the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal (Berna Biotech) is highly immunogenic in subjects who received a single primary dose of this vaccine 18-54 months earlier. There were no significant differences in geometric mean antibody titers (GMTs) among subjects who received the booster dose 18-29 months (GMT, 2330 mIU/mL), 30-41 months (GMT, 2395 mIU/mL), or 42-54 months (GMT, 2432 mIU/mL) after primary vaccination, indicating that delays in the administration of booster vaccination do not lead to a loss of immunogenicity.