Comparative benefit of malaria chemoprophylaxis modelled in United Kingdom travellers.

BACKGROUND: Chemoprophylaxis against falciparum malaria is recommended for travellers from non-endemic countries to malarious destinations, but debate continues on benefit, especially with regard to mefloquine. Quantification of benefit for travellers from the United Kingdom (UK) was modelled to assist clinical and public health decision making. METHODS: The model was constructed utilising: World Tourism Organization data showing total number of arrivals from the UK in countries with moderate or high malaria risk; data from a retrospective UK Clinical Practice Research Datalink (CPRD) drug utilisation study; additional information on chemoprophylaxis, case fatality and tolerability were derived from the travel medicine literature. Chemoprophylaxis with the following agents was considered: atovaquone-proguanil (AP), chloroquine with and without proguanil (C ± P), doxycycline (Dx), mefloquine (Mq). The model was validated for the most recent year with temporally matched datasets for UK travel destinations and imported malaria (2007) against UK Health Protection Agency data on imported malaria. RESULTS: The median (mean) duration of chemoprophylaxis for each agent in weeks (CPRD) was: AP 3.3 (3.5), C ± P 9 (12.1), Dx 8 (10.3), Mq 9 (12.3): the maximum duration of use of all regimens was 52 weeks. The model correctly predicted falciparum malaria deaths and gave a robust estimate of total cases--model: 5 deaths from 1118 cases; UK Health Protection Agency: 5 deaths from 1153 cases. The number needed to take chemoprophylaxis (NNP) to prevent a case of malaria considered against the 'background' reported incidence in non-users of chemoprophylaxis deemed in need of chemoprophylaxis was: C ± P 272, Dx 269, Mq 260, AP 252; the NNP to prevent a UK traveller malaria death was: C ± P 62613, Dx 61923, Mq 59973, AP 58059; increasing the 'background' rate by 50% yielded NNPs of: C ± P 176, Dx 175, Mq 171, AP 168. The impact of substituting atovaquone-proguanil for all mefloquine usage resulted in a 2.3% decrease in estimated infections. The number of travellers experiencing moderate adverse events (AE) or those requiring medical attention or drug withdrawal per case prevented is as follows: C ± P 170, Mq 146, Dx 114, AP 103. CONCLUSIONS: The model correctly predicted the number of malaria deaths, providing a robust and reliable estimate of the number of imported malaria cases in the UK, and giving a measure of benefit derived from chemoprophylaxis use against the likely adverse events generated. Overall numbers needed to prevent a malaria infection are comparable among the four options and are sensitive to changes in the background infection rates. Only a limited impact on the number of infections can be expected if Mq is substituted by AP.

The safety of oseltamivir in pregnancy: an updated review of post-marketing data.

PURPOSE: Influenza infection places pregnant women at greater risk of morbidity and hospitalization. The use of oseltamivir to treat influenza increased markedly in all population groups during the A/H1N1pdm09 pandemic, including pregnant women. Given this increase in exposure, a reassessment of the safety of oseltamivir in pregnancy was conducted. METHODS: The Roche Global Safety Database was searched for all exposures to oseltamivir during pregnancy in the 13 years up to 30 April 2012. RESULTS: Of the 2926 maternal exposures to oseltamivir retrieved from the Safety Database, pregnancy outcomes were known for 2128 women. Most exposures (>90%) were reported during or after the pandemic. The incidence of adverse pregnancy outcomes in exposed women was: spontaneous abortions, 2.9% (61/2128); therapeutic abortions, 1.8% (39/2128); and pre-term deliveries, 4.2% (84 of 2000 live births), values which are lower than background rates in the general population (women with or without influenza). Fetal outcomes were known in 1875 of the 2926 exposures. For the 81 reported birth defect cases, 11 occurred during the sensitive period for the respective defects. A review of these and other case reports of birth defects did not suggest that they resulted from oseltamivir exposure. CONCLUSIONS: The data reviewed in this article reinforce the findings of a previous review, suggesting that oseltamivir is unlikely to cause adverse pregnancy or fetal outcomes.

Malaria chemoprophylaxis regimens: a descriptive drug utilization study.

BACKGROUND: Mefloquine belongs to the priority chemoprophylaxis drugs for travelers to malaria endemic regions. We aimed to assess the prescribing patterns for mefloquine and other antimalarials. METHODS: We conducted a descriptive drug utilization study using the U.K. Clinical Practice Research Datalink (CPRD). We assessed characteristics of individuals with a first-time antimalarial prescription for mefloquine, atovaquone/proguanil, chloroquine and/or proguanil, or doxycycline between 2001 and 2012. RESULTS: Of 165,218 individuals with a first-time antimalarial prescription, 108,344 (65.6%), 25,294 (15.3%), 23,195 (14.0%), and 8385 (5.1%) were prescribed atovaquone/proguanil, mefloquine, doxycycline, and chloroquine and/or proguanil, respectively. Among mefloquine users, 7.5% had a history of a neuropsychiatric disorder (versus 12.6%-13.7% among other antimalarial users) and 0.04% had a history of severe liver disease (versus 0.04%-0.1% among other antimalarial users). A total of 19.4% mefloquine users were children younger than 12 years (versus 0.4%-15.8% among other antimalarials), and 1.3% pregnant or postpartum women (versus 0.4%-1.4% among users of other antimalarials). CONCLUSIONS: The most frequently prescribed antimalarial chemoprophylaxis was atovaquone/proguanil. Mefloquine was occasionally prescribed for patients with comorbidities listed as contraindications, but most practitioners observed contraindications. Mefloquine was often prescribed for children and pregnant women.

Measles, rubella, and varicella among the crew of a cruise ship sailing from Florida, United States, 2006.

BACKGROUND: Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varicella have been previously associated with introduction and spread among susceptible crew members originating from countries with endemic transmission of these diseases. METHODS: During February to April 2006, we investigated a cluster of rash illnesses due to measles, rubella, or varicella on a cruise ship sailing from Florida to the Caribbean. Case-finding measures included review of medical logs, active surveillance for rash illness among crew members, and passive surveillance for rash illness in the ship's infirmary lasting two incubation periods from the last case of measles. Passengers with potential exposure to these VPD were notified by letters. All susceptible crew members with potential exposure were administered the measles, mumps, and rubella vaccine after informed consent. RESULTS: A total of 16 cases were identified only among crew members: 1 rubella, 3 measles (two-generation spread), 11 varicella (three-generation spread), and 1 unknown diagnosis. Of 1,197 crew members evaluated, 4 had proof of immunity to measles and rubella. Based on passive surveillance, no cases were identified among passengers, the majority of whom resided in the United States. CONCLUSION: The international makeup of the population aboard cruise ships combined with their semi-enclosed environment has the potential to facilitate introduction and spread of VPD such as measles, rubella, and varicella onboard and into communities. Cruise lines should ensure crew members have evidence of immunity to these diseases. Passengers should be up to date with all vaccinations, including those that are travel-specific, prior to embarking on cruise travel.