Alois Tschopp

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

Abstract 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.

Influenza Virus Infection in Travelers to Tropical and Subtropical Countries

BACKGROUND Influenza outbreaks have been reported among travelers, but attack rates and incidence are unknown. METHODS A cohort study was conducted. Travelers to subtropical and tropical countries recruited at the University of Zurich Travel Clinic (Switzerland), January 1998 to March 2000, were investigated with pre- and posttravel assessment of hemagglutination inhibition and by questionnaire. RESULTS Among 1450 travelers recruited who completed questionnaires and provided serum samples before departure, 289 (19.9%) reported febrile illness during or after traveling abroad; of these, 211 (73.0%) provided paired serum samples. Additionally, paired serum samples were collected from 321 frequency-matched afebrile control subjects among the remaining 1161 subjects of the study population. Seroconversion for influenza virus infection was demonstrated in 40 (2.8%) of all travelers; 18 participants (1.2%) had a > or = 4-fold increase in antibody titers. This corresponds to an incidence of 1.0 influenza-associated events per 100 person-months abroad. Among the 211 febrile participants, 27 (12.8%) had seroconversion, 13 (6.2%) with a > or = 4-fold increase; among the 321 afebrile control subjects, 13 (4.0%) had seroconversion, 5 (1.6%) with a > or = 4-fold increase. Twenty-five seroconverters (62.5%; P = .747) acquired influenza outside of the European epidemic season. Sixteen patients (40.0%) sought medical attention either abroad or at home, and 32 (80.0%) were asymptomatic at the time of completion of the survey. CONCLUSIONS This survey indicates that influenza is the most frequent vaccine-preventable infection among travelers to subtropical and tropical countries. Infections occur mainly outside the domestic epidemic season, and they have a considerable impact. Pretravel vaccination should be considered for travelers to subtropical and tropical countries.

Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag

To compare the impact of various dosage forms of melatonin and placebo on jet lag symptoms, 320 volunteers who had flights over 6 to 8 time zones were recruited for a double-blind, randomized, placebo-controlled study. The volunteers received either melatonin 0.5-mg fast-release (FR) formulation, melatonin 5-mg FR formulation, melatonin 2-mg controlled-release (CR) formulation, or placebo. The study medication was taken once daily at bedtime during 4 days after an eastward flight. The volunteers completed the Profile of Mood States (POMS), sleep log, and symptoms questionnaires once daily and the Karolinska Sleepiness Scale (KSS) three times daily prior to departure and during the 4 days of medication intake postflight. A total of 234 (73.1%) participants were compliant and completed the study. The FR melatonin formulations were more effective than the slow-release formulation. The 5-mg FR formulation significantly improved the self-rated sleep quality (p < .05), shortened sleep latency (p < .05), and reduced fatigue and daytime sleepiness (p < .05) after intercontinental flight. The lower physiological dose of 0.5 mg was almost as effective as the pharmacological dose of 5.0 mg. Only the hypnotic properties of melatonin, sleep quality and sleep latency, were significantly greater with the 5.0-mg dose.

Incidence and clinical features of traveler's diarrhea in infants and children

To assess the incidence rate and the characteristics of travelers diarrhea in small children ages 0 to 2 years, children ages 3 to 14 years, and adolescents ages 15 to 20 years a retrospective survey was conducted. Of the pretravel visitors to the Zurich University Vaccination Center, all those ages 0 to 20 years were selected between October, 1987, and May, 1988. They received a questionnaire within 2 weeks after returning home. Of the 446 young travelers who were recruited, 363 (81.3%) could be evaluated. Within 14 days in the tropics or subtropics, travelers diarrhea occurred in 8 of 20 (40.0%) small children, in 4 of 47 (8.5%) children ages 3 to 6 years, in 10 of 46 (21.7%) children ages 7 to 14 years and in 90 of 250 (36.0%) adolescents (P = 0.0003). In small children the clinical course tended to be severe and prolonged (average duration, 29.5; median, 17.5 days) when compared with other age groups (3 to 5 days). In 40% of all the children the parents reported that they had consistently practiced dietary preventive measures. For self-treatment oral rehydration solutions were used in 5.0% and loperamide in 33.8%. In conclusion adults should be discouraged from taking small children to developing countries unless necessary. Parents should be instructed about how to prevent travelers diarrhea and about the mainstay of self-therapy in pediatric patients by oral rehydration solutions.

Hepatitis E, Helicobacter pylori, and gastrointestinal symptoms in workers exposed to waste water

Background: Workers exposed to sewage may have an increased risk of infection by Helicobacter pylori and hepatitis E virus (HEV). Aims: To assess the prevalence of clinical hepatitis E (HE) and peptic ulcer disease as well as the seroprevalence of antibodies to H pylori and HEV in workers with and without sewage exposure and to look for symptoms due to exposure to endotoxin. Methods: In the first year of a prospective cohort study 349 sewage exposed workers and 429 municipal manual workers (participation: 61%) underwent a complete medical examination. Travelling to endemic areas, socioeconomic level, age, country in which childhood was spent, and number of siblings were considered as the main confounding factors. Results: Peptic ulcer disease and clinical HE did not occur more often in workers exposed to sewage. Prevalence of antibodies to HEV was 3.3% and overall prevalence of IgG antibodies to H pylori was 42% with large differences between subgroups. Logistic regression did not show an increased risk of seropositivity or antibodies to parietal cells in sewage exposed workers, but disentangling the effect of exposure from that of confounders was extremely difficult. No increase of symptoms due to exposure to endotoxin was found in sewage workers, with the exception of diarrhoea. Conclusions: No clear increased risk of infection by H pylori or by HEV in workers exposed to sewage was found in this cross-sectional study, but these results need to be confirmed by follow up.

Effects of long-term, self-monitored exercise on the serum lipoprotein and apolipoprotein profile in middle-aged men

To study the effects of long-term, self-monitored exercise on the serum lipid profile and body composition of middle-aged non-smoking males, a controlled study was conducted in 61 sedentary, middle-class Swiss men. Thirty-nine men were randomly allocated to jog 2 h/wk for 4 months on an individually prescribed, heart rate-controlled basis, whereas 22 men served as controls. Despite varying adherence to the exercise regimen, the following 4-month net changes (effect in exercise group minus effect in control group) in lipids were seen: HDL cholesterol (C) +0.12 mmol/l (95% CI 0.02, 0.22; P = 0.028), LDL-C +0.08 mmol/l (ns), VLDL-C -0.26 mmol/l (-0.45, -0.07; P = 0.009), total triglycerides (TT) -0.21 mmol/l (ns), HDL-C/total C +0.02 (0.001, 0.05; P = 0.047). The net changes in endurance capacity and resting heart rate in favour of exercisers were significant as well, whereas no significant changes in apolipoprotein levels were seen. Exploratory analyses revealed, for example, associations of the increase in total physical activity with an increase in the HDL-C/total C ratio (r = 0.46; P less than 0.001), and of the change in estimated body fat content with an opposed change in the HDL-C/total C ratio (r = -0.40; P less than 0.001), or an inverse relationship of the change in subcutaneous fat with a change in the HDL2-C level (r = -0.39; P less than 0.001). Multivariable regression analysis suggested that much of the effect of jogging on HDL-C was apparently mediated through a decrease in body fat content. A change in the waist/hip ratio was unrelated to lipoprotein changes but was related to the change of TT level (r = 0.22; P less than 0.05). This study confirms that individually prescribed, unsupervised jogging can increase HDL-C levels and improve the serum lipoprotein profile in self-selected nonsmoking males. Although the effect is modest, it may be relevant to preventive cardiology, given the evidence for a reduction in cardiovascular risk even after apparently small decreases in risk factor levels.

MalaQuick™ versus ParaSight F® as a diagnostic aid in travellers' malaria

In this study we assessed whether travellers can perform malaria rapid tests, following the provided information leaflet, and correctly interpret performed and pre-prepared test strips. Two Plasmodium falciparum testing systems, namely MalaQuick (ICT) and ParaSight F were used. Test performance and test interpretation of pre-prepared tests were compared. There was no significant difference in test performance between the 2 tests. Interpretation of prepared test strips in both test systems was very reliable in blood parasite densities between 0.1% and 2%, but major problems were encountered at low parasitaemia (< 0.1% blood parasites) and also in ParaSight F test strips showing high parasitaemia (> 2% blood parasites). Low parasitaemia ParaSight F test strips were correctly interpreted by 52.1% compared with 10.8% correct interpretations with MalaQuick (P < 0.0001). Correct interpretation of highly positive (> 2% blood parasites) pre-prepared test strips was higher with MalaQuick (96.8%) than with ParaSight F (33.8%), P < 0.0001. Both tests were associated with high levels of false-negative interpretations which render them unsuitable as self-diagnostic kits. Efforts must be made to assist lay individuals in test performance by technical test improvement, by equiping the test strips with an additional reading aid for interpretation, and by providing instruction by a skilled person.

Safety of Early High-Dose Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants.

OBJECTIVE To investigate the safety and short term outcome of high dose recombinant human erythropoietin (rhEpo) given shortly after birth and subsequently over the first 2 days for neuroprotection to very preterm infants. STUDY DESIGN Randomized, double masked phase II trial. Preterm infants (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after birth. RESULTS There were no relevant differences between the groups for short-term outcomes such as mortality, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At day 7-10, we found significantly higher hematocrit values, reticulocyte, and white blood cell counts, and a lower platelet count in the rhEpo group. CONCLUSIONS Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events. TRIAL REGISTRATION ClinicalTrials.gov: NCT00413946.

Anthropometric and lifestyle correlates of serum lipoprotein and apolipoprotein levels among normal non-smoking men and women

The relationship between serologic predictors of coronary risk and anthropometric as well as lifestyle characteristics was investigated in 61 men (37.5 +/- 8.5 yrs) and 33 women (40.1 +/- 9.0 yrs). All subjects were healthy non-smokers, mostly middle-class bank employees. In bivariate analysis, among both genders the ratio of waist-to-hip circumference (WHR) was the single best predictor of levels of serum LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides (positive association) as well as HDL-cholesterol and apolipoprotein A-I (inverse association). In men, body fat as estimated from bioelectrical impedance measurement was the second best predictor of lipoprotein and apoprotein concentrations, whereas in women it was the body mass index (BMI). The additional independent predictive power of WHR and body fat for the lipid profile was tested in multivariate analysis by adding WHR and body fat sequentially to regression models containing already BMI, endurance capacity, exercise, alcohol consumption and age. For example, explained variance of triglyceride distribution rose from 26.3 to 35.1% (P = 0.01 for increase) when body fat was entered into the regression equation, or inclusion of WHR into a model already containing age, the behavioral variables, BMI, and body fat increased the explained variance of LDL/HDL-cholesterol ratio from 20.9 to 27.6% (P = 0.04 for increase). In women, the same regression models were even slightly more predictive for the serum lipid profile. Endurance capacity was related to a low atherogenic risk lipid profile in bivariate analysis but lost much of its predictive power in multivariate analysis, which confirms that the effect of fitness on lipid levels is probably mediated in part by a low body fat content. It is concluded from this cross-sectional investigation that studies which focus on associations between lifestyle and serologic predictors of atherogenic risk should possibly include the WHR and a measure of body fat, since the latter two appear to be closer correlates of serum lipoprotein and apolipoprotein levels than BMI or single behavioral factors, at least among male non-smokers.

Profile of travel-associated illness in children, Zürich, Switzerland.

BACKGROUND The number of families traveling with their children to their country of origin and/or to tropical destinations has increased in Switzerland and includes a changing profile and multinational range of patients. Defining the profile of reported travel-associated illnesses will help to improve the prevention and treatment of such illnesses in children. METHODS This study includes children aged up to 16 years who sought medical advice for a presumed travel-related illness at the emergency room of the University of Zürich Childrens Hospital during the period July 2007 to December 2008. RESULTS We analyzed data on 328 children (58.8% male, mean age: 4.62 y) who presented with travel-associated illness. Our analysis included 155 traditional (mainly tourist) travelers, 162 children who were visiting friends and relatives (VFR), and 11 immigrants. Some 11% were hospitalized. No deaths occurred. The main conditions recorded were diarrheal illness (39%), respiratory (28.7%) and febrile/systemic illness (13.4%). With increasing age, the proportion of children with diarrheal disease increased, while the proportion with respiratory illness declined. There were significant associations between geographic area of exposure and the profile of travel-related disease (p < 0.001). Among 36 children with more serious diseases requiring hospitalization, 12 (3.7% overall) presented with potentially serious diseases: malaria (n = 2), Salmonella typhi (n = 3), Salmonella paratyphi (n = 2), meningococcal meningitis (n = 1), tuberculosis (n = 2), visceral leishmania (n = 1), and hepatitis A (n = 1). Eleven of the 12 children presenting with these potentially serious illnesses were VFR or immigrant children. CONCLUSION The main diagnoses for ill-returned Zürich children who presented for emergency care were diarrhea, respiratory, and febrile/systemic illness. A broad spectrum of morbidity was seen including meningococcal meningitis, malaria, tuberculosis, typhoid fever, leishmania, and hepatitis A. Diagnoses varied between geographic regions visited, and VFR child travelers constituted a large proportion of sick-returned children presenting for emergency care.