[Eosinophilia, diarrhea]. / Eosinophilie, Durchfall.

A 46-year-old Swiss woman presents with intermittent abdominal pain and persistent eosinophilia that is suggestive of helminthic etiology. Though her stay in Africa goes back > 35 years, an imported disease is a possibility. However, contact with a puppy suggests a locally acquired organism. Antibodies to filariae and Toxocara are demonstrated in the serum. Following treatment with albendazole 400 mg daily for 14 days the patient makes a full recovery, and the final diagnosis is active Toxocara canis infection.

[Malaria--chemoprophylaxis 2001]. / Malaria-Chemoprophylaxe 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.

A waterborne outbreak of small round structured virus, campylobacter and shigella co-infections in La Neuveville, Switzerland, 1998.

An outbreak of gastro-enteritis occurred in La Neuveville, township with 3358 inhabitants. A retrospective cohort study of 1915 participants showed that 1607 (84%) had been ill. Campylobacter jejuni was isolated from 28 patient faecal samples, Shigella sonnei from 21 patients and small round structured viruses (SRSV) from 6 patients. More than one pathogen was identified in eight persons. The epidemic curve was characteristic of a point-source outbreak. The risk for illness was significantly higher among persons who had drank unboiled drinking water than among those who had not (1290 [80.3%] of 1607 vs. 86 [27.9%] of 308; RR = 2.87; 95% CI 2.40-3.45). Risk increased significantly with the quantity of water consumed (P < 0.00 x 10(-6)). An SRSV isolate from water and one human faeces had an identical DNA sequence. The outbreak was due to a pump failure producing a spill of sewage into the groundwater. We conclude that transmission was waterborne and that measures including early warning, basic hygiene and sanitation improvements controlled this epidemic.

Isoniazid plus sulphadoxine-pyrimethamine can reduce morbidity of HIV-positive patients treated for tuberculosis in Africa: a controlled clinical trial.

An annual 20% excess mortality rate is observed in HIV-seropositive patients after treatment for tuberculosis. An affordable secondary prophylaxis against main opportunistic diseases is needed, i.e. against tuberculosis, toxoplasmosis, pneumocystosis and other infections occurring in this target population. This open prospective randomized study assessed morbidity and mortality in 2 cohorts of HIV-seropositive patients having recently recovered from pulmonary tuberculosis: 134 patients assigned to prophylactic treatment with isoniazid (INH, 300 mg once daily) plus sulphadoxine-pyrimethamine (S, 500 mg/P, 25 mg once weekly), and 129 were controls, comparable for sex, age, weight and HIV-serology. Patients were followed-up for up to 2 years: 192 person-years (PY) in the prophylaxis group and 142 PY in the control group. Four patients developed tuberculosis and 20 patients died in the prophylaxis group, compared to 10 and 23 controls, respectively. Sick days were reported by 22 patients in the prophylaxis group and by 77 patients in the control group. This prophylaxis was associated with a moderate decrease of mortality (log rank test: p = 0.1736), a significant decrease of tuberculosis incidence (log rank test: p = 0. 0234), a highly significant reduction of adverse events and sick days, and a prevention of wasting (p = 0.008) and anaemia (p = 0. 045). No death from toxoplasmosis occurred in the prophylaxis group as compared to 2 possible cases among controls; toxoplasmosis IgG levels declined in treated patients, but increased in controls (p = 0.01). There was no adverse drug reaction due to SP (10,006 doses) or to INH. Compliance with SP intake was good, but moderate as with INH intake. We conclude that a secondary prophylaxis with INH+SP represents a cost-effective measure to improve health conditions of HIV-infected adults in Côte d'Ivoire, following a full treatment course against tuberculosis.

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.

Malaria chemotherapy trial at a minimal effective dose of mefloquine/sulfadoxine/pyrimethamine compared with equivalent doses of sulfadoxine/pyrimethamine or mefloquine alone.

In murine malaria the addition of mefloquine to sulfadoxine/pyrimethamine has been shown to exert an additive effect and to significantly slow the emergence of resistance to the individual components. In a pilot study carried out in Gabon, a reduced dosage of the triple combination with a mean of 1 mg/kg of mefloquine/2 mg/kg of sulfadoxine/0.1 mg/kg of pyrimethamine (Fansimef; Roche, Basel, Switzerland) had previously been shown to achieve high cure rates in Plasmodium falciparum malaria. To evaluate the additive effect, a randomized, double-blind trial in school children with mild P. falciparum malaria was performed in Gabon. Two hundred thirty-one patients evaluated received a single dose of either the triple combination with a mean of 1.07 mg/kg of mefloquine/2.14 mg/kg of sulfadoxine/0.11 mg/kg of pyrimethamine (group MSP), or 1.07 mg/kg of mefloquine alone (group M), or 2.14 mg/kg of sulfadoxine/0.11 mg/kg of pyrimethamine alone (group SP). In the MSP group and the SP group, 67% and 69% of the patients were parasitologically cured, respectively, compared with only 13% in the M group (P < 0.001). A significantly higher parasitemia was found in the M group compared with the MSP group or the SP group on days 2 and 3 after the start of treatment. The high efficacy of the low dose sulfadoxine/pyrimethamine regimen was the most surprising finding of this study.

Tolerability and Effectiveness of Malaria Chemoprophylaxis with Mefloquine or Chloroquine with or without Co-medication.

Background: To determine the relevance of drug interactions with co-medication for effectiveness and tolerability of antimalarial chemoprophylaxis. Method: A database (MALPRO2) on travelers on their flight home from Africa to Europe between July 1988 and December 1991 was reanalyzed. It contains data on prophylaxis with mefloquine (n = 48,264), with chloroquine (6,752), with chloroquine plus proguanil (19,727), and with no prophylaxis (3,871). The comparison of rates of malaria incidence and adverse events (AEs) between users and nonusers of co-medication was expressed by relative risk (RR). Results: Fifty-three percent of travelers (63% of females, 43% of males) used co-medication in all prophylaxis groups, with an average of 1.35 additional drugs per person and about two AEs reported per person. With the exception of antidiarrheals plus mefloquine, malaria incidence with co-medication was lower (RR = 0.8) than without co-medication. In all regimens, the proportion of travelers reporting AEs was about 1.5-fold with co-medication (p<.01); that reporting severe AEs was twice as high as compared to with no co-medication. Mefloquine AE rates for various classes of co-medication were similar to that of chloroquine, with highest AE and severity rates with neuropsychiatric drugs (excluding antiepileptics, RR = 1.9 and 2.9), and lowest rates with cardiovasculars (RR = 1.1 and 1.0). Various co-medications were used with different frequencies in males and females, and the latter reported more AEs. Conclusion: These data suggest that co-medications commonly used by travelers have no significant clinical impact on safety and effectiveness of prophylaxis with mefloquine or chloroquine. Increased frequency and severity of AEs when using co-medication rather is explained by underlying illness.

[Experiences with the Swiss mandatory disease notification]. / Erfahrungen mit der Schweizer Meldeverordnung.

Advantages and setbacks of the existing Swiss disease notification system are reviewed. The public takes interest in the notification data output. The voluntary sentinels provide useful early warning. Currently, 60 conditions are notifiable. It is intended to lower this number to < 30. Other measures to upgrade the system include annual review and publication of an updated list of notifiable diseases, limitation to an essential core of parameters collected from physicians on initial and follow-up questionnaires, and practical advice on diagnostic and control measures provided for in questionnaires for the infectious disease under query.

Malaria Prophylaxis in Different Age Groups.

Background: There is a perceived increased health risk in senior visitors to malaria endemic countries. Methods: The authors sought to compare effectiveness and tolerability of malaria chemoprophylaxis in senior travelers (>=60 years) with those in younger travelers (20-59 years). The "Malpro 2" database consists of more than 100,000 questionnaires completed by travelers on charter planes returning from East Africa to Europe during July 1988-December 1991. Among them, 9106 (9.1%) of the travelers were 60 years or older, and 84,562 (84.6%) of the travelers reported to be 20-59 years. Variables of demography, travel data, and the effectiveness and tolerability of chemoprophylaxis were compared in the two subgroups. Results: Malaria in Africa was reported by 8 (1/1000) elderly travelers and by 189 (2.2/1000) travelers aged 20-59 years. Adjusting for age, sex, prophylaxis, and duration of stay in Africa in a logistic regression model, malaria was significantly more frequent in younger than in senior travelers (p<.05). Any travel-associated illness was reported by 7.0% in the senior age group and by 13.6% in the younger age group (p<.05). The rates of travelers who indicated they had "side effects" attributable to malaria prophylaxis varied between 9.7% in the elderly and 15.5% in the younger travelers (p<.05). Conclusion: Senior travelers tolerate malaria chemoprophylaxis and visits to the tropics at least as well as younger travelers.

Arteflene compared with mefloquine for treating Plasmodium falciparum malaria in children.

Arteflene is a synthetic peroxide recently developed from an indication of antimalarial activity found in the Chinese plant Artabotrys uncinatus. The new antimalarial was compared against mefloquine in a phase 3, open-labeled, randomized trial in children with uncomplicated Plasmodium falciparum malaria in Gabon. Patients received single oral doses of either 25 mg/kg of arteflene suspension or 15 mg/kg of mefloquine tablets. High-grade (RII and RIII) resistance was observed in eight (40%) of the 20 patients receiving the single dose of arteflene, but in none of the 21 mefloquine-treated patients (P < 0.005). At day 28, only one patient in the arteflene group, compared with all 21 patients in the mefloquine group, was cured (P < 0.001). Arteflene cleared fever slightly but not significantly faster than mefloquine and the 50% and 90% parasite clearance times were comparable in both treatment groups. In vitro results in the arteflene group suggest an increase of arteflene resistance when comparing sensitivity of paired parasite isolates before treatment and at recrudescence. Both treatment regimens were well-tolerated. In conclusion, single dose monotherapy with arteflene was not effective in curing children suffering from uncomplicated P. falciparum malaria in Gabon, while mefloquine proved to be highly effective for this purpose.

Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessments, stereochemistry and compliance.

This longitudinal study of travellers to Africa taking mefloquine (MQ) chemoprophylaxis aimed to quantify and assess non-serious adverse events (AE) occurring during short-term prophylaxis and relate these to concentrations of racemic MQ, its enantiomers and metabolite. A total of 420 volunteers (52% F) participated. AEs with some impact on activities were reported by 11.2% of participants including 7.9% of neurological/psychiatric symptoms. Women were more likely to report AEs (P = 0.02). The standardized questionnaires used showed more pathological indicators in travellers who reported subjective AE with significantly more dizziness, distress, sleep disturbances and a high total mood disturbance (TMD) in the AE group. There was, however, no significant performance deficit in computerized psychomotor tests in those experiencing AE. Furthermore, no significant differences were observed in enantiomer ratios, metabolite concentrations, or racemic MQ levels in participants with or without AEs suggesting that these factors are not the main predictors of mefloquine intolerability.

The chemotherapy of rodent malaria. LII. Response of Plasmodium yoelii ssp. NS to mefloquine and its enantiomers.

A comparison was made between the blood schizontocidal action in mice of racemic mefloquine hydrochloride and the free bases of its (+)- and (-)-enantiomers (Ro 13-7224 and Ro 13-7225) against chloroquine-resistant Plasmodium yoelii ssp. NS. The racemic hydrochloride was two to three times as active against this parasite in mice as either of the enantiomer free bases, which were of similar activity to each other. Under drug selection pressure, the parasites acquired resistance in approximately the same time for each of the three compounds.

Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults.

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The antimalarial drug, Ro 42-1611 (arteflene), does not affect cytoadherence and cytokine-inducing properties of Plasmodium falciparum malaria parasites.

The purpose of this study was to investigate the ability of the antimalarial drug, Ro 42-1611 to block parasite mediated cytokine induction in vitro as well as cytoadherence of infected erythrocytes to melanoma cells in vitro. The biological activity of Ro 42-1611 was confirmed as it blocked Plasmodium falciparum growth in cultures. Ro 42-1611, had no major effect on TNF, IL-alpha or IL-6 cytokine release from mononuclear cells stimulated with malaria antigens or lipopolysaccharide and it did not affect cell viability. Ro 42-1611 only slightly suppressed cytoadherence of infected erythrocytes to melanoma cells. The therapeutic effect of To 42-1611 appears to be confined to its parasite killing activity.

[NANP]19-5.1. A malaria vaccine field trial in Nigerian children.

[NANP]19-5.1 is a recombinant Plasmodium falciparum vaccine consisting of 19 repeats of the sporozoite surface protein [NANP] and the schizont export antigen 5.1. In a previous study, an experimentally infected subject (with a history of malaria exposure and an elevated pre-immunization lymphocyte stimulation index to antigen 5.1) showed parasitaemia but no signs of clinical malaria. In an attempt to find a comparable partially immune population, we tested the vaccine in 194 schoolchildren (6 to 12 years, vaccine and placebo groups of equal size), who already possessed a certain degree of immunity. It was hoped that this immunity would be boosted by the vaccine. During the 12 weeks of observation, no child developed clinical malaria. Analysis of serum taken before and after immunization revealed that, except for eight children, all had considerable levels of antibodies to both antigens. We conclude that the trial should be repeated in younger children who are still vulnerable to clinical malaria.

Ro 42-1611 in the treatment of patients with mild malaria: a clinical trial in Nigeria and Burkina Faso.

An open, non-comparative clinical trial was carried out in Nigeria and Burkina Faso to investigate the safety and efficacy of the novel antimalarial arteflene in patients with mild malaria. Patients were males aged 12 to 16 years, with a Plasmodium falciparum count of 10(4) to 10(5) parasites/microliters and a body temperature of 37.5 to 38.5 degrees C. Twenty-three patients received a single dose of Ro 42-1611 (arteflene), corresponding to 25 +/- 2.5 mg/kg bodyweight. Nineteen patients were evaluable for standard efficacy. Efficacy was assessed at 6, 9, 12, 24, 36, 48 and 72 hours, and at seven days, by: reduction in parasitaemia and time to parasite clearance; resolution of fever; and clinical cure (defined as the absence of signs and symptoms of malaria). Adverse events were reported at each assessment point, and laboratory tests were carried out at baseline and at 2 and 7 days. The parasite count was reduced by 50% or more in 89.5% of patients after 48 hours, and 52.6% were completely free of parasites at the same time. Normal temperature was achieved in 89.5% of patients and clinical cure in 75%, after 48 hours. One patient reported mild vertigo and mild pruritus. The lower than expected effect was thought to be due to inadequate storage of the arteflene suspension. There were no withdrawals due to adverse events and no deaths. A single dose of 25 mg/kg arteflene was found to be an effective and well-tolerated treatment for mild P. falciparum malaria.

Efficacy of Ro 42-1611 (arteflene) in the treatment of patients with mild malaria: a clinical trial in Cameroon.

The novel antimalarial Ro 42-1611 (arteflene) was evaluated for safety and efficacy in an open, non-comparative study of patients with mild malaria in the south of Cameroon. Thirty male patients aged 12 to 42 years, with an initial Plasmodium falciparum count of > 5000 (mean: 21,406) parasites/microliters and a body temperature of 37.7% to 39.8 degrees C, were selected to receive a single dose of arteflene, corresponding to 25 +/- 2.5 mg/kg bodyweight. Efficacy was assessed at 6, 9, 12, 24, 36, 48 and 72 hours, and at seven days by: reduction in parasitaemia and time to parasite clearance; resolution of fever and clinical cure (defined as the absence of signs and symptoms of malaria). Adverse events were reported at baseline and at each assessment point, and laboratory tests were carried out at 2 and 7 days. The mean number of parasites/microliter fell from 21,406 at baseline to 157 after 48 hours, at which point 80% of patients were completely free of parasites. Mean body temperature was reduced from 38.9 degrees C at baseline to 37.3 degrees C 12 hours after arteflene administration, and by this time 80% of patients had a normal temperature. Clinical cure rates were also high, with 70% of patients free of all signs and symptoms after 24 hours. However, by day 7, 6/30 (20%) presented with smears positive for P. falciparum. There were no adverse events considered to be related to treatment. A single dose of 25 mg/kg arteflene was found to be an effective and well-tolerated treatment for mild P. falciparum malaria.