Safety and Immunogenicity of Live Oral Cholera and Typhoid Vaccines Administered Alone or in Combination with Antimalarial Drugs, Oral Polio Vaccine, or Yellow Fever Vaccine

The effects of concomitant administration of antimalarial drugs, oral polio vaccine, or yellow fever vaccine on the immune response elicited by the Vibrio cholerae CVD103-HgR and Salmonella typhi Ty21a live oral vaccines were investigated. Healthy adults were immunized with CVD103- HgR alone or combined with Ty21a. Subjects were randomized to simultaneously receive mefloquine, chloroquine or proguanil, or oral polio or yellow fever vaccine. The vibriocidal antibody seroconversion rate was significantly reduced (P = .008) only in the group that received chloroquine with the CVD103-HgR. The geometric mean vibriocidal antibody titer was significantly decreased in the groups that received chloroquine (P = .001) or mefloquine (P = .02) compared with titers in groups that received CVD103-HgR alone. However, similar immunosuppressive effects were not observed in the groups immunized with Ty21a and CVD103-HgR. Only the concomitant administration of proguanil effected a significant (P = .013) decline in the anti-S. typhi lipopolysaccharide antibody response. These results indicate that chloroquine and proguanil should not be simultaneously administered with the CVD103-HgR and Ty21a vaccine strains, respectivel

Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe

BACKGROUND: Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide. RESULTS: 337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas. CONCLUSIONS: Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas

Screening for Mutations Related to Atovaquone/ Proguanil Resistance in Treatment Failures and Other Imported Isolates of Plasmodium falciparum in Europe

Background. Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. Methods. We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. Results. We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. Conclusions. Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient poo

After a tick bite in a tick-borne encephalitis virus endemic area: current positions about post-exposure treatment.

If a person suffers a tick bite in tick-borne encephalitis (TBE) endemic areas, there is uncertainty on post-exposure treatment of naïve (non-immune) persons in order to protect the patient against TBE. Particularly, there are no distinct positions on the use of TBE active immunization as post-exposure treatment. Of special concern is the possibility of antibody-dependent enhancement of infection and exacerbation of disease in case of post-exposure vaccination. Such phenomena have been reported for other flavivirus infections. In the past, immune globulin treatment was recommended, but these preparations are no longer available. Active immunization by using the current immunization schedules after a tick bite will not result in appropriate neutralizing antibody concentrations within due time. Based on the assumptions that vaccination is not quick acting enough after a tick bite and that the theoretical risk of antibody-dependent enhancement cannot be excluded, no vaccination or other specific measure is currently recommended after a tick bite in non-vaccinated patients, leaving the patient in a completely dissatisfactory position. A risk/benefit analysis has been re-assessed for persons with a history with at least one vaccine injection, certain patient groups and in relation to the vaccination schedule which has been used and to the geographic area where the tick bite has occurred. In order to evaluate the value of the vaccine for post-exposure immunization, new immunization schedules have to be evaluated with respect to their capacity to induce antibodies more quickly

After a tick bite in a tick-borne encephalitis virus endemic area: current positions about post-exposure treatment.

If a person suffers a tick bite in tick-borne encephalitis (TBE) endemic areas, there is uncertainty on post-exposure treatment of naïve (non-immune) persons in order to protect the patient against TBE. Particularly, there are no distinct positions on the use of TBE active immunization as post-exposure treatment. Of special concern is the possibility of antibody-dependent enhancement of infection and exacerbation of disease in case of post-exposure vaccination. Such phenomena have been reported for other flavivirus infections. In the past, immune globulin treatment was recommended, but these preparations are no longer available. Active immunization by using the current immunization schedules after a tick bite will not result in appropriate neutralizing antibody concentrations within due time. Based on the assumptions that vaccination is not quick acting enough after a tick bite and that the theoretical risk of antibody-dependent enhancement cannot be excluded, no vaccination or other specific measure is currently recommended after a tick bite in non-vaccinated patients, leaving the patient in a completely dissatisfactory position. A risk/benefit analysis has been re-assessed for persons with a history with at least one vaccine injection, certain patient groups and in relation to the vaccination schedule which has been used and to the geographic area where the tick bite has occurred. In order to evaluate the value of the vaccine for post-exposure immunization, new immunization schedules have to be evaluated with respect to their capacity to induce antibodies more quickly

Frühsommer-Meningoenzephalitis (FSME) - Grundlagen

Zusammenfassung. Die Frühsommer-Meningoenzephalitis (FSME) ist in weiten Teilen aller deutschsprachigen Länder endemisch verbreitet. In den meisten Regionen besteht ein Trend zur Zunahme der Inzidenz und zur Ausbreitung der befallenen Gebiete. Angesichts der Tatsache, dass bei einem Teil der Patienten die Diagnose nicht gestellt wird und dass der klinische Verlauf mit zunehmendem Alter schwerer ist, muss man vor allem bei Kindern und Adoleszenten von einem erheblichen Underreporting ausgehen. Infizierte Zecken übertragen das FSME-Virus, ein Flavivirus, bereits in den ersten Minuten nach dem Stich. Nach einer Inkubationszeit von 4 bis 28 Tagen treten in der ersten virämischen Phase uncharakteristische grippeartige Symptome auf. Nach einem symptomfreien Intervall kommt es bei einer Minderheit der befallenen Patienten zu unterschiedlichen neurologischen Syndromen, welche durch den Befall des Zentralnervensystems bedingt sind. Bleibende Organschäden sind häufig und bei etwa 1% der Fälle ist der Verlauf letal. Um die FSME zu diagnostizieren ist es essenziell, an diese Infektion zu denken und die Anamnese einer möglichen Exposition zu erheben. Je nach Phase der Krankheit wird man IgM- und/oder IgG-Antikörper feststellen können, dies aus dem Serum und/oder dem Liquor. Seltener und nur in der Anfangsphase der Krankheit lassen sich allenfalls Viren mittels PCR finden. Tick-Borne Encephalitis (TBE) – Fundamentals Abstract. There is widespread endemicity of tick-borne encephalitis (TBE) in all German-speaking countries. In most regions there is a gradual increase in incidence and further territorial spread. As a proportion of the cases is not diagnosed and since the clinical course is getting worse with growing age, substantial underreporting occurs particularly in the pediatric and adolescent patient population. Infected ticks are transmitting the TBE virus, a flavivirus, within a few minutes after the bite. After an incubation period of 4 to 28 days uncharacteristic flu-like symptoms usually occur during a first viremic phase. This is followed by a brief asymptomatic interval before a minority of patients suffer of a variety of symptoms associated with damage of different parts of the central nervous system. This often results in permanent neurological injury and in about 1% the clinical course is fatal. To establish a diagnosis, it is essential to suspect the infection and to obtain a history of exposure. Depending on the phase of illness IgM and/or IgG antibodies can be detected in the serum and/or in the cerebrospinal fluid. In the early phase of the infection the TBE virus may be detected by PCR

Pharmacodynamic Interaction of Doxycycline and Artemisinin in Plasmodium falciparum

Parallel in vitro tests, assessing the inhibition of schizont maturation, were conducted with 31 fresh isolates of Plasmodium falciparum from Thailand, using artemisinin, doxycycline, and combinations of both. The activities of artemisinin and doxycycline are obviously not correlated. Both compounds showed consistent synergism at 50% effective concentration (EC(50)), EC(90), and EC(99) levels