In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron -emission tomography (PET) using [ 18 F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination.We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n ‫؍‬ 6) or signs of clinical progression (n ‫؍‬ 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET. (HEPATOLOGY 2004;39: 509 -517.)

The ecology of Borrelia burgdorferi Johnson et al. s.l. was investigated from 1987 to 1993 in a preserved woodland in western Germany near Bonn. In selected biotopes, host-seeking Ixodes ricinus L. were regularly collected by blanket dragging in 1987, 1988, and 1989 and screened for infection with B. burgdorferi. Rodents were trapped monthly between April and October in 1988, 1990, 1991, and in the winter of 1992-1993, examined for antibodies to B. burgdorferi s.l., and inspected for feeding ticks. Ticks collected from rodents were screened for spirochete infection. High numbers of host-seeking nymphs were consistently collected within a biotope characterized by humid and acid soils. The mean number of ticks was significantly lower in biotopes with permeable soils. All small mammals captured belonged to the species Apodemus flavicollis Melchior, A. sylvaticus L., and Clethrionomys glareolus Schreber. Of 11,680 ticks obtained from rodents, 11,674 were I. ricinus, with 97.9% of the ticks being larvae, 2.0% nymphs, and 0.1% females. Mean numbers of feeding ticks ranged from 3.4 to 117 larvae per rodent and from 0.0 to 0.64 nymph per rodent, respectively. High levels of larval infestation on rodents were recorded in the same biotope where high numbers of host-seeking nymphs were present. Members of the genus Apodemus were more heavily infested with I. ricinus larvae than C. glareolus. The mean infection prevalence in host-seeking ticks was found to be 1% for larvae, 5% for nymphs, and 10-20% for adults. The infection prevalence in host-seeking nymphs ranged from 1.1 to 15.4% according to the particular biotope. The values for specific infectivity for the Apodemus populations were positively correlated with the mean larval infestation, but not with nymphal infestation. The respective estimates for C. glareolus were much higher than those for Apodemus spp. in biotopes with low tick densities. However, specific infectivity of C. glareolus was substantially reduced at sites with high tick abundances. In biotopes with high numbers of infected I. ricinus, significantly more rodents were found to have antibodies to B. burgdorferi than in biotopes with low abundances of ticks. The data show that C. glareolus plays a different role as reservoir host species compared with the 2 Apodemus species. This and previous studies suggest that the degree of infestation with larval I. ricinus differentially modulates infectivity of host species for ticks. We conclude that immune processes in natural reservoir hosts induced by B. burgdorferi or I. ricinus bites (or both) are important regulatory factors in the transmission cycle(s) of B. burgdorferi.

BackgroundAlveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. Differential diagnosis with cystic echinococcosis (CE) caused by E. granulosus and AE is challenging. We aimed at improving diagnosis of AE on paraffin sections of infected human tissue by immunohistochemical testing of a specific antibody.Methodology/Principal FindingsWe have analysed 96 paraffin archived specimens, including 6 cutting needle biopsies and 3 fine needle aspirates, from patients with suspected AE or CE with the monoclonal antibody (mAb) Em2G11 specific for the Em2 antigen of E. multilocularis metacestodes. In human tissue, staining with mAb Em2G11 is highly specific for E. multilocularis metacestodes while no staining is detected in CE lesions. In addition, the antibody detects small particles of E. multilocularis (spems) of less than 1 µm outside the main lesion in necrotic tissue, liver sinusoids and lymphatic tissue most probably caused by shedding of parasitic material. The conventional histological diagnosis based on haematoxylin and eosin and PAS stainings were in accordance with the immunohistological diagnosis using mAb Em2G11 in 90 of 96 samples. In 6 samples conventional subtype diagnosis of echinococcosis had to be adjusted when revised by immunohistology with mAb Em2G11.Conclusions/SignificanceImmunohistochemistry with the mAb Em2G11 is a new, highly specific and sensitive diagnostic tool for AE. The staining of small particles of E. multilocularis (spems) outside the main lesion including immunocompetent tissue, such as lymph nodes, suggests a systemic effect on the host.

SummaryAn entomological study was conducted on vectors of malaria and their relative contribution to Plasmodium falciparum transmission in Mumias, a high-altitude site and large-scale sugarcane growing zone in Kakamega district, western Kenya. Anopheles gambiae s.l., the predominant vector species, represented 84% (n ϭ 2667) of the total Anopheles mosquitoes collected with An. funestus comprising only 16%. Polymerase chain reaction (PCR) identified all 600 specimens of the An. gambiae complex tested as An. gambiae sensu stricto, an indication that it is the only sibling species represented in the high-altitude sites in western Kenya. Plasmodium falciparum sporozoite rates of 6.3% (133/2118) for An. gambiae s.l. and 9.5% (38/402) for An. funestus by ELISA were obtained in Mumias. None of 1600 mosquitoes tested for P. malariae sporozoites was positive. ELISA tests of mosquito blood meals indicated a high tendency of anthropophagy, a behaviour contributing significantly to malaria transmission by the vector species, with 95.9%, 4.86% and 0.2% having taken at least one blood meal on human, bovine and avian hosts, respectively.Malaria transmission intensity was low as revealed by the low entomological inoculation rates (EIR) recorded. The EIR values for An. gambiae s.l. were 29.2 infective bites per person per year (ib/p/year) and 17.5 ib/p/year for An. funestus in Mumias. The highest inoculation rate for both vector species was 7.0 ib/p/month in July. Plasmodium falciparum parasite rate among asymptomatic children was 55.4% and 44% in the wet (July-September) and dry (December-February) seasons, respectively. These results indicate that malaria transmission intensity in the high-altitude site is low but perennial, with transmission being maintained by An. gambiae s.s. and An. funestus.keywords Plasmodium falciparum, sporozoite rates, entomological inoculation rates, high-altitude correspondence Dr J. I.

Immune responses to Borrelia burgdorferi and their influence on spirochete transmission to Ixodes ricinus were analyzed in the natural European reservoir hosts; i.e., the mouse species Apodemus flavicoUis (yellownecked mouse) and Apodemus sylvaticus (wood mouse) and the vole species Ckthrionomys glareolus (bank vole), and, in addition, in the laboratory mouse strain NMRI. Naive and preimmunized rodents were infected either by artificially infected I. ricinus larvae or by intradermal injection of spirochetes. Independent of the species, all animals developed antibodies to various spirochetal antigens. However, antibodies to the outer surface proteins A (OspA) and B (OspB) were not found in recipients infected via ticks. Rodents of the genus Apodemus and of the NMRI strain showed higher levels of B. burgdorfiei-specific antibodies than those of the species C. glareolus. The rate of spirochete transmission to noninfected ticks correlated with both the quality and quantity of spirochete-specific antibodies generated in the various species: high levels of spirochete-specific immunoglobulins correlated with low transmission rates. Furthermore, lower transmission rates were observed with rodents expressing antibodies to OspA and OspB (i.e., intradermally infected or immunized) than with those lacking these specificities (i.e., infected via ticks). The study provides evidence that transmission of B.

More than a decade after a study on the transmission cycle of Borrelia burgdorferi sensu lato in the Siebengebirge, a nature reserve near Bonn, Germany, questing nymphal and adult Ixodes ricinus ticks were collected again in three selected areas of the same low mountain range and examined for infection with B. burgdorferi sensu lato. Between May and October 2001, a total of 1,754 ticks were collected by blanket dragging; 374 ticks were analyzed for B. burgdorferi sensu lato by both an immunofluorescence assay (IFA) and at least two different PCR tests, whereas 171 ticks were analyzed by PCR only. By combining all assays, an average of 14% of the ticks tested positive for B. burgdorferi sensu lato, 5.5, 15.8, and 21.8% in the three collection areas. Of the nymphs and adults examined, 12.9 and 21.1%, respectively, were found to be spirochete infected. A lower total infection prevalence was obtained by IFA (14.4%) than by a nested PCR approach (16.5%), but both were higher than that obtained by a simple PCR approach (11.9%). Compared with data collected over a decade ago, the mean infection prevalence of B. burgdorferi sensu lato in the ticks was significantly higher for all three biotopes, whereas a similar pattern of habitat-specific infection prevalence was observed. Genotyping of B. burgdorferi sensu lato revealed high relative prevalences of B. valaisiana (identified in 43.1% of infected ticks) and B. garinii (32.3%), whereas B. afzelii (12.3%) and B. burgdorferi sensu stricto (1.5%) were relatively rare. We conclude that B. burgdorferi sensu lato infection has increased in this region over the last 15 years due to presently unknown changes in ecological conditions, perhaps related to climate change or wildlife management.

No abstract

Reactions of ozone with simple olefins have been studied between 6 and 800 mtorr total pressure in a 220-m3 reactor. Rate constants for the removal of ozone by an excess of olefin in the presence of 150 mtorr oxygen were determined over the iemperature range 280 to 360" K by continuous optical absorption measurements at 2537 A. The technique was tested by measuring the rate constants kl and k 2 of the reactions ( I ) NO + 0 3 -+ NO2 + 0 2 and (2) NO2 + 0 3 + NO3 + O 2 which are known from the literature. The results for NO, NO*, C2H4, C3H6, 2-butene (mixture of the isomers), 1,3-butadiene, isobutene, and l,l-difluoro-ethylene are 1.7 X (290°K), 3.24 X 1O-l' (289"K), 1.2 X exp (-4.95 &0.20/RT), 1.1 X 10-14exp (-3.91 +0.20/RT),0.94 X 10-14exp (-2.28 + O.l5/RT), 5.45 X exp (-5.33 i 0.20/RT), 1.8 X lo-" (283OK), and 8 X lo-'* cm3/molecule .s(290°K). Product formation from the ozone-propylene reaction was studied by a mass spectrometric technique. The stoichiometry of the reaction is near unity in the presence of molecular oxygen.