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K Dietz

Publications and source records attributed to K Dietz.

At least 37 records · Page 2Linked to original sources

Bayesian age-stage modelling of Plasmodium falciparum sequestered parasite loads in severe malaria patients.

A discrete-time age-stage model is proposed for estimating the number of sequestered parasites in severe malaria patients. A Bayesian Markov chain Monte Carlo (MCMC) approach is used to model the dynamics of Plasmodium falciparum parasitaemia in 107 paediatric patients in a randomized controlled trial of quinine and artemether in Kenya, in whom 4-hourly peripheral parasitaemia determinations were made. The MCMC approach allows the model to be fitted simultaneously to the entire dataset, providing point and interval estimates for both population and individual patient parameters. Analysis of a simulated dataset indicated that the models gave good estimates of the distribution of parasites between different stages on enrolment, for patients with a wide range of initial states. The analysis of the Kenyan patients suggested that there is considerable variation between patients within the same centre, in both the proportion of sequestered parasites and the intrinsic rate of increase of the parasite population in the absence of treatment. The resulting models should prove a useful tool for cross-validating biochemical approaches for estimating the sequestered load.

Animals↗

Evaluation of red blood cell deformability and uterine blood flow in pregnant women with preeclampsia or iugr and reduced uterine blood flow following the intravenous application of magnesium.

OBJECTIVE: Red blood cells (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), RBC deformability and, consequently, microcirculation appear to be impaired. Magnesium sulfate is administered to reduce the risk of seizures in PE. The aim of our study was to detect the effect of 24-hour intravenous (IV) magnesium on RBC deformability and on uterine artery blood flow in pregnant patients with preeclampsia or IUGR and pathologic uterine blood flow. METHODS: Magnesium IV (1 g/h) was administered to 25 pregnant women with reduced uterine blood flow for a period of at least 24 hours. The RBC deformability was measured by uterine artery Doppler. Measurements were taken before the start of magnesium therapy and 24 h later. Magnesium plasma levels were measured at the same time. RESULTS: High plasma levels of magnesium improve RBC deformability from E = 0.109 (SD +/- 0.023) to E = 0.115 (SD +/- 0.021) after 24 h IV magnesium (p = 0.043). There is no correlation of E to the plasma magnesium level either before or after 24 h magnesium treatment. Blood volume flow in the uterine arteries increased significantly from 5.09 mL/s (SD +/- 3.03) to 10.02 mL/s (SD +/- 5.86) after 24 h magnesium (p = 0.0002). The differences in the resistance index do not significantly differ from 0 (p = 0.46). CONCLUSION: A high IV dosage of magnesium over a period of 24 hours dilates the uterine arteries of pregnant women with PE and/or IUGR, reduces uterine blood flow and improves the deformability of RBC. Both parameters enhance the oxygen supply to the fetus, a clinical parameter in these pregnancies. Thus magnesium might not only be effective as phrophylaxis against seizures but also in cases of IUGR with a reduced uterine blood flow. The clinically observed beneficial effect of magnesium in PE could be due to the improved blood supply for the fetus.

Adult↗

Detection and typing of human papillomavirus by e6 nested multiplex PCR.

A nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus primers and type-specific primers was evaluated for the detection and typing of human papillomavirus (HPV) genotypes 6/11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 56, 58, 59, 66, and 68 using HPV DNA-containing plasmids and cervical scrapes (n = 1,525). The performance of the NMPCR assay relative to that of conventional PCR with MY09-MY11 and GP5+-GP6+ primers, and nested PCR with these two primer sets (MY/GP) was evaluated in 495 cervical scrapes with corresponding histologic and cytologic findings. HPV prevalence rates determined with the NMPCR assay were 34.7% (102 of 294) in the absence of cervical intraepithelial neoplasia (CIN 0), 94.2% (113 of 120) in the presence of mild or moderate dysplasia (CIN I/II), and 97.8% (44 of 45) in the presence of severe dysplasia (CIN III). The combination of all four HPV detection methods applied in the study was taken as "gold standard": in all three morphological subgroups the NMPCR assay had significantly (P < 0.0001) higher sensitivities than the MY09-MY11 and GP5+-GP6+ assays and sensitivities comparable or equal to those of the MY/GP assay. All 18 HPV genotypes investigated were detected among the clinical samples. The ratio of high- to low-risk HPV genotypes increased from 4:1 (80 of 103) in CIN 0 to 19:1 (149 of 157) in CIN I to III. Multiple infections were detected in 47.9% (124 of 259) of the patients. In conclusion, the novel NMPCR method is a sensitive and useful tool for HPV DNA detection, especially when exact HPV genotyping and the identification of multiple HPV infections are required.

DNA Primers↗

MRI-based volumetric differentiation of sporadic cerebellar ataxia.

The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Multiple system atrophy is also a sporadic neurodegenerative disorder of unknown origin that may cause prominent cerebellar symptoms (MSA-C). The final neuropathological answer to the question whether IDCA-P and MSA-C represent different varieties of one disease or two distinct entities is still lacking. Three-dimensional MRI-based volumetry allows morphological investigations intra vitam. Volumetric analysis of cerebellum, brainstem and basal ganglia was therefore performed in 46 patients with sporadic cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia were excluded from the study since cognitive impairment is an exclusion criterion for the diagnosis of MSA. Cerebellar patients were clinically divided into two groups: 33 patients with multiple system atrophy with prominent cerebellar symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both cerebellar groups while additional brainstem atrophy was significantly more pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to be restricted to single MSA-C individuals while group comparisons of mean volumes did not yield significant differences from controls. Based on the volumetric data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and 100% of IDCA-P individuals. The finding of specific imaging characteristics strengthens (i) the value of MRI volumetry in separating MSA-C from other types of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent neurodegenerative disorders in MSA-C and IDCA-P.

Adult↗

Evaluation of a commercial IgG/IgM Western blot assay for early postnatal diagnosis of congenital toxoplasmosis.

The aim of this study was to evaluate a commercial Western blot IgG/IgM assay for use in the early serological diagnosis of congenital toxoplasmosis. This assay compares the immunological profile of mother and infant and allows differentiation between passive transmitted maternal antibodies and newly synthesized antibodies of the infant within the first 3 months of life. Over a 6-year period (1995-2001), the sera from 169 mothers and their 175 offspring (6 had twins) were examined for specific anti- Toxoplasma gondii IgG, IgM and IgA antibodies with an enzyme-linked immunosorbent assay or an immunosorbent agglutination assay. All mothers had primary Toxoplasma infection during pregnancy. Serological and clinical follow-up of the infants during the first year of life confirmed 36 cases of congenital toxoplasmosis. In 139 cases, infection could be ruled out. Three hundred fifty-one paired samples from 175 mother-child pairs were tested retrospectively for IgG and IgM patterns by Toxoplasma Western blot IgG/IgM (LDBIO Diagnostics, France). The results of conventional serological analysis (immunosorbent agglutination assay or enzyme-linked immunosorbent assay) to detect IgM or IgA were compared with the results of the Toxoplasma Western blot IgG/IgM on samples obtained within the first 3 months of life. The performance of the combination of the two methods was also assessed. At birth, the sensitivity values of conventional serological analysis and the Toxoplasma Western blot were 52% and 67%, with specificity values being 99% and 96%, respectively. Combination of the Western blot and conventional serological analysis increased the sensitivity at birth to 78% and within the first 3 months of life to 85%. Overall, the combination of both methods detected 94% of congenital infections. Therefore, this commercial Western blot represents a useful tool for early postnatal diagnosis of congenital toxoplasmosis.

Animals↗

On the interpretation of age-intensity profiles and dispersion patterns in parasitological surveys.

The present paper describes how age-intensity profiles of macroparasite burdens are affected by processes underlying the distribution of the parasite numbers in host populations. In a comparative way, we consider the following 6 processes: (i) age-dependent exposure, (ii) parasite-induced host mortality, (iii) heterogeneity within, the host population, (iv) clumped infection, (v) density-dependent parasite mortality and (vi) density-dependent parasite establishment. For each of these processes, we show typical patterns in the age-intensity profile and provide, if possible, explicit and simple solutions for the age-dependent mean parasite burden and the corresponding dispersion patterns. Emphasis is given to density-dependent parasite establishment and to age-intensity profiles resulting from the superposition of different processes. By means of 2 examples we show that the interpretation of observed patterns can be ambiguous if more than 1 process takes place. These findings underline that age-intensity profiles should be interpreted on the basis of available a priori knowledge about the processes assumed to be involved. For purposes of testing different hypotheses, a simulation program is provided with which discrepancies between model prediction and data can be explored.

Aging↗

Immunohistochemical and molecular biological investigations regarding the pathogenesis of extrahepatic biliary atresia. (Part 1: immunohistochemical studies).

INTRODUCTION: The pathogenetic model for biliary atresia presently most favored is that EHBA is the result of a peri- or postnatal bile duct lesion. Several authors demonstrated inflammatory infiltrations in the mesenchymal areas of the liver and thus concluded an infectious genesis. An association of rota-, reo- (and CMV) virus infection with EHBA was suspected, but the presence of these viruses in EHBA could not be reproduced. In view of this controversial debate we found it to be indicated to investigate tissue blocks from the porta hepatis and liver biopsies in children with EHBA by histo- and immunohistochemistry for the quality and quantity of leukocyte infiltrations. METHODS: 31 tissue excidates of the porta hepatis were gained on the occasion of hepatoportoenterostomy, fixed in 4 % buffered formalin and embedded in paraffin. The presence of leukocyte infiltrations and their subpopulations was demonstrated by histochemical reactions and immunohistochemical staining methods using specific antibodies against surface markers. The number of leukocytes and their subpopulations was counted in three different regions of the porta hepatis, the obliterated extrahepatic bile duct, the fibrous mass of the porta hepatis and the transition zone between the fibrous mass and liver parenchyma. A statistical analysis was done. RESULTS: In EHBA, leukocyte infiltrations consist mainly of macrophages. Antigen-presenting cells and lymphatic cells play a minor role. Lymphatic cells could only be detected in 6 out of 31 tissue preparations. Antigen-presenting cells could only be detected via anti-F13a antibody which shows cross-reactivities, i.e. against macrophages and embryonal tissue. Evaluating the density of leukocyte infiltrations with regard to the different anatomical regions of the porta hepatis we could demonstrate that leukocyte infiltrations are scarce around the rudiment of the bile duct whereas the highest leukocyte density could be found in the fibrous mass of the porta hepatis and the intrahepatic fibrous septs interconnecting the fibrous mass of the porta hepatis with liver parenchyma. Liver parenchyma was mainly free of leukocyte infiltrations with the exception of neutrophilic granulocytes. Regardless of the subpopulations, leukocytes were mainly arranged around the bile ducts of the fibrotic septa. CONCLUSIONS: Most tissue preparations from children operated on during the 4th-8th week of life show only small leukocyte infiltrations and in the majority of cases no immunocompetent lymphocytes. This leads to the conclusion that a virus infection as an underlying cause for EHBA is very unlikely. Most probably, the observed leukocyte infiltrations are due to an unspecific phagocytotic activity. Comparing our results to reports from Hadchouel et al (9) and Landing et al (12) led us to believe that a pathologic immunoreaction with a possible defective antigen elimination could also be considered as a reason for EHBA.

Antigens, CD↗

Estimation of the time-dependent vaccine efficacy from a measles epidemic.

We present a method to estimate the time-dependent vaccine efficacy from the cohort-specific vaccination coverage and from data on the vaccination status of cases and apply it to a measles epidemic in Germany which involved 529 cases, 88 of whom were vaccinated and 370 unvaccinated (for the remaining 71 cases the vaccination status is unknown). Our epidemiological model takes into account that maternal antibodies prevent successful vaccination and that vaccine immunity may be lost over time. Model parameters are estimated from the data using maximum likelihood. Vaccination coverage, as determined in school surveys, ranged from 27.6 per cent for the cohort born in 1974 to 85 per cent for the 1986 cohort, which is far too low to prevent measles transmission. Cohorts for which no school surveys were performed are omitted from analysis. Thus, sufficient data are available for only 282 cases, 69 of whom are vaccinated. According to our estimates, measles vaccinations provided no immunity before 1978 (95 per cent CI: 0 to 47 percent), for the period 1978-1982, the estimated vaccine efficacy was 80 percent (95 percent CI: 67 to 89 percent), and for 1982-1990 it was 97 percent (95 percent CI: 93 to 99 percent). After 1990, the estimated value dropped to 89 per cent, but its confidence interval widely overlaps with that of the previous period (95 percent CI: 74 to 97 percent). Loss of immunity was estimated to be zero (95 percent CI: 0 to 0.003/year). Several sensitivity analyses were performed with respect to the model assumptions. A modified model which assumed constant efficacy at all vaccination times yielded a high estimate of 96 per cent (95 percent CI: 92 to 98 percent) for primary vaccine efficacy but also a high loss rate of immunity of 0.007/year (95 percent CI: 0.001 to 0.012) to explain the high fraction of vaccinated cases among older individuals. The likelihood score value is however significantly inferior compared to the score value of the model with time-dependent vaccine efficacy.

Child↗

The problem of long-term ICP drift assessment: improvement by use of the ICP drift index.

BACKGROUND: Intracranial pressure (ICP) monitoring is dependent on the precise measurement of absolute pressures and low drifts of the different transducers in use. Our investigations have shown that probes sometimes appear to reveal positive and negative drifts consecutively. There is no regard for any of these important pressure changes by the mere result of the traditional drift. Therefore, we have developed a more precise way of assessing the behavior of the ICP drift. METHOD: A special laboratory set up for the simulation of constant pressures, at definite temperatures, was designed. We examined the Camino-110-4B, Gaeltec ICT/B, HanniSet and Spiegelberg transducers. Drift index is a new term that has been developed by our group to provide a better description of the actual pressure changes over long-term measurement. The drift index consists of three parameters: the percentage of measurements which show a pressure change during the 10 days of measurement; the maximum absolute pressure deviation that occurred during a ten day measurement; and the mean absolute pressure deviation during a 10 day measurement. FINDINGS: The median proportion of pressure changes during ten days were: Camino: 1.59%; Gaeltec: 0.71%; HanniSet: 0.08%; Spiegelberg: 4.00%; The median maximum absolute pressure changes were 6; 9.5; 1; and 11 mmHg for the four types and the median mean absolute pressure changes were 2.9; 5.1; 0; and 2.4 mmHg, respectively. The median 10 day classical drift in each type of transducer was 4; 9; 0; and 2 mmHg, respectively. INTERPRETATION: We recommend the use of the drift index to be used by manufacturers. This is an additional vital parameter in order to improve ICP measurement accuracy and the proficiency of ICP monitoring.

Equipment Design↗

Reduced red blood cell deformability, an indicator for high fetal or maternal risk, is found in preeclampsia and IUGR.

OBJECTIVE: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. MATERIAL AND METHODS: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. RESULTS: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. CONCLUSION: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.

Adult↗

Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three consecutive studies.

Certain epidemiological and experimental studies raised concerns about the safety of radiofrequency (RF) electromagnetic fields because of a possible increased risk of leukemia and lymphoma. In this study, an RF field used in mobile telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats as a model for human breast cancer. Three experiments were carried out under strictly standardized conditions and were started on the same day of three consecutive years. The field consisted of a GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively low power flux density (100 microW/cm(2) +/- 3 dB) and was applied continuously throughout each experiment to freely moving animals. The specific absorption rates averaged over the whole body were 17.5-70 mW/kg. The highest values in young animals were at or around the exposure limit permissible for the general public (i.e. 80 mW/kg). The animals were palpated weekly for the presence of mammary tumors and were killed humanely when tumors reached a diameter of 1-2 cm to allow a reliable histopathological classification and a distinction between malignant and benign subtypes. The overall results of the three studies are that there was no statistically significant effect of RF-field exposure on tumor latency and that the cumulative tumor incidence at the end of the experiment was unaffected as well. The risk ratios were 1.08 (95% CI: 0.91-1.29) and 0.96 (95% CI: 0.85-1.07) for benign and malignant tumors, respectively. These observations are in agreement with other published findings. In the first experiment, however, the median latency for the development of the first malignant tumor in each animal was statistically significantly extended for RF-field-exposed animals compared to controls (278 days compared to 145 days, P = 0.009). No such differences were detected in the two subsequent experiments. These results show that low-level RF radiation does not appear to possess carcinogenic or cancer-promoting effects on DMBA-induced mammary tumors. To explain the mechanisms underlying the different results obtained in the three experiments, a hypothesis is presented which is based upon the neuroendocrine control mechanisms involved in the promotion of DMBA-induced mammary tumors. Despite the apparent absence of stimulatory effects of low-level RF-field exposure on the development and growth of solid tumors, it will be necessary to verify these results for leukemias and lymphomas, which may have completely different biological control mechanisms.

9,10-Dimethyl-1,2-benzanthracene↗

Cytomegalovirus infection of extremely low-birth weight infants via breast milk.

In addition to seroprevalence and transmission rate, the clinical symptoms of postnatal cytomegalovirus (CMV) infection in infants with a very low birth weight (VLBW; <1500 g; <32 weeks gestational age at birth) were assessed in a 3-year prospective study. CMV monitoring included serologic testing (of the mother and child) and virus culture and PCR (of samples of both breast milk and the infant's urine). Within 3 weeks of the initial virus detection in the infant, clinical and laboratory parameters were evaluated. Of 170 infants, no CMV transmission was found in the 80 infants of seronegative mothers and in the 3 infants of seropositive mothers who did not shed CMV DNA into breast milk. Transmission occurred in 33 of the 87 CMV-exposed infants, 16 of whom presented with such symptoms as hepatopathy, neutropenia, thrombocytopenia, and sepsis-like deterioration. Low birth weight and early postnatal virus transmission were risk factors for symptomatic infection. VLBW infants of CMV-seropositive mothers are at high risk of acquiring a symptomatic CMV infection postnatally via breast milk.

Cytomegalovirus Infections↗

Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding.

BACKGROUND: Breastfeeding practices strongly influence the epidemiology of human cytomegalovirus infection. By contrast with term neonates, few data are available on transmission of infection from mothers to preterm infants during breastfeeding. METHODS: 151 mothers and their 176 preterm infants (gestational age at birth <32 weeks or birthweight <1500 g) were prospectively screened for cytomegalovirus infection by serology, virus culture, and PCR. The roles of cell-free and cell-associated cytomegalovirus excretion during lactation were analysed longitudinally in relation to transmission, by maximum-likelihood estimates. FINDINGS: Of the 69 seronegative breastfeeding control mothers, none had detectable cytomegalovirus DNA in breastmilk and none of their 80 infants shed the virus in urine. The proportion of cytomegalovirus reactivation in seropositive breastfeeding mothers was 96% (73 of 76). The early appearance of viral DNA in milk whey (median 3.5 days post partum in transmitters; 8 days in non-transmitters; p=0.025) and infectious virus in milk whey (10 days and 16 days, respectively; p=0.005) were risk factors for transmission. The cumulative rate of transmission was 37% (27 of 73 mothers; 33 infants). The infection of the neonates had a mean incubation time of 42 days (95% CI 28-69). About 50% of the infected infants had no symptoms, but four had sepsis-like symptoms. INTERPRETATION: The proportion of cytomegalovirus reactivation during lactation almost equals maternal seroprevalence. Breastfeeding as a source of postnatal cytomegalovirus infection in preterm infants has been underestimated and may be associated with a symptomatic infection.

Breast Feeding↗

Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude.

Although microglia are considered to be a sensitive sensor for pathological processes in the central nervous system, there are only a few studies about the distribution and density of microglia in the normal human brain. Therefore, a study of local density of microglial cells was conducted by investigating 20 normal human brains with no clinical neurological symptoms or diseases and no neuropathological alterations. Microglial cells were visualized by immunolabeling of proteins which are known to be expressed either constitutively or facultatively, such as CD68, major histocompatibility complex class II (MHC-II), leukocyte common antigen (LCA), leukocyte chemotactic factor (LCF), macrophage inhibitory factor-related protein (MRP) 8, MRP14, CD4 and allograft-inflammatory factor-1 (AIF-1). CD68, MHC-II and AIF-1 showed the highest densities with significant regional differences ranging from 0.5% to 16.6% of all cells in the brain parenchyma with significantly more microglia in white than in gray matter. LCF and LCA showed a similar pattern of distribution as the proteins described above, but with lower percentages of microglial cells. CD4 was not found in the brain parenchyma. We conclude that CD68, MHC-II and AIF-1 define the main microglial cell population, whereas LCF and LCA are expressed by a subpopulation of microglial cells. The brains showed no or a negligible vascular expression of MRP8 and MRP14. Information about the local microglia density in the normal human brain can serve as a reference for the evaluation of pathological microglial responses.

Adult↗

The relevance of stereopsis for motorists: a pilot study.

PURPOSE: To study the influence of stereoscopic depth perception on automobile driving performance. METHODS: Ten patients with strabismus and defective stereopsis were compared with ten healthy controls with respect to their performance in a series of automobile driving manoeuvres. The two groups were individually matched as to age, annual miles driven, years of licence holding and type of vehicle owned. After an ophthalmologic examination the subjects in each group performed the following series of driving tests: (1) stopping in front of an obstacle, (2) reversing into a parking space, (3) driving through a slalom course, (4) estimating the relative positions of two cars. All tests were performed binocularly and monocularly (with the non-dominant eye covered). RESULTS: Only in the slalom test did the normal subjects perform significantly better than the stereo-deficient subjects (odds ratio 10.5; P<0.01). In estimating position, normal subjects actually performed significantly worse (odds ratio 0.091; P<0.01). A significant distance ratio of 2.5 (95% CI 1.1-5.5; P=0.033) of the monocular with respect to the binocular performance of the normal subjects was found for the stopping task only, while the subjects with defective stereopsis showed no difference between their monocular and binocular performance. CONCLUSION: In this study, stereopsis had a positive effect on driving performance only in dynamic situations at intermediate distances.

Adult↗

Plasmodium falciparum: in vitro growth inhibition by febrile temperatures.

Febrile episodes are the hallmark of malarial infection. We determined the inhibitory effect of febrile temperatures on the in vitro growth of Plasmodium falciparum. Parasites were cultured at various temperatures between 37 degrees C and 40 degrees C for 4 days. A logistic decrease in parasitaemia as a function of temperature was observed for continuous cultures. Incubation of synchronized cultures for different lengths of time during the parasite cycle showed a strong increase of growth inhibition with the maturing of parasites. Febrile temperatures inhibit parasite growth and long, high fevers during malaria may be beneficial for parasite clearance.

Animals↗

Plasmodium falciparum parasitaemia described by a new mathematical model.

A new mathematical model of Plasmodium falciparum asexual parasitaemia is formulated and fitted to 35 malaria therapy cases making a spontaneous recovery after primary inoculation. Observed and simulated case-histories are compared with respect to 9 descriptive statistics. The simulated courses of parasitaemia are more realistic than any previously published. The model uses a discrete time-step of 2 days. Its realistic behaviour was achieved by the following combination of features (i) intra-clonal antigenic variation, (ii) large variations of the variants' baseline growth rate, depending on both variant and case, (iii) innate autoregulation of the asexual parasite density, variable among cases, (iv) acquired variant-specific immunity and (v) acquired variant-transcending immunity, variable among cases. Aspects of the model's internal behaviour, concerning variant dynamics, as well as the respective contributions of the three control mechanisms (iii) - (v), are displayed. Some implications for pathogenesis and control are discussed.

Animals↗

A stochastic model for the aggregation of Onchocerca volvulus in nodules.

A model is presented which describes the aggregation of female Onchocerca volvulus in nodules and their distribution in the human population. The basic model is based on a single parameter, the formation probability q, which represents the probability with which incoming larvae form a new nodule. This parameter describes parasite behaviour which cannot easily be recognized in available data without modelling. The estimate for the average formation probability of muq = 0.39 suggests an attraction of the invading infective larvae to already existing nodules or resident worms with probability 0.61. No significant difference in muq was found between the forest and savanna parasite strains. The model can be used inversely to estimate the worm burden of persons from palpation data. The observed variance in the number of nodules per person requires the assumption of a variance-increasing mechanism which was implemented by heterogeneity within the host population (extended model with 2 parameters). Possible reasons for this heterogeneity are presented and its implications concerning the reproductive biology of the parasite are discussed.

Animals↗