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Biomedical subjects

A Spiegel

Publications and source records attributed to A Spiegel.

At least 37 records · Page 2Linked to original sources

[Diagnosis of malaria attacks in endemic areas: theoretical aspects and practical implications].

What criteria can be used to diagnose malaria in health centers located in endemic areas? Can an algorithm be developed for management of fever episodes? What parameters should be used to assess the morbidity of malaria for public health surveys or for studies to determine the efficacy insecticide-impregnated bednets, drug prophylaxis protocols, or anti-malarial vaccinations? Finding a useful definition for malaria attack is a perennial problem that becomes more difficult to resolve as the transmission rate and immunity level of the population increases. This review presents the fundamental aspects of diagnosing malaria. The choice of diagnostic technique requires knowledge of physiopathological, epidemiological, and clinical features. There is no single method. It depends on the circumstances, epidemiological context, available facilities, and goals. Diagnosis for treatment is one thing. Diagnosis for evaluation is another. In addition to discussing these concepts, this article provides references from the recent literature and up-to-date information needed to deal with the problem of diagnosing malaria attacks in endemic areas.

Diagnosis, Differential↗

[Disease vector control strategy in the French army].

Disease vector control is a major priority for the Medical Health Corps of the French Armed Forces which maintains around 23,000 troops in tropical areas and is involved in numerous military and humanitarian missions throughout the world. Control strategy includes both general and personal control measures. Personal control measures include wearing permetherin-impregnated combat uniforms, application of repellents to the skin, and use of deltamethrin-impregnated bednets. General measures are implemented in facilities and in the environment. Measures in facilities include not only physical deterrents such as screens on openings and air-conditioning but also application of chemical insecticides to walls, curtains, and screening. Environmental measures include control of larval deposits and elimination of potential breeding areas. Low-volume wide-area spraying of imagocides is a supplemental option used in case of disease outbreak. For units stationed in tropical areas, command and surveillance of vector control operations is under the responsibility of the mosquito control committee which includes personnel from the affected field unit. Strategies are chosen in function of local climate and operational conditions. The efficacy of vector control programs is assessed annually by reviewing the incidence in armed forces personnel of the main vector-transmitted diseases: malaria, dengue fever, and leishmaniasis. Documentation and training are dispensed to all units stationed in tropical areas. To ensure that knowledge of military physicians remains current, three courses on malaria control are offered each year at the Tropical Medicine Institute of the Armed Forces Health Corps (Le Pharo) in Marseille. Field research conducted in collaboration with military or civilian organizations independent of the Armed Services Health Corps makes it possible to keep chiefs of staff informed of state-of-the art vector control measures adapted to use by personnel on assignment or mission in tropical areas.

Animals↗

Bayesian analysis of an epidemiologic model of Plasmodium falciparum malaria infection in Ndiop, Senegal.

Plasmodium falciparum has a complex transmission cycle. Public health planning and research would benefit from the ability of a calibrated model to predict the epidemiologic characteristics of populations living in areas of malaria endemicity. This paper describes the application of Bayesian calibration to a malaria transmission model using longitudinal data gathered from 176 subjects in Ndiop, Senegal, from July 1, 1993, to July 31, 1994. The model was able to adequately predict P. falciparum parasitemia prevalence in the study population. Further insight into the dynamics of malaria in Ndiop was provided. During the dry season, the estimated fraction of nonimmune subjects goes down to 20% and then increases up to 80%. The model-predicted time-weighted average incidences contributed by nonimmune and immune individuals are 0.52 cases per day and 0.47 cases per day, respectively. The median times needed to acquire infection (conversion delay) for nonimmune and immune individuals are estimated at 39 days and 285 days, respectively.

Adolescent↗

Increased susceptibility to malaria during the early postpartum period.

BACKGROUND: Pregnancy is associated with increased susceptibility to malaria. It is generally agreed that this increased risk ends with delivery, but the possible persistence of increased susceptibility during the puerperium had not been investigated. METHODS: From June 1, 1990, to December 31, 1998, we monitored exposure to malaria, parasitemia, and morbidity among the residents of a village in Senegal in which the rate of transmission of malaria was high. In this population we analyzed 71 pregnancies in 38 women from the year before conception and through one year after delivery. RESULTS: Among the 38 women, there were 58 episodes of clinical Plasmodium falciparum malaria during 61,081 person-days of observation. The incidence of malaria was 20.2 episodes per 1000 person-months during the year preceding conception and 12.0 episodes per 1000 person-months during the period from 91 to 365 days after delivery. The incidence of episodes of malaria increased significantly during the second and third trimesters of pregnancy and reached a maximum of 75.1 episodes per 1000 person-months during the first 60 days after delivery. The adjusted relative risk of an episode of malaria was 4.1 (95 percent confidence interval, 1.8 to 9.5) during the first 60 days post partum, as compared with the year preceding pregnancy. The duration of fever during the episodes of malaria was longer and the prevalence and density of asymptomatic malarial parasitemia were significantly higher during pregnancy and the early postpartum period than during the other periods. CONCLUSIONS: Among women who live in areas with high rates of transmission of malaria, the susceptibility to malaria is highest during the second and third trimesters of pregnancy and the early postpartum period.

Adolescent↗

Effects of MPEG compression on the quality and diagnostic accuracy of digital echocardiography studies.

The advantages of digital echocardiography studies include ease of retrieval, review, comparison, duplication, and quantitation as well as the potential for moving studies over networks. However, the large amounts of data associated with digital echocardiography studies have posed new problems. Reduction of the amount of data can be accomplished with image compression, in particular MPEG-1 (Moving Pictures Expert Group), which is designed for dynamic image sequences. However the effects of different levels of compression on the quality and diagnostic content of echocardiographic images need to be established. Digital sequences of single cardiac cycles were acquired in 40 consecutive patients, MPEG-1-compressed at different effective ratios (60:1, 80:1, 120:1, 200:1, 300:1, 370:1, 500:1), reviewed, and scored for endocardial visualization. The overall visualization scores and percentages of nonvisualized segments in the compressed images were not different from the uncompressed images up to a compression ratio of 200:1. Differential effects of compression were noted on a segmental basis and also varied with baseline image quality. The ability to correctly identify regional wall motion abnormalities did not decrease until compression ratios of 1:200 or higher were used. Digital echocardiography loops, MPEG-1-compressed at an effective ratio of 200:1, demonstrate no degradation in endocardial visualization quality or diagnostic content. Compression at this ratio has the potential to reduce the storage size of digital echocardiography studies to less than 1% of their current size.

Echocardiography↗

Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection.

In endemic areas, asymptomatic infection by the malaria parasite Plasmodium falciparum was found associated with elevated percentages of human host's mononuclear cell spontaneous in-vitro apoptosis. In Dielmo, a village where malaria is holoendemic, apoptosis was age-and parasite-dependent. In-vitro exposure of peripheral blood mononuclear cells (PBMC) to the parasite extract induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-CD95 antibodies led to a detectable increase in the mean percentage of apoptotic nuclei found in the cultures carried out in the presence of P. falciparum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promoted the viability of PBMC in cultures while IL-1alpha or IFN-gamma had no obvious impact and TNFalpha gave conflicting results. IL-2 was the most efficient cytokine at rescuing PBMC from cell death and this effect was associated with a strong increase in T cell activation. In contrast, IL-4 and IL-10 had no such effect on T cell activation, hence they acted as survival factors and not through their mitogenic activity. Taken together, these different observations suggested that the levels of in-vitro apoptosis observed were not only associated with parasite infection, but also potentially modulated by the human host through different pathways.

Animals↗

Epidemiological and virological influenza survey in Dakar, Senegal: 1996-1998.

An influenza survey was conducted in seven sentinel sites in Dakar, Senegal from June 1996 to December 1998. Throat or nasal swab cultures were randomly collected from 804 patients suffering from influenza-like symptoms. Influenza viruses were isolated at a similar proportion in adults and in children (P = 0.29). Strains of influenza B viruses were isolated from sporadic cases in 1997, whereas type A virus was associated with an isolated peak. Proportions of influenza virus isolation varied from 17.5% to 40.0% between 1996 and 1998 during the peak period (July/September) of acute respiratory infection in Dakar. Rainfall, humidity, and temperatures rose during the same period. Influenza in Dakar seems to be an-all-age groups respiratory infection characterized by high transmission during the hot and rainy season. The antigenic similarity of the A(H3N2) and B viruses to those circulating elsewhere in the world at the same time was confirmed. However, the A(H1N1) strains were found to be more closely related to an Asiatic strain which had not been isolated outside Asia previously. Consequently, the strain close to the A(H1N1)/Wuhan/371/95 strain isolated in Dakar was included in the composition of the 1998/1999 influenza vaccine. This reinforces the importance of setting up a national influenza control strategy in tropical regions.

Adolescent↗

Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

The recombinant R23, PfEB200, and GST-5 antigens derive from conserved antigens associated with the Plasmodium falciparum-infected erythrocyte membrane. They were identified as targets of protective antibodies in the Saimiri sciureus model. We have assessed here the humoral response to these antigens in humans. Cross-sectional surveys were conducted in two Senegalese villages with different levels of endemicity. The prevalence of specific IgG and IgM was similar and influenced by age in both localities. The anti-R23 antibodies decreased after the rainy season, particularly in the children less than ten years old. The anti-PfEB200 response did not show significant seasonal variation. The anti-GST-5 response increased in both the less-than 10-year-old and the greater-than 10-year-old groups after the rainy season in Dielmo, but only in the Ndiop villagers who were more than 10-years-old. Thus, antigen-specific seasonal variations of antibody levels were influenced differently by age in both villages. The isotype distribution was antigen-specific and differed for both seasons.

Adolescent↗

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM). The activity of doxycycline did not differ significantly (P = 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.

Amodiaquine↗

[Microbiological quality of street-vendor ice cream in Dakar].

During a multicenter study initiated by the International Network of Pasteur Institutes and Associated Institutes, microbiological quality of street-vended ice creams in Dakar was evaluated. 313 samples of ice creams from 170 street-vendors were collected and tested for common foodborne pathogens and indicator organisms. Results showed that microbiological quality of 45% of tested samples was unsatisfactory because of large populations of aerobic mesophilic organisms (36.7%), thermotolerant coliforms bacteria (21.4%) and sometimes E. coli. (10.6%). Strict pathogens as Salmonella, Shigella and Vibrio cholerae were not found. An investigation conducted among vendors showed a lack of education and training; these vendors need information about food preparation and storage practices that reduce microbiological contamination of foods.

Adolescent↗

[Specific antibodies to Plasmodium falciparum antigens in immune patients: IV--Cross-sectional analysis of anti-P. falciparum Ab responses in a mesoendemic zone of transmission in Sine-Saloum region].

We report here a comparative study of specific antibody responses to blood stages of P. falciparum in 100 individuals aged from 3 to 76 years, living in the village of Ndiop (an area where parasite transmission is approximately 20 infective bites per year). We have used 2 antigen preparations: crude merozoites and infected erythrocyte ghosts (GRp). High specific antibody responses were found in the villagers' sera, with IgG levels being significantly higher than those directed to the whole P. falciparum schizont Ag preparation; the reverse was found for IgM responses. An imbalanced IgG subclass Ab response was evidenced towards cytophilic IgG1+/gG3+ responses rather than to IgG2+/lgG4+. Mean levels of antibodies increased significantly with age and a strong relationship was evidenced in individual levels of Ab responses towards all the Ag studied. Investigation of the morbidity, recorded as the number of confirmed clinical accesses, underlined a significant inverse relationship only with the levels of IgG to GRp. Taken together, these results proved usefullness of crude P. falciparum Ags for immuno-epidemiological related studies and underlined GRp as a particular target of Ab responses.

Adolescent↗

Flow cytometric analysis of IgG reactive to parasitized red blood cell membrane antigens in Plasmodium falciparum-immune individuals.

Antigens exposed at the surface of Plasmodium falciparum parasitized red blood cells (pRBCs) represent potential targets for protective antibodies involved in opsonization and immune phagocytosis of pRBCs. We measured the recognition of parasitized red blood cell membrane associated antigens by IgG in the plasma of clinically immune individuals by flow cytometry and ELISA. The plasmas were selected on the basis of preexisting IgG antibodies to pRBC membrane associated recombinant proteins. In every plasma sample IgG could bind the surface of live pRBCs in flow cytometry. In addition, there was a significant correlation between the level of IgG recognition of live pRBCs and of pRBC membrane ghost proteins or major identified antigens by ELISA. Flow cytometry thus represents a technique suitable to test for the accessibility and potential functionality of IgG antibodies directed to antigens expressed by the surface of pRBCs.

Adolescent↗

Immune responses to P. falciparum-MSP1 antigen: lack of correlation between antibody responses and the capacity of peripheral cellular immune effectors to respond to this antigen in vitro.

Protective immunity to P. falciparum blood stage infection is thought to be dependent on IgG antibodies, although the mechanisms that underlie such immunity are not clearly understood. One of the antigens thought to be involved in this protective response is MSP1. The present study has examined the levels and distribution of IgG (and IgM) antibodies to the C-terminal 19 kDa fragment of MSP1 in plasma from P. falciparum immune adult Senegalese and the capacity of the peripheral blood mononuclear cells from these patients to either proliferate or secrete IFN-gamma, IL-10 or IL-4 in vitro in response to this antigen. Specific antibodies were found in 74% of individuals' plasma; 44% of mononuclear cells proved capable of proliferating in vitro and IFN-gamma, IL-10 and IL-4 were detected in 37, 23 and 0% of culture supernatants, respectively. No significant association was found between the presence of antibodies and immune cell reactivity under the culture conditions used. This study emphasizes the complexity of the mechanisms responsible for the sustained production of potentially protective antibodies in response to proposed T-cell dependent P. falciparum blood stage antigens.

Adult↗

Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions.

To investigate the impact of transmission on the development of immunity to malaria and on parasite diversity, longitudinal surveys have been conducted for several years in Dielmo and Ndiop, 2 neighbouring Senegalese villages with holo- and mesoendemic transmission conditions, respectively. We analysed Plasmodium falciparum msp1 block 2 and msp2 genotypes of isolates collected from 58% of the Dielmo villagers during the same week as those studied recently from Ndiop. Allele frequencies differed in both villages, indicating considerable microgeographical heterogeneity of parasite populations. The complexity of the infections, estimated using individual or combined msp1 and msp2 genotyping, in Dielmo was more than double that in Ndiop and it was age-dependent in Dielmo but not in Ndiop. Thus, this study confirmed the influence of age on the complexity of asymptomatic malaria infections in a holoendemic area. The age distribution of complexity in Dielmo substantiates the interpretation that the number of parasite types per isolate reflects acquired antiparasite immunity. This cross-sectional survey also confirms that the sickle cell trait has no impact on complexity but influences the distribution of P. falciparum genotypes.

Adolescent↗

Objective evaluation of regional left ventricular wall motion during dobutamine stress echocardiographic studies using segmental analysis of color kinesis images.

OBJECTIVES: To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND: Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS: CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patient's data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segment's response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS: The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS: Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography.

Aged↗

Secretion of parasite-specific immunoglobulin G by purified blood B lymphocytes from immune individuals after in vitro stimulation with recombinant Plasmodium falciparum merozoite surface protein-119 antigen.

The C-terminal 19 000 MW fragment of merozoite surface protein-1 (MSP119) is one of the most promising candidate antigens for a malaria vaccine. Baculovirus recombinant Plasmodium falciparum MSP119 has been used to define conditions for the in vitro production of specific antibodies by purified human blood B cells in a culture system where T-cell signals were provided by the engagement of CD40 molecules and exogenous cytokines. MSP119 preferentially induced surface immunoglobulin G (IgG) -positive (sgamma+) B lymphocytes from P. falciparum-immune donors to differentiate and produce antigen-specific IgG. In contrast, naïve B cells or cells from non-immune donors could not be induced to secrete parasite-specific IgG in vitro. Although IgG secretion was obtained in the absence of exogenous cytokines, it was dependent on B-cell-derived interleukin-10 (IL-10) and/or B-cell factor(s) under the control of IL-10, since IgG levels were significantly decreased in the presence of neutralizing anti-IL-10 antibodies. These results demonstrate at the cellular level that a single malaria vaccine candidate polypeptide can direct parasite-specific antibody production mediated by the secretion of potentiating factors.

Adult↗