Search PubMed⌕ Search

Biomedical subjects

A Spiegel

Publications and source records attributed to A Spiegel.

At least 55 records · Page 3Linked to original sources
PubMed1999

In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs.

The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak correlations in the responses to benflumetol and pyrimethamine, chloroquine, amodiaquine, artemether, quinine, and pyronaridine were observed, and these correlations are insufficient to suggest cross-resistance. Benflumetol may be an important alternative drug for the treatment of chloroquine-resistant malaria.

Animals↗
PubMed1999

[Chikungunya virus outbreak in Senegal in 1996 and 1997].

Chikungunya disease is generally recognized in Africa by serosurveys conducted in rural areas. Epidemics are rarely documented. We report two outbreaks in Senegal: one having occurred near Kaffrine in 1996 during an epidemic of yellow fever (YF), the second in Niakhar in 1997. Both diagnoses were conducted by IgM antibodies captures and confirmed by virus isolations. In Kaffrine, a randomised study was carried out on 447 blood donors whose serum was systematically tested for the most frequently encountered arboviruses in Senegal. The incidence rate was higher for the unrecognized Chikungunya infection (35.3%) than for the notified YF infection (21%). In Niakhar, Chikungunya infection was initially detected through three cases having occurred in health workers. A serosurvey was then conducted to define the area of prevalence. We report the clinical forms of Chikungunya virus infections, the interest in detecting IgM for recent arbovirus infections and the duration of these IgM. The difficulties of diagnosis of Chikungunya infection in malaria endemic areas are stressed. The occurrence of arbovirus infections, Yellow fever and Chikungunya viruses, transmitted by the same vectors (Aedes aegypti) in Kaffrine are also discussed.

Aedes↗
PubMed1999

Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal.

Development of new antimalaria strategies and particularly vaccines, needs an in-depth understanding of the relationships between transmission, infection, immunity, morbidity and mortality. The intensive and longitudinal collection of entomological, parasitological and clinical data from the Senegalese populations of Dielmo (250-300 inhabitants), exposed to a perennial and intense transmission (about 200 infective bites/person/year) and of Ndiop (300-350 inhabitants) exposed to a seasonal transmission (about 20 infective bites/person/year), allows to respond to many questions about this subject. The acquisition of an antimalaria immunity as one gets older appears to reduce parasite density, complexity of infection, risk of new patent infection after a suppressive treatment but does not reduce the prevalence (as assessed by PCR) of infection which is commonly chronic and asymptomatic. The existence of a pyrogenic threshold effect of parasitaemia allows the individual diagnosis of malaria attacks. P. falciparum genotyping suggests that successive malaria attacks are due to distinct recently inoculated parasite populations that multiply initially without restriction, a dominant population is generally responsible of the clinical manifestations and all new populations do not trigger systematically attacks. The initial intensity of clinical manifestations does not differ perceptibly among children and adults, is not related to the duration of the attacks, does not allow the distinction between several types of attacks, is not predictive of their severity, and the clearance of parasites and manifestations is longer among youngest persons. The risk of malaria attacks is lower as one gets older and among carriers of AS haemoglobin, is higher when transmission increases and during pregnancy up to three months after delivery, and vary between children. The risk of malaria attack per infective bite is negatively related to the intensity of transmission. Because of their high sensitivity in malaria case detection, this type of small community-based studies are powerful and useful for the identification of protective immunological mechanisms as well as for testing rapidly and cheaply the clinical efficacy of any intervention such as antimalarial vaccines and drug therapy or prophylaxis. As a lot of vaccine candidates and drug combinations will be screened or tested in the perspective of the 'Roll-Back Malaria' programme, more attention must be given to longitudinal studies of this type.

Adult↗
PubMed1999

[HLA-DQ allele typing in a Senegalese population: comparative study of serology and PCR-SSP].

In this study, we compared the serological standard typing method and the DNA genotyping PCR-SSP for the characterization of HLA-DQ alleles in a senegalese population. For this purpose, 120 individuals leaving in Dielmo were typed using the microlymphocytotoxicity assay and the PCR-SSP DQ low Resolution method. A discordance of 42.5% (51/120) was found between these two methods. Thirty % (36/120) of serological typed persons failed to be typed by PCR-SSP method whereas 1% (1/120) assigned by PCR-SSP failed to be characterized by serology. Advantages and limits of these two typing methods and also the genetic background of our study population were valid arguments to comment our findings. The PCR-SSP, as suggested by several authors, is reliable, accurate and fast for HLA class II alleles characterization. Nevertheless, it needs, to become an alternative HLA typing method, available primers adapted to genetic background of study population.

Alleles↗
PubMed1999

[Antibodies specific to Plasmodium falciparum antigens in immune individuals: III. Seasonal course of the response to a major antigen of the asexual blood forms in two sites of different malaria exposure].

Specific IgG1 and IgG3 antibody responses to a major Plasmodium falciparum blood stage antigen i.e. MSP1 have been measured in plasma obtained from immune individuals living in areas with different endemicities and sampled at different periods corresponding to different levels of parasite transmission. The study shows a significant imbalance between IgG1 and IgG3 antibody responses in Dielmo vs. Ndiop, and a differential regulation of IgG1 and IgG3 responses both in subclasses and in titers (low: 1/200, and high: 1/2,000) depending upon intensity of parasite exposure.

Animals↗
PubMed1998

Imbalanced distribution of IgM and IgG antibodies against Plasmodium falciparum antigens and merozoite surface protein-1 (MSP1) in pregnancy.

In malaria endemic areas, pregnancy is assumed to be associated with a specific reduction in immunity to Plasmodium falciparum malaria. To understand some of the mechanisms which underlie such a poor immunity, we have attempted to examine the frequency and distribution of IgM and IgG antibodies to a crude antigenic extract of parasitized erythrocytes and to the merozoite surface protein-1 (MSP1), in a population of mothers compared to control non-pregnant women, all living in Dakar and suburbs. Specifically, this work describes: (i) the responses of mothers and control women; (ii) the balance between IgM and IgG responses; and (iii) responses to malarial antigen and to MSP1. An unexpected balance between P. falciparum-specific IgM and IgG is shown, associated with a substantial increase in anti-MSP1 IgM, and a decrease in anti-MSP1 IgG in parturients.

Animals↗
PubMed1998

Yellow fever outbreak in Kaffrine, Senegal 1996: epidemiological and entomological findings.

In November 1996 a yellow fever (YF) outbreak occurred near Kaffrine in the central part of Senegal. Thirty-six deaths were notified, all children under 15 years of age. The YF diagnosis was confirmed by MAC-ELISA or by virus isolation. The immune status against YF virus of a sample population of 449 individuals was determined, and 31 confirmed cases and 69 asymptomatic cases were reported. Distribution of YF cases and incidence rate decreased with age, while the attack rate was stable in all age groups. Larva indices were high and Aedes aegypti was common in all villages, causing man-to-man transmission. The greatest risk of YF disease was lack of immunity, especially in individuals <20 years of age. The outbreak was rapidly controlled by an emergency immunization campaign. YF epidemics occurred in Senegal over two consecutive years. The last outbreak reached the main road to Dakar and the risk of spread to urban areas has increased.

Adolescent↗
PubMed1998

[Comparative evaluation of the plasmodial infection of Anopheles using ELISA and dissection. Consequences for the estimation of the transmission of malaria in 1995 in Ndiop, Senegal].

An entomological study was carried out in Ndiop village, Senegal, an area of sudan-type savana, from January to December 1995, to compare the malaria inoculation rate measured by the dissection of salivary glands of anophelines and the enzyme-linked immunosorbent assay (ELISA). Mosquitoes were sampled by night-bite collections. Species from the Anopheles gambiae complex were identified using the polymerase chain reaction. 1292 females Culicidae were collected. 597 anophelines mosquitoes known to be malaria vectors were captured during 148 man-nights of capture. Of the 572 anophelines investigated, 14 were positive using dissection while 21 were found to be positive with ELISA. The sporozoite rates were 2.5%, 2.2% and 3.8% for An. arabiensis, An. gambiae and An. funestus, respectively. The circumsporozoite rates were 3.5%, 2.2% and 7.7% for these three species, respectively. ELISA detected 1.5 times more positive mosquitoes than dissection. These results are discussed with reference to the duration of the sporogonic cycle, the delay before CSP antigens are apparent, and the daily survival rate of Anopheles mosquitoes.

Animals↗
PubMed1998

In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents.

The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum from Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentration) for pyronaridine and amodiaquine were 3.8 nM (95% confidence interval (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectively. Pyronaridine and amodiaquine were more active than chloroquine against susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolates than against chloroquine-susceptible isolates. Based on statistical calculation using the present data (mean IC50 + 2 S.D.), the cut-off value for in-vitro susceptibility to pyronaridine is IC50 < 15 nM; for eight isolates (5%) the IC50 was > 15 nM. No isolates tested showed resistance to amodiaquine (IC50 > 80 nM). Significant positive correlations, suggesting cross-resistance among these drugs in vitro, were found between pyronaridine and chloroquine (r2 = 0.19, P < 0.001), pyronaridine and quinine (r2 = 0.44, P < 0.001), pyronaridine and amodiaquine (r2 = 0.34, P < 0.001), amodiaquine and chloroquine (r2 = 0.14, P < 0.001), and amodiaquine and quinine (r2 = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.

Africa↗
PubMed1996

A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma.

OBJECTIVES: The authors evaluate the results of preoperative imaging protocols and surgical re-exploration in a series of patients with missed parathyroid adenomas after failed procedures for primary hyperparathyroidism. BACKGROUND: The success rate is lower and the complication rate is increased in patients undergoing reoperation for primary hyperparathyroidism compared with initial procedures. Scarring and distortion of tissue planes plus the potential for ectopic gland location leads to this worsened outcome. METHODS: Two hundred eighty-eight consecutive patients with persistent/recurrent hyperparathyroidism were treated at a single institution after a failed procedure or procedures at outside institutions. Two hundred twenty-two of these patients (77%) were believed to have a missed single adenoma, and these patients underwent 228 operations and 227 preoperative work-ups. Preoperative evaluation consisted of a combination of four noninvasive imaging studies--neck ultrasound, nuclear medicine scan, neck and mediastinal computed tomography scan, and neck and mediastinal magnetic resonance imaging. Based on the noninvasive testing alone, 27% patients underwent surgery whereas the other patients underwent invasive studies, including selective angiography (58%), selective venous sampling for parathyroid hormone (43%), or percutaneous aspiration of suspicious lesions (15%). RESULTS: Abnormal parathyroid adenomas were found in 209 of 222 initial procedures and 6 of 6 second procedures, with an overall success rate in terms of resolution of hypercalcemia in 97% (215/222) of patients. The single most common site of missed adenoma glands was in the tracheal-esophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%). The most sensitive and specific noninvasive imaging test is the sestamibi subtraction scan, with 67% true-positive and no false-positive results. The rate of true-positive and false-positive results for ultrasound, computed tomography, magnetic resonance imaging, and technetium thallium scans were 48%/21%, 52%/16%, 48%/14% and 42%/8%, respectively. The incidence of injury to the recurrent laryngeal nerve was 1.3%. CONCLUSIONS: A single missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation. Appropriate use of preoperative imaging tests and knowledge of the potential location or parathyroid adenomas can lead to very high cure rates with minimal morbidity.

Adenoma↗
PubMed1994

Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1-adrenergic stimulation.

alpha 1-Adrenergic agonists activate a hypertrophic response in cultured neonatal ventricular myocytes, which include an increase in cell size, organization of contractile proteins into sarcomeric units, and the induction of the atrial natriuretic factor (ANF) gene. Previous findings have supported a role for ras in this signaling pathway. Utilizing microinjection techniques to delivery affinity-purified neutralizing antibodies to G alpha q,11 into cultured ventricular myocytes, the current studies demonstrate a functional requirement for the heterotrimeric G protein, Gq, in the alpha 1-adrenergic induction of the ANF gene, changes in cell size, organization of myofilaments, and phosphoinositide hydrolysis. Expression of a constitutively active mutant of G alpha q leads to the expression of ANF protein in these cells. Taken together, these data suggest that G q-dependent pathways are necessary and sufficient to activate defined features of the hypertrophic response. In attempts to further delineate the relative roles of ras and Gq in this pathway, we found that G alpha q is required for alpha 1-adrenergic phosphoinositide hydrolysis, though ras does not appear to be necessary for this response. In addition, we coexpressed an inhibitory ras mutant, along with the constitutively active G alpha q. Expression of ANF protein stimulated by the G alpha q mutant was not inhibited. Thus, both ras- and Gq-dependent pathways are necessary to fully transduce defined features of alpha 1-adrenergic-stimulated hypertrophy of neonatal cardiac ventricular myocytes, but activated Gq may be able to induce ANF expression independent of inhibitory ras.

Animals↗
PubMed1994

A 5-year immunization field trial against hepatitis B using a Chinese hamster ovary cell recombinant vaccine in French Polynesian newborns: results at 3 years.

A hepatitis immunization field trial, using a Chinese hamster ovary (CHO) cell recombinant vaccine, was implemented for newborns in the Austral archipelago of French Polynesia in 1988. Three different schedules were used: (1) four vaccine doses at months (M) M0, M1, M2 and M12; (2) three vaccine doses at M0, M1 and M6; and (3) three vaccine doses at M0, M1 and M12. The programme evaluation was performed yearly at fixed dates, i.e. October-November 1989, 1990 and 1991. After the third year, of the 582 children who received one or more doses of vaccine, four were HBsAg carriers. After one or two doses, 88 and 98%, respectively, had seroconverted for at least one of the two measured antibodies, anti-HBs or anti pre-S2. After three doses, seroconversion rates and geometric mean anti-HBs titres were, respectively, 94% and 187 mIU ml-1 using schedule M0, M1, M2; 95% and 507 mIU ml-1 using schedule M0, M1, M6 and 96% and 476 mIU ml-1 using schedule M0, M1, M12. After four doses (M0, M1, M2, M12) the corresponding results were 99% and 1518 mIU ml-1. One of the 16 vaccinated neonates born to HBsAg/HBeAg-positive mothers was an HBsAg carrier, implying a protective rate for the prevention of perinatal transmission of 93%. Overall, these results indicate that, in field conditions, indiscriminate vaccination of newborns with a CHO-recombinant vaccine without hepatitis B immunoglobulin (HiBG) resulted in high immunogenicity. Final evaluation in 1993-1994 will permit confirmation of the effectiveness of the two three-dose vaccine schedules.

Animals↗
PubMed1993

The blackfly Simulium buissoni and infection by hepatitis B virus on a holoendemic island of the Marquesas archipelago in French Polynesia.

The hematophagous blackfly Simulium buissoni causes skin lesions on an island in the Marquesas archipelago that is holoendemic for hepatitis B virus (HBV). To test the hypothesis of the possible role of this fly in the transmission of hepatitis B, 506 children (age range 2-11 years) were examined for the presence of skin lesions, and attempts were made to detect HBV DNA in and on blackflies using two polymerase chain reaction methods. The mean number of skin lesions showed a positive correlation with the age of these children (r = 0.12, P < 0.05). Furthermore, it was significantly higher in the rural zone than in the urban zone (mean +/- SD 41.02 +/- 31.71 versus 17.73 +/- 13.43; P < 0.05), and showed a correlation with a higher infection rate (73.9% versus 41.3%). Of the 45 pools of 10 insects tested, HBV DNA was not detectable on the inside of the insect, but was detectable on the flies (1-10 particles/insect in three positive pools). Infection by HBV conveyed by the flies is theoretically possible, but their indirect role via the numerous skin lesions caused on children is likely to explain such a high level of transmission.

Adolescent↗
PubMed1993

[Effect of 2 vaccination strategies on developments during the epidemic of meningococcal A meningitis in N'Djamena (Chad) in 1988].

From February till May 1988, during an epidemic of group-A meningococcal disease, 4542 cases of meningitis were reported in N'Djamena, the capital of Chad (550,000 inhabitants). A first selective vaccination campaign was carried out between 5 and 14 March; 156,500 vaccine doses (polyvalent: group A and C: Institut Mérieux) were given using jet injectors. The target population for this first campaign consisted of groups such as school-children and the armed forces. As the epidemic continued, a mass vaccination campaign was implemented one month later between 8 and 14 April 1988; this was targeted at the whole population above 1 year of age, not previously immunized, and 266,738 doses of vaccine were injected. One week after the start of the second campaign, the number of reported cases fell sharply and, within four weeks, the epidemic was halted. The vaccination coverage rate, evaluated by a WHO cluster survey method in people above one year of age, was 95.5%. These results show (i) the failure of selective vaccination, restricted to only at-risk groups, to halt the epidemic; (ii) the efficacy of the mass vaccination campaign aimed at the whole population; and (iii) the feasibility in tropical Africa of such a mass campaign which must be carried out in a few days.

Adolescent↗
PubMed1992

Leprosy in French Polynesia. Epidemiological trends between 1946 and 1987.

The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future.

Adolescent↗
PubMed1992

Leprosy in French Polynesia. The possible impact of multidrug therapy on epidemiological trends.

In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.

Clofazimine↗
PubMed1992

[Efficacy of radical treatment with halofantrine on the prevention of imported Plasmodium falciparum malaria].

We carried out in 1989 a non randomized comparative study in French army units which had been in Central Africa (Central African Republic and Gabon) for 4 months, in order to compare in 758 men on return from malaria areas the usual strategy of chemoprophylaxis with chloroquine and a radical cure by halofantrine (Halfan). Chloroquine was taken by 278 men (100 mg daily for 6 weeks after their return to France); the other 480 men were given two doses of 1,500 mg halofantrine on the third and on the tenth day after their return to France. In Africa both of the units were on chloroquine prophylaxis (100 mg daily for 4 months). The Plasmodium falciparum attack rates were, during a period of 5 months after the return to France, 0.2% in the halofantrine group (1/480) and 4.7% (13/228) in the chloroquine group (P < 10(-4)). The radical cure by halofantrine was more effective than chloroquine prophylaxis in preventing falciparum malaria on return from malaria areas.

Adult↗