Resistance of Plasmodium falciparum in vivo to 3 days' treatment with quinine and single-dose Fansidar.
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Animals↗
Biomedical subjects
B Genton
Publications and source records attributed to B Genton.
Cerebrospinal fluid lactate in 78 cases of adult meningitis.
In a retrospective study of 78 cases of adult meningitis, the CSF lactate was measured on the first spinal tap (ST); 25 had a bacterial meningitis, 28 a viral meningitis; 22 other cases had been on antibiotics prior to admission; 3 cases had meningitis of rare aetiology. The median CSF lactate level among the 25 bacterial cases amounted to 13.6 mmol/l (range: 3.5-24.5) whereas it remained low in the 28 viral cases: 2.7 mmol/l (range: 1.4-4.2). These differences are highly significant. The comparison of the CSF lactate level with the other tests routinely performed showed that the CSF lactate level had the highest sensitivity, specificity and predictive values. The CSF lactate level on the first ST had no prognostic value, but a rapid decrease of the CSF lactate during the treatment is indicative of good prognosis. Among the pretreated cases, a high lactate level could be an indication that bacteria were the causal agents. In conclusion, the measurement of the CSF lactate, quickly performed and inexpensive, is worth performing when a meningitis is suspected, as it appears to be the best way of distinguishing bacterial from non-bacterial meningitis.
Adolescent↗
[Medical evaluation of travelers returning from the tropics: which diagnostic studies and for whom?].
Annually ten percent of Swiss people expose themselves to the risk of acquiring a tropical or cosmopolitic disease during travel to exotic countries. A systematic check-up of returning travellers is however indicated only for those with acute or recurrent symptoms or after a prolonged residence in a critical region. Febrile states should be considered medical emergencies. Investigations comprise routine laboratory tests (examination of blood film and feces for presence of parasites) complemented by special tests based on anamnestic and clinical criteria. Special attention is given to fecal analysis which has to be adapted to the search for specific pathogens (Bacteria, Protozoa, Helminths). Serologic tests are of increasing importance for the detection of parasitic infestation allowing for specific therapy in certain cases.
Algorithms↗
[Meningitis in adults at the Vaudois University Hospital Center. Diagnosis, management and development of 112 cases].
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Adolescent↗
Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area?
To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had > or = 10,000 P. falciparum parasites per microL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia > or = 10,000/microL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature > or = 38 degrees C had the best predictive value for a P. falciparum parasitaemia > or = 10,000 microL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia > or = 10,000/microL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considered.
Adolescent↗
Acquired antibody levels to Plasmodium falciparum merozoite surface antigen 1 in residents of a highly endemic area of Papua New Guinea.
The prevalence and concentration of antibodies to a yeast-expressed N-terminal region (195A) and a baculo-virus-expressed C-terminal region (BVp42) of merozoite surface antigen 1 (MSA-1) were measured during a cross-sectional survey in the Wosera area of East Sepik Province, Papua New Guinea, in order to obtain baseline data on naturally acquired antibody response to this antigen in preparation for a vaccine trial. Overall, the seropositivity rate was 78% for 195A and 91% for BVp42. Although antibody prevalence to both molecules increased with age, higher antibody prevalence rates were observed for BVp42 in all age groups studied. In children, significant positive associations were found between parasite prevalence and antibody prevalence for both regions of MSA-1 and between spleen rates and anti-BVp42 antibody prevalence. Concentration of antibody against both regions increased significantly with age, but was always higher for BVp42. In children, antibody levels to both regions of MSA-1 were significantly higher in those infected (symptomatic and asymptomatic), while in adults no significant difference in antibody concentration was observed between those infected and those uninfected. However, enlarged spleens were associated with higher antibody concentration to both regions of MSA-1 in both children and adults. The C-terminal of MSA-1 appeared to be more recognized than the N-terminal, in terms of both antibody prevalence and concentration.
Adolescent↗
Human cerebral malaria: lack of significant association between erythrocyte rosetting and disease severity.
The ability of Plasmodium falciparum isolates from 103 Papua New Guinea children with cerebral malaria and 158 children with uncomplicated malaria to form rosettes in vitro was studied. Of these, 81 isolates from cerebral malaria and 151 isolates from uncomplicated malaria grew to schizogony and were included in the rosetting analysis. Wide variation occurred in the level of rosette formation, with all isolates from both cerebral and uncomplicated malaria patients being able to form rosettes. No statistically significant difference existed between the geometric mean rosetting rate of isolates obtained from cerebral malaria and those from uncomplicated malaria (9% versus 8.6%, P = 0.27). The ability of acute sera to inhibit rosette formation was not significantly different between 18 cerebral malaria cases and 20 controls tested [mean reduction in rosetting rate 6.1% (SD 11.5) versus 8.4% (SD 12.3), P = 0.57]. The rosetting rate of cerebral malaria cases was not associated with the clinical outcome. Among the clinical and laboratory variables tested, only blood group and parasite density were significantly associated with rosetting. These data do not support the hypothesis that rosette formation is associated with cerebral malaria in Papua New Guinea, but indicate that rosetting is an intrinsic property of parasites occurring in all manifestations of the disease.
Adolescent↗
Risk factors for meningococcal meningitis in northern Ghana.
Meningococcal meningitis is a major cause of morbidity and mortality in the meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8-12 years. Risk factors for the disease in this setting remain largely unknown. We carried out a case-control study to investigate possible risk factors among survivors of a meningitis epidemic occurring in 1997 in northern Ghana. A structured questionnaire on socio-economic factors, housing and household overcrowding, smoking and exposure to smoke and close contact with a case was administered to 505 of the survivors and 505 of age-, sex- and location-matched controls. Cooking in kitchens with firewood stoves (OR 9.00, CI 1.25-395) and sharing a bedroom with a case (OR 2.18 CI 1.43-3.4) were found to be risk factors for disease. Socio-economic factors, overcrowding, smoking and passive exposure to tobacco smoke were not found to be risk factors. Exposure to smoke from cooking fires or close contact with a case puts people at risk of contracting meningococcal meningitis. In the hot dry months, exposure to smoke from cooking fires should be minimized by encouraging alternatives to cooking over wood fires, or cooking outside. If wood-burning stoves cannot be avoided, kitchens should be made larger with improved ventilation. Meningitis cases should be nursed in well-ventilated rooms and the number of people sharing a room with a case kept at a minimum.
Adolescent↗
Associations of peak shifts in age--prevalence for human malarias with bednet coverage.
Effects of bednet coverage (C) on prevalence of malaria were analysed using data from 1990-92 from 9 Papua New Guinean villages. Effects of coverage varied by age, resulting in a shift in age of peak prevalence from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum, from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P. malariae. In small areas with no bednets the age distribution of P. falciparum parasitaemia was like that of a holoendemic area. Where coverage was complete the pattern corresponded to mesoendemicity. Thus, protracted use of bednets can result in profound changes in the endemicity of malaria even when coverage is incomplete and without insecticide treatment. Average entomological inoculation rates (EIRs) estimated from indoor landing rates on individuals without bednets were 35, 12 and 10 infectious bites per person per annum for P. falciparum, P. vivax and P. malariae, respectively. Logistic regression analyses indicated that the EIR estimate for P. falciparum was related to prevalence of this species independently of effects of bednet coverage. However, the recent EIR still accounted for much less variation than did the bednets. A similar pattern was seen for P. malariae, while there were no significant relationships between the recent EIR and the parasite positivity for P. vivax. It is concluded that short-term variations in inoculation rate are not important determinants of parasite prevalence in this population.
Adolescent↗
Mosquito nets for the elderly?
Nine-year follow-up (ending 1999) of survival of 3738 individuals in a malaria-endemic area of Papua New Guinea found that the use of mosquito nets was associated with a large reduction in mortality in people aged > or = 40 years as well as in children aged < 5 years. There may be substantial benefits of malaria transmission reduction for older people, that have been overlooked in public health programmes and burden of disease calculations.
Adolescent↗
Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea.
South-east Asian ovalocytosis status was determined in 1629 individuals originating from 12 different geographical areas of Papua New Guinea, representing different ethnic groups and degrees of malaria endemicity. This was achieved by using polymerase chain reaction amplification to demonstrate a 27 base pair deletion in the erythrocyte band 3 (AE1) gene. By using this method, the prevalence of erythrocyte band 3 gene deletion was determined to range from zero in both the lowland inland area of Wosera, East Sepik Province and the highland region of Goroka, Eastern Highlands Province to 35% on the north coast of Madang Province. In general, the prevalence correlated well with altitude, being highest on the coast where malaria transmission is high, intermediate in the lowlands, and lowest in the non-malarious highlands. However, Wosera, a lowland area in the Sepik River Plains, which is hyperendemic for malaria, was an exception in that no ovalocytosis was detected. These results largely confirm the prevalence rates that have been reported in the past using microscopy. In keeping with the autosomal dominant mode of inheritance, the male:female ratio was 1.02 and no homozygote was detected, indicating that homozygosity for the ovalocytosis band 3 gene deletion is lethal.
Adolescent↗
Association between serum levels of reactive nitrogen intermediates and coma in children with cerebral malaria in Papua New Guinea.
Serum levels of reactive nitrogen intermediates (RNI; nitrate plus nitrite) were measured in 92 patients with cerebral malaria in the Madang Province of Papua New Guinea. RNI levels were compared to disease severity and clinical outcome, and correlated with both the depth of coma on admission and its duration. Median levels were higher among children with deeper coma than among those with lighter coma (35.6 microM vs. 16.7 microM; P = 0.008) and also among children with longer duration of coma (72 h; 59.3 microM vs. 19.3 microM; P = 0.004). RNI levels also correlated with clinical outcome, fatal cases having significantly higher RNI levels than survivors (41.2 microM vs. 18.5 microM; P = 0.014). Thus, high RNI levels are associated with indices of disease severity and may predict outcome in children with cerebral malaria. These data are consistent with the hypothesis that nitric oxide is involved in the pathogenesis of coma in human cerebral malaria.
Child↗
Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study.
A prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface proteins.
Adolescent↗
PCR amplification of DNA from malaria parasites on fixed and stained thick and thin blood films.
Under some circumstances, polymerase chain reaction (PCR) amplification of deoxyribonucleic acid (DNA) from Plasmodium may become necessary from infections for which only blood slides are available. Established methods used for DNA preparation do not work in that case. We have developed a reliable and controlled method for DNA preparation from malaria parasites on fixed and stained blood films. 162 slides from 2 different locations, some stored for at least one year, have been analysed by PCR amplification of the polymorphic loci for MSA1 and MSA2. In 92% of microscopically positive slides, a PCR product could be detected using material derived from thick blood films. When thin blood films with scanty parasitaemia were used, a PCR product could be obtained with only 71% of samples. In all unsuccessful cases, DNA preparation was the limiting factor, which was controlled for by amplification of a control human template.
Animals↗
Naturally acquired cellular immune responses to the synthetic malarial peptide SPf66 in children in Papua New Guinea.
A prospective longitudinal study to examine the relationship between cellular immune responses to the synthetic malarial peptide SPf66 and malaria infection and morbidity was carried out in 187 children aged 0.5-15 years in the Wosera area of Papua New Guinea. Cellular responses were assessed by proliferation and stimulation of cytokines representing the Th1 and Th2 cell subsets (interferon gamma [IFN gamma] and interleukin-4 [IL-4]. Most children (66%) did not respond to SPf66 by any measure. Among the responders, the highest response was obtained for IL-4 (19%) followed by IFN gamma (10%), and the least for proliferation (5%). Analyses of the relation of T cell response to malaria infection showed that the IFN gamma response to SPf66 was positively correlated with parasite density (r = 0.27, P = 0.001). There was no association between the cellular response to SPf66 and concurrent or subsequent malaria morbidity, whichever clinical definition was used. Thus none of these cellular immune responses predicted efficacy of SPf66 in this highly endemic area.
Adolescent↗
The correlation between microscopical examination and erythrocyte band 3 (AE1) gene deletion in South-east Asian ovalocytosis.
South-east Asian ovalocytosis status was determined by microscopical examination of peripheral blood samples collected from 137 individuals in Papua New Guinea. The examination was performed separately by 2 microscopists, one of whom was very experienced in examining peripheral blood films for the diagnosis of south-east Asian ovalycytosis and the other was recently trained. The samples were also analysed by polymerase chain reaction (PCR) to determine ovalocytosis status by demonstrating a 27 base pair deletion in erythrocyte band 3 protein of the affected individuals. The microscopists were unaware of each other's results and of those obtained by PCR. Generally, there was very good agreement between the results obtained by both microscopists and the PCR. Although there was considerable inter-observer variation in the final ovalocyte count between the 2 microscopists, this did not affect their ability to discriminate between ovalocytic and normocytic individuals. Taking the PCR results as the standard, for the first, more experienced observer, the most efficient ovalocyte count cut-off point was around 50%. At this ovalocyte count the sensitivity and specificity of microscopical examination were 93.6% and 92.2%, and the positive and negative predictive values 86.3% and 96.5%, respectively. The second microscopist generally underscored the ovalocyte counts and his most efficient cut-off point was 20%, with sensitivity and specificity of 85.1% and 93.3% and positive and negative predictive values of 87.0% and 92.3%, respectively.
Anion Exchange Protein 1, Erythrocyte↗
The ratio of reactive nitrogen intermediates to tumour necrosis factor and clinical outcome of falciparum malaria disease.
Serum levels of reactive nitrogen intermediates (RNI; nitrate + nitrite), interferon gamma (IFN gamma) and tumour necrosis factor (TNF) were measured in 177 Papua New Guinean children with different clinical manifestations of malaria. The groups investigated were asymptomatic parasitaemic, mild malaria, cerebral malaria survivors and cerebral malaria non-survivors. The levels of TNF were highest among the cases of cerebral malaria who died and lowest among the asymptomatic parasitaemic children (mean log TNF levels 2.183 pg/mL vs. 1.455 pg/mL; P = 0.001). Similarly, the levels of IFN gamma were highest among the cerebral and lowest among the asymptomatic patients (mean log TNF levels 0.338 pg/mL vs 0.054 pg/mL; P < 0.0001). RNI levels were high among both the asymptomatic parasitaemic group and those who died due to cerebral malaria (mean log RNI levels 1.56 microM vs. 1.412 microM; P = 0.18). The ratio of RNI to TNF, however, was significantly higher among the asymptomatic parasitaemic children and lowest among those who died due to cerebral malaria (mean log (RNI:TNF) ratio 0.118 vs. -0.789; P < 0.001). We concluded that the ratio of serum RNI to serum TNF is a more useful indicator of outcome of falciparum malaria in this population than the absolute levels of either alone.
Biomarkers↗
Compliance to live oral Ty21a typhoid vaccine, and its effect on viability.
BACKGROUND: Concerns have been expressed that in travelers the efficacy of the live oral Ty21a typhoid vaccine Vivotif could be lower than reported, maybe due to a lack of compliance. The purpose of this study was to examine the level of compliance with the recommendations regarding dosing, timing of dosing with respect to food intake, and storage. METHODS: Travelers were randomized into two groups: one received oral information only, and the second, a combination of oral and written information. Four criteria of compliance were applied to travelers: 3 capsules needed to be swallowed (criterion 1) on day 1, 3 and 5 (criterion 2), at least 1 hour before or 2 hours after a meal (criterion 3) and the vaccine had to be kept refrigerated (2-8 degrees C) (criterion 4). Compliance was evaluated using three different methods: a questionnaire, pill counting, and electronic monitoring using the Medication Event Monitoring System (MEMS). Storage conditions were checked by temperature tags, and viability of the vaccine was assessed by culturing the content of remaining capsules. RESULTS: The data of 115 travelers were analyzed. All the travelers took the 3 capsules. Compliance to all four criteria was complete in 68% of travelers according to the questionnaire, and 53% according to the MEMS (p =.05). Sixty-seven percent of all the doses intervals were of 48 hours +/- 6 hours, 12% being shorter than 36 hours and 7% longer than 60 hours. Eighty-seven travelers (76%) took their capsules on each alternate day. The method of information had no significant impact on compliance. Forty-two percent of tags showed exposure to temperature over 10 degrees C for more than 24 hours. Yet, no difference could be found in the viability of the vaccine compared with controls. CONCLUSIONS: Most travelers take their 3 capsules on alternate days, but many did not follow the other recommendations. Electronic monitoring of compliance provides more accurate results than questionnaires. Emphasis must be put on motivating the travelers to take the vaccine as recommended.
Administration, Oral↗