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Biomedical subjects

M Willcox

Publications and source records attributed to M Willcox.

At least 37 records · Page 2Linked to original sources

QTL for insect resistance and drought tolerance in tropical maize: prospects for marker assisted selection.

Insects and drought cause severe losses in the production of maize in many developing countries. Conventional breeding efforts to enhance the level of resistance to a number of insect pests and tolerance to drought have been successful, although only through large efforts of many breeders and over a large period of time. Continued improvements will only be possible through substantial investment of resources. Recently, success in identifying quantitative trait loci (QTL) in several plant species using various molecular marker systems offers alternative methods for accelerating conventional breeding programs. As the first step towards using molecular markers in CIMMYT's maize breeding program, restriction fragment length polymorphisms (RFLPs) have been used to understand the genetic basis of resistance to two corn borer species, southwestern corn borer and sugarcane borer, and to one major component of drought tolerance, anthesis-silking interval. A number of QTL with effects large enough to be regarded as significant in breeding were detected for each of these traits and many of them presented stable effects over environments. While variability in the number and location of QTL has been found when compared across populations, several loci were found to be quite consistent. Simple calculations can be made which estimate that the total genetic potential in maize for these traits is high. It is argued that to ultimately access and manipulate this potential, the use of linked molecular markers as indirect selectable markers is both feasible and necessary.

Adaptation, Physiological↗

Classification of clinical falciparum malaria and its use for the evaluation of chemosuppression in children under six years of age in Liberia, west Africa.

The possible role of malaria as cause of morbidity was assessed during one year in 262 children aged 6 months to 6 years living in two villages in a rural area of Liberia. The study population was followed by weekly clinics and three-monthly surveys and the children were randomly allocated to receive either chloroquine or placebo every 3 weeks. The morbidity of the children was evaluated by criteria based on the history and the clinical condition into four different stages, in order to describe the probability that an observed clinical event could be attributed to malaria infection, based on the presence of detectable parasites in the blood, the history the previous week, and the clinical status of the child. The level of anaemia, splenomegaly and measured body temperature supported that malaria was the major contributor to the overall morbidity observed. Based on the stage classification of clinical illness, children were classified as having 'possible clinical malaria' or 'probable clinical malaria'. Malaria appeared to be an important cause of febrile episodes during both dry and rainy seasons. During the rainy season more than 60% of the children experienced at least one clinical malaria episode, and during the dry season more than 50% of the children experienced at least one clinical attack of malaria. Children receiving chemosuppression had overall fewer clinical malaria attacks, and the effect of the chemosuppression was most pronounced in the dry season, the odds ratio comparing children receiving regular chemosuppression with children receiving presumptive treatment only was estimated to 0.39 (0.25-0.62).

Anemia↗

Longitudinal study of seroreactivities to Pf155/RESA and its repetitive sequences in small children from a holoendemic area of Liberia.

The seroreactivities to Pf155/RESA antigen and to three oligopeptides (EENV)2, EENVEHDA and K(DDEHVEEPTVA)2, which constitute repeat subunits of the RESA molecule, were investigated between 1980 and 1986 in two cohorts of children (n = 114) with and without monthly chemosuppression (pulsed reduction of parasite load) against malaria from six months to five years of age during development of protective immunity. Serum samples were collected first at half-yearly and then yearly intervals. Positive immunofluorescence against Pf155/RESA (EMIF) was only found in 24% of the samples. The children with chemosuppression were more often seropositive (30%) than the non prophylactic children (17%). This was in contrast to the seroreactivity against crude parasitic antigens which was highest in the non prophylactic children. In these children, there was a general decrease of EMIF titres around two years of age. Immunosuppression by chronic parasitaemia may be suggested as a reason for this. ELISA seroreactivity was found against one, two or three oligopeptides in all children with high EMIF titres (greater than 250) although (EENV)2 appeared to best correlate (92%) with the EMIF seropositivity. While EMIF seropositivity only showed partial correlation to immunoprotection against patent parasitaemia in the non prophylactic children, the individual profiles of the seroreactivities to the different specific epitopes of the Pf155/RESA molecule and their relevance with regards to protective immunity to malaria need to be investigated further.

Amino Acid Sequence↗

Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia.

Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa. The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly. The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs. The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively. In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant. The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006). P. falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively. All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences. In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantification of cells recovered by bronchoalveolar lavage. Comparison of cytocentrifuge preparations with the filter method.

Controversy exists as to the appropriate methods to use in the processing of bronchoalveolar lavage (BAL) fluid for total cell numbers and cellular differential analysis. It has been shown that cell losses (primarily lymphocytes) occur by the most commonly employed methods. Therefore, we examined the total cell and differential counts obtained by several methods of cytocentrifuge preparation and by the filter preparation in 46 consecutive patients with interstitial lung disease and 29 healthy volunteers undergoing bronchoalveolar lavage. The retrieved lavage fluid was pooled, and an aliquot was used to determine the total cell count, cell viability, and the differential cell count by the filter and cytocentrifuge techniques. The remaining fluid was centrifuged (800 g for 10 min), and the cell pellet was resuspended in Hank's balanced salt solution without Ca2+ and Mg2+. An aliquot of these centrifuged and resuspended cells was used for repeat determination of the cell viability, total cell count, and cellular differential by cytocentrifuge technique. Autologous serum was added to another aliquot of these centrifuged and resuspended cells to arrive at a 10% protein solution, and the cellular differential obtained by cytocentrifuged preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vivo and in vitro susceptibility of Plasmodium falciparum to sulphadoxine/pyrimethamine in Liberia, West Africa.

The in vivo response of Plasmodium falciparum to standard treatment with sulphadoxine/pyrimethamine was studied in 19 hospital patients from Yekepa town with hypoendemic malaria and in 28 children, two to nine years old, living in a village with holoendemic malaria. In vitro tests were performed on eight isolates. In the hospital patients all parasites cleared with mean clearance time of 2.2 (range one to three) days and no recrudescence occurred during a 28-day follow-up period. In the village children, despite a high sporozoite inoculation rate, recurrent parasitaemias were only recorded after 28 days, suggesting a rather long-lasting prophylactic effect against reinfection by the drug combination. In vitro, inhibition of parasite multiplication was achieved by 3 X 10(-7) M sulphadoxine and 3.8 X 10(-9) M pyrimethamine.

Adolescent↗

In vitro susceptibility of Plasmodium falciparum to amodiaquine, mefloquine, quinine and chloroquine in Liberia, West Africa.

The in vitro susceptibility of seven Plasmodium falciparum isolates to four schizonticidal drugs was studied in Yekepa area, northern Liberia, by the Rieckmann 24-hour micro method. The seven patients were successfully treated with the standard chloroquine regimen. The results of the individual in vitro tests all indicated full susceptibility to the four drugs. By probit analysis, the drug concentrations achieving 50% (EC 50) and 99% (EC 99) inhibition, respectively, were 0.2 and 0.7 microM chloroquine, 0.04 and 0.2 microM amodiaquine, 0.01 and 0.07 microM mefloquine and 1.4 and 3.0 microM quinine.

Amodiaquine↗

In vivo response of Plasmodium falciparum to different doses of chloroquine in semi-immune children in Liberia, West Africa.

The efficacy of different doses of chloroquine in suppressing patent parasitaemia was investigated in 326 children two to 12 years old, living in six villages with holoendemic malaria. The children were given single doses (2, 3, 5-7 or 9-12 mg base kg-1) or a standard treatment over three days (25 mg base kg-1). Parasite prevalences were recorded after one, two, three, four, six and eight weeks. Complete clearance of Plasmodium falciparum trophozoites (TC) by day 7 was achieved by a dosage of 9-12 mg kg-1. By probit analysis of log dose response, 50% clearance (TC50) was established at about 1.5 mg kg-1, whereas a TC95 required 5.5 mg kg-1. The reappearance of patent parasitaemia was dependent on the dose of chloroquine given and on malaria transmission. After the standard dose treatment, only one re-infection in 56 children appeared within 21 days despite high sporozoite inoculation rates in the area. The dosage of 9-12 mg kg-1 yielded a hundredfold reduction of mean parasite density in the children if calculated over a four-week period. It may represent a suitable monthly regimen in a malaria control scheme in a holoendemic area with high P. falciparum sensitivity to chloroquine.

Child↗

Monthly antimalarial chemotherapy to children in a holoendemic area of Liberia.

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

Antimalarials↗

Serum protein polymorphisms in a Liberian population.

Serum protein variations were studied in a Liberian population living in Buchanan town. Of the alpha 1-antitrypsin genes only M1 and M3 were polymorphic. The frequencies of the haptoglobin and Gc genes were in accordance with earlier known estimates in African populations. There was, however, a relatively low frequency of Hp 0 which may be related to the low malarial parasite prevalence in this group. The transferrin C2 gene was found in a significantly lower frequency among Liberians compared to European and Asiatic populations. A new transferrin variant was observed by isoelectric focusing. This variant could not be identified with conventional starch or polyacrylamide electrophoresis.

Blood Proteins↗

Different malaria control activities in an area of Liberia--effects on malariometric parameters.

The epidemiology of malaria was studied in a West African mining town (Yekepa) and three surrounding zones defined as Close, Middle and Far areas. Malariometric parameters were investigated in children two to nine years of age at the end of the rainy season. In Yekepa, vector control measures and intense suppression of malaria with drugs had created an almost hypoendemic situation with a spleen rate of 11%. In Close area, vector control was applied to some extent and malaria drugs were frequently used for treatment; the spleen rate was 40%. In Middle area, a mobile clinic provided sporadic malaria treatment to small children, but the clinic did not reach out to Far area. The spleen rates were 95 and 99%, respectively. Three species of Plasmodium were found in all areas. The prevalences in Far area were P. falciparum 82%, P. malariae 39% and P. ovale 9%. The crude parasite rates increased from 13% in Yekepa to 92% in Far area, whereas haematocrit levels decreased from 37.6 to 35.2, respectively. Plasmodium falciparum seropositivity, as measured by indirect immunofluorescence, was 74% in Yekepa and 99% in Middle and Far areas. Total IgG concentrations ranged from 18 g1(-1) in Yekepa to 33 g1(-1) in Far area. Three main anopheline species were found in the zones outside Yekepa. Their relative frequencies in Far area were Anopheles funestus 45%, A. hancocki 37%, and A. gambiae 18%. The local inoculation rates gradually increased outwards from Yekepa from less than 0.01 to 0.17 inoculations per man and night at the beginning of the dry season.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Susceptibility of Plasmodium falciparum to chloroquine in northern Liberia after 20 years of chemosuppression and therapy.

The in vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine was investigated in northern Liberia after 20 years of continuous chemosuppression and therapy with 4-aminoquinolines. In all patients studied (n = 53) parasitaemias were cleared within four days. There were no recrudescences in 16 patients followed-up for 28 days. All isolates of P. falciparum tested in vitro (n = 26) showed sensitive patterns. Schizont maturation was inhibited by a chloroquine concentration of between 0.25 and 0.75 mumol-1. In this area of Liberia no resistance to chloroquine was found in spite of extensive use of 4-aminoquinolines. This may support the view that importation of at least partially resistant strains, rather than local mutation of P. falciparum, precedes selection of resistant strains. Hence, we conclude that regular intake of chloroquine by groups at risk is justified if it is combined with regular monitoring of drug susceptibility.

Child↗

Malaria control by chlorproguanil. I. Clinical effects and susceptibility of Plasmodium falciparum in vivo after seven years of monthly chlorproguanil administration to children in a Liberian village.

For seven years, chlorproguanil (1.0 to 2.0 mg kg-1) was administered monthly to the children below 15 years of age in a village with holoendemic malaria. Malariometric indices were recorded every six months. Susceptibility in vivo was monitored by the clearance of Plasmodium falciparum parasitaemia after drug intake. Three parasite species were found initially: P. falciparum (52%), P. malariae (8%) and P. ovale (4%). The parasites found during the study were mainly P. falciparum, and parasite rates ranged from 37 to 87% at the different surveys one month after respective drug intake. A fifty-fold decrease of mean parasite density was generally observed seven days after drug intake. Splenomegaly was initially recorded in all two to nine year old children, with a mean size of 2.64 according to Hackett's index. From 18 months onwards as the mean spleen index was 1.15 in the same age group. Chlorproguanil may represent an important alternative drug to groups at risk in malaria control schemes.

Adolescent↗

Is the working capacity of Liberian industrial workers increased by regular malaria prophylaxis?

In a study of the impact of malaria prophylaxis upon the physical working capacity of Liberian industrial workers, two groups of men, one with and the other without malaria prophylaxis, were compared over a period of one year. At the beginning and at the end of the study, the haemoglobin concentration, haematocrit, blood volume and physical performance--measured by bicycle ergometry and expressed as work load at heart rate 170--were compared. No significant differences were found, either within or between the two groups. Routinely distributed malaria prophylaxis thus seems to be of little importance with respect to working capacity in this type of community, where malaria is meso-endemic.

Blood Volume↗

Pulmonary hypertension, pulmonary edema, and decreased pulmonary compliance produced by increased ICP in cats.

Cats, anesthetized with sodium pentobarbital, were cannulated to measure pulmonary, systemic, and left atrial pressures and pulmonary ventilation, compliance, and resistance. Intracranial pressure was elevated to 30 mm Hg by injecting silicone oil into the extradural space. After an average time of 56 minutes, pulmonary systolic and diastolic pressures more than doubled, systemic systolic pressure sometimes rose and sometimes fell, and diastolic pressure rose 5%. Left atrial pressure never exceeded 8 cm of saline. Pulmonary compliance decreased by one-half, but airway resistance was unchanged. Pulmonary edema was estimated from histological sections. The pulmonary hypertension may be the result of a sympathetic discharge confined to the lung, since no remarkable changes in heart rate or systemic blood pressure occurred. The decrease in pulmonary compliance followed the rise in pulmonary arterial pressure, and is interpreted as the result of interstitial edema. There was no evidence that left heart failure or elevated left atrial pressure caused the pulmonary edema.

Animals↗

A case-control study in northern Liberia of Plasmodium falciparum malaria in haemoglobin S and beta-thalassaemia traits.

A case-control study was carried out on 558 patients with malaria attending a hospital in Yekepa, northern Liberia; 94 patients (16.8%) were aged at least ten years, probably because of a low level of protective immunity in town dwellers due to malaria control. The proportion of sickle cell traits (1.8%) among the patient group was lower than in the population (7.2%) served by the hospital (chi 2, 21.455, 1 df, P less than 0.001). A stratified analysis showed the relative risk for Plasmodium falciparum malaria in sickle cell trait over normal homozygotes, as 0.29 (upper 95%) confidence interval, 0.56). For beta-thalassaemia trait, the proportion among patients was 5.5% as against 9.0% in the general population (chi 2, 6.158, 1 df, 0.025 greater than P greater than 0.010). Stratified analysis gave a weighted relative risk for beta-thalassaemia heterozygotes of 0.49 (upper 95% confidence interval, 0.74). Although there were four beta-thalassaemia traits in the 10-14 year stratum with moderate to high parasitaemias, we consider that the overall results are consistent with relative resistance against P. falciparum malaria of both sickle cell and beta-thalassaemia heterozygotes in this population. No conclusions were possible from this investigation with regard to HbC and the malaria hypothesis. We found no evidence that P. falciparum malaria elevates HbA2 concentrations into the beta-thalassaemia range.

Adolescent↗