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M Willcox

Publications and source records attributed to M Willcox.

48 records · Page 3Linked to original sources

Falciparum malaria and beta-thalassaemia trait in northern Liberia.

In a study in northern Liberia of the malaria and beta-thalassaemia hypothesis, the frequencies of beta-thalassaemia and HbS traits were 9.1 and 3.4% in the Mano and 9.5 and 1.7% in the Gio tribal samples. HbC and HbN were present at low frequency. G6PD deficiency was found in 16% of males. An observed increase with age of beta-thalassaemia trait frequencies was consistent with the selection hypothesis. However, we could not entirely exclude that associated iron deficiency influenced the results in the six to 11 month age group. Malaria was holoendemic; Plasmodium falciparum predominated, P. malariae and P. ovale were also identified. Plasmodium falciparum prevalence rates were similar in normal and beta-thalassaemia trait children but parasite densities were consistently lower in the latter. Using the criterion of a falciparum parasite density of 1 x 10(9) 1(-1) or greater to indicate a potentially important infection, the relative risk in beta-thalassaemia traits one to four years old from the cross-sectional study was 0.45 (upper 95% confidence interval 0.79) and 0.41 (0.61) in two to nine year trait carriers from a longitudinal study. Plasmodium falciparum gametocyte rates were lower in beta-thalassaemia trait children (P less than 0.005). The geometric mean titre of P. falciparum antibodies was lower in beta-thalassaemia trait children from the one to four year group (P less than 0.05). Otherwise immunological studies showed little difference between the different Hb types. Parasitological findings were consistent with relative resistance of HbS trait carriers towards P. falciparum infection. We found no evidence for relative resistance of beta-thalassaemia traits towards P. malariae infection nor that G6PD deficient males were more resistant to P. falciparum than those with normal activity. We conclude that the results are consistent with relative resistance of beta-thalassaemia trait carriers to P. falciparum malaria.

Adolescent↗

The haemoglobin pattern of sickle cell and haemoglobin C beta +-thalassaemia in Liberia.

Haemoglobin components in 21 Liberians with Hb S beta +-thalassaemia and four with Hb C beta +-thalassaemia were measured to classify the forms of beta +-thalassaemia present in the population. In 20 Hb S and all Hb C beta +-thalassaemics the data were consistent with the interaction of these variants with the mild type 2 (Negro) form of beta +-thalassaemia. The data available were insufficient to classify the remaining case, a young child. It was concluded that the clinically more severe type of beta +-thalassaemia giving Hb A levels of 5 to 15% in compound heterozygotes is probably uncommon in Liberia.

Adolescent↗

Malaria and haemoglobin A2 levels in northern Liberia.

The influence of malaria on HbA2 levels was investigated in two groups of children aged two to nine years from the Mano tribe of northern Liberia. One group, 174 children living in a town where there is malaria control, had a parasite rate of 6.5%, only a few having palpable spleens, but 282 children living in an area of intense malaria transmission had a parasite rate of 92%. All but one child in this group had enlarged spleens. However, the difference in proportions of elevated HbA2 values within the limits for beta-thalassaemia, 8% and 10.3% respectively, was not statistically significant (0.5 greater than P greater than 0.1). It was concluded that the influence of malaria on HbA2 levels is not significant and that this parameter is valid for detecting beta-thalassaemia trait in this population. Further, iron deficiency may be a more important factor than malaria to consider when assessing the results of HbA2 estimations.

Child↗

Precipitins in Liberian sera reacting with goat and sheep sera.

Precipitins in nine sera from normal Liberian adults were shown to react with an alpha-globulin in goat and sheep sera. No cross-reaction was demonstrated with bovine sera. Hence these precipitins are different to others previously described. At present their significance, if any, is unknown. They are important as a possible cause of unexplained reactions in serological tests using sheep or goat serum as a source of antigen or antibody.

Adult↗

A longitudinal study of antibodies to the Plasmodium falciparum antigen Pf155/RESA and immunity to malaria infection in adult Liberians.

118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults.

Adult↗

The changing pattern of Plasmodium falciparum susceptibility to chloroquine but not to mefloquine in a mesoendemic area of Somalia.

The response of Plasmodium falciparum to chloroquine and mefloquine was investigated in a mesoendemic area of Somalia from 1986 to 1989. Serial in vivo field tests for chloroquine sensitivity were performed and the sensitivity in vitro to chloroquine and mefloquine was evaluated using the standard WHO in vitro microtest. Chloroquine treatment in vivo (25 mg base/kg body weight) resulted in parasite clearance in all patients within 7 d (S/RI) in 1986, while 17%, 19% and 30% RII/RIII responses were found in 1987, 1988 and 1989 respectively. There was consistent increase of parasite clearance time of the S/RI cases in all years. The sensitivity study in vitro in 1986 showed a low degree of chloroquine resistance in 3 of 29 isolates tested and a mean 50% effective dose (EC50) and EC99 of 0.34 x 10(-6) M and 1.99 x 10(-6) M, respectively. In contrast, in 1989, 12 of the 19 isolates tested were resistant to chloroquine. The mean EC50 and EC99 values had increased to 0.78 x 10(-6) M and 7.50 x 10(-6) M respectively. The data in vivo and in vitro indicate a rapid increase of chloroquine resistance both in frequency and degree. All isolates tested in 1986 and 1989 were fully inhibited by mefloquine at 3.2 x 10(-6) M, suggesting full sensitivity. Thus, increased resistance of P. falciparum to chloroquine did not significantly influence the sensitivity pattern of mefloquine.

Animals↗

A novel apoptotic interaction between HSV-1 and human corneal epithelial cells.

PURPOSE: Herpes simplex virus type 1 (HSV-1) infects the cornea possibly causing blindness. The specific mechanisms of herpetic keratitis are unclear. We aimed to investigate whether HSV-1 would up- or down-regulate the apoptotic pathway of human corneal epithelial (HCE) cells. METHODS: HSV-1 infection of HCE and Vero cells was demonstrated (immunofluorescence) and apoptotic gene expression was quantified (ribonuclease protection assay). Caspase 8 protein activity (colorimetric assay) was quantified and compared to caspase 8 mRNA amounts from RPA experiments. The apoptotic index of HSV-1 infected HCE and Vero cells (apoptotic index = % of apoptotic cells in infected samples/mock treated samples) was obtained and compared to gene expression. RESULTS: A down-regulation in apoptotic gene expression was observed in HSV-1 infected HCE cells in contrast to Vero cells (infected and mock treated). Caspase 8 protein levels mirrored caspase 8 mRNA levels in HSV-1 infected HCE cells. The apoptotic index also supports this down-regulation. HSV-1 infected human corneal epithelial cells and Vero cells at similar rates. CONCLUSION: HSV-1 down-regulates the apoptotic pathway of human corneal epithelial cells. This down-regulation of apoptotic gene expression seems to be cell specific. Also infectivity is excluded in playing a role in regulation of the apoptotic pathway because HSV-1 replicated at similar rates in HCE and Vero cells.

Animals↗