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Biomedical subjects

A I Williams

Publications and source records attributed to A I Williams.

At least 19 recordsLinked to original sources

Lack of association between levels of transplacentally acquired Plasmodium falciparum-specific antibodies and age of onset of clinical malaria in infants in a malaria endemic area of Nigeria.

A cohort of 117 newborns was followed longitudinally for 12 months to determine the age of onset of clinical malaria and the subsequent episodes of malaria, and to investigate the possible existence of a correlation between level of transplacentally acquired Plasmodium falciparum-specific antibodies and age of onset of malaria in the infant. The mean age of onset of malaria in 49 infants was 4.48 +/- 1.54 months. Mean (+/- S.D.) age of onset of clinical malaria in haemoglobin AA infants (4.38 +/- 1.14) was significantly (P < 0.05) lower compared with haemoglobin AS (5.58 +/- 2.43) infants. No correlation was obtained between the age of onset of malaria and the level of cord serum total IgG, IgM and antibodies to P. falciparum antigens. Cord blood seropositivity for antibodies to the blood stage antigen Pf155/RESA and its C-terminal repeat sequence (EENV)6 or to the (NANP)6 peptide representing repeats of the circumsporozoite protein (CSP) did not influence the age of onset of clinical malaria. However, infants with haemoglobin AS whose cord blood was seropositive for antibodies to the (EENV)6 or (NANP)6 peptide showed delayed onset (P < 0.001) of malaria compared with AA seropositive infants. Although our results indicate that transplacentally acquired antibodies to the studied antigens alone offer no significant protection against malaria during the first few months of life, antibodies in concert with other factors such as haemoglobin genotype may contribute to the protection of the newborn.

Age Factors↗

Immunoglobulin levels in malaria infected Nigerians with and without abnormal haemoglobin.

Comparative studies were made between malarial parasitaemia in Nigerians with and without abnormal haemoglobins. The three main classes of immunoglobulins (i.e. IgG, A and M) were assayed in these groups of patients and the mean values were compared. Those with abnormal haemoglobins S or C (HbS or HbC) were compared with those with normal control haemoglobin A (HbA). HbSS malarial patients have the highest mean values of the 3 classes of immunoglobulins. This is followed by HbAS patients while patients with normal Hb have lowest mean values for IgG and IgM. The significance of the results is discussed.

Adolescent↗

Serum ferritin and other iron indices in adult Nigerians with chronic renal failure--review of management of anaemia.

Iron studies were carried out in twenty five adult male and female patients with chronic renal failure and thirty one "healthy" individuals as control. Results showed moderately severe anaemia in all the patients with a mean haemoglobin concentration of 7.4 mg/dl (range 6-9.8 gm/dl). Transferin saturation of 28.8% in the patients was similar to the value of 29.2% in the control group. However, the mean serum ferritin value of 610 micrograms/L in the patients was significantly higher than the corresponding values of 165 micrograms/L and 58 micrograms/L in the control groups respectively. In patients with chronic renal failure, three out of ten bone marrow aspiration showed no stainable iron, and in five patients, iron was grossly increased with corresponding increases in serum ferritin values. In addition, four of the five patients had severe megaloblastic changes in the marrow.

Adult↗

Severe morbidity among children in a trial malaria chemoprophylaxis with pyrimethamine or chloroquine in Ibarapa, Nigeria.

In a controlled trial of weekly malaria chemoprophylaxis with chloroquine and pyrimethamine there were no significant differences in type and frequency of severe morbidity during chemoprophylaxis. Administration of chemoprophylaxis during the current and immediately preceding month was associated with significantly fewer episodes of severe morbidity in the chloroquine and pyrimethamine groups when each was compared with the control multivite group. After chemoprophylaxis had been stopped, significantly more episodes of severe morbidity occurred in the chloroquine group than the control group, but a similar trend in the pyrimethamine group was not statistically significant. In the control group most of the episodes of severe morbidity, including those episodes which were associated with heavy parasitaemia, occurred below the age of 4 years. In contrast, the children who received chemoprophylaxis continued to experience such illness at older ages. The difference between the chloroquine group and the control group in respect of age at time of severe morbidity was statistically significant.

Age Factors↗

Correlation between in vivo and in vitro response of chloroquine-resistant Plasmodium falciparum in Calabar, south-eastern Nigeria.

Since chloroquine-resistant Plasmodium falciparum (CRPF) has emerged in Nigeria, we monitored the susceptibility of the parasite strain to a standard chloroquine (C25) dose in our Children's Emergency Unit. Chloroquine (CQ) is the drug of choice for malaria chemotherapy in Nigeria. The WHO 7-day in vivo evaluation and Rieckmann's microtitre technique (in vitro test) were used. 33 children of mean age 4.9 years were enrolled in the study. 27 (81.8%) of the in vitro cultures were successful. 16 (59.3%) of the successful isolates still showed schizogony at CQ concentration of 5.7 pmol/well and above. 28 (84.8%) of the children completed the in vivo study. 15 (53.6%) were parasitaemic on day 7 and/or day 14 and were regarded as parasitologic failures. The isolates from 14 of these children showed corresponding in vitro resistance of CQ concentrations equal to or above 5.7 pmol/well. The proportion of RIII (= 13.3%) appears to have increased as compared to 5.9% recorded in 1987. We conclude that there appears to be a good correlation between in vivo evaluation of parasitologic failures (53.6%) and in vitro resistance (59.3%). It thus appears that CRPF is definitely increasing in South-Eastern Nigeria. This can be expected not only to complicate malaria chemotherapy in the Children's Emergency Unit of the University of Calabar Teaching Hospital, but will contribute immensely to the deterioration of malaria therapy and control in Nigeria.

Animals↗

Immunological studies on pre-eclampsia in Nigerian women.

Circulating immune complexes, C3b inactivator, C3 activator, C3c, C4 and C-reactive protein were assayed in 49 patients with pre-eclampsia and 35 apparently healthy pregnant Nigerian women. Pre-eclamptic women had significantly higher mean levels of circulating immune complexes, C3c and C-reactive protein. C3 activator mean level was also higher in pre-eclampsia than in normal pregnancy, C3b inactivator concentrations were greatly depressed and the mean level was also significantly lower in the pre-eclamptic group (P less than 0.001). However, C4 mean levels were the same in both groups. From the results, it is postulated that in pre-eclamptic conditions the significantly depressed levels of C3b inactivator could predispose to the persistence of deposited immune complexes in the kidneys, resulting in tissue damage. The findings also generally indicate an immunologic pathogenesis for the renal lesions in pre-eclampsia in Nigerian women.

C-Reactive Protein↗

Immunity in malaria: II. Heterophile and malarial antibodies in acute Plasmodium falciparum infection.

The sera of 55 Nigerian children (30 malarious and 25 healthy) were analysed for heterophile antibodies against normal sheep erythrocytes by the passive haemagglutination technique. Fluorescent antibodies to Plasmodium falciparum were quantified by the indirect immunofluorescence method while the three major immunoglobulins (IgG, IgA and IgM) were estimated by the radial immunodiffusion technique. An increasing age gradient was demonstrated in the heterophile antibody titres within the malarious and control groups, but there was no significant difference in the levels of immunoglobulins and malarial antibodies between the two groups. An indication of higher malarial antibody titre was only observed in the malarious group, particularly in late childhood. These results show an increasing level of heterophile antibodies with age. It is concluded that malarial antigens may play a contributory, but not a dominant role in the acquisition of heterophile antibodies. There is also a need to define the exact serum factors (antibody or non-antibody) which are associated with clinical immunity to malaria in Nigerian children.

Adolescent↗

Immunity in malaria: depression of delayed hypersensitivity reaction in acute Plasmodium falciparum infection.

The effect of acute Plasmodium falciparum malaria infection on the cell-mediated immune response of 30 Nigerian children attending the General Out-patient (GOP) Clinic of the University College Hospital, Ibadan, Nigeria, was assessed in a controlled study. Delayed-type hypersensitivity skin reaction to five tuberculin units (5 TU) of purified protein derivative (PPD) was used as an indicator of cell-mediated immunity. The results showed marked depression of delayed hypersensitivity reaction to PPD in 27 (90%) of the malarious children, compared with four (16%) of the 25 control healthy subjects (P less than 0.0005). This depression was observed despite evidence of previous BCG vaccination in 38 (69.1%) of the 55 children in the study. The possible clinical significance of these observations in tropical paediatric practice, and the immunopathological implications, are discussed.

Acute Disease↗

The effect of substance(s) associated with malarial parasites on C3b inactivator.

The effects of a substance or substances associated with malarial parasites on the inhibitory role of C3b inactivator in immune adherence were investigated. The test system involved adherence of immune complexes of complement-bearing sheep erythrocytes and rabbit antibody, using human group O erythrocytes and human renal glomerular tissues as indicators. Malarial antigen and other soluble by-products of the malarial parasites, presumably present in spent culture medium, did not interfere with the inhibitory role of C3b inactivator. However, malarial pigment, both crude and purified, enhanced immune adherence in the presence of C3b inactivator. It is suggested that malarial pigment, by inhibiting the action of C3b inactivator, may play a significant role in the immunopathogenesis of renal lesions associated with malarial infections.

Animals↗

Granulocyte chemotaxis in acute human Plasmodium falciparum malaria.

The non-lymphoid elements of the peripheral leucocyte pool were examined in the present study to determine their response to chemotactic stimulation. Our results indicate that granulocytes are effectively mobilized during malaria infections and are not deactivated by complement-derived chemotactic factors. These findings provide further evidence for the restriction of immunosuppression to some specific T and B-cell related functions only.

Acute Disease↗

Lymphocyte subpopulations and antibody levels in immunized malnourished children.

1. The proportions of lymphocyte subpopulations (by rosette tests) and the serum antibody levels (using haemagglutination techniques) were estimated in malnourished and well fed Nigerian children before and up to 21 d after immunization with tetanus toxoid or measles virus vaccine. 2. Significantly diminished (P less than 0.01) mean percentage T lymphocyte levels and considerably higher mean percentage null cell levels were observed in the malnourished children before immunization with either of the vaccines. 3. There was comparable in vivo increases in percentage T lymphocytes in malnourished and control children following the administration of each antigen. 4. The mean percentage B lymphocyte levels were similar in the control and malnourished children before and after the immunization. 5. There was a slight depression in the tetanus antibody levels (P greater than 0.2) but a significant diminution (P less than 0.01) in measles virus antibody concentrations in the malnourished children. 6. Rise in mean percentage T lymphocytes corresponded with the elevation in mean tetanus antibody levels in both malnourished and control children following tetanus toxoid immunization. This was however not the situation in the malnourished children following immunization with measles virus. 7. The observed depressed T lymphocyte number in malnourished children may in practice affect their handling of antigens such as measles virus in vivo.

Antibodies, Bacterial↗

IgG subclass levels in malaria-infected Nigerians.

IgG class and subclass levels were measured in the sera of malaria-infected patients who had high serum antibody titres (greater than or equal to 1 in 5,120) as well as in uninfected controls with low serum malaria antibody titres (less than or equal to 1 in 320). The malaria-infected patients had higher IgG and IgGI subclass levels than the uninfected controls (p less than 0.005). There was a slight diminution in the mean IgG3 concentration in the malaria-infected patients.

Adolescent↗

The immunogenicity of malarial antigen obtained from infected human placenta.

Malarial placenta antigen (MPA) was obtained from heavily parasitized human placenta. The immunogenicity of this antigen was tested by immunizing rabbits. The rabbit antiserum to malarial placenta antigen (anti-MPA) was absorbed with homogenate from nonparasitized human placenta. The anti-MPA serum was also absorbed with malarial placenta extract. Evaluation of the anti-MPA serum was done using the Ouchterlony immunodiffusion technique and by immunoelectrophoresis in agar. The results show that human malarial placenta antigen can stimulate the formation of anti-plasmodium antibodies. Although the antiserum produced also contained antibodies to some placental components, absorption studies showed that some malarial specific precipitinogens were produced. The significance of this in efforts to develop an effective malarial vaccine is discussed.

Animals↗

The occurrence and properties of E rosette inhibitory substance in the sera of malnourished children.

In vitro sheep erythrocyte (E) rosette inhibitory activity was observed in the sera of nine out of 22 (41%) children with kwashiorkor, three of 15 (20%) marasmic children, neither of the two children with marasmic-kwashiorkor and in one of 42 (2%) well nourished control children. Sera of children with kwashiorkor containing the E rosette inhibitory substance did not inhibit in vitro rosette formations by autologous lymphocytes whereas rosette formations by homologous lymphocytes were inhibited. Inhibition of E rosette formation occurred when lymphocytes were pretreated with serum having the inhibitory substance before incubation with sheep red cells, but there was no such inhibition when sheep red cells were pretreated with the same serum before incubation with lymphocytes. The inhibitory substance was observed to be stable at 4 degrees C up to about 1 week and migrated electrophoretically with the alpha-2 globulins. It was digested by papain. It is probable that the E rosette inhibitory substance demonstrated in the present study is attached to markers on T lymphocyte surfaces in some malnourished children thereby making the lymphocytes unreactive in vitro and presumably in vivo as well.

Blood Proteins↗

Positive correlation between degree of parasitemia, interferon titers, and natural killer cell activity in Plasmodium falciparum-infected children.

Natural killer (NK) cell activity and interferon levels have been measured in the peripheral blood of children acutely ill with Plasmodium falciparum infection. The NK cell levels were found to be raised in the malaria-infected children, with a positive correlation between the degree of parasitemia and lytic activity. Comparatively high titers of antiviral activity was discovered in sera from the majority of P. falciparum-infected children, again positively correlating with the degree of parasitemia and NK levels. The characteristics of the antiviral factor indicated alpha-type interferon to be the dominating agent involved. Addition of exogenous interferon in vitro potentiated the NK levels of PBL from normal children while having no significant impact on cells from malaria-infected children.

Antibodies, Viral↗