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Biomedical subjects

S Jaffar

Publications and source records attributed to S Jaffar.

At least 55 records · Page 3Linked to original sources
PubMed1997

Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine.

Two hundred twenty-one Gambian children vaccinated previously with one, two, or three doses of a meningococcal conjugate vaccine or two doses of polysaccharide vaccine before the age of 6 months were revaccinated at the age of 18-24 months with either meningococcal polysaccharide, conjugate, or inactivated polio vaccines. Children who had previously received one, two, or three doses of conjugate vaccine had significantly (P < .001) higher anti-group C meningococcal antibody levels following revaccination than did children vaccinated with a polysaccharide vaccine for the first time. Children vaccinated previously with two doses of polysaccharide vaccine had a lower group C antibody response than did control children. Group A antibody responses following revaccination of children who had previously received polysaccharide or conjugate vaccine were not significantly higher than those in control children. Thus, immunologic memory was probably induced by the group C but not by the group A component of the conjugate vaccine.

Antibodies, Bacterial↗
PubMed1997

Predictors of hypoxaemia in hospital admissions with acute lower respiratory tract infection in a developing country.

Since oxygen has to be given to most children in developing countries on the basis of clinical signs without performing blood gas analyses, possible clinical predictors of hypoxaemia were studied. Sixty nine children between the ages of 2 months and 5 years admitted to hospital with acute lower respiratory tract infection and an oxygen saturation (Sao2) < 90% were compared with 67 children matched for age and diagnosis from the same referral hospital with an Sao2 of 90% or above (control group 1), and 44 unreferred children admitted to a secondary care hospital with acute lower respiratory infection (control group 2). Using multiple logistic regression analysis, sleepiness, arousal, quality of cry, cyanosis, head nodding, decreased air entry, nasal flaring, and upper arm circumference were found to be independent predictors of hypoxaemia on comparison of the cases with control group 1. Using a simple model of cyanosis or head nodding or not crying, the sensitivity to predict hypoxaemia was 59%, and the specificity 94% and 93% compared to control groups 1 and 2, respectively; 80% of the children with an Sao2 < 80% were identified by the combination of these signs. Over half of the children with hypoxaemia could be identified with a combination of three signs: extreme respiratory distress, cyanosis, and severely compromised general status. Further prospective validation of this model with other datasets is warranted. No other signs improved the sensitivity without compromising specificity. If a higher sensitivity is required, pulse oximetry has to be used.

Acute Disease↗
PubMed1997

Prolongation of the QTc interval in African children treated for falciparum malaria.

Antimalarial drugs can affect the heart and trigger life-threatening arrhythmias. However, little is known about the frequency with which cardiac abnormalities occur during uncomplicated attacks of malaria. Therefore, we have studied the electrocardiograms of 139 Gambian children with uncomplicated falciparum malaria who were treated with co-artemether, pyrimethamine/sulfadoxine, or chloriquine. The QTc intervals were measured on presentation, and four and eight days after treatment. No significant differences in mean QTc or heart rate were found between children in the three treatment groups on days 0, 4, or 8. After adjustment for the type of antimalarial thearapy in an analysis of variance, the mean (SD) QTc intervals on days 0, 4, and 8 were 402 (22.6), 416 (23.1), and 405 (24.3) msec, respectively. The mean QTc on day 4 was significantly longer than the mean QTc on days 0 or 8 (P < 0.01 in both cases). A quadratic line was fitted for QTc against time for each antimalarial therapy. No significant differences were found between the quadratic lines of the three groups. A weak association was found between QTc and the degree of parasitemia (r = 0.17, P = 0.04) and temperature (r = -0.23, P = 0.01) measured on day 0. The QTcs were measured in 18 children who experienced a second episode of malaria. The changes in QTc observed during second episodes were similar to those observed during the first attack. Changes in QTc in five children who developed severe malaria were similar to those found in the remaining children who did not develop severe malaria. This study indicates that the QTc interval changes during the early phase of malaria and this change is independent of the type of antimalarial therapy given.

Child↗
PubMed1997

Predictors of a fatal outcome following childhood cerebral malaria.

Despite prompt treatment with an effective anti-malarial drug, cerebral malaria still has a mortality of 20-30%. To identify factors that may contribute to this high fatality rate, we have studied the relationship between clinical and laboratory features and a fatal outcome in 624 Gambian children with strictly defined cerebral malaria. One hundred twenty-four children (21.5%) died. Three-quarters of the deaths occurred within 24 hr of admission. Multiple logistic regression analysis showed that a cold periphery (odds ratio [OR] = 2.7), a deep coma (OR = 2.0), and hypoglycemia (OR = 4.1) were the clinical signs and laboratory parameters that predicted death most strongly. More than 90% of the children who died had at least one of these conditions. Also, children with elevated urea levels on admission or those who experienced multiple episodes of hypoglycemia or multiple convulsions subsequently were more likely to die. A combination of clinical and laboratory abnormalities can identify a group of children with cerebral malaria who are most at risk of dying, who require intensive care and who are candidates for new forms of therapy.

Age Factors↗
PubMed1997

Evaluation of an algorithm for the integrated management of childhood illness in an area with seasonal malaria in the Gambia.

Most of the 12.4 million deaths occurring every year among under-5-year-olds in developing countries could be prevented by the application of simple treatment strategies. So that health professionals who have had limited training can identify and classify the common childhood diseases, WHO developed a treatment algorithm (the Integrated Management of Childhood Illness (IMCI) or Sick Child algorithm), a prototype of which was tested in 440 Gambian children aged between 2 months and 5 years. The children were first assessed by a trained field worker using the algorithm, and then by a paediatrician whose clinical diagnosis was supported by laboratory investigations and, when indicated, a chest X-ray. Compared with the paediatrician's diagnosis, the sensitivity and specificity of the draft IMCI algorithm were, respectively, 81% and 89% for the detection of pneumonia, 67% and 96% for dehydration, 87% and 8% for malaria parasitaemia (any level), 100% and 9% for malaria parasitaemia (above 5000 parasites/microliter), 100% and 99% for measles, 31% and 97% for otitis media, and 89% and 90% for malnutrition. Among the children admitted by the physician, 45% had been recommended for admission by the algorithm. Intermittent fever, chills and sweats did not help in discriminating between malaria and non-malarious fevers; shivering or shaking of the body had a sensitivity of only 35%. While the algorithm dealt with the majority of presenting complaints, the most common problems not addressed by the chart were skin rashes (21%), mouth problems (8%), and eye problems (6%). The draft IMCI algorithm proved to be effective in the diagnosis of pneumonia, gastroenteritis, measles and malnutrition, but not malaria where its use without microscopy would result in considerable over-treatment, especially in a low transmission area or during a low transmission season in countries with seasonal malaria. The current algorithm would benefit from expansion to cover management of localized infections as well as skin, mouth and eye problems.

Algorithms↗
PubMed1997

Pallor as a clinical sign of severe anaemia in children: an investigation in the Gambia.

Anaemia associated with malaria is a major public health problem in African countries. Since most primary health facilities have to rely on physical signs and not laboratory tests to detect anaemic patients who need referral for blood transfusion, we have assessed the reliability of simple clinical signs to predict severe anaemia. A trained field assistant examined 368 children admitted to a tertiary care hospital, assessing the pallor of their eyelids (conjunctiva), palms and nailbeds, counting the respiratory rate, and looking for signs of respiratory distress. After the children's admission, their packed cell volume (PCV) was measured, and the need for transfusion and the outcomes were noted. A second observer examined 173 of these children so that interobserver variability in the detection of clinical signs could be assessed. A total of 27% of the 368 children had a PCV of < 15%. In a multiple regression analysis, definite pallor of the conjunctiva, definite pallor of the palms, and a "sick" appearance of the child were identified as independent significant predictors of a PCV of < 15%. The best predictor was a combination of definite pallor of the conjunctiva and pallor of the palms, with a sensitivity of 80% and a specificity of 85%. Inclusion of signs of respiratory distress did not improve the prediction. Pallor was a reproducible sign (weighted kappa statistic for the comparison between two observers: kappa = 0.6 for conjunctival pallor). We conclude that pallor can be used as a sign for referring children who may require blood transfusion.

Anemia↗
PubMed1997

Immune stimulation by syphilis and malaria in HIV-2-infected and uninfected villagers in West Africa.

Co-infections such as Mycobacterium tuberculosis (TB) and Pneumocystis pneumonia may affect the progress of HIV infection and speed the onset of death. As malaria and syphilis are both endemic in West Africa we examined their effects on HIV-2 infection, for these may also accelerate the progress of disease. A community-based case-control study was undertaken in a rural village in Guinea-Bissau, West Africa. One hundred and fifty asymptomatic subjects seropositive for HIV-2 and 154 age- and sex-matched controls were enrolled. Venous blood samples taken into EDTA were stained within six hours of collection with CD4 and CD8 monoclonal antibodies and processed by Q-Prep machine in the field. The stained cells were then transported on ice by road and analysed by FACS-can at the base laboratory in The Gambia within a week. The mean CD4% was significantly lower and geometric mean neopterin and beta 2-microglobulin levels were significantly higher in the HIV-2-infected subjects than in the controls (P < 0.01 for all cases versus all controls). The mean CD4% was lower and beta 2-microglobulin level was higher in both HIV-2 and control subjects with active or past syphilis when compared with subjects with no syphilis; however, syphilis did not have a marked effect on plasma neopterin level. Malaria infection raised neopterin levels, but had little effect on CD4%. Overall multiple regression analysis allowing for HIV-2 infection and other variables showed that syphilis lowered CD4% (P = 0.01) and raised beta 2-microglobulin levels (P = 0.05) and malaria raised neopterin levels (P = 0.05). The conclusions are that HIV-2 infection is associated with lower CD4% and higher neopterin and beta 2-microglobulin levels than controls, and co-infection with syphilis is associated with a further lowering of CD4%, suggesting a worse suppression of the immune system. Co-infection with malaria is associated with a modest immune disturbance.

Adult↗
PubMed1996

A trial of artemether or quinine in children with cerebral malaria.

BACKGROUND: Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance. Artemether is a new antimalarial agent that clears parasites from the circulation more rapidly than quinine, but its effect on mortality is unclear. METHODS: We conducted a randomized, unblinded comparison of intramuscular artemether and intramuscular quinine in 576 Gambian children with cerebral malaria. The primary end points of the study were mortality and residual neurologic sequelae. RESULTS: Fifty-nine of the 288 children treated with artemether died in the hospital (20.5 percent), as compared with 62 of the 288 treated with quinine (21.5 percent). Among the 418 children analyzed at approximately five months for neurologic disease, residual neurologic sequelae were detected in 7 of 209 survivors treated with artemether (3.3 percent) and 11 of 209 survivors treated with quinine (5.3 percent, P = 0.5). After adjustment for potential confounders, the odds ratio for death was 0.84 (95 percent confidence interval, 0.53 to 1.32) in the artemether group, and for residual neurologic sequelae, 0.51 (95 percent confidence interval, 0.17 to 1.47). There were fewer local reactions at the injection site with artemether than with quinine (0.7 percent vs. 5.9 percent, P = 0.001). CONCLUSIONS: Artemether is as effective as quinine in the treatment of cerebral malaria in children.

Antimalarials↗
PubMed1996

Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia.

OBJECTIVE: To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. DESIGN: An open, randomized immunogenicity study. SETTING: A busy urban health center in The Gambia. STUDY PARTICIPANTS: A total of 451 pregnant women enrolled during the third trimester of pregnancy. INTERVENTION: Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age. In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. MAIN OUTCOME MEASURES: Anti-PRP antibody measurements of maternal cord, and infant blood. RESULTS: Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer 9.0 micrograms/mL), which was greatest in women in their first or second pregnancy. Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations. In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35 and 2.84 micrograms/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 micrograms/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 micrograms/mL). CONCLUSIONS: In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization.

Antibodies, Bacterial↗
PubMed1996

Humidification of oxygen with unheated humidifiers in tropical climates.

In developing countries, oxygen therapy in hospitals is frequently humidified with unheated bubble-through humidifiers. We assessed the efficacy of humidification under such circumstances. The water temperature in the humidifier and the ambient air temperature were measured and compared to the oxygen flow rate. It was calculated that oxygen was cooled in the humidifier by 6.12 degrees C (95% CI: 5.88; 6.35) per liter of flow for flow rates up to 2 l/min. Using the average temperatures on the hospital ward in January and August, and the WHO-recommended flow rates of 0.5 l/min and 1 l/min, the relative humidity of the oxygen delivered to a child was estimated to be between 34% and 56%. We conclude that unheated bubble-through humidifiers achieve low humidity in oxygen in tropical climates. Some of the complications associated with the use of nasopharyngeal catheters for the delivery of oxygen might be explained by this, as oxygen of low humidity and temperature is delivered directly into the posterior nasopharynx.

Acute Disease↗
PubMed1996

A randomized trial of chloroquine, amodiaquine and pyrimethamine-sulphadoxine in Gambian children with uncomplicated malaria.

The increasing occurrence of chloroquine-resistant Plasmodium falciparum in sub-Saharan Africa makes it essential to reconsider current recommendations for the treatment of uncomplicated P.falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodiaquine (AQ), and pyrimethamine-sulphadoxine (PS) in rural Gambian children with uncomplicated P.falciparum malaria. Three hundred children were randomly assigned at the time of consultation (Do) to oral treatment with 25 mg/kg CQ, 25 mg/kg AQ (both given over 3 days), or 1.25/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for symptoms, malaria parasitaemia, and packed cell volume (PCV). Significantly more children treated with PS compared to CQ (17 vs 7%, P = 0.03) or AQ (17 vs 3%, P = 0.001) returned with clinical complaints during the first 3 days after treatment. Five of these patients had a generalized convulsion (1 from the AQ group, 4 from the PS group), of whom 4 developed cerebral malaria. At D7, significantly more patients treated with CQ compared to AQ (25 vs 7%, P = 0.0009) or PS (25 vs 4%, P = 0.0001) were parasitaemic. By D28, the cumulative number of parasitological failures was significantly higher in the CQ group compared to the AQ group (65 vs 35%, P = 0.0001), and significantly higher in the AQ group compared to the PS group (35 vs 14%, P = 0.001). Overall, 91% of parasitological failures observed during the study period were symptomatic and were consequently treated with an alternative antimalarial drug. Over the 28-day study period the mean PCV increased significantly less in the CQ group than in the PS group (1.2 vs 3.8%, P = 0.016) and was lower in the CQ group than in the AQ group (1.2 vs 2.7%, P = 0.12, not significant). These results suggest that PS acts more slowly than 4-aminoquinolines in controlling the clinical features of malaria, and that AQ can be considered as an interim alternative to CQ in the first-line therapy of uncomplicated malaria in African areas of high CQ resistance.

Amodiaquine↗
PubMed1996

A comparative study of parenteral chloroquine, quinine and pyrimethamine-sulfadoxine in the treatment of Gambian children with complicated, non-cerebral malaria.

Ninety-two children with complicated, but not cerebral, Plasmodium falciparum malaria, aged 1-9 years, were recruited between August 1992 and December 1994 to an open, randomized trial of parenteral chloroquine (28), pyrimethamine-sulfadoxine (P-S) (36) and quinine (28). The median fever clearance time was shorter for chloroquine (27 hours) than for quinine (42 hours) or for P-S (36 hours) (P = 0.02 and P = 0.06, respectively). The parasite clearance times were similar for chloroquine and P-S, but significantly shorter for chloroquine compared with quinine (54 hours vs 66 hours) (P = 0.007) and for P-S compared with quinine (42 hours vs 66 hours) (P < 0.001). However, three children who received chloroquine and three who received P-S required a change to treatment with quinine because of a clinical failure of their initial treatment. Four children died, one in the chloroquine group, one in the quinine group and two in the P-S group. Despite a high level of chloroquine resistance in the community, the majority of Gambian children with complicated malaria responded satisfactorily to parenteral chloroquine given under supervision. The clinical failure rates of chloroquine and P-S were similar. Parenteral chloroquine and P-S remain adequate treatments for complicated, non-cerebral malaria in Gambian children, provided children can be kept under close clinical observation so as to detect early any treatment failures. Parenteral P-S has the advantage that only one dose is required.

Antimalarials↗
PubMed1996

A community-based study of human immunodeficiency virus type 2 provirus load in rural village in West Africa.

A community-based study of provirus load in human immunodeficiency virus (HIV) type 2-infected subjects was done in a rural village in Guinea-Bissau. HIV-2 provirus load varied considerably, with a geometric mean of 124.3 (95% confidence interval, 86.0-179.6) copies/10(5) CD4 cells, which is a level similar to that found in HIV-1 infection. Neither malaria parasitemia, active syphilis, or human T cell leukemia virus coinfection significantly influenced provirus load, nor did age. Eleven of 104 HIV-2-infected subjects had died after 3 years of follow-up; 9 of those who died had a high provirus load of > or = 100 copies/10(5) CD4 cells and a relatively low CD4 cell percentage of < 29%.

Adult↗
PubMed1996

The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria.

Tumor necrosis factor (TNF) is thought to play a key role in the pathogenesis of cerebral malaria. A double-blind, placebo-controlled trial of an anti-TNF monoclonal antibody (B-C7) comprised 610 Gambian children with cerebral malaria, with mortality and residual neurologic sequelae as primary study end points. Sixty (19.9%) of 302 children who received B-C7 died compared with 64 (20.8%) of 308 children who received placebo (adjusted odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.42). Residual neurologic sequelae were detected in 15 (6.8%) of 221 survivors from the B-C7 group and in 5 (2.2%) of 225 survivors of the placebo group (adjusted OR, 3.35; 95% CI, 1.08-10.4). The monoclonal antibody used in this study did not improve survival in cerebral malaria and was associated with a significant increase in neurologic sequelae. A possible explanation of the latter observation is that the antibody acts to retain TNF within the circulation and thereby prolongs its effects on vascular endothelium.

Antibodies, Monoclonal↗
PubMed1995

HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load.

OBJECTIVES: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load. METHODS: Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2CBL-22 chronically infected C8166 cell line. A biotinylated primer was used to capture the 35S dATP-incorporated secondary PCR product in a quantitative radiometric assay. RESULTS: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r = -0.625, P = 0.003 and r = -0.674, P = 0.001, respectively). CONCLUSION: HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Excreta disposal behaviour and latrine ownership in relation to the risk of childhood diarrhoea in Sri Lanka.

A case-control study of environmental and behavioural risk factors for childhood diarrhoea was conducted in Kurunegala district, Sri Lanka. From five hospitals, 2458 children aged less than 5 years and suffering from diarrhoea were recruited as clinic cases, and a further 4140 reporting with complaints other than diarrhoea were recruited as clinic controls. Community-based cross-sectional surveys were also conducted in three of the five areas served by these hospitals, and from these a further 1659 children were recruited as community controls. Children from households where excreta were reported to be disposed of in a latrine were less likely to have diarrhoea than children whose families improperly disposed of excreta. The results obtained from comparisons of cases with clinic controls (adjusted odds ratio [OR] 1.42, 95% confidence interval [CI] : 1.01-1.98), and of cases with community controls (OR 1.35, 95% CI : 0.85-2.13) were in agreement, suggesting that no important selection bias operated on this association. If the observed proportion (91%) of improper excreta disposal among the population could be reduced to 50%, 12% of childhood diarrhoea episodes would be prevented. Although latrine ownership may be a necessary condition for safe excreta disposal behaviour, diarrhoeal morbidity may only be reduced in Sri Lanka if behavioural changes take place concomitant with the construction of sanitation facilities.

Case-Control Studies↗
PubMedDate not supplied

Can malaria chemoprophylaxis be restricted to first pregnancies?

The harmful effects of malaria are most pronounced during first pregnancies and chemoprophylaxis is most effective when given at this time. However, restriction of chemoprophylaxis to first pregnancies might lead to enhanced susceptibility to malaria during second pregnancies. We have investigated this possibility by studying the outcome of second pregnancies in 165 Gambian women who had received either malaria chemoprophylaxis with Maloprim or placebo during their first pregnancy. Many of these primigravidae did not present until the third trimester of pregnancy so that some are likely to have experienced a malaria infection before they started medication. The prevalence of malaria infection of the blood and of the placenta during second pregnancies was similar in women who had received chemoprophylaxis during their first pregnancy and in those who had not, and the mean birth weights of babies born to women in each group were almost identical. Thus, in areas where the epidemiology of malaria is similar to that of The Gambia and where most women present relatively late in pregnancy, it may be possible to restrict malaria chemoprophylaxis to first pregnancies with consequent savings in cost and a reduction in drug pressure on Plasmodium falciparum.

Antimalarials↗