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Biomedical subjects

U D'Alessandro

Publications and source records attributed to U D'Alessandro.

At least 55 records · Page 3Linked to original sources
PubMed1995

Efficacy trial of malaria vaccine SPf66 in Gambian infants.

SPf66 malaria vaccine is a synthetic protein with aminoacid sequences derived from pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. SPf66 was found to have a 31% protective efficacy in an area of intensive malaria transmission in Tanzanian children, 1-5 years old. We report a randomised, double-blind, placebo-controlled trial of SPf66 against clinical P falciparum malaria in Gambian infants. 630 children, aged 6-11 months at time of the first dose, received three doses of SPf66 or injected polio vaccine (IPV). Morbidity was monitored during the following rainy season by means of active and passive case detection. Cross-sectional surveys were carried out at the beginning and at the end of the rainy season. An episode of clinical malaria was defined as fever (> or = 37.5 degrees C) and a parasite density of 6000/microL or more. Analysis of efficacy was done on 547 children (316 SPf66/231 IPV). No differences in mortality or in health centre admissions were found between the two groups of children. 347 clinical episodes of malaria were detected during the three and a half months of surveillance. SPf66 vaccine was associated with a protective efficacy against the first or only clinical episode of 8% (95% CI -18 to 29, p = 0.50) and against the overall incidence of clinical episodes of malaria of 3% (95% CI -24 to 24, p = 0.81). No significant differences in parasite rates or in any other index of malaria were found between the two groups of children. The findings of this study differ from previous reports on SPf66 efficacy from South America and from Tanzania. In The Gambia, protection against clinical attacks of malaria during the rainy season after immunisation in children 6-11 months old at time of the first dose was not achieved.

Animals↗
PubMed1995

Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme.

After the success of a controlled trial of insecticide-treated bednets in lowering child mortality, The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) in 1992 with the objective of introducing this form of malaria control into all large villages in The Gambia. Five areas (population 115,895) were chosen as sentinel sites for evaluation of the NIBP. During the first year of intervention a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages (rate ratio 0.75 [95% CI 0.57-0.98], p = 0.04). If one area where the programme was ineffective was excluded, the reduction was 38% (0.62 [0.46-0.83), p = 0.001). A decrease in rates of parasitaemia and high-density parasitaemia, an increase in mean packed-cell volume (rate ratio 0.75 [95% CI 0.59-0.98], p = 0.04) and an improvement in the nutritional status of children living in treated villages were also detected. In a country such as The Gambia, where nets were widely used and which has a good primary health care system, it is possible to achieve insecticide-treatment of bednets at a national level with a significant reduction in child mortality; but at a cost which the country cannot afford.

Bedding and Linens↗
PubMed1995

Entomological evaluation of the Gambia's National Impregnated Bednet Programme.

Entomological studies were conducted in paired study villages in three of the five study areas used for the epidemiological assessment of the Gambia's National Impregnated Bednet Programme. Baseline data collected in 1991 were compared with post-intervention data from 1992, when one of each village pair (from areas II, III and V) was included in the treatment programme in which villagers' nets were dipped in permethrin. In a longitudinal study, indoor-resting densities of Anopheles gambiae s.l. in the treated villages were significantly reduced, when compared with their paired untreated village, in areas II (t = 3.32, 13 degrees of freedom, P = 0.006) and III (t = 3.71, 13 degrees of freedom, P = 0.003). However, this was not associated with higher outdoor-biting rates in the evenings in the treated villages than in the controls. The reduction in vector population was most evident in area II, where the treated village was relatively isolated and 74% of the population slept under a treated net. Anopheles gambiae s.l. were also collected during two fortnightly periods in area V, where the sporozoite rates in 1991 had been relatively high (7.65% and 6.07%). There was no significant decrease in the sporozoite rate in the treated village in area V in 1992, despite the fact that this village was over 5 km from its nearest neighbouring village. However, the proportion of villagers sleeping under a treated net in this village was < 50%. No clear evidence for an epidemiologically significant 'mass killing effect', resulting from the village-wide use of treated nets, emerges in this or any other study undertaken in The Gambia. However, such an effect is indicated by results from Salikene, where the village mosquito population was relatively isolated and where the majority of the population slept under a treated net. This situation is unlikely to be repeated in most Gambian villages in the primary-health-care scheme, since treated and untreated villages are generally interspersed and the mosquito populations move freely between them. We must therefore conclude that, on a national scale, the nets provide an exceptionally high level of personal rather than community protection. The mechanisms underlying the personal protection are, however, still unclear.

Animals↗
PubMed1995

A pilot safety and immunogenicity study of the malaria vaccine SPf66 in Gambian infants.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been undertaken in 150 Gambian infants. No significant systemic side effects were recorded but modest local reactions were seen after the administration of a third 1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a 0.5 mg dose. However, antibody levels fell rapidly after administration of the third dose of vaccine and showed little change over the following malaria transmission season. The incidence of clinical malaria was higher among children who received SPf66 than among children who received inactivated polio vaccine, the effect being most marked among children who received 1.0 mg Colombian SPf66. As the trial was not designed to measure the effect of SPf66 on morbidity from malaria, the significance of this finding is uncertain.

Animals↗
PubMed1994

Financing mechanisms for village activities in The Gambia and their implications for financing insecticide for bednet impregnation.

The recent enthusiasm for impregnated bednets as a malaria control measure leaves unresolved the question of how to finance them. The National Impregnated Bednet Programme in The Gambia faced the question of how to obtain funds from villages to finance the cost of insecticide, but knew very little about current village fundraising for development purposes. A survey was conducted of such fundraising, and questions also asked about willingness to pay for insecticide and preferred means of paying. All 53 villages surveyed paid taxes/rates, but 34% of villages reported no voluntary fundraising. The most common reason for collecting money was for the maintenance of wells (40% of villages). Collective farming was used as a means of raising money in 32% of villages. There was some variation in the type and extent of fundraising by region and also by the predominant ethnic groups of the village. Villages with voluntary fundraising activities seemed to have well established collective mechanisms for agreeing on sums to be collected and their use, and for collecting and recording income and expenditure. Non-payment was rare, and misuse of funds was not reported. Respondents were asked how much compounds might be willing to pay for insecticide impregnantion: the most frequently cited maximum amounts were D5 and 10, and minimum D1 and 5 (D15 = 1 pound). The paper discusses payment options for insecticide, such as whether the village should be allowed to decide itself how to raise funds, and whether the payment should be made only by households with nets or by a village-wide mechanism such as collective farming.(ABSTRACT TRUNCATED AT 250 WORDS)

Agriculture↗
PubMed1994

Nationwide survey of bednet use in rural Gambia.

A nationwide survey was carried out to investigate the use of bednets in rural areas of the Gambia, particularly among children under 5 years old and among pregnant women. A stratified multistage design was used; 360 compounds in 60 villages were visited. Overall, 58% of beds had a net, with very little difference between villages with primary health care (PHC) facilities and those without (non-PHC). Bednet use was higher in the Central Region (76%) than in the Western and Eastern Regions (both 51%). It was highest among the Jola ethnic group (77%) and lowest among Sarahulis and other minority groups. Use of bednets was higher among target groups (such as infants, children under 5 years old, and pregnant women) than among the general population, and reached a level of over 90% in these groups in the Central Region. Use was associated with possession of a metal bed and a radio. Previous trials of impregnated bednets in the Gambia have been carried out in the Central Region, where bednet use is highest. The efforts of the National Impregnated Bednet Programme should therefore concentrate on the other regions and among the minority ethnic groups in order to increase bednet ownership.

Adolescent↗
PubMed1993

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 4. Perceptions of the causes of malaria and of its treatment and prevention in the study area.

Perceptions of the causes of malaria, its treatment and prevention were studied among 996 adults, selected randomly from 73 villages and hamlets in a rural area of The Gambia. Structured questionnaires and other interview techniques were used for data collection. Malaria has no specific name in the study area; it is referred to commonly as Fula kajewo (Fula fever). Only 28% of the respondents knew that mosquitoes transmitted malaria. However, most people believed correctly that August to October was the main malaria season. Eighty-six per cent of the subjects were bed net users. The majority of nets were produced locally, usually white in colour and made of sheeting fabrics. Usage of nets was correlated with ethnic group, age and polygamy but not with education, income, occupation or ownership of certain items which indicate high social status. Analysis of expenditure on mosquito coils indicated that non-users of nets spent 43% more on coils than did users. Bed nets have been used for a long time in the study area; 98% of users saw their parents using them during their childhood.

Adult↗
PubMed1992

Treponemal infection and the outcome of pregnancy in a rural area of The Gambia, west Africa.

Of 826 pregnant women studied in a rural area of The Gambia, 77 (9.3%) were seropositive for a treponemal infection (positive rapid plasma reagin [RPR] and Treponema pallidum hemagglutination [TPHA] test). The perinatal death rate recorded prospectively in babies of 77 seropositive women (39.0/1000 births) was less than that among babies of 720 seronegative women (77.6/1000 births; odds ratio, 0.48; 95% confidence interval, 0.15-1.57). No increase in mortality or morbidity was found among the children of 39 seropositive women compared with the children of 39 control women. Seropositivity was found in only 20 (1.1%) of 1872 children less than 14 years old residing in the same community. The finding that the babies of rural Gambian women seropositive for syphilis are not at risk of early death is of importance in determining the priority that should be given to establishing antenatal screening programs in The Gambia and neighboring communities.

Adolescent↗
PubMedDate not supplied

Malaria prevalence is inversely related to vector density in The Gambia, West Africa.

Baseline epidemiological and entomological studies were conducted in 5 different areas of The Gambia before the introduction of a national malaria control programme, the objective of which was to treat all the bed nets belonging to people living in primary health care villages with insecticide. All malariometric indices used (parasite density, parasite rates, splenomegaly, and packed cell volume) indicated that malaria transmission was more intense in the east of the country than elsewhere. High transmission in the east was associated with a high sporozoite rate but not with the greatest vector abundance; the lowest malaria prevalence rates were found in villages which were close to very productive breeding sites of Anopheles gambiae s.l. Bed net usage was strongly correlated with vector density and the highest malaria rates were found in villages where bed net usage was relatively low. These results suggest that in The Gambia malaria prevalence rates are reduced where nuisance biting by mosquitoes is sufficient to encourage the population to protect themselves with bed nets.

Animals↗
PubMedDate not supplied

A comparison of the efficacy of insecticide-treated and untreated bed nets in preventing malaria in Gambian children.

An evaluation of the Gambian national insecticide bed net programme, which has introduced insecticide treatment of bed nets into all primary health care (PHC) villages in The Gambia, provided an opportunity to compare the individual risk of malaria in children who slept under untreated or insecticide-treated bed nets. 2300 children 1-4 years old were selected for a survey at the end of the 1992 rainy season, 1500 from PHC villages and 800 from non-PHC villages. All malariometric indices were lower, and the mean packed cell volume was higher, in children who slept regularly under treated or untreated bed nets than in those who did not use a net. This study suggested that untreated bed nets provide some individual protection against malaria, although not as efficiently as that provided by insecticide-treated bed nets which were particularly effective at preventing infections accompanied by high parasitaemia.

Bedding and Linens↗
PubMedDate not supplied

Intensity of malaria transmission, antimalarial-drug use and resistance in Uganda: what is the relationship between these three factors?

We studied (in 1998 and 1999) some factors that may be linked to the spread of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance in 7 discrete communities in Uganda. Exposure to malaria infection was measured by parasitological surveys in children aged 1-9 years, drug use by community surveys and drug resistance by in-vivo tests on children aged 6-59 months with clinical malaria. CQ use was inversely related to parasite prevalence (r = -0.85, P = 0.01). CQ and SP treatment failure rates varied significantly according to parasite prevalence (P = 0.001 and 0.04 respectively). The highest CQ (42.4%, 43.8%) and SP (12.5%, 14.8%) treatment failure rates were observed in sites characterized by high parasite prevalence. Using areas with medium parasite prevalence as reference, the relative risk (RR) for CQ treatment failure was 3.2 (95% CI 1.6-6.4) in high parasite prevalence sites and 3.1 (95% CI 1.2-7.7) in low parasite prevalence sites. The RR for SP treatment failure was also higher in sites with high parasite prevalence but low in those with low parasite prevalence. According to our findings, drug resistance seems to spread faster in higher transmission areas, regardless of drug pressure. In low transmission areas, drug pressure seems to be the critical factor. A decrease in transmission coupled with rational use of drugs may delay the spread of resistance.

Adolescent↗
PubMedDate not supplied

Efficacy of artesunate plus chloroquine for uncomplicated malaria in children in Sao Tome and Principe: a double-blind, randomized, controlled trial.

We conducted a double-blind, randomized, placebo-controlled trial in Sao Tome and Principe to investigate the safety, tolerability and efficacy of chloroquine (CQ) combined with artesunate (AS) over CQ monotherapy. Four hundred children, aged 6-59 months, with acute uncomplicated Plasmodium falciparum malaria were randomized to receive a standard dose of CQ (25 mg/kg bodyweight) over 3 d or CQ + AS (4 mg/kg bodyweight) daily for 3 d. Children were followed-up for 28 d. The combined treatment was well tolerated and there were no serious drug-related adverse events. By day 2 parasite clearance was significantly faster for children treated with CQ + AS compared with CQ alone (29/194 [14.9%] vs. 168/190 [88.4%] still parasitaemic, P< 0.0001). Day 14 parasitological failure rates were 153/191 (80.1%) for CQ alone compared with 32/193 (16.6%) in the CQ + AS group (odds ratio [OR] =20.2, 95% CI 11.7-35.4, P< 0.001). Corresponding clinical failure rates were 128/161 (67.0%) and 12/193 (6.2%) (OR = 30.6, 95% CI 15.3-62.7, P< 0.001). By day 28 the parasitological failure rates (new infections excluded) were 155/191 (81.1%) in the CQ group and 63/194 (32.4%) in the CQ + AS group (OR = 8.9, 95% CI 5.4-14.7, P< 0.001). Symptoms resolved faster in children who received AS. They were also less likely to be gametocytaemic after treatment. The combination treatment was well tolerated and considerably improved treatment efficacy. However, the current levels of CQ resistance preclude its use in Sao Tome where CQ should be abandoned as first-line drug. However, CQ + AS may be an option in areas where CQ resistance is lower.

Acute Disease↗
PubMedDate not supplied

Population-based validation of dihydrofolate reductase gene mutations for the prediction of sulfadoxine-pyrimethamine resistance in Uganda.

Mutations in the dihydrofolate reductase gene (dhfr) of Plasmodium falciparum have been proposed as molecular markers for the surveillance of sulfadoxine-pyrimethamine (SP)-resistant malaria, but such proposals have not been validated. At 7 Ugandan sites in 1999, we determined the population-based prevalence of infections with mutations and the mutant allele frequency of dhfr codons 108, 51, and 59 using a random sample of infected individuals aged 1-45 years. Sulfadoxine-pyrimethamine treatment failure was independently estimated by in vivo tests in 327 children aged 6-59 months with clinical malaria. The prevalence of infections with the single point mutations and the dhfr codons 108 and 51 mutant allele frequency were not correlated to SP treatment failure. However, the dhfr codon 59 mutant allele frequency was positively correlated to SP treatment failure (r = 0.72, P = 0.06). The ratio of the infections with the mutant to wild genotype (M/W) and that of the mutant to wild allele (MA/WA) had the same values. Both dhfr codon 59 M/W and MA/WA ratio were significantly and positively correlated to SP treatment failure (r = 0.73, P = 0.05). Moreover, the prevalence of infections with only 2 mutations (Asn-108 plus Ile-51) was significantly and inversely correlated to the prevalence of infections with 3 mutations (Asn-108 plus Ile-51 plus Arg-59) (r = 0.92, P = 0.004), suggesting the stepwise accumulation of the dhfr mutations is Asn-108 Ile-51 Arg-59 and further supporting the idea of using the dhfr codon 59 M/W ratio as a molecular index for the prediction of SP treatment failure. Atthe population level, the dhfr codon 59 M/W ratio is a simple and stable index for the estimation of SP treatment failure.

Adolescent↗
PubMedDate not supplied

The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia.

In 1992, the Gambian national impregnated bed net programme (NIBP) introduced insecticide treatment of bed nets into half of the primary health care villages in The Gambia. One component of the evaluation of this programme was the determination of whether it had any impact on the outcome of pregnancy in primigravidae. From February 1992, 651 primigravidae were recruited into the study. Less than 50% of them used an insecticide-treated bednet. During the rainy season the prevalence of Plasmodium falciparum among primigravidae was lower, fewer babies were classified as premature, and the mean birth weight was higher in villages where treated bed nets were used than in control villages. Therefore, during the rainy season, despite the low use of insecticide-treated bed nets by Gambian primigravidae, the NIBP had some impact on the outcome of pregnancy, particularly on the percentage of premature babies, and this was probably due to the decreased risk of malaria infection achieved during this period.

Adolescent↗
PubMedDate not supplied

C-reactive protein and haptoglobin in the evaluation of a community-based malaria control programme.

When cross-sectional surveys are used to evaluate malaria intervention programmes in the community, the prevalence of morbidity is difficult to assess because of the fluctuating nature of malarial fever. We have therefore investigated the impact of bed net usage on 2 surrogate markers of malarial morbidity: (i) elevated C-reactive protein (CRP) (> 8 mg/L) plus detectable parasitaemia, as an indicator of malaria-induced acute-phase response; and (ii) reduced haptoglobin levels (< 180 mg/L), which in this population indicates malaria-induced intravascular haemolysis. Among 1505 Gambian children 1-5 years old, examined on a single occasion at the end of the malarial transmission season, 5% had parasitaemia plus fever, while 24% had parasitaemia plus elevated CRP, and 35% had low haptoglobin. The proportion of children who had parasitaemia plus elevated CRP was significantly lower among those who had slept under insecticide-treated bed nets than among those who did not use a bed net (16% vs. 34%, P < 0.003), and the proportion with low haptoglobin differed similarly (24% vs. 49%, P < 0.003). Use of an untreated bed net had a weaker effect on both indices (22% had parasitaemia plus elevated CRP, 34% had low haptoglobin). CRP and haptoglobin are simple and inexpensive to measure in large numbers of people, and these results suggest that they could be useful for the assessment of malaria intervention programmes.

Bedding and Linens↗
PubMedDate not supplied

The Gambian National Impregnated Bed Net Programme: evaluation of effectiveness by means of case-control studies.

Two case-control studies, one on mortality and the other on malaria morbidity, were carried out in order to evaluate the impact of the Gambian National Insecticide Bed Net Programme during the second year of intervention and to explore the feasibility of such a study for the evaluation of programme effectiveness. For the mortality study, children 1-9 years old who died during the 1993 rainy season were matched by age and sex with 2 healthy controls from the same village. For the morbidity study, children 1-9 years old attending Fatoto or Jahalia Health Centres in The Gambia and who had fever and parasitaemia > or = 5000/microL were matched by age with a child attending the health centres without fever or parasitaemia. An additional healthy control was recruited from the case's village. No impact of insecticide-treated bed nets on mortality was detected and this was in keeping with the results obtained by prospective surveillance. A protective effect of insecticide-treated nets on malaria morbidity was detected when cases were compared with controls recruited at the health centres. However, this disappeared when cases were compared with controls recruited from the cases' villages. The mortality case-control study suggested that reducing the time between onset of disease and treatment may have an important impact on childhood mortality. In order to calculate programme cost-effectiveness, important for informed resource allocations to be made by health managers, it is essential to obtain evidence of effectiveness. This can be done by means of case-control studies, which are easier to carry out and require fewer resources than prospective surveillance. Nevertheless, it is necessary to be conscious of their pitfalls, particularly of the bias involved in the choice of cases and controls. The measurement of insecticide on the nets of the cases or controls is essential for such studies.

Case-Control Studies↗
PubMedDate not supplied

Levels of tumour necrosis factor and soluble TNF receptors during malaria fever episodes in the community.

The pyrogenic cytokine, tumour necrosis factor (TNF), is a mediator of malaria fever. Since high plasma levels of TNF are sometimes found in afebrile individuals with Plasmodium falciparum parasitaemia, it has been suggested that soluble forms of TNF receptors (sTNF-R55 and sTNF-R75) in the plasma may act to inhibit the pyrogenic effect of TNF. We have investigated plasma levels of TNF, sTNF-R55 and sTNF-R75 in relation to episodes of malaria fever detected in a cross-sectional study of 313 rural Gambian children during the malaria transmission season. Levels of TNF were significantly higher in the 20 children who had parasitaemia associated with fever than in 120 children who were afebrile despite malaria infection and 173 who had no detectable parasitaemia. In contrast, soluble TNF receptor levels did not differ between these clinical groups and, in a logistic regression model which included level of parasitaemia, we found TNF but not soluble TNF receptor levels to be associated with the presence of fever. These data support the role of TNF in malaria fever but suggest that soluble TNF receptors are not a major factor in modulating the fever.

Child, Preschool↗