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Biomedical subjects

U D'Alessandro

Publications and source records attributed to U D'Alessandro.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plasmodium berghei development in irradiated sporozoite-immunized C57BL6 mice.

The C57BL6 strain of mice is highly susceptible to Plasmodium berghei sporozoite infections and consequently requires repeated immunizations with irradiated sporozoites to obtain protective immunity. After a live sporozoite challenge in the immunized hosts, hepatic-stage parasites found in the liver after 48 h are of different sizes--small schizonts corresponding to blocked forms (derived from irradiated sporozoites), and schizonts of intermediate size (derived from live sporozoites). Large schizonts corresponding to mature hepatic forms are found only in unimmunized but challenged C57BL6 mice. Using monoclonal and polyclonal antibodies directed to liver-stage parasites, different patterns of binding reactivity to the above forms are observed. More than 20% of the irradiated sporozoites transform into blocked forms after immunization and persist in the liver. Upon sporozoite challenge in such immunized animals the rate of transformation of sporozoites into hepatic parasites is less than 2%. These observations shed light on the fate of live sporozoite development in irradiated sporozoite-immunized C57BL6 mice.

Animals↗
PubMed1999

Serological responses of Gambian children to immunization with the malaria vaccine SPf66.

Antibody responses to the malaria vaccine SPf66 and to its constituent peptides were measured over a period of 2 years in Gambian children who had been immunized with SPf66 or with a control vaccine (inactivated polio vaccine). Three hundred and six of 308 children (99%) who had received three doses of SPf66 vaccine had antibodies to SPf66 at a level above that found in European controls who had not been exposed to malaria. Responses to the constituent peptides derived from 35.1, 55.1 and 83.1-kDa proteins were found in 88%, 97% and 97% of children, respectively; 26% had an antibody response to the NANP repeat peptide of circumsporozoite protein which is also included in the SPf66 vaccine. A response to SPf66 was found in 22% of children who had received the control vaccine. Antibody responses to NANP, 35.1, 55.1 and 83.1-kDa peptide were found in 3%, 33%, 49% and 33% of these children. Overall, no significant correlation was found between the level of anti-SPf66 antibody at the beginning of the malaria transmission season following vaccination and the subsequent risk of malaria. However, further analysis showed that among the control children who had acquired antibodies to SPf66 as a result of natural exposure to malaria, those with high levels of anti-SPf66 were less at risk of malaria, perhaps reflecting their greater previous exposure and thus immunity. In contrast, among children who had received three doses of SPf66, those with high antibody levels were at greater risk of have malaria during the subsequent malaria transmission season.

Animals↗
PubMed1999

Predicting malaria infection in Gambian children from satellite data and bed net use surveys: the importance of spatial correlation in the interpretation of results.

In line with the renewed World Health Organization Global Malaria Control Strategy, we have advocated the use of satellite imagery by control services to provide environmental information for malaria stratification, monitoring, and early warning. To achieve this operationally, appropriate methodologies must be developed for integrating environmental and epidemiologic data into models that can be used by decision-makers for improved resource allocation. Using methodologies developed for the Famine Early Warning Systems and spatial statistics, we show a significant association between age related malaria infection in Gambian children and the amount of seasonal environmental greenness as measured using the normalized difference vegetation index derived from satellite data. The resulting model is used to predict changes in malaria prevalence rates in children resulting from different bed net control scenarios.

Animals↗
PubMed1998

An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of follow-up.

In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%, 30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.

Animals↗
PubMed1998

The Gambian National Impregnated Bednet Programme: costs, consequences and net cost-effectiveness.

Clinical trials have indicated that treating mosquito nets with insecticide could be a potentially cost-effective method of preventing malaria. As malaria is one of the most common causes of death in children under five in developing countries, there has been substantial interest in whether such findings can be replicated for a country's control programme in practice. The cost-effectiveness of the Gambian National Insecticide-impregnated Bednet Programme (NIBP), from the viewpoint of providers (government and non-governmental agencies) and the community, has been calculated. Information was collected from existing records, interviews with NIBP personnel, observation and household surveys. Information is provided on the resource use consequences of the NIBP in terms of reduced expenditure on anti-malaria preventive measures, treatment in government health services, household financed treatment and "charity" (burial, funeral and mourning activities), as well as cash income lost as a result of child death. The annual implementation cost of the NIBP was D757,875 (US$91,864), of which 86% was recurrent cost. The estimated number of death averted was 40.56. The net implementation cost-effectiveness ratio per death averted and discounted life years gained were D3884 (US$471) and D260 (US$31.5), respectively. Adding the cost of all mosquito nets would increase the cost-effectiveness ratios by over five times, which is an important consideration for countries with a lower coverage of mosquito nets per capita. It is concluded that insecticide-impregnated mosquito nets are one of the more efficient ways of reducing deaths in children under 10 years in rural Gambia.

Bedding and Linens↗
PubMed1998

Relative versus absolute risk of dying reduction after using insecticide-treated nets for malaria control in Africa.

Four recently completed large-scale randomized controlled trials have assessed the impact of insecticide-treated bednets and curtains on overall child mortality in Africa. These results have sparked numerous discussions among implementing agency representatives and researchers about the public health significance of the results. For the interpretation of impact, most of the arguments have been based on the observed decrease in protective efficacy (a relative measure of impact) with increasing malaria transmission (range: 14-29%, regression for trend: F = 245 on 1,2 DF, P < 0.003). However, an analysis of the absolute measure of impact (the risk difference) showed a different pattern. The impact ranges from 3.8 to 6.9 lives saved per 1000 children protected per year, without a significant trend (F = 2.8 on 1,2 DF, P = 0.2) and with equally high values in both low and high transmission sites. When assessing the public health importance of an intervention, both relative and absolute decrease in risk should be considered.

Africa↗
PubMed1998

Decreased antitoxic activities among children with clinical episodes of malaria.

Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children with clinical symptoms. Concentrations of soluble tumor necrosis factor receptor I and C-reactive protein were associated with levels of parasitemia. We detected antitoxic activities in sera as measured by their capacity to block toxin-induced Limulus amoebocyte lysate (LAL) activation. Symptomatic children had decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum erythrocyte membrane protein 1 and "Pfalhesin" (band #3) peptides, indicating that such IgG antibodies are stimulated by acute disease but are lost rapidly after the disease episode. Half of the children with symptomatic infections had low levels of haptoglobin, suggesting that these children had chronic P. falciparum infections which may have caused symptoms previously. Only a few of the children with asymptomatic P. falciparum infections had high parasite counts, and antitoxic immunity in the absence of antiparasite immunity appears to be rare among children in this community.

Amino Acid Sequence↗
PubMed1997

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6-11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant.

Child↗
PubMed1997

Plasmodium falciparum chloroquine and quinine sensitivity in asymptomatic and symptomatic children in São Tomé Island.

Plasmodium falciparum sensitivity to quinine in São Tomé was determined by in vivo and in vitro tests in 56 children with mild or cerebral malaria. Chloroquine sensitivity was assessed by in vitro tests in 105 parasitaemic asymptomatic children from the same community as the cases. The WHO standard methodology was used. No resistance to quinine was found by in vivo or in vitro tests in either group of patients or in asymptomatic children, although some degree of chloroquine resistance was found with the in vitro test. This was more common in patients than in asymptomatic children. Chloroquine resistance may be explained by the recent history of malaria in São Tomé Island, which caused an important decrease of immunity among the population and consequently the emergence of resistant strains. Implications of the use of in vivo/in vitro tests for determining the antimalarial drug policy within the primary health care system are discussed.

Adolescent↗
PubMed1997

The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.

During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77% of nets were treated with insecticide. In contrast, in villages where charges were made coverage was only 14%. During the first year of the NIBP, mortality in children was significantly lower in villages where insecticide was provided free than in the control villages. Introduction of a charge for insecticide into the first group of villages and the provision of free insecticide in the latter abolished this difference. The cash income of rural Gambians is very limited and payment of even $2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia.

Bedding and Linens↗
PubMed1996

Geographical perspectives on bednet use and malaria transmission in The Gambia, West Africa.

Insecticide-impregnated bednets are now widely accepted as an important tool in reducing malaria-related deaths in children in Africa. Defining the circumstances in which net treatment programmes are likely to be effective is essential to a rational development of this control strategy. In The Gambia a National Impregnated Bednet Programme was introduced into the primary health care system in 1992. Prior to its introduction baseline epidemiological and entomological studies were conducted throughout the country. These studies showed that in areas where mosquito biting nuisance was high, people protected themselves with bednets and that where mosquito densities (and therefore bednet usage) was low malaria prevalence rates were relatively high. Since the national programme is designed to assist only those people who already own a bednet (by providing the insecticide) an understanding of the factors which determine bednet ownership is needed to help evaluate the programme's effectiveness and provide guidelines for increasing bednet usage. Village scale bednet usage rates and malaria prevalence rates obtained from the baseline survey were correlated with certain geographical variables: dominant ethnic group, area, habitat, distance from the River Gambia and distance from the 'bluffline' (the interface between the sandstone soils and alluvial soils which border the river system). In a multiple regression analysis, bednet usage was independently associated with area (P < 0.001), ethnic group (P = 0.010), habitat (P = 0.006) and distance from the river (P = 0.013). A negative association of bednet usage with malaria prevalence persisted after allowing for the other variables. Malaria prevalence was not independently associated with area, ethnic group, habitat or distance from the river. Our analysis showed that the impregnated bednet programme is likely to be most effective in villages which are sited near to or on the alluvial soils in the middle and lower river zones. These villages, which were originally settled for easy access to the river (for transport) and its swampy margins (for rice production) are within the flight distance of mosquitoes that have their breeding sites on the poorly drained alluvial soils. Variation in malaria prevalence rates (after bednet usage has been taken into account) may be related to factors such as poverty and access to health care, and/or to localized differences in the ecology of The Gambia, which determine the duration and intensity of transmission. If the National Bednet Programme is to be effective throughout The Gambia it is vital to develop promotional activities which will encourage bednet usage in areas where nuisance biting by mosquitoes is low.

Animals↗
PubMed1996

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections.

A proportion of children with Plasmodium falciparum infection have a high parasitaemia without accompanying fever, indicative of different clinical thresholds of parasitaemia. Higher levels of IL-10, IL-1Ra and sIL-4R but not sIL-2R were found in children with P. falciparum malaria, compared with levels in children with asymptomatic P. falciparum infections and in healthy children. Concentrations of IL-10 and IL-1Ra were correlated with levels of parasitaemia, but the association of cytokine levels with disease was independent of the association with parasitaemia. Children may tolerate a high parasitaemia by neutralizing the parasite-derived toxins. When studying potential anti-toxic molecules we found that children with symptomatic infections had lower concentrations of a phospholipid-binding molecule, beta 2-glycoprotein I (beta 2-GPI), compared with children with asymptomatic infections or healthy children. In conclusion, cytokines were found in much higher concentrations in children with symptomatic P. falciparum malaria than in children with asymptomatic infections, whilst the former had lower concentrations of beta 2-GPI.

Antibodies, Antiphospholipid↗
PubMed1996

An efficacy trial of a malaria vaccine in Gambian infants and comparison with insecticide-treated bednets.

The SPf66 hybrid malaria vaccine is a polymeric, synthetic protein with amino-acid sequences derived from the pre-erythrocytic and asexual-blood-stage proteins of Plasmodium falciparum. SPf66 has already been found to have a 31% protective efficacy in Tanzanian children aged 1-5 years who lived in an area of intensive malaria transmission. A randomized, double-blind, placebo-controlled trial of SPf66 was carried out in Gambian infants. Overall, 630 children, aged 6-11 months at the time of the first dose, each received three doses of SPf66 or inactivated 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. Analysis of efficacy was restricted to 547 of the children (316 receiving SPf66 and 231 IPV). Although the efficacy of SPf66 on the first or only clinical attack was found to be 8% when results were compared with those for the children given the placebo (IPV), the malarial vaccine had no significant effect on fever with any parasitaemia, the overall incidence of clinical attacks, packed-cell volumes, parasite prevalences or spleen rates. Compared with the present vaccine, insecticide-treated bednets appear to offer better prospects for control of malaria in Africa.

Child, Preschool↗
PubMed1996

Implementing a nationwide insecticide-impregnated bednet programme in The Gambia.

Earlier studies in The Gambia suggested that the use of impregnated bednets might prove to be a useful malaria control strategy. Based on the results of these studies, in 1992 the Government of The Gambia was encouraged to initiate a National Impregnated Bednet Programme (NIBP) as part of the National Malaria Control Programme Strategy. This paper describes the implementation process/procedure of the NIBP. Evaluation results showed that, overall, 83% of the bednets surveyed has been impregnated, and 77% of children under the age of five years and 78% of women of childbearing age were reported to be sleeping under impregnated bednets.

Adolescent↗