S. Bennett

Climate change: Migration as adaptation

Mobility can bring opportunities for coping with environmental change, say Richard Black, Stephen R. G. Bennett, Sandy M. Thomas and John R. Beddington.

Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity

Summary We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, Pf MSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3‐ to 8‐year‐old children was conducted to examine the relationship between naturally acquired immune responses to Pf MSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross‐sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lymphoproliferation and interferon‐gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of Pf MSP1 were also significantly associated with protection.

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.

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.

The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.

The interaction between Plasmodium falciparum and P. vivax in children on Espiritu Santo island, Vanuatu

Studies of the prevalence and incidence of malaria were conducted in children < 10 years old living in 10 rural villages on the island of Espiritu Santo, Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout the year but the relative contributions of the 2 major species were highly dependent on season. Plasmodium falciparum predominated in the long wet season (November-May) and P. vivax in the dry season (June-October). Case definitions for malaria, derived using a multiple logistic regression method, showed that parasite densities associated with clinical disease were low; case definitions for P. falciparum (> 1000 parasites/microL in children > 1 year old and > 500 microL in infants) and P. vivax (> 500 parasites/microL at all ages) were both associated with a specificity and sensitivity of > 90%. Like prevalence data, malaria morbidity was highly seasonal; 80% of clinical P. falciparum infections occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed infections were rare. Malaria was important cause of morbidity with children < 5 years old experiencing 1.3-3.0 episodes of clinical malaria per year and 23% of fevers being attributable to malaria in this age group. Children aged 5-9 years continued to suffer one episode of clinical malaria per year. The peak incidence of P. vivax malaria occurred earlier in life than the peak incidence of P. falciparum malaria. The possible interactions between these 2 parasite species are discussed.

Socio-economic risk factors for malaria in a peri-urban area of The Gambia

Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value.

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.

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.

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.