C. Menendez

Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania

Effective, safe antimalarial vaccines have proved elusive. The synthetic polypeptide SPf66 vaccine is based on preerythrocytic and asexual blood-stage proteins of Plasmodium falciparum. We report here a randomised double-blind placebo-controlled trial of the efficacy of the SPf66 vaccine against clinical P falciparum malaria in idete, southern Tanzania, an area of intense perennial malaria transmission. 586 children aged 1-5 years received three doses of vaccine (n = 274) or placebo (n = 312). The incidence and density of parasitaemia were assessed through repeated cross-sectional surveys on subgroups of children. Morbidity was monitored over a 1 year period through passive case detection in all children plus active case detection in a subgroup of 191. An episode of clinical malaria was defined as measured fever (> or = 37.5 degrees C) and parasite density > 20,000/microL. No severe side-effects were seen and the frequency of mild side-effects after the third dose was less than 6%. The vaccine was highly immunogenic and after three doses all vaccine recipients had detectable anti-SPf66 antibodies: the geometric mean index of response was 8.3 in the vaccine group and 0.7 in the placebo group. The incidence of parasitaemia was similar in both groups. 123 children had at least one episode of clinical malaria during the follow-up period after the third dose and annual incidence rates were 0.25 in the vaccine group and 0.35 in the placebo group. Estimated vaccine efficacy was 31% (95% confidence interval 0-52%; p = 0.046). After the third dose there were 6 deaths among the study cohort (1 vaccine, 5 placebo). This study confirms that SPf66 is safe, immunogenic and reduces the risk of clinical malaria among children exposed to intense P falciparum transmission.

The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria

A randomized, double-blind, placebo-controlled community-based trial of oral iron supplementation (200 mg ferrous sulphate daily) administered to multigravid pregnant women by traditional birth attendants (TBAs) was carried out in a rural area of The Gambia. Iron supplementation led to a significant reduction in the prevalence of anaemia and of iron deficiency. Iron supplementation was not accompanied by increased susceptibility to malaria infection; there was no difference in the prevalence and severity of peripheral blood or placental malaria infection between the 2 groups of women. The birth weight of children born to women who received iron prophylaxis was increased by an average of 56 g. It is concluded that oral iron prophylaxis can be successfully delivered through TBAs integrated into a primary health care programme. This simple intervention can produce significant beneficial effects on the health of the mother without inducing increased susceptibility to malaria and has the potential for reducing perinatal mortality by increasing birth weight.

Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission

A longitudinal study of Plasmodium falciparum malaria in infants in Idete village, south‐eastern Tanzania, was conducted over a period of 14 months in order to determine the incidence of P. falciparum infection and clinical malaria in the first year of life. Of 1356 blood slides from cross‐sectional surveys, 52.1% were positive for asexual stages of P. falciparum. There were marked increases in P. falciparum prevalence, parasite densities, overall fever incidence and the incidence of malaria fevers with age for the first 6 months of life. The average attack rate, estimated from a reversible catalytic model, was 0.029 per day with a slight increase with age but there was no initial period of protection against infection in neonates. Estimated average duration of infections was 64 days, with infections in older infants lasting much longer than those contracted during the first 2 months of life.

Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

Summary backgroundu2002Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women

The distribution of birth weights among the infants of 172 Gambian primigravidae who had received chemoprophylaxis with Maloprim (pyrimethamine+dapsone) during pregnancy was compared with that of the infants of 149 primigravidae who had received placebo. Administration of chemoprophylaxis led to a reduction in the prevalence of low birth weight babies and to an increase in the median birth weight. However, these changes were not accompanied by a comparable increase in the prevalence of high birth weight babies. The perinatal mortality rate was lower, although not significantly so, among the babies of women who had received chemoprophylaxis. Thus, no evidence was found to support the view that administration of chemoprophylaxis might increase the risks of delivery by causing cephalo/pelvic disproportion.

The Response to Iron Supplementation of Pregnant Women With the Haemoglobin Genotype AA or AS

The influence of haemoglobin genotype on the response to iron supplementation was studied in a randomized, double blind, placebo-controlled trial involving 497 multigravid pregnant women from a rural area of The Gambia. Women were randomly allocated to receive either oral iron (60mg elemental iron per day) or placebo. At 36 weeks of pregnancy, women who had received oral iron during pregnancy had higher mean haemoglobin, packed cell volume, plasma iron and ferritin levels than did women who received placebo. Iron supplementation of pregnant women with the AA haemoglobin genotype also resulted in increases in the packed cell volume (PCV) and haemoglobin level measured after delivery, and in the birth weight of the infant. However, in AS women PCV and haemoglobin level at delivery were lower in the supplemented group and supplementation was also associated with reduced birth weights. In malaria endemic areas, pregnant women with the haemoglobin genotype AS may not benefit from iron supplementation during pregnancy.

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.

The incidence of clinical malaria detected by active case detection in children in Ifakara, southern Tanzania.

Between July 2000 and June 2001, we used weekly active case detection (ACD) of clinical malaria episodes in 618 children aged < 5 years to describe the epidemiology of malaria in Ifakara, southern Tanzania. Plasmodium falciparum-positive blood slides prepared from children with axillary temperature 37.5 degrees C were used to define clinical malaria and a rolling cross-sectional survey documented the prevalences of parasitaemia and anaemia. A random subsample of children was visited daily for 1 month at the end of the study to assess the effect of more frequent visits on estimated incidence rates. Only 50 (8%) children had 1 or more episodes of clinical malaria during the year, an overall incidence of 0.275 episodes/100 child-weeks-at-risk, with no age dependence. The maximum parasite prevalence of 25% was reached in children aged 4 years. The incidence of illness was significantly lower in children visited daily than in those visited weekly, suggesting a marked effect of frequent visits on estimated incidence rates. We conclude that the age pattern of malaria detected through ACD is a more robust epidemiological indicator than absolute incidence rate estimates and that, in contrast to the surrounding area, Ifakara town is subject to only moderate perennial malaria transmission.

A trial of the synthetic malaria vaccine SPf66 in Tanzania: rationale and design

The development of a safe, affordable and effective malaria vaccine to form part of control schemes in malaria endemic countries is a priority for researchers and public health officials. SPf66 is the first malaria vaccine to have shown partial protection against natural challenge in a phase III trial carried out in a hypoendemic area of Colombia. This paper describes the rationale and design of the first field trial of SPf66 outside South America, and the first to be conducted in an area of high perennial transmission.

Inter-observer variation in the assessment of clinical signs in sick Tanzanian children

We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged < 5 years admitted to hospital in January-June 1999 in Ifakara, southern Tanzania. Children with diagnoses of malaria, pneumonia, diarrhoea, anaemia and malnutrition were examined independently by 2 clinical officers. Findings were recorded on a standard proforma. The Kappa-statistic was used to assess inter-observer agreement for each sign. Physical signs were more likely to be agreed upon by clinicians if they involved inspection than if they involved auscultation. The signs included in the Integrated Management of Childhood Illness (IMCI) algorithm were found to be largely appropriate (Kappa-scores > 0.41) although there was only fair agreement (Kappa-score 0.21-0.40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0.199). All objective neurological signs were less reliably assessed in infants than in older children. The difficulties surrounding the diagnosis of impaired consciousness in young children should increase vigilance in the diagnosis and management of neurological complications of illnesses in infancy.