Malaria parasitaemia in relation to HIV status and vitamin A supplementation among pre-school children

OBJECTIVES: To ascertain whether malaria parasitaemia in children is associated with HIV status. To examine the effect of vitamin A supplementation on malaria parasitaemia in children. METHODS: We studied the cross-sectional associations between HIV status and malaria parasitaemia among 546 children 6-60 months of age who participated in a double-blind, randomized clinical trial of vitamin A supplementation. Prevalence ratios and 95% confidence intervals (CI) were estimated for the presence of malaria parasites at baseline by HIV status in uni- and multivariate models that adjusted for sociodemographic and environmental variables. Among children with malaria, correlates of high parasite loads were identified. Next, we examined the effect of vitamin A supplementation on the risk of malaria parasitaemia and high parasite density at 4-8 months of the first dose in a subset of children. RESULTS: The prevalence of malaria parasitaemia was 11.4% among HIV-infected children, compared with 27.6% among uninfected. After adjusting for season, anaemia, use of bednets, maternal education and indicators of socioeconomic status, we found some evidence for lower prevalence of parasitaemia among HIV positive compared with HIV-negative children (prevalence ratio=0.56; 95% CI=0.29, 1.09; P=0.09). Other important correlates of malaria parasitaemia at baseline included low level of maternal education, poor quality of water supply, and the presence of animals at home. Vitamin A supplementation did not have a significant effect on malaria parasitaemia at 4-8 months of follow-up, overall or within levels of potential effect modifiers. CONCLUSION: HIV infection appears to be negatively correlated with malaria parasitaemia in this group of children. Investing in women's education is likely to decrease the prevalence of malaria parasitaemia in children. Vitamin A supplementation does not seem to have an effect on malaria parasitaemia in this population; possible benefits against clinical episodes and severe malaria deserve further examination.     

Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

Objectives To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)₅ GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. Methods Cross‐sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. Results Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non‐responders [(NANP)₅ (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46–0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48–0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50–1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32–0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38–1.05; P = 0.08). Conclusion Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.     

Changing pattern of malaria in Bissau, Guinea Bissau

Objective To describe the epidemiology of malaria in Guinea‐Bissau, in view of the fact that more funds are available now for malaria control in the country. Methods From May 2003 to May 2004, surveillance for malaria was conducted among children less than 5 years of age at three health centres covering the study area of the Bandim Health Project (BHP) and at the outpatient clinic of the national hospital in Bissau. Cross‐sectional surveys were conducted in the community in different malaria seasons. Results Malaria was overdiagnosed in both health centres and hospital. Sixty‐four per cent of the children who presented at a health centre were clinically diagnosed with malaria, but only 13% of outpatient children who tested for malaria had malaria parasitaemia. Only 44% (963/2193) of children admitted to hospital with a diagnosis of malaria had parasitaemia. The proportion of positive cases increased with age. Among hospitalized children with malaria parasitaemia, those less than 2 years old were more likely to have moderate anaemia (RR = 1.27; 95% CI: 1.02–1.56) (P = 0.03) or severe anaemia (RR = 1.67; 95% CI: 1.25–2.24) (P = 0.0005) than older children. The prevalence of malaria parasitaemia in the community was low (3%, 53/1926). Conclusion In Bissau, the prevalence of malaria parasitaemia in the community is now low and malaria is over‐diagnosed in health facilities. Laboratory support will be essential to avoid unnecessary use of the artemisinin combination therapy which is now being introduced as first‐line treatment in Bissau with support from the Global Fund.     

The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial

Objective To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria‐related morbidity in children <5 years of age who already had access to home‐based management of malaria (HMM) for presumptive treatment of fevers. Method Thirty community‐based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate‐amodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross‐sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children. Results During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: ?9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2–78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration. Conclusion In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.     

The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea

Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases. To determine the influence of zinc on malaria morbidity we conducted a randomized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea. A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136) or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center. Cross-sectional surveys were conducted at the beginning, middle, and end of the study to assess infection rates, parasite density, spleen enlargement, and hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P = 0.037) reduction in Plasmodium falciparum health center-based episodes, defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever. Episodes accompanied by any parasitemia were also reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or = 100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum. Zinc had no consistent effect on cross-sectional malariometric indices. Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo, such changes were absent at the mid-study survey. These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum.     

Seasonal profiles of malaria infection,anaemia, and bednet use among age groups and communities in northern Ghana

We conducted all-age point prevalence surveys to profile the severity and seasonality of malaria and anaemia in Kassena-Nankana District of northern Ghana. Random cross-sectional surveys were timed to coincide with the end of low (May 2001) and high (November 2001) malaria transmission seasons and to yield information as to the potential value of haemoglobin (Hb) levels and parasitaemia as markers of malaria morbidity and/or malaria vaccine effect. Parasitaemia was found in 22% (515 of 2286) screened in May (dry-low transmission), and in 61% of the general population (1026 of 1676) screened in November (wet-high transmission). Malaria prevalence in May ranged from 4% (infants <6 months and adults 50-60 years) to 54% (children 5-10 years). Age-specific malaria prevalence in November ranged from 38% (adults 50-60 years) to 82% (children 5-10 years). Differences between low- and high-transmission periods in the prevalence of severe anaemia (SA) among young children (6-24 months) were unexpectedly comparable (low, 3.9%vs. high, 5.4%; P = 0.52) and greatly reduced from levels measured in this same community and age group in November 2000 (12.5%) and November 1996 (22.0%). Despite the lower frequency of anaemia/SA in young children surveyed in 2001, it was still clear that this condition was strongly associated with parasitaemia and that children under 5 years of age experienced a significant drop in their mean Hb levels by the end of the high transmission season. Prevalence of parasitaemia was significantly lower (P < 0.01) among infants and young children (<2 years) whose parents reported the use of bednets. There was a significantly lower risk of parasitaemia among infants [odds ratio (OR) 6-8] and young children (OR 3-4) living in the central, more urbanized sector of the study area.     

Iron deficiency and malaria among children living on the coast of Kenya

Both iron deficiency and malaria are common in much of sub-Saharan Africa, and the interaction between these conditions is complex. To investigate the association between nutritional iron status, immunoglobulins, and clinical Plasmodium falciparum malaria, we determined the incidence of malaria in a cohort of children between the ages of 8 months and 8 years who were living on the Kenyan coast. Biochemical iron status and malaria-specific immune responses were determined during 2 cross-sectional surveys. We found that the incidence of clinical malaria was significantly lower among iron-deficient children (incidence-rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.51-0.99; P<.05), that the incidence of malaria was significantly associated with plasma ferritin concentration (IRR for log ferritin concentration, 1.48; 95% CI, 1.01-2.17; P<.05), and that iron status was strongly associated with a range of malaria-specific immunoglobulins. We conclude that iron deficiency was associated with protection from mild clinical malaria in our cohort of children in coastal Kenya and discuss possible mechanisms for this protection.     

Malaria, anemia, and malnutrition in african children--defining intervention priorities

BACKGROUND: Malaria, anemia, and malnutrition contribute substantially to childhood morbidity in sub-Saharan Africa, but their respective roles and interactions in conferring disease are complex. We aimed to investigate these interactions. METHODS: In 2002, we assessed plasmodial infection, anemia, and nutritional indices in 2 representative surveys comprising >4000 children in northern Ghana. RESULTS: Infection with Plasmodium species was observed in 82% and 75% of children in the rainy and dry season, respectively. The fraction of fever attributable to malaria was 77% in the rainy season and 48% in the dry season and peaked in children of rural residence. Anemia (hemoglobin level, <11 g/dL) was seen in 64% of children and was, in multivariate analysis, associated with young age, season, residence, parasitemia, P. malariae coinfection, and malnutrition (odds ratio [OR], 1.68 [95% confidence interval [CI], 1.38-2.04]). In addition, malnutrition was independently associated with fever (axillary temperature, > or = 37.5 degrees C; OR, 1.59 [95% CI, 1.13-2.23]) and clinical malaria (OR, 1.67 [95% CI, 1.10-2.50]). CONCLUSIONS: Malnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia, even if the latter exhibits multifactorial patterns. Our data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs.     

Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait

Sickle cell trait (HbAS) is known to be protective against Plasmodium falciparum malaria, but it is unclear when during the course of infection this protection occurs and whether protection is innate or acquired. To address these questions, a cohort of 601 children 1-10 years of age were enrolled in Kampala, Uganda, and followed for 18 months for symptomatic malaria and asymptomatic parasitemia. Genotyping was used to detect and follow individual parasite clones longitudinally within subjects. Children with HbAS were protected against the establishment of parasitemia, as assessed by the molecular force of infection at older but not younger ages (at 2 years of age: incidence rate ratio [IRR] = 1.16; 95% confidence interval [95% CI], 0.62-2.19; P = .6; at 9 years of age: IRR = 0.50; 95% CI, 0.28-0.87; P = .01), suggesting an acquired mechanism of protection. Once parasitemic, children with HbAS were less likely to progress to symptomatic malaria, with protection again being the most pronounced at older ages (at 2 years of age: relative risk [RR] = 0.92; 95% CI, 0.77-1.10; P = .3; at 9 years of age: RR = 0.68; 95% CI, 0.51-0.91; P = .008). Conversely, the youngest children were best protected against high parasite density (at 2 years of age: relative density = 0.24; 95% CI, 0.10-0.54; P = .001; at 9 years of age: relative density = 0.59; 95% CI, 0.30-1.19; P = .14), suggesting an innate mechanism of protection against this end point.     

Risk factors for malaria infection and anemia for pregnant women in the Sahel area of Bandiagara, Mali

Malaria infection and anemia during pregnancy are the primary causes of maternal and fetal morbidity and mortality. The aims of this study were to identify risk factors for malaria infection and to assess the relationship between malaria infection and anemia in pregnant women. Two cross-sectional surveys were conducted in September 1993 and then again in May 1994 (the end of the rainy and dry seasons respectively). A total of 235 pregnant women were randomly selected from both the rural and urban areas of Bandiagara, Mali. According to results from multivariate analysis, the risk of malaria infection was significantly higher during the rainy season (OR= 4.85, 95% CI 2.42-9.75) the first trimester of gestation (OR= 2.21, 95% CI 1.00-4.87, in younger women (OR= 2.48, 95% CI 1.19-5.16), and in women living in the rural area (2.49, 95% CI 0.99-6.27). The risk of anemia was also higher during the rainy season (OR= 1.93, 95% CI 1.10-3.39, in the rural area (OR= 3.55, 95% CI 1.46-8.62). The risk of anemia was lower during the first trimester of gestational age (OR= 0.45, 95% CI 0.22-0.92). The relationship between malaria infection and anemia also varied with season. During the rainy season, the risk for anemia was similar among malaria-infected and non-infected pregnant women. In contrast, the risk was higher among infected pregnant women during the dry season (OR= 3.43, 95% CI 1.09-10.07). In conclusion, the data suggest, that earlier gestation age, living in the rural area, and young age rather than parity are important risk factors for malaria infection in pregnant women. Further, malaria infection is strongly associated with anemia in pregnant women particularly during the dry season and is most likely the cause of anemia. Thus, control measures against malaria infection should target younger rural women in their first trimester of pregnancy.     

Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali

BACKGROUND: Modelling malaria parasitaemia as function of fever has been proposed as best alternative to estimate the attributable fraction of malaria fever and the sensitivity and specificity of different case definitions of malaria disease. OBJECTIVES: To determine the prevalence of fever and its relation to malaria parasitaemia and to establish a pyrogenic threshold for malaria disease in the area. METHODS: We conducted two cross-sectional surveys in children of 6 months to 9 years of age (2434 during the rainy season of 1993 and 2353 during the dry season of 1994) randomly selected from 21 areas of Bandiagara district, Mali. RESULTS: The relationship between fever and Plasmodium falciparum parasitaemia depends strongly on the season, thus affecting the malaria-attributable fraction of fever cases and the sensitivity and specificity of malaria case definitions. The overall proportion of fever attributable to malaria parasitaemia was 33.6% during the rainy season and 23.3% during the dry season, with the highest proportion occurring among the youngest children. The cut-off value, where the sensitivity curve crosses the specificity curve, was around 3200 pf/microl for all age categories during the rainy season and 200 pf/microl during the dry season. CONCLUSIONS: Malaria remains a main cause of fever in this area of Mali. The pyrogenic threshold of parasitaemia depends strongly on the season, and different cut-off levels of parasitaemia should be used during the two seasons to define malaria cases in this area.     

Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.     

Anti-malarial drug use among preschool children in an area of seasonal malaria transmission in Kenya

The aims of this study were to estimate the proportion of asymptomatic Kenyan preschool children using anti-malarial drugs, to identify factors associated with chloroquine use, and to assess the validity of frequency of febrile episodes and drug use reported by mothers or carers. Of 318 children studied, 38% (95% confidence interval [CI] = 30-47%]) tested positive for chloroquine or sulfadoxine. Of chloroquine-positive children, 15% had concentrations exceeding the estimated minimum therapeutically effective values. Among those testing negative for sulfadoxine, chloroquine-positive children were more frequently parasitemic (odds ratio = 2.6, 95% CI = 1.3-5.2), and had lower mean hemoglobin concentrations (6.1 g/L, 95% CI = 2.1-10.1) than chloroquine-negative children. Mothers over-reported the frequency of malaria or fever episodes as usually defined in medical studies, and underreported anti-malarial drug use. We conclude that anti-malarials are frequently given for treatment of malaria or malaria-associated illness, rather than prophylactically or for symptoms unrelated to malaria. Questionnaire surveys cannot replace biochemical markers to obtain information on anti-malarial drug use.     

A case-control study of protection against tuberculosis by BCG revaccination in Recife, Brazil.

SETTING: Metropolitan region of Recife, Brazil. OBJECTIVE: To estimate the additional protection against tuberculosis (TB) provided by a second dose of bacille Calmette-Guérin (BCG) vaccine. DESIGN: Case-control study. Cases were cases of TB newly diagnosed by the TB control programme, independent of clinical form. Three matched neighbourhood controls were selected using a systematic routine, starting from the case's address. The matching was within the age groups 7-9, 10-14 and 15-19 years. RESULTS: Analysis was conducted among 169 cases and 477 controls. For the efficacy of BCG revaccination against TB overall, matched (crude) vaccine effectiveness (VE) was -3 (95% CI -50-29) and matched (adjusted) VE was 8 (95% CI -77-52). CONCLUSIONS: This study suggests that a second dose of BCG does not offer additional protection. Revaccination should not be offered. As large numbers of subjects are already vaccinated and vaccine appears to offer some protection in older subjects, further studies with larger sample sizes could investigate the potential efficacy of revaccination with BCG in the age group > or = 15 years.     

Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana

Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month-old infants and young children randomly selected from this community at the end of the high (May-October, n = 347) and low (November-April, n = 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800-900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.     

Insecticide-treated curtains reduce the prevalence and intensity of malaria infection in Burkina Faso

A large, randomized controlled trial to investigate the impact of insecticide-treated curtains (ITC) on child mortality was conducted in an area of seasonal, holoendemic malaria in Burkina Faso. 158 communities totalling some 90,000 people were censused and grouped into 16 geographical clusters, 8 of which were randomly selected to receive ITC in June-July 1994, just prior to the rainy season. In September-October 1995, at the peak period of malaria transmission, a cross-sectional survey was conducted in 84 of the villages. A random sample of 905 children aged 6-59 months was identified and visited. 763 children (84%) were present at the time of the visit and recruited into the study. Mothers were asked about fever in the past 24 h, the child's temperature was taken, and a sample of blood collected to identify and quantify malaria infections and to measure haemoglobin (Hb) levels. Children protected by ITC were less likely to be infected with Plasmodium falciparum (risk ratio = 0.92; 95% CI 0.86, 0.98) or P. malariae (risk ratio = 0.42, 95% CI 0.19, 0.95). The mean intensity of P. falciparum infections was lower among children protected by ITC (899 vs. 1583 trophozoites/microliter; P < 0.001), while the mean Hb level was 0.4 g/dl higher (P < 0.001). While we found no evidence that ITC had an impact on the prevalence of malaria-associated fever episodes, the confidence intervals around our estimates of the impact of ITC on malaria morbidity were wide. We conclude that widespread implementation of ITC in this area of high malaria transmission led to a modest reduction in the prevalence of malaria infection and to a more substantial reduction in the intensity of these infections which caused increased Hb levels. We were unable to demonstrate any impact of ITC on malaria morbidity, but the wide confidence intervals around our point estimates do not preclude the possibility of a substantial impact.     

Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong.

SETTING: Revaccination of tuberculin-negative school-children is a regular practice in Hong Kong. OBJECTIVE: To assess the efficacy of BCG revaccination guided by tuberculin skin testing. METHOD: A cohort of 303,692 children vaccinated at birth was followed through the tuberculosis notification register for the development of active disease. The percentage of cohort who participated in the BCG revaccination program during primary school was estimated from the vaccination statistics of the Hong Kong Department of Health. The BCG revaccination history of identified cases was ascertained through vaccination cards and clinic records. RESULTS: A total of 85.2% of the cohort participated in the BCG revaccination programme; 79.7% of the participants were tuberculin-negative and revaccinated; 343 developed tuberculosis after the age of 11; 302 were among the participants in the programme while 41 were not. The tuberculosis incidence was 16.5 and 12.9 per 100,000 person-years for participants and non-participants, respectively (RR 1.28, 95%CI 0.92-1.77). Among the participants, tuberculosis incidence was 12.5 and 32.0/100,000 person-years, respectively, for the tuberculin-negative/BCG revaccinated group and the tuberculin-positive/non-revaccinated group (RR 0.39, 95%CI 0.31-0.49). CONCLUSION: This study failed to demonstrate any significant difference in the incidence rates of tuberculosis among participants and non-participants in a school BCG revaccination programme. The increased risk for tuberculosis in the tuberculin-positive group does not support the use of the tuberculin testing for detection of immunity conferred by neonatal BCG vaccination.     

The epidemiology of malaria among pregnant women attending antenatal clinics in an area with intense and highly seasonal malaria transmission in northern Ghana

Objective  To describe the factors associated with malaria infection and anaemia in pregnancy in northern Ghana.
Method  We studied 3642 pregnant women of all gravidities and gestational age of 18–32 weeks who attended an antenatal clinic in the Kassena-Nankana district of Ghana between June 2004 and July 2006. Blood samples were examined for haemoglobin concentrations and parasitaemia, and we obtained socio-demographic data, an obstetric history, information on their past and current state of health and bed net use.
Results  The overall prevalence of malaria parasitaemia during pregnancy was 47%. Older age [adjusted odds ratio (AOR) 0.65, 95% CI 0.54–0.78], multigravidity (AOR 0.51, 95% CI 0.42–0.61) and third trimester of pregnancy (AOR 0.85, 95% CI 0.73–0.99) were associated with a decreased risk of parasitaemia. Enrolment during the rainy or post-rainy season was associated with an increased risk of parasitaemia (AOR 2.59, 95% CI 2.20–3.04 and AOR 3.12, 95% CI, 2.60–3.74 respectively). Malaria infection was associated with an increased risk of anaemia among young women. The prevalences of anaemia (Hb<11.0 g/dl) and severe anaemia (Hb<7.0 g/dl) during pregnancy were 72% and 2% respectively. The risk of anaemia was lower in older women (AOR 0.79, 95% CI, 0.64–0.97), multigravidae (AOR 0.67, 95% CI 0.55–0.83) and in educated women (AOR 0.81, 0.68–0.98).
Conclusion  The prevalence of malaria parasitaemia and anaemia among pregnant women in Kassena-Nankana district is high with marked seasonal variation. Targeting of interventions to the high transmission season and to paucigravidae may be appropriate in this setting.     

Impact of malaria control on childhood anaemia in Africa -- a quantitative review

OBJECTIVE: To review the impact of malaria control on haemoglobin (Hb) distributions and anaemia prevalences in children under 5 in malaria-endemic Africa. METHODS: Literature review of community-based studies of insecticide-treated bednets, antimalarial chemoprophylaxis and insecticide residual spraying that reported the impact on childhood anaemia. Anaemia outcomes were standardized by conversion of packed cell volumes into Hb values assuming a fixed threefold difference, and by estimation of anaemia prevalences from mean Hb values by applying normal distributions. Determinants of impact were assessed in multivariate analysis. RESULTS: Across 29 studies, malaria control increased Hb among children by, on average, 0.76 g/dl [95% confidence interval (CI): 0.61-0.91], from a mean baseline level of 10.5 g/dl, after a mean of 1-2 years of intervention. This response corresponded to a relative risk for Hb < 11 g/dl of 0.73 (95% CI: 0.64-0.81) and for Hb < 8 g/dl of 0.40 (95% CI: 0.25-0.55). The anaemia response was positively correlated with the impact on parasitaemia (P = 0.005, P = 0.008 and P = 0.01 for the three outcome measures), but no relationship with the type or duration of malaria intervention was apparent. Impact on the prevalence of Hb < 11 g/dl was larger in sites with a higher baseline parasite prevalence. Although no age pattern in impact was apparent across the studies, some individual trials found larger impacts on anaemia in children aged 6-35 months than in older children. CONCLUSION: In malaria-endemic Africa, malaria control reduces childhood anaemia. Childhood anaemia may be a useful indicator of the burden of malaria and of the progress in malaria control.     

Asymptomatic parasitaemia as a risk factor for symptomatic malaria in a cohort of Ugandan children

OBJECTIVES:To assess the prevalence of asymptomatic parasitaemia, determine its association with symptomatic malaria, and identify independent predictors of asymptomatic parasitaemia in a cohort of children from Kampala, Uganda. METHODS:A total of 316 children aged 6 months to 5 years were recruited from the community. The prevalence of asymptomatic parasitaemia was assessed at enrollment and approximately every 30 days during follow-up. Participants received all of their health care in our clinic, including a standardized approach to the diagnosis and treatment of symptomatic malaria. RESULTS:A total of 283 (90%) subjects completed the full 1-year follow-up and were included in this study, yielding 2557 routine smears. The prevalence of asymptomatic parasitaemia was 17% at enrollment, but 5-8% for the remainder of the study. The risk of developing symptomatic malaria within 30 days was significantly higher in those with a positive routine than in those with a negative one (50%vs. 9%, P < 0.001). Higher parasite densities were associated with increased odds of developing symptomatic malaria within 30 days (P = 0.003). Only 11% of episodes of asymptomatic parasitaemia, involving 6% of subjects, arose and cleared without therapy. In multivariate analysis the only significant risk factor for asymptomatic parasitaemia was whether a child had any episode of symptomatic malaria during the course of the study (OR = 3.0, P = 0.02). CONCLUSION:In our cohort of children from an urban meso-endemic environment, asymptomatic parasitaemia was uncommon and frequently followed by symptomatic malaria. This suggests that presumptive treatment of asymptomatic parasitaemia in such settings would be an efficient means of preventing symptomatic malaria.