Studies on Plasmodium falciparum isotypic antibodies and numbers of IL-4 and IFN-gamma secreting cells in paired maternal cord blood from South West Cameroon.

OBJECTIVES: In this study, the effect of maternal peripheral and placental Plasmodium falciparum parasitaemia on the level of antibody and cytokine immune responses in the neonate was investigated. METHODS: Malaria parasites were detected by light microscopy. Levels of malaria-specific isotypic antibodies were measured in maternal and cord blood by indirect ELISA. The numbers of IFN-gamma and IL-4 cells produced by maternal/cord blood after in vitro stimulation were enumerated using the ELISPOT assay. RESULTS: Malaria parasite rate of maternal, placental biopsy and cord blood was 32.8%, 33.7% and 7.8% respectively. Overall, ELISA seropositivity rates for P. falciparum-specific IgG, IgM, IgE and IgA in the maternal plasma samples were 71%, 85%, 29.3%, and 0% respectively, while those for the cord samples were 69%, 6.0%, 4.4% and 0% respectively. Mean IgM ELISA OD(405) values of neonates born from positive placentas, or whose mothers had peripheral malaria parasitaemia were higher than those who were parasite negative. The mean number of maternal cells producing IFN-gamma was higher (P=0.0001) than that of the paired cord samples. The mean number of IL-4 producing cells of neonates born of mothers who were positive (P<0.05) or from malaria-positive placentas (P<0.025) was higher than from those who were malaria negative. Neonates born of malaria-positive mothers or from parasitized placentas mounted predominantly Th2 type immune responses. CONCLUSION: It appears from this study that neonates born from malaria-infected mothers or placentas may relatively be more susceptible to malaria attack during the first years of life.     

Relationships between maternal malaria and malarial immune responses in mothers and neonates

Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection. Maternal and cord malarial IgG levels correlated ( P < 0–001). Malarial IgG was raised in cord blood in active placental malaria; IgM was not detected. Mean lymphoproliferation and the proportion of responders to soluble P. falciparum antigens (F32) and conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher Cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established.     

Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates

Objective Animal studies suggest pathological foetal programming of hypothalamic circuits regulating food intake in the setting of leptin deficiency and intrauterine growth restriction (IUGR). We aimed to compare placental leptin synthesis and leptin‐binding capability in venous cord blood between IUGR newborns and neonates born appropriate for gestational age (AGA). Design Prospective controlled multicentre study. Patients Twenty‐one ultrasound‐proven IUGR and 33 AGA neonates. Measurements The concentration of leptin and soluble leptin receptor (sOB‐R) in venous cord blood at birth was determined. Moreover, placental gene and protein expression of leptin and placental mRNA expression of functional and total leptin receptor isoforms were measured. Results Whereas log‐leptin concentration in venous cord blood did not differ between IUGR and AGA newborns, the concentration of log‐sOB‐R was elevated in IUGR neonates (p^{confounder adjusted} = 0·009). Placental leptin protein synthesis as well as leptin mRNA was significantly higher in IUGR than in AGA infants (log‐transformed, relative gene expression, p^{confounder adjusted} = 0·004). Analysis of gene expression of functional and total leptin receptor isoforms did not show any difference between both groups. Conclusions Leptin‐binding capability in venous cord blood is increased in IUGR newborns. Thus, via foetal programming, reduced biologically active leptin levels might contribute to a perturbed regulation of appetite.     

Placental Plasmodium falciparum parasitaemia in East Sepik (Papua New Guinea) women of different parity: the apparent absence of acute effects on mother and foetus.

The effects of malaria were studied in a group of parturient women of East Sepik Province, Papua New Guinea. Further information was gathered from a search of hospital records and interviews with village aid post orderlies. Examination of placental blood revealed a Plasmodium falciparum parasitaemia rate of 41% of the primiparae, 23% in parous 2, 25% in parous 3, and 3% in multiparae greater than 3. Approximately one-half of those with placental parasitaemia had a concomitant detectable peripheral parasitaemia. Placental parasitaemias were of relatively low density, averaging 1.6%. There were no instances in the observed series of births, hospital records, or village studies of the occurrence of severe malaria in the mother or its acute effects on the foetus. Neither birthweight nor maternal or cord blood haematocrit was related to the presence or absence of placental parasitaemia. Neonatal birthweight and risk of delivering a low birthweight (less than 2.5 kg) baby was statistically associated only with maternal parity. The possible reasons for the relatively benign effect of malaria in the pregnant women of this population are discussed.     

Chloroquine prophylaxis, iron/folic-acid supplementation or case management of malaria attacks in primigravidae in western Uganda: effects on congenital malaria and infant haemoglobin concentrations

A randomized, double-blind, placebo-controlled trial, which compared the effects of three interventions (weekly chloroquine prophylaxis, daily iron and weekly folic-acid supplementation, and case management of malaria) on congenital malaria, maternal haemoglobin (Hb) and foetal outcome, was conducted among primigravidae resident in Hoima district, Uganda. Among 473 babies examined at birth or within 7 days of birth, 198 (42%) were parasitaemic, the level of parasitaemia in an infant being strongly correlated with those of placental (P< 0.01) and maternal, peripheral parasitaemia (P < 0.01). However, 33 (17%) of the parasitaemic babies were born to mothers who had placental but not peripheral parasitaemia, 22 (11%) to mothers who had peripheral but not placental parasitaemia, and 12 (6%) to mothers with neither peripheral nor placental parasitaemia. Overall, 163 babies were each examined for malarial parasites at birth and 1 month later. Of the 76 (47%) found to have parasitaemia at birth, 37 (23%) appeared aparasitaemic at the 1-month follow-up but 28 (17%) were still parasitaemic at that time. Among the babies born to the mothers who only received case management of malaria during pregnancy, parasitaemia at birth was associated with infant anaemia at birth (i.e. < 140 g Hb/litre; P = 0.03). Infants found to be parasitaemic at the 1-month follow-up had lower mean concentrations of Hb at that time than their aparasitaemic counterparts (P= 0.03). Parasitaemia at birth was not significantly associated with low birthweight, in any of three intervention groups. The intervention given to the mother had no significant effect on the parasitaemia of her baby, either at birth or at the age of 1 month. Congenital malaria per se may have little influence on birthweight but may have an impact on infant anaemia. In conclusion, congenital parasitaemia was not associated with birthweight, but was related to anaemia at birth in infants born to women who had only received active case management during their pregnancies.     

Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya

BACKGROUND: In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-than-expected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. METHODS: A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. RESULTS: Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%-67%) in newborns of HIV-infected women and by 48% (95% CI, 26%-62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. CONCLUSION: Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.     

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.     

Congenital malaria in a hyperendemic area

The prevalence of Plasmodium falciparum malaria was evaluated in all near-term pregnant women and their newborns at the Macha Hospital in the Southern Province of Zambia during part of the rainy season, when malaria prevalence is at its peak. Peripheral parasitemia was noted in 19 (29%) of 65 newborns and in 40 (63%) of 63 mothers. All but one of the infected neonates had an infected mother, and 17 of 40 infected mothers gave birth to infected newborns. The parasite densities measured were uniformly low (less than 25,000/cc), and only seven of 19 infected neonates had fever within 48 hours of delivery suggestive of malaria infection. Parasitized newborns had a 469-gm lower average birthweight, but they did not have a higher incidence of prematurity or preterm delivery compared with uninfected newborns. In addition, the Apgar scores of infected and uninfected newborns were not significantly different. There was no correlation between neonatal parasitemia and either the sex of the child or the parity of the mother. Maternal chloroquine prophylaxis did not appear to be effective in preventing infection in the fetus or the gravida, and the emergence of chloroquine resistance may explain, in part, the greater prevalence of congenital malaria in endemic areas in recent years.     

The prevalence of congenital malaria among neonates with suspected sepsis in Calabar, Nigeria

We studied the prevalence of congenital malaria among neonates with suspected sepsis and its outcome at the University of Calabar Teaching Hospital, Calabar, Nigeria. All in-born neonates admitted to the newborn unit with clinical features suggestive of sepsis were recruited. They were screened for bacterial sepsis and malaria. The mothers of the neonates that had parasitaemia were further screened for malaria and anaemia. A total of 546 in-born neonates were admitted to the neonatal unit and 202 (37%) presented with clinical signs suggested of sepsis. Of these, 71 babies (35% of 202 or 13% of the total in-born nursery admissions) had congenital malaria and 14 also had sepsis. Sixty-three (88.7%) of the parasitaemic babies were delivered by mothers who received antenatal care at our centre. Eighty-six percent of the mothers of the 71 babies also had the malaria parasite in their blood. The majority (67%) of the 71 mothers were gravidae 2 and below. Thirty (42.3%) of the affected neonates were anaemic and 5 (7%) of them required a blood transfusion. Congenital malarial is not uncommon in Calabar among babies with suspected sepsis. It appears that the antenatal chemoprophylaxis with pyrimethamine (25 mg weekly) currently used for malaria in our centre no longer protects the mother and fetus. An alternative is needed in order to stem maternal, fetal and neonatal morbidity and wastage. Babies with features of sepsis should be routinely screened for malaria.     

Malaria in pregnancy and its consequences for the infant in rural Malawi

Maternal malaria and anaemia, pregnancy and infant outcomes are reviewed among a cohort of mothers and their babies living in Chikwawa district, southern Malawi. Overall, 4104 women were screened at first antenatal visit and 1523 at delivery. Factors independently associated with moderately severe anaemia (MSA; < 8 g haemoglobin/dl) in primigravidae were malaria (relative risk = 1.9; 95% confidence interval = 1.6-2.3) and iron deficiency (relative risk = 4.2; 95% confidence interval = 3.5-5.0). Only iron deficiency was associated with MSA in multigravidae. After controlling for antimalarial use, parasitaemia was observed in 56.3% of the HIV-infected primigravidae and 36.5% of the non-infected (P = 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P = 0.002). Over 33% of the infants born alive to primigravidae were of low birthweight (LBW; < 2500 g), and 23.3% of all newborns had foetal anaemia (< 12.5 g haemoglobin/dl cord blood). LBW was significantly associated in primigravidae with pre-term delivery, placental malaria and frequency of treatment with sulfadoxine-pyrimethamine (SP), and in multigravidae with pre-term delivery, adolescence, short stature and MSA. LBW was significantly reduced with a second SP treatment in primigravidae, and with iron-folate supplementation in multigravidae. Mean haemoglobin concentrations were significantly lower in the infant who had been LBW babies than in the others, and significantly associated with parity, peripheral parasitaemia at delivery and placental malaria. At 1 year post-delivery, life status was known for 364 (80.7%) of the 451 infants enrolled in the follow-up study. Independent risk factors for post-neonatal mortality were maternal HIV infection, LBW, and iron deficiency at delivery. This study identifies priorities for improving the health of pregnant women and their babies in this rural area of Malawi.     

Umbilical cord-blood infections with Plasmodium falciparum malaria are acquired antenatally in Kenya

BACKGROUND: It is unknown whether the presence of Plasmodium falciparum malaria parasites in umbilical cord blood denotes infection acquired antenatally or contamination with infected maternal blood at delivery. METHODS: Parasites were quantified by real-time quantitative polymerase chain reaction (RTQ-PCR) and were genotyped in paired maternal- and cord-blood samples obtained from 632 pregnant Kenyan women and their newborns. Placental alkaline phosphatase (PLAP) and polyclonal immunoglobulin E levels were also quantified in paired maternal- and cord-blood samples, as markers of admixture of maternal blood with cord blood. RESULTS: Sixty-six cord-blood samples (10.4%) contained falciparum malaria, as detected by RTQ-PCR. For 25 of the infected cord-blood samples, either absence of infection was noted in paired maternal-blood samples at delivery (n=16) or amplicon levels in cord-blood samples were 10-fold higher than those in maternal-blood samples (n=9). Of the paired maternal- and cord-blood samples that were both infected, 57% showed discordant malaria parasite strains. There was no correlation between maternal parasitemia and levels of PLAP and immunoglobulin E in cord blood. PLAP levels, however, were significantly higher in cord-blood samples obtained from newborns of primigravid or secundigravid women with placental malaria, compared with cord-blood samples obtained from newborns of women without placental malaria or multigravid women. These findings indicate that parity and placental malaria are risk factors for maternofetal transfusion. CONCLUSIONS: Malaria parasites identified in cord blood are acquired antenatally by transplacental transmission of infected erythrocytes. Primigravid and secundigravid women with placental malaria are at increased risk for congenital infection.     

Patterns of pseudo‐reticulocytosis in malaria: fluorescent analysis with the Cell‐Dyn® CD4000

This study of Plasmodium falciparum malaria evaluated patterns of fluorescent reticulocyte measurements as determined with the Abbott Cell‐Dyn^® CD4000. The parasitaemia of positive samples (n=180) ranged from 0.04% to 25.5%, with those (19/180) showing gametocytes having lower parasitaemia levels (mean 0.31%, median 0.2%) compared to those that did not (mean 2.59%, median 0.8%). There was a reasonable association (R²=0.60) between parasitaemia level and CD4000 reticulocyte percentages, although there was overall a small statistical bias towards higher parasitaemia estimates determined microscopically. Consistently high immature reticulocyte fraction (IRF) values of >0.5 were observed in cases with a parasitaemia exceeding 5%, while samples with lower parasitaemia levels showed more variable IRF values. Visual examination of CD4000 reticulocyte histograms revealed that 81/100 malaria‐positive samples with an IRF above 0.5 showed the presence of a fluorescent population `spike' consistent with the staining of intracellular malaria parasites. Only three of the 80 malaria‐positive samples with an IRF below 0.5, and none of the 237 malaria‐negative samples, showed this histogram pattern. These observations indicate that samples with malaria parasites give erroneously high CD4000 reticulocyte estimates that essentially comprise the sum total of true reticulocytes and parasite‐infected red cells (pseudo‐reticulocytes). This limitation is common to all automated reticulocyte procedures but recognizing the differences between homogenous staining parasitized red cells and heterogeneous staining reticulocytes has potential applications in monitoring parasitaemia levels both at patient presentation and during subsequent treatment.     

Placental Transfer of Respiratory Syncytial Virus-Specific IgG in Iranian Mothers

Background: Respiratory Syncytical virus infection is the most common cause of bronchiolitis and viral pneumonia in infancy. Objective: To investigate the placental transfer of RSV-specific IgG in Iranian mothers. Methods: The antibodies were measured in sera of 146 mother/newborn pairs using a commercially available indirect Enzyme Linked Immunosorbent Assay (ELISA). The studied subjects were among healthy pregnant women who attended to the Zeinabieh Hospital of Shiraz University of Medical Sciences in a one year period. Results: A highly significant correlation was observed between RSV-specific IgG in newborns and mothers (r = 0.88). However, mean RSV-specific IgG antibodies in neonates was significantly higher than that of their mothers (P = 0.019). In addition, the mean cord/maternal ratio of RSV-specific IgG was detected to be 1.27 ± 0.60. Maternal blood group, age, parity, previous abortions and neonatal gestational age had no correlation with placental transfer of RSV-specific IgG antibodies. Conclusion: Our finding demonstrates that placental transfer of RSV-specific IgG antibodies is an active process and the main factor that influences this transfer is maternal concentration of these immunoglobulins.     

Associations between placental and cord blood malaria infection and fetal malnutrition in an area of malaria holoendemicity

The objective of this study was to determine the role of malaria in the etiology of fetal malnutrition in Nigeria. This study took place at the Neonatal and Maternity Units of the Wesley Guild Hospital, Ilesa, Nigeria. This is a prospective study of 304 consecutive, singleton, term live births delivered between January and August 2002. Anthropometric and clinical data were recorded. Fetal malnutrition (FM; failure to acquire adequate quantum of fat and muscle mass during intrauterine growth) was diagnosed using clinical assessment of fetal nutritional status (CANS) and the score (CANSCORE) adapted by Metcoff. The placenta tissues were examined for malaria pigments and parasites, and placental and cord blood smears were examined for parasites. Babies were followed up in the neonatal period for clinical malaria. Babies were grouped into those with malaria-infected placental and cord blood specimens and those without. The two groups were compared with regard to the proportions with FM and complications of FM. Three hundred four placental and cord blood specimens were examined for malaria. Of the 304, 101 (33.2%) of the placental and 67 (22.0%) of the cord blood specimens were positive for malaria. Sixty-six (21.7%) of the 304 babies had FM. Forty-four (66.7%) of the 66 placental blood specimens of babies with FM were positive for malaria, whereas 57 (24.0%) of the 238 placentae of babies without FM had placental malaria (chi(2) =42.5, P < 0.0001). Similarly, 27 (40.9%) of 66 babies with FM compared with 40 (16.8%) among 238 babies without FM had malaria parasites in the cord blood (chi(2) =17.5, P < 0.001). The means of birth weight, ponderal index, and placenta weight were significantly lower among the babies of mothers with malaria-infected placentae than those without (P < 0.05 in all cases). Lack of antenatal care, primiparity, and failure to have chemoprophylaxis against malaria were the maternal factors found to be associated with placental malaria infection. Placental malaria is a major factor in the etiology of FM in Nigeria.     

Individual efficacy of intermittent preventive treatment with sulfadoxine–pyrimethamine in primi- and secundigravidae in rural Burkina Faso: impact on parasitaemia, anaemia and birth weight

Objective To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp‐SP) in primi‐ and secundigravidae in rural Burkina Faso. Methods Data of 1441 women enrolled in a health centre randomized trial and delivering a live‐singleton between September 2004 and October 2006 were analysed at individual level. Prevalence of peripheral and placental parasitaemia, anaemia (PCV <33%), low‐birth weight (<2500 g; LBW), mean packed cell volume (PCV) and birth weight were compared in relation to the number of directly observed SP doses. Results Two or more doses of SP significantly reduced the risk of placental parasitaemia [adjusted odds ratio (AOR) = 0.04, 95%CI = 0.003–0.60, P = 0.023] and anaemia at delivery (AOR = 0.31, 95%CI = 0.18–0.52, P < 0.001). IPTp was associated with reduced risk of LBW in primigravidae (AOR = 0.11, 95%CI = 0.07–0.17, P < 0.001) but not secundigravidae (AOR = 0.70, 95%CI = 0.26–1.91, P = 0.452). For each increment in number of SP doses mean PCV increased by 1.0% (95%CI = 0.4–1.7, P = 0.005) at 32 weeks gestation, by 1.2% (95%CI = 0.2–2.2, P = 0.025) at delivery and mean birth weight by 220 g (95%CI = 134–306 P < 0.001) in primigravidae and by 102 g (95%CI = 55–148, P = 0.001) in secundigravidae. Conclusion The risk of malaria infection was significantly reduced by IPTp with SP in primi‐ and secundigravidae in rural Burkina Faso. The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW. Incomplete uptake of IPTp‐SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions. This needs to be taken into account when evaluating interventions at community level.     

Cord blood leptin concentrations in relation to intrauterine growth

OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.     

Vitamin D, PTH and calcium levels in pregnant women and their neonates

Objectives To determine the prevalence of vitamin D deficiency in pregnant women and their neonates and to examine factors associated with vitamin D deficiency. Design and patients Population‐based study of pregnant women and their neonates from South‐eastern Sydney, Australia. Measurements Serum 25 hydroxy‐vitamin D (25‐OHD), PTH, calcium, albumin, phosphate and alkaline phosphatase were measured in women at 23–32 weeks gestation and on cord blood at delivery. Maternal skin phototype was recorded using the Fitzpatrick scale. Results Vitamin D deficiency (defined as 25‐OHD ≤ 25 nmol/l) was found in 144 of 971 (15%) women and 98 of 901 (11%) neonates. Median 25‐OHD was 52 nmol/l (range 17–174) in mothers and 60 nmol/l (17–245) in neonates. Maternal 25‐OHD levels varied by season, with lowest levels in late winter/early spring (P < 0·001). Factors associated with maternal vitamin D deficiency in multiple logistic regression were (OR, 95% CI): maternal birthplace outside Australia: 2·2 (1·4–3·5, P = 0·001), dark skin phototype: 2·7 (1·6–4·5, P < 0·001), wearing a veil: 21·7 (11·7–40·3, P < 0·001) and younger maternal age: 0·93 (0·89–0·97, P = 0·001). Maternal vitamin D deficiency increased the risk of neonatal vitamin D deficiency (OR 17·2, 95% CI 8·8–34·3) and birth weight was lower among infants of deficient vs. sufficient mothers: mean (SD) 3245 g (545) vs. 3453 g (555), P < 0·001. Conclusions Vitamin D deficiency is common among pregnant women; immigrant, veiled and dark skinned women are at greatest risk. Maternal vitamin D deficiency increases the risk of neonatal vitamin D deficiency and lower birth weight.     

Impact of a double dose of sulphadoxine-pyrimethamine to reduce prevalence of pregnancy malaria in southern Mozambique

Malarial infection during pregnancy increases the risks of severe sequelae for the pregnant woman and the risk of delivering a low birthweight baby. The aim of this intervention study was to reduce significantly the prevalence of malaria parasitaemia in adolescent parturients in Matola and Boane in Mozambique. The study was focused upon the most malaria-vulnerable group, adolescent nulliparous and primiparous women. After completing the usual antenatal clinic and giving informed consent, 600 pregnant women were randomly chosen in a double blind manner to one of two regimens comparing the prevailing routine (placebo) for malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine (SP). The first dose was given at enrollment with a second dose at the beginning of the third trimester. At delivery maternal and placental malaria parasitaemia as well as birthweight and gestational duration were analysed. At booking the prevalence of malaria parasitaemia was 35.3% in the placebo group and 30.6% in the SP group. At the second dose, the prevalence of malaria parasitaemia in the placebo group and SP group was 19.7% and 8.7%, respectively. This implies a relative risk (RR) of 2.24 with 95% CI (1.34, 3.75). The corresponding figures at delivery were 13.6% and 6.3% with an RR of 2.22 (1.07, 4.60) and in placenta 13.3% and 2.4% with an RR of 4.87 (1.58, 15.0). Newborns with malaria within 7 days were significantly more frequent in the placebo group, 6.4% and 0.7% respectively, with an RR of 6.55 (1.20, 35.7). Almost all (approximately 98%) of the women studied had Plasmodium falciparum, the remainder had P. malariae and P. ovale. The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g. The estimated mean difference between the two groups was 151 g with 95% CI (51, 252). The mean placental weight in the placebo group was 596 and 645 g in the SP group, implying a difference of 49 g with a 95% CI (11, 88). The mean gestational duration was 6.1 days longer in the SP group, 95% CI (1.5, 10.6). In the placebo group there were two cases of urticaria and one case of nausea; in the SP group there was one case of vomiting. No newborn showed any sign of serious SP side-effect. Two doses of SP were enough to significantly reduce the prevalence of peripheral and placental malaria parasitaemia among young nulliparous and primiparous pregnant women in Matola and Boane.     

Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria

Objectives

Malaria infection may impact on mother‐to‐child transmission (MTCT) of HIV‐1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV‐1 MTCT in southern Mozambique.

Methods

A total of 207 HIV‐positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo‐controlled trial of two‐dose sulfadoxine‐pyrimethamine (SP) IPTp in women receiving single‐dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age.

Results

There were 19 transmissions of HIV in 153 mother–infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076–69 296) HIV‐1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471–74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3–172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7–32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06–0.89; P=0.034).

Conclusions

IPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.     

Comparison of the therapeutic efficacy of chloroquine and sulphadoxine-pyremethamine in children and pregnant women

Objective To compare the parasitological failure rates of under‐fives and pregnant women with parasitaemia treated with chloroquine (CQ) or sulphadoxine‐pyrimethamine (SP). Methods During a clinical trial of CQ, SP, amodiaquine (AQ) and SP plus AQ combination for malaria treatment in pregnant women in Ghana, a parallel study of treatment of children below 5 years of age with symptomatic malaria with CQ and SP was undertaken. Four hundred and fifty pregnant women with malaria parasitaemia and 203 children with malaria parasitaemia were randomized to receive CQ or SP. They were followed up and parasitological failure by days 14 and 28 after the start of treatment was assessed. Results Polymerase chain reaction (PCR)‐uncorrected parasitological failure rates by day 28 after the start of treatment with CQ were 58.5% (55/94), 38.5% (45/117), 31% (13/42) and 8.2% (4/49) in children, primigravidae, secundigravidae and multigravidae, respectively. For those treated with SP the rates by day 28 were 36.4% (32/88), 27.1% (29/107), 6.1% (3/49) and 3.8% (2/52) in children, primigravidae, secundigravidae and multigravidae, respectively. In both CQ and SP treatment arms, children were twice as likely to experience recrudescence as pregnant women (RR 2.1 [95% CI 1.6–2.6] P < 0.0001) by day 28 after the start of treatment. Conclusions Parasitological failure rates were significantly lower in asymptomatic pregnant women, particularly in multigravidae, compared with symptomatic children. Reliance on drug sensitivity results observed in children only to decide on antimalarial regimes for pregnant women may not be appropriate.