Caroline Shulman

Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial

BACKGROUND In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies. We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District, Kenya. METHODS Between January, 1996, and April, 1997, 1264 primigravid women were recruited when they attended for antenatal care, and randomly assigned sulphadoxine-pyrimethamine (640) or placebo (624). Women received one, two, or three doses of study medication depending on the duration of gestation at enrolment. Primary outcome measures were severe anaemia (haemoglobin <8 g/dL) and malaria parasitaemia, assessed at 34 weeks of gestation. Analyses were based on intention to treat among women who had study blood tests at 34 weeks. FINDINGS 30 (5.3%) of 567 women in the sulphadoxine-pyrimethamine group and 199 (35.3%) of 564 in the placebo group had peripheral parasitaemia (protective efficacy 85% [95% CI 78-90], p<0.0001). 82 (14.5%) and 134 (23.7%) had severe anaemia (protective efficacy 39% [22-52], p<0.0001). Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention. The effects were seen both in women who owned insecticide-treated bednets and in women who did not. INTERPRETATION Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective, practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas.

Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria

BACKGROUND Pregnancy-associated malaria caused by Plasmodium falciparum adherence to chondroitin sulfate A in the placental intervillous space is a major cause of low birthweight and maternal anaemia in areas of endemic P falciparum transmission. Adhesion-blocking antibodies that specifically recognise parasite-encoded variant surface antigens (VSA) are associated with resistance to pregnancy-associated malaria. We looked for a possible relation between VSA-specific antibody concentrations, placental infection, and protection from low birthweight and maternal anaemia. METHODS We used flow cytometry to measure VSA-specific IgG concentrations in plasma samples taken during child birth from 477 Kenyan women selected from a cohort of 910 women on the basis of HIV-1 status, gravidity, and placental histology. We measured VSA expressed by one placental P falciparum isolate and two isolates selected or not selected for chondroitin sulfate A adhesiveness in-vitro. FINDINGS Concentrations of plasma IgG specific for VSA, expressed by chondroitin sulfate A-adhering parasites (VSA in pregnancy-associated malaria or vsa-pam), increased with gravidity and were associated with placental histological findings. Women with chronic pregnancy-associated malaria and low or absent VSA-PAM-specific IgG had lower haemoglobin values (reduced by 17 g/L; 95% CI 8.1-25.2) and delivered smaller babies (birthweight reduced by 0.26 kg; 0.10-0.55) than did corresponding women with high VSA-PAM-specific IgG. No such relation was shown for concentrations of IgG with specificity for non-pregnancy-associated malaria VSA. INTERPRETATION VSA-PAM-specific IgG protects against low birthweight and maternal anaemia. Our data indicate an important mechanism of clinical protection against malaria and raise hope for the clinical effectiveness of a potential VSA-based vaccine against pregnancy-associated malaria.

Malaria is an important cause of anaemia in primigravidae: evidence from a district hospital in coastal Kenya

A study was undertaken in order to determine the prevalence and aetiology of anaemia in pregnancy in coastal Kenya, so as to establish locally important causes and enable the development of appropriate intervention strategies. 275 women attending the antenatal clinic at Kilifi district hospital, Kenya, were recruited in November 1993. The prevalence of anaemia (haemoglobin [Hb] < 11 g/dL) was 75.6%, and the prevalence of severe anaemia (Hb < 7g/dL) was 9.8% among all parities; 15.3% of 73 primigravidae were severely anaemic, compared with 7.9% of 202 multigravidae (P = 0.07). In primigravidae, malaria infection (Plasmodium falciparum) was strongly associated with moderate and severe anaemia (chi 2 test for trend, P = 0.003). Severe anaemia was more than twice as common in women with peripheral parasitaemia as in those who were aparasitaemic, and parasitaemia was associated with a 2.2g/dL decrease in mean haemoglobin level (P < 0.001). In multigravidae, iron deficiency and hookworm infection were the dominant risk factors for anaemia. Folate deficiency and human immunodeficiency virus infection were not strongly associated with anaemia. It is suggested that an intervention that can effectively reduce malaria infection in primigravidae could have a major impact on the health of these women and their infants.

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae

BACKGROUND In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active‐acute, active‐chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities.

Importance and prevention of malaria in pregnancy

Malaria in pregnancy is one of the most important preventable causes of low birthweight deliveries worldwide. It is also a major cause of severe maternal anaemia contributing to maternal mortality. It is estimated that 40% of the worlds pregnant women are exposed to malaria infection during pregnancy. The clinical features of Plasmodium falciparum malaria in pregnancy depend to a large extent on the immune status of the woman, which in turn is determined by her previous exposure to malaria. In pregnant women with little or no pre-existing immunity, such as women from non-endemic areas or travellers to malarious areas, infection is associated with high risks of severe disease with maternal and perinatal mortality. Women are at particular risk of cerebral malaria, hypoglycaemia, pulmonary oedema and severe haemolytic anaemia. Fetal and perinatal loss has been documented to be as high as 60-70% in non-immune women with malaria. Adults who are long-term residents of areas of moderate or high malaria transmission, including large parts of sub-Saharan Africa, usually have a high level of immunity to malaria. Infection is frequently asymptomatic and severe disease is uncommon. During pregnancy this immunity to malaria is altered. Infection is still frequently asymptomatic, so may go unsuspected and undetected, but is associated with placental parasitization. Malaria in pregnancy is a common cause of severe maternal anaemia and low birthweight babies, these complications being more common in primigravidae than multigravidae. Preventative strategies include regular chemoprophylaxis, intermittent preventative treatment with antimalarials and insecticide-treated bednets.

Neonatal Measles Immunity in Rural Kenya: The Influence of HIV and Placental Malaria Infections on Placental Transfer of Antibodies and Levels of Antibody in Maternal and Cord Serum Samples

INTRODUCTION Young infants are protected from measles infection by maternal measles antibodies. The level of these antibodies at birth depends on the level of antibodies in the mother and the extent of placental transfer. We investigated predictors of levels of measles antibodies in newborns in rural Kenya. METHODS A total of 747 paired maternal-cord serum samples (91 from human immunodeficiency virus [HIV]-infected and 656 from HIV-uninfected mothers) were tested for measles immunoglobulin G antibodies. Placental malaria infection was determined by biopsy. Data on pregnancy history, gestational age, and anthropometric and socioeconomic status were collected. RESULTS Infants born to HIV-infected mothers were more likely (odds ratio, 4.6 [95% confidence interval {CI}, 2.2-9.7]) to be seronegative and had 35.1% (95% CI, 9.8%-53.2%) lower levels of measles antibodies than did those born to HIV-uninfected mothers. Preterm delivery, early maternal age, and ethnic group were also associated with reduced levels of measles antibodies. There was little evidence that placental malaria infection was associated with levels of measles antibodies in newborns. CONCLUSION Our results suggest that maternal HIV infection may reduce levels of measles antibodies in newborns. Low levels of measles antibodies at birth render children susceptible to measles infection at an early age. This is of concern in sub-Saharan African countries, where not only is the prevalence of HIV high, but measles is the cause of much morbidity and mortality.

Geophagy, Iron Status and Anaemia Among Pregnant Women on the Coast of Kenya

In a cross sectional survey based in an antenatal clinic at Kilifi District Hospital, Coast Province, Kenya, 154 of 275 pregnant women (56%) reported eating soil regularly. Geophagous women had lower haemoglobin and serum ferritin concentrations than non-geophagous women (mean haemoglobin level 9.1 vs. 10.0 g/dL, P < 0.001; median ferritin level 4.5 vs. 9.0 micrograms/L, P < 0.001). In multiple linear regression analyses, geophagy was a significant predictor of haemoglobin (beta = -6.4, P = 0.01) and serum ferritin concentrations (beta = -6.6, P = 0.002), while controlling for gestational age and malaria and hookworm infection. Another 38 pregnant women, who reported eating soil regularly, participated in focus group discussions and were interviewed on geophagy. The most commonly eaten soil was from the walls of houses. The median estimated daily intake was 41.5 g (range 2.5-219.0 g). Twenty-seven of these women assisted in the collection of soil samples which were then analysed for their content of iron, zinc and aluminium after extraction with 0.1 M HC1. The average daily soil intake supplied the geophagous women with 4.3 mg of iron, corresponding to 14% of the recommended dietary allowance of iron for pregnant women. The study revealed a strong negative association between geophagy and both haemoglobin and ferritin status. At the same time it demonstrated the potential of soil as a source of dietary iron for geophagous women. These seemingly contradictory results might be due to other components in the soil interfering with iron uptake or metabolism. Alternatively, it may be that the geophagous women had extremely depleted iron stores before starting to eat soil. From these cross-sectional data, no inference about causality could be made.

Labour complications remain the most important risk factors for perinatal mortality in rural Kenya

OBJECTIVES To identify and quantify risk factors for perinatal mortality in a Kenyan district hospital and to assess the proportion of perinatal deaths attributable to labour complications, maternal undernutrition, malaria, anaemia and human immunodeficiency virus (HIV). METHODS A cross-sectional study of 910 births was conducted between January 1996 and July 1997 and risk factors for perinatal mortality were analysed. FINDINGS The perinatal mortality rate was 118 per 1000 births. Complications of labour such as haemorrhage, premature rupture of membranes/premature labour, and obstructed labour/ malpresentation increased the risk of death between 8- and 62-fold, and 53% of all perinatal deaths were attributable to labour complications. Placental malaria and maternal HIV, on the other hand, were not associated with perinatal mortality. CONCLUSIONS Greater attention needs to be given to the quality of obstetric care provided in the rural district-hospital setting.

A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine–pyrimethamine in Gambian multigravidae

We investigated the ability of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine/pyrimethamine to prevent anaemia and low birthweight in Gambian multigravidae. Between July 2002 and February 2004, 2688 multigravidae living in a rural area of The Gambia received SP (1346 women) or placebo (1342 women) up to four times during pregnancy and were followed until 6‐weeks post‐partum. Shortly after delivery, 10.7% of women in the intervention group and 8.8% in the control group were severely anaemic [Hb < 7 g/dl, risk difference = 0.02 (95% CI −0.01, 0.04), P = 0.17]. The overall mean birthweight of infants born to women who had received SP (3103 g) was very similar to that observed in infants born to women in the control group [3075 g; difference = 28 g (95% CI −11 g, 67 g), P = 0.16]. However, among women who did not use a bednet (either insecticide treated or untreated), infants born to women who had received SP weighed more than infants born to women in the control group [3147 g vs. 3044 g; difference 143 g (95% CI 53 g, 232 g), interaction test P < 0.001]. This study did not show that IPTp with SP benefited Gambian multigravidae overall but that it may benefit a sub‐group of women who do not use a bednet. In areas such as The Gambia, provision of insecticide‐treated bednets to multigravidae may provide an adequate means of protection against malaria in pregnancy without the need for additional IPTp.

A Comparison of the Kampala Trauma Score (KTS) with the Revised Trauma Score (RTS), Injury Severity Score (ISS) and the TRISS Method in a Ugandan Trauma Registry. Is Equal Performance Achieved with Fewer Resources?

AbstractBackground:The public health significance of injuries that occur in developing countries is now recognized. In 1996, as part of the injury surveillance registry in Kampala, Uganda, a new score, the Kampala Trauma Score (KTS) was instituted. The KTS, developed in light of the limited resource base of sub-Saharan Africa, is a simplified composite of the Revised Trauma Score (RTS) and the Injury Severity Score (ISS) and closely resembles the Trauma Score and Injury Severity Score (TRISS).Patients and Methods:The KTS was applied retrospectively to a cohort of prospectively accrued urban trauma patients with the RTS, ISS and TRISS calculated. Using ROC (receiver operating characteristics) analysis, logistic regression models and sensitivity and specificity cutoff analysis, the KTS was compared to these three scores.Results:Using logistic regression models and areas under the ROC curve, the RTS proved a more robust predictor of death at 2 weeks in comparison to the KTS. However, differences in screening performance were marginal (areas under the ROC curves were 87% for the RTS and 84% for the KTS) with statistical significance only reached for an improved specificity (67% vs. 47%; p < 0.001), at a fixed sensitivity of 90%. In addition, the KTS predicted hospitalization at 2 weeks more accurately.Conclusion:The KTS statistically performs comparably to the RTS and ISS alone as well as to the TRISS but has the added advantage of utility. Therefore, the KTS has potential as a triage tool in resource-poor and similar health care settings.