Malaria Prevention with IPTp during Pregnancy Reduces Neonatal Mortality

In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.ClinicalTrials.gov NCT00209781

Clinical malaria in African pregnant women

<p>Abstract</p> <p>Background</p> <p>There is a widespread notion, based on limited information, that in areas of stable malaria transmission most pregnant women with <it>Plasmodium falciparum </it>infection are asymptomatic. This study aim to characterize the clinical presentation of malaria in African pregnant women and to evaluate the adequacy of case management based on clinical complaints.</p> <p>Methods</p> <p>A hospital-based descriptive study between August 2003 and November 2005 was conducted at the maternity clinic of a rural hospital in Mozambique. All women attending the maternity clinic were invited to participate. A total of 2,330 women made 3,437 eligible visits, 3129 were analysed, the remainder were excluded because diagnostic results were unavailable or they were repeat visits. Women gave a standardized clinical history and had a medical exam. Malaria parasitaemia and haematocrit in capillary blood was determined for all women with signs or symptoms compatible with malaria including: presence and history of fever, arthromyalgias, headache, history of convulsions and pallor. Outcome measure was association of malaria symptoms or signs with positive blood slide for malaria parasitaemia.</p> <p>Results</p> <p>In 77.4% of visits pregnant women had symptoms suggestive of malaria; 23% (708/3129) were in the first trimester. Malaria parasitaemia was confirmed in 26.9% (842/3129) of visits. Headache, arthromyalgias and history of fever were the most common symptoms (86.5%, 74.8% and 65.4%) presented, but their positive predictive values for malaria parasitaemia were low [28% (27–30), 29% (28–31), and 33% (31–35), respectively].</p> <p>Conclusion</p> <p>Symptoms suggestive of malaria were very frequent among pregnant women attending a rural maternity clinic in an area of stable malaria transmission. However, less than a third of them were parasitaemic. In the absence of microscopy or rapid diagnostic tests, a large proportion of women, including those in the first trimester of gestation, would be unnecessarily receiving antimalarial drugs, often those with unknown safety profiles for pregnancy. Accessibility to malaria diagnostic tools needs to be improved for pregnant women and drugs with a safety profile in all gestational ages are urgently needed.</p

VAR2CSA Signatures of High Plasmodium falciparum Parasitemia in the Placenta

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49–91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria

Women’s advancement and leadership in the biomedical research centres of Catalonia II: bringing about change

Women; Leadership; Biomedical research centresMujeres; Liderazgo; Centros de investigación biomédicaDones; Lideratge; Centres de recerca biomèdicaNew demands for biomedical research centres are related to gender balance in research teams, gender balance in decision-making, integrating gender in research, and the implementation of Gender-Equality Action Plans (GEAPs). Several approaches for the new demands andchallenges for gender equality where proposed in the Girona Summit. The approaches are related to: analysing gender equality issues, removing unconscious bias through cultural awareness, improving research by integrating a gender perspective, fostering women’s career advancement and development, ensuring gender balance and transparency in decision-making positions, modernising policies and management practices, and representing the points of view of each stakeholder (individual, research centre, funding agency and policy-maker). Although not exhaustive of all possible options, the value of these approaches is being formulated on the basis of the experiences of the delegates of the Catalan research centres. The Hypatia of Alexandria Charter was proposed, discussed, endorsed and signed by the 19 centres of health and biomedical research of Catalonia, and the policy-making and assessment responsibilities of the Health Department of the Catalan Government

Malaria in rural Mozambique. Part II: children admitted to hospital

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VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria

An autopsy study of maternal mortality in Mozambique: the contribution of infectious diseases

Background Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. Methods and Findings We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. Conclusions In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement

Impact of Maternal Human Immunodeficiency Virus Infection on Birth Outcomes and Infant Survival in Rural Mozambique

Sub-Saharan Africa harbors more than two-thirds of the world’s 33.2 million persons infected with human immunodeficiency virus (HIV) and 80% of the world’s HIV-infected women. In parts of southern Africa, more than 30% of pregnant women attending antenatal clinics are infected with HIV, thus making HIV infection one of the most common complications of pregnancy in sub-Saharan Africa. With successful interventions, mother-to-child transmission (MTCT) of HIV has been reduced to less than 2% in developed countries. However, in untreated populations, MTCT of HIV during pregnancy, delivery, and breastfeeding still occurs at an approximate overall rate of 25–40%, and accounts for almost 420,000 new HIV infections in children and 270,000–320,000 pediatric deaths annually. Until 2004, single-dose intrapartum and neonatal nevirapine (sd-NVP) was the recommended regimen by the World Health Organization to prevent MTCT of HIV among women without access to antiretroviral therapy. Preventive MTCT programs with an sd-NVP have been shown to decrease perinatal HIV transmission to 8% in controlled clinical trial settings. However, there is great concern about the rapid development of resistance. In addition, in predominantly breastfeeding populations of sub- Saharan Africa, most MTCT of HIV still occurs during the postnatal period. Currently, MTCT prevention programs in sub-Saharan African countries include zidovudine and lamivudine during the final weeks of pregnancy and sd-NVP at delivery. In addition, the newborn receives sd-NVP at birth and zidovudine for seven days. Nevertheless, effectiveness of these strategies relies on the great challenge of availability of the drugs and compliance with them, given that these preventive regimens are prolonged and unsupervised. Several studies from the Africa have reported that HIVinfected pregnant women are at increased risk of adverse pregnancy outcomes such as spontaneous abortion, stillbirths, and preterm labor. However, this analysis is complicated by many factors associated with HIV infection and poor pregnancy outcomes such as malnutrition, anemia, and other frequent infections such as syphilis or malaria. These factors may contribute to the observation that the association between HIV infection and adverse pregnancy outcomes is stronger in women from developing countries. Maternal HIV infection has also been associated with an increased risk of infant death. It is well documented that up to 35% of HIV-infected infants may die before the first year of age, but HIV-negative children born to HIV-infected mothers are also at high risk of mortality. There have been few studies characterizing the impact of HIV infection during pregnancy on the mother and her infant and even fewer from rural African settings. The main aim of this study was to assess the impact of HIV infection on birth outcomes and infant survival in a rural area of southern Mozambique. Furthermore, the study also evaluated the effect of unsupervised sd-NVP administration for prevention of MTCT of HIV on HIV RNA viral load at delivery and the prevalence of NVP resistance mutations

Malaria in rural Mozambique. Part I: Children attending the outpatient clinic

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High antibody responses against Plasmodium falciparum in immigrants after extended periods of interrupted exposure to malaria.

Background Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. Methods A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142 (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Results Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142 (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria. Conclusions Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures