Azucena Bardají

Publications (33)149.05 Total impact

• Article: Weighing for results: assessing the effect of IPTp.

  Julie Gutman, Erin Eckert, Viviana Mangiaterra, Azucena Bardají, John J Aponte, Clara Menéndez, Bernard Nahlen, Laurence Slutsker
  The Lancet Infectious Diseases 04/2013; 13(4):292. · 17.39 Impact Factor
• Article: Rosetting in Plasmodium vivax: A Cytoadhesion Phenotype Associated with Anaemia.

  Alejandro Marín-Menéndez, Azucena Bardají, Flor E Martínez-Espinosa, Camila Bôtto-Menezes, Marcus V Lacerda, Jon Ortiz, Pau Cisteró, Mireia Piqueras, Ingrid Felger, Ivo Müeller, Jaume Ordi, Hernando Del Portillo, Clara Menéndez, Mats Wahlgren, Alfredo Mayor
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  ABSTRACT: Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates. Rosetting and adhesion to CSA, CD36, ICAM1, placental and brain cryosections were determined in P. vivax peripheral isolates from 12 pregnant women, 24 non-pregnant women and 23 men from Manaus (Brazil). P. falciparum co-infection was excluded by PCR and P. vivax isolates were genotyped by assessing the size polymorphism of microsatellites ms2, ms20 and msp1F3 through capillary electrophoresis of PCR products. P. vivax monoinfection was confirmed by PCR in 59 isolates, with 50 (85%) of them being single-clone infections. One P. vivax haplotype was more frequently found among pregnant women (33%) than in non-pregnant women (0%) and men (4%; p = 0.010). Rosetting was observed in 64% of the isolates, adhesion to CSA in 15%, to ICAM1 in 12% and to placental cryosections in 9%, being similar among pregnant and non-pregnant groups. Intensity of rosetting was higher among anaemic individuals compared to non-anaemic (p = 0.010) and decreased with increasing haematocrit (p = 0.033) and haemoglobin levels (p = 0.015). P. vivax peripheral isolates from pregnant women do not exhibit a prominent adhesion to CSA, although other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones observed among pregnant hosts. Rosetting is a frequent cytoadhesive phenotype in P. vivax infections that may contribute to the development of anaemia.
  PLoS Neglected Tropical Diseases 04/2013; 7(4):e2155. · 4.69 Impact Factor
• Article: Improved pregnancy outcomes in women exposed to malaria with high antibody levels against Plasmodium falciparum.

  Alfredo Mayor, Urwashi Kumar, Azucena Bardají, Pankaj Gupta, Alfons Jiménez, Amel Hamad, Betuel Sigaúque, Bijender Singh, Llorenç Quintó, Sanjeev Kumar, Puneet K Gupta, Virander S Chauhan, Carlota Dobaño, Pedro L Alonso, Clara Menéndez, Chetan E Chitnis
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  ABSTRACT: Background. Antibodies against VAR2CSA, the Plasmodium falciparum variant surface antigen that binds placental chondroitin sulfate A, have been suggested to mediate protection against malaria in pregnancy but also to be markers of infection. Here, we aimed to identify clinically relevant antibody responses taking into consideration variations in parasite exposure and HIV infection.Methods. IgGs against placental and pediatric isolates, VAR2CSA (DBL2X, DBL3X, DBL5ε, DBL6ε domains) and other blood stage antigens (DBLγ, DBLα, MSP119, AMA1, EBA175) were measured in plasmas from 293 Mozambican women at delivery. Associations between antibody responses, factors influencing malaria exposure, HIV infection and pregnancy outcomes were assessed.Results. Maternal antibodies were affected by placental infection, parity, season and neighbourhood of residence. HIV infection modified these associations and attenuated the parity-dependent increase of IgGs. High antibody levels against AMA1, DBL3X, DBL6ε, placental and paediatric isolates were associated with increased weight and gestational age of newborns (p≤0.036) among women with malaria episodes during pregnancy.Conclusions. Anti-parasite IgGs in women at delivery are affected by HIV infection as well as by variations in the exposure to P. falciparum. Heterogeneity of malaria transmission needs to be considered to identify IgGs against VAR2CSA and other parasite antigens associated with improved pregnancy outcomes.
  The Journal of Infectious Diseases 02/2013; · 6.41 Impact Factor
• Article: Cytokine and Antibody Responses to Plasmodium falciparum in Naïve Individuals during a First Malaria Episode: Effect of Age and Malaria Exposure.

  Gemma Moncunill, Alfredo Mayor, Alfons Jiménez, Augusto Nhabomba, Laura Puyol, Maria N Manaca, Diana Barrios, Pau Cisteró, Caterina Guinovart, Ruth Aguilar, Azucena Bardají, María-Jesús Pinazo, Evelina Angov, Sheetij Dutta, Chetan E Chitnis, José Muñoz, Joaquim Gascón, Carlota Dobaño
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  ABSTRACT: Age- and exposure-dependent immune responses during a malaria episode may be key to understanding the role of these factors in the acquisition of immunity to malaria. Plasma/serum samples collected from naïve Mozambican children (n = 48), European adults (naïve travelers, n = 22; expatriates with few prior malaria exposures, n = 15) and Mozambican adults with long-life malaria exposure (n = 99) during and after a malaria episode were analyzed for IgG against merozoite proteins by Luminex and against infected erythrocytes by flow cytometry. Cytokines and chemokines were analyzed in plasmas/sera by suspension array technology. No differences were detected between children and adults with a primary infection, with the exception of higher IgG levels against 3D7 MSP-1(42) (P = 0.030) and a P. falciparum isolate (P = 0.002), as well as higher IL-12 (P = 0.020) in children compared to other groups. Compared to malaria-exposed adults, children, travelers and expatriates had higher concentrations of IFN-γ (P≤0.0090), IL-2 (P≤0.0379) and IL-8 (P≤0.0233). Children also had higher IL-12 (P = 0.0001), IL-4 (P = 0.003), IL-1β (P = 0.024) and TNF (P = 0.006) levels compared to malaria-exposed adults. Although IL-12 was elevated in children, overall the data do not support a role of age in immune responses to a first malaria episode. A T(H)1/pro-inflammatory response was the hallmark of non-immune subjects.
  PLoS ONE 01/2013; 8(2):e55756. · 4.09 Impact Factor
• Article: Plasmodium vivax congenital malaria in an area of very low endemicity in Guatemala: implications for clinical and epidemiological surveillance in a malaria elimination context.

  María Eugenia Castellanos, Azucena Bardají, Michela Menegon, Alfredo Mayor, Meghna Desai, Carlo Severini, Clara Menéndez, Norma Padilla
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  ABSTRACT: This is a report of the first Plasmodium vivax congenital malaria case in Guatemala and the first case in Latin America with genotypical, histological and clinical characterization. The findings show that maternal P. vivax infection still occurs in areas that are in the pathway towards malaria elimination, and can be associated with detrimental health effects for the neonate. It also highlights the need in very low transmission areas of not only maintaining, but increasing awareness of the problem and developing surveillance strategies, based on population risk, to detect the infection especially in this vulnerable group of the population.
  Malaria Journal 12/2012; 11(1):411. · 3.19 Impact Factor
• Article: Placental infection with Plasmodium vivax: a histopathological and molecular study.

  Alfredo Mayor, Azucena Bardají, Ingrid Felger, Christopher L King, Pau Cisteró, Carlota Dobaño, Danielle I Stanisic, Peter Siba, Mats Wahlgren, Hernando Del Portillo, Ivo Mueller, Clara Menéndez, Jaume Ordi, Stephen Rogerson
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  ABSTRACT: Background. Evidence of the presence of Plasmodium vivax in the placenta is scarce and inconclusive. This information is relevant to understanding whether P. vivax affects placental function and how it may contribute to poor pregnancy outcomes.Methods. Histopathological examination of placental biopsies from 80 Papua New Guinean pregnant women was combined with quantitative polymerase chain reaction (qPCR) to confirm P. vivax infection and rule out co-infection with other Plasmodium species in placental and peripheral blood. Leukocytes and monocyte/macrophages were detected in placental sections by immunohistochemistry.Results. Mono-infection by P. vivax and P. falciparum was detected by qPCR in eight and ten placentas, respectively. Seven of the eight women with P. vivax placental mono-infection were negative in peripheral blood. By histology, three placentas with P. vivax mono-infection showed parasitized erythrocytes in the intervillous space but no hemozoin in macrophages nor increased intervillous inflammatory cells. In contrast, seven placentas positive for P. falciparum presented parasites and hemozoin in macrophages or fibrin as well as intervillous inflammatory infiltrates.Conclusions. P. vivax can be associated with placental infection. However, placental inflammation is not observed in P. vivax mono-infections, suggesting other causes of poor delivery outcomes associated with P. vivax infection.
  The Journal of Infectious Diseases 10/2012; · 6.41 Impact Factor
• Article: Comparison of placental blood microscopy and the ICT HRP2 rapid diagnostic test to detect placental malaria.

  Ruth Aguilar, Sonia Machevo, Clara Menéndez, Azucena Bardají, Augusto Nhabomba, Pedro L Alonso, Alfredo Mayor
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  ABSTRACT: Monitoring interventions to prevent malaria in pregnancy requires sensitive detection of placental infection. Rapid diagnostic tests (RDTs) are good candidates, but little information is available on their sensitivity on placental blood. We have evaluated the agreement (kappa coefficient) between microscopy and a Plasmodium falciparum histidine-rich protein 2 (HRP2)-based immuno-chromatographic test (ICT) on placental blood from 1151 women at delivery. Prevalences of placental infection by microscopy and RDT were 5.1% and 5.0%, respectively, showing 82.9% agreement (p<0.0001). Discordances were found at low parasitemias (<500 parasites/μL) or negative microscopy. The results suggest that the HRP2-RDTs from ICT diagnostics is a good alternative to microscopy for diagnosing placental malaria at delivery.
  Transactions of the Royal Society of Tropical Medicine and Hygiene 07/2012; 106(9):573-5. · 2.16 Impact Factor
• Article: Intermittent preventive treatment of malaria in pregnant women and infants: making best use of the available evidence.

  Azucena Bardají, Quique Bassat, Pedro L Alonso, Clara Menéndez
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  ABSTRACT: INTRODUCTION: Malaria continues to represent a huge global health burden on the most vulnerable populations. The Intermittent Preventive Treatment (IPT) strategy has been shown to be an efficacious intervention in preventing most of the deleterious effects of malaria in pregnant women and infants. Yet, the effectiveness of the IPT strategy may be impaired by the increasing resistance to sulfadoxine-pyrimethamine (SP), and the scarcity of alternative antimalarial drugs. AREAS COVERED: This review examines all the available information on IPT, in an aim to provide the scientific community with a framework to understand the benefits and limitations of this malaria control strategy. It includes the understanding of the historical background of the IPT strategy, the drug's mechanisms of actions, updated information on current available evidence, the implications of drug resistance and choice of alternative drugs, and a comprehensive discussion on the perspectives of IPT for malaria control in pregnant women and infants. EXPERT OPINION: IPT in pregnancy and infants is a cost-effective strategy that can contribute significantly to the control of malaria in endemic areas. Monitoring its effectiveness will allow tracking of progress, evaluation of the adequacy of currently used drugs and will highlight the eventual need for new therapies or alternative interventions.
  Expert Opinion on Pharmacotherapy 07/2012; 13(12):1719-36. · 3.20 Impact Factor
• Article: Immunoglobulins against the surface of Plasmodium falciparum-infected erythrocytes increase one month after delivery.

  Alfredo Mayor, Elisa Serra-Casas, Eduard Rovira-Vallbona, Alfons Jiménez, Llorenç Quintó, Betuel Sigaúque, Carlota Dobaño, Azucena Bardají, Pedro L Alonso, Clara Menéndez
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  ABSTRACT: The risk of Plasmodium falciparum malaria increases during pregnancy and at early postpartum. Immunological and physiological alterations associated with pregnancy that persist after delivery may contribute to the susceptibility to P. falciparum during early postpartum period. To determine changes in antibody-mediated responses after pregnancy, levels of Immunoglobulin G (IgGs) specific for P. falciparum were compared in 200 pairs of plasmas collected from Mozambican women at delivery and during the first two months postpartum. IgGs against the surface of erythrocytes infected with a P. falciparum chondroitin sulphate A binding line (CS2) and a paediatric isolate (MOZ2) were measured by flow cytometry. IgG levels against CS2 and MOZ2 were higher at postpartum than at delivery (p = 0.033 and p = 0.045, respectively) in women without P. falciparum infection. The analysis stratified by parity and period after delivery showed that this increase was significant in multi-gravid women (p = 0.023 for CS2 and p = 0.054 for MOZ2) and during the second month after delivery (p = 0.018 for CS2 and p = 0.015 for MOZ2). These results support the view that early postpartum is a period of recovery from physiological or immunological changes associated with pregnancy.
  Malaria Journal 04/2012; 11:130. · 3.19 Impact Factor
• Source

  Available from: Laura Moro

  Article: How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.

  Alfredo Mayor, Laura Moro, Ruth Aguilar, Azucena Bardají, Pau Cisteró, Elisa Serra-Casas, Betuel Sigaúque, Pedro L Alonso, Jaume Ordi, Clara Menéndez
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  ABSTRACT: Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated. P. falciparum infections were assessed in 272 Mozambican women at delivery by microscopy, placental histology, quantitative polymerase chain reaction (qPCR) and detection of histidine-rich protein 2 (HRP2) in plasma by enzyme-linked immunosorbent assay (ELISA) and a rapid diagnostic test (RDT). Association between infection and delivery outcomes was determined. Among the 122 women qPCR-positive for P. falciparum in peripheral and/or placental blood samples, 87 (71.3%) did not receive a positive diagnosis by peripheral microscopy, 75 (61.5%) by HRP2 ELISA, and 74 (60.7%) by HRP2 RDT in plasma. Fifty-seven of the 98 qPCR-positive placental infections (58.2%) were not detected by histology. Women who were qPCR-positive but negative in their peripheral blood by microscopy or HRP2 RDT in plasma (n = 62) were at increased risk of anemia, compared with negative women (n = 141; odds ratio, 2.03; 95% confidence interval, 1.07-3.83; P = .029). Microscopy, placental histology and HRP2-based plasma diagnostic methods fail to identify the majority of the P. falciparum infections detected by qPCR in peripheral and placental blood. Undetected infections were associated with maternal anemia, highlighting the urgent need for more accurate malaria diagnostic tools for pregnant women to avoid the negative clinical impact that hidden infections can have during pregnancy. NCT00209781.
  Clinical Infectious Diseases 03/2012; 54(11):1561-8. · 9.15 Impact Factor
• Article: Drug exposure and pregnancy outcome in Mozambique.

  Esperança Sevene, Azucena Bardají, Alda Mariano, Sónia Machevo, Edgar Ayala, Betuel Sigaúque, John J Aponte, Xavier Carné, Pedro L Alonso, Clara Menendez
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  ABSTRACT: The intake of medicines during pregnancy can have negative or toxic effects on the fetus, possibly leading to adverse pregnancy outcomes. The aim of this study was to describe the level of drug exposure during pregnancy in a rural area of Mozambique and its relation to pregnancy outcome. A total of 3105 pregnant women were interviewed in a cohort study. Information on disease, treatments received during pregnancy, and pregnancy outcome was collected. Newborns were examined at birth for clinical signs, birthweight, and presence of any congenital malformation. Malaria and sexually transmitted diseases were the most frequently reported diseases (30.5% and 24.1%, respectively), and 41% (1276/3105) of participants reported at least one drug exposure. The mean number of drugs taken per pregnant woman was 3.9 (SD 2.1). Antibiotics were the most commonly (41.2%) reported agents, followed by antimalarials (23.8%). There were more stillbirths (p < 0.007) among those reporting to be exposed to drugs compared with no exposure. Polydactyly was the most frequent malformation observed. Drug exposure during pregnancy, including drugs with recognized potential pregnancy risk, was high in this rural area of southern Africa. The association of stillbirths with drug exposure might be a consequence of the disease that led to drug administration, although a direct causality of the drugs cannot be excluded. These findings emphasize the need for reinforcing pharmacovigilance systems in rural Africa, especially, or at least, in pregnant women.
  Paediatric Drugs 02/2012; 14(1):43-9. · 1.79 Impact Factor
• Article: Reduction of antimalarial antibodies by HIV infection is associated with increased risk of Plasmodium falciparum cord blood infection.

  Denise Naniche, Elisa Serra-Casas, Azucena Bardají, Llorenç Quintó, Carlota Dobaño, Betuel Sigauque, Pau Cisteró, Virander S Chauhan, Chetan E Chitnis, Pedro L Alonso, Clara Menéndez, Alfredo Mayor
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  ABSTRACT: Plasmodium falciparum infection in pregnancy can lead to congenital malaria, which has detrimental health consequences for infants. Human immunodeficiency virus (HIV) might increase cord blood P. falciparum infection by decreasing maternal antimalarial-specific antibodies. HIV-negative (n=133) and HIV-positive (n=55) Mozambican pregnant women were assessed at delivery for maternal and cord P. falciparum infection by quantitative polymerase chain reaction (qPCR) and P. falciparum-specific antibodies by enzyme-linked immunosorbent assay and flow cytometry. Prevalence of qPCR-detected cord blood infection was 8.0%. Risk of cord infection was increased in presence of HIV (adjusted odds ratio [AOR], 3.80; P=.04) and placental malaria (AOR, 22.08; P=.002) after adjusting for clinical variables. The odds of having a high immunoglobulin G response to chondrotin sulphate A-binding infected erythrocytes, parasite lysate, and erythrocyte-binding antigen-175 were reduced among HIV-positive women (P < .001, .048, and .056, respectively) and among women with cord P. falciparum infection (P = .009, .04, and .046, respectively). In multivariate analysis including maternal HIV status, placental malaria, and antibody responses, HIV was no longer associated with cord blood infection (P = .11). HIV-associated impairment of antibody responses in pregnant women may contribute to a higher transmission of P. falciparum to their infants.
  The Journal of Infectious Diseases 02/2012; 205(4):568-77. · 6.41 Impact Factor
• Article: Development of vaccines to prevent malaria in pregnant women: WHO MALVAC meeting report.

  Clara Menéndez, Vasee S Moorthy, Zarifah Reed, Azucena Bardají, Pedro Alonso, Graham V Brown
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  ABSTRACT: The major public health consequences of malaria in pregnancy have long been acknowledged. However, further information is still required for development and implementation of a malaria vaccine specifically directed to prevent malaria in pregnant women and improve maternal, fetal and infant outcomes. The WHO Malaria Vaccine Advisory Committee (MALVAC) provides guidance to the WHO on strategic priorities and research needs for development of vaccines to prevent malaria. Here we summarize the discussions and conclusions of a MALVAC scientific forum meeting on considerations in the development of vaccines to prevent malaria in pregnant women. This report includes brief summaries of what is known, and major knowledge gaps in disease burden estimation, pathogenesis and immunity, and the challenges with current preventive strategies for malaria in pregnancy. We conclude with the formulation of a conceptual framework for research and development for vaccines to prevent malaria in pregnant women.
  Expert Review of Vaccines 09/2011; 10(9):1271-80. · 4.25 Impact Factor
• Article: Transcription of var genes other than var2csa in Plasmodium falciparum parasites infecting Mozambican pregnant women.

  Eduard Rovira-Vallbona, Carlota Dobaño, Azucena Bardají, Pau Cisteró, Cleofé Romagosa, Elisa Serra-Casas, Llorenç Quintó, Quique Bassat, Betuel Sigaúque, Pedro L Alonso, Jaume Ordi, Clara Menéndez, Alfredo Mayor
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  ABSTRACT: Increased susceptibility to Plasmodium falciparum infection during pregnancy has been attributed to the accumulation of infected erythrocytes in the placenta. This phenomenon is mediated by a var gene coding for VAR2CSA, which adheres to chondroitin sulphate A. However, the contribution of parasites transcribing other var genes to maternal infections has not been well characterized. Transcription of var2csa and var groups A, B, and C was measured by real-time polymerase chain reaction in 30 placental and 21 peripheral P. falciparum isolates from pregnant women and in 42 isolates from nonpregnant adults and children. Associations of infections with non-var2csa isolates with maternal parasitemia and immune responses were assessed. Placental parasites showed the highest levels of var2csa. ABC var genes were transcribed by 20 (67%) of 30 placental isolates and were associated with higher parasitemia compared with infections by parasites only transcribing var2csa (P = .004). Peripheral isolates from pregnant women transcribed ABC var genes at levels similar to those of parasites infecting nonpregnant adults with clinical malaria (P[varA] = .420, P[varB] = .808, and P[varC] = .619). Transcripts of var2csa are abundant in pregnancy-associated P. falciparum infections; however, ABC var types are also common, especially in peripheral blood, with transcription levels similar to those of infections out of pregnancy. These findings are of interest for the design of malaria vaccines for pregnant women.
  The Journal of Infectious Diseases 07/2011; 204(1):27-35. · 6.41 Impact Factor
• Article: Grading schemes for placental malaria.

  Jaume Ordi, Azucena Bardají, Paola Castillo, Mamudo R Ismail, Clara Menéndez
  The Journal of Infectious Diseases 06/2011; 203(11):1694-5; author reply 1695-6. · 6.41 Impact Factor
• Source

  Available from: Sergi Sanz

  Article: Impact of malaria at the end of pregnancy on infant mortality and morbidity.

  Azucena Bardají, Betuel Sigauque, Sergi Sanz, María Maixenchs, Jaume Ordi, John J Aponte, Samuel Mabunda, Pedro L Alonso, Clara Menéndez
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  ABSTRACT: There is some consensus that malaria in pregnancy may negatively affect infant's mortality and malaria morbidity, but there is less evidence concerning the factors involved. A total of 1030 Mozambican pregnant women were enrolled in a randomized, placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine, and their infants were followed up throughout infancy. Overall mortality and malaria morbidity rates were recorded. The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed. There were 58 infant deaths among 997 live-born infants. The risk of dying during infancy was increased among infants born to women with acute placental infection (odds ratio [OR], 5.08 [95% confidence interval (CI), 1.77-14.53)], parasitemia in cord blood (OR, 19.31 [95% CI, 4.44-84.02]), low birth weight (OR, 2.82 [95% CI, 1.27-6.28]) or prematurity (OR, 3.19 [95% CI, 1.14-8.95]). Infants born to women who had clinical malaria during pregnancy (OR, 1.96 [95% CI, 1.13-3.41]) or acute placental infection (OR, 4.63 [95% CI, 2.10-10.24]) had an increased risk of clinical malaria during infancy. Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy. Effective clinical management and prevention of malaria in pregnancy may improve infant's health and survival.
  The Journal of Infectious Diseases 03/2011; 203(5):691-9. · 6.41 Impact Factor
• Article: HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment.

  Clara Menéndez, Elisa Serra-Casas, Michael D Scahill, Sergi Sanz, Augusto Nhabomba, Azucena Bardají, Betuel Sigauque, Pau Cisteró, Inacio Mandomando, Carlota Dobaño, Pedro L Alonso, Alfredo Mayor
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  ABSTRACT: Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections. SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique. Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of 30 samples; P = .025), more prevalent in women who received IPTp-SP than in those who received placebo (odds ratio [OR], 8.13; 95% confidence interval [CI], 1.69-39.08), and more prevalent in HIV-positive women than in HIV-negative women (OR, 5.17; 95% CI, 1.23-21.66). No association was found between mutant infections and increased parasite density or malaria-related morbidity in mothers and children. IPTp with SP increases the prevalence of resistance markers in the placenta and in HIV-infected women at delivery, which suggests that host immunity is key for the clearance of drug-resistant infections. However, this effect of IPTp is limited to the period when blood levels of SP are likely to be significant and does not translate into more-severe infections or adverse clinical outcomes.
  Clinical Infectious Diseases 01/2011; 52(1):41-8. · 9.15 Impact Factor
• Source

  Available from: PubMed Central

  Article: Costs associated with low birth weight in a rural area of Southern Mozambique.

  Elisa Sicuri, Azucena Bardají, Betuel Sigauque, Maria Maixenchs, Ariel Nhacolo, Delino Nhalungo, Eusebio Macete, Pedro L Alonso, Clara Menéndez
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  ABSTRACT: Low Birth Weight (LBW) is prevalent in low-income countries. Even though the economic evaluation of interventions to reduce this burden is essential to guide health policies, data on costs associated with LBW are scarce. This study aims to estimate the costs to the health system and to the household and the Disability Adjusted Life Years (DALYs) arising from infant deaths associated with LBW in Southern Mozambique. Costs incurred by the households were collected through exit surveys. Health system costs were gathered from data obtained onsite and from published information. DALYs due to death of LBW babies were based on local estimates of prevalence of LBW (12%), very low birth weight (VLBW) (1%) and of case fatality rates compared to non-LBW weight babies [for LBW (12%) and VLBW (80%)]. Costs associated with LBW excess morbidity were calculated on the incremental number of hospital admissions in LBW babies compared to non-LBW weight babies. Direct and indirect household costs for routine health care were 24.12 US$ (CI 95% 21.51; 26.26). An increase in birth weight of 100 grams would lead to a 53% decrease in these costs. Direct and indirect household costs for hospital admissions were 8.50 US$ (CI 95% 6.33; 10.72). Of the 3,322 live births that occurred in one year in the study area, health system costs associated to LBW (routine health care and excess morbidity) and DALYs were 169,957.61 US$ (CI 95% 144,900.00; 195,500.00) and 2,746.06, respectively. This first cost evaluation of LBW in a low-income country shows that reducing the prevalence of LBW would translate into important cost savings to the health system and the household. These results are of relevance for similar settings and should serve to promote interventions aimed at improving maternal care.
  PLoS ONE 01/2011; 6(12):e28744. · 4.09 Impact Factor
• Article: Persistence of Plasmodium falciparum parasites in infected pregnant Mozambican women after delivery.

  Elisa Serra-Casas, Clara Menéndez, Carlota Dobaño, Azucena Bardají, Llorenç Quintó, Llorençc Quintó, Jaume Ordi, Betuel Sigauque, Pau Cisteró, Inacio Mandomando, Pedro L Alonso, Alfredo Mayor
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  ABSTRACT: Pregnant women are susceptible to Plasmodium falciparum parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known. Here, we aimed to identify host factors contributing to the risk of postpartum infections and to determine the origin of postpartum parasites by comparing their genotypes with those present at the time of delivery. To address this, blood samples were collected at delivery (n = 402) and postpartum (n = 354) from Mozambican women enrolled in a trial of intermittent preventive treatment in pregnancy (IPTp). P. falciparum was detected by real-time quantitative PCR (qPCR), and the parasite merozoite surface protein 1 (msp-1) and msp-2 genes were genotyped. Fifty-seven out of 354 (16%) women were infected postpartum as assessed by qPCR, whereas prevalence by optical microscopy was only 4%. Risk of postpartum infection was lower in older women (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.15 to 0.81) and higher in women with a placental infection at delivery (OR = 4.20, 95% CI = 2.19 to 8.08). Among 24 women with matched infections, 12 (50%) were infected postpartum with at least one parasite strain that was also present in their placentas. These results suggest that parasites infecting pregnant women persist after delivery and increase the risk of malaria during the postpartum period. Interventions that reduce malaria during pregnancy may translate into a lower risk of postpartum infection.
  Infection and immunity 11/2010; 79(1):298-304. · 4.21 Impact Factor
• Article: The effect of intermittent preventive treatment during pregnancy on malarial antibodies depends on HIV status and is not associated with poor delivery outcomes.

  Elisa Serra-Casas, Clara Menéndez, Azucena Bardají, Llorenç Quintó, Carlota Dobaño, Betuel Sigauque, Alfons Jiménez, Inacio Mandomando, Virander S Chauhan, Chetan E Chitnis, Pedro L Alonso, Alfredo Mayor
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  ABSTRACT: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in sub-Saharan Africa. However, studies reporting the effect of IPTp on malaria-specific immunity are scarce and are based on findings in human immunodeficiency virus (HIV)-negative primigravidae. Plasma samples obtained from 302 pregnant women (177 who were HIV negative, 88 who were HIV positive, and 37 who were of unknown HIV status) participating in a placebo-controlled trial of IPTp with SP (IPTp-SP) were analyzed for the presence of antibodies against merozoite antigens, whole asexual parasites, and variant surface antigens from chondroitin sulfate A-binding and nonbinding lines. Antibody levels were compared between intervention groups, and their association with morbidity outcomes was assessed. HIV-positive mothers receiving SP had lower levels of peripheral antibodies against apical membrane antigen-1 and variant surface antigens, as well as lower levels of cord antibodies against erythrocyte-binding antigen-175 and parasite lysate, than did HIV-positive placebo recipients. No difference between intervention groups was observed among HIV-negative mothers. High antibody levels were associated with maternal infection and an increased risk of a first malaria episode in infants. Antibody responses were not consistently associated with reduced maternal anemia, prematurity, or low birth weight. The IPTp-associated reduction in antibodies in HIV-infected women, but not in HIV-uninfected women, may reflect a higher efficacy of the intervention in preventing malaria among HIV-positive mothers. This reduction did not translate into an enhanced risk of malaria-associated morbidity in mothers and infants. Trial registration. Clinicaltrials.gov identifier NCT00209781.
  The Journal of Infectious Diseases 01/2010; 201(1):123-31. · 6.41 Impact Factor