Malaria during pregnancy and transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV) antibodies: a cohort study of Kenyan mother and child pairs

Background Kaposi sarcoma-associated herpesvirus (KSHV) seroprevalence in sub-Saharan African children can range up to 50% by age 2 years but factors affecting early age of KSHV infection are not well understood. Malaria during pregnancy has been associated with hindered transplacental transfer of antibodies to several pathogens but whether it affects transplacental transfer of KSHV antibodies is unknown. We aimed to determine if in utero malaria exposure reduced the transfer of KSHV antibodies across the placenta. Methods A cohort study in Kisumu, Kenya enrolled pregnant women at their first antenatal clinic (ANC) visit and followed them through delivery. We included 70 KSHV-positive, HIV-negative mothers and their children. KSHV antibody levels were measured by ELISA (K8.1, ORF73) and multiplex assay (K8.1, ORF73, K10.5, ORF38, ORF50). Transplacental transfer of antibodies was measured by the cord to maternal blood ratio (CMR) of KSHV antibodies. Malaria during pregnancy was defined as detection of Plasmodium falciparum (Pf) DNA at any ANC visit or delivery. Among women with malaria during pregnancy, we examined time of last malaria infection prior to delivery (< 27 vs. 27+ weeks gestation) and malaria incidence rate (MIR) (episodes/100 person-weeks). Results KSHV seroprevalence (positive for K8.1 or ORF73 by ELISA) among pregnant women was 88%. Neither malaria during pregnancy, malaria infection timing, nor MIR were associated with maternal delivery KSHV antibody blood levels. Maternal delivery and cord blood KSHV antibody levels were highly correlated but these correlations did not differ by malaria during pregnancy. KSHV transplacental antibody transfer was not associated with malaria during pregnancy, malaria infection timing, nor MIR. Conclusions Malaria during pregnancy does not appear to affect transfer of KSHV antibodies across the placenta.

Malaria in Early Pregnancy and the Development of the Placental Vasculature

Background Pregnancy malaria has a negative impact on fetal outcome. It is uncertain whether infections in early pregnancy have a clinical impact by impeding the development of the placental vasculature. Methods Tanzanian women (n = 138) were closely monitored during pregnancy. Placentas collected at birth were investigated using stereology to establish the characteristics of placental villi and vessels. Placental vasculature measures were compared between women infected with malaria and controls. Results Compared with controls, placentas from women infected with malaria before a gestational age (GA) of 15 weeks had a decreased volume of transport villi (mean decrease [standard deviation], 12.45 [5.39] cm3; P = .02), an increased diffusion distance in diffusion vessels (mean increase, 3.33 [1.27] µm; P = .01), and a compensatory increase in diffusion vessel surface area (mean increase, 1.81 [0.74 m2]; P = .02). In women who had malaria before a GA of 15 weeks diffusion vessel surface area and transport vessel length distance were positive predictors for birth weight (multilinear regression: P = .007 and P = .055 for diffusion surface area and transport length, respectively) and GA at delivery (P = .005 and P = .04). Conclusions Malaria infection in early pregnancy impedes placental vascular development. The resulting phenotypic changes, which can be detected at delivery, are associated with birth weight and gestational length. Clinical Trials Registration NCT02191683.

Convulsions: Eclampsia or Malaria or Both!

ABSTRACT Introduction Prevalence of malaria in pregnancy is 1.4%. A high index of suspicion is most important in the diagnosis of malaria and should be differentiated from other complications like eclampsia, intrauterine sepsis. Case Report Gravida 3 para 2 living 1 (G3P2L1) with 28 weeks gestation was referred with high blood pressure (BP), severe anemia. She was afebrile, severe pallor +, pedal edema +, pulse rate (PR)—110/ min, BP—140/80 mm Hg, per abdomen (P/A)— Ut 28 to 30 weeks size relaxed with fetal heart sounds (FHS) regular. Hemoglobin (HB) 5.3 gm%, platelet count 80,000. After 3 days, patient threw one convulsion. Low dose MgSO4 regime given. Peripheral smear (PS) for malarial parasite (MP) vivax positive and injection quinine 1200 mg in 10% dextrose started. She was induced and delivered. Discussion In pregnancy malaria is more common, more atypical, more severe and more fatal. Once diagnosed treatment should be started immediately and pregnant woman should be given full doses of antimalarials. Both eclampsia and malaria are to be treated. How to cite this article Jaju PB, Bhavi SB. Convulsions: Eclampsia or Malaria or Both! J South Asian Feder Obst Gynae 2015;7(3):245-246.

Multilaboratory Approach to Preclinical Evaluation of Vaccine Immunogens for Placental Malaria

ABSTRACTPregnancy malaria is caused byPlasmodium falciparum-infected erythrocytes that adhere to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta; women become resistant to pregnancy malaria as they acquire antiadhesion antibodies that target surface proteins of placental parasites. VAR2CSA, a member of theP. falciparumEMP1 variant surface antigen family, is the leading candidate for a pregnancy malaria vaccine. Because VAR2CSA is a high-molecular-weight protein, a vaccine based on the full-length protein may not be feasible. An alternative approach has been to develop a vaccine targeting individual Duffy binding-like (DBL) domains. In this study, a consortium of laboratories under the Pregnancy Malaria Initiative compared the functional activity of antiadhesion antibodies elicited by different VAR2CSA domains and variants produced in prokaryotic and eukaryotic expression systems. Antisera were initially tested against laboratory lines of maternal parasites, and the most promising reagents were evaluated in the field against fresh placental parasite samples. Recombinant proteins expressed inEscherichia colielicited antibody levels similar to those expressed in eukaryotic systems, as did the two allelic forms of the DBL4 and DBL5 domains. The procedures developed for this head-to-head comparison will be useful for future evaluation and down-selection of malaria vaccine immunogens.

Efecto de la infección submicroscópica o policlonal de Plasmodium falciparum sobre la madre y el producto de la gestación: revisión sistemática

ANTECEDENTES: La malaria gestacional es causa importante de morbi-mortalidad materno-infantil y puede transcurrir con parasitemias no detectadas con microscopía; además, por la diversidad genética parasitaria, es común encontrar infecciones policlonales. OBJETIVOS: Conocer la frecuencia de infecciones submicroscópicas (ISM) y/o policlonales (IP) durante la gestación y analizar el impacto que tienen en la presentación clínica y el desarrollo de inmunidad y sus consecuencias en la madre y el producto de gestación. METODOLOGÍA: Se hizo búsqueda en Medline con los términos (MeSH) "pregnancy", "malaria", "PCR", "microscopy", "genotype", "clones". Se seleccionaron los estudios que diagnosticaron la infección por microscopía y PCR. RESULTADOS: Se incluyeron 16 estudios, todos realizados en África. El promedio ponderado (PP) de ISM en el total de mujeres fue del 36% y según fuese la infección microscópica (IM), submicroscópica o negativa, los PP de anemia materna y bajo peso al nacer (BPN) fueron 51%, 42% y 33% y 19%, 16% y 11%, respectivamente. Con referencia al grupo sin infección, los riesgos (OR) fueron: a) para anemia materna 2,12 en IM y 1,48 en ISM; b) para BPN 1,89 en IM y 1,56 en ISM. El PP de IP fue 75% y el promedio de clones por muestra fue tres. CONCLUSIONES: Las ISM y policlonales con P. falciparum son muy comunes durante la gestación, pero poco estudiadas y su impacto debe evaluarse en cada región, porque depende de la intensidad y estabilidad de la transmisión, la edad y paridad maternas, entre otras variables, que son influenciadas por las condiciones socioeconómicas y ambientales específicas.

Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum-Infected Erythrocytes

ABSTRACTPregnancy-associated malaria is a severe clinical syndrome associated with the sequestration ofPlasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, a member of the large and diverseP. falciparumerythrocyte membrane 1 (PfEMP1) protein family. To better understand if conserved regions in VAR2CSA can be targeted by antibodies, we immunized rabbits with VAR2CSA-DBL1 and -DBL5 recombinant proteins produced inPichia pastorisand developed a panel of seven chondroitin sulfate A (CSA)-binding parasites from diverse geographic origins. Overall, no two parasites in the panel expressed the same VAR2CSA sequence. The DBL1 domains averaged 80% amino acid identity (range, 72 to 89%), and the DBL5 domains averaged 86% amino acid identity (range, 83 to 99%), similar to a broader sampling of VAR2CSA sequences from around the world. Whereas antibodies generated against the VAR2CSA-DBL1 recombinant protein had only limited breadth and reacted with three or four parasites in the panel, immunization with DBL5 recombinant proteins elicited broadly cross-reactive antibodies against all or most parasites in the panel, as well as to fresh clinical isolates from pregnant women. These findings demonstrate that the major PfEMP1 variant expressed by placental isolates exposes strain-transcendent epitopes that can be targeted by vaccination and may have application for pregnancy malaria vaccine development.