Placental Pathology in Malaria: A Histological, Immunohistochemical, and Quantitative Study MAMUDO R. ISMAIL, MD, JAUME ORDI, MD, CLARA MENENDEZ, MD, PERE JOAN VENTURA, BSc, JOHN J. APONTE, MD, ELIZEUS KAHIGWA, MD, ROSEMARY HIRT, BSc, ANTONIO CARDESA, MD, AND PEDRO L. ALONSO, MD To characterize the histological changes in malarial placentas and their relationship with parity and maternal and cord parasitemias, we conducted a histological study on 1,179 placentas from Ifakara, Tanzania, an area with intense and perennial malaria transmission. Immunohistochemical and quantitative studies for CD45, fibrin, and villous area were performed in 60 cases. Four hundred fifteen placentas (35.2%) showed parasites (active infections); in 303 of them, parasites co-exlsted with pigment covered by fibrin (chronic infections), and in 112 only parasites were detected (acute infectious). Four hundred seventy-five cases (40.3%) showed hemozoin deposi- tion without parasites (past infections). Of women with parasitized placentas, 46.3% did not show parasites in the peripheral blood. Basal membrane thickening (P = .002), fibrlnoid necrosis (P = .004), and prominence of syncytial knots (P = .031) were associated with active malarial infection. No quantitative differences for perivillous fibrin deposition or villous area were found. The most significant associa- tion with active malarial infection was intervillous infiltration by Pregnant women are much more prone to develop malaria than nonpregnant individuals. 1 This is particu- larly true for primiparas, who have more severe disease and significantly higher prevalence rates of malarial infection, which decrease in subsequent pregnancies. 2,~ Moreover, malarial parasites seem to affect the placenta selectively. Examination of smears obtained from placen- tal blood at the time of delivery sometimes demon- strates parasites and pigment, even when peripheral parasitemia is negative. 4,5 The reasons for the markedly increased malaria susceptibility in pregnancy are still not well understood. 5 A certain degree of immune suppression during pregnancy, leading to an increased From the Instituto Nacional de Salud. Universidade Eduardo Mondlane. Maputo. Mogambique and Centro de Investigagao em Saude, Manhiga, Mogambique; Department of Pathology and Epide- miology and Biostatistics Unit, Insfitut d'Investigacions M~diques August Pi i Sunyer (IDIBAPS) Hospital Clinic, Facultat de Medicina, Universitat de Barcelona; St Francis Designated District Hospital (SFDDH), Ifakara, Tanzania; and Ifakara Health, Research and Development Centre (IHRDC), Ifakara, Tanzania. Accepted for publication September 28, 1999. The IHRDC and the SFDDH receive major core funding from the Swiss Agency for Development and Cooperation. The study has been supported through grants of the Spanish Agency for Interna- tional Cooperation and Fondo de Invesfigaciones Sanitarias (number 95/863). This trial received financial support from the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases. Address correspondence and reprint requests to Jaume Ordi, MD, Departament d'Anatomia Patol6gica, Hospital Clinic, Universi- tat de Barcelona, Villarroel 170, 08036 Barcelona, Spain. Copyright © 2000 by W.B. Saunders Company 0046-8177/00/3101-0014510.00/0 mononuclear inflammatory cells (P < .001). Chronic infectious were associated with the most severe changes, particularly interviUous mononuclear inflammation (OR, 28.7; 95% CI = 16.0 to 51.5, P < .001). Past infections showed only minimal differences with noninfected placentas. Primiparas showed chronic infectious more frequently than multiparas (52% v 15%, P < .001). They also showed significantly higher placental parasitemias and intervillous inflamma- tory infiltrate. In conclusion, placental histology is more sensitive than peripheral blood examination in detecting malarial infection during pregnancy. Most malarial infections recover during pregnancy, leaving few residual changes in the placenta. Intervillous inflammation is the most frequent finding associated with malaria and is especially severe in primiparas, suggesting that mechanisms other than immunosuppres- sion axe responsible for the high susceptibility in this group. HUM PATHOL 31:85-93. Copyright © 2000 by W.B. Saunders Company Key words: placenta, malaria, pregnancy. Abbreviation: H&E, hematoxylin and eosin. susceptibility of the pregnant woman to a number of pathologies, has been reported. 6,7 Recently, a different model involving a subpopulation of Plasmodiumfalcipa- rum that specifically adhere to condroitin sulfate A present in human placenta has been proposed to account for the high susceptibility against malaria. 8,9 Malarial infection during pregnancy has been re- ported to be a major cause of low birth weight in endemic areas) ,5 It has also been associated with mater- nal anemia and death, 5 abortion, and stillbirth, 4 al- though the relationship of these conditions to malaria infection is not so well established. 5 Several histological lesions such as fibrin deposition, fibrinoid necrosis, trophoblastic damage and proliferation, basal mem- brane thickening, and inflammatory infiltration have been reported in placentas with malarial infection, 1°-14 but their specific significance has not been clearly established. The aim of this report is to describe the frequency and severity of the histological features associated with placental malarial infection evaluated by both semiquan- titative and quantitative methods. The evaluation was conducted in a large series of specimens from an area with intense and perennial malaria transmission, and was correlated with peripheral maternal and cord blood parasitemia and parity. 85 MATERIALS AND METHODS Placental samples were obtained from 1,179 women, after obtaining their consent, as part of a study on prevention of