decline of placental malaria in southern ghana after the implementation of intermittent preventive treatment in pregnancy

Malaria Journal BioMed Central Open Access Research Decline of placental malaria in southern Ghana after the implementation of intermittent preventive treatment in pregnancy Lena Hommerich1, Christa von Oertzen2, George Bedu-Addo3, Ville Holmberg1,4, Patrick A Acquah2, Teunis A Eggelte5, Ulrich Bienzle1 and Frank P Mockenhaupt*1 Address: 1Institute of Tropical Medicine and International Health, Charité – University Medicine, Berlin, Germany, 2Presbyterian Mission Hospital, Agogo, Ghana, 3Dept of Medicine, Komfo Anoyke Teaching Hospital, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Ghana, 4Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland and 5Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, The Netherlands Email: Lena Hommerich - l.hommerich@web.de; Christa von Oertzen - c.v.oertzen@gmx.de; George Bedu-Addo - gbeduaddo@gmail.com; Ville Holmberg - ville.holmberg@helsinki.fi; Patrick A Acquah - padjeiacquah@yahoo.co.uk; Teunis A Eggelte - t.a.eggelte@amc.uva.nl; Ulrich Bienzle - ulrich.bienzle@charite.de; Frank P Mockenhaupt* - frank.mockenhaupt@charite.de * Corresponding author Published: November 2007 Malaria Journal 2007, 6:144 doi:10.1186/1475-2875-6-144 Received: 13 August 2007 Accepted: November 2007 This article is available from: http://www.malariajournal.com/content/6/1/144 © 2007 Hommerich et al; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Abstract Background: Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) has been adopted as policy by many countries in sub-Saharan Africa However, data on the post-implementation effectiveness of this measure are scarce Methods: Clinical and parasitological parameters were assessed among women delivering at a district hospital in rural southern Ghana in the year 2000 when pyrimethamine chemoprophylaxis was recommended (n = 839) and in 2006 (n = 226), approximately one year after the implementation of IPTp-SP Examinations were performed in an identical manner in 2000 and 2006 including the detection of placental Plasmodium falciparum infection by microscopy, histidine-rich protein 2, and PCR Results: In 2006, 77% of the women reported to have taken IPTp-SP at least once (26%, twice; 24%, thrice) In 2006 as compared to 2000, placental P falciparum infection was reduced by 43–57% (P < 0.0001) and maternal anaemia by 33% (P = 0.0009), and median birth weight was 130 g higher (P = 0.02) In 2006, likewise, women who had taken ≥ dose of IPTp-SP revealed less infection and anaemia and their children tended to have higher birth weights as compared to women who had not used IPTp-SP However, placental P falciparum infection was still observed in 11% (microscopy) to 26% (PCR) of those women who had taken three doses of IPTp-SP Conclusion: In southern Ghana, placental malaria and maternal anaemia have declined substantially and birth weight has increased after the implementation of IPTp-SP Likely, these effects can further be increased by improving IPTp-SP coverage and adherence However, the remnant prevalence of infection in women having taken three doses of IPTp-SP suggests that additional antimalarial measures are needed to prevent malaria in pregnancy in this region Page of (page number not for citation purposes) Malaria Journal 2007, 6:144 Background Malaria in pregnancy is a major cause of maternal, foetal and infant morbidity and mortality in sub-Saharan Africa Although frequently asymptomatic, consequences of Plasmodium falciparum infection in pregnancy comprise maternal anaemia, abortion, stillbirth, intrauterine growth retardation, low birth weight (LBW), preterm delivery, and up to 200,000 attributable infant deaths per year [1-5] Primiparae are particularly vulnerable as immune mechanisms preventing placental sequestration of pregnancy-specific parasite strains are weak or absent [6,7] Intermittent preventive treatment in pregnancy (IPTp) denotes the administration of a curative dose of an antimalarial, commonly sulphadoxine-pyrimethamine (SP), during routine antenatal care, irrespective of parasitaemia being present or not Given twice or thrice in the second and third trimester of pregnancy, IPTp-SP has been shown to be safe and to reduce placental malaria, maternal anaemia, and LBW [8-13] IPTp with ≥2 doses of SP is currently recommended by the World Health Organisation [14], and has become policy in much of sub-Saharan Africa Nevertheless, coverage with IPTp still needs to be substantially improved [15,16] and the effectiveness of IPTp may be endangered by spreading and intensifying SP resistance [17,18] Although most clinical trials on IPTp-SP were conducted in East Africa [8-10,19] the strategy was rapidly adopted also in West Africa where its effectiveness is less well documented [20] Consequently, there is an urgent need to monitor the post-implementation effectiveness of IPTp in this region In southern Ghana, malaria in pregnancy and related morbidity are frequent [21-23] Ghana started the implementation of IPTp with three recommended doses of SP at the end of 2004 In this country, SP achieves cure rates within 28 days of follow-up of 14% and 11% in children and pregnant women with uncomplicated malaria, respectively [24,25] Here, parasitological and clinical parameters were compared among women delivering at the Presbyterian Mission Hospital in Agogo, southern Ghana, before (2000) and after (2006) the implementation of IPTp In addition, these parameters were examined with respect to the usage of IPTp among women delivering in 2006 and the number of doses taken http://www.malariajournal.com/content/6/1/144 gleton delivery were recruited Both study protocols were reviewed and approved by the Ethics Committee, University of Science and Technology, Kumasi, and all women provided informed written consent Sample collection as well as clinical and parasitological examinations were performed in an identical manner in 2000 and 2006 and have previously been described [23] In brief, women were clinically examined and socio-demographic data documented Information on chemoprophylaxis or IPTpSP was collected from antenatal care cards and verified by interviewing the women Venous peripheral and placental blood samples were collected into EDTA Malaria parasites were counted microscopically on Giemsa-stained thick blood films per 500 white blood cells (WBCs) for peripheral samples and per 100 high-power fields (1,000x) for placental samples In the latter, the presence of leukocyte-associated haemozoin was also recorded Slides were declared negative after having examined microscopic fields corresponding to 500 WBCs, or 100 high-power fields Based on placental thick blood film microscopy, the stage of placental infection was categorized [27] as early, only parasites visible; late, both parasites and pigment present; resolved, only pigment visible; and none, neither parasites nor haemozoin present In placental samples, P falciparum was additionally diagnosed by detection of histidine-rich-protein (HRP2) and nested PCR assays [28] In 2000, HRP-2 was measured using the ICT Malaria P.f/P.v (Becton Dickinson, Germany) and, in 2006, using Malaria NOW P.f./P.v (Inverness Medical, Germany) Haemoglobin (Hb) was measured by a HemoCue photometer (Ångelholm, Sweden) and anaemia and severe anaemia defined as Hb < 11 and < g/dL, respectively Fever was defined as an axillary temperature ≥ 37.5°C and LBW as a birth weight < 2500 g For subsequent comparisons, three groups were formed, i) 226 women recruited in 2006, ii) 839 women recruited in 2000, and iii) 197 women who delivered in 2000 during a period exactly matching the recruitment phase in 2006 (29.04.-27.06.) Geometric mean parasite densities (GMPDs) and 95% confidence intervals (95%CIs) were calculated Continuous variables were compared between groups by the non-parametric Mann-Whitney U and Kruskal-Wallis tests as applicable, and proportions by χ2 test, Fisher's exact test and logistic regression models Results Methods Agogo is a community of some 30,000 inhabitants; subsistence farming, trade and mining are the main income sources in that region, and malaria is hyper- to holoenedemic [26] The characteristics of 839 women with live singleton delivery recruited in 2000 have been described in detail elsewhere [23] Between April and June 2006, i.e during the rainy season, further 226 women with live sin- The baseline characteristics of the three groups of delivering women are shown in Tables and In 2000, virtually all women stated to have used pyrimethamine (25 mg weekly) for chemoprophylaxis during pregnancy In 2006, 76.5% (173/226) of women reported to have taken IPTp-SP at least once, one women had used chloroquine chemoprophylaxis, and 23.0% (52/226) neither IPTp nor chemoprophylaxis Eight percent of the women (17/208) Page of (page number not for citation purposes) Malaria Journal 2007, 6:144 http://www.malariajournal.com/content/6/1/144 Table 1: Characteristics of women with live singleton delivery at Agogo Hospital, southern Ghana, in 2000 and 2006 Year of delivery Parameter 2000 2000, matching dates subset 2006 2006 vs 2000, P 2006 vs 2000 subset, P No Residence in Agogo (%) Age (years; median, range) Proportion without school degree (%) Parity (median, range) Primiparae (%) Proportion caesarean section (%) No of ANC visits (mean, range) Proportion with > ANC visits Birth weight (g; median, range) LBW (%) Haemoglobin (g/dL; median, range) Maternal anaemia (%) Severe anaemia (Hb < 7; %) Fever (%) 839 48.9 25 (15–47)a 15.4 (128/829) (1–11) 36.5 (304/832) 22.1 3.9 (0–12) 52.3 (429/821) 2,950 (1,280–4,500)c 16.0 (134/838) 11.5 (4.6–16.8) 35.2 1.8 2.8 (23/826) 197 50.3 25 (16–42)b 13.8 (27/195) (1–9) 34.2 (66/193) 18.3 3.9 (0–11) 48.7 (93/191) 2,900 (1,450–4,350) 19.3 11.7 (4.6–15.0) 33.0 1.5 1.5 (3/196) 226 42.5 26 (16–42) 10.4 (23/222) (1–11) 32.7 24.8 4.5 (0–14) 58.7 (131/223) 3,080 (1,600–5,460)d 12.4 (28/225) 12.0 (7.2–15.9) 23.5 6.6 0.09 0.12 0.06 0.14 0.29 0.38 0.01 0.08 0.02 0.19 < 0.0001 0.0009 0.05 0.006 0.13 0.31 0.27 0.43 0.75 0.11 0.047 0.04 0.0008 0.05 0.04 0.03 0.10 0.01 ANC, antenatal care; LBW, low birth weight; a, n = 827; b, n = 192; c, n , = 838; d, n = 225 in 2006 reported to have slept under a bed net the night before delivery taemia was more than halved (reduction by 57%) in 2006 as compared to 2000, and parasite density reduced at boderline statistical significance Similar reductions in the prevalence of infection were observed considering the results of pigment detection (by 43%), HRP2 tests, and PCR (both by 46%) The stage of placental infection, peripheral blood film positivity and peripheral parasite densisty were not significantly changed, however (Table 2) Comparing these parameters between women delivering in 2006 and women delivering during the matching As compared to 2000, women in 2006 more frequently had attended antenatal care, tended to be older, less likely to originate from Agogo, and more commonly to have a school degree Maternal anaemia was reduced by 33% in 2006, severe anaemia absent, and median Hb (+0.5 g/dL) and median birth weight (+130 g) were higher Fever occurred more often in 2006 than in 2000 (Table 1) The prevalence of microscopically confirmed placental parasi- Table 2: Parasitological indices of delivering women at Agogo Hospital, southern Ghana, in 2000 and 2006 Year of delivery Parameter 2000 2000, matching dates subset 2006 2006 vs 2000, P 2006 vs 2000 subset, P No Placental infection (%) Microscopy Pigment HRP2 PCR Stage of placental infection Resolved Late Early Placental parasite density (GMPD, 95%CI) Peripheral blood film positive (%) Peripheral parasite density (GMPD, 95%CI) 839 197 226 34.9 30.9 40.8 59.4 29.9 31.0 38.6 51.3 15.0 17.7 22.1 31.9