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Journal of Infectious Diseases Advance Access published September 9, 2011

MAJOR ARTICLE

Highly Effective Therapy for Maternal Malaria
Associated With a Lower Risk of Vertical
Transmission
J. R. Poespoprodjo,1,2 W. Fobia,3 E. Kenangalem,1,3 A. Hasanuddin,4 P. Sugiarto,4 E. Tjitra,5 N. M. Anstey,2,6 and
R. N. Price2,6,7
1DistrictHealth Authority, Timika, Indonesia; 2Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia;
3Menzies School of Health Research-National Institute of Health Research and Development Malaria Research Program; 4Mitra Masyarakat Hospital,
Timika, and 5National Institute of Health Research and Development, Jakarta, Indonesia; 6Division of Medicine, Royal Darwin Hospital, Darwin,
Australia; and 7Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill
Hospital, Oxford, United Kingdom

Background. The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance
study in Papua, Indonesia.

Downloaded from jid.oxfordjournals.org at Charles Darwin University on September 21, 2011
Methods. From April 2005 to January 2010, 4878 delivering women and their newborns underwent prospective
clinical review and malaria screening by peripheral blood microscopy.
Findings. Congenital malaria occurred in 8 per 1000 (38/4884) live births, with Plasmodium falciparum
accounting for 76.3% (29) and P. vivax for 15.8% (6) of infections. Maternal malaria at delivery (adjusted odds ratio
[AOR], 9.5; 95% confidence interval [CI], 4.2–21.5; P , .001), age # 16 years (AOR, 4; 95% CI, 1.4–12.1; P 5 .011),
and prior malaria during pregnancy (AOR, 2.2; 95% CI, 1.1–4.4, P 5 .022) were independent risk factors for vertical
transmission. Of 29 mothers and neonates with contemporaneous peripheral parasitemia, 17% (5) had discordant
parasite species, suggesting possible antenatal malaria transmission. Newborns with malaria were at significantly
greater risk of low birth weight (AOR, 2.8; 95% CI, 1.2–6.6; P 5 .002). Following introduction of dihydroartemisinin-
piperaquine for uncomplicated malaria in the second and third trimesters of pregnancy, congenital malaria incidence
fell from 3.2% to 0.2% (odds ratio, 0.07; 95% CI, .03–.15; P , .001).
Conclusions. Congenital malaria is an important cause of neonatal morbidity in this region co-endemic for
P. falciparum and P. vivax malaria. The introduction of artemisinin-combination therapy was associated with
a significant risk reduction in the vertical transmission of malaria.

In areas where malaria is endemic, the risk of malaria In highly endemic areas of Africa, up to a third of
starts in the early neonatal period, with congenital in- infants acquire malaria in utero [7–10]. Vertical trans-
fections recognized as an important cause of morbidity mission is less well described in the Asia Pacific region,
[1–4]. The asymptomatic nature of infection in the early descriptions of its epidemiology often relying on case
stages is likely to result in its true incidence being un- series/reports or maternal or placental malaria studies
derestimated [5, 6]. that are generally of small sample size [11–15]. In the
present study we sought to define the risks of vertical
malaria transmission along with its treatment and pre-
Received 6 March 2011; accepted 24 June 2011. vention in . 4000 neonates born in the local hospital in
Correspondence: R. N. Price, MD, FRCP, Menzies School of Health Research, Timika, Papua-Indonesia, an area with highly prevalent
PO Box 41096, Casuarina, Darwin, NT 0811 Australia (rprice@menzies.edu.au).
drug-resistant Plasmodium falciparum and P. vivax [16].
The Journal of Infectious Diseases
Ó The Author 2011. Published by Oxford University Press on behalf of the
Infectious Diseases Society of America. All rights reserved.
METHODS
This is an Open Access article distributed under the terms of the Creative Commons
Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/
3.0), which permits unrestricted non-commercial use, distribution, and reproduction Study Site
in any medium, provided the original work is properly cited.
0022-1899 (print)/1537-6613 (online)/2011/00-0001$14.00
The study was conducted in southern Papua, Indonesia.
DOI: 10.1093/infdis/jir558 This area is largely forested, with both coastal and

Vertical Transmission of Malaria d JID d 1

committees of the National Institute of Health Research and cough. 28 days) mon cause of morbidity in the first year of life. Rumah Sakit Mitra Masyarakat (RSMM) hospital. Hospital policy dictates that all patients presenting with quinine for 7 days (intravenous quinine was used for severe a febrile illness.02 software (EpiData Association). identified and invited to be part of the study. restlessness. The infant Development. Data were as having a low birth weight (LBW). Venous sam- 68 per 1000 live births [18]. not conforming to a normal distribution were compared by the fication of Diseases 10 [21].5°C.5 g/dL [23]. Multiple logistic regression was used to analyze independent risk termine late congenital manifestations. vivax infections 200 white blood cells (WBC) on Giemsa-stained thick films. and pulse. and at RSMM were to be screened for malaria within 3 days of birth. and A. followed by with peripheral malaria parasitemia unless requested by the diarrhea and lower respiratory tract infections [19]. respectively [4]. Due to economic migration. As clinically indicated. The annual considered negative after review of 200 high-power fields. 2 d JID d Poespoprodjo et al . lowland Papuans. and a trained research nurse or with intravenous artesunate [24]. local protocols were changed to blood film examination for malaria. falciparum and P. all infants younger than factors for congenital malaria by entering all significant risk 3 months old admitted with malaria to the pediatric wards were factors in univariate analysis. [17]. calculating the v2 with Yates’s correction or by Fisher’s exact test If the newborn had malaria. with highland tocol. A. 5 kg and in pregnant Data Collection women in the second and third trimesters of pregnancy. young infants and pregnant women Papuans. with fever defined as a temperature lowland area. punctulatus. After obtaining parental/legal guardian consent.37. 2500 g were defined into EpiData 3. clinical and laboratory data was completed. Until No. Severe anemia was defined as having hemoglobin Anopheles koliensis. irrespective of other symptoms. 200 per 48% after chloroquine plus sulfadoxine-pyrimethamine for 200 WBC. and the presence of Research Ethics Committee of the Menzies School of Health splenomegaly and hepatomegaly were recorded. a more detailed questionnaire on and the odds ratio (OR) with 95% confidence intervals (CIs). venous blood samples (1–5 mL) were drawn from infants admitted with malaria to the pediatric Study Population wards for complete blood counts and hemoglobin concen- The infant mortality rate in southern Papua is estimated as tration (using electronic counterdCoulter JT). respiratory rate. research physician performed systematic physical examination of the baby to assess clinical signs. with a population of 200 000 people. farauti. Babies with a birth weight . Data malformation was diagnosed based on the International Classi. Maternal clinical and laboratory data Mann–Whitney U test. accounts for 30% and 14% of infant hospital admissions and All infants with peripheral parasitemia received standard Downloaded from jid. Neo- From April 2004 hospital protocol dictated that all infants born nates weighing . vember 2008. asite counts were determined from the number of parasites per divided 60:40 between P. Ministry of Health. and those with gestational analyzed using SPSS vs 17. vivax and species and used for quantification if parasitemia was . women in the first trimester. age of . A thin smear was also examined to confirm parasite reaching 65% after chloroquine monotherapy for P. 2011 outpatient visits. pling was not routinely conducted in neonates (age .org at Charles Darwin University on September 21. Australia. 37 weeks. was the only hospital in this district servicing an area of blood films. and the presence of external congenital Data from the questionnaire and the laboratory were entered malformations. In this region. In order to de. Malaria transmission is restricted to the was recorded per axilla. Indonesia. with quinine and clindamycin.0 for Windows software (SPSS Inc). recommend dihydroartemisinin-piperaquine (DHP) for un- complicated malaria in infants weighing . with malaria being the most com. gestational age (using New Statistical Analysis Ballard Score) [20]. and breathlessness) and weight of the infants. Categorical data were compared by at delivery were also collected as described elsewhere [22]. should have malaria). A research nurse documented Ethical approval for this study was obtained from the ethics history of illness (including fever. falciparum [16]. the malaria Neonates and pregnant women with severe malaria were treated smear results were documented. Temperature Research and Department of Health.oxfordjournals. poor feeding. high levels of antimalarial drug resistance Peripheral parasitemia was calculated from the recorded white are present in both species. Malaria attending clinician. 5 kg were treated with oral quinine. After March 2006. Before March 2006. and the Human was examined. Malaria was diagnosed by microscopy of Giemsa-stained Timika. Slides were read by an expert microscopist and 21 522 km2. External congenital Normally distributed data were compared by Student t test. the risk of failure within 28 days cell count. Darwin. In the latter case maternal data at delivery were retrieved from hospital records if Ethical Approval the infant was born at RSMM. Par- incidence of malaria in the region is 876 per 1000 person-years. concentration . where it is associated with 3 mosquito vectors: . antimalarial therapy and supportive care as per hospital pro- the ethnic origin of the local population is diverse. P. and non-Papuans all resident in the with uncomplicated malaria of any species were treated with region.mountainous areas. as being premature.

16/642) comparable to symptomatic parasitemic 95% CI. vivax (125 lL21. 6. In the multivariate models. his- Antimalarials were given to all parasitemic newborns. intravenous artesu. . The status at delivery. The median parasitemia was similar between infants with the population attributable risk of congenital infection infected with P. for discordance in 18% of cases (Table 1).org at Charles Darwin University on September 21.0). oral DHP alone.4% [12/37] having with malaria had a risk of transmitting the parasites verti- LBW).3% (29) of infections. adjusted odds mothers without any history of malaria infections (P .8%) neonates were diagnosed with congenital in. 95% CI.oxfordjournals.1 (95% CI. with 32 tory of malaria during pregnancy. vivax. Of the 37 recorded cases of early bies born at RSMM were screened for malaria (Figure 1). for 5. In the remaining 28 women with malaria at delivery. Table 2. and maternal age # 16 years receiving quinine (oral 6 intravenous). range. nitude of maternal peripheral parasitemia even after control- Newborns with congenital malaria had a lower birth weight ling for the species of infection (Table 3). The risk of vertical transmission was 3% in women with the exception of 1 baby with high parasitemia and severe with peripheral parasitemia at delivery compared with 0. All newborns were asymptomatic. 95% CI. the prevalence of maternal malaria Between April 2004 and January 2010. old remained as independent risk factors for vertical trans- nate followed with DHP. range. in those aparasitemic (OR.6.21).2%. P 5 . . 3031. P 5 .5.4–28. congenital infections. Afebrile mothers (mean.3% (2). In vertical transmission.2% malaria manifest as neonatal sepsis syndrome. with 32. women with possible history of malaria in- effect of congenital malaria on LBW remained after controlling fection during pregnancy had a 4. mothers. 50–26 688 lL21) being 70%. mothers (4. being 19% (928. falciparum. P 5 . All malaria mission (Table 2). maternal malaria. P . 2553–2975 g.03).9. P. 4884 (85%) of 5728 ba. 1. 2.8% (6). falciparum accounted for 5 had neonates with different parasite species. There was 1 pair of twins with congenital malaria. both of whom had P. 2. Maternal Risk Factors The median parasite density of the newborns was 100 lL21 Maternal risk factors for vertical transmission are shown in (range. and severe anemia. P 5 1. giving rise to 76. P. 2011 Figure 1. 13. and 4.9) for other known risk factors in this population (maternal age. ratio [AOR]. viously [25]. 2764. 50–300 lL21. greater risk of vertical transmission to the fetus compared with parity. 95% CI.7. 2997–3028 g.001).02). The risk of transmission did not vary with mag- and P.6% (1). Downloaded from jid.002). 2. Study profile. 9 (24%) were born from aparasitemic total. 12/284.001). 1. as reported pre.1-fold (95% CI. cally (2. for 15. P. RESULTS Maternal Parasitemia and Vertical Transmission Data on the blood film examination of the mothers were Congenital Malaria available in 4878 women.1–7. maternal malaria at delivery. 50–26 700 lL21). and mixed species.6–6. 38 (0. falciparum (100 lL21.5%.1–6. Vertical Transmission of Malaria d JID d 3 . fection within the first 3 days of life. ovale. P 5 . 13. Together these factors explained 89% of all smears were negative at time of discharge from hospital. Regardless of parasitemia the OR for LBW being 3. 2.3. compared with newborns without malaria (mean.3% (642/4838) with LBW. Table 1).

.001 16% Maternal fever 365/4877 (7. . 1 1 .5–13..8) 3 (0.4) 1 (0.5 (4.001 30% P.. 3950/4878 (81) 9/37 (24) . P.5) . hospitalization. ..7–3.Table 1. 0..1–4. and 2 sets of twin) were readmitted to medication.4–12.001 30% 1.2) 12 (2.1–5. and mixed species for 4% (3) of the a history of DHP treatment during pregnancy had a significantly infections. 95% 7..05 (.4) .5) P. 3. 95% CI. 1.8) 8 (0. 95% CI.2) 0 0 7 (2.7) 0 (0) 0 (0) 1 (33.7–14.260 .6 (6.6% 4. . . adjusted odds ratio. CI. P 5 . a Where deliveries included multiple births.3- founding factors.3) .8) 3/36 (8.2% Primipara 1527/4878 (31) 12/37 (32.3) 1..8.6) 1. On readmission.2) P.6 (. 2.9. vertical transmission was reported if at least 1 of the babies was found to be parasitemic. falciparum and lower risk of malaria (0. respectively.4–28. 0.8–3.7) . The number of congenital after a median of 3 days’ (interquartile range. 95% CI. vivax (n 5 321) 314 (97.024). .9) .032–. confidence interval. There has been no reported congenital malaria case since P . All of these infants had been screened at birth with negative Downloaded from jid.5) 13/37 (35) 6. The major maternal factors associated with admission of an laria treatment policy. odds ratio.. 95% CI.2–21.5 (. calculated as [(proportion of cases exposed to risk factor) 3 (OR – 1)]/OR.9) 9.. .3) P.011 8.. . malaria treatment policy change remained fold (95% CI. 4 d JID d Poespoprodjo et al .9) ..2) P.9–27..1) . .207 13% Maternal history of febrile illness 925/4881 (19) 18/37 (48.. 17/348. malaria cases declined significantly following the change in ma.3) 8/37 (21.3) .012 8.1 (1. population attributable risk.001 32% 7.4) .2) 1 (0. 4 half twins.4) . falciparum (n 5 501) 488 (97..8.. falciparum malaria 501/4878 (10) 13/37 (35) 11. After controlling for other con.6 (4. OR. 74 infants from 72 mothers (66 during their pregnancy and were treated with antimalarial singletons.1–7.oxfordjournals.6– as a protective factor for congenital malaria (AOR. vivax P.2% (29/907) before policy change infant to hospital with malaria in the first 3 months of life to 0.03–. were maternal malaria at delivery (OR. 2011 uncomplicated malaria in the second and third trimesters of blood films.4–19. .7 (3.02) 0 0 9 (0.4–3.9) 4 (1.. Malaria Treatment in Pregnancy Possible Late Manifestation of Congenital Infection In total 905 pregnant women described a prior febrile episode Of 4878 hospital deliveries. malariae (n 5 50) 49 (98) 1 (2) 0 (0) 0 0 1 (2) Mixed infection (n 5 53) 47 (88.2 (1.8) 5 (1.. Table 2..5-fold (95% CI.3. those with normal birth weight and singletons.9) .18. ..001) and a history of malaria during pregnancy (OR. Vertical Malaria Transmission Profile Parasitemia at birtha Plasmodium Mixed Overall vertical Maternal parasitemia Negative falciparum P.001 36% 2. 16 years old) 118/4879 (2. 0.8)/2 6 (11) All data are no. ovale infection transmission Negative (n 5 3948) 3939 (99.001).15. LBW infants and twins had a 2.4) .3–3. Abbreviations: AOR. 1. P 5 . .. 1/471) compared with those with P. from 3.4) . of cases (%).3. P.001 70% 9.04. vivax malaria had severe anemia and died within 24 hours of prior exposure to chloroquine/quinine treatment (4.6 (2. Severe anemia 333/4740 (6. ..2% (9/3912) after (OR.3) 0 1 (33.9 (2. 1. P 5 .2%.9%.001 17% 6.001)..860 . All other children were discharged from hospital OR.org at Charles Darwin University on September 21. .01) higher risk of malaria in early life compared with CI. P . P .89.5)/3 0 (0) 0 2 (3..1–3.001 68% at birth No. .036)..1) .4) 1.4) 4/37 (10. DHP was introduced as first-line treatment of laria.. 1–2) inpatient stay...07. Maternal Risk Factors for Vertical Malaria Transmission Prevalence of cases Univariate analysis Multivariate analysis Prevalence n/valid exposed to factor Risk factor cases (%) n/valid cases (%) OR (95%CI) P value PAR AOR (95%CI) P value PAR Maternal peripheral parasitemia 928/4878 (19) 28/37 (75) 13... vivax malaria 321/4878 (6. One infant (92 days old) with mixed P.. 1. ...6–26.6) 4 (2.9 (3. ..9–19.2 (. P. ovale (n 5 3) 2 (66.005–. falciparum accounted for 20% pregnancy since March 2006.74 .2) 0 0 13 (2. with vertical transmission of infection observed in the hospital in the first 3 months of life with symptomatic ma- 18 (2%) births.3. Preterm delivery 748/4865 (15.. October 2008 (Figure 2).5–2. Babies born of mothers with (15). P 5 .005) and 3....6) 7/37 (18.. PAR. vivax for 76% (56).4) .7) 4 (7.022 26% Young mother (.

where peripheral parasitemia discordant with the peripheral parasitemia of the mother. 10]. vivax congenital infection (alone or mixed) occurred donesia. 11. Treatment policy for pregnant women in second and third trimesters changed to dihydroartemisinin-piperaquine in March 2006. where P. Contrary to previous hypotheses. the vertical trans- mission of infection may reflect the species of placental infection. falciparum. In such settings neonatal Number of Cases 5 4 3 2 1 0 Figure 2. has generally ranged from 5% to 33% [8–10] and even symptomatic in an African study undertaking active screening. Ver. 29]. In the present study we routinely screened all babies within 3 days of birth and were thus This large surveillance study defines the epidemiology of con. 9. The epidemiology of congenital infection in Asia a One case only. 14. In these regions. women with peripheral parasitemia at delivery. 14]. Maternal Parasitemia at Delivery and Vertical Malaria 25.Table 3. Number of congenital malaria cases per month.098 Saharan Africa.6 per 1000 live births and accounted for 22% of all con- malaria. higher (19%–50%) in women with peripheral parasitemia These findings could not be explained by early detection since in [7.8% of live births. increasing maternal immunity [27]. able to reliably exclude infections acquired early in the postnatal genital malaria and its outcome after treatment in Papua. which. Vertical Transmission of Malaria d JID d 5 . 8–200 lL21) [9]. 33]. suggest that vertical transmission may be determined by other Fetal exposure to malarial parasites in utero has been pro- factors than just the level of malaria exposure and associated posed to modify the immune response of newborns. Although the median P. vertical transmission DISCUSSION can occur with either species [11.oxfordjournals. falciparum 403 (81–1998) 1480 (1211–1998) . 28. falciparum and P. 50–26 688 lL21) than that reported in Africa (48 lL21. compared with a third of infections being [26]. sitemia and clinical malaria [27. falciparum para- with the risk of vertical transmission rising almost 10-fold in sitemia observed in newborns in Papua was higher (100 lL21.. these findings both studies active screening was conducted at birth. However.. an area co-endemic for both vivax and falciparum in 1. In addition. vivax 2186a 665 (200–1998) . infections in Papua were almost all Downloaded from jid.org at Charles Darwin University on September 21. we were unable to investigate this further. was significantly lower than that reported from areas of high range. with some exceptions asymptomatic. P. In. This incidence range. where the majority of infections are due to P. and this may explain some of the materno-neonatal Transmission discordance in parasite species. Congenital malaria was observed in 0. Vertical in which case the peripheral parasitemia may be an incidental malaria Maternal transmission finding. their susceptibility to symptomatic malaria infections at birth In almost 20% of cases the parasite species in the baby was and later in life [30–32]. genital infections. and placental malaria are highly prevalent. vivax are co-endemic. In Africa. (geometric mean/lL) Present Absent P value Most reports of congenital malaria originate from sub- P. 9. because we did not routinely examine pla- parasitemia cental tissue. period. this increased sus- tical transmission of malaria occurring antenatally is well de. 2011 malaria transmission in Africa. P. ceptibility is associated with a greater risk of neonatal para- scribed in both African and Southeast Asian settings [8. and South America is less well described.

This work was supported by the Wellcome Trust– contribute to reductions in congenital malaria [26]. Chloroquine and sulfadoxine- 4. J Trop Pediatr 1995. Am J Trop Med Hyg 1996. treatment options in this region are limited [4]. tomatic congenital malaria untreated may be significantly as. 38]. 55(Suppl 1):71–6. At our study site all infants with positive blood films were sociated with greater malaria morbidity in early life [4]. intravenous artesunate followed with DHP. is supported by an There are a number of limitations to our study.screening is often reserved for symptomatic infants. 36]. of congenital malaria by missing low-parasitemia infections and Potential conflicts of interest. Currently. effective anti- have been the main treatment options for maternal malaria in malarial treatment could reduce malaria burden in early life even most parts of Africa [9. these treatments can no longer be advocated lower-transmission areas the consequence of leaving asymp. References genital malaria [9.oxfordjournals.5 kg LBW than aparasitemic infants [7. 65:822–7. by an NHMRC Practi- reliant on microscopy of peripheral blood film for diagnosing tioner Fellowship. Am J Trop Med Hyg 2001. 41:330–3. the staff of reliable treatment strategies in pregnancy. Therefore. 10]. P. Afolabi BM. local guidelines recommend that infants . 2011 associated with a large reduction in the incidence of congenital therapy for malaria treatment in the second and third trimesters malaria. This may in part explain the high rates of congenital malaria Notes reported from a number of sites in the continent [7. misdiagnosis of the species of infection [37]. despite screening almost 1416 ba. Ibhanesebhor SE. our study provides insights into the epidemi- changed from chloroquine plus sulfadoxine-pyrimethamine or ology of congenital malaria in endemic areas outside Africa. 29]. Indeed we have not witnessed a case of congenital of pregnancy was associated with a marked decrease in the risk malaria since October 2008. Clinical characteristics of neonatal malaria. falciparum and P. by high rates of aminoquinoline and antifolate drug resistance. and as a result. The Timika Translational Research Facility is supported by AusAID. late recurrence rates are treatment of maternal malaria. Timika. All authors: No reported conflicts. [16. suggesting that malaria McGready for her support and advice in carrying out the study and analysis. and this is likely to have underestimated the real burden Fellowship in Clinical Science (091625). et al. We are grateful to the Mimika District Govern- further emphasizes the need for exploring more effective and ment. In addition. DHP has excellent efficacy high [16]. vivax. Hightower AW. ital falciparum malaria [7. 6 d JID d Poespoprodjo et al . reliable short-course treatment regimens is urgently required In March 2006 local guidelines for the treatment of maternal for malaria in neonates and young infants. N. Malaria infection in the case management of congenital malaria. M. and a similar observation in weight with malaria should be treated with either a 7-day was apparent in our Papuan study. early detection by active screening of all babies is warranted however. We were AusAID Australian Leadership Award. there are no consensus international guidelines for 2. Malaria in the first 6 months of article are therefore conservative estimates. lack of cord blood parasitemia and placental malaria data in our study will have also underestimated the true burden of con. The reality is that compliance with unsupervised 7-day courses Our study highlights the importance of ensuring the effective of oral quinine is rare. if unable to tolerate oral medication. vivax [16]. in drug resistance. Mafe AG. control interventions targeting the whole community may also Financial support. Kenangalem E. P. et al. ated with maternal malaria could not explain this increased risk. 10] and Acknowledgements. 39]. although they were insufficiency may play a crucial role in reducing fetal growth not systematically followed up after discharge from hospital. tomatic congenital malaria is often left untreated if the parasites 3. Khoromana CO. [34]. 35. All authors have submitted the ICMJE Form for Disclosure of Potential merase chain reaction diagnostics in previous reports may have Conflicts of Interest. Routine screening of newborns for bies for malaria. Okoseray and Pak Erens Meokbun. Chloroquine and sulfadoxine-pyrimethamine asymptomatic parasitemia followed by prompt. Fobia W. However. The risks to the baby documented in this 1. As such. Premature delivery associ. the content of the manuscript have been disclosed. falciparum African infants with congenital malaria are at greater risk of and P. the heads of the District Health Office. evidence for the safety and efficacy of against both multidrug-resistant P. Over the ensuing 3 years this policy has been introduction of a highly effective artemisinin combination Downloaded from jid. of congenital malaria. a major cause of morbidity in early infancy. Due to where resources permit. In Africa asymp. by a Wellcome Trust Senior Research malaria. research facility. the high prevalence of multidrug resistance in both P. Poespoprodjo JR.org at Charles Darwin University on September 21. malaria in the second and third trimesters of pregnancy were In conclusion. and Dr Rose general community malaria burden. and R. but with increasing antimalarial 48:1704–12. Dr Maurits J. are cleared within 3 days [10]. 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