Prevalence of Malaria and Sexually Transmitted and Reproductive Tract Infections in Pregnancy in Sub-Saharan Africa a Systematic Review

REVIEW CLINICIAN’S CORNER

Prevalence of Malaria and Sexually Transmitted and Reproductive Tract Infections in Pregnancy in Sub-Saharan Africa A Systematic Review

R. Matthew Chico, MPH Context Malaria and sexually transmitted infections/reproductive tract infections (STIs/ Philippe Mayaud, MD RTIs) in pregnancy are direct and indirect causes of stillbirth, prematurity, low birth weight, and maternal and neonatal morbidity and mortality. Cono Ariti, MSc Objective To conduct a systematic review and meta-analysis of malaria and STI/ David Mabey, MD RTI prevalence estimates among pregnant women attending antenatal care facilities Carine Ronsmans, MD in sub-Saharan Africa. Daniel Chandramohan, PhD Data Sources PubMed, MEDLINE, EMBASE, the World Health Organization Inter- national Clinical Trials Registry, and reference lists were searched for studies reporting 1 HERE ARE 880 000 STILLBIRTHS malaria, syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vagi- and 1.2 million neonatal deaths2 nalis, or bacterial vaginosis among pregnant women attending antenatal care facili- each year in sub-Saharan Africa. ties in sub-Saharan Africa. Ͻ Low birth weight ( 2.5 kg), at- Study Selection Included studies were conducted in 1990-2011 with open enroll- Ttributable to intrauterine growth retar- ment. Studies from South Africa, where malaria is no longer endemic, were excluded. dation, preterm delivery, or both, is the Data Extraction Point prevalence estimates were corrected for diagnostic preci- leading risk factor for neonatal mortal- sion. A random-effects model meta-analysis was applied to produce pooled preva- 3 ity. Intrauterine infection is implicated lence estimates. in stillbirth4 and is associated with 25% 5 Results A total of 171 studies met inclusion criteria, providing 307 point prevalence es- to 40% of preterm births. Sexually trans- timates for malaria or STIs/RTIs and including a total of 340 904 women. The pooled preva- mitted infections and reproductive tract lence estimates (with 95% CIs and number of women with positive diagnosis) among stud- infections (STIs/RTIs)6 and malaria7 are ies in 1990-2011 in East and Southern Africa were as follows: syphilis, 4.5% ( 3.9%-5.1%; associated with adverse birth outcomes, n=8346 positive diagnoses), N gonorrhoeae, 3.7% (2.8%-4.6%; n=626), C trachoma- but both may be mitigated with preven- tis, 6.9% (5.1%-8.6%; n=350), T vaginalis, 29.1% (20.9%-37.2%; n=5502), bacterial tive or presumptive treatment or by re- vaginosis, 50.8% (43.3%-58.4%; n=4280), peripheral malaria, 32.0% ( 25.9%-38.0%; peated screening and treatment through- n=11 688), and placental malaria, 25.8% (19.7%-31.9%; n=1388). West and Central out the antenatal period. The extent to Africa prevalence estimates were as follows: syphilis, 3.5% (1.8%-5.2%; n=851), N gonorrhoeae, 2.7% (1.7%-3.7%; n=73), C trachomatis, 6.1% (4.0%-8.3%; n=357), T vagi- which either approach may be beneficial nalis, 17.8% (12.4%-23.1%; n=822), bacterial vaginosis, 37.6% (18.0%-57.2%; n=1208), depends on the underlying prevalence of peripheral malaria, 38.2% (32.3%-44.1%; n=12 242), and placental malaria, 39.9% (34.2%- STIs/RTIs and malaria in pregnancy. This 45.7%; n=4658). systematic review and meta-analysis pro- Conclusion The dual prevalence of malaria and STIs/RTIs in pregnancy among women vide estimates for the dual prevalence of who attend antenatal care facilities in sub-Saharan Africa is considerable, with the com- STIs/RTIs and malaria in pregnancy bined prevalence of curable STIs/RTIs being equal to, if not greater than, malaria. among women attending antenatal care JAMA. 2012;307(19):2079-2086 www.jama.com facilities in sub-Saharan Africa. ber 2011 using Medical Subject Head- International Clinical Trials Registry; METHODS ings and free text terms, respectively; and relevant reference lists to identify We searched 3 databases, PubMed, the World Health Organization (WHO) studies conducted between 1990- MEDLINE, and EMBASE, in Novem- Author Affiliations: Departments of Disease London School of Hygiene and Tropical Medicine, Control (Mr Chico and Dr Chandramohan), Clinical London, England. CME available online at Research (Drs Mayaud and Mabey), Medical Corresponding Author: R. Matthew Chico, MPH, www.jamaarchivescme.com Statistics (Mr Ariti), and Infectious Disease Epidemi- London School of Hygiene and Tropical Medicine, and questions on p 2109. ology (Dr Ronsmans) and the Malaria Centre Keppel Street, Room 445, London WC1E 7HT, (Mr Chico and Drs Mabey and Chandramohan), England ([email protected]).

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lence estimates without intervention, Figure 1. Identification, Screening, and Eligibility of Studies in the Meta-analysis the potential for publication bias should

3604 Records identified from 14 Records identified from be minimal. database searches other sources Point prevalences and 95% confidence intervals were calculated for each

1682 Duplicate records excluded study. We then applied a standard method9 for correcting errors of mag- 1936 Records screened nitude with the known sensitivity and specificity of individual assays (eAp- 1484 Articles excluded 936 Unrelated end points pendix 2 and eAppendix 3) to in- 59 Ineligible country crease the precision of each point preva- 348 Some or all data prior to 1990 lence estimate. Corrected point 141 Selective antenatal care facility enrollment prevalence data were then used to generate pooled prevalence estimates and 452 Full-text articles reviewed corresponding 95% confidence intervals. We stratified results by subre- 281 Articles excluded 197 Unrelated end points gion (East and Southern Africa vs West 9 Ineligible country 14 Same data in ≥2 articlesa and Central Africa) because of under- 19 Some or all data prior lying differences in epidemiology, par- to 1990 42 Selective antenatal care ticularly the extent to which HIV modu- facility enrollment lates the transmission of malaria and STIs/RTIs. 171 Articles included in systematic review and meta-analysis We conducted the meta-analysis with random-effects models,10 accounting for a Data believed to have appeared in more than 1 article were reviewed in full text and therefore do not appear the possibility of heterogeneity be- under records excluded. tween studies, and assessed our results with the Q statistic. Separate sen- 2011 that reported point prevalence es- veys were also excluded. Multiyear sitivity analyses were performed for timates for STIs/RTIs, malaria, or both studies that included pre-1990 data studies conducted before and after the among pregnant women attending an- were excluded, as were studies from year 2000 to examine temporal changes tenatal care facilities in sub-Saharan South Africa, where malaria is no lon- in prevalence. Using Stata/IC version 12 Africa (eAppendix 1; available at http: ger endemic. software11 to generate the random- //www.jama.com). If 2 or more preva- Records retrieved were all in Eng- effects meta-analysis model, we pro- lence estimates were reported— lish, although several abstracts had been duced forest plots to display the point whether the result of a comparative translated from Chinese, Danish, Dutch, prevalence and 95% confidence inter- diagnostic study, use of the same diag- French, German, Italian, Portuguese, vals of individual studies as well as the nostic method on multiple occasions, and Swedish. One author (R.M.C.) con- pooled estimates and 95% confidence or subsequent use of a more sensitive ducted the data retrieval. Data abstrac- intervals for all strata. assay—we used the higher/highest mea- tion was not blinded to author or surement in our analysis. publication but was performed inde- RESULTS Our aim was to establish the dual pendently and in duplicate by R.M.C. A total of 171 studies met inclusion cri- prevalence of these infections in preg- and a research assistant, reviewing rec- teria, providing 307 point prevalence es- nancy among women receiving ante- ords against inclusion/exclusion crite- timates and including a total of 340 904 natal care without inflating estimates ria to identify 3618 records of inter- women. Search results are summarized by including studies that selectively en- est. Any discrepancies were resolved by in FIGURE 1. The TABLE summarizes the rolled women from high-risk groups. D.C. Two authors (P.M. and D.M.) and pooled mean prevalence estimates of Thus, studies that enrolled subsets of another researcher assisted R.M.C. in 1990-2011 with subanalyses for 1990- women from the antenatal care popu- the identification and classification of 1999 and 2000-2011. Results for the pe- lation were excluded (eg, only preg- STI/RTI diagnostic methods; D.C. did riod 1990-2011 are presented in nant women with human immunode- the same with R.M.C. for malaria stud- FIGURE 2, plotted by subregion along ficiency virus [HIV]). Studies of ies. No evidence of publication bias was with the lowest and highest point es- commercial sex workers, women seek- found using funnel-plot assessment as timates reported. Detailed analyses by ing treatment at STI facilities or family described by Sterne et al.8 Given that infection type and subregion are avail- planning facilities, or nonpregnant data for this review have been drawn able online (eTable 1 and eFigure 1 women tested in community-based sur- from studies reporting point preva- [syphilis], eTable 2 and eFigure 2

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Table. Pooled Mean Prevalence Estimates Among Pregnant Women Attending Antenatal Care Facilities in Sub-Saharan Africa No. of Women

Median ANC Pooled Mean No. With Study Facilities Prevalence, % Positive Sample Size, No. of No. of per Study, Heterogeneity, Infection by Subregion (95% CI)a Positive Tested Diagnosis Range Countries Studies Range % 1990-2011 East and Southern Africa Syphilis 4.5 (3.9 to 5.1) 8346 136 686 54 85-52 405 11 41 1-57 c N gonorrhoeae 3.7 (2.8 to 4.6) 626 17 220 20 145-9104 7 14 1-13 87.5 C trachomatis 6.9 (5.1 to 8.6) 350 5159 34 151-964 8 10 1-13 85.9 T vaginalis 29.1 (20.9 to 37.2) 5502 28 189 86 100-9137 9 18 1-13 c Bacterial vaginosis 50.8 (43.3 to 58.4) 4280 14 112 245 100-3046 8 11 1-13 c Peripheral parasitemia 32.0 (25.9 to 38.0) 11 688 47 443 195 86-5093 8 35 1-10 c Placental parasitemia 25.8 (19.7 to 31.9) 1388 6649 86 85-2502 7 12 1-9 c West and Central Africa Syphilis 3.5 (1.8 to 5.2) 851 10 797 18 205-4100 9 11 1-98 c N gonorrhoeae 2.7 (1.7 to 3.7) 73 2737 17 230-1160 8 5 1-4 67.2 C trachomatis 6.1 (4.0 to 8.3) 357 5414 35 261-1160 8 10 1-4 94.7 T vaginalis 17.8 (12.4 to 23.1) 822 9806 57 86-2657 7 12 1-4 c Bacterial vaginosis 37.6 (18.0 to 57.2) 1208 7435 138 350-2657 6 7 1-3 c Peripheral parasitemia 38.2 (32.3 to 44.1) 12 242 43 312 127 26-6370 10 56 1-55 c Placental parasitemia 39.9 (34.2 to 45.7) 4658 27 535 168 36-8310 8 23 1-6 c 1990-1999 East and Southern Africa Syphilis 6.1 (5.0 to 7.2) 6168 97 055 79 85-52 405 8 21 1-23 c N gonorrhoeae 3.7 (2.7 to 4.6) 547 15 446 18 151-9104 6 9 1-12 82.5 C trachomatis 9.4 (6.0 to 12.7) 194 2395 36 151-964 4 5 1-12 88.2 T vaginalis 32.8 (18.6 to 47.1) 4314 17 710 74 100-9137 5 10 1-12 c Bacterial vaginosis 51.5 (35.5 to 67.5) 1876 7039 109 100-3046 5 6 1-1 c Peripheral parasitemia 34.9 (25.1 to 44.7) 7563 29 068 327 102-5093 7 16 1-10 c Placental parasitemia 25.2 (16.0 to 34.3) 588 3271 124 232-2502 3 3 1 c West and Central Africa Syphilis 3.8 (1.5 to 6.2) 773 7106 13 205-4100 6 17 1-4 c N gonorrhoeae 3.0 (1.8 to 4.2) 70 2507 18 350-1160 7 4 1-4 67.2 C trachomatis 7.5 (4.6 to 10.0) 339 4632 44 350-1160 7 5 1-4 94.7 T vaginalis 23.5 (15.6 to 31.5) 721 4585 73 86-1160 6 8 1-4 c Bacterial vaginosis 46.0 (24.2 to 67.8) 640 2645 132 350-646 5 5 1-3 c Peripheral parasitemia 43.4 (34.1 to 52.7) 5543 16 671 178 26-2104 7 19 1-17 c Placental parasitemia 42.6 (34.9 to 50.3) 2445 19 582 233 64-8310 6 9 1-2 c 2000-2011 East and Southern Africa Syphilis 2.9 (2.1 to 3.6) 2178 39 631 32 245-17 277 8 17 1-57 c N gonorrhoeae 4.9 (1.8 to 7.9) 79 1774 21 145-835 6 4 1-13 91.9 C trachomatis 5.2 (3.4 to 7.1) 156 2764 25 151-835 6 5 1-13 79.6 T vaginalis 24.9 (18.3 to 31.5) 1188 10 479 98 151-2917 8 8 1-13 c Bacterial vaginosis 50.3 (43.9 to 56.7) 2404 7073 253 247-2555 6 5 1-13 c Peripheral parasitemia 29.5 (22.4 to 36.5) 4125 18 375 157 86-2459 8 19 1-9 c Placental parasitemia 26.5 (16.7 to 36.4) 800 3378 58 85-726 3 9 1-9 c West and Central Africa Syphilis 2.5 (0.4 to 4.6) 78 3691 21 230-2133 4 5 1-98 88.6 N gonorrhoeae 1.6 (0.0 to 3.3) 3 230 3 230 3 1 1-1 NAb C trachomatis 1.9 (0.2 to 3.5) 18 782 9 261-521 2 2 1-2 55.8 T vaginalis 4.5 (2.5 to 6.6) 101 5221 25 201-2657 2 4 1-4 92.7 Bacterial vaginosis 16.7 (−12.6 to 46.1) 604 4790 302 2133-2657 2 2 1-2 c Peripheral parasitemia 35.1 (28.2 to 41.9) 6699 26 641 97 38-6370 8 36 1-55 c Placental parasitemia 38.0 (28.4 to 47.6) 2213 7953 84 36-1875 6 15 1-6 c Abbreviation: ANC, antenatal care; C trachomatis, Chlamydia trachomatis; N gonorrhoeae, Neisseria gonorrhoeae; T vaginalis, Trichomonas vaginalis. a Note that dividing total No. of positive diagnoses by total No. of tested women does not account for diagnostic errors. A standard method9 of correcting errors of known magnitude has been applied to these data based on the sensitivity and specificity of individual diagnostic tests. Uncorrected and corrected point estimates from each study are presented in the eTables. b Not applicable (NA) because there is only 1 study. c Heterogeneity greater than 97.0%.

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[Neisseria gonorrhoeae], eTable 3 and mate of 16.3% (95% CI, 15.2%-17.4%) CI, 16.5%-29.9%) as detected by an en- eFigure 3 [Chlamydia trachomatis], using a T pallidum hemagglutination as- zyme immunoassay.15 In West and Cen- eTable 4 and eFigure 4 [Trichomonas say that confirms syphilis infection, al- tral Africa, the pooled mean preva- vaginalis], eTable 5 and eFigure 5 [bac- though not necessarily active cases.13 lence was 6.1% (95% CI, 4.0%-8.3%). terial vaginosis], eTable 6 and eFigure The highest prevalence, 16.4% (95% CI, 6 [peripheral malaria], and eTable 7 and Neisseria gonorrhoeae 12.6%-20.1%) based on culture or en- eFigure 7 [placental malaria]), with key In East and Southern Africa, the pooled zyme immunoassay, was observed in findings reported herein. In all in- prevalence was 3.7% (95% CI, 2.8%- Pikine, Senegal.16 stances, prevalence estimates have been 4.6%), with the highest point estimate corrected to account for diagnostic er- of 23.3% (95% CI, 16.4%-30.2%) ob- Trichomonas vaginalis rors as previously described. served in Manhic¸a, Mozambique.12 The The pooled prevalence of T vaginalis in- pooled mean prevalence of N gonor- fection was 29.1% (95% CI, 20.9%- Syphilis rhoeae in West and Central Africa was 37.2%) among women in East and The pooled mean prevalence of syphilis 2.7% (95% CI, 1.7%-3.7%); the highest Southern Africa, compared with 17.8% in East and Southern Africa was 4.5% individual estimate, 4.6% (95% CI, 2.8%- (95% CI, 12.4%-23.1%) in West and (95% CI, 3.9%-5.1%), with the highest 6.3%), came from a study in Abidjan, Central Africa. The highest point esti- estimate, 13.7% (95% CI, 9.0%- Coˆte d’Ivoire, that used culture diag- mate in East and Southern Africa was 18.5%), in Vilanculos, Mozambique, nostic methods.14 51.7% (95% CI, 41.9%-61.5%), re- based on rapid plasma reagin (RPR) test- ported in a refugee camp of Rwandans ing and Treponema pallidum hemagglu- Chlamydia trachomatis in Tanzania,17 as diagnosed by wet- tination confirmation.12 In West and The pooled prevalence of C trachoma- mount microscopy. The highest preva- Central Africa, the pooled mean preva- tis infection in East and Southern Africa lence estimate in West and Central lence of serological syphilis was 3.5% was 6.9% (95% CI, 5.1%-8.6%), with Africa, 52.0% (95% CI, 47.6%-56.4%), (95% CI, 1.8%-5.2%). Yaounde´, Cam- Khartoum, Sudan, reporting the high- was in Jos, Nigeria, where T vaginalis was eroon, reported the highest point esti- est prevalence estimate of 23.2% (95% identified by the same method.18

Figure 2. Curable STI/RTI and Malaria Infection Among Pregnant Women Attending Antenatal Facilities in Africa by Subregion

East and Southern Africa

No. of Women

Positive Pooled Prevalence Lowest to Highest Point Infection Diagnosis Tested Estimates, % (95% CI) Estimates, Range, % Syphilis 8346 136 686 4.50 (3.90-5.10) 0.10-13.70 Neisseria gonorrhoeae 626 17 220 3.70 (2.80-4.60) 1.40-23.30 Chlamydia trachomatis 350 5159 6.90 (5.10-8.60) 2.00-23.20 Trichomonas vaginalis 5502 28 189 29.10 (21.00-37.20) 3.90-51.70 Bacterial vaginosis 4280 14 112 50.80 (43.30-58.40) 23.50-85.50 Peripheral malaria 11 688 47 443 32.00 (25.90-38.00) 2.10-87.90 Placental malaria a 1388 6649 25.80 (19.70-31.90) 8.50-74.70

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 Prevalence, %

West and Central Africa

No. of Women

Positive Pooled Prevalence Lowest to Highest Point Infection Diagnosis Tested Estimates, % (95% CI) Estimates, Range, % Syphilis 851 10 797 3.50 (1.80-5.20) 0.10-16.30 Neisseria gonorrhoeae 73 2737 2.70 (1.70-3.70) 1.60-4.60 Chlamydia trachomatis 357 5414 6.10 (4.00-8.30) 1.40-16.40 Trichomonas vaginalis 822 9806 17.80 (12.40-23.10) 1.60-52.00 Bacterial vaginosis 1208 7435 37.60 (18.00-57.20) 18.00-74.50 Peripheral malaria 12 242 43 312 38.20 (37.30-44.10) 0.90-94.50 Placental malaria a 4658 27 535 39.90 (34.20-45.70) 9.00-91.60

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 Prevalence, %

Diamonds indicate pooled mean prevalence estimates; the extremes of the diamonds indicate 95% CIs. Horizontal bars indicate lowest to highest point prevalence estimates. STI/RTI indicates sexually transmitted infection/reproductive tract infection. a Placental malaria is measured at delivery.

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Bacterial Vaginosis of the only published data on coinfec- period covered in this review. The ad- The burden of bacterial vaginosis was tion: 48.3% of RPR-positive women also vent of molecular tests such as PCR and higher than any other STI/RTI in both had placental parasitemia and 35.0% of ligase chain reaction has allowed re- subregions. In East and Southern Africa, RPR-negative women had malaria- searchers in recent years to detect infec- the pooled prevalence estimate was infected placentas (PϽ.001).29 tion where older diagnostic methods may 50.8% (95% CI, 43.4%-58.4%). The have failed to do so. Although our sta- highest point estimate was 85.5% (95% COMMENT tistical correction for diagnostic errors CI, 82.8%-88.1%) in Blantyre, Ma- This systematic review of STIs/RTIs and can make data more comparable, the lawi, where Amsel criteria were used for malaria prevalence estimates over a 20- pooled mean prevalence of STIs/RTIs and diagnosis.17 In West and Central Africa, year period suggests that a consider- malaria is still probably an underesti- the pooled prevalence estimate was able burden of malaria and STIs/RTIs mate of the true burden of disease. 37.6% (95% CI, 18.0%-57.2%), with the exists at the population level among Among 59 studies providing estimates for highest point estimate at 74.5% (95% pregnant women attending antenatal fa- syphilis prevalence, 45 used the non- CI, 70.0%-79.1%) in Praia, Cape Verde, cilities in sub-Saharan Africa. How- treponemal RPR or venereal disease re- based on clue cell count.19 ever, the absence of reports on coin- search laboratory tests confirmed by a fection makes it impossible to describe Treponema-specific test, reflecting wide Malaria the prevalence of malaria only, cur- acceptance of the diagnostic gold stan- Peripheral Malaria. The pooled preva- able STIs/RTIs only, or coinfection in dard. Because biological false-positive lence of peripheral malaria in East and pregnancy. nontreponemal test results can be pro- Southern Africa was 32.0% (95% CI, The GRADE approach to data qual- duced by malaria and other infections, 25.9%-38.0%). The highest subre- ity assessment30 was considered inap- the burden of syphilis in studies that did gional prevalence, 87.9% (95% CI, propriate for this particular meta- not use treponemal confirmatory test- 85.7%-90.1%), was reported from analysis. It is a useful and transparent ing may be overstated. Hoima, Uganda, where diagnosis was tool for the analysis of treatment out- A variety of diagnostic methods were made by microscopy.20 In West and comes following contrasting interven- used for identifying N gonorrhoeae and Central Africa, the pooled prevalence tions produced by different study de- C trachomatis infections, whereas wet- of peripheral malaria parasitemia was signs. However, because we included mount microscopy was used in all but 38.2% (95% CI, 32.3%-44.1%). The studies that had open enrollment in the 2 studies reporting trichomoniasis preva- highest point estimate was 94.9% (95% antenatal care setting and we were not lence, a method notoriously lacking sen- CI, 88.0%-102.0%) in Ngali II, Cam- investigating the effect of medical in- sitivity compared with culture or mo- eroon, as identified by polymerase chain tervention, we did not expect the popu- lecular tests.32,33 Bacterial vaginosis was reaction (PCR) diagnosis.21 lation prevalence of STIs/RTIs and ma- diagnosed using 4 methods: Nugent Placental Malaria. For placental malaria in pregnancy to vary across study score, Spiegel criteria, Amsel criteria, and laria, measurable only after delivery,the designs. In addition, the GRADE sys- clue cell prevalence estimates. The Nu- pooled prevalence in East and South- tem requires ranking of evidence by gent score34 is the preferred objective ern Africa was 25.8% (95% CI, 19.7%- outcomes of interest, scored as high, in- method and was used in studies report- 31.9%); the highest point estimate, 74.7% termediate, low, or very low. In this re- ing the 7 highest rates of infection from (95% CI, 65.5%-84.0%), was based on view, we could have assigned quality East and Southern Africa. Thus, the histological diagnosis in Kisumu, scores to point prevalence estimates, but pooled mean prevalence would likely Kenya.22 In West and Central Africa, the that would have introduced a limited have been higher had the Nugent score pooled prevalence was 39.9% (95% CI, but unavoidable level of subjectivity. been used in all studies. 34.2%-45.7%), and the highest point Thus, we chose instead to improve the Peripheral parasitemia may be un- prevalence was 91.6% (95% CI, 84.8%- precision of each point estimate with derrepresented for 2 reasons. Infec- 94.4%) as diagnosed by placental histol- a standard method9 for correcting er- tion tends to be highest between ges- ogy, impression, and smears with mi- rors of known magnitude before incor- tational weeks 9 through 16, declining croscopy in Ebolowa, Cameroon.23 porating data into the random-effects until term.35,36 No studies appeared to models. This same approach has been have measured peripheral parasitemia Dual Prevalence of STIs/RTIs used with prevalence data from Tan- during this peak period. Another im- and Malaria zania to compare STI/RTI estimates de- portant source of underestimated dis- Only 5 publications reported the preva- rived by disparate diagnostic tests.31 We ease burden is that most malaria diag- lence of syphilis and malaria,24-28 and present corrected and uncorrected point noses were based on microscopy no single article reported coinfection of prevalence estimates by study in eTable without molecular test correction. A malaria and STIs/RTIs. Subanalysis in 1 through eTable 7. study in Blantyre, Malawi, illustrates the a prospective cohort study of preg- Diagnostic methods and tools have extent to which underdiagnosis may oc- nant women in Tanzania provided some changed for many pathogens during the cur with conventional microscopy; the

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prevalence of peripheral parasitemia of sulfadoxine-pyrimethamine as intermit- Untreated C trachomatis infects the eyes 51.9% (95% CI, 43.4%-60.3%) was tent preventive treatment during preg- of50%ofnewbornsatdelivery,andpneu- found by PCR, while microscopy de- nancy (IPTp) when administered to HIV- moniawilldevelopin10%to20%ofthese tected infection only in 14.9% (95% CI, positive women.41 The interaction infants.49,50 Neisseria gonorrhoeae and C 11.8%-18.0%) of pregnant women.37 between STIs/RTIs and HIV has been trachomatis are common causes of oph- The dual prevalence of STIs/RTIs and well established, although providing pre- thalmia neonatorum and may lead to cor- malaria varied in the subregions we ana- sumptive treatment for STIs/RTIs to preg- neal scarring and blindness if untreated. lyzed. Overall, East and Southern Africa nant women in Rakai, Uganda, has not Trichomonas vaginalis infection is asso- has a greater burden of STIs/RTIs com- shown protective effect against mater- ciated with a 2-fold increase in preterm pared with West and Central Africa. Sev- nal to child transmission of HIV.42 How- delivery,51 asisbacterialvaginosis,theodds eral factors that are linked to exposure ever, malaria chemoprophylaxis was not of which are 7 times higher when the may contribute to this difference, includ- provided in this study; therefore, the po- condition manifests prior to 16 weeks’ ing higher prevalence of STIs/RTIs cir- tential modulating effect of malaria on gestation.52 Bacterial vaginosis is also sig- culating at the community level, patterns maternal to child transmission in the nificantlyassociatedwiththeriskofspon- of male circumcision as well as sexual be- presence of STIs/RTIs remains un- taneous abortion.52 Within this context, havior related to age of sexual debut, age known. progress toward the maternal and child atfirstmarriage,premaritalsex,andnum- Our study has several limitations. An healthtargetsofMillenniumDevelopment ber of total partners and concurrent sex unavoidable but important limitation Goals may be possible by improving ma- partners. The prevalence of HIV, for ex- is the inherent delay between gather- lariaandSTI/RTIcontrolmeasureswithin ample, remains substantially higher in ing evidence at the clinic level and pub- the antenatal care package. East and Southern Africa compared with lic dissemination. This is important in Several current infection control strat- the West and Central subregion. Accord- our study because HIV prevention cam- egies are included in the antenatal care ing to the Joint United Nations Pro- paigns, including STI/RTI screening and package. In areas of stable malaria trans- grammeonHIV/AIDS,34%oftheworld’s treatment programs, have made in- mission, WHO recommends that preg- HIV-positive population was living in 10 roads in reducing transmission in many nant women sleep under insecticide- countries of Southern Africa in 2010.38 settings. To capture these reductions treated mosquito bed nets and receive The epidemic in East Africa has declined with greater precision, more recent data 2 to 3 treatment courses of SP-IPTp over the past decade, but HIV prevalence are needed. Another limitation is that during antenatal consultations. Drug remains higher than in West and Central even after stratifying by geography and resistance to SP has compromised the Africa. age of study, heterogeneity among stud- protective effect of SP-IPTp in recent Peripheral and placental malaria is ies persisted. The random-effects mod- years, prompting a need to identify effi- slightly higher in West and Central els, in turn, produced wide 95% con- cacious drugs and new strategies to Africa compared with the East and fidence intervals in some instances. In prevent malaria in pregnancy.53 Southern subregion. This may be due addition, because we relied on evi- WHO recommends syphilis screen- to greater seasonal variation in trans- dence from English-language sources ing and treatment for pregnant women mission within West and Central Africa. and abstracts that had been translated at their first antenatal visit. For other cur- Recent declines in malaria transmis- into English, we may have identified able STIs/RTIs, WHO suggests using syn- sion within selected locales of Africa will fewer studies from researchers who drome-based algorithms to guide diag- likely translate into fewer pregnant publish in other languages. nosis and treatment. However, the vast women acquiring immunity from one There is a major risk of adverse birth majority of gonococcal (80%) and chla- pregnancy to the next. Thus, all women outcomes associated with malaria and mydial (70%-75%) infections in women in their reproductive years (rather than STIs/RTIsinpregnancy.Morethan30mil- are asymptomatic54 and therefore never just those in their first or second preg- lion pregnant women are at risk of infec- diagnosed. Consequently, the algo- nancies) may remain vulnerable to ma- tioneachyearinsub-SaharanAfrica.43 Ma- rithm based on vaginal discharge syn- laria in the years ahead until the abso- lariaisassociatedwithintrauterinegrowth drome has a low sensitivity (30%-80%) lute risk of exposure is negligible. retardation, preterm delivery, low birth and specificity (40%-80%) for N gonor- Human immunodeficiency virus and weight,44,45 stillbirth,44 early neonatal rhoeae and C trachomatis among preg- malaria interact to increase parasitic in- death,44 and maternal anemia.45 In Tan- nant women.55-57 Syndromic manage- fection of the placenta and incidence of zania, T pallidum is associated with 51% ment has slightly higher sensitivity for low birth weight.39 Plasmodium falci- of stillbirths and 24% of preterm live T vaginalis (54%-83%) and bacterial vagi- parum infection also increases viral load births.46 Neisseria gonorrhoeae is associ- nosis (51%-69%), with moderate speci- among HIV-positive pregnancy women.40 ated with a 2-fold increase in the risk of ficity (40%-54% for T vaginalis and 40%- New evidence suggests that malaria para- preterm delivery,47 whereas the risk of 58% for bacterial vaginosis).58 sites are more likely to develop wild- early preterm delivery in the presence of In addition, potential new directions type mutations following exposure to Ctrachomatisinfectionis4timeshigher.48 for the antenatal care package have been

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suggested, including use of novel drugs tention given its high prevalence. Clini- of Potential Conflicts of Interest. Mr Chico reports hav- ing previously received funding as part of 2 studies and rapid diagnostic tests. Several trials cal trials are needed to investigate the pro- co-financed by Pfizer and the Medicines for Malaria ofazithromycin-basedcombinationthera- tective effect of presumptive treatment of Venture that are investigating the use of azithromycin plus chloroquine in IPTp. No other disclosures were pies are under investigation for use in bacterial vaginosis with metronidazole at reported. IPTp. Azithromycin has modest antima- time points that are biologically optimal Online-Only Material: eAppendixes 1 through 3, larial properties but needs a partner an- and operationally feasible. It is less clear eTables 1 through 7, and eFigures 1 through 7 are available at http://www.jama.com. 59 timalarial drug against P falciparum. De- whether pregnancy outcomes would be Additional Contributions: We are grateful to Ro- spite concerns about drug resistance,60 a improved more with point-of-care tests sanna Peeling, PhD, London School of Hygiene and Tropical Medicine, for reviewing the data and assist- 2-g dose of azithromycin has resulted in and treatment for HIV, syphilis, and ma- ing in the classification of methods by quality, and cure rates of 97.7% (95% CI, 94.0%- laria,whilesyndromicmanagementispro- Mythili Ramakrishna, BDS, MSc, London School of Hy- giene and Tropical Medicine, for screening studies 99.4%) of syphilis cases in a study in vided for the remaining curable STIs/ against inclusion/exclusion criteria separately from Mr Tanzania.61 A single 2-g dose of azithro- RTIs—or if maternal, fetal, and newborn Chico. Dr Ramakrishna was compensated for her con- mycin was 98.9% (95% CI, 97.9%-100%) health will be better if women are given tribution. No other compensation was received. efficacious against N gonorrhoeae in the point-of-care tests for HIV and syphilis REFERENCES United States,62 while meta-analysis along with azithromycin-based combina- 1. Stanton C, Lawn JE, Rahman H, Wilczynska-Ketende showed that 1 g cures 96.5% (95% CI, tion therapy in IPTp. Rigorously con- K, Hill K. Stillbirth rates: delivering estimates in 190 95.3%-97.7%) of C trachomatis infec- ducted clinical trials are urgently needed. countries. Lancet. 2006;367(9521):1487-1494. tions.63 A trial in Malawi using1gof 2. Black RE, Cousens S, Johnson HL, et al; Child Health CONCLUSION Epidemiology Reference Group of WHO and UNICEF. azithromycinadministeredtwicewithSP- Global, regional, and national causes of child mortal- IPTp reduced the risk of T vaginalis 35% The dual prevalence of malaria and ity in 2008: a systematic analysis. Lancet. 2010; 64 375(9730):1969-1987. (P=.02). Azithromycin-basedcombina- STIs/RTIs is evident among pregnant 3. McCormick MC. The contribution of low birth tions could protect against bacterial vagi- women who attend antenatal facilities weight to infant mortality and childhood morbidity. N Engl J Med. 1985;312(2):82-90. nosis if administered early in pregnancy; in sub-Saharan Africa. As malaria con- 4. Goldenberg RL, Thompson C. The infectious ori- a meta-analysis of antibiotic therapy for trol and elimination efforts are brought gins of stillbirth. Am J Obstet Gynecol. 2003;189 to scale, the relative contribution of (3):861-873. thetreatmentofbacterialvaginosisinpreg- 5. Zhou X, Brotman RM, Gajer P, et al. Recent ad- nancy prior to gestational week 20 is as- STIs/RTIs to adverse birth outcomes vances in understanding the microbiology of the fe- sociatedwithasignificantreductioninthe most likely will increase proportion- male reproductive tract and the causes of premature 65 birth. Infect Dis Obstet Gynecol. 2010;2010:737425. risk of preterm birth. ately. Coinfection prevalence esti- 6. Mullick S, Watson-Jones D, Beksinska M, Mabey Novel use of rapid diagnostic tests mates for malaria and STIs/RTIs need D. Sexually transmitted infections in pregnancy: prevalence, impact on pregnancy outcomes, and ap- may replace IPTp with sulfadoxine- to be established and routinely re- proach to treatment in developing countries. Sex pyrimethamine altogether if used for in- ported. Rigorous studies using molecu- Transm Infect. 2005;81(4):294-302. 7. Desai M, ter Kuile FO, Nosten F, et al. Epidemiol- termittentscreeningandtreatmentforma- lar diagnostic methods are needed to ogy and burden of malaria in pregnancy. Lancet In- laria during antenatal visits. Intermittent characterize more accurately the preva- fect Dis. 2007;7(2):93-104. screening and treatment with artesunate- lence of these infections and their clini- 8. Sterne JAC, Egger M, Davey Smith G. Investigat- ing and dealing with publication and other bias. In: amodiaquinewasnoninferiortoIPTpwith cal consequences. Clinical trials are Egger M, Smith GD, Altman DG, eds. Systematic Re- sulfadoxine-pyrimethamine in Ghana in needed to compare birth outcomes, op- views in Health Care: Meta-Analysis in Context. 2nd ed. London, England: BMJ Books; 2001:189-208. anareawheresulfadoxine-pyrimethamine erational feasibility/acceptability, and 9. Kelsey JL, Whittemore AS, Evans AS, Thompson resistance was low; the incidence of low cost-effectiveness of IPTp with azithro- WD. Methods in Observational Epidemiology. 2nd ed. New York, NY: Oxford University Press; 1996. birthweightwassimilarbetweentheIPTp mycin-based combination therapy 10. DerSimonian R, Laird N. Meta-analysis in clinical with sulfadoxine-pyrimethamine and in- against an approach of integrated trials. Control Clin Trials. 1986;7(3):177-188. screening and treatment for malaria and 11. Sterne J. Meta-analysis in Stata: An Updated Col- termittentscreeningandtreatmentgroups lection From the Stata Journal. College Station, TX: among multigravid mothers (11.3% vs STIs/RTIs. Stata Press; 2009. 12. Vuylsteke B, Bastos R, Barreto J, et al. High preva- 11.3%) and among primigravid mothers Author Contributions: Mr Chico and Dr Chandramo- 66 lence of sexually transmitted diseases in a rural area (16.1% vs 17.2%). Rapid point-of-care han had full access to all of the data in the study and in Mozambique. Genitourin Med. 1993;69(6): tests for HIV have revolutionized the up- take responsibility for the integrity of the data and the 427-430. accuracy of the data analysis. 13. Mbopi Ke´ ou FX, Mbu R, Mauclère P, et al. An- take and performance of voluntary coun- Study concept and design: Chandramohan. tenatal HIV prevalence in Yaounde, Cameroon. Int J seling and testing67 and are used in some Acquisition of data: Chico. STD AIDS. 1998;9(7):400-402. Analysis and interpretation of data: Chico, Mayaud, 14. Diallo MO, Ettiègne-Traore´ V, Maran M, et al. antenatal settings in Africa. Point-of-care Mabey, Ariti, Ronsmans, Chandramohan. Sexually transmitted diseases and human immuno- testsforsyphilisareincreasinglyavailable, Drafting of the manuscript: Chico. deficiency virus infections in women attending an an- Critical revision of the manuscript for important in- making possible same-day results and tenatal clinic in Abidjan, Coˆ te d’Ivoire. Int J STD AIDS. tellectual content: Chico, Mayaud, Mabey, Ariti, 1997;8(10):636-638. 68,69 prompt treatment. Ronsmans, Chandramohan. 15. Ortashi OM, El Khidir I, Herieka E. Prevalence of Mitigating the dual prevalence of ma- Statistical analysis: Chico, Ariti. HIV, syphilis, Chlamydia trachomatis, Neisseria gon- Administrative, technical, or material support: Chico, orrhoeae, Trichomonas vaginalis and candidiasis laria and STIs/RTIs will require improve- Mayaud, Mabey, Ariti, Ronsmans, Chandramohan. among pregnant women attending an antenatal clinic ments in the Safe Motherhood package.70 Study supervision: Chandramohan. in Khartoum, Sudan. J Obstet Gynaecol. 2004; Conflict of Interest Disclosures: All authors have com- 24(5):513-515. Bacterial vaginosis requires particular at- pleted and submitted the ICMJE Form for Disclosure 16. Van Dyck E, Samb N, Sarr AD, et al. Accuracy of

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2 enzyme immunoassays and cell culture in the de- 33. van Der Schee C, van Belkum A, Zwijgers L, et al. 52. Leitich H, Bodner-Adler B, Brunbauer M, Kaider tection of Chlamydia trachomatis in low and high risk Improved diagnosis of Trichomonas vaginalis infec- A, Egarter C, Husslein P. Bacterial vaginosis as a risk populations in Senegal. Eur J Clin Microbiol Infect Dis. tion by PCR using vaginal swabs and urine speci- factor for preterm delivery: a meta-analysis. Am J Ob- 1992;11(6):527-534. mens compared to diagnosis by wet mount micros- stet Gynecol. 2003;189(1):139-147. 17. Mayaud P, Msuya W, Todd J, et al. STD rapid as- copy, culture, and fluorescent staining. J Clin Microbiol. 53. Chico RM, Chandramohan D. Intermittent pre- sessment in Rwandan refugee camps in Tanzania. Geni- 1999;37(12):4127-4130. ventive treatment of malaria in pregnancy: at the cross- tourin Med. 1997;73(1):33-38. 34. Nugent RP, Krohn MA, Hillier SL. Reliability of di- roads of public health policy. Trop Med Int Health. 18. Ogbonna CI, Ogbonna IB, Ogbonna AA, Anosike agnosing bacterial vaginosis is improved by a stan- 2011;16(7):774-785. JC. Studies on the incidence of Trichomonas vagina- dardized method of Gram stain interpretation. J Clin 54. World Health Organization. Global Prevalence and lis amongst pregnant women in Jos area of Plateau Microbiol. 1991;29(2):297-301. Incidence of Selected Curable Sexually Transmitted State, Nigeria. Angew Parasitol. 1991;32(4):198- 35. Brabin BJ. An analysis of malaria in pregnancy in Infections: Overview and Estimates. Geneva, Swit- 204. Africa. Bull World Health Organ. 1983;61(6):1005- zerland: World Health Organization; 2001. 19. Wessel HF, Herrmann B, Dupret A, Moniz F, Brito 1016. 55. Mayaud P, ka-Gina G, Cornelissen J, et al. Vali- C, Bergstro¨ m S. Genital infections among antenatal 36. Brabin B. The Risks and Severity of Malaria in Preg- dation of a WHO algorithm with risk assessment for care attendees in Cape Verde. Afr J Reprod Health. nant Women: Applied Field Research in Malaria the clinical management of vaginal discharge in 1998;2(1):32-40. Reports. Geneva, Switzerland: Special Programme for Mwanza, Tanzania. Sex Transm Infect. 1998;74 20. Ndyomugyenyi R, Magnussen P. Anaemia in preg- Research and Training in Tropical Diseases, World (suppl 1):S77-S84. nancy: Plasmodium falciparum infection is an impor- Health Organization; 1991. 56. Vuylsteke B, Laga M, Alary M, et al. Clinical al- tant cause in primigravidae in Hoima district, western 37. Mankhambo L, Kanjala M, Rudman S, Lema VM, gorithms for the screening of women for gonococcal Uganda. Ann Trop Med Parasitol. 1999;93(5): Rogerson SJ. Evaluation of the OptiMAL rapid anti- and chlamydial infection: evaluation of pregnant 457-465. gen test and species-specific PCR to detect placental women and prostitutes in Zaire. Clin Infect Dis. 1993; 21. Leke RF, Bioga JD, Zhou J, et al. Longitudinal stud- Plasmodium falciparum infection at delivery. J Clin 17(1):82-88. ies of Plasmodium falciparum malaria in pregnant Microbiol. 2002;40(1):155-158. 57. Costello Daly C, Wangel AM, Hoffman IF, et al. Vali- women living in a rural Cameroonian village with high 38. Joint United Nations Programme on HIV/AIDS. dation of the WHO diagnostic algorithm and develop- perennial transmission. Am J Trop Med Hyg. 2010; Report on the Global AIDS Epidemic 2010. Geneva, ment of an alternative scoring system for the manage- 83(5):996-1004. Switzerland: Joint United Nations Programme on ment of women presenting with vaginal discharge in 22. Kassam SN, Nesbitt S, Hunt LP, Oster N, Soothill HIV/AIDS; 2010. Malawi. Sex Transm Infect. 1998;74(suppl 1):S50- P, Sergi C. Pregnancy outcomes in women with or with- 39. Ayisi JG, van Eijk AM, ter Kuile FO, et al. The ef- S58. out placental malaria infection. Int J Gynaecol Obstet. fect of dual infection with HIV and malaria on preg- 58. Tann CJ, Mpairwe H, Morison L, et al. Lack of ef- 2006;93(3):225-232. nancy outcome in western Kenya. AIDS. 2003; fectiveness of syndromic management in targeting vagi- 23. Cot M, Le Hesran JY, Miailhes P, Esveld M, Etya’ale 17(4):585-594. nal infections in pregnancy in Entebbe, Uganda. Sex D, Breart G. Increase of birth weight following chlo- 40. Ayisi JG, van Eijk AM, Newman RD, et al. Ma- Transm Infect. 2006;82(4):285-289. roquine chemoprophylaxis during the first preg- ternal malaria and perinatal HIV transmission, west- 59. Chico RM, Pittrof R, Greenwood B, Chandramohan nancy: results of a randomized trial in Cameroon. Am ern Kenya. Emerg Infect Dis. 2004;10(4):643-652. D. Azithromycin-chloroquine and the intermittent pre- J Trop Med Hyg. 1995;53(6):581-585. 41. Mene´ ndez C, Serra-Casas E, Scahill MD, et al. HIV ventive treatment of malaria in pregnancy. Malar J. 2008; 24. Ayisi JG, van Eijk AM, ter Kuile FO, et al. Risk fac- and placental infection modulate the appearance of 7(1):255. tors for HIV infection among asymptomatic preg- drug-resistant Plasmodium falciparum in pregnant 60. Mabey D. Azithromycin resistance in Treponema nant women attending an antenatal clinic in western women who receive intermittent preventive treatment. pallidum. Sex Transm Dis. 2009;36(12):777-778. Kenya. Int J STD AIDS. 2000;11(6):393-401. Clin Infect Dis. 2011;52(1):41-48. 61. Riedner G, Rusizoka M, Todd J, et al. Single-dose 25. Luja´ n J, de On˜ ate WA, Delva W, et al. Preva- 42. Gray RH, Wabwire-Mangen F, Kigozi G, et al. Ran- azithromycin vs penicillin G benzathine for the treat- lence of sexually transmitted infections in women at- domized trial of presumptive sexually transmitted dis- ment of early syphilis. N Engl J Med. 2005;353(12): tending antenatal care in Tete province, Mozambique. ease therapy during pregnancy in Rakai, Uganda. Am 1236-1244. S Afr Med J. 2008;98(1):49-51. J Obstet Gynecol. 2001;185(5):1209-1217. 62. Handsfield HH, Dalu ZA, Martin DH, Douglas JM Jr, 26. Mene´ ndez C, Castellsague´ X, Renom M, et al. 43. Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter McCarty JM, Schlossberg D; Azithromycin Gonorrhea Prevalence and risk factors of sexually transmitted in- Kuile FO. Quantifying the number of pregnancies at Study Group. Multicenter trial of single-dose azithro- fections and cervical neoplasia in women from a rural risk of malaria in 2007: a demographic study. PLoS mycin vs ceftriaxone in the treatment of uncompli- area of southern Mozambique. Infect Dis Obstet Med. 2010;7(1):e1000221. cated gonorrhea. Sex Transm Dis. 1994;21(2):107- Gynecol. 2010;2010:609315. doi:10.1155/2010 44. van Geertruyden JP, Thomas F, Erhart A, 111. /609315. D’Alessandro U. The contribution of malaria in preg- 63. Lau CY, Qureshi AK. Azithromycin vs doxycycline 27. Montoya PJ, Lukehart SA, Brentlinger PE, et al. nancy to perinatal mortality. AmJTropMedHyg. 2004; for genital chlamydial infections: a meta-analysis of ran- Comparison of the diagnostic accuracy of a rapid im- 71(2)(suppl):35-40. domized clinical trials. Sex Transm Dis. 2002;29(9): munochromatographic test and the rapid plasma re- 45. Kalilani L, Mofolo I, Chaponda M, Rogerson S, 497-502. agin test for antenatal syphilis screening in Meshnick S. The effect of timing and frequency of ma- 64. Luntamo M, Kulmala T, Mbewe B, Cheung YB, Mozambique. Bull World Health Organ. 2006; laria infection during pregnancy on low birth weight Maleta K, Ashorn P. Effect of repeated treatment of preg- 84(2):97-104. and maternal anemia. Am J Trop Med Hyg. 2006; nant women with sulfadoxine-pyrimethamine and 28. van den Broek NR, White SA, Goodall M, et al. 75(5):414. azithromycin on preterm delivery in Malawi: a random- The APPLE study: a randomized, community-based, 46. Watson-Jones D, Changalucha J, Gumodoka B, ized controlled trial. Am J Trop Med Hyg. 2010; placebo-controlled trial of azithromycin for the pre- et al. Syphilis in pregnancy in Tanzania, I: impact of 83(6):1212-1220. vention of preterm birth, with meta-analysis. PLoS Med. maternal syphilis on outcome of pregnancy. J Infect 65. McDonald HM, Brocklehurst P, Gordon A. Antibi- 2009;6(12):e1000191. Dis. 2002;186(7):940-947. otics for treating bacterial vaginosis in pregnancy. Coch- 29. Watson-Jones D, Weiss HA, Changalucha JM, et al. 47. Goldenberg RL, Culhane JF, Iams JD, Romero R. rane Database Syst Rev. 2007;(1):CD000262. Adverse birth outcomes in United Republic of Epidemiology and causes of preterm birth. Lancet. 66. Tagbor H, Bruce J, Agbo M, Greenwood B, Tanzania—impact and prevention of maternal risk 2008;371(9606):75-84. Chandramohan D. Intermittent screening and treat- factors. Bull World Health Organ. 2007;85(1): 48. Rours GI, Duijts L, Moll HA, et al. Chlamydia tra- ment vs intermittent preventive treatment of malaria in 9-18. chomatis infection during pregnancy associated with pregnancy: a randomised controlled non-inferiority trial. 30. Guyatt GH, Oxman AD, Vist GE, et al; GRADE preterm delivery: a population-based prospective co- PLoS One. 2010;5(12):e14425. Working Group. GRADE: an emerging consensus on hort study. Eur J Epidemiol. 2011;26(6):493-502. 67. Dewsnap CH, Mcowan A. A review of HIV point- rating quality of evidence and strength of 49. Schachter J, Grossman M, Sweet RL, Holt J, Jordan of-care tests. Int J STD AIDS. 2006;17(6):357-359. recommendations. BMJ. 2008;336(7650):924- C, Bishop E. Prospective study of perinatal transmis- 68. Peeling R. The Sexually Transmitted Diseases Di- 926. sion of Chlamydia trachomatis. JAMA. 1986;255 agnostics Initiative: Laboratory Based Evaluation of 31. Orroth KK, Korenromp EL, White RG, et al. Com- (24):3374-3377. Rapid Syphilis Diagnostics. Geneva, Switzerland: World parison of STD prevalences in the Mwanza, Rakai, and 50. Hammerschlag MR. Chlamydial and gonococcal Health Organization; 2003. Masaka trial populations: the role of selection bias and infections in infants and children. Clin Infect Dis. 2011; 69. Peeling RW, Ye H. Diagnostic tools for preventing diagnostic errors. Sex Transm Infect. 2003;79(2): 53(suppl 3):S99-S102. and managing maternal and congenital syphilis: an 98-105. 51. French JI, McGregor JA, Parker R. Readily treat- overview. Bull World Health Organ. 2004;82(6): 32. Fouts AC, Kraus SJ. Trichomonas vaginalis: re- able reproductive tract infections and preterm birth 439-446. evaluation of its clinical presentation and laboratory among black women. Am J Obstet Gynecol. 2006; 70. Mahler H. The Safe Motherhood initiative: a call to diagnosis. J Infect Dis. 1980;141(2):137-143. 194(6):1717-1726. action. Lancet. 1987;1(8534):668-670.

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Chico RM, Mayaud P, Ariti C, Mabey D, Ronsmans C, Chandramohan D. Prevalence of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review. JAMA. 2012;307(19):10.1001/jama.2012.3428.

eFigure 1a. Syphilis: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 1b. Syphilis: West and Central Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 2a. Neisseria gonorrhoeae: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 2b. Neisseria gonorrhoeae: West and Central Africa Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 3a. Chlamydia trachomatis: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 3b. Chlamydia trachomatis: West and Central Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 4a. Trichomonas vaginalis: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 4b. Trichomonas vaginalis: West and Central Africa: Pooled mean prevalence estimate among pregnant women at antenatal care facilities eFigure 5a. Bacterial vaginosis: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 5b. Bacterial vaginosis: West and Central Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 6a. Peripheral malaria: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 6b. Peripheral malaria: West and Central Africa: Pooled mean prevalence estimate among pregannt women at antenatal care facilities eFigure 7a. Placental malaria: East and Southern Africa: Pooled mean prevalence estimate among pregannt women at delivery eFigure 7b. Placental malaria: West and Central Africa: Pooled mean prevalence estimate among pregannt women at delivery

eTable 1. Syphilis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 2. Neisseria gonorrhoeae Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 3. Chlamydia trachomatis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 4. Trichomonas vaginalis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 5. Bacterial Vaginosis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 6. Peripheral Malaria Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa eTable 7. Placental Malaria Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub-Saharan Africa

eAppendix 1. Search Terms eAppendix 2. Published Sensitivity and Specificity Measures for Diagnostic Methods Used eAppendix 3. References for Studies Used in Meta-analysis and eAppendix 2

This supplementary material has been provided by the authors to give readers additional information about their work.

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Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 1. Syphilis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Blantyre, Malawi (1990‐93) Taha 1999 1 1001 9309 10.8 10.2, 11.4 RPR and TPHA 10.0 9.3, 10.6 1 Umzingwane Zimbabwe (1991) Rutgers 1993 2 197 1,433 13.8 12.0, 15.5 RPR only 10.5 8.9, 12.0 1 Vilanculos, Mozambique (1991‐92) Vuylsteke 1993 3 29 201 14.4 9.6, 19.3 RPR and TPHA 13.7 9.0, 18.5 1 Zambizai, Mozambique (1992‐93) Cossa 1994 4 212 1,728 12.2 10.7, 13.8 RPR and MHA‐TP 11.5 10.0, 13.0 14 Nairobi, Kenya (1992‐94) Jenniskens 1995 5 854 13,131 6.5 6.1, 6.9 RPR only 2.3 2.0, 2.5 9 Mwanza, Tanzania (1992‐93) Mayaud 1995 6 97 964 10.1 8.2, 12.0 RPR and TPHA 9.3 7.4, 11.1 12 Nairobi, Kenya (1992‐97) Temmerman 1999 7 2,701 52,405 5.2 5.0, 5.3 RPR only 0.7 0.7, 0.8 10 Dar es Salaam, Tanzania (1993) Mwakagile 1996 8 31 777 4.0 2.6, 5.4 RPR and TPHA 0.1 1.8, 4.3 1 Blantyre, Malawi (1993) Taha 1998 9 264 2,161 12.2 10.8, 13.6 RPR and TPHA 11.5 9.4, 17.5 1 Debretabor, Ethiopia (1994) Azeze 1995 10 37 270 13.7 9.6, 17.8 VDRL only 13.5 9.4, 17.5 1 Nairobi, Kenya (1994) Thomas 1996 11 9 286 3.2 1.1, 5.2 RPR and TPHA 2.2 0.5, 3.9 1 Rwandan camp, Tanzania (1994) Mayaud 1997 12 2 100 2.0 ‐0.7, 4.7 RPR and TPHA 1.0 ‐1.0, 3.0 1

1999 13 ‐ Mwanza, Tanzania (not reported) Mayaud 1997 173 2,380 7.3 6.2, 8.3 RPR and TPHA 6.4 5.4, 7.4 12 Mwanza, Tanzania (1994) Mayaud 1998 14 55 660 8.3 6.2, 10.4 RPR and TPHA 7.5 5.5, 9.5 1 9

1990 Blantyre, Malawi (1995) Taha 1998 98 808 12.1 9.9, 14.4 RPR and TPHA 11.4 9.2, 13.5 1 Dar es Salaam, Tanzania (1995‐97) Urassa 2001 15 62 1,058 5.9 4.4, 7.3 VDRL and TPHA 5.0 3.7, 6.3 4 Addis Ababa, Ethiopia (1995‐2001) Tsegaye 2002 16 135 4,731 2.9 2.4, 3.3 RPR and TPHA 1.9 1.5, 2.3 4 Blantyre, Malawi (1996) Taha 1998 9 92 829 11.1 9.0, 13.2 RPR and TPHA 10.3 8.2, 12.4 1 Kisumu, Kenya (1996‐97) Ayisi 2000 17 65 2,844 2.3 1.7, 2.8 VDRL only 0.3 0.1, 0.5 1 Addis Ababa, Ethiopia (1997) Kebede 2000 18 12 410 2.9 1.3, 4.6 VDRL and TPHA or VDRL and FTA‐Abs 2.0 0.6, 3.3 3 Nairobi, Kenya (1997) Fonck 2000 19 22 334 6.6 3.9, 9.3 RPR only 2.4 0.7, 4.0 2 Gutu, Zimbabwe (not reported) Majoko 2003 20 9 85 10.6 4.1, 17.1 RPR only 6.9 1.5, 12.3 23 21 Kisumu, Kenya (1996‐99) Ayisi 2003 55 2,288 2.4 1.8, 3.0 RPR only 0.5* 0.2, 0.8 1 Nairobi, Kenya (1997‐98) Fonck 2001 22 928 27,377 3.4 3.2, 3.6 RPR only 0.5* 0.4, 0.6 10 Khartoum, Sudan (1999) Ortashi 2004 23 11 151 7.3 3.1, 11.4 RPR and TPHA 6.4 1.5, 12.3 1 Harare, Zimbabwe (Not reported) Pham 2005 24 74 2,969 2.5 1.9, 3.1 RPR and TPHA 1.5 1.1, 2.0 1 Moshi, Tanzania (1999‐2004) Msuya 2007 25 39 3,046 1.3 0.9, 1.7 RPR and MHA‐TP 0.3 0.1, 0.5 3 Gaborone, Botswana (2000‐01) Romoren 2006 26 32 703 4.6 3.0, 6.1 RPR and TPHA 3.6 2.2, 5.0 13 Blantyre, Malawi (2000‐04) Kwiek 2008 27 198 3,824 5.2 4.5, 5.9 RPR and TPHA 4.3 3.6, 4.9 1 Manhiça, Mozambique (2000) Menendez 2010 28 31 258 12.0 8.1, 16.0 RPR and IgG ELISA 11.24 7.39, 15.1 1 Harare, Zimbabwe (2002‐03) Kurewa 2010 29 8 678 1.2 0.4, 2.0 RPR and TPHA 0.2 ‐0.1, 0.5 3 Mwanza, Tanzania (2002) Watson‐Jones 2002 30 106 1,809 5.9 4.8, 6.9 RPR and TPHA 5.0 3.0, 6.0 2 Harare, Zimbabwe (2002‐04) Mapingure 2010 31 8 662 1.2 0.4, 2.0 RPR and Determine Syphilis TP 0.2 ‐0.1, 0.5 1 Moshi, Tanzania (2002‐04) Mapingure 2010 31 23 2654 0.9 0.5, 1.3 RPR and Determine Syphilis TP 0.5* 0.2, 0.8 1

2011 32 ‐ Multicenter, Tanzania (2003‐04) Swai 2006 1,261 17,277 7.3 6.9, 7.7 RPR only 3.2 2.9, 3.4 57 Sofala, Mozambique (2003‐04) Montoya 2006 33 32 381 8.4 5.6, 11.2 RPR and TPHA 7.5 4.9, 10.2 6 34 2000 Rural Tanzania (2003‐04) Yahya‐Malima 2008 21 1,296 1.6 1.0, 2.5 RPR and TPHA 0.6 0.2, 1.1 6 Manhiça, Mozambique (2003‐05) Menendez 2008 35 122 1,030 11.8 9.9, 13.8 RPR only 8.3 4.9, 10.2 1 Entebbe, Uganda (2004) Tann 2006 36 4 245 1.6 0.1, 3.2 RPR and TPHA 0.7 ‐0.4, 1.7 1 Multicenter, Mozambique (2004) Lujan 2008 37 53 1,117 4.7 3.5, 6.0 RPR and TPHA 3.8 2.7, 5.0 2 Entebbe, Uganda (2003‐05) Woodburn 2009 38 18 2,507 0.7 0.4, 1.0 RPR and TPHA 0.5* 0.2, 0.8 1 Southern Malawi (2004‐05) Van Den Broek 2009 39 163 2,297 7.1 6.1, 8.2 VDRL only 5.9 4.9, 6.8 4 Northwest Somalia (2004) Abdalla 2010 40 21 1,559 1.3 0.8, 1.9 RPR and TPHA 0.4 ‐0.1, 0.2 4 Gondar, Ethiopia (2005) Mulu 2007 41 5 480 1.0 0.1, 2.0 RPR and TPHA 4.5 3.9, 5.1 1

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eTable 1. Syphilis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐Saharan Africa (continued)

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities West and Central Africa Kinshasa, Zaire (1990) Vuylsteke 1993 42 13 1,160 1.1 0.5, 1.7 RPR and TPHA 0.1 ‐0.1, 0.3 4 Abidjan, Côte d’Ivoire (1992) Diallo 1997 43 6 545 1.1 0.2, 2.0 RPR and TPHA 0.1 ‐0.2, 0.4 1 Cotonou, Benin (1993) Rodier 1995 44 5 205 2.4 0.3, 4.5 VDRL and TPHA 1.5 ‐0.2, 3.1 1 Multicenter, Burkina Faso (1994) Meda 1997 45 23 645 3.6 2.1, 5.0 RPR and TPHA 2.6 1.4, 3.9 2

1999 46 ‐ Libreville, Gabon (1994‐95) Bourgeois 1998 19 646 2.9 1.6, 4.2 RPR only 0.5* 0.05, 1.0 3 Yaounde, Cameroon (1994‐96) Mbopi Keou 1998 47 696 4,100 17.0 15.8, 18.1 TPHA only 16.3 15.2, 17.4 1 48 1990 Bangui, Central African Rep (1996) Blankhart 1999 30 451 6.7 4.4, 9.0 RPR and TPHA or VDRL and TPHA 5.8 3.6, 7.9 3 Bobo‐Dioulasso, Burkina Faso (1995‐98) Sombie 2000 49 26 10,980 0.2 0.2, 0.3 RPR and TPHA 0.5* 0.4, 0.6 3 Enugu, Nigeria (1997‐2001) Ikeme 2006 50 86 6,881 1.3 1.0, 1.5 VDRL only 0.5* 0.4, 0.7 1 Ilorin, Nigeria (2000) Aboyeji 2003 51 4 230 1.7 0.1, 3.4 RPR and TPHA 0.8 ‐0.4, 1.9 1 Maiduguri, Nigeria (1999‐2008) Bukar 2009 52 9 18,101 0.1 0.0, 0.1 RPR and TPHA 0.5* 0.4, 0.6 1 Accra, Ghana (2000‐01) Apea‐Kubi 2004 53 21 294 7.1 4.2, 10.1 RPR and TPHA 6.3 3.5, 9.0 1

2011 54 ‐ Jos, Nigeria (2002‐03) Sagay 2005 7 2657 0.3 0.1, 0.5 RPR and TPHA 0.5* 0.2, 0.8 1 Multicenter, Burkina Faso (2003) Kirakoya 2010 55 38 2133 1.8 1.2, 2.3 VDRL and TPHA 0.8 0.4, 1.2 98 56 2000 Kinshasa, DRC (2004) Kinoshita‐Moleka 2008 0 529 0.0 0.0, 0.0 RPR and TPHA 0.5* ‐0.1, 1.1 2 Osogbo, Nigeria (2004‐06) Taiwo 2007 57 15 505 3.0 1.5, 4.5 RPR and TPHA 2.0 0.8, 3.2 2

RPR = Rapid plasma reagin VDRL = Venereal disease research laboratory TPHA = Treponema pallidum haemagglutination MHA‐TP = Micro haemagglutination assay–Treponema pallidum IgG = Immunoglobulin G FTA‐Abs = Fluorescent treponemal antibody absorption * The corrected point prevalence estimate was equal to zero with no variance and is not shown in the eFigure

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 2. Neisseria gonorrhoeae Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐ Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Blantyre, Malawi (1990‐93) Taha 1999 1 376 9104 4.1 3.7, 4.5 Culture 5.2 4.7, 5.6 1 Vilanculos, Mozambique (1991‐92) Vuylsteke 1993 3 14 201 7.0 3.5, 10.5 Culture 8.7 4.8, 12.6 1 Mwanza, Tanzania (1992‐93) Mayaud 1995 6 20 964 2.1 1.2, 3.0 Culture 2.6 1.6, 3.6 12 Dar es Salaam, Tanzania (1993) Mwakagile 1996 8 28 777 3.6 2.3, 4.9 Culture 4.5 3.1, 6.0 1 Blantyre, Malawi (1993) Taha 1998 9 54 2,161 2.5 1.8, 3.2 Culture 3.1 2.4, 3.9 1

1999 11 ‐ Nairobi, Kenya (1994) Thomas 1996 7 286 2.5 0.7, 4.2 Culture 3.1 1.1, 5.1 1 Mwanza, Tanzania (1994) Mayaud 1998 14 15 660 2.3 1.1, 3.4 Culture 2.8 1.6, 4.1 1 12 1990 Rwandan camp, Tanzania (1994) Mayaud 1997 3 100 3.0 ‐0.3, 6.3 Gram stain 0.5* ‐0.9, 1.9 1** Blantyre, Malawi (1995) Taha 1998 9 20 808 2.5 1.4, 3. Culture 3.1 1.9, 4.3 1 Nairobi, Kenya (1997) Fonck 2000 19 10 334 3.0 1.2, 4.8 Culture 3.7 1.7, 5.8 10 Khartoum, Sudan (1999) Ortashi 2004 23 3 151 2.0 ‐0.2, 4.2 Culture 2.5 0.0, 5.0 1 Gaborone, Botswana (2000‐01) Romoren 2004 58 21 561 3.7 2.2, 5.3 LCR cervical swab 2.8 1.5, 4.2 13 Manhiça, Mozambique (2000) Menendez 2010 28 27 145 18.6 12.3, 25.0 Culture and gram stain 23.3 16.4, 30.2 1 Dar es Salaam, Tanzania (2001‐03) Aboud 2008 59 1 428 0.2 ‐0.2, 0.7 Gram stain 0.5* ‐0.2, 1.2 1 Blantyre, Malawi (2001‐03) Aboud 2008 59 2 474 0.4 ‐0.2, 1.0 Gram stain 0.5* ‐0.1, 1.1 1

2011 59 ‐ Lilongwe, Malawi (2001‐03) Aboud 2008 26 748 3.5 2.2, 4.8 Gram stain 0.5* ‐0.01, 1.0 1 Lusaka, Zambia (2001‐03) Aboud 2008 59 10 642 1.6 0.6, 2.5 Gram stain 0.5* ‐0.05, 1.0 1 25 2000 Moshi, Tanzania (1999‐2004) Msuya 2007 17 3,046 0.6 0.3, 0.8 Culture or gram stain 0.5* 0.3, 0.8 3 Entebbe, Uganda (2004) Tann 2006 36 10 233 4.3 1.7, 6.9 PCR cervical swab 1.4 ‐0.1, 3.0 1 Multicenter, Mozambique (2004) Lujan 2008 37 21 835 2.5 1.5, 3.6 PCR urine 2.8 1.7, 3.9 2 West and Central Africa Kinshasa, Zaire (1990) Vuylsteke 1993 42 19 1,160 1.6 0.9, 2.3 Culture 2.1 1.2, 2.9 4 60

Ile‐Ife, Nigeria (1990‐91) Okonofua 1995 9 86 10.5 4.0, 17.0 Gram stain 0.5* ‐1.0, 2.0 1 Abidjan, Côte d’Ivoire (1992) Diallo 1997 43 20 546 3.7 2.1, 5.2 Culture 4.6 2.8, 6.3 1 61

1999 Praia, Cape Verde (1993) Wessel 1998 17 350 4.9 2.6, 7.1 PCR cervical swab 2.1 0.6, 3.6 1 ‐ Multi‐ Burkina Faso (1994) Meda 1997 45 23 645 3.6 2.1, 5.0 Gram stain 0.5* ‐0.05, 1.0 2 Libreville, Gabon (1994‐95) Bourgeois 1998 46 12 646 1.9 0.8, 2.9 Culture or gram stain 0.5* ‐0.05, 1.0 3 1990 Bangui, Cent African Rep (1996) Blankhart 1999 48 14 451 3.1 1.5, 4.7 Culture 3.9 2.1, 5.7 3 Abidjan, Côte d’Ivoire (1996‐97) Faye‐Kette 2000 62 9 551 1.6 0.6, 2.7 Gram stain 0.5* ‐0.1, 1.1 1 Ilorin, Nigeria (2000) Aboyeji 2003 51 3 230 1.3 ‐0.2, 2.8 Culture 1.6 ‐0.0, 3.3 1 2000‐ 53 2011 Accra, Ghana (2000‐01) Apea‐Kubi 2004 1 261 0.4 ‐0.4, 1.1 PCR cervical swab 0.5* ‐0.4, 1.4 1 Kinshasa, Dem Rep Congo (2004) Kinoshita‐Moleka 2008 56 2 521 0.4 ‐0.2, 0.9 PCR cervical swab 0.5* ‐0.1, 1.1 2

PCR = Polymerase chain reaction LCR = Ligase chain reaction * The corrected point prevalence estimate was equal to zero with no variance and is not shown in the eFigure ** Refugee camp

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 3. Chlamydia trachomatis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐ Saharan Africa

Vilanculos, Mozambique (1991‐92) Vuylsteke 1993 11 141 7.8 3.4, 12.2 Culture cervical swab 0.5* ‐0.7, 1.7 1 Mwanza, Tanzania (1992‐93) Mayaud 1995 6 64 964 6.6 5.1, 8.2 EIA 6.0 4.5, 7.5 12 11

1999 Nairobi, Kenya (1994) Thomas 1996 25 286 8.7 5.5, 12.0 EIA 8.8 5.5, 12.0 1 ‐ Mwanza, Tanzania (1994) Mayaud 1998 14 39 660 5.9 4.1, 7.7 EIA 5.1 3.4, 6.8 1 Nairobi, Kenya (1997) Fonck 2000 19 36 334 10.8 7.5, 14.1 PCR cervical swab 10.4 7.2, 13.7 2 1990 Khartoum, Sudan (1999) Ortashi 2004 23 30 151 19.9 13.5, 26.2 EIA 23.2 16.5, 29.9 1 Gaborone, Botswana (2000‐01) Romoren 2004 58 42 557 7.5 5.4, 9.7 LCR cervical swab 7.6 5.3, 9.7 13 28

Manhiça, Mozambique (2000) Menendez 2010 15 151 9.9 5.2, 14.7 DNA ID‐assay cervical swab 9.1 4.5, 13.7 1 Lusaka, Zambia (2001‐03) Aboud 2008 59 39 642 6.1 4.2, 7.9 EIA 5.3 3.6, 7.0 1 59

2011 Dar es Salaam, Tanzania (2001‐03) Aboud 2008 12 343 3.5 1.6, 5.4 EIA 2.0 0.5, 3.4 1 ‐ Blantyre, Malawi (2001‐03) Aboud 2008 59 4 474 0.8 0.0, 1.7 EIA 0.5* ‐0.1, 1.2 1 Lilongwe, Malawi (2001‐03) Aboud 2008 59 2 748 0.3 ‐0.1, 0.6 EIA 0.5* 0.01, 1.0 1 2000 Entebbe, Uganda (2004) Tann 2006 36 14 236 5.9 2.9, 9.0 PCR cervical swab 5.5 2.6, 8.4 1 Multicenter, Mozambique (2004) Lujan 2008 37 34 835 4.1 2.7, 5.4 PCR urine 4.3 2.9, 5.7 2 West and Central Africa Pikine, Senegal (1990) Van Dyck 1992 63 55 377 14.6 11.0, 18.2 Culture or EIA 16.4 12.6, 20.1 1 42

Kinshasa, Zaire (1990) Vuylsteke 1993 60 1,160 5.2 3.9, 6.5 EIA 4.1 3.0, 5.3 4 Abidjan, Côte d’Ivoire (1992) Diallo 1997 43 25 452 5.5 3.4, 7.6 EIA 4.6 2.7, 6.5 1 61

1999 Praia, Cape Verde (1993) Wessel 1998 46 350 13.1 9.6, 16.7 PCR cervical swab 12.9 9.3, 16.3 1 ‐ Multicenter, Burkina Faso (1994) Meda 1997 45 20 645 3.1 1.8, 4.4 EIA 1.4 0.5, 2.4 2 Libreville, Gabon (1994‐95) Bourgeois 1998 46 64 646 9.9 7.6, 12.2 EIA 10.3 7.9, 12.6 3 1990 Bangui, CAR (1996) Blankhart 1999 48 28 451 6.2 4.0, 8.4 Indirect immunofluorescence 4.3 2.5, 6.2 3 Abidjan, Côte d’Ivoire (1996‐97) Faye‐Kette 2000 62 41 551 7.4 5.3, 9.6 EIA 7.1 4.9, 9.2 1 2000‐ Accra, Ghana (2000‐01) Apea‐Kubi 2004 53 9 261 3.5 1.2, 5.7 PCR cervical swab 3.0 0.9, 5.1 1 2011 Kinshasa, DRC (2004) Kinoshita‐Moleka 2008 56 9 521 1.7 0.6, 2.9 PCR cervical swab 6.1 4.0, 8.3 2

PCR = Polymerase chain reaction LCR = Ligase chain reaction EIA = Enzyme immunoassay * The corrected point prevalence estimate was equal to zero with no variance and is not shown in the eFigure

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 4. Trichomonas vaginalis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐ Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Blantyre, Malawi (1990‐93) Taha 1999 1 2838 9,137 31.1 30.2, 32.1 Wet‐mount microscopy 51.6 50.5, 52.6 1 Vilanculos, Mozambique (1991‐92) Vuylsteke 1993 3 46 201 22.9 17.1, 28.7 Wet‐mount microscopy 38.1 31.4, 44.9 1 Mwanza, Tanzania (1992‐93) Mayaud 1995 6 264 964 27.4 24.6, 30.2 Wet‐mount microscopy 45.6 42.5, 48.8 12 Dar es Salaam, Tanzania (1993) Mwakagile 1996 8 176 777 22.7 19.7, 25.6 Wet‐mount microscopy 37.8 34.3, 41.2 1 Blantyre, Malawi (1993) Taha 1998 9 62 2,161 2.9 2.2, 3.6 Wet‐mount microscopy 4.8 3.8, 5.7 1

1999 11 ‐ Nairobi, Kenya (1994) Thomas 1996 57 286 19.9 15.3, 24.6 Wet‐mount microscopy 33.2 27.8, 38.7 1 Mwanza, Tanzania (1994) Mayaud 1998 14 108 660 16.4 13.5, 19.2 Wet‐mount microscopy 27.3 23.9, 30.7 1 12 1990 Rwandan camp, Tanzania (1994) Mayaud 1997 31 100 31.0 21.9, 40.1 Wet‐mount microscopy 51.7 41.9, 61.5 1* Mwanza, Tanzania (not reported) Mayaud 1997 13 627 2,282 27.5 25.6, 29.3 Wet‐mount microscopy 45.8 43.8, 47.8 12 Blantyre, Malawi (1995) Taha 1998 9 19 808 2.4 1.3, 3.4 Wet‐mount microscopy 3.9 2.6, 5.3 1 Nairobi, Kenya (1997) Fonck 2000 19 86 334 25.8 21.1, 30.4 Wet‐mount microscopy 42.9 37.6, 48.2 2 Khartoum, Sudan (1999) Ortashi 2004 23 11 151 7.3 3.1, 11.4 Wet‐mount microscopy 12.1 6.9, 17.4 1 Moshi, Tanzania (1999‐2004) Msuya 2007 25 207 2,917 7.1 6.2, 8.0 Wet‐mount microscopy 11.8 10.7, 13.0 3 Gaborone, Botswana (2000‐01) Romoren 2007 64 132 703 18.8 15.9, 21.7 Wet‐mount microscopy 31.3 27.9, 34.7 13 28

Manhiça, Mozambique (2000) Menendez 2010 78 254 30.7 25.0, 36.4 Wet‐mount microscopy 51.2 45.0, 57.3 1 Lilongwe, Malawi (2001‐03) Aboud 2008 59 180 748 24.1 21.0, 27.1 Wet‐mount microscopy 40.1 36.6, 43.6 1 59

2011 Lusaka, Zambia (2001‐03) Aboud 2008 134 642 20.9 17.7, 24.0 Wet‐mount microscopy 34.8 31.1, 38.5 1 ‐ Blantyre, Malawi (2001‐03) Aboud 2008 59 98 474 20.7 17.0, 24.3 Wet‐mount microscopy 34.5 30.2, 38.7 1 Dar es Salaam, Tanzania (2001‐03) Aboud 2008 59 18 428 4.2 2.3, 6.1 Wet‐mount microscopy 7.0 4.6, 9.4 1 2000 Moshi, Tanzania (2002‐04) Mapingure 2010 31 127 2555 5.0 4.2, 5.9 Wet‐mount microscopy 8.3 7.2, 9.4 1 Harare, Zimbabwe (2002‐04) Mapingure 2010 31 80 680 11.8 9.4, 14.2 Wet‐mount microscopy 19.6 16.6, 22.6 1 Harare, Zimbabwe (2002‐03) Kurewa 2010 29 80 678 11.8 9.4, 14.2 Wet‐mount microscopy 19.7 16.7, 22.7 3 Entebbe, Uganda (2004) Tann 2006 36 43 249 17.3 12.6, 22.0 In‐pouch culture 18.0 13.2, 22.8 1 West and Central Africa Jos, Nigeria (not reported) Ogbonna 1991 65 156 500 31.2 27.1, 35.3 Wet‐mount microscopy 52.0 47.6, 56.4 2 42

Kinshasa, Zaire (1990) Vuylsteke 1993 213 1,160 18.4 16.1, 20.6 Wet‐mount microscopy 30.6 28.0, 33.3 4 Ile‐Ife, Nigeria (1990‐91) Okonofua 1995 60 2 86 2..3 ‐0.9, 5.5 Wet‐mount microscopy 3.9 ‐0.2, 8.0 1 43

1999 Abidjan, Côte d’Ivoire (1992) Diallo 1997 72 546 13.2 10.3, 16.0 Wet‐mount microscopy 22.0 18.5, 25.5 1 ‐ Multicenter, Burkina Faso (1994) Meda 1997 45 90 645 14.0 11.3, 16.6 Wet‐mount microscopy 23.3 20.0, 26.5 2 Libreville, Gabon (1994‐95) Bourgeois 1998 46 69 646 10.7 8.3, 13.1 Wet‐mount microscopy 17.8 14.9, 20.8 3 1990 Bangui, Central African Rep (1996) Blankhart 1999 48 45 451 10.0 7.2, 12.7 Wet‐mount microscopy 16.6 13.2, 20.1 3 Abidjan, Côte d’Ivoire (1996‐97) Faye‐Kette 2000 62 74 551 13.4 10.6, 16.3 Wet‐mount microscopy 22.4 18.9, 25.9 1 Ilorin, Nigeria (2000) Aboyeji 2003 51 11 230 4.8 2.0, 7.5 Wet‐mount microscopy 8.0 4.5, 11.5 1 ‐ Jos, Nigeria (2002‐03) Sagay 2005 54 41 2,657 1.5 1.0, 2.0 Wet‐mount microscopy 2.6 2.0, 3.2 1 North‐eastern Nigeria (2003‐04) Nwosu 2007 66 17 201 8.4 4.6, 12.3 Wet‐mount microscopy 14.1 9.3, 18.9 1 2000 2011 Multicenter, Burkina Faso (2003) Kirakoya 2008 67 32 2,133 1.5 1.0, 2.0 In‐pouch culture 1.6 1.0, 2.1 4

* Refugee camp

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eTable 5. Bacterial Vaginosis Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Blantyre, Malawi (1990) Taha 1999 1 640 2077 30.8 28.8, 32.8 Amsel 58.8 56.7, 60.9 1 Blantyre, Malawi (1993) Taha 1999 1 290 661 43.9 40.1, 47.7 Amsel 85.5 82.8, 88.1 1 Nairobi, Kenya (1994) Thomas 1996 11 59 286 20.6 15.9, 25.3 Clue cell count 47.7 41.9, 53.4 1

1999 12 ‐ Rwandan camp, Tanzania (1994) Mayaud 1997 16 100 16.0 8.8, 23.2 Clue cell count 35.1 25.8, 44.5 1* Mwanza, Tanzania (1994) Mayaud 1998 14 159 660 24.1 20.8, 27.4 Clue cell count 57.0 53.2, 60.8 1 68 1990 Multicenter, Zimbabwe (1999‐2001) Tolosa 2006 51 209 24.4 18.6, 30.2 Nugent 23.5 17.8, 29.3 1** Moshi, Tanzania (1999‐2004) Msuya 2007 25 661 3,046 21.7 20.2, 23.2 Amsel 40.2 38.5, 42.0 3 Gaborone, Botswana (2000‐01) Romoren 2007 64 264 703 37.6 34.0, 41.1 Nugent 39.5 35.9, 43.1 13 Lilongwe, Malawi (2001‐03) Aboud 2008 59 329 748 44.0 40.4, 47.5 Nugent 47.3 43.7, 50.8 1 Blantyre, Malawi (2001‐03) Aboud 2008 59 239 474 50.4 45.9, 54.9 Nugent 55.1 50.6, 59.6 1 Lusaka, Zambia (2001‐03) Aboud 2008 59 251 642 39.1 35.3, 42.9 Nugent 41.3 37.5, 45.14 1

2011 59 ‐ Dar es Salaam, Tanzania (2001‐03) Aboud 2008 255 428 59.6 54.9, 64.2 Nugent 66.2 61.7, 70.7 1 Harare, Zimbabwe (2002‐04) Mapingure 2010 31 195 598 32.6 28.8, 36.4 Amsel 62.5 58.6, 66.4 1 31 2000 Moshi, Tanzania (2002‐04) Mapingure 2010 533 2555 20.9 19.3, 22.5 Amsel 38.5 36.6, 40.4 1 Harare, Zimbabwe (2002‐03) Kurewa 2010 29 221 678 32.6 29.1, 36.1 Amsel 62.4 58.8, 66.1 3 Entebbe, Uganda (2004) Tann 2006 36 117 247 47.4 41.1, 53.6 Nugent 51.4 45,1, 58.0 1 West and Central Africa Praia, Cape Verde (1993) Wessel 1998 61 107 350 30.6 25.7, 35.4 Clue cell count 74.5 70.0, 79.1 1 45

‐ Multicenter, Burkina Faso (1994) Meda 1997 83 645 12.9 10.3, 15.5 Amsel 22.2 19.0, 25.4 2 Libreville, Gabon (1994‐95) Bourgeois 1998 46 148 646 22.9 19.7, 26.2 Nugent 21.8 18.5, 24.9 3

1999 48 1999 Bangui, Central African Rep (1996) Blankhart 1999 132 453 29.1 25.0, 33.3 Unspecified clue cell count 70.7 66.5, 74.8 3 Abidjan, Côte d’Ivoire (1996‐97) Faye‐Kette 2000 62 170 551 30.9 27.0, 34.7 Spiegel 41.1 37.0, 45.3 1 2000‐ Jos, Nigeria (2002‐03) Sagay 2005 54 466 2657 17.5 16.1, 18.9 Amsel 31.7 29.9, 33.5 1 2011 Multicenter, Burkina Faso (2003) Kirakoya‐Moleka 2008 67 138 2,133 6.5 5.4, 7.5 Nugent 1.8 1.2, 2.3 2

* Refugee camp * Multi‐center study with only one site in sub‐Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Kilifi, Kenya (1993) Shulman 1996 69 65 275 23.6 18.6, 28.7 Giemsa stain microscopy 28.7 23.3, 34.0 1 Chikwawa, Malawi (1993‐94) Verhoeff 1998 70 109 575 18.9 15.7, 22.1 Giemsa stain microscopy 21.5 18.1, 24.8 1 Chikwawa, Malawi (1993‐95) Verhoeff 1999 71 743 3,913 19.0 17.8, 20.2 Giemsa stain microscopy 21.5 20.2, 22.8 1 Kisumu, Kenya (1994‐96) Parise 1998 72 330 736 44.8 41.2, 48.4 Giemsa stain microscopy 61.3 57.8, 64.8 2 Hoima, Uganda (1996‐98) Ndyomugyenyi 1999 73 530 853 62.1 58.9, 65.4 Giemsa stain microscopy 87.9 85.7, 90.1 1 17

Kisumu, Kenya (1996‐97) Ayisi 2000 583 2,844 20.5 19.0, 22.0 Giemsa stain microscopy 23.9 22.3, 25.4 1 Kisumu, Kenya (1996‐98) Van Eijk 2001 74 953 4,608 20.7 19.5, 21.9 Giemsa stain microscopy 24.1 22.9, 25.4 1 75

1999 Kisumu, Kenya (1996‐97) Van Eijk 2003 380 2,502 15.2 13.8, 16.6 Giemsa stain microscopy 15.7 14.3, 17.1 1 ‐ Kisumu, Kenya (1996‐99) Van Eijk 2002 76 1,105 5,093 21.7 20.6, 22.8 Giemsa stain microscopy 25.7 24.5, 26.9 1 Kigoma, Tanzania (not reported) Mnyika 2000 77 66 705 9.4 7.2, 11.5 Giemsa stain microscopy 6.7 4.9, 8.6 1 1990 Blantyre, Malawi (1997‐98) Rogerson 2000 78 2,034 4,764 42.7 41.3, 44.1 PCR 41.1 39.7, 42.5 1 Kwale, Kenya (1997‐98) Tobian 2000 79 54 102 52.9 43.3, 62.6 PCR** 53.6 43.9, 63.3 1 Blantyre, Malawi (1997‐99) Rogerson 2000 80 85 339 25.1 20.5, 29.7 Giemsa stain microscopy 30.9 26.0, 35.8 1 Medani, Sudan (1997) Ahmed 2002 81 324 550 58.9 54.8, 63.0 Giemsa stain microscopy** 82.9 80.0, 86.1 1 Kampala, Uganda (1998) Kasumba 2000 82 46 537 8.6 6.2, 10.9 Giemsa stain microscopy** 5.5 3.6, 7.4 1 Manhiça, Mozambique (1998) Saute 2002 83 156 672 23.2 20.0, 26.4 Giemsa stain microscopy 28.0 24.6, 31.4 10 Blantyre, Malawi (2000) Mankhambo 2002 84 70 135 51.9 43.4, 60.3 PCR** 52.3 43.8, 60.7 1 Multi‐ (stable trans), Ethiopia (2000‐01) Newman 2003 85 26 249 10.4 6.6, 14.2 Giemsa stain microscopy 0.5* ‐0.4, 1.5 1 Multi‐(unstable trans), Ethiopia (2000‐01) Newman 2003 85 13 713 1.8 0.8, 2.8 Giemsa stain microscopy 8.4 4.9, 11.8 3 New Halfa, Sudan (2001‐02) Elghazali 2003 86 15 86 17.4 9.4, 25.5 Giemsa stain microscopy 19.1 10.8, 27.5 1 Morogoro, Tanzania (2001‐02) Wort 2006 87 494 1684 29.3 27.1, 31.5 Giemsa stain microscopy** 37.4 35.1, 39.8 1 Multicenter, Rwanda (2002) Van Geertruyden 2005 88 195 1,432 13.6 11.8, 15.4 Giemsa stain microscopy 13.3 11.5, 15.0 6 Blantyre, Malawi (2002‐03) Kalilani 2006 89 372 1,172 31.7 29.1, 34.4 Giemsa stain microscopy 41.1 38.3, 44.0 2 Multicenter, Kenya (2003) Parise 2003 90 157 339 46.3 41.0, 51.6 Giemsa stain microscopy 63.6 58.4, 68.7 9 New Halfa, Sudan (2003‐04) Adam 2005 91 102 744 13.7 11.2, 16.2 Giemsa stain microscopy 54.1 45.9, 62.3 1 New Halfa, Sudan (2003‐04) Adam 200592 57 142 40.1 32.0, 48.2 Giemsa stain microscopy 13.4 11.0, 15.9 1

2011 33 ‐ Sofala, Mozambique (2003‐04) Montoya 2006 78 587 13.3 10.5, 16.0 Giemsa stain microscopy 12.8 10.1, 15.5 6 Multicenter, Mozambique (2003‐04) Brentlinger 2007 93 255 684 37.3 33.7, 40.9 Giemsa stain microscopy 49.7 45.9, 53.4 5 94 2000 Kisumu, Kenya (2003‐04) Ouma 2007 123 684 18.0 15.1, 20.9 Giemsa stain microscopy 20.0 17.0, 23.0 1 Entebbe, Uganda (2003‐05) Hillier 2008 95 268 2,459 10.9 9.7‐, 2.1 Giemsa stain microscopy 9.1 7.9, 10.2 1 Masindi, Uganda (2003‐04) Ndyomugyenyi 2008 96 281 802 35.0 31.7, 38.4 Giemsa stain microscopy 46.2 42.8, 49.7 1 Mangochi, Malawi (2003‐06) Rantala 2010 97 51 475 10.7 7.9, 13.5 PCR 2.1 0.8, 3.4 1 Manhiça, Mozambique (2003‐05) Serra‐Casas 2011 98 120 399 30.0 25.5, 34.5 PCR 25.7 21.4, 30.0 1 Southern Malawi (2004‐05) Van Den Broek 2009 39 572 2,297 24.9 23.1, 26.7 Giemsa stain microscopy 30.6 28.7, 32.5 4 Mbarara, Uganda (2006‐09) Piola 2009 99 329 1197 27.5 25.0, 30.0 Giemsa stain microscopy 34.6 31.9, 37.3 1 Mukono, Uganda (not reported) Mbonye 2008 100 573 2,344 24.5 22.7, 26.2 Giemsa stain microscopy 30.0 28.1, 31.8 3*** Multicenter, Mozambique (2004) Lujan 2008 37 53 1,117 4.7 3.5, 6.0 Giemsa stain microscopy 0.5* 0.1, 1.0 2

PCR = Polymerase chain reaction * The corrected point prevalence estimate was equal to zero with no variance and is not shown in the eFigure ** Measured at delivery *** ANC delivered through facilities and out‐reach teams

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 6. Peripheral Malaria Point Prevalence Estimates Among Pregnant Women at Antenatal Care Facilities in Sub‐Saharan Africa (continued) Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities West and Central Africa North Kivu, DRC (not reported) Meuris 1993 101 80 461 17.4 13.9, 20.8 Giemsa stain microscopy 19.0 15.4, 22.6 1 Freetown, Sierra Leone (not reported) Morgan, 1994 102 142 768 18.5 15.7, 21.2 Giemsa stain microscopy 20.8 17.9, 23.6 1 Ibadan, Nigeria (not reported) Achidi 1997 103 26 116 22.4 14.8, 30.0 Giemsa stain microscopy** 26.8 18.7, 34.9 1 Dabou, Côte d’Ivoire (not reported) Watson, 1998 104 11 26 42.3 23.3, 61.3 Giemsa stain microscopy 57.4 38.4, 76.4 1 Multicenter, Nigeria (1992) Egwunyenga 1997 105 292 656 44.5 40.7, 48.3 Giemsa stain microscopy** 60.8 57.1, 64.5 3 Farafenni, Gambia (1994) Menendez 1994 106 72 262 27.5 22.1, 32.9 Giemsa stain microscopy 34.6 28.8, 40.4 NA*** Bauchi, Nigeria (1994‐95) Egwunyenga 1996 107 181 830 21.8 19.0, 24.6 Giemsa stain microscopy 25.9 22.9, 28.9 1 Jos, Nigeria (1994‐95) Egwunyenga 1996 107 150 652 23.0 19.8, 26.2 Giemsa stain microscopy** 27.7 24.3, 31.1 1 Eku, Nigeria (1994‐95) Egwunyenga 1996 107 74 423 17.5 13.9, 21.1 Giemsa stain microscopy** 19.2 15.5, 23.0 1 Kassena‐Nankana, Ghana (1994‐95) Browne 2001 108 527 928 56.8 53.6, 60.0 PCR 58.3 55.1, 61.5 17

Yaounde, Cameroon (1994) Tako 2005 109 405 1,895 21.4 19.5, 23.2 Giemsa stain microscopy 25.2 23.2, 27.1 2 Multicenter, Cameroon (1995‐98) Zhou 2002 110 334 719 46.5 42.8, 50.1 Giemsa stain microscopy 63.7 60.3, 67.3 2 1999 ‐ Yaounde, Cameroon (1995‐98) Walker‐Abbey 2005 111 77 278 27.7 22.4, 33.0 Giemsa stain microscopy 34.9 29.3, 40.5 3 Yaounde, Cameroon (1996‐2001) Tako, 2005 109 297 1,866 15.9 14.3, 17.6 Giemsa stain microscopy 16.8 15.1, 18.5 2 1990 Jos, Nigeria (1997‐98) Egwunyenga 2001 112 816 2,104 38.8 36.7, 40.9 Giemsa stain microscopy 52.0 49.8, 54.1 3 Ebolowa, Cameroon (1997‐98) Salihu 2002 113 55 125 44.0 35.3, 52.7 Giemsa stain microscopy 60.0 51.4, 68.6 1 Bansang, Gambia (1997) Okoko 2002 114 116 313 37.1 31.7, 42.4 Giemsa stain microscopy 49.3 43.8, 54.9 1 Lagos, Nigeria (1998) Anorlu 2001 115 174 477 36.5 32.2, 40.8 Giemsa stain microscopy 48.4 43.9, 52.9 1 Agogo, Ghana (1998) Mockenhaupt 2008 116 335 530 63.2 59.1, 67.3 PCR** 66.1 62.1, 70.1 1 Sagamu, Nigeria (not reported) Sule‐Odu 2002 117 140 564 24.8 21.3, 28.4 Giemsa stain microscopy** 30.5 26.7, 34.3 1 Lagos, Nigeria (1999) Okwa, 2003 118 480 800 60.0 56.6, 63.4 Giemsa stain microscopy 84.6 82.1, 87.1 4 Fako, Cameroon (1999‐2001) Achidi 2005 119 511 1143 44.7 41.8, 47.6 Giemsa stain microscopy 61.1 58.3, 63.9 1 Fako, Cameroon (1999‐2000) Akum 2005 120 248 735 33.7 30.3, 37.2 Giemsa stain microscopy** 44.2 40.6, 47.8 1

** Measured at delivery *** ANC delivered as part of a national village‐based system

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities West and Central Africa Enugu, Nigeria (not reported) Ekejindu 2006 121 23 108 21.3 13.6, 29.0 Giemsa stain microscopy 25.1 16.9, 33.3 1 Abeokuta, Nigeria (not reported) Idowu 2006 122 266 466 57.4 52.6, 61.6 Giemsa stain microscopy 80.1 76.5, 83.8 2 Yaounde, Cameroon (not reported) Mbanya 2007 123 251 1,124 22.3 19.9, 24.8 Giemsa stain microscopy 26.7 24.1, 29.3 2 Ibadan, Nigeria (not reported) Akanbi 2009 124 110 262 42.0 36.0, 48.0 Giemsa stain microscopy 56.9 50.9, 62.9 1 Abakaliki, Nigeria (not reported) Nwonwu 2009 125 56 193 29.0 22.6, 35.4 Giemsa stain microscopy 37.0 30.1, 43.8 2 Ebonyi, Nigeria (not reported) Ogbodo 2009 126 163 272 59.9 54.1, 65.8 Giemsa stain microscopy 84.5 80.2, 88.8 2 Katsina, Nigeria (not reported) Okusanya 2009 127 53 150 35.3 27.7, 43.0 Giemsa stain microscopy 46.7 38.7, 54.7 1 Kano, Nigeria (not reported) Gajida 2010 128 141 360 39.2 34.1, 44.2 Giemsa stain microscopy 52.6 47.4, 57.7 55 Agogo, Ghana (2000‐01) Mockenhaupt 2006 129 445 839 53.0 49.7, 56.4 PCR 53.7 50.3, 57.1 1 Koupéla, Burkina Faso (2001) Sirima 2003 130 129 370 34.9 30.0, 39.7 Giemsa stain microscopy 46.0 40.1, 51.0 6 Koupela, Burkina Faso (2001) Singer 2004 131 204 690 30.0 26.6, 33.4 RDT (MAKROmed) 8.5 6.5, 10.7 2 Nnewi, Nigeria (2001) Nnaji 2007 132 241 420 57.4 52.7, 62.1 Giemsa stain microscopy 80.6 76.8, 84.4 1 Ngali II, Cameroon (2001‐05) Leke 2010 133 33 38 85.6 76.1, 97.6 PCR 94.9 88.0, 102.0 1 Jos, Nigeria (2002) Vanderjagt 2005 134 22 268 8.2 4.9, 11.5 Giemsa stain microscopy 4.9 2.3, 7.5 2 Bamako, Mali (2002) Ayoya 2006 135 14 131 10.7 5.4, 16.0 Giemsa stain microscopy 8.8 3.9, 13.6 1 Nkoranza, Ghana (2003‐04) Tagbor 2006 136 1,338 4,500 29.7 28.4, 31.1 Giemsa stain microscopy 38.1 36.6, 39.5 1 137

Enugu, Nigeria (2003‐04) Okafor 2006 356 625 57.0 53.1, 60.9 Giemsa stain microscopy*** 79.9 76.8, 83.1 1 Kumasi, Ghana (2003‐04) Tagbor 2006 138 1,382 6,370 21.7 20.7, 22.7 Giemsa stain microscopy 25.7 24.6, 26.8 1 139

2011 Farafenni, Gambia (2003‐04) Mbaye 2006 91 1,010 9.0 7.2, 10.8 Giemsa stain microscopy 6.2 4.7, 7.7 14 ‐ Ibadan, Nigeria (2003‐04) Falade 2007 140 29 171 17.0 11.3, 22.6 Giemsa stain microscopy 18.4 12.6, 24.2 1 Boromo, Burkina Faso (2003) Coulibaly 2007 141 128 543 23.6 20.0, 27.1 Giemsa stain microscopy 28.6 24.8, 32.4 12 2000 Ibadan, Nigeria (2003‐04) Falade 2008 142 155 1,848 8.4 7.1, 9.7 Giemsa stain microscopy 5.2 4.2, 6.2 1 Ibadan, Nigeria (2003‐04) Falade 2010 143 125 983 12.7 10.6, 14.8 Giemsa stain microscopy*** 11.9 9.9, 13.9 1 Kinshasa, DRC (2004) Lukuka 2006 144 37 196 18.9 13.4, 24.4 Giemsa stain microscopy*** 21.4 15.6, 27.1 4 Koupéla, Burkina Faso (2004) Sirima 2006 145 22 59 37.3 24.9, 49.6 Giemsa stain microscopy 49.7 36.9, 62.4 8 Benin City, Nigeria (2004‐05) Enato 2007 146 18 199 9.0 5.1, 13.0 Giemsa stain microscopy 6.2 2.9, 9.6 1 Nguru, Nigeria (2005‐06) Kagu 2007 147 230 1,040 22.1 19.6, 24.6 Giemsa stain microscopy 26.3 23.7, 29.0 1 Edo, Nigeria (2005) Enato 2009 148 14 55 25.5 13.9, 37.0 PCR 20.1 9.5, 30.7 2 Agogo, Ghana (2006) Mockenhaupt 2008 116 102 277 36.8 31.1, 42.5 PCR 33.9 28.4, 39.5 1 Abakaliki, Nigeria (2006) Uneke 2008 149 59 300 19.7 15.2, 24.2 Giemsa stain microscopy 22.6 17.8, 27.3 1 Enugu, Nigeria (2006‐07) Nwagha 2009 150 73 125 58.4 49.8, 67.0 PCR 60.2 51.7, 68.8 3 Kumasi, Ghana (2006) Yatich 2010 151 147 746 19.7 16.9, 22.6 Antigen assay 22.6 19.6, 25.6 2 Fako, Cameroon (2007) Anchang‐Kimbi 2009 152 16 287 5.6 2.9, 8.2 Giemsa stain microscopy*** 0.9 ‐0.2, 2.0 1 Lagos, Nigeria (2007‐08) Agomo 2009 153 83 1084 7.7 6.1, 9.2 Giemsa stain microscopy 4.1 2.9, 5.3 2 Accra, Ghana (2009) Wilson 2010 154 72 161 44.7 65.1, 78.9 Giemsa stain microscopy 61.1 53.6, 68.6 1 Enugwu‐Ukwu, Nigeria (not reported) Ekejindu 2011 155 81 100 81.0 73.3, 88.7 Giemsa stain microscopy Corrected prevalence >100%** 1 Ouidah, Benin (2006‐07) Koura 2011 156 13 300 4.3 2.0, 6.6 Giemsa stain microscopy 0.5* ‐0.3, 1.4 2 Benin City, Benin (2009) Aziken 2011 157 71 371 19.1 15.1, 23.1 Giemsa stain microscopy*** 21.8 17.6, 26.0 1

PCR = Polymerase chain reaction * The corrected point prevalence estimate was equal to zero with no variance and is not shown in the eFigure. ** The corrected point prevalence estimate was greater than 100 with no variance and is not shown in the eFigure. ***Measured at delivery

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eTable 7. Placental Malaria Point Prevalence Among Pregnant Women at Delivery in Sub‐Saharan Africa

Site Reference No. women No. women Uncorrected 95% CI Diagnostic method Corrected 95% CI No. ANC (year study conducted) positive tested prevalence (%) prevalence (%) facilities East and Southern Africa Kisumu, Kenya (1996‐99) Van Eijk 2002 76 475 2,502 19.0 17.4, 20.5 Placental impression and blood smears with microscopy 20.0 18.4, 21.6 1 1990‐ Blantyre, Malawi (1997‐99) Rogerson 2000 80 77 232 33.2 27.1, 39.2 Placental impression and blood smears with microscopy 35.8 29.6, 41.9 1 1999 Kampala, Uganda (1998) Kasumba 2000 82 36 537 6.7 4.6, 8.8 Placental blood microscopy 8.5 6.1, 10.8 1 Blantyre, Malawi (not reported) Rogerson 2003 158 124 464 26.7 22.7, 30.8 Placental histology, impression, smears with microscopy 28.6 24.5, 32.7 1 Multicenter, Kenya (not reported) Parise 2003 90 163 726 22.5 19.4, 25.5 Placental blood microscopy 34.1 30.6, 37.5 9

Muheza, Tanzania (2002‐05) Kabyemela 2008 159 55 445 12.4 9.3, 15.5 Placental impress and blood smears with microscopy 25.8 19.7, 32.0 1 Kisumu, Kenya (2003) Kassam 2006 160 58 85 68.2 58.3, 78.1 Placental histology, impression, smears with microscopy 74.7 65.5, 84.0 3

2011 161 ‐ New Halfa, Sudan (2003‐07) Adam 2007 94 293 32.1 26.7, 37.4 Placental histology, impression, smears with microscopy 34.5 29.1, 40.0 1 Manhiça, Mozambique (2003‐05) Serra‐Casas 2011 98 110 343 32.1 27.2, 37.0 PCR 9.3 6.2, 12.4 1 162

2000 Chikwawa, Malawi (2004‐05) Senga 2007 124 636 19.5 16.4, 22.6 Placental blood microscopy and tissue histology 20.6 17.4, 23.7 1 Gadarif, Sudan (2007‐08) Abdelrahim 2009 163 26 150 17.3 11.3, 23.4 Placental histology, impression, smears with microscopy 18.2 12.0, 24.3 1 Gadafir, Sudan (2007‐08) Adam 2009 164 46 236 19.5 14.4, 25.5 Placental histology, impression, smears with microscopy 20.6 15.4, 25.7 1 West and Central Africa North Kivu, DRC Meuris 1993 101 242 461 52.5 47.9, 57.1 Placental histology 57.0 52.5, 61.5 1 Ebolowa, Cameroon (1991‐92) Cot 1995 165 37 64 57.8 45.7, 69.9 Placental blood microscopy 91.6 84.8, 98.4 1

Farafenni, Gambia (1994) Menendez 1994 106 116 198 58.6 51.7, 65.4 Placental blood microscopy and tissue histology 64.0 57.3, 70.7 NA*** Basse, Gambia (not reported) Rasheed 1995 166 60 97 61.9 52.2, 71.5 Placental blood microscopy and tissue histology 67.6 58.3, 76.9 1

1999 111 ‐ Yaounde, Cameroon (1995‐98) Walker‐Abbey 2005 229 278 82.4 77.9, 86.9 Placental blood microscopy Corrected prevalence >100%** 3 Yaounde, Cameroon (1996‐2001) Tako 2005 109 371 1,866 19.9 18.1, 21.7 Placental impression and blood smears with microscopy 21.0 19.1, 22.8 2 114

1990 Bansang, Gambia (1997) Okoko 2002 160 313 51.1 45.6, 56.7 Placental blood microscopy and tissue histology 55.7 50.2, 61.2 1 Guediawaye, Senegal (1998‐99) Ndao 2003 167 674 8310 8.1 7.5, 8.7 Placental blood microscopy 10.8 10.1, 11.4 1 Dakar, Senegal (1998‐99) Ndao 2006 168 785 8273 9.5 8.9, 10.1 Placental impression and blood smears with microscopy 9.4 8.8, 10.1 1 Fako, Cameroon (1999‐2001) Akum 2005 120 233 711 32.8 29.3, 36.2 Placental impression and blood smears with microscopy 23.0 20.6, 25.4 1 Fako, Cameroon (1999‐2001) Achidi 2005 119 248 1143 33.7 19.3, 24.1 Placental impression and blood smears with microscopy 35.3 31.8, 38.8 1 Agogo, Ghana (2000‐01) Mockenhaupt 2006 129 495 839 59.0 55.7, 62.3 PCR 47.5 44.1, 50.9 1 Koupéla, Burkina Faso (2001) Sirima 2003 130 19 61 31.1 19.5, 42.8 Placental blood microscopy 48.2 35.7, 60.8 6 Koupela, Burkina Faso (2001) Singer 2004 131 247 484 51.0 46.6, 55.5 PCR 36.2 31.9, 40.5 2 133 Ngali II, Cameroon (2001‐05) Leke 2010 25 36 69.4 54.4, 84.5 Placental histology, impression, smears with microscopy 76.1 62.1, 90.0 1 Kumasi, Ghana (2003) Owens 2006 169 33 104 31.7 22.8, 40.6 Placental blood microscopy and tissue histology 34.2 25.0, 43.3 1 170

2011 Multicenter, Nigeria (2003‐04) Mokuolu 2009 267 1,875 14.2 12.7, 15.8 Placental blood microscopy and tissue histology 14.7 13.1, 16.3 4 ‐ Ibadan, Nigeria (2003‐04) Falade 2007 140 29 171 17.0 11.3, 22.6 Method not reported ‐ ‐ 1 Ibadan, Nigeria (2003‐04) Falade 2010 143 128 983 13.1 11.0, 15.2 Placental blood microscopy 18.7 16.3, 21.2 1 2000 Koupéla, Burkina Faso (2004) Sirima 2006 145 18 59 30.5 18.8, 42.3 Placental blood microscopy 47.2 34.4, 59.9 1 Kinshasa, Dem Rep Congo (2004) Lukuka 2006 144 42 196 21.4 15.7, 27.2 Placental impression and blood smears with microscopy 22.7 16.8, 28.6 4 Owerri, Nigeria (2004‐05) Ukaga 2007 171 175 586 29.9 26.2, 33.6 Placental blood microscopy 46.1 2 Benin City, Nigeria (2004‐05) Enato 2007 146 14 199 7.0 3.5, 10.6 Placental blood microscopy 9.0 5.0, 13.0 1 Fako, Cameroon (2007) Anchang‐Kimbi 2009 152 185 306 60.5 55.0, 65.9 Placental histology, impression, smears with microscopy 66.1 60.8, 71.4 1 Benin City, Benin (2009) Aziken 2011157 84 371 22.6 18.3, 26.9 Placental blood microscopy 34.4 34.2, 45.7 1

PCR = Polymerase chain reaction ** The corrected point prevalence estimate was greater than 100 with no variance and is not shown in the eFigure. *** ANC delivered as part of a national village‐based system

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eAppendix 1. Search Terms

Infection MeSH terms Free text terms Syphilis Treponema pallidum OR Syphilis AND Topic=(“Syphilis” OR “Treponema pallidum”) Treponema pallidum AND Pregnant AND Africa Treponema pallidum AND Pregnancy AND Africa “Pregnant Women” AND “Africa South of the AND Topic=(Prenatal OR Antenatal OR Syphilis AND Pregnant AND Africa Sahara" Pregnant or Pregnancy) OR Topic=(women) Syphilis AND Pregnancy AND Africa Screen AND Syphilis AND Pregnant AND Africa AND Topic=(Africa) Screen AND Syphilis AND Pregnancy AND Africa Test AND Syphilis AND Pregnant AND Africa Test AND Syphilis AND Pregnancy AND Africa Neisseria Neisseria gonorrhoeae OR Gonorrhea OR Topic=("Neisseria gonorrhoeae") OR Neisseria gonorrhoeae AND Pregnant AND Africa Neisseria gonorrhoeae AND Pregnancy AND Africa gonorrhoeae Gonorrhoea AND Pregnant Women AND Topic=(Gonorrhea) OR Topic=(Gonorrhoea) Gonorrhoea AND Pregnant AND Africa “Africa South of the Sahara” AND Topic= (Prenatal OR Antenatal OR Gonorrhoea AND Pregnancy AND Africa Gonorrhea AND Pregnant AND Africa Pregnant OR Pregnancy) OR Topic=(women) Gonorrhea AND Pregnancy AND Africa AND Topic=(Africa) Screen AND Gonorrhea AND Pregnant AND Africa Screen AND Gonorrhoea AND Pregnant AND Africa Test AND Gonorrhea AND Pregnant AND Africa Test AND Gonorrhoea AND Pregnant AND Africa Chlamydia Chlamydia trachomatis AND Pregnant Topic=(“Chlamydia”) AND Topic= Chlamydia trachomatis AND Pregnant AND Africa Chlamydia trachomatis AND Pregnancy AND Africa trachomatis Women AND "Africa South of the Sahara" (trachomatis) AND Topic=(Prenatal OR Chlamydia AND Pregnant AND Africa Antenatal OR Pregnant OR Pregnancy) OR Chlamydia AND Pregnancy AND Africa Screen AND Chlamydia AND Pregnant AND Africa Topic=(women) AND Topic=(Africa) Screen AND Chlamydia AND Pregnancy AND Africa Test AND Chlamydia AND Pregnant AND Africa Test AND Chlamydia AND Pregnancy AND Africa Trichomonas Trichomonas vaginalis AND Pregnant Topic=("Trichomonas vaginalis OR Trichomonas vaginalis AND Pregnant AND Africa Trichomonas vaginalis AND Pregnancy AND Africa vaginalis Women AND "Africa South of the Sahara" Trichomoniasis") Trichomoniasis AND Pregnant AND Africa AND Topic=(Prenatal OR Antenatal OR Trichomoniasis AND Pregnancy AND Africa Screen AND Trichomoniasis AND Pregnant AND Africa Pregnant OR Pregnancy) OR Topic=(women) Screen AND Trichomoniasis AND Pregnancy AND Africa AND Topic=(Africa) Test AND Trichomoniasis AND Pregnant AND Africa Test AND Trichomoniasis AND Pregnancy AND Africa Bacterial Bacterial vaginosis AND Pregnant Women Topic=("Bacterial vaginosis") AND Bacterial vaginosis AND Pregnant AND Africa Bacterial vaginosis AND Pregnancy AND Africa vaginosis AND "Africa South of the Sahara" Topic=(Prenatal OR Antenatal OR Pregnant Screen AND Bacterial vaginosis AND Pregnant AND Africa OR Pregnancy OR Pregnant) OR Screen AND Bacterial vaginosis AND Pregnancy AND Africa Test AND Bacterial vaginosis AND Pregnant AND Africa Topic=(women) AND Topic=(Africa) Test AND Bacterial vaginosis AND Pregnancy AND Africa Malaria Malaria AND Pregnant Women AND "Africa Topic=("Malaria") AND Topic=(Prenatal OR Malaria AND Pregnant AND Africa Malaria AND Pregnancy AND Africa South of the Sahara" Antenatal OR Pregnancy OR Pregnant) OR Screen AND Malaria AND Pregnant AND Africa Topic=(women) AND Topic=(Africa) Screen AND Malaria AND Pregnancy AND Africa Test AND Malaria AND Pregnant AND Africa Test AND Malaria AND Pregnancy AND Africa

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eAppendix 2. Diagnostic Method Quality Scoring and Published Sensitivity and Specificity Measures

Infection Diagnostic method Sensitivity (%) Specificity (%) Source Syphilis 47 Treponema pallidum haemagglutination (TPHA) only* 100 100 Rapid plasma reagin (RPR) only 86‐100 93‐98 172 Venereal disease research laboratory (VDRL) only 78‐100 98 172 RPR or VDRL and TPHA ‐ 100 100 RPR and TPHA 100 100 ‐

RPR and Determine Syphilis TP 100 100 RPR and Microhemagglutination assay–Treponema pallidum (MHA‐TP) 100 100 ‐

RPR and Immunoglobulin G (ELISA test) 100 100 ‐ 173 Neisseria Gram stain 50‐70 50‐70 Culture or gram stain (score based on less precise method, i.e. mean of gram stain) 50‐70 50‐70 ‐ gonorrhoeae 174 Polymerase chain reaction (PCR) with urine 36‐75 98‐100 175 Culture 80 100 Culture and gram stain (score based on more precise method, i.e. mean of culture) ~80 100 ‐ Ligase chain reaction (LCR) with cervical swab 95‐100 98‐100 175 PCR with cervical swab 89‐97 94‐100 175 Indirect immunofluorescence 46‐64 94‐98 176 Chlamydia 175 trachomatis Culture cervical swab 74‐90 98‐99 Enzyme immunoassay (EIA) 71‐87 97‐99 175 Culture cervical swab or EIA (score based on the less precise method, i.e. mean of EIA) 71‐87 97‐99 ‐ 174 PCR urine 78‐89 99‐100 LCR cervical swab 90‐97 99‐100 175 175 PCR cervical swab 99 99‐100 DNA ID‐assay cervical swab 100 100 ‐ Trichomonas Wet‐mount microscopy 38‐82 100 175 177 vaginalis In‐pouch culture 96 100 178 Clue cells > 20% of epithelium 40 97 Bacterial vaginosis Unspecified clue cell count NA NA ‐ Amsel criteria: 3 or 4 of 4 51 98 178 Spiegel criteria 75 100 179 Nugent score >7 of 10 86‐89 94‐96 180‐181 Peripheral 182‐184 Giemsa stain microscopy 50‐90 95 parasitaemia PCR 91 91 97 Antigen assay (reported as equal to microscopy) RDT (as reported) 89 76 Diagnostic method not reported NA NA ‐ Placental 158 parasitaemia Placental blood microscopy 63 98‐99 PCR 93‐99 73‐76 185 Placental histology 91 98‐99 158

Placental blood microscopy and tissue histology (score based on more precise method, i.e. histology) 91 100 ‐

Placental histology, impression, smears with microscopy (score based on most precise method, i.e. histology) 91 100 ‐ 152 Placental impression and blood smears with microscopy (score based on more precise method, i.e. impression) 91 100 * TPHA is a confirmatory assay and is not recommended for use used alone. Authors of the one paper that cited using TPHA alone wrote that a positive TPHA was considered to be related only to syphilis.47 Thus, sensitivity and specificity of TPHA only, in this epidemiological context, are assumed to be similar to RPR and TPHA or VDRL and TPHA.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 eAppendix 3. References for Meta‐analysis and eAppendix 2

1. Taha TE, Gray RH, Kumwenda NI, et al. HIV infection and disturbances of vaginal flora during pregnancy. J Acquir Immune Defic Syndr Hum Retrovirol. Jan 1 1999;20(1):52-59. 2. Rutgers S. Syphilis in pregnancy: a medical audit in a rural district. Cent Afr J Med. 1993 1993;39(12):248-253. 3. Vuylsteke B, Bastos R, Barreto J, et al. High prevalence of sexually transmitted diseases in a rural area in Mozambique. Genitourin Med. Dec 1993;69(6):427-430. 4. Cossa HA, Gloyd S, Vaz RG, et al. Syphilis and HIV infection among displaced pregnant women in rural Mozambique. Int J STD AIDS. Mar-Apr 1994;5(2):117-123. 5. Jenniskens F, Obwaka E, Kirisuah S, et al. Syphilis control in pregnancy: decentralization of screening facilities to primary care level, a demonstration project in Nairobi, Kenya. Int J Gynaecol Obstet. Jun 1995;48 Suppl:S121-128. 6. Mayaud P, Grosskurth H, Changalucha J, et al. Risk assessment and other screening options for gonorrhoea and chlamydial infections in women attending rural Tanzanian antenatal clinics. Bull World Health Organ. 1995;73(5):621-630. 7. Temmerman M, Fonck K, Bashir F, et al. Declining syphilis prevalence in pregnant women in Nairobi since 1995: another success story in the STD field? Int J STD AIDS. 1999 1999;10(6):405-408. 8. Mwakagile D, Swai ABM, Sandstrom E, Urassa E, Biberfeld G, Mhalu FS. High frequency of sexually transmitted diseases among pregnant women in Dar es Salaam, Tanzania: Need for intervention. East African Medical Journal. 1996;73(10):675-678. 9. Taha TE, Dallabetta GA, Hoover DR, et al. Trends of HIV-1 and sexually transmitted diseases among pregnant and postpartum women in urban Malawi. AIDS. Jan 22 1998;12(2):197-203. 10. Azeze B, Fantahun M, Kidan KG, Haile T. Seroprevalence of syphilis amongst pregnant women attending antenatal clinics in a rural hospital in north west Ethiopia. Genitourin Med. Dec 1995;71(6):347-350. 11. Thomas T, Choudhri S, Kariuki C, Moses S. Identifying cervical infection among pregnant women in Nairobi, Kenya: Limitations of risk assessment and symptom- based approaches. Genitourinary Medicine. 1996;72(5):334-338. 12. Mayaud P, Msuya W, Todd J, et al. STD rapid assessment in Rwandan refugee camps in Tanzania. Genitourin Med. Feb 1997;73(1):33-38. 13. Mayaud P, Mosha F, Todd J, et al. Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomized controlled trial. AIDS. Dec 1997;11(15):1873-1880. 14. Mayaud P, Uledi E, Cornelissen J, et al. Risk scores to detect cervical infections in urban antenatal clinic attenders in Mwanza, Tanzania. Sex Transm Infect. Jun 1998;74 Suppl 1:S139-146. 15. Urassa WK, Kapiga SH, Msamanga GI, Antelman G, Coley J, Fawzi WW. Risk factors for syphilis among HIV-1 infected pregnant women in Dar es Salaam, Tanzania. Afr J Reprod Health. Dec 2001;5(3):54-62.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 16. Tsegaye A, Rinke De Wit TF, Mekonnen Y, et al. Decline in prevalence of HIV-1 infection and syphilis among young women attending antenatal care clinics in Addis Ababa, Ethiopia: results from sentinel surveillance, 1995-2001. J Acquir Immune Defic Syndr. 2002 Jul 2002;30(3):359-362. 17. Ayisi JG, van Eijk AM, ter Kuile FO, et al. Risk factors for HIV infection among asymptomatic pregnant women attending an antenatal clinic in western Kenya. Int J STD AIDS. Jun 2000;11(6):393-401. 18. Kebede E, Chamiso B. Prevalence of syphilis in pregnancy in Addis Ababa. East Afr Med J. Apr 2000;77(4):212-216. 19. Fonck K, Kidula N, Jaoko W, et al. Validity of the vaginal discharge algorithm among pregnant and non-pregnant women in Nairobi, Kenya. Sex Transm Infect. Feb 2000;76(1):33-38. 20. Majoko F, Munjanja S, Nystrom L, Mason E, Lindmark G. Field efficiency of syphilis screening in antenatal care: lessons from Gutu District in Zimbabwe. Cent Afr J Med. Jul-Aug 2003;49(7-8):90-93. 21. Ayisi JG, van Eijk AM, ter Kuile FO, et al. The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya. Aids. Mar 7 2003;17(4):585-594. 22. Fonck K, Claeys P, Bashir F, Bwayo J, Fransen L, Temmerman M. Syphilis control during pregnancy: effectiveness and sustainability of a decentralized program. Am J Public Health. May 2001;91(5):705-707. 23. Ortashi OM, El Khidir I, Herieka E. Prevalence of HIV, syphilis, Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis and candidiasis among pregnant women attending an antenatal clinic in Khartoum, Sudan. J Obstet Gynaecol. Aug 2004;24(5):513-515. 24. Pham L, Woelk GB, Ning Y, et al. Seroprevalence and risk factors of syphilis infection in pregnant women delivering at Harare Maternity Hospital, Zimbabwe. Cent Afr J Med. Mar-Apr 2005;51(3-4):24-30. 25. Msuya SE, Mbizvo EM, Stray-Pedersen B, et al. Decline in HIV prevalence among women of childbearing age in Moshi urban, Tanzania. International Journal of Std & Aids. 2007;18:680-687. 26. Romoren M, Rahman M. Syphilis screening in the antenatal care: a cross-sectional study from Botswana. BMC Int Health Hum Rights. 2006;6:8. 27. Kwiek JJ, Mwapasa V, Alker AP, et al. Socio-demographic characteristics associated with HIV and syphilis seroreactivity among pregnant women in Blantyre, Malawi, 2000-2004. Malawi Med J. Sep 2008;20(3):80-85. 28. Menendez C, Castellsague X, Renom M, et al. Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women from a rural area of southern Mozambique. Infect Dis Obstet Gynecol. 2010;2010. 29. Kurewa NE, Mapingure MP, Munjoma MW, Chirenje MZ, Rusakaniko S, Stray- Pedersen B. The burden and risk factors of Sexually Transmitted Infections and Reproductive Tract Infections among pregnant women in Zimbabwe. BMC Infect Dis. 2010;10:127.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 30. Watson-Jones D, Changalucha J, Gumodoka B, et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J Infect Dis. Oct 1 2002;186(7):940-947. 31. Mapingure MP, Msuya S, Kurewa NE, et al. Sexual behaviour does not reflect HIV-1 prevalence differences: a comparison study of Zimbabwe and Tanzania. J Int AIDS Soc. 2010;13:45. 32. Swai RO, Somi GG, Matee MI, et al. Surveillance of HIV and syphilis infections among antenatal clinic attendees in Tanzania-2003/2004. BMC Public Health. 2006;6:91. 33. Montoya PJ, Lukehart SA, Brentlinger PE, et al. Comparison of the diagnostic accuracy of a rapid immunochromatographic test and the rapid plasma reagin test for antenatal syphilis screening in Mozambique. Bull World Health Organ. Feb 2006;84(2):97-104. 34. Yahya-Malima KI, Evjen-Olsen B, Matee MI, Fylkesnes K, Haarr L. HIV-1, HSV-2 and syphilis among pregnant women in a rural area of Tanzania: prevalence and risk factors. BMC Infect Dis. 2008;8:75. 35. Menendez C, Bardaji A, Sigauque B, et al. A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic. PLoS ONE. 2008;3(4):e1934. 36. Tann CJ, Mpairwe H, Morison L, et al. Lack of effectiveness of syndromic management in targeting vaginal infections in pregnancy in Entebbe, Uganda. Sex Transm Infect. Aug 2006;82(4):285-289. 37. Lujan J, de Onate WA, Delva W, et al. Prevalence of sexually transmitted infections in women attending antenatal care in Tete province, Mozambique. S Afr Med J. Jan 2008;98(1):49-51. 38. Woodburn PW, Muhangi L, Hillier S, et al. Risk factors for helminth, malaria, and HIV infection in pregnancy in Entebbe, Uganda. PLoS Negl Trop Dis. 2009;3(6):e473. 39. van den Broek NR, White SA, Goodall M, et al. The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis. PLoS Med. Dec 2009;6(12):e1000191. 40. Abdalla E, Ekanem E, Said D, Arube P, Gboun M, Mohammed F. The need for a comprehensive response to HIV/ AIDS in north-western Somalia: evidence from a seroprevalence survey. East Mediterr Health J. Feb;16(2):141-145. 41. Mulu A, Kassu A, Tessema B, et al. Seroprevalence of syphilis and HIV-1 during pregnancy in a teaching hospital in northwest Ethiopia. Jpn J Infect Dis. 2007 2007;60(4):193-195. 42. Vuylsteke B, Laga M, Alary M, et al. Clinical algorithms for the screening of women for gonococcal and chlamydial infection: evaluation of pregnant women and prostitutes in Zaire. Clin Infect Dis. Jul 1993;17(1):82-88. 43. Diallo MO, Ettiegne-Traore V, Maran M, et al. Sexually transmitted diseases and human immunodeficiency virus infections in women attending an antenatal clinic in Abidjan, Cote d'Ivoire. Int J STD AIDS. Oct 1997;8(10):636-638.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 44. Rodier MH, Berthonneau J, Bourgoin A, et al. Seroprevalences of toxoplasma, malaria, rubella, cytomegalovirus, HIV and treponemal infections among pregnant women in Cotonou, Republic of Benin. Acta Tropica. 1995;59(4):271-277. 45. Meda N, Sangare L, Lankoande S, et al. Pattern of sexually transmitted diseases among pregnant women in Burkina Faso, West Africa: Potential for a clinical management based on simple approaches. Genitourinary Medicine. 1997;73(3):188- 193. 46. Bourgeois A, Henzel D, Malonga-Mouelet G, et al. Clinical algorithms for the screening of pregnant women for STDs in Libreville, Gabon: which alternatives? Sex Transm Infect. Feb 1998;74(1):35-39. 47. Mbopi Keou FX, Mbu R, Mauclere P, et al. Antenatal HIV prevalence in Yaounde, Cameroon. Int J STD AIDS. Jul 1998;9(7):400-402. 48. Blankhart D, Muller O, Gresenguet G, Weis P. Sexually transmitted infections in young pregnant women in Bangui, Central African Republic. International Journal of Std & Aids. 1999;10(9):609-614. 49. Sombie I, Meda N, Cartoux M, et al. Seroprevalence of syphilis among women attending urban antenatal clinics in Burkina Faso, 1995-8. The DITRAME Study Group. DIminunation de la TRAnsmission Mere-Enfant. Sex Transm Infect. Aug 2000;76(4):314-316. 50. Ikeme AC, Okeke TC. The relevance of VDRL as routine test in pregnant women: a critcal study. Niger J Clin Pract. Jun 2006;9(1):65-67. 51. Aboyeji AP, Nwabuisi C. Prevalence of sexually transmitted diseases among pregnant women in Ilorin, Nigeria. J Obstet Gynaecol. Nov 2003;23(6):637-639. 52. Bukar M, Audu BM, Takai UI, Ajayi BB, Kullima AA. Is routine antenatal screening for syphilis in Nigeria still justified clinically and economically? Saudi Med J. Oct 2009;30(10):1311-1315. 53. Apea-Kubi KA, Yamaguchi S, Sakyi B, Kishimoto T, Ofori-Adjei D, Hagiwara T. Neisseria gonorrhoea, Chlamydia trachomatis, and Treponema pallidum infection in antenatal and gynecological patients at Korle-Bu Teaching Hospital, Ghana. Jpn J Infect Dis. Dec 2004;57(6):253-256. 54. Sagay AS, Kapiga SH, Imade GE, Sankale JL, Idoko J, Kanki P. HIV infection among pregnant women in Nigeria. Int J Gynaecol Obstet. Jul 2005;90(1):61-67. 55. Kirakoya-Samadoulougou F, Defer MC, Yaro S, et al. Low seroprevalence of syphilis in Burkina Faso. Sex Transm Infect. Feb;87(1):35-37. 56. Kinoshita-Moleka R, Smith JS, Atibu J, et al. Low prevalence of HIV and other selected sexually transmitted infections in 2004 in pregnant women from Kinshasa, the Democratic Republic of the Congo. Epidemiol Infect. Sep 2008;136(9):1290- 1296. 57. Taiwo SS, Adesiji YO, Adekanle DA. Screening for syphilis during pregnancy in Nigeria: a practice that must continue. Sex Transm Infect. Aug 2007;83(5):357-358. 58. Romoren M, Rahman M, Sundby J, Hjortdahl P. Chlamydia and gonorrhoea in pregnancy: effectiveness of diagnosis and treatment in Botswana. Sexually Transmitted Infections. 2004;80(5):395-400.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 59. Aboud S, Msamanga G, Read JS, et al. Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia. International Journal of Std & Aids. 2008;19(12):824-832. 60. Okonofua FE, Ako-Nai KA, Dighitoghi MD. Lower genital tract infections in infertile Nigerian women compared with controls. Genitourin Med. Jun 1995;71(3):163-168. 61. Wessel HF, Herrmann B, Dupret A, Moniz F, Brito C, Bergstrom S. Genital infections among antenatal care attendees in Cape Verde. Afr J Reprod Health. Apr 1998;2(1):32-40. 62. Faye-Kette H, La Ruche G, Ali-Napo L, et al. Genital mycoplasmas among pregnant women in Cote d'Ivoire, West Africa: prevalence and risk factors. International Journal of Std & Aids. 2000;11(9):599-602. 63. Van Dyck E, Samb N, Sarr AD, et al. Accuracy of two enzyme immunoassays and cell culture in the detection of Chlamydia trachomatis in low and high risk populations in Senegal. Eur J Clin Microbiol Infect Dis. Jun 1992;11(6):527-534. 64. Romoren M, Velauthapillai M, Rahman M, Sundby J, Klouman E, Hjortdahl P. Trichomoniasis and bacterial vaginosis in pregnancy: inadequately managed with the syndromic approach. Bull World Health Organ. Apr 2007;85(4):297-304. 65. Ogbonna CI, Ogbonna IB, Ogbonna AA, Anosike JC. Studies on the incidence of Trichomonas vaginalis amongst pregnant women in Jos area of Plateau State, Nigeria. Angew Parasitol. Nov 1991;32(4):198-204. 66. Nwosu CO, Djieyep NA. Candidiasis and trichomoniasis among pregnant women in a rural community in the semi-arid zone, north-eastern Nigeria. West Afr J Med. Jan- Mar 2007;26(1):17-19. 67. Kirakoya-Samadoulougou F, Nagot N, Defer MC, Yaro S, Meda N, Robert A. Bacterial vaginosis among pregnant women in Burkina Faso. Sex Transm Dis. Dec 2008;35(12):985-989. 68. Tolosa JE, Chaithongwongwatthana S, Daly S, et al. The International Infections in Pregnancy (IIP) study: Variations in the prevalence of bacterial vaginosis and distribution of morphotypes in vaginal smears among pregnant women. American Journal of Obstetrics and Gynecology. 2006;195(5):1198-1204. 69. Shulman CE, Graham WJ, Jilo H, et al. Malaria is an important cause of anaemia in primigravidae: evidence from a district hospital in coastal Kenya. Trans R Soc Trop Med Hyg. Sep-Oct 1996;90(5):535-539. 70. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Russell WB, Broadhead RL. An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi. Ann Trop Med Parasitol. Mar 1998;92(2):141-150. 71. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead RL. Malaria in pregnancy and its consequences for the infant in rural Malawi. Ann Trop Med Parasitol. Dec 1999;93 Suppl 1:S25-33. 72. Parise ME, Ayisi JG, Nahlen BL, et al. Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 and human immunodeficiency virus infection. Am J Trop Med Hyg. Nov 1998;59(5):813-822. 73. Ndyomugyenyi R, Magnussen P. Anaemia in pregnancy: Plasmodium falciparum infection is an important cause in primigravidae in Hoima district, western Uganda. Ann Trop Med Parasitol. Jul 1999;93(5):457-465. 74. van Eijk AM, Ayisi JG, Ter Kuile FO, et al. Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya. American Journal of Tropical Medicine and Hygiene. 2001;65(5):623-630. 75. van Eijk AM, Ayisi JG, ter Kuile FO, et al. HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya. Aids. Mar 7 2003;17(4):595-603. 76. van Eijk AM, Ayisi JG, ter Kuile FO, et al. Risk factors for malaria in pregnancy in an urban and peri-urban population in western Kenya. Trans R Soc Trop Med Hyg. Nov-Dec 2002;96(6):586-592. 77. Mnyika KS, Kabalimu TK, Rukinisha K, Mpanju-Shumbusho W. Randomised trial of alternative malaria chemoprophylaxis strategies among pregnant women in Kigoma, Tanzania: I. Rationale and design. East African Medical Journal. 2000;77(2):98-104. 78. Rogerson SJ, van den Broek NR, Chaluluka E, Qongwane C, Mhango CG, Molyneux ME. Malaria and anemia in antenatal women in Blantyre, Malawi: a twelve-month survey. Am J Trop Med Hyg. Mar 2000;62(3):335-340. 79. Tobian AA, Mehlotra RK, Malhotra I, et al. Frequent umbilical cord-blood and maternal-blood infections with Plasmodium falciparum, P. malariae, and P. ovale in Kenya. J Infect Dis. Aug 2000;182(2):558-563. 80. Rogerson SJ, Chaluluka E, Kanjala M, Mkundika P, Mhango C, Molyneux ME. Intermittent sulfadoxine-pyrimethamine in pregnancy: effectiveness against malaria morbidity in Blantyre, Malawi, in 1997-99. Trans R Soc Trop Med Hyg. Sep-Oct 2000;94(5):549-553. 81. Ahmed SM, Abd Al-Rhim SK, Mohamedani AA, Habour AB, Sadek AA. Malaria parasitemia during delivery. Saudi Med J. Jun 2002;23(6):684-688. 82. Kasumba IN, Nalunkuma AJ, Mujuzi G, et al. Low birthweight associated with maternal anaemia and Plasmodium falciparum infection during pregnancy, in a periurban/urban area of low endemicity in Uganda. Annals of Tropical Medicine and Parasitology. 2000;94(1):7-13. 83. Saute F, Menendez C, Mayor A, et al. Malaria in pregnancy in rural Mozambique: the role of parity, submicroscopic and multiple Plasmodium falciparum infections. Trop Med Int Health. Jan 2002;7(1):19-28. 84. Mankhambo L, Kanjala M, Rudman S, Lema VM, Rogerson SJ. Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery. J Clin Microbiol. Jan 2002;40(1):155-158. 85. Newman RD, Hailemariam A, Jimma D, et al. Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis. 2003 Jun 1 (Epub 2003 May 2003;187(11):1765-1772.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 86. Elghazali G, Adam I, Hamad A, El-Bashir MI. Plasmodium falciparum infection during pregnancy in an unstable transmission area in eastern Sudan. East Mediterr Health J. Jul 2003;9(4):570-580. 87. Wort UU, Warsame M, Brabin BJ. Birth outcomes in adolescent pregnancy in an area with intense malaria transmission in Tanzania. Acta Obstet Gynecol Scand. 2006;85(8):949-954. 88. Van Geertruyden JP, Ntakirutimana D, Erhart A, Rwagacondo C, Kabano A, D'Alessandro U. Malaria infection among pregnant women attending antenatal clinics in six Rwandan districts. Trop Med Int Health. Jul 2005;10(7):681-688. 89. Kalilani L, Mofolo I, Chaponda M, Rogerson S, Meshnick S. The effect of timing and frequency of malaria infection during pregnancy on low birth weight and maternal anemia. American Journal of Tropical Medicine and Hygiene. 2006;75(5):414. 90. Parise ME, Lewis LS, Ayisi JG, et al. A rapid assessment approach for public, health decision-making related to the prevention of malaria during pregnancy. Bulletin of the World Health Organization. 2003;81(5):316-323. 91. Adam I, Khamis AH, Elbashir MI. Prevalence and risk factors for anaemia in pregnant women of eastern Sudan. Trans R Soc Trop Med Hyg. Oct 2005;99(10):739- 743. 92. Adam I, IE AE, Salih I, Elbashir MI. Submicroscopic Plasmodium falciparum infections during pregnancy, in an area of Sudan with a low intensity of malaria transmission. Ann Trop Med Parasitol. Jun 2005;99(4):339-344. 93. Brentlinger PE, Dgedge M, Correia MA, et al. Intermittent preventive treatment of malaria during pregnancy in central Mozambique. Bull World Health Organ. Nov 2007;85(11):873-879. 94. Ouma P, van Eijk AM, Hamel MJ, et al. Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya. Trop Med Int Health. Dec 2007;12(12):1515-1523. 95. Hillier SD, Booth M, Muhangi L, et al. Plasmodium falciparum and helminth coinfection in a semiurban population of pregnant women in Uganda. Journal of Infectious Diseases. 2008;198(6):920-927. 96. Ndyomugyenyi R, Kabatereine N, Olsen A, Magnussen P. Malaria and hookworm infections in relation to haemoglobin and serum ferritin levels in pregnancy in Masindi district, western Uganda. Trans R Soc Trop Med Hyg. Feb 2008;102(2):130- 136. 97. Rantala AM, Taylor SM, Trottman PA, et al. Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J. 2010;9:269. 98. Serra-Casas E, Menendez C, Dobano C, et al. Persistence of Plasmodium falciparum parasites in infected pregnant Mozambican women after delivery. Infect Immun. Jan 2011;79(1):298-304. 99. Piola P, Nabasumba C, Turyakira E, et al. Efficacy and safety of artemether- lumefantrine compared with quinine in pregnant women with uncomplicated

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. Nov 2010;10(11):762-769. 100. Mbonye AK, Bygbjerg I, Magnussen P. Intermittent preventive treatment of malaria in pregnancy: a community-based delivery system and its effect on parasitemia, anemia and low birth weight in Uganda. Int J Infect Dis. Jan 2008;12(1):22-29. 101. Meuris S, Piko BB, Eerens P, Vanbellinghen AM, Dramaix M, Hennart P. Gestational malaria: assessment of its consequences on fetal growth. Am J Trop Med Hyg. May 1993;48(5):603-609. 102. Morgan HG. Placental malaria and low birthweight neonates in urban Sierra Leone. Ann Trop Med Parasitol. Dec 1994;88(6):575-580. 103. Achidi EA, Salimonu LS. Malaria parasitaemia and immunoglobulin levels in paired maternal-cord sera from south western Nigeria. Afr J Med Med Sci. Sep-Dec 1997;26(3-4):167-170. 104. Watson PA. Asymptomatic Plasmodium falciparum parasitaemia in pregnant women. Trans R Soc Trop Med Hyg. Mar-Apr 1998;92(2):236. 105. Egwunyenga OA, Ajayi JA, Duhlinska-Popova DD. Transplacental passage of Plasmodium falciparum and seroevaluation of newborns in northern Nigeria. J Commun Dis. Jun 1995;27(2):77-83. 106. Menendez C, Todd J, Alonso PL, et al. The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria. Trans R Soc Trop Med Hyg. Sep-Oct 1994;88(5):590-593. 107. Egwunyenga OA, Ajayi JA, Popova-Duhlinska DD, Nmorsi OP. Malaria infection of the cord and birthweights in Nigerians. Cent Afr J Med. Sep 1996;42(9):265-268. 108. Browne EN, Maude GH, Binka FN. The impact of insecticide-treated bednets on malaria and anaemia in pregnancy in Kassena-Nankana district, Ghana: a randomized controlled trial. Trop Med Int Health. Sep 2001;6(9):667-676. 109. Tako EA, Zhou A, Lohoue J, Leke R, Taylor DW, Leke RF. Risk factors for placental malaria and its effect on pregnancy outcome in Yaounde, Cameroon. Am J Trop Med Hyg. Mar 2005;72(3):236-242. 110. Zhou A, Megnekou R, Leke R, et al. Prevalence of Plasmodium falciparum infection in pregnant Cameroonian women. Am J Trop Med Hyg. Dec 2002;67(6):566-570. 111. Walker-Abbey A, Djokam RR, Eno A, et al. Malaria in pregnant Cameroonian women: the effect of age and gravidity on submicroscopic and mixed-species infections and multiple parasite genotypes. Am J Trop Med Hyg. Mar 2005;72(3):229- 235. 112. Egwunyenga AO, Ajayi JA, Nmorsi OP, Duhlinska-Popova DD. Plasmodium/intestinal helminth co-infections among pregnant Nigerian women. Mem Inst Oswaldo Cruz. Nov 2001;96(8):1055-1059. 113. Salihu HM, Naik EG, Tchuinguem G, Bosny JPL, Dagne G. Weekly chloroquine prophylaxis and the effect on maternal haemoglobin status at delivery. Tropical Medicine and International Health. 2002;7(1):29-34.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 114. Okoko BJ, Ota MO, Yamuah LK, et al. Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor. J Health Popul Nutr. Mar 2002;20(1):4-11. 115. Anorlu RI, Odum CU, Essien EE. Asymptomatic malaria parasitaemia in pregnant women at booking in a primary health care facility in a periurban community in Lagos, Nigeria. Afr J Med Med Sci. 2001;30 Suppl:39-41. 116. Mockenhaupt FP, Bedu-Addo G, Eggelte TA, et al. Rapid increase in the prevalence of sulfadoxine-pyrimethamine resistance among Plasmodium falciparum isolated from pregnant women in Ghana. Journal of Infectious Diseases. 2008;198(10):1545- 1549. 117. Sule-Odu AO, Ogunledun A, Olatunji AO. Impact of asymptomatic maternal malaria parasitaemia at parturition on perinatal outcome. J Obstet Gynaecol. Jan 2002;22(1):25-28. 118. Okwa OO. The status of malaria among pregnant women: a study in Lagos, Nigeria. Afr J Reprod Health. Dec 2003;7(3):77-83. 119. Achidi EA, Kuoh AJ, Minang JT, et al. Malaria infection in pregnancy and its effects on haemoglobin levels in women from a malaria endemic area of Fako Division, South West Province, Cameroon. J Obstet Gynaecol. Apr 2005;25(3):235-240. 120. Akum AE, Kuoh AJ, Minang JT, Achimbom BM, Ahmadou MJ, Troye-Blomberg M. The effect of maternal, umbilical cord and placental malaria parasitaemia on the birthweight of newborns from South-western Cameroon. Acta Paediatr. Jul 2005;94(7):917-923. 121. Ekejindu IM, Udigwe GO, Chijioke IR. Malaria and anaemia in pregnancy in Enugu, south east Nigeria. Afr J Med Med Sci. Mar 2006;35(1):1-3. 122. Idowu OA, Mafiana CF, Dapo S. Malaria among pregnant women in Abeokuta, Nigeria. Tanzan Health Res Bull. Jan 2006;8(1):28-31. 123. Mbanya D, Tayou Tagny C, Takoeta E, Mbu R, Kaptue L. [Factors associated with thrombocytopenia among pregnant women in Cameroon]. Sante. Oct-Dec 2007;17(4):213-217. 124. Akanbi OM, Odaibo AB, Ademowo OG. The burden of malaria infection on pregnant women and birth weight of infants in south western Nigeria. East Afr J Public Health. Apr 2009;6(1):63-68. 125. Nwonwu EU, Ibekwe PC, Ugwu JI, Obarezi HC, Nwagbara OC. Prevalence of malaria parasitaemia and malaria related anaemia among pregnant women in Abakaliki, South East Nigeria. Niger J Clin Pract. Jun 2009;12(2):182-186. 126. Ogbodo SO, Nwagha UI, Okaka AN, Ogenyi SC, Okoko RO, Nwagha TU. Malaria parasitaemia among pregnant women in a rural community of eastern Nigeria; need for combined measures. Niger J Physiol Sci. Dec 2009;24(2):95-100. 127. Okusanya BO, Eigbefoh JO, Ohiosimuan O, Isabu PA, Okpere EE, Inyang NJ. Utility of intradermal blood smear in the detection of asymptomatic malaria parasitaemia in pregnancy. Niger Postgrad Med J. Sep 2009;16(3):182-185. 128. Gajida AU, Iliyasu Z, Zoakah AI. Malaria among antenatal clients attending primary health care facilities in Kano state, Nigeria. Ann Afr Med. 2010 2010;9(3):188-193.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 129. Mockenhaupt FP, Bedu-Addo G, von Gaertner C, et al. Detection and clinical manifestation of placental malaria in southern Ghana. Malar J. 2006;5:119. 130. Sirima SB, Sawadogo R, Moran AC, et al. Failure of a chloroquine chemoprophylaxis program to adequately prevent malaria during pregnancy in Koupela District, Burkina Faso. Clin Infect Dis. Jun 1 2003;36(11):1374-1382. 131. Singer LM, Newman RD, Diarra A, et al. Evaluation of a malaria rapid diagnostic test for assessing the burden of malaria during pregnancy. American Journal of Tropical Medicine and Hygiene. 2004;70(5):481-485. 132. Nnaji GA, Ikechebelu JI. An evaluation of the use of reported febrile illness in predicting malaria in pregnancy. J Obstet Gynaecol. 2007 2007;27(8):791-794. 133. Leke RF, Bioga JD, Zhou J, et al. Longitudinal studies of Plasmodium falciparum malaria in pregnant women living in a rural Cameroonian village with high perennial transmission. Am J Trop Med Hyg. Nov 2010;83(5):996-1004. 134. VanderJagt TA, Ikeh EI, Ujah IO, Belmonte J, Glew RH, VanderJagt DJ. Comparison of the OptiMAL rapid test and microscopy for detection of malaria in pregnant women in Nigeria. Trop Med Int Health. Jan 2005;10(1):39-41. 135. Ayoya MA, Spiekermann-Brouwer GM, Traore AK, Stoltzfus RJ, Garza C. Determinants of anemia among pregnant women in Mali. Food and Nutrition Bulletin. 2006;27(1):3-11. 136. Tagbor H, Bruce J, Browne E, Randal A, Greenwood B, Chandramohan D. Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial. Lancet. Oct 14 2006;368(9544):1349-1356. 137. Okafor UH, Oguonu T, Onah HE. Risk factors associated with congenital malaria in Enugu, South Eastern Nigeria. J Obstet Gynaecol. Oct 2006;26(7):612-616. 138. Tagbor H, Bruce J, Browne E, Greenwood B, Chandramohan D. Performance of the OptiMAL dipstick in the diagnosis of malaria infection in pregnancy. Ther Clin Risk Manag. Jun 2008;4(3):631-636. 139. Mbaye A, Richardson K, Balajo B, et al. A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in Gambian multigravidae. Trop Med Int Health. Jul 2006;11(7):992-1002. 140. Falade CO, Yusuf BO, Fadero FF, Mokuolu OA, Hamer DH, Salako LA. Intermittent preventive treatment with sulphadoxine-pyrimethamine is effective in preventing maternal and placental malaria in Ibadan, south-western Nigeria. Malaria Journal. 2007;6. 141. Coulibaly SO, Gies S, D'Alessandro U. Malaria burden among pregnant women living in the rural district of Boromo, Burkina Faso. Am J Trop Med Hyg. Dec 2007;77(6 Suppl):56-60. 142. Falade CO, Olayemi O, Dada-Adegbola HO, Aimakhu CO, Ademowo OG, Salako LA. Prevalence of malaria at booking among antenatal clients in a secondary health care facility in Ibadan, Nigeria. Afr J Reprod Health. Aug 2008;12(2):141-152. 143. Falade C.O., Tongo O.O., Ogunkunle O. O., Orimadegun A. E. Effects of malaria in pregnancy on newborn anthropometry. J Infect Dev Ctries. Jul 2010;4(7):448-453.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 144. Lukuka KA, Fumie OS, Mulumbu MR, Lokombe BJ, Muyembe TJ. [Malaria prevalence at delivery in four maternity hospitals of Kinshasa City, Democratic Republic of Congo]. Bull Soc Pathol Exot. Jul 2006;99(3):200-201. 145. Sirima SB, Cotte AH, Konate A, et al. Malaria prevention during pregnancy: assessing the disease burden one year after implementing a program of intermittent preventive treatment in Koupela District, Burkina Faso. Am J Trop Med Hyg. Aug 2006;75(2):205-211. 146. Enato EF, Okhamafe AO, Okpere EE, Oseji FI. Prevalence of malaria during pregnancy and antimalarial intervention in an urban secondary health care facility in Southern Nigeria. Med Princ Pract. 2007;16(3):240-243. 147. Kagu MB, Kawuwa MB, Gadzama GB. Anaemia in pregnancy: a cross-sectional study of pregnant women in a Sahelian tertiary hospital in Northeastern Nigeria. J Obstet Gynaecol. Oct 2007;27(7):676-679. 148. Enato EF, Mens PF, Okhamafe AO, Okpere EE, Pogoson E, Schallig HD. Plasmodium falciparum malaria in pregnancy: prevalence of peripheral parasitaemia, anaemia and malaria care-seeking behaviour among pregnant women attending two antenatal clinics in Edo State, Nigeria. J Obstet Gynaecol. May 2009;29(4):301-306. 149. Uneke CJ, Iyare FE, Oke P, Duhlinska DD. Assessment of malaria in pregnancy using rapid diagnostic tests and its association with HIV infection and hematologic parameters in South-Eastern Nigeria. Haematologica. Jan 2008;93(1):143-144. 150. Nwagha UI, Ugwu VO, Nwagha TU, Anyaehie BU. Asymptomatic Plasmodium parasitaemia in pregnant Nigerian women: almost a decade after Roll Back Malaria. Trans R Soc Trop Med Hyg. Jan 2009;103(1):16-20. 151. Yatich NJ, Funkhouser E, Ehiri JE, et al. Malaria, intestinal helminths and other risk factors for stillbirth in Ghana. Infect Dis Obstet Gynecol. 2010;350763; 01-Apr-10. 152. Anchang-Kimbi JK, Achidi EA, Nkegoum B, Sverremark-Ekstrom E, Troye- Blomberg M. Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women. Malar J. 2009;8:126. 153. Agomo CO, Oyibo WA, Anorlu RI, Agomo PU. Prevalence of malaria in pregnant women in Lagos, South-West Nigeria. Korean J Parasitol. Jun 2009;47(2):179-183. 154. Wilson NO, Ceesay FK, Obed SA, et al. Intermittent preventive treatment with sulfadoxine-pyrimethamine against malaria and anemia in pregnant women. Am J Trop Med Hyg. Jul 2011;85(1):12-21. 155. Ekejindu IM, Okeke EK, Akah B, Okpala E, Ezeagwuna DA, Onwurah O. Malaria and hookworm co-infection among pregnant and non-pregnant women in a semiurban area in Anambra state, Nigeria. World Journal of Medical Sciences. 2011;6(1):33-35. 156. Koura KG, Briand V, Massougbodji A, Chippaux JP, Cot M, Garcia A. [Determination of prevalence and etiology of anemia during pregnancy in southern Benin, in conjunction with revision of national management policy]. Med Trop (Mars). Feb 2011;71(1):63-67.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 157. Aziken ME, Akubuo KK, Gharoro EP. Efficacy of intermittent preventive treatment with sulfadoxine-pyrimethamine on placental parasitemia in pregnant women in midwestern Nigeria. Int J Gynaecol Obstet. Jan 2011;112(1):30-33. 158. Rogerson SJ, Mkundika P, Kanjala MK. Diagnosis of Plasmodium falciparum malaria at delivery: comparison of blood film preparation methods and of blood films with histology. J Clin Microbiol. Apr 2003;41(4):1370-1374. 159. Kabyemela ER, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE. Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency. Journal of Infectious Diseases. 2008;198(2):163-166. 160. Kassam SN, Nesbitt S, Hunt LP, Oster N, Soothill P, Sergi C. Pregnancy outcomes in women with or without placental malaria infection. Int J Gynaecol Obstet. Jun 2006;93(3):225-232. 161. Adam I, Babiker S, Mohmmed AA, Salih MM, Prins MH, Zaki ZM. ABO blood group system and placental malaria in an area of unstable malaria transmission in eastern Sudan. Malar J. 2007;6:110. 162. Senga E, Loscertales MP, Makwakwa KE, et al. ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women. Malar J. 2007;6:102. 163. Abdelrahim, II, Adam GK, Mohmmed AA, et al. Anaemia, folate and vitamin B12 deficiency among pregnant women in an area of unstable malaria transmission in eastern Sudan. Trans R Soc Trop Med Hyg. May 2009;103(5):493-496. 164. Adam I, Adam GK, Mohmmed AA, Salih MM, Ibrahuim SA, Ryan CA. Placental malaria and lack of prenatal care in an area of unstable malaria transmission in eastern Sudan. J Parasitol. Jun 2009;95(3):751-752. 165. Cot M, Le Hesran JY, Miailhes P, Esveld M, Etya'ale D, Breart G. Increase of birth weight following chloroquine chemoprophylaxis during the first pregnancy: results of a randomized trial in Cameroon. Am J Trop Med Hyg. Dec 1995;53(6):581-585. 166. Rasheed FN, Bulmer JN, De Francisco A, et al. Relationships between maternal malaria and malarial immune responses in mothers and neonates. Parasite Immunol. Jan 1995;17(1):1-10. 167. Ndao CT, Ndiaye JL, Gaye A, Le Hesran JY. Placental infection by Plasmodium falciparum in urban area in Senegal. [French]. Bulletin De La Societe De Pathologie Exotique. 2003;96(3):161-164. 168. N'Dao CT, N'Diaye JL, Gaye A, Le Hesran JY. [Placental malaria and pregnancy outcome in a peri urban area in Senegal]. Rev Epidemiol Sante Publique. Apr 2006;54(2):149-156. 169. Owens S, Harper G, Amuasi J, Offei-Larbi G, Ordi J, Brabin BJ. Placental malaria and immunity to infant measles. Arch Dis Child. Jun 2006;91(6):507-508. 170. Mokuolu OA, Falade CO, Orogade AA, et al. Malaria at parturition in Nigeria: current status and delivery outcome. Infect Dis Obstet Gynecol. 2009;2009:473971. 171. Ukaga CN, Nwoke BE, Udujih OS, et al. Placental malaria in Owerri, Imo State, south-eastern Nigeria. Tanzan Health Res Bull. Sep 2007;9(3):180-185.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012 172. Peeling RW, Ye H. Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview. Bull World Health Organ. Jun 2004;82(6):439-446. 173. Kuypers J, Gaydos CA, Peeling RW. Principles of Laboratory Diagnosis of STIs. In: Holmes KK SF, Stamm WE, Piot P, Wasserheit JN, Corey L, Cohen M,, ed. Sexually Transmitted Diseases. 4th ed. New York: McGraw Hill; 2008:937-957. 174. Cook RL, Hutchison SL, Ostergaard L, Braithwaite RS, Ness RB. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. Jun 7 2005;142(11):914-925. 175. Kuypers J, World Health Organization. Laboratory tests for the detection of reproductive tract infections. In: Jejeebhoy S, Koenig M, Elias C, eds. Reproductive Tract Infections and other Gynaecological Disorders. Cambridge: Cambridge University Press; 2003:225-260. 176. Thejls H, Rahm VA, Gnarpe J, Gnarpe H. Diagnostic efficacy of chlamydial antibodies in cervical secretions from pregnant women and adolescent girls. Genitourin Med. Dec 1995;71(6):370-374. 177. Meehan M, Wawer M, Swerwadda D, Gray R, Quinn T. Laboratory methods for the diagnosis of reprodutive tract infections and selecged conditions in population-based studies. In: Jejeebhoy S, Koenig M, Elias C, eds. Reproductive Tract Infections and other Gynaecological Disorders. Cambridge: Cambridge University Press; 2003:261- 282. 178. Dadhwal V, Hariprasad R, Mittal S, Kapil A. Prevalence of bacterial vaginosis in pregnant women and predictive value of clinical diagnosis. Arch Gynecol Obstet. Jan 2010;281(1):101-104. 179. Goyal R, Sharma P, Kaur I, Aggarwal N, Talwar V. Bacterial vaginosis and vaginal anaerobes in preterm labour. J Indian Med Assoc. Oct 2004;102(10):548-550, 553. 180. Thomason JL, Anderson RJ, Gelbart SM, et al. Simplified gram stain interpretive method for diagnosis of bacterial vaginosis. Am J Obstet Gynecol. Jul 1992;167(1):16-19. 181. Schwebke JR, Hillier SL, Sobel JD, McGregor JA, Sweet RL. Validity of the vaginal gram stain for the diagnosis of bacterial vaginosis. Obstet Gynecol. Oct 1996;88(4 Pt 1):573-576. 182. Reyburn H, Ruanda J, Mwerinde O, Drakeley C. The contribution of microscopy to targeting antimalarial treatment in a low transmission area of Tanzania. Malar J. 2006;5:4. 183. Reyburn H, Mbatia R, Drakeley C, et al. Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ. Nov 20 2004;329(7476):1212. 184. Barat L, Chipipa J, Kolczak M, Sukwa T. Does the availability of blood slide microscopy for malaria at health centers improve the management of persons with fever in Zambia? Am J Trop Med Hyg. Jun 1999;60(6):1024-1030. 185. Mockenhaupt FP, Ulmen U, von Gaertner C, Bedu-Addo G, Bienzle U. Diagnosis of placental malaria. J Clin Microbiol. Jan 2002;40(1):306-308.

Downloaded From: http://jama.jamanetwork.com/ by a University of Liverpool User on 08/18/2012