Prevalence and predictors of maternal peripheral malaria parasitemia in central Mozambique

Am. J. Trop. Med. Hyg., 77(2), 2007, pp. 228–234 Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

Prevalence and Predictors of Maternal Peripheral Malaria Parasitemia in Central Mozambique Paula E. Brentlinger,* Pablo Montoya, Ana Judith Blanco Rojas, Maria Ana Chadreque Correia, Martinho Dgedge, Francisco Saúte, Kenneth Gimbel-Sherr, Mary Anne Mercer, and Stephen Gloyd Department of Health Services, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; Health Alliance International, Beira, Mozambique; Health Alliance International, Chimoio, Mozambique; Department of Human Resources, Ministry of Health, Maputo, Mozambique; National Malaria Control Program, Maputo, Mozambique

Abstract. Malaria infection during pregnancy (MiP) is heterogeneously distributed even in malaria-endemic countries. Program planners require data to facilitate identification of highest-priority populations for MiP control. Using data from two cross-sectional studies of 5,528 pregnant women in 8 neighboring sites in Mozambique, we described factors associated with maternal peripheral parasitemia by using logistic regression. Principal multivariate predictors of maternal peripheral parasitemia were gravidity (odds ratio [OR] ⳱ 2.29, 95% confidence interval [CI] ⳱ 1.60–3.26 for primigravidae and OR ⳱ 1.61, 95% CI ⳱ 1.29–2.01 for secundigravidae compared with gravidity ⱖ 3); age (OR ⳱ 0.96 per year, 95% CI ⳱ 0.94–0.99); study site (OR ⳱ 1.45, 95% CI ⳱ 1.34–1.56 to 5.32, 95% CI ⳱ 4.92–5.75) for comparison with the reference site; and no maternal education (OR ⳱ 1.38, 95% CI ⳱ 1.15–1.66) compared with any education. Other predictors (in subgroups) were bed net use (OR ⳱ 0.49, 95% CI ⳱ 0.48–0.50); preventive sulfadoxinepyrimethamine doses (OR ⳱ 0.25, 95% CI ⳱ 0.24–0.25); and infection with human immunodeficiency virus (HIV) (OR ⳱ 1.49, 95% CI ⳱ 1.11–2.00). Programmatic priorities should respond to heterogeneous distribution of multiple risk factors, including prevalance of malaria and infection with HIV, and maternal socioeconomic status. riparian rural regions where malaria transmission was thought to be most intense. Thus, vigorous debate ensued about selection of the highest-priority individuals and populations for establishment of the first new MiP services. Only two studies had formally measured the prevalence of maternal peripheral malaria parasitemia in Sofala and Manica Provinces. With the aim of providing data to inform the provincial policy-making process, we analyzed predictors of maternal malaria infection in the combined data sets from the two investigations.

INTRODUCTION Malaria infection during pregnancy (MiP) commonly has adverse consequences for both mother and infant, and contributes substantially to both maternal and infant mortality.1–3 The burden of MiP is greatest in sub-Saharan Africa. Based on the results of several clinical trials, the World Health Organization, as part of the Roll Back Malaria initiative, has now recommended insecticide-treated bed nets (ITNs), intermittent preventive treatment (IPTp) with an effective antimalarial during the latter two trimesters of pregnancy, and good case management of malaria and/or severe anemia for all pregnant women living in areas of sub-Saharan Africa where transmission of Plasmodium falciparum is stable.4–9 However, existing health-sector capacity in many sub-Saharan African countries is inadequate to support the introduction of all of these measures in all at-risk populations simultaneously, and MiP prevalence in different populations is known to be heterogeneous (Table 1). Identification of highest-risk populations would facilitate definition of highestpriority target groups for introduction of new interventions, so that the most vulnerable might be reached first.10 In central Mozambique, malaria has historically been thought to be ubiquitous. In 2004 and 2005, the Mozambican Ministry of Health (MOH) hoped to extend IPTp and ITNs to all pregnant women in the central provinces of Sofala and Manica. However, it was not logistically possible to introduce IPTp simultaneously in all districts, and existing funding was inadequate to support population-level coverage of this intervention. Because of known links between human immunodeficiency virus (HIV) infection and malaria, some donors had stipulated that their funds (approximately half of the available IPTp and ITN funding) could only be directed toward women with confirmed HIV infection.11,12 However, existing HIV services were concentrated in urban areas, not in the

METHODS Study design and aims. The methods for both studies have been previously summarized.13,14 Briefly, we conducted two cross-sectional observational studies of maternal peripheral malaria parasitemia, hereafter called “the syphilis study” and “the IPTp study.” Syphilis study. Between August 2003 and January 2004 (low-transmission season for malaria), a cross-sectional study was conducted in six urban and peri-urban antenatal clinics operated by the MOH in the city of Beira and the adjacent district of Dondo, both in Sofala Province. The primary aim of the study was to evaluate the diagnostic accuracy of a new rapid test for maternal syphilis. Because malaria infection had been reported to affect the diagnostic accuracy of some syphilis tests, maternal peripheral blood smears were evaluated by microscopy for the presence of malaria parasitemia in all study subjects.15,16 IPTp was not yet available for this population. IPTp study. Between April and June 2004 (peak transmission season), a cross-sectional study of maternal peripheral malaria parasitemia prevalence (again using microscopy) was conducted in two MOH IPTp pilot sites: Gondola district (Manica Province) and Nhamatanda district (Sofala Province). The primary aim of this study was to compare malaria and anemia prevalence in women who had used ITNs and/or had received IPTp with sulfadoxine-pyrimethamine (SP) to that in women who had not used either intervention. Study settings. The city of Beira (four syphilis study clinics) is the second largest city in Mozambique. Its antenatal HIV

* Address correspondence to Paula E. Brentlinger, Department of Health Services, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195. E-mail: brentp2@ u.washington.edu

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TABLE 1 Reported prevalence of maternal peripheral parasitemia in selected studies* Subgroup

Maternal peripheral Plasmodium falciparum prevalence

Primigravidae, Kisumu (n ⳱ 59) Secundigravidae, Kisumu (n ⳱ 46) Primigravidae, Mombasa (n ⳱ 58) Secundigravidae, Mombasa (n ⳱ 37) Primigravidae (n ⳱ 801) Secundigravidae (n ⳱ 646) Multigravidae (n ⳱ 2,229) HIV-infected (n ⳱ 152) HIV-uninfected (n ⳱ 2,601) Primigravidae, HIV-infected (n ⳱ 359) Primigravidae, no HIV (n ⳱ 1,590) Secundigravidae, HIV-infected (n ⳱ 241) Secundigravidae, no HIV (n ⳱ 778) Multigravidae, HIV-infected (n ⳱ 383) Multigravidae, no HIV (n ⳱ 1,691) All gravidities, dry season (n ⳱ 75) All gravidities, rainy season (n ⳱ 97) Primigravidae (n ⳱ 220) Secundigravidae (n ⳱ 131) Multigravidae (n ⳱ 322) Grand multigravidae (n ⳱ 71; g ⱖ 5) HIV-infected women (all gravidities), hemoglobin < 85g/L (n ⳱ 293) HIV-infected women (all gravidities), hemoglobin < 110g/L (n ⳱ 870)

69.5% 45.7% 41.4% 37.8% 35.3% (51.4% in April) 19.9% (56.0% in April) 12.8% (25.3% in April) 54.4% 41.7% 34.3% 25.2% 30.6% 16.0% 21.2% 10.2% 28.0% 41.2% 14.5% 10.7% 13.4% 18.3% 25.3% 19.1%

Country and reference

Kenya10

Malawi23 Malawi12 Malawi and western Kenya11

Mali3 Sudan21

Tanzania

22

* HIV ⳱ human immunodeficiency virus.

prevalence (29.1–34.4% in sentinel surveillance) is thought to be the highest in the country.17 Malaria transmission occurs year round with seasonal peaks, but has been somewhat attenuated by spraying campaigns and widespread commercial access to ITNs. The adjacent district of Dondo (two syphilis study sites) is part of the Beira peri-urban area; only part of it is routinely sprayed. Nhamatanda (one IPTp study site) is approximately 100 km west of Beira in a rural agricultural region that undergoes frequent seasonal flooding. Gondola (one IPTp study site) is approximately 80 km west of Nhamatanda. It is also rural and agricultural, but less subject to flooding because of its higher elevation. Malaria transmission occurs year round with seasonal peaks in both towns, but no spraying campaigns are conducted, and access to ITNs was still very limited at the time of the study.18 In all four districts, more than half the population were thought to live in poverty.19 Figure 1 describes the study locations. Eligibility and enrollment. In the syphilis study, all women coming for antenatal care at the participating clinics during the study period were considered eligible for enrollment. In the IPTp study, all women who had previously enrolled in a pilot IPTp intervention program and who came for routine antenatal care at the study facilities during the study period were considered eligible for enrollment. In both instances, eligible women were approached in their own languages by Mozambican nurses and asked for their consent. Consenting women were interviewed to determine their age, parity, gravidity, and educational levels in both studies. In the IPTp study, women were also asked about use of ITNs on the night preceding the evaluation, and antenatal records were reviewed to determine the number and timing of previous preventive doses of SP. In the syphilis study, women were also asked about other indicators of socioeconomic status, such as presence or absence of piped water and electricity in the home.

Laboratory evaluation. In both studies, capillary blood was taken by finger prick; blood smears were stained with Giemsa and read independently by two microscopists who counted asexual P. falciparum parasites against 500 leukocytes. The parasite count was normalized to a presumed leukocyte count of 8,000/␮L. If the two readings differed, a third microscopist examined the slide. The same microscopists were responsible for quality control of malaria smears from both studies. In the ¨ ngelholm, IPTp study only, HemoCue (HemoCue Ltd., A Sweden) devices were used to measure maternal hemoglobin levels, again using capillary blood obtained by fingerprick. Syphilis status of participating women was ascertained by rapid plasma reagin (RPR) and Treponema pallidum hemagglutination (performed by clinic staff and in a reference laboratory) in the syphilis study, and by on-site RPR or rapid testing (performed by clinic staff) in the IPTp study. In both studies, women who elected to undergo voluntary counseling and testing for HIV-1 as a routine option in antenatal care were asked to share their test results with the investigators, but HIV testing was not a study procedure, and the study team did not confirm the results obtained by local MOH staff. At the time of the study, HIV testing had been available in some sites for nearly two years, was in the process of becoming available in other sites, and still had not been introduced in two sites. Antiretroviral therapy was available in two regional sites. Data analysis. Means and proportions were calculated to describe the characteristics of the two patient populations. Differences between the two populations were described using t-tests and chi-square tests of significance, using P ⳱ 0.05 as the upper boundary of statistical significance. Bivariate and multivariate logistic regression, using robust confidence limits to reflect possible correlation of responses within health units, were then used to estimate associations between the primary outcome measure (presence of any asexual P. falciparum

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FIGURE 1. Map showing districts of Beira, Dondo, Gondola, and Nhamatanda, and the provinces of Sofala and Manica, Mozambique. The syphilis study was conducted in six sites in Beira and the district of Dondo. The intermittent preventive treatment study was conducted in the districts of Gondola and Nhamatanda. SP ⳱ sulfadoxine-pyrimethamine; MOH ⳱ Ministry of Health, HIV ⳱ human immunodeficiency virus.

parasites on at least two readings of a peripheral blood smear) and patient factors. The initial models included factors previously known to be associated with malaria infection (e.g., gravidity), as well as factors of intrinsic interest to the investigators (e.g., study site); non-significant covariates (as determined by the Wald test) were then eliminated serially. We conducted separate multivariate analyses for subjects of known HIV status and all subjects because women with known HIV serostatus comprised less than half of the study subjects and could not be assumed to be a representative sample of the overall study population. We did not adjust for gestational age because its assessment is highly imprecise in this setting, and because it is based almost entirely on fundal height, which could in turn be affected by malaria-related or HIV-related intrauterine growth retardation.14 Ethical considerations. Informed consent was obtained from all participants in Portuguese or local languages. Both studies were reviewed and approved by the pertinent committees at the Mozambican National Institutes of Health and at the University of Washington, and by the Provincial Health Directorates of Sofala and/or Manica Provinces. RESULTS The characteristics of the study subjects are described in Table 2. The study populations were dissimilar in several respects. The syphilis study subjects were younger and of lower gravidity, their educational levels were higher, and they were predominantly urban. They were also more likely to be infected with HIV and/or syphilis. Results of malaria smears were available for 4,450 women from the syphilis study and 1,078 women from the IPTp study. Parasitemia was detected in 15.5% of subjects overall, in

13.0% of the syphilis study subjects, and in 25.7% of the IPTp study subjects. Site-specific prevalences ranged from 8.8% to 31.0% (calculated without adjustment for previous use of preventive SP). The association of site with malaria prevalence was similar to the association between season of data collection and malaria prevalence. The unadjusted odds ratio (OR) for comparison of malaria prevalence between the highest-prevalence syphilis site and the lowest-prevalence syphilis site (both evaluated during the low-transmission season) was 2.18 (95% confidence interval [CI] ⳱ 1.64–2.90), which was similar to the unadjusted OR for comparison of IPTp sites (studied during the wet-season transmission peak) to syphilis sites, which was 2.31 (95% CI ⳱ 1.97–2.72). Results of HIV serologic analysis were available for 1,884 women (1,563 from the syphilis study and 321 from the IPTp study). The HIV prevalence varied significantly by site, from 9.1% in 1 IPTp site to 27.1% in 1 syphilis site. This prevalence was significantly increased in women 20–29 years of age (OR ⳱ 1.73, 95% CI ⳱ 1.39–2.15 for comparison with both younger and older women) and was negatively associated with gravidity (OR ⳱ 0.92, 95% CI ⳱ 0.87–0.97 per pregnancy). In bivariate analyses (Table 3), younger age, lower gravidity, lower socioeconomic status, non-use of bed nets, lower maternal hemoglobin levels, and more frequent or more recent IPTp administration were all significantly associated with maternal peripheral malaria parasitemia, as expected. Malaria prevalence in bed net users was 14.2% versus 27.6% in non-users; malaria prevalence in women who had had any preventive SP was 5.1% versus 39.3% in women who had not yet had their first dose. There was also significant heterogeneity among study sites, as described above. Of note, there was no significant association between false-positive RPR test

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TABLE 2 Characteristics of study subjects* Characteristic

All women (n ⳱ 5,528)

Syphilis study (n ⳱ 4,450)

IPTp study (n ⳱ 1,078)

P value for comparison of groups

Age, years (mean ± SD) Gravidity (mean ± SD) Primigravida (no. %) Secundigravida (no. %) Gravida ⱖ 3 (no. %) Dirt floor (no. %) No electricity (no. %) No piped water (no. %) No formal education (no. %) Used insecticide-treated bed net (no. %) Number of doses of preventive sulfadoxine-pyrimethamine (no. %) 0 1 2 3 Syphilis screening test positive at health unit (no. %) False positive RPR (no. %) HIV status known (no. %) HIV-infected (no. % of those tested) Peripheral malaria parasitemia (no. %) Peripheral malaria parasitemia (no. %), IPTp recipients excluded

23.4 ± 5.9 3.1 ± 2.1 1,571 (28.3) 1,229 (22.1) 2,754 (49.1) Syphilis study only Syphilis study only Syphilis study only 1,894 (34.3) IPTp study only IPTp study only – – – – 685 (12.7) Syphilis study only 1,884 (33.8) 436 (23.1) 856 (15.5) IPTp study only

23.3 ± 5.8 2.9 ± 2.0 1,323 (29.6) 1,041 (23.3) 2,113 (47.2) 1,217 (28.3) 3,422 (79.2) 1,090 (25.3) 1,365 (30.7) – – – – – – 611 (13.9) 45 (1.0) 1,563 (34.8) 381 (24.4) 579 (13.0)

23.9 ± 6.3 3.6 ± 2.4 248 (23.0) 188 (17.5) 641 (59.5) – – – 529 (49.3) 155 (14.4)

0.002 < 0.001 < 0.001 < 0.001 < 0.001 – – – < 0.001 – – – – – – < 0.001 – 0.002 0.005 < 0.001

649 199 163 67 74 321 55 277 255

(60.2) (18.5) (15.1) (6.2) (7.2) – (29.8) (17.1) (25.7) (39.3)

* IPTp ⳱ intermittent preventive treatment; RPR ⳱ rapid plasma reagin; HIV ⳱ human immunodeficiency virus.

results and malaria parasitemia (OR ⳱ 1.41, 95% CI ⳱ 0.78– 2.54) in the syphilis study group. In both groups (Figure 2), HIV infection was associated with higher prevalence of malaria parasitemia regardless of

gravidity, and the IPTp study subjects had higher prevalences of parasitemia than the syphilis study subjects regardless of HIV serostatus or level of gravidity. HIV infection was significantly associated with malaria parasitemia in syphilis study

TABLE 3 Bivariate predictors of malaria parasitemia* Covariate

Maternal age, years (continuous) Gravidity Primigravida Secundigravida Gravida ⱖ 3 No formal education HIV infection present HIV status known Dirt-floor housing No electricity at home No running water at home Use of bed net on night preceding study Preventive SP during this pregnancy 3 doses 2 doses 1 dose None Days since last preventive SP dose Undefined (no SP) ⱖ 57 days ⱕ 56 days Hemoglobin < 11g/dL Study site IPTp site 1, Nhamatanda district IPTp site 2, Gondola district Syphilis site 1, Beira district Syphilis site 2, Dondo district Syphilis site 3, Beira district† Syphilis site 4, Beira district Syphilis site 5, Dondo district† Syphilis site 6, Beira district

Odds ratio

95% CI

0.92

0.91, 0.94

2.61 1.72 1.00 1.28 1.21 1.06 1.47 2.12 1.63 0.43

1.99, 3.41 1.38, 2.16 – 0.98, 1.67 0.93, 1.58 0.63, 1.81 1.07, 2.02 1.44, 3,13 1,18, 2.25 0.27, 0.73

0.12 0.07 0.08 1.00

0.04, 0.38 0.02, 0.25 0.05, 0.12 –

21.0 9.18 1.00 1.75

13.96, 33.39 5.46, 15.41 – 1.50, 2.04

4.69 2.69 2.18 1.97 1.68 1.52 1.44 1.00

3.55, 6.20 2.00, 3.62 1.64, 2.90 1.43, 2.70 1.25, 2.26 1.15, 2.02 1.00, 2.07 –

Study

Both Both

Both Both Both Syphilis only Syphilis only Syphilis only IPTp only IPTp only

IPTp only

* CI ⳱ confidence interval; HIV ⳱ human immunodeficiency virus; IPTp ⳱ intermittent preventive treatment; SP⳱ sulfadoxine-pyrimethamine. † HIV testing services unavailable at this site.

IPTp only IPTp only Syphilis only

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FIGURE 2. The prevalence of maternal peripheral malaria parasitemia was consistently higher in women from the IPTp sites, paucigravidae, and HIV–infected women. (Women who had received preventive sulfadoxine-pyrimethamine were excluded from these calculations.)

subjects (OR ⳱ 1.43, 95% CI ⳱ 1.02–2.00), but not in the IPTp subjects (OR ⳱ 1.22, 95% CI ⳱ 0.67–2.21). However, few women in the IPTp study had been tested for HIV. In multivariate analyses (Table 4), age, gravidity, educational level, and study site retained their significance for both groups. In the syphilis study group, HIV infection and absence of electricity were also significantly associated with malaria parasitemia. In the IPTp study group, use of ITNs and SP both retained their significance without substantial changes in ORs, which suggested that ITNs and SP contribute independently to reduction of malaria risk in pregnancy. An

alternative analysis of the IPTp data showed that elapsed time since the last dose of preventive SP also retained its significance in multivariate analysis (OR ⳱ 9.01, 95% CI ⳱ 3.19– 25.38 for association of malaria parasitemia and last SP dose ⱖ 57 days prior to study, and OR ⳱ 22.05, 95% CI ⳱ 1.44– 336.96 for no SP compared with the reference category of SP administration ⱕ 56 days previously). However, collinearity prevented concurrent insertion of the two measures (number of IPTp doses, elapsed time since last IPTp dose) into the same model. Some OR estimates appeared to change substantially when

TABLE 4 Multivariate predictors of maternal peripheral malaria parasitemia* All women Covariate

Age (continuous) Gravidity Gravida 1 Gravida 2 Gravida ⱖ 3 Site IPTp site 1, Nhamatanda district IPTp site 2, Gondola district Syphilis site 1, Beira district Syphilis site 2, Dondo district Syphilis site 3, Beira district† Syphilis site 4, Beira district Syphilis site 5, Dondo district† Syphilis site 6, Beira district No formal education No electricity Used insecticide-treated bed net Number of doses of preventive sulfadoxine-pyrimethamine HIV infection

Both studies combined N ⳱ 5,376

Syphilis study only N ⳱ 4,157

Women of known HIV serostatus IPTp study only N ⳱ 1,070

Both studies combined N ⳱ 1,818

Syphilis study only N ⳱ 1,459

IPTp study only N ⳱ 320

0.96 (0.94, 0.99)

0.95 (0.92, 0.99) 0.97 (0.95, 0.98)

0.98 (0.98, 0.99)

1.00 (0.99, 1.00) 0.97 (0.97, 0.97)

2.29 (1.60, 3.26) 1.61 (1.29, 2.01) 1.00

2.12 (1.27, 3.54) 2.84 (2.16, 3.73) 1.54 (1.18, 2.02) 1.66 (1.04, 2.63) 1.00 1.00

3.15 (2.08, 4.76) 1.66 (1.14, 2.40) 1.00

3.23 (1.80, 5.78) 3.69 (2.93, 4.65) 1.74 (1.03, 2.95) 1.41 (0.95, 2.08) 1.00 1.00

5.32 (4.92, 5.75) 2.87 (2.60, 3.17) 2.30 (2.23, 2.37) 2.15 (2.05, 2.25) 1.69 (1.62, 1.77) 1.46 (1.38, 1.55) 1.45 (1.34, 1.57) 1.00 1.38 (1.15, 1.66) – –

– 2.41 (2.37, 2.45) – 1.00 1.95 (1.79, 2.12) – 1.86 (1.73, 2.00) – 1.50 (1.43, 1.58) – 1.21 (1.10, 1.33) – 1.26 (1.16, 1.36) – 1.00 – 1.37 (1.09, 1.72) 1.05 (0.77, 1.43) 1.71 (1.19, 2.47) – – 0.49 (0.48, 0.50)

8.90 (7.78, 10.18) 3.63 (3.36, 3.91) 1.18 (1.11, 1.26) 2.71 (2.54, 2.88) – 1.55 (1.48, 1.61) – 1.00 1.67 (1.54, 1.82) – –

– 3.76 (3.59, 3.94) – 1.00 1.02 (0.86, 1.22) – 2.35 (2.02, 2.73) – – – 1.31 (1.08, 1.58) – – – 1.00 – 1.64 (1.32, 2.05) 1.43 (1.18, 1.73) 1.88 (0.71, 4.95) – – 0.41 (0.38, 0.45)

– 1.49 (1.11, 2.00)

– 0.22 (0.15, 0.33) 1.63 (1.08, 2.45) 1.37 (0.95, 1.96)

– –

– –

0.25 (0.24, 0.25) –

* Values are odds ratios (95% confidence intervals). HIV ⳱ human immunodeficiency virus; IPTp ⳱ intermittent preventive treatment. † HIV testing services unavailable at this site.

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a covariate for HIV status was added to the multivariate model (Table 4). However, subjects with known HIV status comprised a small subgroup of the study population as a whole, and HIV testing was unavailable in two sites. Evaluation for interaction between HIV status and other covariates failed to yield important interaction terms; the observed change in ORs appeared to be caused primarily by the exclusion of two entire study sites and 65% of the study subjects from the analyses that included HIV status. DISCUSSION Although the study communities were all located within 200 km of each other in a region previously thought to be at uniformly high risk of malaria infection, the heterogeneity of observed maternal peripheral parasitemia prevalence does not justify previous program planners’ assumptions of similar malaria risk in the study districts. The site with the lowest observed prevalence (8.8%) was an urban clinic characterized by high HIV seroprevalence (27.1% in those tested), higher proportion of women tested for HIV (50.7%), higher socioeconomic status, regular coverage by an indoor residual spraying campaign, and data collection during the dry (low-transmission) season. The highest observed level was 48.1% (31.0% if women who had previously received preventive SP were included) in a rural site with lower socioeconomic status, lower HIV seroprevalence (18.4%), a similar proportion of women tested for HIV (52.1%), no coverage by spraying, and data collection during the rainy season. Overall, only 35.1% of the parasitemic women were of known HIV status, and only 9.1% of the parasitemic women had documented HIV infection. Our findings suggest that differences in socioeconomic status, HIV prevalence, access to malaria-prevention interventions (especially bed nets and spraying), and geographic location are as important as seasonal effects in this setting. Previous studies conducted in Mozambique support this contention. For example, a study conducted in Beira and Dondo in 2002 found a malaria parasitemia prevalence of 30.3% in 413 individuals from the unsprayed sectors of Dondo, and 6.7% in a contemporary sample of 705 individuals from the sprayed sectors of Beira, with parallel differences in the observed density of anopheline vectors (João FI and others, unpublished data). The demographic and health survey in 2003 found that only 4.1% of young children in Sofala Province and 6.6% in Manica Province slept under ITNs, and that ITN use was 2.2 times more likely in urban children compared with rural children nationwide. 20 Our own programevaluation data in 2004 indicated that household-level ITN coverage ranged from under 15% in rural subsistence-farming communities to more than 50% in urban settings.18 Because HIV prevalence was substantially higher at sites with higher socioeconomic status, better access to bed nets and spraying, and lower levels of maternal peripheral malaria parasitemia, and because IPTp and ITN use had substantially reduced the prevalence of malaria parasitemia in IPTp program participants, our data may actually underestimate the association between socioeconomic status, geographic location, and malaria. The primary limitation of our analyses is that the methods for the syphilis study and the IPTp study were not identical. In addition to the above-noted difference in season of data col-

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lection, socioeconomic data were not collected for the IPTp study participants (with the exception of educational level), and data on bed net use and antimalarial treatment were not collected for the syphilis study participants. Another important limitation is that HIV serostatus was unknown for most participants, particularly in the rural areas and in the IPTp study participants. This is consistent with national-level patterns of HIV testing in Mozambique. In 2003, only 5.4% of urban women and 0.6% of rural women were believed to know their HIV status.20 Also, HIV disease stage was unknown in seropositive subjects, and women who elected both to be tested for HIV and to share their results with us may not have been representative of the study population as a whole. However, we believe that these weaknesses are offset by benefits of the large sample size, the consistency of methods used to determine maternal malaria status, and the heterogeneity of the eight study sites. Our study findings have multiple implications for priority setting in MiP program implementation. Based on the observed heterogeneity of HIV and malaria parasitemia prevalence in the study subjects, and on observed patterns of participation in HIV testing, we believe that preferential implementation of MiP interventions for communities with larger populations and higher burdens of HIV, as had been proposed by some funders and advocacy groups, would not serve to correct inequities in the observed burden of malaria in the sites we evaluated because resources would be directed to regions of lower, rather than higher, malaria prevalence. Similarly, restriction of MiP interventions to individuals with documented HIV infection would have missed more than 90% of the parasitemic women we studied. A better strategy for identifying high priority populations would be based on consideration of malaria transmission intensity and socioeconomic status, in addition to HIV prevalence, population size, and availability of preventive interventions, with universal provision of MiP interventions where vulnerability is great. This was the method adopted by the Sofala and Manica provincial health authorities in the aftermath of our study. Both the poorest and most malariaendemic districts and the sites with highest estimated HIV seroprevalence were targeted for early expansion of IPTp programs. Later, new funding from bilateral donors permitted one-time targeted free bed net distribution for rural and periurban sites without access to spraying campaigns; future campaigns are now in the planning stages. Teams responsible for implementation and supervision of IPTp and antenatal HIV services were merged; the resulting increase in efficiency supported IPTp implemention in every single district in both provinces. As of this writing, the combination of political will, data-driven strategic analysis, and increased funding has begun to reduce the onerous burden of deciding which of many vulnerable women and infants should or should not be protected from malaria and its sometimes fatal consequences. Received September 25, 2006. Accepted for publication April 12, 2007. Acknowledgments: We are grateful to the following entities and individuals for technical support and/or assistance with study implementation: Direcção Provincial de Saúde, Província de Sofala; Direcção Provincial de Saúde, Província de Manica; Direcção Distrital de Saúde, Distrito de Gondola; Direcção Distrital de Saúde, Distrito de Nhamatanda; the National Malaria Control Program of Mozambique, the Malaria Branch of the Centers for Disease Control and

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Prevention (Atlanta, GA), Pedro João Corda, David Ehlert, Maria Felicidade Faria, Florência Floriano, Sheila Lukehart, Marquês Machaieie, Tom Martin, Josefa Sairosse, Benjamin Stubbs, and Fernanda Toalha. Financial support: This study was supported by a cooperative agreement from the Centers for Disease Control and Prevention through the Association of Schools of Public Health (grant U36/CCU30043020), and by the Bill and Melinda Gates Foundation. Authors’ addresses: Paula E. Brentlinger, Kenneth Gimbel-Sherr, Mary Anne Mercer, and Stephen Gloyd, Department of Health Services, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, Telephone: 206-543-8382, Fax: 206-543-3964, E-mails: [email protected], ksherr@ u.washington .edu, [email protected], and gloyd@ u.washington.edu. Pablo Montoya and Ana Judith Blanco Rojas, Health Alliance International, Rua Mayor Serpa Pinto 294, 4° Andar, Sector da Repartição de Saúde da Comunidade, Beira, Mozambique, Telephone: 258-3-324-271, Fax: 258-3-325-882, E-mails: pablom@ teledata.mz and [email protected]. Maria Ana Chadreque Correia, Health Alliance International, Rua Dr. Araújo de Lacerda 147 CP 266 Chimoio, Mozambique, Telephone: 258-51-23251, E-mail: [email protected]. Martinho Dgedge, Training Department, Department of Human Resources, Ministry of Health, Av Eduardo Mondlane c/Salvador Allende, C.P. 264 Maputo, Mozambique, E-mail: [email protected]. Francisco Saúte, National Malaria Control Program of Mozambique, Communicable Disease Division, Ministry of Health, Av Eduardo Mondlane c/Salvador Allende, C.P. 264 Maputo, Mozambique, Telephone: 258-82-326-527, Fax: 258-1-311-621, E-mail: [email protected].

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