Coinfections of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review and individual participant data meta-analysis protocol.

INTRODUCTION: Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa, the prevalence of malaria and curable STIs/RTIs is high and, where coinfection is common, combination interventions may be needed to improve pregnancy outcomes. The aim of this systematic review is to estimate the prevalence of malaria and curable STI/RTI coinfection during pregnancy, risk factors for coinfection and prevalence of associated adverse pregnancy outcomes. METHODS AND ANALYSIS: We will use three electronic databases, PubMed, EMBASE and Malaria in Pregnancy Library to identify studies involving pregnant women attending routine antenatal care facilities in sub-Saharan Africa and reporting malaria and curable STI/RTI test results, published in any language since 2000. We will search databases in the second quarter of 2023 and repeat the search before completion of our analyses. The first two authors will screen titles and abstracts, selecting studies that meet inclusion criteria and qualify for full-text screening. If agreement on inclusion/exclusion cannot be reached, the last author will serve as arbiter. We will extract data from eligible publications for a study-level meta-analysis. We will contact research groups of included studies and request individual participant data for meta-analysis. The first two authors will conduct a quality appraisal of included studies using the GRADE system. The last author will adjudicate if the first two authors do not agree on any appraisals. We will conduct sensitivity analyses to test the robustness of effect estimates over time (by decade and half-decade periods), geography (East/Southern Africa vs West/Central Africa), gravidity (primigravidae, secundigravidae, multigravidae), treatment type and dosing frequency, and malaria transmission intensity. ETHICS AND DISSEMINATION: We obtained ethics approval from the London School of Hygiene & Tropical Medicine (LSHTM Ethics Ref: 26167). Results of this study will be disseminated via peer-reviewed publication and presentation at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42021224294.

Assessment of syndromic management of curable sexually transmitted and reproductive tract infections among pregnant women: an observational cross-sectional study.

BACKGROUND: This study estimated the prevalence of curable sexually transmitted and reproductive tract infections (STIs/RTIs) among pregnant women attending antenatal care (ANC) in rural Zambia, evaluated the effectiveness of syndromic management of STIs/RTIs versus reference-standard laboratory diagnoses, and identified determinants of curable STIs/RTIs during pregnancy. METHODS: A total of 1086 pregnant women were enrolled at ANC booking, socio-demographic information and biological samples were collected, and the provision of syndromic management based care was documented. The Piot-Fransen model was used to evaluate the effectiveness of syndromic management versus etiological testing, and univariate and multivariate logistic regression analyses were used to identify determinants of STIs/RTIs. RESULTS: Participants had a mean age of 25.6 years and a mean gestational age of 22.0 weeks. Of 1084 women, 700 had at least one STI/RTI (64.6%; 95% confidence interval [CI], 61.7, 67.4). Only 10.2% of infected women received any treatment for a curable STI/RTI (excluding syphilis). Treatment was given to 0 of 56 women with chlamydia (prevalence 5.2%; 95% CI, 4.0, 6.6), 14.7% of participants with gonorrhoea (prevalence 3.1%; 95% CI, 2.2, 4.4), 7.8% of trichomoniasis positives (prevalence 24.8%; 95% CI, 22.3, 27.5) and 7.5% of women with bacterial vaginosis (prevalence 48.7%; 95% CI, 45.2, 51.2). An estimated 7.1% (95% CI, 5.6, 8.7) of participants had syphilis and received treatment. Women < 20 years old were more likely (adjusted odds ratio [aOR] = 5.01; 95% CI: 1.23, 19.44) to have gonorrhoea compared to women ≥30. The odds of trichomoniasis infection were highest among primigravidae (aOR = 2.40; 95% CI: 1.69, 3.40), decreasing with each subsequent pregnancy. Women 20 to 29 years old were more likely to be diagnosed with bacterial vaginosis compared to women ≥30 (aOR = 1.58; 95% CI: 1.19, 2.10). Women aged 20 to 29 and ≥ 30 years had higher odds of infection with syphilis, aOR = 3.96; 95% CI: 1.40, 11.20 and aOR = 3.29; 95% CI: 1.11, 9.74 respectively, compared to women under 20. CONCLUSIONS: Curable STIs/RTIs were common and the majority of cases were undetected and untreated. Alternative approaches are urgently needed in the ANC setting in rural Zambia.

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

BACKGROUND: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. METHODS: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. RESULTS: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. CONCLUSION: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections.

Background: We conducted a prospective cohort study in Zambia among pregnant women who received intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP). Methods: We calculated the odds ratios (ORs) of adverse birth outcomes by IPTp-SP exposure, 0-1 dose (n = 126) vs ≥2 doses (n = 590) and ≥2 doses (n = 310) vs ≥3 doses (n = 280) in 7 categories of malaria infection and sexually transmitted and reproductive tract infections (STIs/RTIs). Results: We found no significant differences in baseline prevalence of infection across IPTp-SP exposure groups. However, among women given 2 doses compared to 0-1 dose, the odds of any adverse birth outcome were reduced 45% (OR, 0.55; 95% confidence interval [CI], 0.36, 0.86) and 13% further with ≥3 doses (OR, 0.43; 95% CI, 0.27, 0.68). Two or more doses compared to 0-1 dose reduced preterm delivery by 58% (OR, 0.42; 95% CI, 0.27, 0.67) and 21% further with ≥3 doses (OR, 0.21; 95% CI, 0.13, 0.35). Women with malaria at enrollment who received ≥2 doses vs 0-1 had 76% lower odds of any adverse birth outcome (OR, 0.24; 95% 0.09, 0.66), and Neisseria gonorrhoeae and/or Chlamydia trachomatis had 92% lower odds of any adverse birth outcome (OR, 0.08; 95% CI, 0.01, 0.64). Women with neither a malaria infection nor STIs/RTIs who received ≥2 doses had 73% fewer adverse birth outcomes (OR, 0.27; 95% CI, 0.11, 0.68). Conclusions: IPTp-SP appears to protect against malaria, STIs/RTIs, and other unspecified causes of adverse birth outcome.

Malarial Infection and Curable Sexually Transmitted and Reproductive Tract Infections Among Pregnant Women in a Rural District of Zambia.

Malarial infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes. Reducing the burden of these infections in pregnancy requires interventions that can be easily integrated into the antenatal care (ANC) package. However, efforts to integrate the control of malarial infection and curable STIs/RTIs in pregnancy have been hampered by a lack of evidence related to their coinfection. Thus, we investigated the prevalence of coinfection among pregnant women of rural Zambia. A prospective cohort study was conducted in Nchelenge District, Zambia, involving 1,086 first ANC attendees. We screened participants for peripheral malarial infection and curable STIs/RTIs (syphilis, Chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis), and collected relevant sociodemographic data at booking. Factors associated with malarial and STI/RTI coinfection were explored using univariate and multivariate regression models. Among participants with complete results (N = 1,071), 38.7% (95% confidence interval [CI] = 35.7-41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI = 16.5-21.2) were infected with malaria parasites only; 26.0% (95% CI = 23.5-28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI = 14.1-18.6) had no infection. Human immunodeficiency virus (HIV)-infected women had a higher risk of being coinfected than HIV-uninfected women (odds ratio [OR] = 3.59 [95% CI = 1.73-7.48], P < 0.001). The prevalence of malarial and STI/RTI coinfection was high in this population. An integrated approach to control malarial infection and STIs/RTIs is needed to reduce this dual burden in pregnancy.

High burden of malaria infection in pregnant women in a rural district of Zambia: a cross-sectional study.

BACKGROUND: Malaria continues to be a major health problem in low-income countries. Consequently, malaria control remains a public health priority in endemic countries such as Zambia. Pregnant women and children under 5 years of age are among groups at high risk of malaria infection. Malaria infection is associated with adverse birth outcomes that affect the mother, foetus, and infant. Infection with HIV has been shown to increase the risk of malaria infection in pregnancy. The prevalence and the predictors of malaria infection among pregnant women resident in the Nchelenge District of northern Zambia were investigated. METHODS: Between November 2013 and April 2014, pregnant women in the catchment areas of two health centres were recruited during their first antenatal care visit. HIV testing was conducted as part of routine care. In addition, blood samples were collected from 1086 participants and tested for malaria infection using standard microscopy and polymerase chain reaction (PCR) techniques specific for Plasmodium falciparum. Multivariate logistic regression were conducted to examine the predictors of malaria infection. RESULTS: The prevalence of malaria identified by microscopy was 31.8 % (95 % confidence intervals [CI], 29.0-34.5; N = 1079) and by PCR was 57.8 % (95 % CI, 54.9-60.8; N = 1074). HIV infection was 13.2 % among women on their first antenatal visit; the prevalence of malaria detected by PCR among HIV-uninfected and HIV-infected women was 56.7 % (531/936) and 65.2 % (90/138), respectively. In the final model, the risk of malaria infection was 81 % higher among pregnant women recruited from Nchelenge health centre compared to those attending the Kashikishi health centre (adjusted odds ratio = 1.81; 95 % CI, 1.38-2.37, P < 0.001), and HIV-infected women across health centres had a 46 % greater risk of malaria infection compared to HIV-uninfected women (adjusted odds ratio = 1.46; 95 %, 1.00-2.13, P = 0.045). CONCLUSION: High burden of malaria detected by PCR in these pregnant women suggests that past prevention efforts have had limited effect. To reduce this burden of malaria sustainably, there is clear need to strengthen existing interventions and, possibly, to change approaches so as to improve targeting of groups most affected by malaria.