Malaria and curable sexually transmitted and reproductive tract infections in pregnancy: a dual-burden of disease and challenge for the antenatal care package.

Malaria in pregnancy is associated with adverse maternal, fetal, and newborn outcomes, as are curable sexually transmitted and reproductive tract infections (STIs/RTIs). Estimates of pregnancies at risk of malaria have not been generated since 2007. Data on the burden of curable STIs/RTIs in pregnancy are sparse, and challenges remain in the diagnosis and treatment of these infections. The aim of this thesis was to better understand the dual burden of malaria and curable STIs/RTIs among pregnant women attending antenatal care (ANC) in sub-Saharan Africa and to investigate how integrated approaches to prevention and treatment can maximise the benefits of ANC for maternal, fetal, and newborn health. The research objectives of this thesis are: 1. To generate new global, regional, and national estimates of pregnancies at risk of Plasmodium falciparum and P. vivax in 2020 and investigate changes since 2000; 2. To investigate prevalence and risk factors for malaria and curable STIs/RTIs among pregnant women enrolled in a large randomised controlled trial (RCT) at ANC booking in Kenya, Malawi, and Tanzania; 3. To develop and validate a risk-prediction model which could be used at ANC booking to direct chlamydia and/or gonorrhoea diagnosis towards those most likely to be positive; and 4. To investigate changes in the prevalence of malaria and curable STIs/RTIs over the course of pregnancy, disaggregating by intermittent preventative treatment in pregnancy (IPTp) regimen. In chapter 1, I summarise research related to malaria and curable STIs/RTIs in pregnancy and current key questions concerning prevention and treatment at ANC. In chapter 2, addressing objective 1, I use estimates from Malaria Atlas Project and WorldPop to show that while the global number of pregnancies at risk of malaria has decreased over the past two decades, the number of pregnancies requiring IPTp has increased, standing at 34.8 million in 2020. In chapter 3, I elaborate on some of the challenges and opportunities in generating estimates of pregnancies at risk of malaria. In chapters 4 and 5, I analyse molecular diagnostic data collected at ANC booking to estimate prevalence and risk factors, using regression methods, for curable STIs/RTIs, STI/RTI co-infection, and malaria and STI/RTI co-infection (objective 2). Almost half of women (45.9%) were positive for at least one STI/RTI, three times as many as had malaria (14.6%), and one-in-ten women were co-infected with multiple STIs/RTIs. The high prevalence of these often asymptomatic infections, associated with adverse pregnancy outcomes, highlights the urgent need for alternatives to syndromic case management. In chapter 6 (objective 3) I develop and validate the sensitivity and efficacy of a chlamydia and/or gonorrhoea risk-prediction model. The high prevalence of infection among women with no, or few, identified risk factors meant that a risk score cut-off with an acceptable level of sensitivity would require screening large proportions of women, therefore limiting the advantage over universal screening. In chapter 7 (objective 4) I report changes in the prevalence of malaria and curable STIs/RTIs over the course of pregnancy by IPTp regimen. Regression methods are used to investigate differences in the relative risk of having a curable STI/RTI between IPTp regimens and between ANC booking and the third trimester. In the third trimester, chlamydia prevalence was almost five times higher in the dihydroartemisinin‐piperaquine (DP) group than in the sulfadoxine-pyrimethamine (SP) group (Relative Risk (RR)=4.5 [95% CI: 2.2, 9.1]) and three time higher in the DP plus azithromycin group than in the SP group (RR=3.1 [95% CI: 1.5, 6.4]). Chapter 8 is a summary of the results from preceding chapters, discussion, and conclusions regarding future research required to optimise malaria and curable STI/RTI management at ANC.