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Title: The epidemiology of malaria, curable sexually transmitted and reproductive tract infections and their coinfection among pregnant women in a catchment area in Nchelenge District, Zambia
Author: Chaponda, E. B.
ISNI:       0000 0004 6425 4755
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2017
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Introduction: Malaria and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes (ABO) and are both prevalent in most parts of sub-Saharan Africa. From a public health perspective, control of these infections requires interventions that are part of an integrated antenatal care package. The extent to which there may be coinfection increases the importance of such an integrated approach to reduce ABO. A systematic review and meta-analysis published in 2012 showed that the prevalence of malaria and curable STIs/RTIs among antenatal attendees in sub-Saharan Africa is considerable. However, the prevalence of malaria and curable STI/RTI coinfection has not been reported in any epidemiological setting. The primary objective of this thesis is to address this knowledge gap by estimating the prevalence of malaria, curable STIs/RTIs and their coinfection and to highlight the importance of an integrated approach to control malaria and STIs/RTIs in pregnancy. Secondary objectives of the study were to: (1) determine risk factors for malaria, curable STIs/RTIs and their coinfection; (2) estimate the prevalence of ABO and identify risk factors for ABO; (3) measure the in vivo efficacy and the prophylactic effect of sulphadoxine-pyrimethamine (SP) in pregnant women, and (4) characterise the molecular markers associated with parasite resistance to SP among pregnant women. Methods: A prospective cohort study of 1,086 antenatal attendees was conducted in Nchelenge District, Zambia. Consenting women visiting two health centres for their first antenatal care (ANC) visit were screened for malaria and curable STIs/RTIs (Chlamydia, gonorrhoea, trichomoniasis, bacterial vaginosis [BV] and syphilis). Socio-demographic data and maternal characteristics were also collected at enrolment. Sulphadoxine-pyrimethamine was administrated as intermittent preventive treatment to eligible women and they were followed up at day 28 for a second 13 malaria screening to determine the therapeutic and prophylactic failure of SP. At delivery participants were screened for placental malaria and data on birth outcomes were recorded. Univariate and multivariate analyses were conducted to determine the association between the potential risk factors for infection and ABO. Results: Of the 1086 women recruited 729 were successfully followed to delivery. The prevalence of malaria infection measured by microscopy was 31.8% (95% CI, 29.1-34.6) and by PCR was 57.8% (95% CI, 54.9-60.8). The risk of malaria infection was higher among pregnant women recruited from Nchelenge health centre compared to those attending the Kashikishi health centre (adjusted odds ratio [aOR] = 1.81; 95% CI, 1.38-2.37, P < 0.001), and HIV-infected women across health centres had a greater risk of malaria infection compared to HIV-uninfected women (aOR = 1.46; 95%, 1.00-2.13, P = 0.045). Infection with at least one STI/RTI was observed in 64.8% (95% CI, 61-67.4) of the participating women. With the exclusion of BV the prevalence of infection with at least one curable STI was 34.5% (95% CI, 31.7-37.4). Infection with at least one STI was associated with BV. In comparison to uninfected women, women infected with BV were at a higher risk of being infected with at least one STI (aOR 1.44; 95% CI, 1.08-1.92, P = 0.012). HIV-infected women had a higher risk of infection with BV than HIV-uninfected women (aOR 1.87; 95% CI, 1.24-2.83, P = 0.003) and women infected with at least one STI had a higher risk of BV (aOR 1.40; 95% CI (1.07 -1.84, P = 0.01). Among participants with complete results (n=1071), 38.7% (95% 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. The risk of malaria and curable STI/RTI coinfection was higher among HIV infected women than HIV-uninfected women (OR; 3.59 [95% CI, 1.73-7.48], P < 0.001). The prevalence of composite ABO was 35.1%. Women shorter than 1.5m were at a higher risk of experiencing at least one ABO (aOR 1.55; 95% CI, 1.10-2.18, P = 0.02). The risk of having ABO among para II was less than half of the risk observed in 14 primiparous women (aOR 0.41; 95% CI, 0.27-0.61, P < 0.001) and much lower among multiparous women (aOR 0.32; 95% CI, 0.22-0.48, P < 0.001). Having taken two or more doses of SP during pregnancy was protective against ABO (aOR 0.47; 95% CI, 0.31-0.72, P = 0.001). None of the infections (malaria, curable STIs/RTIs and their coinfection) diagnosed at first ANC were associated with ABO. The prevalence of highly resistant quintuple mutant was 68.8% among first ANC attendees. Despite the moderate prevalence of the quintuple mutant among pregnant women, SP cleared parasitaemia in 86% of the asymptomatic malaria cases among HIV-negative women Conclusion: The prevalence of malaria, STI/RTI and their coinfection at first ANC in this study population was considerable. However, no association was found between ABO and infection with malaria or STI/RTI or their coinfection. This lack of association is partially a result of interventions within the ANC package including treatment of some STI/RTI, intermittent preventive treatment in pregnancy with SP and iron and folic acid supplementation. Sulphadoxine-pyrimethamine retains partial efficacy against P. falciparum malaria in this area with moderate prevalence of the quintuple mutant. While continuing the policy of offering intermittent preventive treatment with SP during pregnancy, an alternative preventive therapy that is effective against both malaria and STIs/RTIs needs to be considered.
Supervisor: Chandramohan, D. ; Chico, M. ; Michelo, C. ; Vwalika, B. Sponsor: International Centres of Excellence for Malaria Research ; Southern Africa Consortium for Research Excellence ; National Institutes of Health, USA
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral