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Background Despite efforts to make maternal health care services available in rural Ethiopia, utilisation status remains low. Therefore, this study aimed to assess maternal health care services’ status and determinants in rural Ethiopia. Methods The study used quasi-experimental pre- and post-comparison baseline data. A pretested, semi-structured, interviewer-administered questionnaire was used to collect data. A multilevel, mixed-effects logistic regression was used to identify individual and communal level factors associated with utilisation of antenatal care (ANC), skilled birth attendance (SBA), and postnatal care (PNC). The adjusted odds ratio (AOR) and corresponding 95% confidence intervals (CI) were estimated with a p-value of less than 0.05, indicating statistical significance. Results Seven hundred and twenty-seven pregnant women participated, with a response rate of 99.3%. Four hundred and sixty-one (63.4%) of the women visited ANC services, while 46.5% (CI: 42–50%) of births were attended by SBA, and 33.4% (CI: 30–36%) had received PNC. Women who reported that their pregnancy was planned (aOR = 3.9; 95% CI: 1.8–8.3) and were aware of pregnancy danger signs (aOR = 6.8; 95% CI: 3.8–12) had a higher likelihood of attending ANC services. Among the cluster-level factors, women who lived in lowlands (aOR = 4.1; 95% CI: 1.1–14) and had easy access to transportation (aOR = 1.9; 95% CI: 1.1–3.7) had higher odds of visiting ANC services. Moreover, women who were employed (aOR = 3.1; 95% CI: 1.3–7.3) and attended ANC (aOR = 3.3; 95% CI: 1.8–5.9) were more likely to have SBA at delivery. The likelihood of being attended by SBA during delivery was positively correlated with shorter travel distances (aOR = 2.9; 95% CI: 1.4–5.8) and ease of access to transportation (aOR = 10; 95% CI: 3.6–29) to the closest healthcare facilities. Being a midland resident (aOR = 4.7; 95% CI: 1.7–13) and having SBA during delivery (aOR = 2.1; 95% CI: 1.2–3.50) increased the likelihood of attending PNC service. Conclusions Overall, maternal health service utilisation is low in the study area compared with the recommended standards. Women’s educational status, awareness of danger signs, and pregnancy planning from individual-level factors and being a lowland resident, short travel distance to health facilities from the cluster-level factors play a crucial role in utilising maternal health care services. Working on women’s empowerment, promotion of contraceptive methods to avoid unintended pregnancy, and improving access to health care services, particularly in highland areas, are recommended to improve maternal health service utilisation.

Since the largest Ebola outbreak in West Africa (2013-2016) highlighted the potential threat of the Ebola virus to the world, several vaccines have been under development by different pharmaceutical companies. To obtain vaccine licensure, vaccine trials assessing the safety, immunogenicity and efficacy of new vaccines among different populations (e.g. different in age, gender, race, and ethnicity) play a crucial role. However, while this deadly disease mainly affects Central and West Africa, clinical trial regulations are becoming increasingly complex and consequently more expensive, influencing the affected low- and middle-income countries (LMICs) in performing high quality clinical trials. Consequently, the completion of such trials in LMICs takes more time and vaccines and drugs take longer to be licensed. To overcome some of the obstacles faced, the EBOVAC3 consortium, funded by the European Union's Innovative Medicines Initiative and the Coalition for Epidemic Preparedness Innovations, enabled high quality vaccine trials in Central and West Africa through extensive North-South collaborations. In this article, the encountered challenges, mitigations, recommendations and lessons learned from setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of Congo are presented. These challenges are grouped into eight categories: (1) Regulatory, political and ethical, (2) Trial documents, (3) International collaborations, (4) Local trial staff, (5) Community engagement and sensitization, (6) Logistics, (7) Remoteness and climate conditions, (8) Financial. By sharing the encountered challenges, implemented mitigations and lessons learned for each of these categories, we hope to prepare and inform other researchers aspiring a well-functioning clinical trial unit in similar remote settings in LMICs. ClinicalTrials.gov identifier: NCT04186000.

Introduction Family planning knowledge is poor and use is low in Ugandan fishing communities. We compared the effectiveness of enhanced family planning (FP) education with routine counselling on FP knowledge and use. Methods Individuals aged 15–49 years were randomly assigned to intervention or control arm. The intervention constituted enhanced FP education based on a simplified handout extracted from the WHO FP guidance tool called, “Family planning: A global handbook for FP providers” which participants took home for additional reading. The control arm constituted FP counselling following Uganda Ministry of Health guidelines. FP knowledge score and contraceptive prevalence rate (CPR) were compared between trial arms at baseline and at 12 months. Negative binomial regression models were used to estimate the effect of the intervention on FP knowledge and use. Results Overall, 1410 participants were screened to enrol 1004 (502 per study arm, 48.5% women). Subsequently, 384 (76.5%) and 383 (76.3%) completed the 12 months’ follow-up in the intervention and control arms respectively. At baseline, a median FP knowledge score of 8 and a p p p p Interpretation Enhanced FP education using a simplified FP education handout was more effective in increasing FP knowledge and use compared to routine FP counselling for people living in fishing communities. Innovative FP education interventions are recommended for improving FP knowledge and optimizing uptake in remote-rural settings where literacy levels are low. Trial registration The study was registered by the Pan African Clinical Trial Registry on 03 July 2021 with a Trial Registration Number PACTR202107891858045. “Retrospectively registered”.

Introduction: Diarrheal diseases are one of the leading causes of death among children younger than 5 years of age in the world in general and in sub-Saharan Africa in particular. Mothers are predominantly responsible for child care and housekeeping in this region. The objective of this study was to determine the prevalence of diarrhea and identify its maternal determinants in children under five in the city of Lubumbashi. Methods: A cross-sectional study conducted throughout March 2018 collected data from 299 mothers through a household survey. A pretested structured questionnaire was used to collect data in face-to-face interviews. Results: The prevalence of diarrhea in children under 5 in Lubumbashi was 35.8%. In the univariate analysis, the variables associated with diarrhea were single motherhood, soap-free hand-washing after latrine use, and the presence of feces around the latrines. Multivariate analysis revealed that the presence of feces around latrines (OR adjusted = 2.12 [1.18-3.80]) was associated with diarrhea. Conclusion: Defective cleaning by mothers, specifically their failure to keep latrine areas clean and free of feces, is associated with the risk of diarrhea in children under five in the study area. A hygiene intervention program must be designed to promote healthy behavior to alleviate the burden of diarrhea in children.

This study aimed to determine the feasibility of vaginal/cervical nurse-assisted self-sampling (NASS) and the agreement between human papilloma virus (HPV) tests on self-samples versus clinician-taken (CT) specimens. Women participated voluntarily for cervical cancer screening at St. Aklesia Memorial Hospital. Eighty-three women provided a total of 166 coupled self-taken and CT specimens collected. Specimens were stored at room temperature for a maximum of 10 months and analyzed using validated the RIATOL qPCR HPV genotyping test, a quantitative polymerase chain reaction (qPCR) high-throughput HPV E6, E7 assay. The average age of the participating women was 32 years. Seventy-three women (87.9%) felt that NASS was easy to use. An overall HPV, high-risk (HR) HPV, and low-risk HPV prevalence was 22.7% (15/66), 18.2% (12/66), and 6.1% (4/66), respectively. The overall HR HPV prevalence was 17.2% (NASS) and 15.5% (CT). The most prevalent HPV type was HPV51; HPV 16 was only detected in 1 woman (CT+NASS) and HPV18 only in 1 woman (CT). The overall measurement agreement between self-taken and CT samples was moderate with a kappa value of 0.576 (P 2 men were associated with HR HPV positivity (P

Objective: To evaluate the efficacy of AntiViral 2 (AV2) in the regression of moderate and severe colposcopic lesions, when compared to placebo. Materials and Methods: Women, aged over 18 years with a colposcopic diagnosis of moderate to severe dysplasia were randomized to receive either two applications of AV2 or placebo within four days. Both examining physician and patients were blinded to the treatment option. Follow-up colposcopy was performed on days 11, 21, and 60. Results: A total of 50 patients were enrolled in this study. There was no statistically significant difference in screening entry criteria between the two groups. The results showed that the application of AV2 yielded a reduction of more than 50% for 21 out of 28 (75%) patients who received the active treatment versus a 0% for the comparable placebo group (p < 0.001). Conclusions: The authors conclude that AV2 can have a place in the treatment of colposcopically-detected cervical lesions. Due to the proven broad spectrum antiviral activity of AV2, a plausible explanation is that the lesions regress due to deactivation of the virus. Further trials with larger numbers and detailed cytology and histology are needed to confirm these results.

In medical research, the ethical principle of respect for persons is operationalized into the process of informed consent. The consent tools should be contextualized and adapted to the different socio-cultural environment, especially when research crosses the traditional boundaries and reaches poor communities. We look at the challenges experienced in the malaria Quinact trial, conducted in the Democratic Republic of Congo, and describe some lessons learned, related to the definition of acceptable representative, the role of independent witness and the impact of socio-economic vulnerability. To ensure children's protection, consent is required by the parents or, in their absence, by a legally mandated representative. In our setting, children's responsibility is often entrusted permanently or temporarily to relatives or friends without a tribunal mandate. Hence, a notion of culturally acceptable representative under supervision of the local Ethics Committee may be more suitable. To ensure protection of illiterate subjects, an independent witness is required to confirm that the consent was freely given. However, in low-literacy contexts, potential witnesses often don't have any previous relationship with patient and there may be power-unbalance in their relationship, rather than genuine dialogue. In poor communities, trial participation may be seen as an opportunity to secure access to healthcare. Poverty may also lead to competition to access the research-related benefits, with a risk of disturbance at societal or household level. Adjusting consent procedures to sociocultural and socioeconomic realities is essential for fulfilling the underlying ethical principles. This requires a collaborative dialogue between researchers, regulators and ethics committees.

Background Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda. Methods In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD. Results Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months’ long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs. Conclusion Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems.

Despite the increased prevalence of malaria, malaria-associated morbidities, and their major contribution to malaria transmission dynamics, SAC were not given the emphasis that they deserve from the national malaria programs. Their adherence to malaria prevention was the lowest as compared to other age groups. Consequently, several research groups recommend well-tailored malaria prevention education (MPE). However, little is known about how and where MPE should be given. Therefore this thesis is aimed to assess perceptions and impact of MPE on the use of malaria prevention measures and the incidence of malaria among schoolchildren in Southern. Methods: The thesis employed a cluster randomized controlled trial with an embedded qualitative evaluation. To develop MPE, the findings from parents’ perceptions of the cause of malaria and their malaria prevention experiences among SAC in Kutcha district were used. The quantitative data were analyzed by using R statistical software while the qualitative data were analyzed thematically and managed by NVivo software. Results: Parents of SAC perceive that hunger, mosquito bite, exposure to hot sunshine, poor sanitation and hygiene, and eating some sweet foods and unripe maize were the causes of malaria. These perceptions highly influenced the malaria prevention practices among their SAC. At the baseline of the trial, the ownership of at least one LLIN by households of SAC, their bed net utilization, and the prevalence of malaria infection was 19.3%, 7.8%, and 1.6% respectively. The MPE did not significantly influence bed net ownership, bed net utilization reported incidence of malaria, and treatment seeking from a health facility as a first choice. In the qualitative evaluation of MPE, four themes were identified: setup of the training, challenges for the success of the training, anticipated challenges for practice as per the protocol, and experienced immediate influences. There are certain context-specific factors that affect bed net utilization and prompt diagnosis and treatment of malaria from a health facility as the 1st choice. Conclusions: The prevalence of malaria was very low and all the infections were asymptomatic. Parents of SAC associated malaria with multiple causes. The MPE had no effect on the use of malaria prevention measures considered and reported cumulative incidence of malaria. The functional literacy adult education program in Ethiopia may be one of the platforms to be strengthened by giving due emphasis to malaria in the health theme section of the program.

Compared to the general population, school-aged children harbour high malaria parasitaemia in most endemic areas of sub-Saharan Africa. In most cases, these children remain asymptomatic, which makes them vulnerable for anaemia and impaired cognitive ability. Data from malaria preventive therapies support the hypothesis that clearing, otherwise untreated, asymptomatic infections may provide a window of opportunity for haematological recovery by decreasing the rate of destruction and removal of parasitized red blood cells and improving the erythrocyte production rate in the bone marrow. Several studies have shown intermittent preventive treatment of malaria in schoolchildren (IPTsc) to be a feasible and effective tool to reduce malaria and malaria related anaemia. Despite this, well-known concepts to help school aged children, none has generated solution ready to use in a pragmatic way leading to policy and practice of the suggested intervention (IPTsc). This thesis show evidence on the burden of asymptomatic malaria in school children (chapter 3,4 and 5), then evidence on impact of IPTsc intervention on schoolchildren (chapter 6) and how could such an intervention be scaled up pragmatically and into policy (chapter 7,8 and 9). Research findings are based from two studies conducted in Muheza (clinical trial covering 7 primary schools recruiting 1566 schoolchildren- NCT03640403) and Handeni (TC and DC) and Kilindi DC (implementation research covering over 127 primary schools with over 73000 schoolchildren- NCT04245033). This thesis has generated enough evidence that IPTsc is an important intervention reducing the malaria burden and its consequences in school age children with additional benefit on shrinking the reservoir in high endemic communities. The thesis comes up with a policy brief (chapter 9) developed to guide the introduction and practice of IPTsc in moderate to high endemic areas as recommended by the WHO malaria guideline 2023.

Family planning (FP) use prevents unwanted pregnancy, excessive population growth, and improves the health of women, children and the entire population. In Uganda, an estimated 310–438 women die of pregnancy-related causes per 100,000 live births. Approximately 41 infants per 1,000 births die during or within one month after birth. Many Ugandan women suffer severe morbidity, often as a result of unsafe abortion following unwanted or unintended pregnancies. Most of these mortalities and morbidities could be averted if FP use was optimized across the region. Data from the 2016 Uganda Demographic and Health Survey (UDHS) indicate that 39% of married women and 51% of sexually active unmarried women in Uganda use a FP method. Although the 2016 UDHS does not specifically report on FP knowledge, findings from research on FP in the country indicate that FP knowledge is generally high being higher among those with formal education than those with no education. Higher levels of contraceptive use tend to be higher among those with higher education levels. The 2016 UDHS shows that women with no education were less likely than women who have any education to use FP. Currently, only about 35% of the fisher folk are using FP which is lower than in the general population. Since the fisher folk are characterized by low education levels, it is important to evaluate their FP knowledge. To improve FP service provision in fishing communities, all barriers and facilitators of FP use among the fisher folk ought to be understood. Unintended pregnancies tend to be common where Contraceptive Prevalence Rates (CPRs) are low and these usually end in abortions. Establishing the rate of abortion and its correlates among the fisher folk will inform improvements in their reproductive health services. As Uganda moves towards achieving universal health coverage for FP, it is inevitable to understand the knowledge, behaviors and practices related to FP use in marginalized populations and how they may be leveraged to meet the country’s FP goals. The goal of this doctoral research project was to contribute to the urgently needed data to improve contraceptive uptake in the country but more so in the remote-rural fishing communities which are marginalized. The specific objectives of the doctoral research project were: 1) To determine the knowledge of family planning and its correlates among people in the reproductive age group from fishing communities (Paper I); 2) To determine the proportion using family planning, barriers to and facilitators of family planning use among people living in fishing communities (Paper II); 3) To determine the rate of abortion and its correlates among female fisher-folk along Lake Victoria in Uganda (Paper III); and 4) To evaluate the effect of enhanced FP education using a FP education tool on knowledge and use of FP among people living in fishing communities of Lake Victoria, Uganda (Paper IV). In paper IV, HIV and Syphilis prevalence and incidence rates in fishing communities were also determined. Findings of this research project will establish the evidence to recommend alternative FP education strategies for remote- rural settings with the aim of optimizing their FP knowledge and uptake. This research project will highlight some of the gaps in attaining the national SDGs and challenges in achieving national targets of the costed implementation plan. Methods To determine knowledge of FP and its correlates, a comparative cross-sectional study was conducted among 1410 people aged between 15-49 years in two fishing communities; Kigungu a mainland community and Nsazi an island community in Uganda (Sub-study I, Paper I). Through the same cross-sectional study, barriers and facilitators of FP use were determined (Sub-study I, Paper II); the rate of abortion and its correlates among female fisher-folk along Lake Victoria in Uganda was also determined (Sub-study I, Paper III). To get a deeper understanding of individual or community perceptions, behaviors and practices regarding FP, Focus Group Discussions (FGDs) and In-depth interviews (IDIs) were conducted. Through a randomized controlled trial among 1004 participants, the effect of enhanced FP education on knowledge and use of FP compared with routine FP counseling was determined (Sub-study II, Paper IV). The study intervention constituted FP education using the fourth cornerstone of the World Health Organization’s (WHO) FP guidance tool called “Family planning: A global handbook for providers”. This handbook contains medical information that helps health care providers deliver FP methods appropriately and effectively to clients. It contains tools for counseling and education on different FP methods. It also covers related health issues that may arise in the context of FP. It provides specific guidance on 20 FP methods, their doses, and contraindications and it addresses many of clients’ different needs, from correcting misunderstandings to managing side effects. Participants in the intervention arm were offered FP handouts which they took home for reference and further reading. The tool and other study questionnaires were piloted in a non-study community before use. Participants in the control arm received FP counseling following the Ministry of Health FP guidelines which in this study constituted the standard of care. No handouts were offered to participants in the control arm. Participants in both arms were offered FP methods of their choice, HIV Counseling and Testing, syphilis testing and treatment free of charge. The two sub-studies followed a logical sequence, and they collectively contributed to the overall aim of the research project. Results At baseline, nearly all (94.5%) participants were aware of the concept of FP and were able to name at least one FP method. However, just over a third (38%) had good knowledge of FP. Correlates of knowledge of FP were; being female (aOR: 1.92 95% CI: 1.39-2.67), residing on the mainland (aOR: 4.01 95% CI: 2.77-5.81), being married (aOR: 1.59 95% CI: 1.11-2.28) and being in a sexual relationship (aOR: 1.75 95% CI: 1.18-2.60) (Paper I). The proportion using all FP methods was 35.6%. Short acting reversible methods such as condoms, pills and injectables were the most commonly used methods. Participants from the Anglican and Muslim religions were more likely to use FP than Catholics ((aOR: 1.45; 95%CI: 1.05-1.99) and (aOR: 1.45; 95%CI: 1.05-2.07) respectively). Participants were more likely to use FP if they had good FP knowledge compared to those with didn’t have good FP knowledge (aOR: 1.79; 95%CI: 1.23-2.61), or if they were married compared to those who were single (aOR: 1.84; 95%CI: 1.32-2.57). Participants were more likely to use FP if they had two or more sexual partners in the last 12 months than those who had less than two sexual partners (aOR: 1.41 95%CI: 1.07-1.87). Excessive bleeding and delayed fecundity; fertility desire; gender preferences of children; method stock outs and lack of FP trained personnel constituted main reasons reported for not using FP. From the qualitative component of the study, it was further revealed that barriers to FP use were related to accessibility challenges, limited FP knowledge, limited available options, cultural and religious beliefs (Paper II). Misconceptions on effects of FP like sterility, cancers and fetal abnormalities were also found to be common barriers to FP use. Of the 713 women interviewed at baseline, majority (600, 84.2%) reported ever being pregnant. Approximately 45% of the pregnancies were un-intended. A third of those who had ever been pregnant (195, 32.5%) reported having aborted before while only 34.6 % reported ever using or currently using FP. Women aged 30+ years were more likely to abort compared to those aged 15-29 years (aOR: 2.7; 95% CI: 1.23-5.91) (Paper III). Results from the randomized control trial revealed that the FP knowledge score was 47% higher in the intervention arm than in the control arm (score ratio: 1.47, 95%CI: 1.43-1.51, p

Although 20 million women are eligible for cervical screening in Ethiopia, less than 1% of women have been screened. The reasons for the low uptake of cervical cancer (CC) screening may also be due to health beliefs and lack of knowledge regarding the primary risk factors causing cervical cancer; the collection method of the cervical samples as well as the distance to travel in order to reach a health facility which provides cervical cancer screening. The general purpose of this research study is: •to endeavor to improve the uptake of cervical cancer screening service by evaluating the feasibility of self-sampling as well as HPV testing as alternative screening options in Ethiopia, •to investigate the cervical cancer screening uptake where women's health beliefs and risk factors lead them to decide whether to be part of the cervical cancer screening program, •to do a systematic review of the self-sampling HPV detection rate by comparing results from samples collected by clinicians in Africa, and •to explore HPV genotype distribution as well as cervical cytology abnormality prevalence rates. Seventy-three women (87.9%) of the participants felt that nurse assisted self-sampling (NASS), using the ThinPrep plastic spatula and endocervical brush rinsed in Preservecyt Solution vial, was comfortable to use. An overall HPV, HR (High Risk) HPV, and LR (Low Risk) HPV prevalence was 22.7% (15/66), 18.2% (12/66) and 6.1% (4/66) respectively. The overall HR HPV prevalence was 17.2% (NASS) and 15.5% Clinician-taken (CT). The most prevalent HR-HPV type was HPV 51, and the overall measurement agreement between NASS- and clinician-taken samples was moderate with a kappa value of 0.576 (p

Schistosomiasis is a major public health problem in the world, especially in (sub)tropical countries. It affects more than 78 countries in the world, of which more than 90% are in sub-Saharan Africa. Linked to poverty, its consequences are of great importance for individuals, households, communities and countries. In Burundi, the disease is known for several decades. Only S. mansoni is endemic in the country. The main objective of this thesis was to explore the capacities of Burundi to integrate schistosomiasis control into the PHC system and provide evidence-based recommendations for the integration of schistosomiasis case management, disease surveillance, and other schistosomiasis control activities. The integration of schistosomiasis case management in the routine activities of health centres requires the improvement of health care providers’ knowledge — in charge of consultations and patient referrals — and the availability of praziquantel. Despite the obvious shortcomings, routine monthly reporting from health centres to DNHIS of intestinal schistosomiasis cases after confirmation by DS of stools, appeared to be able to monitor the impact of MDA with praziquantel in the general population; therefore, it could be used as an indicator for the disease surveillance in the country. However, more sensitive tests are recommended and desirable, such as the point-of-care Circulating Cathodic Antigen (POC-CCA) test, especially in low endemic settings such as Burundi and in view of the country elimination goal. For the integration of the four remaining activities beyond case management at the health centre level, the integration is favourable for health education, but not for the control of snail, clean water supply and sanitation, which require the (technical) involvement of other sectors beyond the MOH and international financial support which may not be sustainable in Burundi.

This PhD thesis entitled “Postpartum Infection at Mbarara Regional Referral Hospital, South Western Uganda - Epidemiology, Microbiology and Control” assessed the burden, causes and risk factors for maternal deaths at Mbarara Regional Referral Hospital (MRRH) in south-Western Uganda. With puerperal sepsis as the leading cause of maternal deaths at MRRH and the drivers of mortality being late referrals, non-attendance of antenatal care, un-education and HIV sero-positivity, further work was done to describe the microbiology and epidemiology of sepsis. We described the incidence of postpartum infection among women with postpartum fever or hypothermia presenting for delivery or postpartum care, compared clinical outcomes and examined the risk factors associated with incident fever/hypothermia. A composite infection outcome sepsis among mothers delivering at MRRH was done. Cesarean section was independently associated with in-hospital postpartum infection while antenatal clinic attendance was associated with reduced odds of postpartum infection. With Cesarean section being the commonest operation done on the Maternity ward at MRRH, there’s need to explore factors contributing to the high Cesarean section rates at MRRH and other factors that contribute to the occurrence of post-operative infection before delivery, during delivery and post-operatively. We further looked at whether vaginal colonization with GBS, E. coli, or Enterococcus was associated with increased morbidity among women with obstructed labor and determined the risk factors for colonization. There was no difference in maternal or neonatal morbidity between women with vaginal colonization with E. coli, GBS, and Enterococcus and those who were not colonized. Assessment of microbiology of infections is challenging especially in cases where the numbers are few. There are however contributors to infection and colonization such as poor hygiene and also nosocomial infections. Duration of labor was associated with increased risk of vaginal colonization in women with obstructed labor. This would mean that there are other factors that drive poor clinical maternal and neonatal outcomes in women who are colonized with potential pathogens and not necessarily the long labor duration. An intervention of the WHO Surgical Safety Checklist and pre-operative antibiotics for Cesarean section was introduced there was an increase of 77.6% and 69% in the use of WHO checklist and pre-operative antibiotics for Cesarean respectively. There was also a drop in surgical site infection by 6.9%.

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Cancer of the cervix is theoretically, the most preventable cancer. In the last 3 to 4 decades, the burden associated with cancer of the cervix was dramatically reduced in most developed countries where screening with papanicolaou test was successfully implemented in organised screening programmes. Since late 1990s, evidence has emerged that persistent HPV infection is the most important risk factor for cervical cancer development and later on, screening paradigm has changed from pap test based to HPV-based screening. Since more than a decade, HPV-type specific vaccination programmes have been implemented in majority of developed countries worldwide. Evaluation of these vaccination programmes show promising results towards cervical cancer control. Despite these developments, the burden associated with cervical cancer is still overwhelmingly high in low and middle income countries where implementation of sustainable screening programmes failed mainly due to limited financial investment, lack of well-trained healthcare workforce and infrastructure requirements. Burundi is a low income country with one of the highest cervical cancer incidence-to-mortality rate. Burundian Ministry of Health has recently undertaken some actions towards cervical cancer prevention: (1) a HPV vaccination project took place from 2016 to 2018 in two health districts and was deemed successful; the national rollout is planned for 2020 with the support of GAVI; (2) a cancer strategic plan has been elaborated and cervical cancer prevention activities include VIA screening implementation in a screen and treat approach. Other preventive activities such as male circumcision and promotion of condom use are part of the HIV control programme’s package. However, the circulating HPV strains and the preparedness of the healthcare workforce to contribute in cervical cancer control activities are not documented. In this regards, the scientific contribution contained in this thesis strongly supports the efforts to alleviate cervical cancer burden since it provides relevant information related to critical aspects that need to be addressed to better control the disease.

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Background and Rationale Women in the Democratic Republic of the Congo (DRC), Cervical cancer (CC) remains the first most common cancer diagnosed in with an estimated number of 3839 cases per year. Vaccination against human papillomavirus (HPV), the main cause of CC, has not been introduced yet in DRC. Cytology screening is opportunistic due to high cost, lack of infrastructure and scarcity of cytotechnicians. Data on the epidemiology of circulating HPV types is limited and the strains involved in invasive CC are not known in the DRC. Objectives Main objective: to contribute to the improvement of cervical cancer prevention and control strategies in low-resource settings. Specific objectives: - to assess the clinical efficacy of the viricide AV2® in the topical treatment of HPV-associated lesions of the uterine cervix; - to assess the prevalence and the distribution of HPV genotypes in a community of Kinshasa, DRC. Design and methods A phase 2 clinical trial first assessed the efficacy and safety of the antiviral AV2® in the treatment of cervical colposcopic lesions. Then a phase 3 randomized clinical trial (RCT) on the efficacy of AV2® in the treatment of HPV-associated precancerous lesions of the cervix was conducted. The main outcome was the regression of cervical lesions after the application of the topical drug AV2®. Major findings Efficacy of AV2® In the phase 2 clinical trial AV2®, application of AV2® resulted in regression of lesions in 21 out of 28 (75%) women, compared to 0% (0 out of 5) in the placebo group. The difference between the two groups was statistically significant (p < 0.001). During the phase 3 RCT, 327 women were enrolled. At 2 months, regression of lesions occurred in 127 (89.4%) out of 142 women in AV2® group compared to 120 (91.6%) out of 131 women in the placebo group (P = 0.708). Prevalence and genotype distribution of HPV in a community of Kinshasa The overall HPV prevalence was 28.2 %. Women younger than 30 years had the highest prevalence (42.2%). HPV68 was the most prevalent genotype. HPV genotypes distribution was different from other regions of the world. Conclusion and perspectives for research The high prevalence of HPV-related cervical diseases warrants improvement of the health system and the need for a nationwide and sustainable implementation of cervical cancer control strategies in DRC. Assessment of HPV genotypes involved in invasive CC will help in the design of future vaccines.

Leishmaniasis is a neglected tropical disease that affects over 1 million people worldwide. In India, it remains one of the major neglected conditions, affecting the poorest and most vulnerable in society, and has been marked for elimination as a public health problem. One of the pillars of the elimination strategy is the use of effective treatment for patients. The first chapter is a comprehensive literature review covering the last 10 years of evidence covering all aspects of leishmaniasis worldwide, with a focus on the clinical management. Major advances, as well as remaining lacunae are identified for both cutaneous and visceral forms of the disease. The second chapter focuses on the use of liposomal amphotericin B (LAMB) as a treatment for visceral leishmaniasis in Bihar, the most endemic state in India. It analyses the characteristics and outcomes of 8749 patients treated under programme conditions with 20mg/kg LAMB, including the use of the regimen at PHC level through task shifting. It then describes the risk factors for relapse and also the characteristics of post-kala azar dermal leishmaniasis (PKDL) following treatment. The third chapter examines a much under-stated aspect of treatment related studies – how patients perceive the treatments that they are receiving. It describes a qualitative study on cohorts of patients whom have received different regimens of treatment to determine the psychosocial determinants and perceptions of treatment, and how policy makers should consider these drivers when making rational treatment policy guidelines. The fourth chapter focuses on an area that was previously considered to be an issue confined to East Africa – VL in patients co-infected with HIV. It describes the prevalence of co-infection in a cross-sectional cohort study of 2077 patients presenting with VL, and then treatment outcomes using two different treatment regimens. It then describes through a qualitative study the quality of life perceptions in patients with VL-HIV co-infection, and suggest how their experiences and perceptions can be leveraged by policy makers to improve quality, access and standards of care. The final section of the thesis describes emerging issues in India and the sub-continent related to increasing knowledge and experience of immunosuppression in leishmaniasis.

Comment inK13-Propeller Mutations and Malaria Resistance, http://www.nejm.org/doi/full/10.1056/NEJMe1604520; International audience; BACKGROUND:Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.METHODS:We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.RESULTS:We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.CONCLUSIONS:No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).