Objective: To look at the Red Cross and the Red Crescent societies integrated campaigns between 2002 and 2006 with free distribution of insecticide treated nets (ITN)that have taken place and its contribution to the Millennium Development Goals(MDG) and the Abuja target.  Method: Review of surveys, evaluations and reports from the International Federation of Red Cross and Red Crescent integrated campaigns. Published articles up to 2007 have been accessed from electronic databases Medline, PubMed, the Cochrane Library and website`s from WHO, UNICEF, GFATM , and related articles available from international organisations web sites in addition to informal discussions and meetings with key stakeholders. Results: The integrated vaccination and free distribution of long lasting insecticidal nets (LLINs) achieved a rapid, high and equal LLIN coverage among all wealth quintiles. The MDG and Abuja target for ITN coverage at household level were reached within a week giving a unique opportunity for a significant reduction in malaria incidences, morbidity and mortality. The ITN possession remained higher than utilisation, but utilisation increased if a follow up visit, ensuring nets being hung and properly used, had taken place at household level post campaign. Conclusion: Large scale free distribution of LLINs  bridge the equity gap between poor and rich and increased the use rate among children under five and pregnant women. The low utilisation versus possession remains a challenge and thus a “minimum standard” of a two phased strategy is recommend to reach maximum impact and the MDG; Phase one preparing for pre campaign data, logistical planning and distribution while phase two should focus on a post campaign Keep Up program providing health education at household level to ensure proper net hanging and use. / <p>ISBN 978-91-85721-42-9</p>

Malaria is a vector-borne disease that presents the most persistent and serious public health burden in Liberia. Numerous studies have examined the relationship between ITN use and malaria prevalence. However, little research has explored the effectiveness of ITNs in controlling malaria among children in postwar Liberia. The aim of this study was to examine the association between ITN ownership, parental economic status, ITN installation support, and malaria prevalence among children. This was a quantitative cross-sectional study guided by the health belief model. The study used secondary data from the 2011 Liberia Malaria Indicator Survey. Chi-square for association and Logistic regression were used to analyze the data. The results revealed a significant association between parental education and malaria prevalence. There was also a significant association between parental economic status and malaria prevalence. However, there was no significant association between ITN ownership and malaria prevalence after controlling for parental education and ownership of structure. These findings may foster social change by helping public health authorities in Liberia integrate ITN use with other strategies like mosquito larvae elimination and indoor/outdoor insecticide spraying as part of a comprehensive approach to malaria control. Additionally, massive awareness and economic capacity building should be undertaken to empower malaria endemic communities with the understanding that malaria can be rapidly reduced with other robust strategies in combination with ITN use. These strategies, if implemented, may effectively control malaria prevalence among children and the emotional and financial burdens endure by their families.

My graduate work focused on the syntheses and pharmacology of species-selective aryl methylcarbamate acetylcholinesterase inhibitors to combat the malaria-transmitting mosquito, Anopheles gambiae. We identified six novel carbamates that demonstrated levels of target selectivity exceeding our project milestone of 100-fold. Among the C2-substituted phenylcarbamates examined (class II), 2'-(2- ethylbutoxy)phenyl N-methylcarbamate (9bd*) was extraordinarily selective (570-fold ± 72). The high level of selectivity observed for many of the class II carbamates was attributed to a helical displacement within the active site of An. gambiae acetylcholinesterase, able to accommodate carbamates with larger C2-substituted secondary β-branching side chains. Conversely, this type of side chain forms unfavorable interactions within the active site of human acetylcholinesterase. The C3-substituted carbamates (class I), such as terbam (9c), were less selective than many of the class II carbamates; however, class I carbamates related to terbam (9c) were highly toxic to An. gambiae. In particular, the contact toxicity measured for 9c (LC₅₀ = 0.037 mg/mL) was equal to the commonly used agricultural insecticide, propoxur (9a, LC₅₀ = 0.037 mg/mL). In total, seventy aryl carbamates were screened for their inhibition potency and contact toxicity towards An. gambiae. The common final step in all of these syntheses was the carbamoylation of a phenol, which normally proceeded in a 70 to 90% yield. Thirty seven novel carbamates are reported out of the seventy two prepared. Although sixteen of the phenols were commercially available, the others were prepared with known and adapted synthetic methodologies. The emerging structure-activity relationships led us to focus on the synthesis of 3-tert-alkylphenols (Class I) and 2-alkoxy or 2-alkylthio-substituted phenols (Class II). Three methods particularly stand out: First, we applied the methods of Tanaka to prepare 3-tert-alkylphenols wherein a methyl group was replaced by a trifluoromethyl group. Second, we adapted the methods of Tanaka to prepare 3-tert-alkylphenols that lack fluorine substitution. This method is competitive with the little known method of Reetz to convert aryl ketones to the corresponding 1,1-dimethylalkyl group and allows one to access electron rich tert-alkyl-substituted aromatics that are not accessible by the Friedel-Crafts alkylation (Friedel-Crafts restricted). Third, we found a convenient and high-yielding method for selective S-alkylation of 2-mercaptophenol. In addition to the synthesis of carbamates, the preparation of one hundred three intermediates, phenols, and electron rich tert-alkyl arenes are reported. / Ph. D.

In the 20th century, microfinance went through a revolution: the number of microfinance was expanding exponentially all over the world. Microfinances are supposed to be one of the most efficient tools in alleviating poverty. The paper, Microfinance: Development Aid tool is analyzing whether microfinance institutions provide, beside the credit services, also preventive antimalarial services so as to lower malaria cases. Theoretical part is focused on definition and familiarization with 'microfinance, development aid and malaria' terms. Practical part analyses the malaria problem in connection with microfinance market and microfinance organizations in the three above mentioned countries.

Background: The effect of Malaria attack on maternal and child health in Nigeria is high compared with other countries in sub Saharan Africa. This problem has been a persistent issue in Nigeria and many researchers have tried to proffer solutions. Insecticide treated nets (ITN) have been identified as providing approximately 80% protection against malaria attack. However, all the measures put in place to control malaria failed to meet up with the set target of the Roll Back Malaria Initiative, which aimed at reducing malaria deaths in Nigeria by half by 2010 in line with the Millennium Development Goals (Anyaehie et al., 2009). As part of the global initiative to reduce malaria deaths before 2015 (Amoran, Senbanjo and Asagwara, 2011) the Nigerian government introduced intervention programmes to protect pregnant women, and children under-five years of age (Anyaehie et al., 2011). However, although there has been considerable and effective intervention in controlling this preventable disease in the African continent, marked inconsistency in the distribution of the ITN, scarcity and low usage in Nigeria (Amoran, Senbanjo and Asagwara, 2011) are apparent, despite emphasis on community-based strategies for malaria control (Obinna, 2011). For midwives in rural Nigeria the disproportionate vulnerability of pregnant women and young children is of great concern. This particular issue is the focus of a hermeneutic phenomenological inquiry into the experiences of pregnant women and mothers in their efforts to protect their families and themselves from malaria attack. The study contends that the ‘big (pan-African/national) story’ of malaria has found many voices, speaking from a predominantly positivist perspective. While some more interpretivist approaches to exploring experience have been employed elsewhere in Sub-Saharan Africa (Rachel and Frank 2005), there remains a need for more participatory research related to health care issues in Nigeria (Abdullahi et al 2013). Women and children make up the majority of the Nigeria population of over 160 million. An attack of malaria on them affects entire households and the economy of the nation. Therefore, the purpose of this study was to give voice to the ‘small (household) stories’ of Nigerian women (mothers and health workers), living and working in impoverished rural communities, and consider how their viewpoints, perspectives and imaginings might contribute to the fight for a malaria-free Nigeria. Methodological approach: The research draws on the philosophy of Martin Heidegger, Hans-Georg Gadamer, and Maurice Merleau-Ponty. The participants’ accounts are interpreted in terms of Africana ‘Womanism’ as defined by Hudson-Weems (1993), the socio-narratology approach elaborated by Frank (2010), and Igbo world-view. Research procedure: Individual semi-structured interviews and focus groups were conducted with Igbo women in three rural communities in Enugu State in eastern Nigeria (Nsukka, Ngwo, and Amechi). This was a three-phase process involving an initial orientation visit to engage with local gatekeepers and community health workers. A first round of interviews and discussion took place in three communities in 2014, followed by the first phase of interpretation. A second field trip took place in 2015, during which participants discussed the ongoing interpretation and elaborated further on some of the issues raised. Interpretive phases 2 and 3 followed this visit. Interpretive process: Interpretive shifts in understanding were accomplished in three ways: 1. Seeking thematic connections between participants’ accounts of living with the threat of malaria. 2. Engaging in dialogical narrative analysis to explore the work done by the stories embedded in individual accounts of living under the threat of malaria. 3. Crafting found poetry from within the collective accounts to produce an evocative text that could mediate an emotional response and understanding of the malaria experience. Key outcomes: The research was a response to calls for more participatory research into the detailed experiences of people in Africa facing up to the threat of malaria. It has provided a vehicle for the voices of a group of Nigerian women and health workers to bring attention to the continuing plight of pregnant women and their families with limited access to insecticide-treated bed nets in poor living conditions. They have told how they seek to empower themselves in their own small and particular ways. It has provided insights into their worldview(s) and what others might see from where they stand. As such it has added to their own call expressed during the research to “Keep malaria on the agenda.” The research has used the women’s own testimony to create an oral resource designed https://youtu.be/XelMXLUzTV0 to facilitate education and action among small local groups of women and their families, and for health workers in local rural communities.

Background: Insecticide-treated nets (ITNs) are one of the most effective prevention measures against malaria. Malaria is highly endemic in Ghana. The country implemented mass distribution campaigns of ITNs to cover 80% to 95% of the population but the rate of ITNs use among children under 5 years was 52%, which was lower than the universal coverage target of 100%. Objective: The objective of this study was to identify the socio-demographic factors associated with ITNs utilization among children under 5 years in Ghana. Methods: This was a secondary analysis from cross-sectional data of 3,029 children under five years obtained from Ghana Malaria Indicator Survey 2016. Logistic regression analysis was done to identify the determinants of ITNs utilization among children under 5 years in Ghana. Results: Size of the household, number of children ≤5 years old in the household, household wealth index, education level of mother, knowledge of mother on the protection of mosquito nets, place of residence, and region of residence were found to be significantly associated with ITNs utilization in children under 5 years. Conclusion: More interventions are needed to promote the use of ITNs to protect children against malaria. Interventions should focus on households with more than 7 members, households with more than 3 childrens ≤5 years, and on promoting girl’s education.

Malaria continues to cause significant mortality in sub-Saharan Africa and elsewhere, and existing vector control measures are being threatened by growing resistance to pyrethroid insecticides. With the goal of developing new human-safe, resistance-breaking insecticides we have explored several classes of acetylcholinesterase inhibitors. In vitro assay studies demonstrate that tri- and difluoromethyl ketones can potentially inhibit An. gambiae AChE (AgAChE). These compounds inhibit the enzyme by making a covalent adduct with the catalytic serine of AChE. Trifluoromethyl ketones however are poor inhibitors of the G119S resistant mutant of AgAChE. However difluoromethyl ketones can inhibit G119S AgAChE and compound 3-10g showed an IC₅₀ value of 25.1 nM after 23h incubation time. Despite this potent inhibition of AgAChE, the tri-, di-, and (mono)fluoroketones showed very low toxicity to An. gambiae, perhaps due to hydration and rapid clearance. In an attempt to improve An. gambiae toxicity, oximes and oxime ethers of these compounds were prepared as potential prodrugs. These structures identified trifluoromethyl ketone oxime 3-2d as a potent toxin against both wild-type (G3-strain) and a multiply resistant (Akron) strain of An. gambiae. This compound is within 3-fold of the toxicity of propoxur to wild type An. gambiae (LC₅₀ values of 106 and 39 µg/mL, respectively). Most significantly, 3-2d was much more toxic than propoxur to multiply-resistant (Akron) strain An. gambiae (LC₅₀ = 112 and >5,000 µg/mL, respectively). However, thus far we have not been able to link the toxicity of these compounds to a cholinergic mechanism. Pre-incubation studies suggest that significant hydrolysis of these compounds to TFKs does not occur over 22 h at pH 7.7 or 5.5. The mechanism of action of 3-2d remains unknown. Our enzyme inhibition studies have demonstrated that 3-2d does not hydrolyze to the trifluoromethyl ketone 2-9d at pH 7.7. The high Akron toxicity of 3-2d and poor inhibition of G119S AgAChE by 2-9d argue against enzyme mediated conversion of 3-2d to 2-9d within the mosquito. Thus, we can rule out an AChE inhibition mechanism for toxicity. Additional experiments by our collaborator (Dr. Jeffrey Bloomquist, University of Florida) also rule out inhibition of mitochondrial respiration or agonism of the muscarinic acetylcholine receptor. Future work will address other potential insecticidal modes of action. / Ph. D.

Malaria is one of the deadliest diseases known to mankind. In 2010, 219 million cases were reported, and 666,000 deaths were attributed to this disease. In the past, pyrethroid-treated mosquito nets have shown efficacy in reducing malaria transmission in many malaria endemic regions. However, an upsurge in the mosquito population that is resistant to pyrethroids threatens to compromise the efficacy of pyrethroid-treated bed nets. In an effort to develop another class of insecticide with a different mode of action, we have explored three classes of five membered heterocyclic carbamates (isoxazol-3-yl, pyrazol-5-yl, and pyrazol-4-yl), and 3-oxoisoxazole- 2(3H)-carboxamide as acetylcholinesterase inhibitors (AChE) targeting wild type (G3) and resistant (Akron) malaria mosquito Anopheles gambiae (Ag). Isoxazole carboxamide and carbamates were obtained regioselectively through judicious use of two different protocols. The final products were characterized and identified using ¹H and ¹³C NMR, and mass spectroscopy. In addition, the carboxamide structure was confirmed using X-ray diffraction. Several of the novel carbamates and carboxamides evaluated exhibited excellent toxicity towards susceptible G3 and resistant Akron strain An. gambiae (48f LC₅₀ G3 = 41 μg/mL, LC₅₀ Akron = 58 μg/mL, and 47i LC₅₀ G3 = 38 μg/mL, LC₅₀ Akron = 40 μg/mL). Hence, achieving the resistance- breaking goal. On the contrary, the commercial aryl methylcarbamates currently approved for indoor residual sprays (IRS) showed no potency towards the resistant strain An. gambiae (LC₅₀ G3 = 16-42 μg/mL, and LC₅₀ Akron >5,000 μg/mL). Further, we observed low toxicological cross-resistance ratios (RR) for the toxic isoxazol-3-yl and pyrazol-4-yl carbamates, and 3- oxoisoxazole-2(3H)-carboxamides (RR = 0.5-2.0). Amongst the commercial AChE inhibitors approved for IRS, only aldicarb exhibited such low RR (RR = 0.5), whereas the RR for commercial aryl methylcarbamates exceed 130-fold. The low RR observed for these novel heterocyclic inhibitors would certainly be favorable for a new anticholinesterase-based mosquitocide targeting both the susceptible and resistant strain mosquitoes. Although the overall selectivity (Ag vs human) did not exceed 24-fold, the heterocyclic carbamates and carboxamides synthesized by the author showed appreciable inhibition of resistant AChE (G119S) in comparison to commercial aryl carbamates, which showed no inhibition at all. During the course of this project, the isoxazol-3-yl and pyrazol-5-yl methylcarbamates proved to be unstable, and thus could not be isolated. The synthesis of pyrazol-4-yl methylcarbamates using N-methylcarbamoyl chloride proved particularly challenging due to the formation of by-products called allophanates. The similar Rf of the by-product and the desired final product made the isolation laborious and time-consuming. We have successfully overcome this problem by employing a new protocol, where triphosgene served as the carbonylating agent and N-methylamine in THF was used as the amine source. In addition, we have also developed another one-pot protocol for a safer synthesis of pyrazol-4-yl methylcarbamates utilizing 1,1- carbonyldiimidazole (CDI), and N-methylamine hydrogen chloride salt. With the pyrazol-4-yl core, apart from achieving excellent toxicity towards both strains of An. gambiae, we have also achieved excellent AgAChE vs hAChE selectivity (Ag vs h >100-fold). Due to our continued interest in developing this core, we have devised a convenient, scalable, no-column approach for the synthesis an intermediate 103 that can be utilized to synthesize these compounds more efficiently. / Ph. D.

Master of Public Health - MPH / The Health Extension Program (HEP) is an innovative, community based comprehensive primary health care program that Ethiopia introduced in 2003. It gives special emphasis to the provision of preventive and promotive services at community and household level. However, utilization of the HEP packages is low and reasons for this underutilization are not well known. The aim of this study is to assess the availability and utilization of the Health Extension Program Service in Akaki District of Oromia Region, Ethiopia. Quantitative study using a cross-sectional survey design. The study was conducted in Akaki District of Oromia Regional State in Ethiopia with 79,162 inhabitants. Random sampling was used to select 355 households. A structured data collection tool/ questionnaire was employed to collect data from the study participants. Data were analyzed using SPSS for Windows version 19. Descriptive statistics were used to analyze socio demographic characteristics of the study participants and to assess the availability and utilization of each service component. The response rate of the study was 100% with complete data obtained from 335 (94.4%) of the households. The majority (93.1%) of respondents were women. The availability of HEP services as described by the household visit of Health Extension Workers (HEWs) is very high with 86.6% visiting at least monthly and 11.3% visited sometimes. There was a highly significant association between the health extension workers’ visit to households and health extension service utilization during pregnancy (OR=16.913, 95% CI 8.074-35.427 at p<0.001). HIV testing utilization showed a tenfold increase among households who received education. Participation of households in the Model family initiative was another key factor associated with high levels of HEP services utilization. Though HEP services are available for most households, the frequency of household visits by HEWs and the involvement of Households in model family training greatly influenced service utilization. Improving frequency of services availability at household level and consistent health education will greatly improve services utilization.