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研究生:Owen Nkoka
研究生(外文):Owen Nkoka
論文名稱:Assessment of malaria interventions in Malawian children
論文名稱(外文):Assessment of malaria interventions in Malawian children
指導教授:陳怡樺陳怡樺引用關係
指導教授(外文):CHEN, YI-HUA
口試委員:黃心苑張書森莊定武莊坤洋
口試委員(外文):HUANG, NICOLECHANG, SHU-SENCHUANG, TUNG-WUCHUANG, KUN-YANG
口試日期:2020-12-21
學位類別:博士
校院名稱:臺北醫學大學
系所名稱:公共衛生學系博士班
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2020
畢業學年度:109
語文別:英文
論文頁數:166
外文關鍵詞:Infant mortalityInsecticide-treated netsMalawi
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Background
Malaria is a public health problem with the disease having adverse effects on children who are the most vulnerable population. Different interventions have been implemented to avert as well as reduce the effects of malaria on child health outcomes such as low birth weight (LBW) and infant mortality. However, apart from inadequate and mixed findings on the effects of such interventions on child health outcomes, recent reports have raised concerns on the efficacy of interventions such as intermittent preventive treatment for malaria during pregnancy using sulphodoxine-pyrimethamine (IPTp-SP) due to the emergence of insecticide resistant parasites. Additionally, early detection and management of malaria is crucial to avoid the progression from uncomplicated to severe malaria. Thus, early treatment-seeking is critical in the overall management of malaria. Therefore, this study assessed the effects of household malaria interventions on child health outcomes (LBW and infant mortality), and identified factors associated with treatment-seeking behaviour for caregivers with febrile children.
Methods
In study I, using pooled datasets from the 2004, 2010, and 2015–16 Malawi Demographic and Health Surveys (MDHS), a total of 18,285 births were analyzed. Generalized linear models with a log-link function and a binomial distribution were conducted to explore the association between intermittent preventive treatment for malaria during pregnancy (IPTp), insecticide treated nets (ITN), and LBW as well as the associated effect modifiers.
In study II, a Cox proportional hazard model were applied to the MDHS data to determine the association between ITN access and use and infant mortality between 2004 to 2015-2016.
In study III, a two-level multilevel analysis was carried out to assess the effects of individual- and community-level factors on treatment seeking behaviors among caregivers with febrile children. The 2015-16 MDHS was used for this analysis.
Results
Study I: The overall LBW prevalence was 10.3%. LBW was lower in children whose mothers used adequate IPTp [adjusted prevalence ratio (APR) = 0.88, 95% confidence interval (CI) = 0.79–0.99] or used ITNs (APR = 0.89, 95% CI = 0.79–0.99) than their respective counterparts. LBW was 20.0% lower among children whose mothers adequately used both IPTp and ITN compared with those without IPTp or ITN use (APR = 0.80, 95% CI = 0.68–0.93). Iron supplement consumption and survey year were significant effect modifiers on IPTp and LBW relationship.
Study II: The overall infant mortality rate for the entire period was 47.9/1000 live births. Infants from the ITN-user households exhibited a lower risk of mortality [adjusted Hazard Ratio (aHR)=0.61, 95% Confidence Interval (CI)=0.44–0.85] than those from the ITN-nonuser households. Similarly, the infants from the high-access households exhibited a lower risk of death (aHR=0.63, 95% CI=0.46–0.86) than those from the no-access households. Infants from the ITN-user and high-access households exhibited a significantly lower risk of death (aHR=0.57, 95% CI=0.40–0.82) than those from the ITN-nonuser and no-access households. The relationship between ITN access and use and infant mortality was significant among female infants with a second or higher birth order and interval of ≥2 years.
Study III: Approximately 67.3% of the caregivers reported seeking treatment for their febrile child, whereas only 46.3% reported promptly seeking treatment. Children from communities with moderate and high percentages of educated caregivers were more likely to be taken for treatment (adjusted odds ratio [aOR] = 1.26, 95% CI = 1.01–1.58 and aOR = 1.31, 95% CI = 1.02–1.70, respectively) than those from communities with a low percentage of educated caregivers. Children from communities with moderate and high percentages of caregivers complaining about the distance to a health facility were less likely to be taken for treatment (aOR = 0.74, 95% CI = 0.58–0.96 and aOR = 0.67, 95% CI = 0.51–0.88, respectively). At the individual level, having a cough in the last 2 weeks, region, religion, and having better health behaviors in other health dimensions were associated with fever treatment-seeking behaviors among Malawian caregivers.
Conclusions
Results from study I revealed that there were evident benefits of independent and combined use of IPTp and ITN on LBW, thereby supporting the use of these interventions during pregnancy. The reduced protective effects of IPTp over time highlight the need for innovative MIP preventive methods.
The findings of study II emphasized the importance of ITN access and use in providing optimal protection against malaria to infants in Malawi. Malaria control programs should ensure high ITN access and use in Malawi to reduce infant mortality.
Programs aimed at improving treatment-seeking behaviors should consider these factors and the regional variations observed in study III.
Malaria interventions had protective effects on child health outcomes (i.e., birth weight and infant mortality). This study supports findings from other areas, and highlights the effect modifiers that affect the relationship between the interventions and child health outcomes for effective designing of malaria-related programs. Additionally, the contextual factors associated with treatment-seeking behaviors for caregivers with febrile children provide an opportunity for improving prompt diagnosis and treatment of malaria.
Background
Malaria is a public health problem with the disease having adverse effects on children who are the most vulnerable population. Different interventions have been implemented to avert as well as reduce the effects of malaria on child health outcomes such as low birth weight (LBW) and infant mortality. However, apart from inadequate and mixed findings on the effects of such interventions on child health outcomes, recent reports have raised concerns on the efficacy of interventions such as intermittent preventive treatment for malaria during pregnancy using sulphodoxine-pyrimethamine (IPTp-SP) due to the emergence of insecticide resistant parasites. Additionally, early detection and management of malaria is crucial to avoid the progression from uncomplicated to severe malaria. Thus, early treatment-seeking is critical in the overall management of malaria. Therefore, this study assessed the effects of household malaria interventions on child health outcomes (LBW and infant mortality), and identified factors associated with treatment-seeking behaviour for caregivers with febrile children.
Methods
In study I, using pooled datasets from the 2004, 2010, and 2015–16 Malawi Demographic and Health Surveys (MDHS), a total of 18,285 births were analyzed. Generalized linear models with a log-link function and a binomial distribution were conducted to explore the association between intermittent preventive treatment for malaria during pregnancy (IPTp), insecticide treated nets (ITN), and LBW as well as the associated effect modifiers.
In study II, a Cox proportional hazard model were applied to the MDHS data to determine the association between ITN access and use and infant mortality between 2004 to 2015-2016.
In study III, a two-level multilevel analysis was carried out to assess the effects of individual- and community-level factors on treatment seeking behaviors among caregivers with febrile children. The 2015-16 MDHS was used for this analysis.
Results
Study I: The overall LBW prevalence was 10.3%. LBW was lower in children whose mothers used adequate IPTp [adjusted prevalence ratio (APR) = 0.88, 95% confidence interval (CI) = 0.79–0.99] or used ITNs (APR = 0.89, 95% CI = 0.79–0.99) than their respective counterparts. LBW was 20.0% lower among children whose mothers adequately used both IPTp and ITN compared with those without IPTp or ITN use (APR = 0.80, 95% CI = 0.68–0.93). Iron supplement consumption and survey year were significant effect modifiers on IPTp and LBW relationship.
Study II: The overall infant mortality rate for the entire period was 47.9/1000 live births. Infants from the ITN-user households exhibited a lower risk of mortality [adjusted Hazard Ratio (aHR)=0.61, 95% Confidence Interval (CI)=0.44–0.85] than those from the ITN-nonuser households. Similarly, the infants from the high-access households exhibited a lower risk of death (aHR=0.63, 95% CI=0.46–0.86) than those from the no-access households. Infants from the ITN-user and high-access households exhibited a significantly lower risk of death (aHR=0.57, 95% CI=0.40–0.82) than those from the ITN-nonuser and no-access households. The relationship between ITN access and use and infant mortality was significant among female infants with a second or higher birth order and interval of ≥2 years.
Study III: Approximately 67.3% of the caregivers reported seeking treatment for their febrile child, whereas only 46.3% reported promptly seeking treatment. Children from communities with moderate and high percentages of educated caregivers were more likely to be taken for treatment (adjusted odds ratio [aOR] = 1.26, 95% CI = 1.01–1.58 and aOR = 1.31, 95% CI = 1.02–1.70, respectively) than those from communities with a low percentage of educated caregivers. Children from communities with moderate and high percentages of caregivers complaining about the distance to a health facility were less likely to be taken for treatment (aOR = 0.74, 95% CI = 0.58–0.96 and aOR = 0.67, 95% CI = 0.51–0.88, respectively). At the individual level, having a cough in the last 2 weeks, region, religion, and having better health behaviors in other health dimensions were associated with fever treatment-seeking behaviors among Malawian caregivers.
Conclusions
Results from study I revealed that there were evident benefits of independent and combined use of IPTp and ITN on LBW, thereby supporting the use of these interventions during pregnancy. The reduced protective effects of IPTp over time highlight the need for innovative MIP preventive methods.
The findings of study II emphasized the importance of ITN access and use in providing optimal protection against malaria to infants in Malawi. Malaria control programs should ensure high ITN access and use in Malawi to reduce infant mortality.
Programs aimed at improving treatment-seeking behaviors should consider these factors and the regional variations observed in study III.
Malaria interventions had protective effects on child health outcomes (i.e., birth weight and infant mortality). This study supports findings from other areas, and highlights the effect modifiers that affect the relationship between the interventions and child health outcomes for effective designing of malaria-related programs. Additionally, the contextual factors associated with treatment-seeking behaviors for caregivers with febrile children provide an opportunity for improving prompt diagnosis and treatment of malaria.
Table of contents
List of Figures .................................................................................................................................. viii
List of Tables ...................................................................................................................................... ix
1. CHAPTER 1: GENERAL INTRODUCTION ........................................................................ 1
1.1 Background ......................................................................................................................... 1
1.1.1 Malaria Epidemiology .................................................................................................. 1
1.1.2 Global malaria distribution ........................................................................................... 1
1.1.3 Malaria in sub-Saharan Africa ...................................................................................... 3
1.1.4 Malaria Situation analysis in Malawi ........................................................................... 3
1.1.5 Malaria in Children ....................................................................................................... 4
1.1.6 Malaria in Pregnancy .................................................................................................... 6
1.1.7 Malaria Prevention and Disease Management .............................................................. 7
1.2 Study focus ........................................................................................................................ 10
1.3 Aim ..................................................................................................................................... 11
1.3.1 Specific Objectives for study I (Low Birth Weight) ....................................................12
1.3.2 Specific Objectives for study II (Infant Mortality) .....................................................12
1.3.3 Specific Objectives for study III (Treatment-seeking behavior) ................................12
1.4 Conceptual framework ..................................................................................................... 13
1.5 Organization of the Dissertation ..................................................................................... 14
2. CHAPTER 2 LITERATURE REVIEW .................................................................................16
2.1 Brief history of malaria and elimination efforts ............................................................ 16
2.2 Preventive therapy strategy ............................................................................................. 17
2.2.1 IPTp ...................................................................................................................................17
2.2.2 IPTp in Malawi ..................................................................................................................18
2.3 Vector control strategy ..................................................................................................... 18
2.3.1 ITNs ...................................................................................................................................18
2.3.2 ITNs in Malawi ..................................................................................................................20
2.4 Malaria case management strategy ................................................................................. 20
2.4.1 Treatment-seeking behaviors .............................................................................................20
2.4.2 Treatment-seeking behavior in Malawi .............................................................................21
2.5 Child Health Outcomes .................................................................................................... 22
2.5.1 Low Birth Weight ..............................................................................................................22
2.5.2 Infant mortality ..................................................................................................................23
2.6 Impact of malaria interventions on health outcomes .................................................... 24
2.6.1 Influence of IPTp on LBW ................................................................................................24
2.6.2 Influence of IPTp on malaria and other infections ............................................................24
2.6.3 Influence of ITNs on LBW and mortality ..........................................................................25
2.6.4 ITNs and malaria infections ...............................................................................................25
2.6.5 Other factors that are associated with child health outcomes ............................................26
2.7 Factors associated with treatment-seeking behaviors for caregivers with febrile
children .......................................................................................................................................... 35
2.8.1 Individual-level factors ......................................................................................................35
2.8.2 Community-level factors ...................................................................................................38
2.8 Knowledge gap .................................................................................................................. 40
2.8.1 Malaria interventions and LBW ........................................................................................40
2.8.2 ITN access and usage and Infant mortality ........................................................................40
2.8.3 Contextual analysis of treatment-seeking behaviors ..........................................................41
2.8.4 Assessment of effect modification ..............................................................................42
2.9 Significance of the study ................................................................................................... 43
3. CHAPTER 3 Effects of malaria interventions during pregnancy on low birth weight
among Malawian children: a pooled cross-sectional study ...........................................................45
3.1 Chapter summary ...................................................................................................................... 45
3.2 Materials and methods .............................................................................................................. 45
3.2.1 Study design and data source .............................................................................................45
3.3.2 Measures ............................................................................................................................46
3.2.4 Statistical analyses .............................................................................................................48
3.3 Results....................................................................................................................................... 49
3.4 Discussion ................................................................................................................................. 52
4. CHAPTER 4 Effects of insecticide-treated net access and use on infant mortality in
Malawi: a pooled analysis of demographic health surveys ...........................................................74
4.1 Summary ................................................................................................................................... 74
4.2 Materials and methods .............................................................................................................. 74
4.2.1 Design and data source ......................................................................................................74
4.2.2 Measures ............................................................................................................................75
4.2.3 Ethics statement .................................................................................................................78
4.2.4 Statistical analyses .............................................................................................................78
4.3 Results....................................................................................................................................... 79
4.4 Discussion ................................................................................................................................. 81
5. CHAPTER 5 Multilevel analysis of factors associated with treatment-seeking behaviors
among caregivers with febrile children in Malawi ........................................................................97
5.1 Summary ................................................................................................................................... 97
5.2 Materials and methods .............................................................................................................. 97
5.2.1 Study design and data source .............................................................................................97
5.2.2 Measures ............................................................................................................................98
5.2.3 Statistical analyses ...........................................................................................................100
5.2.4 Ethical considerations ......................................................................................................102
5.3 Results..................................................................................................................................... 102
5.3.1 Descriptive statistics ........................................................................................................102
5.4 Discussion ............................................................................................................................... 106
6. CHAPTER 6 General Discussion and Conclusion ..............................................................124
6.1 Main Findings and its Specific Contribution of the Current State of Knowledge .................. 124
6.2 Contribution to scientific literature ......................................................................................... 125
6.3 Recommendations for further research ................................................................................... 127
7. REFERENCES .......................................................................................................................131
8. APPENDICES .........................................................................................................................164
Appendix 1: First page of the published article for study I .......................................................... 164
Appendix II: First page for published article for study II ............................................................. 165
Appendix II: First page for published article for study III ............................................................ 166

List of Figures

Figure 1 1 Map of malaria case incidence rate (cases per 1000 population at risk) by country, 2018 2
Figure 1 2 Trends in malaria case incidence rate globally, 2010 – 2018 2
Figure 1 3 Map of Malawi and the distribution of malaria cases 4
Figure 1 4 Effects of malaria in pregnancy on maternal, newborn, infant and child health 5
Figure 1 5 Effects of malaria in pregnancy 7
Figure 1 6 Causal pathway for malaria infection and child health outcomes 8
Figure 1 7 Summarized key malaria intervention strategies 10
Figure 1 8 The conceptual diagram of the associations related to malaria preventive strategies 14
Figure 2 1 Timeline of malaria and selected associated interventions 17
Figure 2 2 Description of ITN indicators 19
Figure 2 3 Low birth weight estimates by country and region, 2015 23
Figure 3 1 Distribution of birth weight among the selected subjects 72
Figure 4 1 Subgroup analysis of effects of ITN use on infant mortality. 94
Figure 4 2 Subgroup analysis of effects of intra-household ITN access on infant mortality 95



List of Tables

Table 3 1 Distribution of participants according to the statuses of IPTp uptake and bed net use 58
Table 3 2 Distribution of background characteristics by birth weight and potential factors associated with low birth weight 60
Table 3 3 Association between IPTp uptake and low birth weight stratified using ITN usage 62
Table 3 4 Stratified analysis of the association between uptake of intermittent preventive treatment and low birth weight 63
Table s3 5 Association between IPTp uptake and low birth weight stratified using ITN usage – IPTp cut-off at 2 doses across surveys 64
Table s3 6 Association between IPTp uptake and low birth weight stratified using ITN usage – IPTp cut-off at 3 doses across surveys 65
Table s3 7 Association between IPTp uptake and low birth weight stratified using ITN usage – IPTp cut-off at 4 doses across surveys 66
Table s3 8 Association between IPTp uptake and low birth weight stratified using ITN usage – Infants only (n = 6,747) 67
Table s3 9 Association between IPTp uptake and low birth weight stratified using ITN usage based on pooled data from MDHS 2010, 2015–16 (n = 15, 406) – controlling for health behavior variable 68
Table s3 10 Association between IPTp uptake and low birth weight stratified using ITN usage– written records on birth weight (n = 6,691) 69
Table s3 11 Association between IPTp uptake and low birth weight stratified using ITN usage– mother’s recall records on birth weight (n = 11,594) 70
Table s3 12 Association between IPTp uptake, ITN usage, and low birth weight (3-levels) – Results from multinomial logistic regression models 71
Table 4 1 Distribution of participants according to the statuses of malaria indicators 87
Table 4 2 Infant mortality rate according to background characteristics and potential factors affecting infant mortality 90
Table 4 3 Risks of infant mortality stratified by ITN use and ITN access 92
Table 4 4 Risks of infant mortality stratified by ITN use and ITN access at different age ranges (excluding neonates) 93
Table 5 1 Bivariate analysis of individual and community level factors associated with fever treatment-seeking behaviors 113
Table 5 2 Measures of association between individual- and community-level factors and fever treatment-seeking behavior 115
Table 5 3 Measures of association between individual- and community-level factors and promptness in fever treatment-seeking behavior 118
Table 5 4 Multilevel multinomial logistic regression analysis of factors associated with treatment-seeking behaviors 121
Table 5 5 Multilevel multinomial logistic regression analysis of factors associated with treatment-seeking behaviors continued… 122
Table 5 6 Multilevel multinomial logistic regression analysis of factors associated with treatment-seeking behaviors continued… 123
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