Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda

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This study analyzed malaria incidence from 2011-2017 across three altitudinal zones on Mount Elgon, Uganda, revealing seasonal variations, a general decline over time, and a shift of malaria becoming a hotspot in the high-altitude region.

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This study analyzed time-series malaria case patterns from 2011–2017 across three altitudinal zones (low, mid, high) in Kween District on Mount Elgon, using retrospective records from four level III health centers and meteorological rainfall and temperature data. Using inverse distance weighted interpolation, Mann–Kendall trend testing, and ARIMA forecasting, the authors found malaria seasonality with higher monthly incidence during May–August (89±88/1000) versus November–February (40±33/1000) and a general decline over time across all altitude zones, with annual averages of 587±750/1000 (lower), 345±321/1000 (mid), and 338±351/1000 (high). A key caveat is that malaria diagnoses relied on health-center testing records and could involve either microscopic or rapid diagnostic testing rather than both consistently, alongside purposive sampling of centers. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract Background Malaria remains a major tropical vector-borne disease of immense public health concern owing to its debilitating effects in sub-Saharan Africa. In the recent past, the high altitude areas in Eastern Africa have been reported to experience dramatic cases of malaria. However, its patterns following intensified control and prevention interventions remains and the changing climate remains widely unexplored in these regions. This study thus analyzed malaria patterns across altitudinal zones of Mount Elgon, Uganda. Methods Times-series data on malaria cases (2011 - 2017) from five level III local health centers occurring across three altitudinal zones; low, mid and high altitude was utilized. Inverse Distance Weighted (IDW) interpolation regression and Mann Kendall trend test were used to analyze malaria patterns. Autoregressive Integrated Moving Average (ARIMA) model was used to project malaria patterns for a seven year period. Results On average, 66±69/1000 individuals suffered from malaria on a monthly basis. This was most pronounced in the months of May-August 89±88/1000 compared to the months of November-February (40±33/1000). Malaria patterns varied with season and altitude and declined over time across the three altitudinal zones. Observed cases, revealed an annual average of 587±750/1000; 345±321/1000 and 338±351/1000 cases in lower, mid and high altitudes respectively. Conclusions Despite observed decline in malaria cases across the three altitudinal zones, the high altitude zone became a malaria hotspot as cases variably occurred in the zone. The projections of malaria revealed declining patterns of malaria cases in all the altitudinal zones. Malaria control interventions thus ought to be strengthened and strategically designed to achieve no malaria cases across all the altitudinal zones. Integration of climate information within malaria interventions can also strengthen eradication strategies of malaria in such differentiated altitudinal zones.
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In the recent past, the high altitude areas in Eastern Africa have been reported to experience dramatic cases of malaria. However, its patterns following intensified control and prevention interventions remains and the changing climate remains widely unexplored in these regions. This study thus analyzed malaria patterns across altitudinal zones of Mount Elgon, Uganda. Methods Times-series data on malaria cases (2011 - 2017) from five level III local health centers occurring across three altitudinal zones; low, mid and high altitude was utilized. Inverse Distance Weighted (IDW) interpolation regression and Mann Kendall trend test were used to analyze malaria patterns. Autoregressive Integrated Moving Average (ARIMA) model was used to project malaria patterns for a seven year period. Results On average, 66±69/1000 individuals suffered from malaria on a monthly basis. This was most pronounced in the months of May-August 89±88/1000 compared to the months of November-February (40±33/1000). Malaria patterns varied with season and altitude and declined over time across the three altitudinal zones. Observed cases, revealed an annual average of 587±750/1000; 345±321/1000 and 338±351/1000 cases in lower, mid and high altitudes respectively. Conclusions Despite observed decline in malaria cases across the three altitudinal zones, the high altitude zone became a malaria hotspot as cases variably occurred in the zone. The projections of malaria revealed declining patterns of malaria cases in all the altitudinal zones. Malaria control interventions thus ought to be strengthened and strategically designed to achieve no malaria cases across all the altitudinal zones. Integration of climate information within malaria interventions can also strengthen eradication strategies of malaria in such differentiated altitudinal zones. Infectious Diseases Afromontane ecohealth malaria ecotones climate change infectious diseases Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Malaria is an infectious disease that globally affects more than 200 million people and whose morbidity and mortality is most pronounced in Africa [ 1 ]. Through bites of infected mosquitoes, disease causing parasites are transmitted [ 2 ]. In 2013 alone, a total of 584, 000 deaths attributed to malaria occurred [ 2 ]. Interventions over the last decade have led to observed decline in the malaria burden in sub-Saharan Africa. However, it still remains a major public health threat of international and regional concern [ 4 ]. Malaria occurrence has traditionally been observed in the low-land areas, bogs and generally in the plains within the tropical regions [ 5 ]. Comparative analysis have shown the occurrence of such patterns in Africa, Latin America and Caribbean as well as in south east Asia [ 6 ] [ 7 ] [ 8 ] [ 9 ]. Meanwhile, the Afromontane areas characterized with unique biota [ 11 ], that had hitherto been known for being malaria free zones due to altitudinal effect, have seen increased malaria incidences with some areas experiencing a rise while others declining [ 12 ] [ 13 ]. Malaria cases have lately been observed to be on the rise in the afromontane ecotones within sub-Saharan Africa such as in the Rwenzori highlands of south western Uganda [ 14 ][ 15 ]. Similar patterns have been experienced in the neighboring highlands of Butare (Rwanda) as well as in the Mount Kilimanjaro area (Tanzania) [ 16 , 17 ]. These patterns in malaria have led to increased cost of malaria interventions [ 18 , 19 ]. Such trends have been attributed to climate change that is creating ambient conditions within the highland altitudinal belts [ 17 ]. Malaria in Uganda has been endemic in the savannah areas of northern and eastern Uganda especially in Apac district, followed by Tororo district [ 20 ]. All these areas are within 1,100 m altitude. However, highland areas especially Elgon region have experienced a surge in malaria cases despite intensified interventions by both government, private sector and development partners [ 15 ]. Climate has been pointed out as a key risk factor for spatial-temporal patterns of malaria, especially in the highland areas [ 18 ]. Studies [ 19 , 20 ] on malaria patterns in different mountainous areas have been undertaken but only a few [ 21 , 22 ] have focused on the patterns of malaria within different altitudinal zones (ecotones). Yet ecotones are characterized with varying environmental conditions that can influence mosquito biology and malaria patterns [ 23 , 24 ]. These studies have not documented patterns of malaria following intensified control and prevention interventions in mountainous areas such as Elgon region. This study analysed malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention interventions in the area. Methods Study area The study was undertaken in the Mount Elgon highland region within Kween District located between 0125N and 3431E (Figure 1). Kween district borders the districts of Nakapiripirit to the north, Amudat to the northeast, Bukwo to the east, Kapchorwa to the west and Bulambuli to the northwest [22]. In the South, it boarders the Republic of Kenya and it is located on the northern slopes of Mount Elgon, at an average altitude of about 1,900 meters (6,200 Feet) above sea level [22]. It has administrative units ranging from Sub county, Parish and village [23] The area is characterized by high and well-distributed rainfall (averaging 1,200 mm/year) and consists of two seasons, a rainy season (March–September) and a dry season (October–April) [25]. It has cool temperatures which are on average 17˚C [26]. The human population of the district has been rising in the last three census conducted; 1991, 2002 and 2012 from 37,300, 67,200 to 103,300 respectively [27]. Its population is majorly consisting of subsistence farmers cultivating a range of crops including: maize, beans, bananas, wheat, barley and cowpeas and also rear some livestock [22]. The district has health centers with levels: IV, III and II with numbers amounting to 1, 9 and 13 respectively [22]. These health centres are supported by a team of village health teams also known as heath service providers constituting Health Center I and are mainly responsible for mobilization of communities to access health services. Study design This study employed a retrospective cross-sectional study design utilizing past records from health center IIIs across the three altitude zones (High, Middle and Lower) of Mount Elgon [28]. Data on climate variables was obtained across seven years (2011 to 2017). Data on confirmed malaria cases (using both microscopic and rapid diagnostic kits) from 2011 to 2017 was considered for this study and were computed to average number of true malaria cases per 1000 for each of the altitudinal zones. The rates of malaria cases was computed per month for each year. Climate data was obtained in retrospect for the seven year period (2011 to 2017). Rainfall and temperature parameters were the key climate parameters considered in this study as they play key roles in influencing breeding and survival of mosquitoes [29]. Analysis for the spatial temporal patterns was computed at parish level across the three altitudinal zones in the study area. Confounding factors like human population were checked for their effect on the patterns of malaria incidences. There was however no effect of human population on the spatiotemporal patterns of malaria in the study area. Forecasts for malaria were made using ARIMA models for a period of 7 years (84 months) from the year 2017 [30]. Rates of malaria and time in terms of months were included in the model to understand the trends. Data collection In this study, health centers from where data was collected were purposively selected basing on their capacity to confirm and report malaria cases, as well as the volume of their malaria records. Accordingly, the most suitable health centres that were used to collect data were the health center IIIs owing to their capacity to conduct malaria tests (both microscopic and Rapid Diagnostic Test kits). The cases selected for this study at least underwent through one of these tests but not both. These health centres were also fairly well distributed across the different altitude zones divided into higher (above 7150ft), middle (between 4317-7150ft) and lower altitudes (below 4317ft) in the district. Data was then collected from four out of nine Health Center IIIs in the four sub-counties of Benet, Binyiny, Kwanyiy and Ngenge. Data on the number of malaria cases for the past seven years was obtained from the Health Center IIIs records. Data collected included; malaria occurrence, parish of residence, tests as well as a range of socio-demographic characteristics (gender, age and location) of each patients were obtained for a period of seven years. Data for climate variables (temperature and rainfall) was obtained from the Uganda National Meteorological authority [27]. Data analysis Malaria patterns were determined using descriptive statistics of means and standard deviations (SD). These were compared across different altitudinal zones; low, mid and high altitude. Mean malaria cases per month per 1000 cases were computed over the years (2011 to 2017) for each of the three altitude zones (Higher, Middle and Lower). Secondly, in order to depict the spatial-temporal variation of malaria cases, an Inverse Distance Weighted (IDW) interpolation regression [28] at a distance of 15km was undertaken. The IDW is a deterministic regression procedure that estimates values at prediction points (V) using the following equation [29]: (see Equation 1 in the Supplementary Files) Where d is the distance between prediction and measurement points, V 1 is the measured parameter value, and p is a power parameter. The advantage of IDW is that it uses non-Euclidean “path distances” for d. These path distances are calculated using an algorithm that accounts for the malaria cases from one cell to the next [30]. Trend analysis were done similarly to the approach by [35]. The average monthly numbers of malaria cases per 1000 were calculated for the full time-series (January 2009–December 2015). These were plotted to show temporal patterns in malaria and climate variables. The time series of malaria incidence was decomposed using seasonal-trend decomposition based on locally weighted regression to show: the seasonal pattern, the temporal trend and the residual variability. The time series data, the seasonal component, the trend component and the remainder component are denoted by Y t , S t , T t , R t respectively, for month t = 1 to N, and: Y t = S t + T t + R t The parameter setting “periodic” was used for the seasonal extraction, and all other parameters were by default. In the study, logarithmic transformations were used for the time series data [35]. Mann Kendal trend test [36] was used to depict the actual trends of the climate parameters and malaria. Relational analysis for malaria, temperature and precipitation was done in XLSTAT [37]. Results Time series decomposition of malaria patterns revealed existence of seasonality of malaria across the years (2011 – 2017) in all the altitude zones (Figure 3). The number of cases of malaria declined from 2011 to least number of cases towards 2017 (Figure 3). There was statistical significant difference (p<0.05) in the number malaria cases per 1000 individuals across the three altitude zones (lower, mid and higher altitude) in each of the years (2011-2017) except the years 2013 and 2017 (Table 1 and Figure 2). The cases of malaria per 1000 in high, mid and lower altitude were 49 (SD = 40), 67 (SD = 55) and 84 (SD = 96) respectively. Malaria cases revealed a normal curve-shaped trend over each year in the three areas (lower, middle and higher altitude areas) (Figure 3). Also the months of June revealed highest numbers of malaria cases (94, SD = 73; 103, SD = 73 and 128, SD = 134 in high, mid and lower altitudes respectively) over the years (2011 to 2017). The months of January (41, SD = 29; 45, SD = 41 and 52, SD = 67 in high, mid and lower altitudes respectively) and December (28, SD = 23; 29, SD = 21 and 38, SD = 23 in high, mid and lower altitudes respectively) had the least number of malaria cases. Spatial variation of malaria (Figure 4) revealed higher number of cases of malaria in the lower altitude areas of Kween district. Higher and mid-altitude areas of the district had relatively lower number of malaria cases (49, SD = 40 and 67, SD = 55 respectively), while lower altitude areas had the highest (84, SD = 96) number of malaria cases. The trends however declined from 2011 to 2017 in all the altitudinal zones (Figure 4). Mann-Kendal trend test revealed a Sen’s slope of -29.0 and -10.9 (CI = 0.95) for malaria cases in the periods of March to September and October to February respectively in the higher altitude areas of Kween district. It also revealed a drastic decline of malaria cases over the seven year period (from 2011 to 2017) with Sen’s value of -21.5 (CI = 0.95). In the middle altitude areas, the Sen’s slope were -44.8, -56.0 and -29 annually, March to September, and October to February respectively (CI = 0.95). In the lower altitude, the Sen’s values were -87.8, -120.7 and -41.9 annually, March to September and October to February respectively (CI = 0.95). Malaria cases, rainfall and temperature interaction in different altitude zones The mean temperatures in higher, mid and lower altitude areas of Kween district between 2011 and 2017 were 15.7ᴼC (SD = 2.8), 18.4ᴼC (SD = 1.3) and 21.4ᴼC (SD = 1.8), respectively. Higher altitude areas experienced a very low positive correlation (0.47) between precipitation and number of malaria cases (Table 2 and Figure 5). Similarly, there was a very low negative correlation (-0.46) between temperature and number of malaria cases. Annually, there was a high positive correlation (0.79) between number of malaria cases and precipitation. The relationship between temperature and malaria cases showed a negatively high correlation (-0.84). For mid-altitude there was a very low positive correlation (0.47) between precipitation and malaria cases (Table 2 and Figure 5). Similarly, there was a low negative correlation (-0.64) between temperature and malaria cases. Also annually, there was a low positive correlation (0.59) between precipitation and malaria cases. Meanwhile, temperature and malaria cases showed a negatively low correlation (-0.45). Lower altitude reflected a positively high correlation (0.72) between precipitation and malaria cases (Table 2 and Figure 5). Similarly, there was a negatively high correlation (-0.78) between temperature and malaria cases. Annually, there was a positive moderate correlation (0.70) between malaria cases and precipitation. Meanwhile, temperature and malaria trends showed a negatively high correlation (-0.83). Forecasting of malaria patterns Forecasts for all the three altitudinal zones revealed malaria cases to continue to decrease if the conditions were kept constant and/or intervention efforts are strengthened (Figure 6). However, relaxation of the malaria control interventions would greatly allow for more increased number of cases of malaria (Figure 6). Discussions There was a declining number of malaria cases across all the altitudinal zones during the study period. This can be attributed to the intensified malaria control and prevention interventions within the area. Such patterns are similar to results in other studies in western Kenya on the Elgon area [38]. Malaria patterns revealed a normal curve trend of malaria with the highest peak being in the middle (June-August) of each of the seven years (Figure 3). This corresponded to the trends in temperature and precipitation. However, the months of January and December had the least number of malaria cases. This can be linked to the low precipitation amounts during this period limiting availability of water for breeding of mosquitoes. This trend is similar to the results by [31] for the whole country (Uganda). This can be linked to the conditions suitable for growth and development of mosquitoes. Increase in temperature and availability of water sources favors mosquito breeding and its transmission of malaria parasites [40]. Results of this study revealed an overall malaria decline in the seven years of analysis. Similarly, analysis performed by [31] had shown declining trend in malaria over Uganda. These patterns could be attributed to significant intervention efforts by the Ministry of Health in malaria prevention and control through increasing access to health services including basic diagnostics, provision of insecticide-treated mosquito nets [34]. Spatially, the hotspot of malaria varied over the seven year period dominating the lowland areas of the district (Figure 4). The highland areas had lower number of malaria cases compared to the lowland areas. There was a positive correlation between malaria patterns in the lower belt and temperature. Temperature plays a key role in malaria transmission by influencing vector and parasite life cycles. Studies have highlighted the biological amplification nature of temperature on mosquitoes [32]. This study showed that the mean temperatures within the three altitudes varied. The difference in the contribution of maximum temperature to malaria cases between different altitudes is attributed to the differences in prevailing temperatures in the three zones. The study area (Kween district) being colder, temperature was probably the limiting factor in malaria vector development in the highland and lowland areas; hence a rise in the maximum temperature increased vector and parasite development rates [33]. Since temperature influences the development and survival rates of both vectors and parasites, malaria transmission rates tend to increase with increasing temperature but up to a given threshold [34]. The highland areas of the district that experienced a decline can be attributed to the increased malaria control interventions like use of mosquito nets. The question on existence of malaria in the higher altitude areas in East Africa raised by [36] is thus partly answered by this study. Relational analysis results revealed a positive association between precipitation and malaria patterns (Table 2 and Figure 5). Malaria cases were more pronounced in the lower altitude zones compared to the higher altitude zones. This can probably be linked to environmental conditions favorable for mosquito growth and development. This result is in agreement with previous studies in Kabale, a highland region in southwestern Uganda [31] where lowland areas expirience higher number of malaria cases compared to highland areas. The alternating trends can be alluded to temperature and precipitation as the latter can either favor or discourage optimal growth and development of mosquitoes. [37] notes that mosquito growth and development greatly depend on ambient air temperature and rainfall not forgetting any changes within the norm greatly affects mosquito growth and development which in turn affects the malaria incidence in malaria endemic areas [38]. Forecasts of malaria patterns revealed a continued decline of malaria cases given conditions are remain constant. However, the number of malaria cases may significantly explode if temperature and rainfall increase. This implies that interventions at this point ought to be intensified. There is also a window of opportunity for eradication of malaria in the event that the existing control and prevention interventions are intensified. This thus calls for more studies to inform modification of the interventions. One of the limitations of this study was the use of data from ministry departments in Uganda. There is therefore no proof of validity of this data as some of it was not complete. However, it gives a general picture of what can be done so as to curtail malaria infections within high altitude areas. Conclusion And Recommendations Malaria patterns decreased in all the zones. Also, malaria belt was highly variable in in the altitudinal zones with the higher altitude areas becoming hotspots at some points. This calls for strengthening of malaria control interventions irrespective of altitudinal ranges. The government of Uganda ought to design strategic malaria interventions to cater for different altitude zones. More large-scale studies should be undertaken in an attempt to understand the factors associated with such variations of malaria in different altitudinal zones. These studies should ensure validity of data by undertaking prospective studies within the population. Declarations Ethics approval and consent to participate The study was approved by the Research Ethics Committee of Makerere University College of Veterinary Medicine, Animal Resources and Biosecurity (Reference number SBLS.SA.2018). The study followed guidelines and regulations stated in the approval document. Written and informed consent was also obtained from participants to participate in this study. Written and informed consent was sought from the participants to publish and disseminate the research findings. Consent for publication Informed consent from participants was obtained after information about the study was availed to respondents. Availability of data and materials The datasets used and analyzed during this study are available from corresponding author on reasonable request. Competing interests The authors declare that they have no competing interest. Funding The study was privately funded by the corresponding author. Authors’ contributions AS designed the study, supervised the data collection, analysis and interpretation. AS wrote the first draft. AE, BJK and ATL participated in the data analysis and interpretation of results and assisted in manuscript write-up., BS assisted in drawing the maps for spatial distribution analysis. All authors read and approved the final draft. Acknowledgement Special thanks go to Ministry of Health Uganda, Uganda National Meteorological Authority, Kween district local government, and health service providers for providing data for malaria and weather. Also thanks to Makerere University College of Veterinary Medicine, Animal Resources and Biosecurity for providing necessary documents for this study. References Phillips MA, Burrows JN, Manyando C, Van Huijsduijnen RH, Van Voorhis WC, Wells TNC. Malaria. Nat Rev Dis Prim. 2017;3. Ogbu UC, Arah OA. World Health Organization. In: International Encyclopedia of Public Health. 2016. Yegorov S, Galiwango RM, Ssemaganda A, Muwanga M, Wesonga I, Miiro G, et al. Low prevalence of laboratory-confirmed malaria in clinically diagnosed adult women from the Wakiso district of Uganda. Malar J. 2016;15:1–8. Gething PW, Casey DC, Weiss DJ, Bisanzio D, Bhatt S, Cameron E, et al. Mapping Plasmodium falciparum Mortality in Africa between 1990 and 2015. N Engl J Med. 2016. 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Performance of a high-sensitivity rapid diagnostic test for Plasmodium falciparum malaria in asymptomatic individuals from Uganda and Myanmar and naive human challenge infections. Am J Trop Med Hyg. 2017. Paaijmans KP, Read AF, Thomas MB. Understanding the link between malaria risk and climate. Proc Natl Acad Sci. 2009. Paaijmans KP, Blanford S, Bell AS, Blanford JI, Read AF, Thomas MB. Influence of climate on malaria transmission depends on daily temperature variation. Proc Natl Acad Sci. 2010. Lunde TM, Bayoh MN, Lindtjørn B. How malaria models relate temperature to malaria transmission. Parasites and Vectors. 2013. Tables Table 1: Patterns of malaria cases across three altitudes (lower, middle and higher altitude in Kween district Year Lower altitude Mid altitude Higher altitude P-value 2011 192±111 107±51 60±30 0.0004 2012 188±108 104±48 58±27 0.0003 2013 113±53 106±41 91±53 0.5268 2014 40±19 98±42 79±23 0.0001 2015 6±3 19±11 7±4 0.000 2016 23±13 13±5 26±17 0.0571 2017 23±11 17±10 21±9 0.3558 Table 2: Correlation between climate variability and malaria cases in Kween district Altitude and time Variable T Df P-value Corr. Higher altitude Monthly Precipitation and malaria 1.69 10 0.1219 0.4713 Temperature and malaria -1.65 10 0.1305 -0.4620 Annually Precipitation and malaria 2.89 5 0.0343 0.7906 Temperature and malaria -3.49 5 0.0175 -0.8418 Mid altitude Monthly Precipitation and malaria 1.70 10 0.1208 0.4725 Temperature and malaria -2.70 10 0.0224 -0.6492 Annually Precipitation and malaria 1.70 5 0.1605 0.5930 Temperature and malaria -1.13 5 0.3091 -0.4516 Lower altitude Monthly Precipitation and malaria 3.30 10 0.0080 0.7219 Temperature and malaria -3.91 10 0.0029 -0.7773 Annually Precipitation and malaria 2.16 5 0.08 0.6955 Temperature and malaria -3.28 5 0.02 -0.8264 Supplementary Files Equation1.jpg Cite Share Download PDF Status: Published Journal Publication published 17 Jun, 2020 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Major revision 07 Mar, 2020 Review # 1 received at journal 06 Mar, 2020 Review # 2 received at journal 05 Mar, 2020 Reviewer # 3 agreed at journal 20 Feb, 2020 Reviewer # 2 agreed at journal 19 Feb, 2020 Submission checks completed at journal 18 Feb, 2020 Editor assigned by journal 18 Feb, 2020 Reviewers invited by journal 18 Feb, 2020 Reviewer # 1 agreed at journal 18 Feb, 2020 Editor invited by journal 17 Feb, 2020 First submitted to journal 12 Feb, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-14505","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":357083,"identity":"cae2d1bd-387d-4fd1-bafa-a980d30788ce","order_by":1,"name":"Siya Aggrey","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDACZhiDvQFIGFiQooXnAEiLBCnWSSSAScIK5dt5DD9++XVPzuDm86sbfhRIMPC3dyfg1WJwmMdYWrav2Njgdk7ZzR6gwyTOnN2AXwszj4G0ZE9C4obbOWk3eIBaDCRy8WuRb+Yx/g3UUr/h5pm0m3+I0cJwmMdM8sOPhASDG+zHbhNli8FhtjJrxoYEw5lncthuyxhI8BD0i3z/4c03f/xJkOc7fvzZzTd/bOT423sJOIyBw4CZt42BQeEAjwGIy0NAOQiwP2D88QdoXQP7AyJUj4JRMApGwUgEAGYrSogBQtScAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-9627-656X","institution":"Makerere University","correspondingAuthor":true,"prefix":"","firstName":"Siya","middleName":"","lastName":"Aggrey","suffix":""},{"id":357084,"identity":"4358f706-bb64-48e3-b506-387d50cd36c5","order_by":2,"name":"Egeru Anthony","email":"","orcid":"","institution":"Makerere University College of Agricultural and Environmental Sciences","correspondingAuthor":false,"prefix":"","firstName":"Egeru","middleName":"","lastName":"Anthony","suffix":""},{"id":357085,"identity":"bd7513bd-4ec3-4234-8530-99d6b4ad7354","order_by":3,"name":"Kalule Bosco John","email":"","orcid":"","institution":"Makerere University","correspondingAuthor":false,"prefix":"","firstName":"Kalule","middleName":"Bosco","lastName":"John","suffix":""},{"id":357086,"identity":"5ed4251a-f9a7-46cf-8af9-83593dc15493","order_by":4,"name":"Lukwa Tafadzwa Akim","email":"","orcid":"","institution":"University of Cape Town","correspondingAuthor":false,"prefix":"","firstName":"Lukwa","middleName":"Tafadzwa","lastName":"Akim","suffix":""},{"id":357087,"identity":"932ea13a-ed0a-4a0c-a765-a5d00a94cafc","order_by":5,"name":"Ssentongo Benard","email":"","orcid":"","institution":"Makerere University College of Agricultural and Environmental Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ssentongo","middleName":"","lastName":"Benard","suffix":""}],"badges":[],"createdAt":"2020-02-18 14:08:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.2.23944/v1","doiUrl":"https://doi.org/10.21203/rs.2.23944/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-020-05158-5","type":"published","date":"2020-06-17T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":514673,"identity":"a19d7c71-e834-47fc-9104-00fd2c24a177","added_by":"auto","created_at":"2020-02-19 15:44:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":175745,"visible":true,"origin":"","legend":"Location of Kween district","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 1.png"},{"id":514674,"identity":"d18b4bbf-0108-43c2-babd-8fa0425675cf","added_by":"auto","created_at":"2020-02-19 15:44:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10247,"visible":true,"origin":"","legend":"Malaria patterns across different altitudes (Low = Lower, Moderate =Middle altitude, High = Higher altitude) in Kween district (Low = Lower, Moderate =Middle altitude, High = Higher altitude)","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 2.png"},{"id":514675,"identity":"4d16af17-eb45-41fb-abc0-38b024cffd09","added_by":"auto","created_at":"2020-02-19 15:44:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":231032,"visible":true,"origin":"","legend":"Annual trends in malaria cases in different altitudes in Mount Elgon from 2011 to 2017","description":"","filename":"fig3.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 3.png"},{"id":514676,"identity":"5cbb2fb9-4a04-4bcf-89a5-57a090e0f742","added_by":"auto","created_at":"2020-02-19 15:44:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":476568,"visible":true,"origin":"","legend":"Spatial variation of malaria cases from 2011 to 2017 in Kween district","description":"","filename":"fig4.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 4.png"},{"id":514677,"identity":"d37e8d49-cc51-4a44-ba14-205c95e93c87","added_by":"auto","created_at":"2020-02-19 15:44:12","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":37275,"visible":true,"origin":"","legend":"Correlation between climate variability and malaria patterns in Kween district","description":"","filename":"fig5.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 5.png"},{"id":514678,"identity":"1eefc938-e652-4c25-8953-a1547f854eb1","added_by":"auto","created_at":"2020-02-19 15:44:12","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":100640,"visible":true,"origin":"","legend":"Forecasts for malaria patterns in different altitude zones (lower, mid and higher altitude)","description":"","filename":"fig6.png","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/fig 6.png"},{"id":13489958,"identity":"00cf6e9e-b542-4cb1-ba3b-ca478844864d","added_by":"auto","created_at":"2021-09-16 22:21:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1319440,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-14505/v1/f49b0c33-d531-4f44-b86d-fe4208ed650d.pdf"},{"id":514672,"identity":"ed7b506e-8c2b-4a95-bc5c-6c9fbcc5259c","added_by":"auto","created_at":"2020-02-19 15:44:11","extension":"jpg","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":9303,"visible":true,"origin":"","legend":"","description":"","filename":"Equation1.jpg","url":"https://assets-eu.researchsquare.com/files/735b4d51-0c34-4775-b9fe-5da68dfa5dd0/v1/Equation 1.jpg"}],"financialInterests":"","formattedTitle":"Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda","fulltext":[{"header":"Background","content":" \u003cp\u003eMalaria is an infectious disease that globally affects more than 200\u0026nbsp;million people and whose morbidity and mortality is most pronounced in Africa [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Through bites of infected mosquitoes, disease causing parasites are transmitted [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In 2013 alone, a total of 584, 000 deaths attributed to malaria occurred [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Interventions over the last decade have led to observed decline in the malaria burden in sub-Saharan Africa. However, it still remains a major public health threat of international and regional concern [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMalaria occurrence has traditionally been observed in the low-land areas, bogs and generally in the plains within the tropical regions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Comparative analysis have shown the occurrence of such patterns in Africa, Latin America and Caribbean as well as in south east Asia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Meanwhile, the Afromontane areas characterized with unique biota [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], that had hitherto been known for being malaria free zones due to altitudinal effect, have seen increased malaria incidences with some areas experiencing a rise while others declining [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Malaria cases have lately been observed to be on the rise in the afromontane ecotones within sub-Saharan Africa such as in the Rwenzori highlands of south western Uganda [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e][\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similar patterns have been experienced in the neighboring highlands of Butare (Rwanda) as well as in the Mount Kilimanjaro area (Tanzania) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These patterns in malaria have led to increased cost of malaria interventions [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Such trends have been attributed to climate change that is creating ambient conditions within the highland altitudinal belts [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMalaria in Uganda has been endemic in the savannah areas of northern and eastern Uganda especially in Apac district, followed by Tororo district [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All these areas are within 1,100\u0026nbsp;m altitude. However, highland areas especially Elgon region have experienced a surge in malaria cases despite intensified interventions by both government, private sector and development partners [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Climate has been pointed out as a key risk factor for spatial-temporal patterns of malaria, especially in the highland areas [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Studies [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] on malaria patterns in different mountainous areas have been undertaken but only a few [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] have focused on the patterns of malaria within different altitudinal zones (ecotones). Yet ecotones are characterized with varying environmental conditions that can influence mosquito biology and malaria patterns [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These studies have not documented patterns of malaria following intensified control and prevention interventions in mountainous areas such as Elgon region. This study analysed malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention interventions in the area.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy area\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was undertaken in the Mount Elgon highland region within Kween District located between 0125N and 3431E (Figure 1). Kween district borders the districts of Nakapiripirit to the north, Amudat to the northeast, Bukwo to the east, Kapchorwa to the west and Bulambuli to the northwest [22]. In the South, it boarders the Republic of Kenya and it is located on the northern slopes of Mount Elgon, at an average altitude of about 1,900 meters (6,200 Feet) above sea level [22]. It has administrative units ranging from Sub county, Parish and village [23]\u0026nbsp; The area is characterized by high and well-distributed rainfall (averaging 1,200 mm/year) and consists of two seasons, a rainy season (March\u0026ndash;September) and a dry season (October\u0026ndash;April) [25]. It has cool temperatures which are on average 17˚C [26]. The human population of the district has been rising in the last three census conducted; 1991, 2002 and 2012 from 37,300, 67,200 to 103,300 respectively [27]. Its population is majorly consisting of subsistence farmers cultivating a range of crops including: maize, beans, bananas, wheat, barley and cowpeas and also rear some livestock [22]. The district has health centers with levels: IV, III and II \u0026nbsp;with numbers amounting to 1, 9 and 13 respectively [22]. These health centres are supported by a team of village health teams also known as heath service providers constituting Health Center I and are mainly responsible for mobilization of communities to access health services.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study employed a retrospective cross-sectional study design utilizing past records from health center IIIs across the three altitude zones (High, Middle and Lower) of Mount Elgon [28]. Data on climate variables was obtained across seven years (2011 to 2017). Data on confirmed malaria cases (using both microscopic and rapid diagnostic kits) from 2011 to 2017 was considered for this study and were computed to average number of true malaria cases per 1000 for each of the altitudinal zones. The rates of malaria cases was computed per month for each year. Climate data was obtained in retrospect for the seven year period (2011 to 2017). Rainfall and temperature parameters were the key climate parameters considered in this study as they play key roles in influencing breeding and survival of mosquitoes [29]. Analysis for the spatial temporal patterns was computed at parish level across the three altitudinal zones in the study area. Confounding factors like human population were checked for their effect on the patterns of malaria incidences. There was however no effect of human population on the spatiotemporal patterns of malaria in the study area. Forecasts for malaria were made using ARIMA models for a period of 7 years (84 months) from the year 2017 [30]. Rates of malaria and time in terms of months were included in the model to understand the trends.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, health centers from where data was collected were purposively selected basing on their capacity to confirm and report malaria cases, as well as the volume of their malaria records. Accordingly, the most suitable health centres that were used to collect data were the health center IIIs owing to their capacity to conduct malaria tests (both microscopic and Rapid Diagnostic Test kits). The cases selected for this study at least underwent through one of these tests but not both. These health centres were also fairly well distributed across the different altitude zones divided into higher (above 7150ft), middle (between 4317-7150ft) and lower altitudes (below 4317ft) in the district. Data was then collected from four out of nine Health Center IIIs in the four sub-counties of Benet, Binyiny, Kwanyiy and Ngenge. Data on the number of malaria cases for the past seven years was obtained from the Health Center IIIs records. Data collected included; malaria occurrence, parish of residence, tests as well as a range of socio-demographic characteristics (gender, age and location) of each patients were obtained for a period of seven years.\u003c/p\u003e\n\u003cp\u003eData for climate variables (temperature and rainfall) was obtained from the Uganda National Meteorological authority [27].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMalaria patterns were determined using descriptive statistics of means and standard deviations (SD). These were compared across different altitudinal zones; low, mid and high altitude. Mean malaria cases per month per 1000 cases were computed over the years (2011 to 2017) for each of the three altitude zones (Higher, Middle and Lower). Secondly, in order to depict the spatial-temporal variation of malaria cases, an Inverse Distance Weighted (IDW) interpolation regression [28] at a distance of 15km was undertaken. The IDW is a deterministic regression procedure that estimates values at prediction points (V) using the following equation [29]: (see Equation 1 in the Supplementary Files)\u003c/p\u003e\n\u003cp\u003eWhere d is the distance between prediction and measurement points, V\u003csub\u003e1\u003c/sub\u003e is the measured parameter value, and p is a power parameter. The advantage of IDW is that it uses non-Euclidean \u0026ldquo;path distances\u0026rdquo; for d. These path distances are calculated using an algorithm that accounts for the malaria cases from one cell to the next [30]. Trend analysis were done similarly to the approach by [35]. The average monthly numbers of malaria cases per 1000 were calculated for the full time-series (January 2009\u0026ndash;December 2015). These were plotted to show temporal patterns in malaria and climate variables. The time series of malaria incidence was decomposed using seasonal-trend decomposition based on locally weighted regression to show: the seasonal pattern, the temporal trend and the residual variability. The time series data, the seasonal component, the trend component and the remainder component are denoted by \u003cem\u003eY\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e, S\u003cem\u003e\u003csub\u003et\u003c/sub\u003e, T\u003csub\u003et\u003c/sub\u003e, R\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e\u0026nbsp;respectively, for month\u0026nbsp;\u003cem\u003et\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1 to N, and:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eY\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e\u0026nbsp;=\u0026nbsp;\u003cem\u003eS\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e\u0026nbsp;+\u0026nbsp;\u003cem\u003eT\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e\u0026nbsp;+\u0026nbsp;\u003cem\u003eR\u003csub\u003et\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe parameter setting \u0026ldquo;periodic\u0026rdquo; was used for the seasonal extraction, and all other parameters were by default. In the study, logarithmic transformations were used for the time series data [35].\u003c/p\u003e\n\u003cp\u003eMann Kendal trend test [36] was used to depict the actual trends of the climate parameters and malaria. Relational analysis for malaria, temperature and precipitation was done in XLSTAT [37].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTime series decomposition of malaria patterns revealed existence of seasonality of malaria across the years (2011 \u0026ndash; 2017) in all the altitude zones (Figure 3). The number of cases of malaria declined from 2011 to least number of cases towards 2017 (Figure 3). There was statistical significant difference (p\u0026lt;0.05) in the number malaria cases per 1000 individuals across the three altitude zones (lower, mid and higher altitude) in each of the years (2011-2017) except the years 2013 and 2017 (Table 1 and Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe cases of malaria per 1000 in high, mid and lower altitude were 49 (SD = 40), 67 (SD = 55) and 84 (SD = 96) respectively. Malaria cases revealed a normal curve-shaped trend over each year in the three areas (lower, middle and higher altitude areas) (Figure 3). Also the months of June revealed highest numbers of malaria cases (94, SD = 73; 103, SD = 73 and 128, SD = 134 in high, mid and lower altitudes respectively) over the years (2011 to 2017). The months of January (41, SD = 29; 45, SD = 41 and 52, SD = 67 in high, mid and lower altitudes respectively) and December (28, SD = 23; 29, SD = 21 and 38, SD = 23 in high, mid and lower altitudes respectively) had the least number of malaria cases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpatial variation of malaria (Figure 4) revealed higher number of cases of malaria in the lower altitude areas of Kween district. Higher and mid-altitude areas of the district had relatively lower number of malaria cases (49, SD = 40 and 67, SD = 55 respectively), while lower altitude areas had the highest (84, SD = 96) number of malaria cases. The trends however declined from 2011 to 2017 in all the altitudinal zones (Figure 4).\u003c/p\u003e\n\u003cp\u003eMann-Kendal trend test revealed a Sen\u0026rsquo;s slope of -29.0 and -10.9 (CI = 0.95) for malaria cases in the periods of March to September and October to February respectively in the higher altitude areas of Kween district. It also revealed a drastic decline of malaria cases over the seven year period (from 2011 to 2017) with Sen\u0026rsquo;s value of -21.5 (CI = 0.95). In the middle altitude areas, the Sen\u0026rsquo;s slope were -44.8, -56.0 and -29 annually, March to September, and October to February respectively (CI = 0.95). In the lower altitude, the Sen\u0026rsquo;s values were -87.8, -120.7 and -41.9 annually, March to September and October to February respectively (CI = 0.95).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMalaria cases, rainfall and temperature interaction in different altitude zones\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean temperatures in higher, mid and lower altitude areas of Kween district between 2011 and 2017 were 15.7ᴼC (SD = 2.8), 18.4ᴼC (SD = 1.3) and 21.4ᴼC (SD = 1.8), respectively. Higher altitude areas experienced a very low positive correlation (0.47) between precipitation and number of malaria cases (Table 2 and Figure 5). Similarly, there was a very low negative correlation (-0.46) between temperature and number of malaria cases. Annually, there was a high positive correlation (0.79) between number of malaria cases and precipitation. The relationship between temperature and malaria cases showed a negatively high correlation (-0.84).\u003c/p\u003e\n\u003cp\u003eFor mid-altitude there was a very low positive correlation (0.47) between precipitation and malaria cases (Table 2 and Figure 5). Similarly, there was a low negative correlation (-0.64) between temperature and malaria cases. Also annually, there was a low positive correlation (0.59) between precipitation and malaria cases. Meanwhile, temperature and malaria cases showed a negatively low correlation (-0.45).\u003c/p\u003e\n\u003cp\u003eLower altitude reflected a positively high correlation (0.72) between precipitation and malaria cases (Table 2 and Figure 5). Similarly, there was a negatively high correlation (-0.78) between temperature and malaria cases. Annually, there was a positive moderate correlation (0.70) between malaria cases and precipitation. Meanwhile, temperature and malaria trends showed a negatively high correlation (-0.83).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eForecasting of malaria patterns\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eForecasts for all the three altitudinal zones revealed malaria cases to continue to decrease if the conditions were kept constant and/or intervention efforts are strengthened (Figure 6). However, relaxation of the malaria control interventions would greatly allow for more increased number of cases of malaria (Figure 6).\u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eThere was a declining number of malaria cases across all the altitudinal zones during the study period. This can be attributed to the intensified malaria control and prevention interventions within the area. Such patterns are similar to results in other studies in western Kenya on the Elgon area [38]. Malaria patterns revealed a normal curve trend of malaria with the highest peak being in the middle (June-August) of each of the seven years (Figure 3). This corresponded to the trends in temperature and precipitation. However, the months of January and December had the least number of malaria cases. This can be linked to the low precipitation amounts during this period limiting availability of water for breeding of mosquitoes. This trend is similar to the results by [31] for the whole country (Uganda). This can be linked to the conditions suitable for growth and development of mosquitoes. Increase in temperature and availability of water sources favors mosquito breeding and its transmission of malaria parasites [40]. Results of this study revealed an overall malaria decline in the seven years of analysis. Similarly, analysis performed by [31] had shown declining trend in malaria over Uganda. These patterns could be attributed to significant intervention efforts by the Ministry of Health in malaria prevention and control through increasing access to health services including basic diagnostics, provision of insecticide-treated mosquito nets [34].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpatially, the hotspot of malaria varied over the seven year period dominating the lowland areas of the district (Figure 4). The highland areas had lower number of malaria cases compared to the lowland areas. There was a positive correlation between malaria patterns in the lower belt and temperature. Temperature plays a key role in malaria transmission by influencing vector and parasite life cycles. Studies have highlighted the biological amplification nature of temperature on mosquitoes [32]. This study showed that the mean temperatures within the three altitudes varied. The difference in the contribution of maximum temperature to malaria cases between different altitudes is attributed to the differences in prevailing temperatures in the three zones. The study area (Kween district) being colder, temperature was probably the limiting factor in malaria vector development in the highland and lowland areas; hence a rise in the maximum temperature increased vector and parasite development rates [33]. Since temperature influences the development and survival rates of both vectors and parasites, malaria transmission rates tend to increase with increasing temperature but up to a given threshold [34].\u003c/p\u003e\n\u003cp\u003eThe highland areas of the district that experienced a decline can be attributed to the increased malaria control interventions like use of mosquito nets. The question on existence of malaria in the higher altitude areas in East Africa raised by [36] is thus partly answered by this study.\u003c/p\u003e\n\u003cp\u003eRelational analysis results revealed a positive association between precipitation and malaria patterns (Table 2 and Figure 5). Malaria cases were more pronounced in the lower altitude zones compared to the higher altitude zones. This can probably be linked to environmental conditions favorable for mosquito growth and development. This result is in agreement with previous studies in Kabale, a highland region in southwestern Uganda [31] where lowland areas expirience higher number of malaria cases compared to highland areas. The alternating trends can be alluded to temperature and precipitation as the latter can either favor or discourage optimal growth and development of mosquitoes. [37] notes that mosquito growth and development greatly depend on ambient air temperature and rainfall not forgetting any changes within the norm greatly affects mosquito growth and development which in turn affects the malaria incidence in malaria endemic areas [38].\u003c/p\u003e\n\u003cp\u003eForecasts of malaria patterns revealed a continued decline of malaria cases given conditions are remain constant. However, the number of malaria cases may significantly explode if temperature and rainfall increase. This implies that interventions at this point ought to be intensified. There is also a window of opportunity for eradication of malaria in the event that the existing control and prevention interventions are intensified. This thus calls for more studies to inform modification of the interventions.\u003c/p\u003e\n\u003cp\u003eOne of the limitations of this study was the use of data from ministry departments in Uganda. There is therefore no proof of validity of this data as some of it was not complete. However, it gives a general picture of what can be done so as to curtail malaria infections within high altitude areas.\u003c/p\u003e"},{"header":"Conclusion And Recommendations","content":"\u003cp\u003eMalaria patterns decreased in all the zones. Also, malaria belt was highly variable in in the altitudinal zones with the higher altitude areas becoming hotspots at some points. This calls for strengthening of malaria control interventions irrespective of altitudinal ranges. The government of Uganda ought to design strategic malaria interventions to cater for different altitude zones. More large-scale studies should be undertaken in an attempt to understand the factors associated with such variations of malaria in different altitudinal zones. These studies should ensure validity of data by undertaking prospective studies within the population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Research Ethics Committee of Makerere University College of Veterinary Medicine, Animal Resources and Biosecurity (Reference number SBLS.SA.2018). The study followed guidelines and regulations stated in the approval document. Written and informed consent was also obtained from participants to participate in this study. Written and informed consent was sought from the participants to publish and disseminate the research findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent from participants was obtained after information about the study was availed to respondents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during this study are available from corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was privately funded by the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAS designed the study, supervised the data collection, analysis and interpretation. AS wrote the first draft. AE, BJK and ATL participated in the data analysis and interpretation of results and assisted in manuscript write-up., BS assisted in drawing the maps for spatial distribution analysis. All authors read and approved the final draft.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpecial thanks go to Ministry of Health Uganda, Uganda National Meteorological Authority, Kween district local government, and health service providers for providing data for malaria and weather. Also thanks to Makerere University College of Veterinary Medicine, Animal Resources and Biosecurity for providing necessary documents for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePhillips MA, Burrows JN, Manyando C, Van Huijsduijnen RH, Van Voorhis WC, Wells TNC. Malaria. Nat Rev Dis Prim. 2017;3.\u003c/li\u003e\n\u003cli\u003eOgbu UC, Arah OA. World Health Organization. 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Malar J. 2010.\u003c/li\u003e\n\u003cli\u003eDas S, Jang IK, Barney B, Peck R, Rek JC, Arinaitwe E, et al. Performance of a high-sensitivity rapid diagnostic test for Plasmodium falciparum malaria in asymptomatic individuals from Uganda and Myanmar and naive human challenge infections. Am J Trop Med Hyg. 2017.\u003c/li\u003e\n\u003cli\u003ePaaijmans KP, Read AF, Thomas MB. Understanding the link between malaria risk and climate. Proc Natl Acad Sci. 2009.\u003c/li\u003e\n\u003cli\u003ePaaijmans KP, Blanford S, Bell AS, Blanford JI, Read AF, Thomas MB. Influence of climate on malaria transmission depends on daily temperature variation. Proc Natl Acad Sci. 2010.\u003c/li\u003e\n\u003cli\u003eLunde TM, Bayoh MN, Lindtj\u0026oslash;rn B. How malaria models relate temperature to malaria transmission. Parasites and Vectors. 2013.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;\"\u003e\n \u003cp\u003e\u003cspan style=\"line-height:200%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;font-size:16px;\"\u003eTable 1: Patterns of malaria cases across three altitudes (lower, middle and higher altitude in Kween district\u003c/span\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:504.7pt;border-collapse:collapse;\" width=\"673\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003eYear\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003eLower altitude\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003eMid altitude\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003eHigher altitude\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003eP-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2011\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;border: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e192±111\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e107±51\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e60±30\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.0004\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2012\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;border: none;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e188±108\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e104±48\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e58±27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.0003\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid rgb(127, 127, 127);padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2013\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e113±53\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e106±41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e91±53\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.5268\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid rgb(127, 127, 127);padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2014\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e40±19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e98±42\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e79±23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.0001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid rgb(127, 127, 127);padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2015\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e6±3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e19±11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e7±4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid rgb(127, 127, 127);padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2016\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e23±13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e13±5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e26±17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.0571\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid rgb(127, 127, 127);padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"16.939078751857355%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e2017\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"24.071322436849925%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e23±11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"25.85438335809807%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e17±10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"19.61367013372957%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e21±9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.7pt;vertical-align: top;\" valign=\"top\" width=\"13.521545319465082%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:normal;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align:center;\"\u003e\u003cspan style=\"font-size:16px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;color:black;\"\u003e0.3558\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\u003cbr\u003e\u003cbr\u003e\n\u003cdiv style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;\"\u003e\n \u003cp\u003e\u003cspan style=\"line-height:200%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;font-size:16px;\"\u003eTable 2: Correlation between climate variability and malaria cases in Kween district\u003c/span\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:527.1pt;border-collapse:collapse;\" width=\"703\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131.35pt;border: 1pt solid windowtext;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eAltitude and time\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eVariable\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eT\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eDf\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"11.379800853485063%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eP-value\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid rgb(127, 127, 127);border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 20.35pt;vertical-align: top;\" valign=\"top\" width=\"16.500711237553343%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eCorr.\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 527.1pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 18.1pt;vertical-align: top;\" valign=\"top\" width=\"100%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eHigher altitude\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 131.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eMonthly\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003ePrecipitation and malaria\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e1.69\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"11.379800853485063%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.1219\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"16.500711237553343%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.4713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"38.25757575757576%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eTemperature and malaria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-1.65\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"15.151515151515152%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.1305\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"21.96969696969697%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-0.4620\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 131.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eAnnually\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003ePrecipitation and malaria\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e2.89\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"11.379800853485063%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.0343\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"16.500711237553343%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.7906\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"38.25757575757576%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eTemperature and malaria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-3.49\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"15.151515151515152%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.0175\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"21.96969696969697%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-0.8418\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 527.1pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"100%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eMid altitude\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 131.35pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: none;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eMonthly\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003ePrecipitation and malaria\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e1.70\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"11.379800853485063%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.1208\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"16.500711237553343%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.4725\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151.15pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"38.25757575757576%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eTemperature and malaria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-2.70\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"15.151515151515152%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.0224\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"21.96969696969697%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-0.6492\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 131.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eAnnually\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003ePrecipitation and malaria\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e1.70\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"11.379800853485063%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.1605\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"16.500711237553343%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.5930\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"38.25757575757576%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eTemperature and malaria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-1.13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"12.31060606060606%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"15.151515151515152%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e0.3091\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.9pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"21.96969696969697%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e-0.4516\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 527.1pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: none;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"100%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eLower altitude\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 131.35pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-bottom: none;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"24.893314366998577%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cem\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003eMonthly\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151.15pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"28.733997155049785%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan style=\"font-size:13px;line-height:150%;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003ePrecipitation and malaria\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.9pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.65pt;vertical-align: top;\" valign=\"top\" width=\"9.246088193456615%\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:.0001pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\u0026quot;Calibri\u0026quot;,sans-serif;text-align: justify;\"\u003e\u003cspan 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\u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Afromontane, ecohealth, malaria, ecotones, climate change, infectious diseases","lastPublishedDoi":"10.21203/rs.2.23944/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.23944/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Malaria remains a major tropical vector-borne disease of immense public health concern owing to its debilitating effects in sub-Saharan Africa. In the recent past, the high altitude areas in Eastern Africa have been reported to experience dramatic cases of malaria. However, its patterns following intensified control and prevention interventions remains and the changing climate remains widely unexplored in these regions. This study thus analyzed malaria patterns across altitudinal zones of Mount Elgon, Uganda. Methods Times-series data on malaria cases (2011 - 2017) from five level III local health centers occurring across three altitudinal zones; low, mid and high altitude was utilized. Inverse Distance Weighted (IDW) interpolation regression and Mann Kendall trend test were used to analyze malaria patterns. Autoregressive Integrated Moving Average (ARIMA) model was used to project malaria patterns for a seven year period. Results On average, 66±69/1000 individuals suffered from malaria on a monthly basis. This was most pronounced in the months of May-August 89±88/1000 compared to the months of November-February (40±33/1000). Malaria patterns varied with season and altitude and declined over time across the three altitudinal zones. Observed cases, revealed an annual average of 587±750/1000; 345±321/1000 and 338±351/1000 cases in lower, mid and high altitudes respectively. Conclusions Despite observed decline in malaria cases across the three altitudinal zones, the high altitude zone became a malaria hotspot as cases variably occurred in the zone. The projections of malaria revealed declining patterns of malaria cases in all the altitudinal zones. Malaria control interventions thus ought to be strengthened and strategically designed to achieve no malaria cases across all the altitudinal zones. Integration of climate information within malaria interventions can also strengthen eradication strategies of malaria in such differentiated altitudinal zones.\u003c/p\u003e","manuscriptTitle":"Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-02-19 15:44:11","doi":"10.21203/rs.2.23944/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-03-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-03-06T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nMalaria patterns across altitudinal zones of Mount Elgon following intensified control and\nprevention programs in Uganda\nThis is an important study focusing on malaria patterns across altitudinal zones of Mount Elgon. In this study, the authors reported that forecasting of malaria patterns in different altitudes for predicting number of malaria cases ahead of time, timely prevention and control measures can be designed and avoiding vector breeding places, spraying insecticides, and enhancing community awareness before the peak season of malaria. However, the reviewer of this paper has the following concerns:\n\nBackground section\nLine 10\"Through bites of infected mosquitoes\", should be changed to \"Through bites of infected Anopheles mosquitoes\".\nThe authors have to describe the primary malaria vectors and its distribution along different altitude in Uganda the background sections.\nMethods section\nLine 14: should delete \"were\"\nWhich types of malaria parasites were detected in all altitudinal zones using both microscopic and rapid diagnostic kits?\nDid the authors use any standard for altitudinal classification such as high, middle and low altitudes, your references?\nWhy the authors didn't consider humidity in the analysis?\nStatements Line 14-31: the authors should rewrite again, the statements are not clear for readers.\nNo results reported on socio-demographic characteristics (gender, age and location) of each patient but the authors described in the methodology, why?\nDuring the study period, is there any record of death due to the cause of malaria?\nWhy the authors didn't measure the vegetation index relating to the malaria cases in different altitudinal structure?\nResult Section\nWhat is the different Statement line 33-35 \"Similarly, there was a very low negative correlation (-0.46) between temperature and number of malaria cases\" and \"The relationship between temperature and malaria cases showed a negatively high correlation (-0.84)\".\n\nLine 16-19: Forecasting of malaria patterns subsection, Figure 6 shows only the forecasting patterns in different altitude, it is not indicated the intervention activities with malaria cases; try to make clear in your result section.\nDiscussion Section\nCan you explain the malaria interventions methods frequently used in Uganda? Clearly describe in the discussion sections.\nLine 48-53: The statement \"The highland areas of the district that experienced a decline can be attributed to the increased malaria control interventions like use of mosquito nets. The question on existence of malaria in the higher altitude areas in East Africa raised by [36] is thus partly answered by this study\", is not clear, rewrite again.\nCan you explain why malaria is occurred at high altitude?\nCan you describe the optimum temperature which is suitable for mosquito breeding in Uganda?\nWhat is the implication of this study?\nAvoid repetition in the manuscript\nWhy malaria cases have detected at high altitude? Besides to climatic factors, did the authors observe population movement and migration from lowland to highland?\nConclusion and recommendations\nLine 57: \"Malaria patterns decreased in all the zones\", which zones? describe clearly\nLine 57: Delete \"in\", it is repetition.\nYour conclusion should provide an explanation of the importance and relevance of the study to the field as well as malaria cases and climate variable relations.\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"editorInvitedReview","content":"","date":"2020-03-05T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nManuscript Number: INFD-D-20-00366\nTitle: Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda\nReviewer: Adugna Woyessa (PhD)\nGeneral comments\nThe Eastern African countries including Uganda are at the highest risk of epidemic malaria, particularly in high altitude areas adjacent to malaria endemic localities during El Nino years. Thus, understanding the epidemiology of those areas helps to guide interventions targeted to 'hot spot' localities. Better informed health system with such evidence could channel its resources and improving alert system. However, author(s) of the present scientific undertakings gave less emphasis to the ongoing efforts in the fight against malaria (background part) and interpreting/application of their findings and recommendations.\nWhat is the main message to the decision-makers and how they improve the existing practice and/or gap in their research to be addressed in the future endeavors in this regard, on the basis of the local context. The researchers should generate a statement that goes to informed decision local and regional consumption from their findings. According to a recent WMR 2019 Uganda is among the top high burden countries globally and in the continent. A statement from the report is read as ''Nineteen countries in sub-Saharan Africa and India carried almost 85% of the global malaria burden. Six countries accounted for more than half of all malaria cases worldwide: Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda (5%), and Côte d'Ivoire, Mozambique and Niger (4% each).'' In most of the cases, the NMCP is specializing in improving the access and quality of the health care in which evidence generation is performed by academia and research institutions. Moreover, some global partners engaged in funding malaria research prioritize areas not well addressed by the rest of their counterparts. The research team could draw more attention in high altitude areas, Mount Elgon area, by taking the country and local context into consideration in its MS submitted for publication.\n1. Originality, importance and clarity of research question\n1.1. As already addressed malaria in high altitude areas categorized into varying zones is relevant for targeting interventions and learn more about the progress in the extent to which interventions in progress are impacting malaria burden with the contexts of linking the role of climate whether in favoring the transmission or its decline. The scope of the study is expected in informing the local control activities and further elimination plan.\nRevisions required\nMinor essential revisions\n2. Suitability of the methods\n2.1. Consider including the altitude range of each category: low, mid and higher; possibly in meters based on the local context utilized by health system for planning. This information should be available clearly to the audience throughout the text.\n2.2. Presumably, there is variability in threshold for malaria transmission in high altitude areas across Africa, particularly in The East African Highland areas. Accordingly, the upper cut-off altitude for malaria transmission in Uganda is hardly clear to the reader and draw conclusion between the three altitude categories from the present MS. Altitude is a proxy measurement for temperature variability, which is playing a driver for malaria transmission (presence/absence, intensity and seasonality).\nIn fact, the research team is familiar with this information and including in the text will also help the audience in the region and elsewhere make a good comparison/explanation the trends of malaria in similar areas, where transmission is precluded due to cold night time or minimum temperature. However, it appears that minimum temperature is undermined in the methods (analysis) and the rest of the text.\n2.3. The malaria dataset comprised the years 2015 and 2016, which has been El Nino years that frequently affected malaria distribution and climate-sensitive diseases as well in most parts of the East African Highlands. Historical evidences showed that this cyclic climatic event influences in exaggerating malaria incidence in most parts of the high altitude areas through its effect on minimum temperature and shifting the rainfall patterns. There is a limited information on the impacts of El Nino on malaria incidence in the study area, except describing the declining of malaria in the recent years without mentioning the possible positive and negative influence of the climatic events. The author(s) could comment that even if favorable climatic conditions were available but the intensified and extensive interventions managed to reduce malaria in those years (2015 and 2016). Still, field reports and areas experiencing exaggerated malaria incidence might be locally documented but aggregated data overwhelmingly masks the issue in smaller areas.\n2.4. The research team collected confirmed malaria cases in health centers classified into IV, III and I. Both RDT and light malaria microscopy are utilized in those facilities. Possibly, the author(s) consider including explicit information on the differences among those classifications such as facilities in rendering diagnostic service using either RDT or microscopy. The malaria parasite species distribution and approaches in place for quality control is also helpful.\n3. Strengths and weaknesses of the methods\n3.1. Strength of the methods\nStratifying the study areas into varying altitude is relevant to the audience both practicing the interventions and undertaking evidence generation (local and region). They also addressed the relationship between climate and malaria cases along the altitudinal transect.\n3.2. Weakness of the methods\n3.2.1. As presented earlier a remarkable role of El Nino in determining malaria incidence is less emphasized and subsequent relevance of climate variables in developing early warning system for areas similar to the present areas vulnerable to temperature remain questionable.\n3.2.2. Which malaria species is dominant? Description on the seasonal variability of the dominant species and the possibility experiencing vivax malaria in the coldest high altitude area.\n3.2.3. Many malaria vectors are known in the study area. Is there any difference and similarity among various vectors for the two malaria parasites? If the difference predominates transmission of both species variably, there is a need to inform readers.\n3.2.4. A persistent correlation between precipitation and malaria case reported along the three altitude zones unlike temperature (monthly, cumulative annual). Author(s) should give adequate explanations like the role of human activities that modify the classical effects of temperature on malaria distribution in high altitude areas. Otherwise the presence of correlation simply (although not implying association) might obscure the established fact.\n4. References\n4.1. It appears that the present study utilized references as old as 2005 \u0026 2006 and 2010-2012 are cited (Background), which could be to complement historical malaria data set that ranged between 2011 and 2017. The author(s) should justify why they relied on those materials older might be failing to fulfill the knowledge gap coming from malaria research as frequently as possible, at least.\n4.2. The author(s) cited the reference #20, which referring to a viral disease. Any rational for using the reference as the impacts of climate on viral and protozoan diseases vary based on the ecology of the vector of interest and other biological parameters of the agents. Check also #34 is pertinent to malaria.\n5. Data presentation\nAs altitude classification is an important parameter (mentioned by author) to describe patterns of malaria, there is a need to clearly present elevation ranges of low, mid and higher strata for each year (Fig 4).\n6. Discussion and conclusion supported by the data\nAs shown in the general comments, there is a need to link findings with ongoing interventions and planned approaches like elimination. Eradication is mentioned without adequately addressing the elimination in progress /planned. Elimination sis a continuum process of a successful control but eradication is beyond the local context, a global perspective.\n\nDiscretionary revisions (a table attached for editorial and detailed issues)\nTable 1. A summary of detailed comments and inputs\nSection Subtitle Page Line (s) Phrases/Statements Comments or inputs\n\nAbstract Background 2 50 … recent past Replace with year\n2 52 … dramatic Replace with either increase or decrease\n2 55 …remained Replace the repeated word\nResults 3 33 … altitudes respectively … altitudes, respectively (insert comma throughout the MS)\nConclusions 3 36-52 … the role of climate role is underestimated and the possibility of including in the surveillance system and improving the alert system is diminished despite its coverage in the results and discussion part\nKey words 3 55 Afromontane, eco-health, ecotones Possibly include Altitude, Time Series, Patterns (optional)\nMain Text Background 4 7 200 million Use current WHO annual estimate\n4 12 2013 Use recent information, example, year 2019\n4 17 … international … tropical and subtropical\n4 28 … South east Asia … South East Asia\n\n\nSection Subtitle Page Line (s) Phrases/Statements Comments or inputs\nMain Text Background 4 4-7 Ref. #15 (2011), old reference to be cited for such a sensitive issue while the declining of malaria is presented in different parts of the MS. Suggest to consider time period and associated factors implying its relevance in the present situation\n4 47-56 Refs. #18, 19\u002620 (2011), old references unless there is no option Suggest to replace with a recent reference that could better inform the audiences\n5 9 Refs. #18, 19\u002620 Suggest to replace\nMethods: study area 5 44 Kween district Replace with Kween District ( maintain this for name of districts throughout the MS)\nMethods: data collection 7 28-29 feet meter (maintain the unit of measurement for elevation throughout the MS)\nMethods: analysis 8 32-33 … by[35] Revision is required to make the so statement complete (account this editorial comment for references cited in this way throughout the MS).\nResult 9 17-18 … statistical … statistically\n\n\nSection Subtitle Page Line (s) Phrases/Statements Comments or inputs\nMain text Result 26-56 … SD is higher Suggest to revisit an appropriate measurement for a single figure that represent your observation (central tendency) in the case of such a strong variability among the observed malaria cases\n10 25-26 Mean temperature Possibly consider minimum (data analysis part)\n(at the end of the main text) Consistency in altitudinal zones in Figures 2, 3 and 4\n11 15-18 Check the interpretation of figure 6, forecasting malaria in the future From the data, practically, it is observable that malaria would remained stable in both the mid and higher altitudes but with a pronounced variability in higher altitude. However, malaria showed a declining trends in low altitude areas.\n11 18-23 Make sure this statement belongs to this section Possibly move the statement to the discussion part\nDiscussion 11 35-38 … attributed to intensified interventions. What about the role of climate in such a high altitude area where temperature, especially night time, is playing a vital role in modifying malaria transmission Revise the discussion by taking climate parameters considered in the results possibly minimum temperature accounted in the analysis.\n\n\nSection Subtitle Page Line (s) Phrases/Statements Comments or inputs\nMain text Discussion 12 Refs.#34\u0026 36 Does this reference support the statement? Check these references are cited where they should do so.\n14 29-34 Although the study is stated as a retrospective study how did the research team managed contacting patients for the years 2011-2017 Give explanation who gave the consent. Otherwise revise the statement in the ethical consideration section accordingly.\n\n\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-02-20T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-19T12:00:00+00:00","index":2,"fulltext":""},{"type":"checksComplete","content":"","date":"2020-02-18T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-02-18T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-02-18T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-18T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvited","content":"","date":"2020-02-17T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-02-12T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bbda8e0e-6584-45be-bf9f-9e303ce5f724","owner":[],"postedDate":"February 19th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":60223,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2020-06-21T15:01:10+00:00","versionOfRecord":{"articleIdentity":"rs-14505","link":"https://doi.org/10.1186/s12879-020-05158-5","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2020-06-17 12:00:00","publishedOnDateReadable":"June 17th, 2020"},"versionCreatedAt":"2020-02-19 15:44:11","video":"","vorDoi":"10.1186/s12879-020-05158-5","vorDoiUrl":"https://doi.org/10.1186/s12879-020-05158-5","workflowStages":[]},"version":"v1","identity":"rs-14505","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-14505","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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