Temporal distribution of HPAI H5N1 outbreaks in Menofia governorate, Egypt
Six epidemic waves (EW1-6) of H5N1 outbreaks were noted throughout the study's period (2006–2017) Fig. 1. The 1st EW, in which the governorate reported 66 outbreaks, lasted for about three months, Fig. 1, started in February 2006, peaked in mid-March 2006, and ended in May 2006. In Fig. 1. the 2nd EW began on the 21st of November 2006, peaked in last December 2006, and ended in mid-April 2007, with 57 estimated outbreaks that lasted for four months. The third epidemic wave (3rd EW), Menofia governorate reported 30 outbreaks that lasted for three months, Fig. 1, began on December 2nd, 2007, peaked in the period from 22 December 2007 to 20 January 2008, and ended in mid-March 2008. The fourth epidemic wave (4th EW) considered one of the longest epidemic waves that reflects the endemic situation, started on December 16th, 2008, and ended on February 11th, 2012. Multiple consecutive peaks of the HPAI H5N1 outbreaks were continuously reported for more than three years with 378 reported outbreaks, Fig. 1. Four epidemic cycles were found, the first of which lasted from January 2009 to August 2009, the second of which lasted from January 2010 to August 2010, the third of which lasted from January 2011 to August 2011, and the last one peaked in January 2012. The fifth epidemic wave (5th EW) started in September 2012 and ended in late May 2013 with multiple consecutive peaks reported in October 2012, late November 2012, early February 2013, and mid-April 2013, with 58 reported outbreaks. While the sixth epidemic wave (6th EW) started in October 2013 and recorded 70 outbreaks continuously to December 10th, 2016. There was only one definitive peak observed in February 2015, Fig. 1.
Figure 2., and Fig. 3 declare the distribution of the numbers of outbreaks for each one of the six epidemic waves by localities. During the whole period of the study (Fig. 2A), the highest numbers of outbreaks have been reported in Ashmun, Minuf, and Qwesna respectively. The second-highest category is Berkat_ElSabae, ElBagur and Shibin_ElKom followed by the third-highest category of Tala, ElShohadaa, and Sadat_City (Fig. 2A). According to Table 1, and Fig. 2B, most outbreaks in the 1st EW have been reported in Qwesna, Berkat ElSabae, and Ashmun with 34.8%, 18.2%, and 16.7% of total cases, respectively. As seen in Table 1, and Fig. 2C the largest number of outbreaks have been reported in the 2nd EW, were found in Berkat ElSabae, Minuf, and Shibin_ElKom with 28.1%, 15.8%, and 12.3% of total cases, respectively. The areas with the most outbreak notifications in 3rd EW are Ashmun, Shibin_ElKom, and Tala, with 33.3%, 26.7%, and 13.3% of total cases, respectively (Table 1 and Fig. 2D). The highest numbers of outbreaks in the governorate have been notified in 4th EW in Minuf, Ashmun, and Qwesna with 24.6%, 17.7%, and 14% of total cases, respectively (Table 1 and Fig. 2E). Ashmun has been reported to have the most outbreaks in the Menofia governorate in 5th EW with 43.1% of total cases, followed by Qwesna with 34.5% of total cases (Table 1 and Fig. 2F). The Menofia governorate has received the most outbreak notifications in Ashmun, Minuf, and Shibin_ElKom, correspondingly in 6th EW with 34.3%, 22.9%, and 12.9% of total cases, respectively (Table 1 and Fig. 2G).
The spatial pattern of HPAI H5N1 outbreak in Menofia governorate, Egypt
Spatial distribution of HPAI H5N1 outbreaks in Menofia governorate illustrated in Fig. 3, divided into six EW (epidemic waves) and depicted in the village-based map for visual comparison using ARCGIS 10.5 software (ESRI, Redlands, CA, USA).
Based on the raster risk map in Fig. 4, which displays the interpolated surface based on ordinary kriging, provides predictions of outbreak occurrence risk for each location in the Menofia governorate at each EW. Berkat ElSabae and Qwesna in the northeast border of the governorate were determined to have the highest predicted risk of HPAI H5N1 spatial occurrence in the 1st EW. In the next occurred wave, the outbreaks spread all over the governorate with a generally high density, the highest predicted risk was observed in the northeast part of the governorate (Berkat ElSabae and Qwesna cities) and extended risk to the center of the governorate (Minuf, ElShohadaa, and Shibin_ElKom cities) to Ashmun city. While at the 3rd EW, the northeast part of the governorate (Berkat ElSabae and Qwesna cities) had the lowest predicted risk of HPAI H5N1 occurrence. The spatial highest predicted risk was noted in the northwestern borders of the governorate (Tala city), extended to the center (Shibin_ElKom city), and down to Ashmun city. In the 4th EW, the outbreaks spread with the highest predicted risk at the north governorate borders. While in the 5th EW, the outbreaks spread all over the governorate with the highest predicted risk at the north and south governorate borders. However, in the 6th EW, a generally low density was detected with the highest predicted risk at Minuf, and ElBagur.
In the current study, outbreak density and cluster analysis of HPAI H5N1 outbreaks over six epidemic waves in Menofia governorate were depicted in Table (2, 3) and Fig. (5). Outbreak density in the Menofia governorate was determined by adaptive kernel density estimation, highlighted in monochromatic grey (the higher the density, the darker the color) and outbreaks were represented by green dots. The first epidemic wave (1st EW) of outbreaks in the Menofia governorate had the highest outbreak density in Qwesna and Shibin_ElKom, while the second epidemic wave (2nd EW) had outbreak densities in Qwesna, Berkat ElSabae, ElShohadaa, Minuf, and Ashmun. The spread of the outbreak density during the third epidemic wave (3rd EW) covered Tala, Berkat ElSabae, Shibin_ElKom, and Ashmun. In the fourth epidemic wave (4th EW), the outbreaks covered the whole governorate with the highest densities found at Qwesna, Berkat ElSabae, ElBagur, and Ashmun. While in the fifth epidemic wave (5th EW), the spatial distribution of outbreaks was confined to Qwesna and Ashmun. By the sixth epidemic wave (6th EW), Qwesna, Shibin_ElKom, ElShohadaa, Minuf, and Ashmun had shown a high outbreak density.
Spatiotemporal clusters
Clustering is an aggregation of diseases in space and/or time in amounts that are believed to be greater than could be expected [48]. To determine the outbreak clusters at each EW, spatiotemporal cluster analysis is performed. The current study couldn't take into account various control measures, detection bias, or even changes in the demographic features of at-risk groups, and that is considered one of its limitations. Tables (2,3) and figure (5) provide a detailed description of the location and the extent of different clusters in the Menofia governorate.
Throughout the six epidemic waves in the Menofia governorate, there were spatial patterns and spatiotemporal clusters of HPAI subtype H5N1 outbreaks that occurred on a daily, weekly, and monthly basis. Significant spatiotemporal clusters detected from the space-time permutation scan statistics are represented by the most likely cluster (red circle) and by a secondary cluster (blue dashed circles) in tables (2, 3) and figure (5).
Based on the daily and weekly outbreak data, the primary cluster, and the most likely occurring one in the 1st EW, was found in Tala city at the end of the wave. The secondary cluster in Tala city was also detected as the highest relative risk cluster, in addition to the one found in Tala, ElShohadaa, Shibin_ElKom, Minuf, Qwesna, and Berkat ElSabae at a 26.37 Km radius, based on monthly outbreak data. During the 2nd EW, the primary cluster of radius 6.56 km was observed in Tala, ElShohadaa, and Shibin_ElKom at the end of the wave, based on weekly and monthly outbreak data. While the primary cluster based on the daily outbreak data was observed in the same cities but with a bigger radius of 12.60 Km including Minuf city. The secondary clusters covered the whole governorate during 2nd EW, and the highest RR clusters were observed in small villages in Ashmun, ElBagur, and Shibin_ElKom.
In 3rd EW, the daily based outbreaks showed a primary cluster at the end of the wave of a 6.87 Km radius in ElBagur and Ashmun, while with the monthly outbreaks, the primary cluster and the most likely occurred one was found in Ashmun of a smaller radius (2.14 Km radius). Although the primary cluster with weekly outbreaks was detected in ElBagur, Shibin_ElKom, Qwesna, and Berkat ElSabae with a 9.29 Km radius at the end of the wave. The secondary clusters predominate the majority of the cities, and the most likely occurred clusters were found in the villages of Shibin_ElKom, Ashmun, Berkat ElSabae, and Tala. The primary cluster in 4th EW was located in ElBagur, Qwesna, and Shibin_ElKom at the middle of the wave, characterized by a 10.21 Km radius size as shown in Fig. 5, based on daily and weekly outbreak data. While the analysis of monthly-based outbreaks showed a primary cluster of a smaller radius size of 5.17 Km in Qwesna and Berkat ElSabae. The secondary clusters occurred consecutively -one following the other- to cover the whole governorate geographic surface during the whole period of 4th EW. The secondary clusters of the highest relative risk were found mainly in Minuf and Tala.
At the end of the 5th EW, the primary cluster of a 14.01 Km radius was observed in Minuf, Ashmun, and ElBagur based on weekly outbreak data. The monthly based outbreaks showed smaller primary clusters of 6.46 Km in the same cities with the highest relative risk. While the primary cluster based on the daily outbreak data includes only Shibin_ElKom and Qwesna within a 4.04 Km radius. The highest relative risk (RR) secondary clusters were determined in Tala, Berkat ElSabae, Ashmun, and Minuf.
In the 6th EW, the primary clusters were observed to occur anytime during the wave with analysis of daily, weekly, and monthly outbreak data with secondary clusters that cover the whole governorate. The daily-based outbreaks showed primary clusters of a 7.97 Km radius in Minuf, and Ashmun at the end of 2014. While the monthly-based outbreaks showed a primary cluster of a 10.06 Km radius in Minuf, Shibin_ElKom, and ElBagur from January 2015 and lasted six months. The primary cluster according to the weekly based outbreak was detected in Tala, Berkat ElSabae, and Shibin_ElKom of a 6.02 Km radius at the end of 2015. Secondary clusters of high relative risk (RR) were determined in Ashmun, Qwesna, ElShohadaa, Shibin_ElKom, ElBagur, and Minuf which are almost all cities of the Menofia governorate.