Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden. We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms (ER) in Pakistan, recording patient health-seeking behaviors, access to care and analyzed spatial distribution of cases from Karachi. A total of 6212 dog-bite cases were identified over two years starting in February 2009 with largest number reported from Karachi (59. 7%), followed by Peshawar (13. 1%) and Hyderabad (11. 4%). Severity of dog-bites was assessed using the WHO classification. Forty percent of patients had Category I (least severe) bites, 28. 1% had Category II bites and 31. 9% had Category III (most severe bites). Patients visiting a large public hospital ER in Karachi were least likely to seek immediate healthcare at non-medical facilities (Odds Ratio = 0. 20,95% CI 0. 17–0. 23, p-value<0. 01), and had shorter mean travel time to emergency rooms, adjusted for age and gender (32. 78 min, 95% CI 31. 82–33. 78, p-value<0. 01) than patients visiting hospitals in smaller cities. Spatial analysis of dog-bites in Karachi suggested clustering of cases (Moran' s I = 0. 02, p value<0. 01), and increased risk of exposure in particular around Korangi and Malir that are adjacent to the city' s largest abattoir in Landhi. The direct cost of operating the mHealth surveillance system was USD 7. 15 per dog-bite case reported, or approximately USD 44,408 over two years. Our findings suggest significant differences in access to care and health-seeking behaviors in Pakistan following dog-bites. The distribution of cases in Karachi was suggestive of clustering of cases that could guide targeted disease-control efforts in the city. Mobile phone technologies for health (mHealth) allowed for the operation of a national-level disease reporting and surveillance system at a low cost.
Infectious disease surveillance continues to remain challenging in developing countries with resource constraints, weak health systems and poor reporting mechanisms [1], [2]. Existing limitations in achieving these core capacities of the International Health Regulations (IHR) have been further compounded in Pakistan by the closure of the Ministry of Health in 2011 and devolution of some of its roles to the provinces, which has disrupted central information collection and dissemination processes [3], [4]. Donor resources for surveillance are currently dedicated towards certain high priority programs such as active surveillance for acute flaccid paralysis under the polio eradication initiative, while surveillance for other endemic or emerging infectious diseases has been given far less attention. Determining a more accurate burden of these less-studied illnesses is necessary to design appropriate preventative measures and to establish best clinical practice. Recent innovations in mobile phone technologies and the rapid growth of the telecommunications sector in developing countries like Pakistan provide possible solutions to filling this knowledge gap. Rabies is a notifiable disease in most developed countries; however, cases are generally underreported in countries like Pakistan and there is a poor understanding of the disease burden [5]. South Asia is one of the few regions of the world where the epidemiology of rabies is driven through the urban cycle (primary transmission of the virus occurs through dog-bites rather than wildlife), even though effective control and preventative measures for the disease have long been established [6]. In resource-constrained settings, high-risk areas need to be identified to target interventions for effective rabies control and elimination. In addition, gaps need to be identified in clinical and public health practice where appropriate preventative treatment is either delayed or is inadequate following dog-bites. Routine surveillance of dog-bites and rabies in Pakistan is currently conducted under the government' s HMIS (Health Management Information System) reporting program but poor quality of collected data prevents evidence-based disease control efforts. Published journal articles on the other hand have relied upon retrospectively collected data from hospital records [7]–[9] and may not adequately capture information regarding key rabies prevention measures recommended by the WHO or to guide efforts towards local canine rabies elimination [10]. We present an analysis of prospectively collected data utilizing mobile phone based health technologies, or mHealth, for dog-bite and rabies surveillance across nine sites in Pakistan, with technical and financial support from the World Health Organization (WHO).
The aims of this study were to: 1) estimate the burden of dog-bites in Pakistan; 2) describe the frequency, age and gender distributions and severity of dog-bite cases across the reporting sites; 3) assess differences in patient health-seeking behavior and patient access to care amongst the reporting sites; 4) identify high-risk neighborhoods for dog-bite exposure in Karachi, Pakistan' s most populous city; 5) describe implementation costs of the mHealth surveillance system from a health services perspective. Surveillance was carried out from February 2009 to February 2011. Figure 1 shows the locations of participating Emergency Rooms (ER) in Hyderabad, Thatta, Bahawalpur, Abbottabad, Peshawar, Mansehra, Quetta and two sites in Karachi (one public and one private). ERs were based in high volume tertiary care hospitals that were well known as major referral hospitals for dog-bites and provided rabies vaccination, either the sheep-brain tissue vaccine from the government or cell-culture vaccine from philanthropic donors. The hospital ERs served as reporting centers for the study. Several other public and private facilities providing emergency medical care exist in these cities, particularly in Karachi. For the remaining cities, the selected hospitals were the primary facilities for emergency care serving a mix of urban and rural populations. Reporting from two centers in Lahore and Rawalpindi ceased during the course of the study due to deteriorating security at the time and poor institutional support for surveillance. Limited data was collected from these centers and is not included in the present analysis. Cases were defined as all patients presenting with dog-bites to emergency rooms at enlisted centers and patients with dog-bites referred from other facilities. If dog-bite victims did not seek healthcare, or sought care with traditional healthcare providers and alternative medical centers from where referrals were not made to an enlisted center, those cases would not be reported through our system. In addition, information on some cases was not captured because of refusals to take part in the questionnaire and could not be included. Lay persons with at least 12 years of education were recruited on recommendation of local hospital administrators, and were provided training for the role of “screener” to implement the study protocols regarding informed consent procedures and phone-based screening. The training emphasized basic research ethics and the necessity of voluntary informed consent. Training was provided onsite for data entry and storage using the mobile phone and included role-play to enable screeners to familiarize themselves with the study tools. The administrative heads of ERs were involved in supervision of screeners and in providing local logistical support. Screeners were provided a monthly stipend of approximately USD 80 per month. Dog-bite cases were approached immediately after initial treatment, introduced to the study and its objectives and consent was requested for an interview. A standardized questionnaire using a mobile phone based application was completed for all consenting patients. The questionnaire was created using the openXdata software package for low-cost mobile devices. OpenXdata is an open source software for service providers and researchers to design and manage forms for data collection using mobile devices and remotely monitor data collection activity in the field. OpenXdata has two components, a web-based server application and openXdata mobile which is installed on low cost phones. We provided a GPS-enabled Nokia 6220 mobile phone (costing USD 250 each) to screeners at each site programmed with forms to collect patient demographics, details about the nature of the bite and geographic location of the incident. A patient' s attendants provided history of exposure and treatment in cases where rabies was suspected and the patient was incapable of responding. The use of openXdata allowed for predefined validation checks as data was being entered into the phone, and eliminated the use of paper forms other than for consent. Date and time stamps were automatically recorded along with GPS coordinates each morning immediately outside the site to monitor the screeners attendance at the hospital. All data entered via mobile phones was uploaded on to the centralized openXdata server, using a GPRS connection. Ethical approval for the study was obtained from the Institutional Review Board (IRB) at Interactive Research & Development (IRD) which is registered with the U. S. Department of Health and Human Services (DHHS), Office for Human Research Protections (IRB # 00005148). Informed consent was obtained from patients or from guardians in the case of children, through signatures or thumbprints (for illiterate patients) onto paper consent forms, each of which was bar-coded with the patient ID to enable linking with electronic forms. Approval for the use of thumb ink prints in patients unable to provide signed consent as well as for guardians in the case of children was provided by the IRB. An IRB exemption was subsequently obtained for retrospective analysis of surveillance data following closure of the study and data collection activities. Statistical analysis was carried out using Stata version 12. 1 (College Station, TX: StataCorp LP). We calculated summary statistics by center for total number of cases, patient demographics and severity of bites based on the WHO classification [10]. Type of care immediately sought after the bite, included visits to hospitals, general practitioners, homeopathic facilities, spiritual healers or self-treatment at home. These were categorized as a binary variable to compare treatment at a medical facility versus treatment at a non-medical facility and administering self-treatment. Summary statistics by center were calculated for type of immediate care sought after dog-bites and patient travel time to emergency room. We subsequently fitted a multiple logistic regression to the binary variable as a measure of assessing differences in health-seeking behavior with reporting center, age (centered at the mean) and gender as explanatory variables. Reporting center was a categorical variable with nine levels and we set the public hospital in Karachi as the reference level. Due to its more central urban location we hypothesized that the victims presenting to this center would have the greatest health access and shortest travel times. In addition, it reported the largest number of cases therefore was a suitable center to select as a reference category for fitting the model. Pearson' s chi-squared was used to test for goodness of fit. The test was appropriate as the model consisted mostly of non-unique covariate patterns [11]. Multiple regression analyses were performed with travel time to ER as the response variable, in order to assess differences in health access of patients following dog-bites with reporting center, age (centered at the mean) and gender as explanatory variables. During model validation, time data (recorded in minutes) were log-transformed for the residuals to approximate a normal distribution. Robust regression using bootstrapping for 95% confidence intervals was utilized in order to take into account the effect of outliers, but these were not excluded from the analysis as they may represent cases that were travelling to centers from distant locations and provide valuable information with regards to medical access. Spatial analyses were limited to the city of Karachi as it had the highest number of cases and administrative boundaries for the city (as distinct town units) were easily available to permit geocoding of addresses. In addition, an insufficient number of addresses in other cities were deemed appropriately detailed for inclusion in spatial analysis, or were outside city limits. Due to the presence of a large stray dog population and wide variations in social determinants of health such as poverty and homelessness we hypothesized a non-uniform distribution of dog-bite incidence in the city [12]. As a predominantly Muslim country, dog-ownership is quite low in Pakistan. Stray-dogs are frequently encountered in Karachi, particularly in low-income areas and are therefore less likely to be vaccinated [12]. Each patient' s address was manually geocoded to an administrative town in Karachi as most respondents did not know the zip (postal) codes for their house address for automated matching to administrative towns. Counts were aggregated up to area-levels for each of the administrative towns and were utilized to generate choropleth maps using ArcGIS (ESRI 2011. ArcGIS Desktop: Release 10. Redlands, CA: Environmental Systems Research Institute). Population estimates were obtained from the last available census carried out in the city in 1998 using a uniform annual population growth rate of 3. 5% for each town up to the year of the study [13]. This growth rate accounts for both natural growth of population as well as increases due to migration into the city. Distribution of dog-bites was examined for spatial dependence and clustering of cases using the Moran' s I test statistic, a global index for spatial autocorrelation that compares differences in counts amongst contiguous area-units after adjusting for population in the overall dataset. We used a Poisson regression, with counts of bites as the response variable and town as the explanatory variable, to indicate whether there was spatial dependence between towns. Population estimates were log transformed and used as an offset for the two years to assess differences in incidence rate ratios between individual towns. Risk estimates of dog-bites for each of Karachi' s 18 towns were calculated using the ratio of observed cases to the expected (based on total population) to identify towns with increased risk of exposure. A spatial cluster detection analysis for increased rates was subsequently carried out using a discrete Poisson model, with the maximum spatial cluster size as <50% of the population (on SaTScan version 8. 0) to identify primary and secondary clusters with increased rates [14], [15]. The costs of the mHealth surveillance system have been described in US Dollars and International US Dollars (I$), a conceptual currency which adjusts costs for purchasing power parities between countries. The costs have been calculated from a health services perspective and do not include patient related variables such as lost productivity.
A total of 6,470 cases of animal-bites were reported during the 24 months of surveillance, of which 96% (6,212) were due to dog-bites. The largest number of cases was reported at the public tertiary care hospital in Karachi (48. 26%), as shown in Table 1. Females accounted for only 20. 6% of the total and their proportions remained low after adjusting for centers. The median age for cases was 20 years (inter-quartile range, 10–35) and 38. 9% of cases were under 15 years of age. Using the WHO classification system for severity of dog bites with Category III being the most severe, 40% of patients had Category I (least severe) bites, 28. 1% had Category II bites and 31. 9% had Category III bites. Following adjustment for center, two public hospitals in Bahawalpur and Karachi reported a greater proportion of Category I bites, where as the other centers reported greater numbers of Category III bites. Less than 1% of cases reported receiving pre-exposure vaccination across all study sites. A previous study from a major public-sector tertiary care hospital in Karachi estimated that 25–35% of cases in the city visited its facility for management of dog-bites, [7]. The estimation was based on interviews with hospital staff and the hospital' s proportion of total vaccines consumed in the city. The ERs included in this study were tertiary care referral centers of similar size therefore we used the total number of cases notified and the same estimated range of the proportion of dog-bites reported to extrapolate the incidence of dog-bites in the catchment areas of these centers. For the two centers in Karachi this equates to 8,565 to 11,992 (2,998/0. 25 to 2,998/0. 35) dog-bite cases for the public hospital and 2,031 to 2,844 (711/0. 25 to 711/0. 35) for the private hospital. For the centers outside of Karachi this equates to a total of 7,151 to 10,012 (2,503/0. 25 to 2,503/0. 35) cases of dog-bites. The estimated range of dog-bites over the two-year period in the catchment area of these centers is therefore, 17,774 to 24,848. Based on the total populations where these centers are located the estimated incidence of dog-bites is 38 to 53 per 100,000 per year. Overall, a greater proportion of cases sought immediate healthcare at a non-medical facility or administered self-treatment (52. 29%) (Table 2). The median time to ER was 30 minutes (IQR 5–1,800 minutes) and ranged from 5 to 7,800 minutes. A proportionately higher number of cases from the Karachi public hospital sought immediate care at medical facility (80. 92%) whereas non-medical or self-treatment was more commonly reported for the remaining centers. Cases reporting from Hyderabad had the shortest median travel time to ER (20 minutes) where as those reporting from Mansehra had the highest (120 minutes). Table 3 describes results of the regression analyses of patient health-seeking behavior and travel time to ER. Patients from all other centers, relative to those visiting the public hospital in Karachi (reference level) were more likely to seek immediate healthcare at a non-medical facility, adjusted for age and gender (p<0. 01). Peshawar and Bahawalpur were most likely to seek immediate health care at a non-medical facility or administer self-treatment compared to visiting a medical facility (adjusted odds ratio 144. 45 and 131. 36 respectively). These odds ratios imply that cases from Peshawar and Bahawalpur were over a hundred times more likely to seek immediate care at a non-medical facility as compared to the public hospital in Karachi. Excluding Karachi, cases from Abbottabad (adjusted odds ratio 5. 12) and Hyderabad (adjusted odds ratio 6. 87) were relatively less likely to seek immediate care at a non-medical facility or administer self-treatment as compared to the remaining centers. Cases reporting to the Hyderabad center had the shortest travel time to the ER compared to the rest of the centers, while those at Mansehra and Abbottabad had the longest travel times. Age and gender were not significantly associated with health-seeking behaviors or travel times to ER. Overall 13 cases died due to rabies at an Emergency Room, 8 of which took place in Mansehra. Only one case was confirmed using the Fluorescent Antibody Test (FAT) on post-mortem examination, with the remaining diagnoses based on clinical symptoms. Figure 2 displays aggregated counts of dog-bite cases for the city of Karachi. Korangi, Jamshed, Landhi and Malir had the highest number of cases of dog-bites. Figure 3 displays incidence rates of dog-bites in the city. The incidence rates are higher in the central towns of Korangi, Malir and Jamshed, although high rates were also observed in the more peripheral towns (Bin Qasim and Gadap). The Moran' s I index for spatial autocorrelation was 0. 20, statistically significant for spatial clustering of cases (p-value<0. 01). There were significant differences in incidence rates between administrative units (towns) based upon Poisson regression analyses, further suggestive of spatial dependence. Figure 4 shows the highest risk estimates for dog-bites in Korangi, Malir and Karachi Cantonment, although Landhi, Jamshed, Gadap and Bin Qasim also had risk estimates of greater than 1. Cluster analysis (Figure 5) identified Korangi as the primary cluster with a relative risk of 7. 14 (log likelihood ratio 942. 16, p-value<0. 01). Karachi Cantonment (log likelihood ratio 91. 95, p-value<0. 01) and Jamshed (log likelihood ratio 35. 08, p-value<0. 01) were identified as secondary clusters, each with a relative risk of 2. 10. These three towns of Karachi represent contiguous area-units where a clustering of high dog-bite rates was observed. As described in Table 4, our experience highlights low deployment and operations costs for our mHealth system across a wide geographic region. The total direct costs of equipment and staffing for two years of surveillance at 8 sites was USD 44,408 with approximately USD 19,385 for capital costs and USD 25,023 for salary support and other operational costs. We estimated the cost per case detected was USD 7. 15 (I$ 17. 26). The average cost per center was USD 4,934 per center enrolled. Costs did not vary significantly between centers and differences were largely attributable to travel expenses for management and program staff for on-site trainings.
We identified a high burden of severe (World Health Organization category III) dog-bites and substantial variation in patient health-seeking behavior and access to care across different regions of Pakistan. Spatial analyses were suggestive of clustering of dog-bite cases in Karachi and can facilitate preventive efforts. Low-cost mobile phone technologies have the potential to address gaps in surveillance systems in low-resource settings. Further cost-effectiveness studies are required of large-scale implementations of mHealth based infectious diseases surveillance systems in developing countries to generate evidence for necessary resources for scale-up and sustainability.
Resource constraints prevent adequate surveillance of neglected infectious diseases such as rabies in developing countries leading to a poor understanding of the disease burden and limited evidence with which to design effective control measures. We utilized a low cost mobile-phone based system to carry out the first prospective surveillance of dog-bites and rabies in Pakistan by screening all patients presenting to nine emergency rooms in eight cities over a two-year period. We found a large number of dog-bite cases (nearly a third of which were severe based on a World Health Organization classification) with substantial geographical variability in time to presentation as well as health-seeking behavior following dog-bites across the reporting sites. Spatial analyses of collected data from Karachi, Pakistan' s largest city identified areas with increased risk of dog-bite exposure, which has implications for the design of necessary control measures such as dog vaccination. While mobile phone based technologies have the potential to address limitations in disease surveillance in developing countries, the cost-effectiveness of large scale implementations of such strategies need to be explored and further evaluated where appropriate.
Geographic Variation in Access to Dog-Bite Care in Pakistan and Risk of Dog-Bite Exposure in Karachi: Prospective Surveillance Using a Low-Cost Mobile Phone System