Strengths and limitations of this study

The study conducted a thorough analysis of acute watery diarrhoea (AWD) cases at Aleppo University Hospital following the declaration of a cholera outbreak in Syria, providing valuable insights into the impact of the disease and its management.

By encompassing all patients with AWD, regardless of age or admission status, the research captured a wide range of cases, enhancing the diversity and inclusivity of the findings.

The research, which was non-interventional and based solely on observation, included all patients with AWD, regardless of age or whether they were admitted to the hospital or discharged on the same day.

The study provides detailed management and clinical assessment data, along with a 2-week to 1-month follow-up period.

Positioned at the primary medical facility in the city where the initial cholera case emerged, this research serves as an essential tool for comprehending and combating the ongoing outbreak.

Introduction

Acute watery diarrhoea (AWD) is a condition that typically lasts for less than 14 days and is caused by enterotoxigenic bacteria or viral infections in the gastrointestinal system. The bacterial aetiologies of AWD are diverse and can include Vibrio cholerae, Shigella spp, Salmonella spp, Escherichia coli or Campylobacter spp infections.

AWD outbreaks present significant challenges to healthcare systems due to their rapid onset and often unknown sources of infection. These outbreaks are frequently concentrated in areas where potential sources of infection, such as contaminated drinking water, inadequate water filtration infrastructure, animal exposure, and sewage-contaminated food and beverages are prevalent. The response and impact of these outbreaks vary between countries based on factors such as healthcare infrastructure, emergency response capabilities, food and water sanitation practices, and population awareness of infectious diseases. Alarmingly, several countries with historically low AWD rates have experienced recent outbreaks, with nearly 70 106 reported AWD cases in three Middle Eastern and North African countries, according to the WHO’s December 2022 reports.1–3

Cholera, a waterborne intestinal infection transmitted through the faecal-oral route, is a well-known cause of AWD cases. Despite being easily treatable, cholera can become life-threatening if rehydration is delayed, leading to rapid volume depletion. While many developed countries successfully eradicated cholera years ago, low-income and middle-income countries continue to face occasional outbreaks.1 2 In late 2022, countries in the Eastern Mediterranean region, such as Iraq and Lebanon, reported significant cholera outbreaks, with Syria experiencing a resurgence of cholera after nearly two decades.3

By 10 December 2022, Syria had reported 61 671 suspected and confirmed cholera cases, along with 100 deaths across its 14 governorates. The outbreak began on 10 September 2022, when the Ministry of Health (MoH) declared a cholera outbreak in Aleppo Governorate. Following this declaration, other governorates began to report cases of AWD and suspected cholera cases. The most affected areas included Deir Ez-Zor with 20 103 cases, Idleb with 14 142 cases, Raqqa with 12 818 cases and Aleppo with 11 617 cases, as indicated by reports from the WHO and the Syrian MoH. These reports also highlighted a case fatality rate of 0.2% and an overall cholera positivity rate of 46%.3

Despite the high prevalence of AWD and cholera outbreaks in the region, there is limited detailed information available on the quality of the response and patient outcomes during these emergencies. By examining the cases at Aleppo University Hospital (AUH) during the outbreak period, we aim to provide valuable insights into the effectiveness of response measures implemented by health authorities and the challenges encountered in managing AWD and cholera cases in a resource-limited environment. This information can inform future outbreak preparedness and response strategies, potentially reducing the morbidity and mortality rates associated with these infectious diseases.

This study focuses on reporting AWD cases at AUH in Aleppo Governorate during the outbreak from 20 September to 20 October. The objective is to assess the quality of the response and patient outcomes within 30 days of the cases being reported in order to gain a better understanding of the healthcare system’s management of AWD and cholera cases during this critical period.

MethodsStudy design and participants

This study in Syria is a localised, longitudinal study involving individuals of all ages. We conducted a prospective cohort study to enhance our understanding of AWD and to collect a comprehensive and high-quality data set on the condition. Patients were admitted to AUH between 20 September 2022 and 20 October 2022. The process began with a request for verbal informed consent by physicians prior to the questionnaire administration, in compliance with the Strengthening the Reporting of Observational Studies in Epidemiology statement.4

Sample size calculation

The sample size for this study was calculated based on the estimated prevalence of AWD in the population. Using a conservative estimate of 2%, a confidence level of 95% and a margin of error of 0.5%, the required sample size was calculated to be 385 participants. To account for potential dropouts and incomplete data, we aimed to recruit more than 385 participants for this study during the chosen period for the study.

Ethical approval

The data used in this study were fully anonymised before being accessed by the authors.

Bias

The dean of the Faculty of Medicine, the heads of the Department of Internal Medicine and the Department of Paediatric Medicine, and the general director of AUH conducted an overall review and validation of the project. Medical staff members were also involved in the research. Investigators conducted fieldwork, with interviewers responsible for conducting interviews and collecting data, and doctors responsible for the health assessments. All efforts were made to ensure accurate registration of all data.

Data collection and variables

Patients were interviewed using a structured questionnaire to collect information on patient characteristics, including demographics (such as age, gender and place of residence), admission details (eg, dehydration, fluid loss and stool description), comorbidities and previous medications.

Clinical examinations and patient history data were recorded, including measurements of blood pressure and heart rate, and assessment of clinical symptoms such as diarrhoea, nausea, vomiting, fever, among others. Additionally, details on cholera diagnosis, laboratory findings, rehydration, management and follow-up were recorded. The questionnaire was designed following international standards.

All laboratory analyses were carried out by the central laboratory at AUH, including complete blood count and blood biochemistry (blood glucose, serum creatinine, urea, potassium, sodium).

Patients were categorised into five grades based on their health status using the American Society of Anesthesiologists (ASA) Physical Status Classification.5 Habits such as smoking and alcohol consumption were evaluated using the WHO’s Smoking and Tobacco Use Policy, which classifies patients into four categories: daily smoker, occasional smoker, former smoker and never smoker.6

The patients’ ages were categorised into several age groups. Patients were assessed, and their data were recorded during their hospital stay and 2 weeks after discharge. Those whose condition did not improve after 2 weeks were followed up for 30 days. Evaluation of patients occurred at discharge and 2 weeks later, with classification into several health categories: good health, indicating the absence of symptoms or presence of mild symptoms from the recovery stage; moderate health, indicating ongoing disease symptoms without serious complications or organ damage; poor health, indicating disease complications and lack of improvement; and deceased patients. Complications of AWD were documented, and dehydration severity was evaluated. The Patient Data Collection Form is provided in online supplemental file A.

Patient and public involvement

The patients did not participate in the questionnaire design, biological measurements or outcome measures; neither did they participate in the design, recruitment and conduct of the study. Furthermore, all patients or their families were informed about the use of the data for research purposes in this study.

Statistical methods

Patient data were entered into an Excel database and analysed using SPSS statistical software V.26.0. Descriptive statistics, such as frequencies and percentages, were used to summarise patients’ key results, including gender, age category, geographical location, shock index, ASA Classification and infection source. Quantitative variables were categorised, and frequencies and percentages for each category were calculated. Subgroup analyses by age groups for all primary study variables provided a comprehensive data assessment. The last observation carried forward technique was employed to address missing data, involving carrying forward the most recent recorded observation to fill in missing data points during follow-up. The follow-up period lasted 2 weeks but extended up to a month for deteriorating patients. This method allowed for systematic management of missing data and ensured analyses were conducted using the most complete data set available.

ResultsMain characteristics of the patients

A total of 1061 patients with AWD were admitted to AUH between 22 September and 22 October 2022, with a notable gender distribution showcasing 46.5% as male. The majority were in the middle-age category (30–60 years) and early childhood (<2 years). A predominant proportion of patients (58.6%) were residents from urban areas, and 40.3% were residents from rural areas. According to the ASA Score, 74.4% were healthy (ASA1).

In most cases (63%) patients could not define the infection source. It seems that the recent AWD outbreak in Syria is not associated with tap water contamination, as no clear clustering of cases was identified. Intriguingly, a diverse range of potential infection sources emerged from patient data within our hospital, including uncontrolled well water, vegetables (notably parsley and mint, might have been irrigated with contaminated water), and faecal-oral transmission through contaminated street food/fast food particularly those integrating vegetables. The summary of the patients' characteristics is shown in table 1.

Table 1

Main characteristics of the patients

Clinical manifestations and laboratory findings

The most frequent clinical manifestations of the patients besides diarrhoea were nausea and vomiting, and abdominal cramps (73.6% and 54.3%, respectively). Except for leucocyte count, most of the patients had normal laboratory tests. 47.6% of patients had haemoglobin between 10 g/dL and 17 g/dL. Platelets were also within the normal range in 77.5% of patients. On the other hand, 55.8% of patients had white blood cells over 10×109 /L. All laboratory tests and clinical manifestations are demonstrated in detail in table 2.

Table 2

Clinical manifestations and laboratory findings

Patients management

The mainstay of treatment is aggressive volume repletion with adjuvant antibiotic therapy. 77.7% of patients needed intravenous rehydration, 33.4% were given lactated Ringer solution, and 23.6% received isotonic sodium chloride solution. Also, 65.7% were given oral rehydration salts. Regarding antibiotics, doxycycline and ciprofloxacin were prescribed in most cases (61%). Other antibiotics were also used in some cases, such as tetracycline, trimethoprim/sulfamethoxazole, furazolidone and others. The accurate proportions are shown in table 3.

Table 3

Patients management

Outcome of the study

Among the 1061 cases, the majority of patients were discharged on the same day as admission (69.8%), with fewer discharged the following day (3.0%) or after a longer period (27.1%). A small percentage of patients required intensive care unit care (0.9%) and dialysis (1%). At discharge, most patients were in good health (79.7%), followed by moderate health (17.6%) and poor health (2.3%). A minimal number of patients passed away before discharge (0.4%).

Reported complications at admission and during hospital stays included severe dehydration (16.3%), electrolyte imbalance (28.2%), acute kidney injury (0.9%), shock (2.0%), hypoglycaemia (3.0%) and other issues (1.8%). The most common complications were electrolyte imbalance (28.2%) followed by severe dehydration (16.3%).

In the follow-up period, the majority of patients continued to show good health (81.0%), followed by moderate health (14.6%) and poor health (3.4%). A small number of patients passed away during follow-up, with four deaths at AUH and six at other hospitals (0.9% in total) (table 4).

Table 4

Outcomes of the study

In the subgroup analysis 2 weeks to 1 month postadmission, the majority of patients in all age groups exhibited positive health outcomes, ranging from 69.5% to 88.9%. The Age 7 (>60 years) category had the highest percentage of patients with poor health outcomes at 8.4%, with the highest death rate in the same age group at 4.2%, followed by patients under 2 years at 1.5%. Overall, the data suggest varying health outcomes based on age, with younger individuals showing a higher likelihood of recovery compared with older age groups (online supplemental file 2).

Discussion

Between September and October 2022, AUH admitted 1061 patients with AWD, most of whom were middle-aged or young children. The results of the 2017 outbreak in Yemen also show a similar pattern to our findings, with the middle-aged (15–49 years) and children (less than 15 years) groups being the most affected.7 8 In the same context, 69% of those infected with the Nigerian outbreak in 2005 were 15 years old and above, and 90% of the deaths were in this age group, according to Shittu et al, 9 as well as in the 2004 Nepal outbreak.10 What may explain these results is that these age groups are more exposed to known sources of infection than others. Women are slightly more affected, but there is no statistical significance for the incidence rates related to sex. This is due to the fact that cholera is an infectious disease. Data from Bangladesh confirm this finding.11

The previous outbreak in Syria does not appear to be linked to tap water contamination, but rather to potential sources such as uncontrolled well water and contaminated vegetables, similar to outbreaks in other countries like Yemen and Nigeria.7 9

The association of severe watery diarrhoea with nausea and vomiting in many unmanaged cases worsens the situation and leads the patient to dehydration and electrolyte disturbance, which may be dangerous in many cases. Only a few studies in the medical literature have highlighted this association, including the study that highlighted the AWD during the 2017–2019 Rohingya crisis in Cox’s Bazar, Bangladesh.10

We relied on case management based on what was previously known. We determined the amount and type of fluid resuscitation according to the level of volume depletion. Mild cases, which constitute most cases, were treated with oral rehydration. As for moderate and severe cases, urgent intravenous rehydration through lactated Ringer solution or isotonic sodium chloride solution was the key to restoring circulation. Nevertheless, antibiotics were also considered in many patients, and electrolyte replacement in selective patients.12

38.7% of patients experienced significant complications after being diagnosed with AWD. The most common complications were electrolyte imbalance (28.2%) and severe dehydration (16.3%). Other complications, such as acute kidney injury, volume shock and hypoglycaemia, occurred in smaller numbers. Additionally, only a small percentage of patients (0.4%) died while in the hospital. This is consistent with outbreaks in other countries. Iraq, for instance, confirmed 3063 cholera cases and 19 (0.6%) deaths, while Lebanon announced 5372 confirmed and suspected cholera cases with 23 (0.4%) deaths.4

This study has several limitations that impact the generalisability and validity of the findings. First, the limited sample size, as the study was conducted at AUH, may not accurately represent all cases of AWD in Syria. Additionally, selection bias was introduced as only cases admitted to the hospital were included, potentially skewing the results. The lack of long-term follow-up limited the assessment of outcomes beyond 30 days postdischarge. The study was limited to a specific region in Syria and may not be applicable to other regions with different healthcare settings, demographics and environmental factors.

Conclusion

This study has yielded descriptive results reminiscent of studies conducted during prior AWD outbreaks in developing countries like Yemen, Nigeria and Lebanon. We have outlined the sources of infection, including contaminated well water and vegetables. Regrettably, we observed a stagnation in outcomes, with no discernible improvement in terms of morbidity or mortality compared with past outbreaks. Consequently, it is imperative that future research endeavours delve deeper into the risk factors that contribute to the proliferation and severity of the disease, as well as explore optimal management strategies.

Data availability statement

Data are available upon reasonable request. The creation of a data set consisting of over 1000 patients with AWD during the 2022 cholera outbreak in Aleppo, Syria, along with detailed patient observations, is of great significance. Through the documentation and analysis of this extensive data set, we are better equipped to comprehend the characteristics, trends and outcomes of cholera cases during this specific outbreak. This data set can serve as a valuable resource for public health officials, researchers and healthcare providers as they develop more effective strategies for the prevention, treatment and control of cholera in similar settings. The data set is accessible through the corresponding author. We encourage any research group interested in using these data to submit a research proposal outlining background information, research questions, methods and authorship for potential collaborations. All research proposals will undergo review by a scientific committee. Furthermore, proper citation is required when referencing or using these research data in order to acknowledge the source and credit the original researchers and contributors. Adherence to these guidelines upholds transparency, ethics and integrity in the utilization of the valuable data gathered and analysed in this study.

Ethics statementsPatient consent for publication

Consent obtained directly from patient(s).

Ethics approval

This study involves human participants and was conducted in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent amendments, following ethical approval from the ethics committee at the Faculty of Medicine, University of Aleppo, with registered reference number 1932, to ensure compliance with ethical standards and guidelines for research involving human subjects.