Abstract

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 70106 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 61671 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 20103 cases, Idleb with 14142 cases, Raqqa with 12818 cases and Aleppo with 11617 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.

Methods

Results

Main 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

	AWD cases	Per cent	Total
Gender (male, n)	493	46.5	1061
Age category, years			1061
<2	206	19.4
2–5	99	9.3
5–10	86	8.1
10–18	140	13.2
18–30	146	13.8
30–60	289	27.2
>60	95	9.0
Geographical			1058
Urban life	620	58.6
Rural life	426	40.3
Nomad life	12	1.1
Shock Index (SI)			862
Under 0.6	52	6.0
0.6~1 normal	399	46.3
1~1.4	268	31.1
1.4–2	126	14.6
More than 2	17	2.0
ASA classification			1061
ASA I	789	74.4
ASA II	224	21.1
ASA III	42	4.0
ASA IV	6	0.6
ASA V	0
Infection source (as reported by patient)			1061
Contaminated fruits	25	2.4
Contaminated water	2	0.2
Corn cobs	1	0.1
Falafel, peanut and fatteh	15	1.4
Fast food	57	5.4
Fish	1	0.1
Ice cream	11	1.0
Ice cubes	15	1.4
Meat	4	0.4
Milk	13	1.2
Rice	1	0.1
Swimming in a contaminated pool	3	0.3
The infection passed from his/her family	30	2.8
Vegetables such as parsley and mint	136	12.8
Well water	79	7.4
Unknown	668	63.0

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ASA, American Society of Anesthesiologists; ASA I, healthy person; ASA II, mild systemic disease; ASA III, severe systemic disease; ASA IV, a moribund person who is not expected to survive without the operation or severe systemic disease that is a constant threat to life.; ASA V, a declared brain-dead person whose organs are being removed for donor purposes; AWD, acute watery diarrhoea.

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 17g/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

	AWD cases	Per cent	Total
Clinical presentation in addition to diarrhoea
Nausea and vomiting	781	73.6	1061
Abdominal cramps	576	54.3	1061
Other	139	13.1	1061
Severity of dehydration			1003
Severe	174	17.3
Some	507	50.5
None	322	32.1
Laboratory findings
Haemoglobin (g/dL)			845
Less than 10	197	23.3
10–12	243	28.8
12–17	387	45.8
More than 17	18	2.1
Platelets (103/µL)			821
Less than 15	3	0.4
15–30	6	0.7
30–50	4	0.5
50–150	50	6.1
150–450	636	77.5
More than 450	122	14.9
Serum creatinine (mg/dL)			812
Less than 0.6	311	38.3
0.6–1.3	344	42.4
More than 1.3	157	19.3
Serum urea (mg/dL)			821
10–50	639	77.8
More than 50	182	22.2
WBC (109/L)			744
Less than 4.5	34	4.6
4.5–10	295	39.7
More than 10	415	55.8
Random glucose (mg/dL)			579
Less than 40	32	5.5
40–120	365	63
120–200	150	25.9
More than 200	32	5.5
Serum potassium (mEq/L)			817
Less than 3.5	270	33
3.5–5	516	63.2
More than 5	31	3.8
Serum sodium (mEq/L)			814
Less than 135	352	43.2
135–145	446	54.8
More than 145	16	2

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Severity of dehydration: severe (general inspection: lethargic, unconscious, floppy, eyes: sunken, dry, absent tears, unable to drink, drinks poorly), some (restless, irritable, sunken, tears absent, thirsty, drinks eagerly), none (general inspection well, alert, skin pinch normal, eyes normal, tears present, tongue moist, no thirst).

AWD, acute watery diarrhoea; WBC, white blood cells.

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

	AWD cases	Per cent (of total AWD cases)
Intravenous rehydration
Lactated Ringer solution	354	33.4
Isotonic sodium chloride solution	250	23.6
Other	138	20.7
Total	728	68.6
ORS	697	65.7
Antibiotic treatment
Total	682	64.3
Tetracycline	7	0.7
Doxycycline	328	30.9
Trimethoprim/sulfamethoxazole	2	0.2
Furazolidone	5	0.5
Ciprofloxacin	319	30.1
Ampicillin	0	0
Other	233	22
Potassium supplementation
Oral	18	1.6
Intravenous	233	22.0
Potassium-sparing diuretics	3	0.3
Total	254	23.9

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AWD, acute watery diarrhoea; ORS, oral rehydration solution.

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

	AWD cases	Per cent	Total
Patient discharge			1061
Same day with admission	741	69.8
Next day	32	3.0
After	288	27.1
Need for intensive care unit	10	0.9	1061
Need for dialysis	9	1	907
Patient health at discharge*			1061
Good	846	79.7
Moderate	187	17.6
Poor	24	2.3
Died before discharge	4	0.4
Complications at admission and in the hospital
All	411	38.7	1061
Severe dehydration	173	16.3	1061
Electrolyte imbalance	299	28.2	1061
Acute kidney injury	10	0.9	1061
Shock	21	2	1061
Hypoglycaemia	32	3	1061
Other	19	1.8	1061
Patient’s health after follow-up			1061
Good	858	81.0
Moderate	155	14.6
Poor	36	3.4
Died	10 (4 in AUH and 6 in another hospital)	0.9

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*Good health: the patient no longer had any symptoms or mild symptoms from the convalescent stage. Moderate health: the patient is still suffering from the symptoms of the disease, but without any serious complications or damage to the organs. Poor health: the patient suffers from complications of the disease and his condition is poor and has never improved.

AUH, Aleppo University Hospital; AWD, acute watery diarrhoea.

In the subgroup analysis 2weeks to 1month 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).

Supplementary data

bmjopen-2023-082385supp002.pdf

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.

Supplementary Material

Footnotes

References