Introduction

Dengue fever is a severe, flu-like illness that affects infants, young children, and adults, but seldom causes death. There are four dengue virus serotypes (Den1, Den2, Den3, Den4) and all can cause dengue fever. The dengue virus belongs to the genus Flavivirus and the Flaviviridae family. ‘Dengue virus is primarily transmitted by Aedes mosquitoes, particularly Aedes Aegypti.[1] There is no specific treatment for dengue fever.’ Only symptom management, which can vary from oral rehydration therapy at home with close follow-up to hospital admission with administration of intravenous fluids and/or blood transfusion, is used for dengue treatment. The mortality of dengue infections is 1-5% without treatment, and less than 1% with adequate treatment.[1] Previous studies revealed that the reasons for death include lack of access to prompt treatment (late health-seeking behavior), late diagnosis or diagnosis errors, fluid accumulation (leading to heart failure or pulmonaire edema), respiratory distress, severe organ involvement, severe bleeding, and shock.[4]

Dengue virus infection is a global health threat and is currently endemic in more than 125 countries worldwide. There are estimated 50 to 100 million dengue infections worldwide every year, with half a million cases requiring hospitalization and approximately   25,000 deaths.[2] In the Western Pacific Region, dengue infections are most common during the rainy season (April to October) peaking in late August and September historically.[3] Dengue is endemic in the Lao People’s Democratic Republic. Between 2006 and 2012, the annual dengue notification rate ranged between 62 and 367 cases per 100,000 population. The case fatality ratio (CFR) was 0.2% for all years except 2008 at 0.5%. In the epidemic year of 2010, 22 890 cases and 46 deaths were reported; with an estimated 367 cases per 100,000 population.[5]

In 2013, a large dengue epidemic occurred with cases reported from all 17 provinces and deaths occurring in eleven provinces in Lao People’s Democratic Republic. The 2013 epidemic was detected in January 2013 by the National Center for Laboratory and Epidemiology (NCLE) through the national routine surveillance system, Lao Early Warning Alert and Response (LaoEWARN), which receives daily reports from central and provincial hospitals through all provincial health departments. In week 38, the CFR of Vientiane Capital and Champasack Province were 0.32% and 0.67%, respectively; the CFRs were much higher than the previous national ones and most of the dengue deaths were from these two provinces.

This study was conducted to reveal the underlying causes of the increased dengue CFRs by investigating the dengue fatal cases in Vientiane Capital and Champasack Province in 2013, to deduce specific recommendations to improve dengue case management and reduce the severity of dengue infections in Lao People’s Democratic Republic in future.

Methods

We conducted a descriptive analysis that comprised all dengue death cases who were admitted in hospitals from Vientiane Capital and Champasack Province in the Lao People’s Democratic Republic from August 2013 to January 2014. Five hospitals from Vientiane Capital and two from Champasack Province were included in the analysis.

Case Definitions

Dengue cases were defined according to the 2009 World Health Organization revised case definitions for dengue. A clinical dengue case was defined as a person with a fever of 2–7 days and having two of the following symptoms: nausea/vomiting, rash, aches and pains, and a tourniquet-positive test of leukopenia. A dengue case with warning signs was defined as a clinical dengue case with any warning signs including abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, liver enlargement >2cm, and/or increase in hematocrit concurrent with rapid decrease in platelet count. A severe dengue case was defined as a dengue with warning signs case and had severe plasma leakage, leading to shock syndrome; fluid accumulation with respiratory distress; severe bleeding; or severe organ involvement.[6]

Data Collection and Analysis

Data were collected from the hospitals using a standard mortality form and from the Integrated Dengue Case Management form. Data collected included demographics, clinical and treatment details, cause of death, and laboratory results of the cases.’ Data on dengue laboratory confirmation and serotyping from the National Center for Laboratory and Epidemiology (NCLE) were collected. These included the results of the NS1 dengue rapid test (Microbix Biosystems Inc., Mississauga, Canada), Enzyme-Linked Immunosorbent Assay (Panbio® Dengue IgM Capture ELISA, Alere Inc., Waltham, Massachusetts, USA) and polymerase chain reaction test (Invitrogen, ThermoFisher Scientific, Waltham, Massachusetts, USA).

All data were analyzed descriptively using Epi Data software (Version 3.1) and Microsoft Excel (Version 2010).

Results

In 2013, there were 44,171 cases of dengue and 95 deaths reported in the Lao People’s Democratic Republic (CFR = 0.21%). Of the 95 deaths, 61 (64.2%) were residents of Vientiane Capital or Champasack province. Most deaths (74%) occurred among people aged under 15 years. No sex differences were found among the cases (male-to-female ratio = 1:1.03). Most of the death cases (51/61, 84%) presented with severe dengue; and the rest (10/61, 16%) presented with dengue with warning signs.

Comorbidity was present in 38% of the fatal cases, including thalassemia, cardiovascular diseases, hypertension, asthma, epistaxis, menstruation, and chronic otitis. About 75% of the cases sought health care prior to death; 56% sought health care only once; 10% sought care again after initial treatment. Almost half (48%) of all cases visited medical personnel in the villages. About one-third (34%) had therapy before admission, mostly Intravenous (IV) fluids (Table 1). The median time from symptom onset to hospital admission was 4 days in Vientiane Capital (range 1 – 5) and 3 days in Champasack Province (range 1-4). The median time from admission to death was one day in both provinces (range 0-1). The time for admission to death ranged from 0-8 days (Table 1).

Table 1: Characteristics of dengue death cases, Vientiane Capital and Champasack Province, 2013. (n=61)*

The proximate cause of death was documented in all cases. Of 36 patients who died due to severe bleeding, 11 (30%) received blood products more than 24 hours after the blood transfusion request by the doctor and 11 did not receive them at all. Of 25 patients whose proximate cause of death was fluid overload, 19 (76%) had received IV fluid infusion from another Health care facility prior to admission, and six (24%) at admission. Late or incorrect diagnosis for dengue with warning signs was common among the death cases. Lack of constant monitoring of vital signs (due to the shortfall of doctors and nurses) was reported among 61 death cases.

Twenty-eight (46%) of death cases had specimens submitted for laboratory testing. All 28 (100%) specimens tested were positive by at least one laboratory assay, including 14.2% (4/28) by rapid test, 71.4% (20/28) by ELISA, and 14.2% (4/28) by PCR.

The CFR was higher in Champasack Province than in Vientiane Capital but was less than 1% in both districts (Table 2).

Table 2: Mortality (per 10,000 population) of dengue cases, Vientiane Capital and Champasack Province, Lao People’s Democratic Republic, 2013 (n=61)

The CFR for dengue in Vientiane Capital and Champasack province was higher than that of the annual national average of the Lao People’s Democratic Republic.[5] This is most likely due to the hospitals in these provinces being overwhelmed with cases. In Champasack Province, one provincial hospital and nine district hospitals managed around 5000 dengue cases, while in Vientiane Capital, seven central hospitals managed 8453 dengue cases in 2013. Champasack province had a much lower doctor-patient ratio which might explain the higher CFR, in comparison to Vientiane Capital. Shortfalls of doctors and nurses might result in incomplete constant monitoring of vital signs.

Late or incorrect diagnosis for dengue with warning signs was common among the fatal cases. Healthcare-seeking delays resulting in high fever development and delay of hospital admissions probably contributed to this observation. There were delays in blood transfusion for patients with severe bleeding, which resulted in patients not being stabilized for the administration of normal saline or polyglukin for treatment. The results also revealed an excess use of IV fluids prior to hospitalization in several death cases, as these dengue patients presented with symptoms of fluid overload. This indicated that treatment guidelines from WHO [6] were not used in the early stages of the outbreak.

Measures from the Lao People’s Democratic Republic government were implemented to control the outbreak in July 2013. These included: (i) Strengthen case management resources in hospitals to manage the high dengue case numbers and (ii) Advocacy meetings with multi-sectoral dengue task forces at all levels. (iii) Strengthen NCLE dengue surveillance by receiving daily reports for rapid response to cluster (vi) Information Education for Health campaigns to improve early healthcare-seeking behavior. Also, the government provided extra medical students to each hospital to assist with case management, reporting of dengue cases, and conducting vector control measures. Training on dengue clinical management in healthcare facilities was also provided before raining season in 2013. The cases had been reduced dramatically after these interventions.

There were some limitations in this study. The analysis was done by using secondary data sources. Some data were missing from the records, especially those in Champasack province. Certain analyses could not be conducted due to the large amount of data missing in certain variables. Also, data collection was time-consuming and we could not avoid human errors during the process.

Based on the results, we recommend better recognition and diagnosis of dengue, especially early in the dengue season; also, better treatment and monitoring of patients through ongoing staff training, including urgent requests for blood when required, closely following up evaluations, and documenting all interventions are encouraged. As fluid overload was a common factor for severe dengue outcomes, we should ensure that patients who have already received IVF at home or in other hospitals do not repeat the treatment when admitted. It is also useful to use standardized reporting forms at all levels for documenting the case details.

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2. Fact Sheet: Dengue and severe dengue. Geneva. World Health Organization. (2015).
3. Arima Y. (2015). Epidemiological update on the dengue situation in the Western Pacific Region, 2012.Western Pac Surveill Response J. 6(2): 82-89.
4. Surveillance weekly summarized. (2015).  Nonthaburi, Bureau of Epidemiology Department of Disease Control.
5. Khamphaphongphan. (2014). National dengue surveillance in the Lao People's Democratic Republic, 2006–2012: epidemiological and laboratory findings. Western Pac Surveill Response J. 5(1): 7–13.
6. Dengue guidelines for diagnosis, treatment, prevention and Control: Geneva. (2009). World Health Organization.
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