Fourth Dengue Fever Outbreak Investigation in Ethiopia: A Case Control Study, July 2015

Background: Dengue fever is a rapidly emerging vector born infectious disease caused by Dengue virus and it is now one of WHO reportable diseases. About 50 -200 million cases, 20,000 deaths occur annually. In Ethiopia the first outbreak of Dengue fever appeared in Dire Dawa city in 2013, where 9441 cases were recorded. The second Dengue fever outbreak occurred in Afar Region. Third and fourth was in Somali Region in Godey town, 2014 and 2015. In Godey town acute febrile illness cases of unknown cause become increased started from May 27, 2015. We investigated to identify risk factors of Dengue fever outbreak and commence control measures. Methods: A case-control study was conducted in Godey town, Ethiopia from 8-22 July 2015. Cases were defined according to the WHO guideline and controls were individuals with no sign and symptoms living in the same town with cases. We recruited 50 cases and 100 controls in the study. Medical records and line lists were reviewed. Data were collected at household level using structured questionnaires. Twenty-four serum samples collected from cases. Data was analyzed using SPSS 20 software. Result: We identified 223 cases with 0 death, 116 (52%) were male. The mean age of cases was 25.8 years. Ten cases were positive for Dengue fever by PCR at national laboratory. Lack of formal education (AOR=3.1; 95%CI: 1.30-7.49), living with ill person (AOR=2.8; 95%CI: 1.22-6.52), open containers in household (AOR=3.6; 95%CI: 1.34-9.38) and presence of larvae in the water containers (AOR=5.4; 95%CI: 2.33-12.44) were risk factors for the outbreak. Conclusion: Poor household water handling, living with ill person and lack of formal education contributes for occurrence of Dengue fever outbreak in Godey town. Health education and all other interventions associated with use of water and sanitation needs to be part of long-term control of Dengue.


Background
Dengue Fever is a rapidly emerging vector born viral disease associated with significant public health impact. It is responsible for about 50 -200 million cases, 20,000 deaths annually. It had sporadic distribution in the 19 th century and nine countries around the world reported Dengue fever epidemic in the year 1970. Since then the global epidemiology of Dengue fever changed rapidly and currently it is endemic in 110 countries with 2.5 billion populations at risk in the tropical and subtropical regions. Dengue fever is one of an International Public Health Emergency Concern (PHEC) as recommended by World Health Organization and it is now one of WHO reportable diseases (1).
In Africa, Dengue fever reported in at least 22 countries but is likely to be present in all of them with 20% of the population at risk (2).
In Ethiopia Dengue fever has become a new emerging public health problem. Infection with Dengue viruses present with severe headache, fever, muscle and joint pain, characteristic skin rash and in a small proportion of cases the disease develops into the lifethreatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome. There is no specific treatment for dengue/ severe dengue, but early detection and access to proper medical care lowers fatality rates below 1%. Dengue prevention and control solely depends on effective vector control measures (3).
Dengue fever transmitted by a day biting mosquito AidesHYPERLINK "http://en.wikipedia.org/wiki/Aedes_aegypti" HYPERLINK "http://en.wikipedia.org/wiki/Aedes_aegypti"aegypti which bite particularly during in the early morning and in the evening, but they are able to bite at any time and thus spread infection at any time of day all during the year. There are four distinct serotypes of Dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4) and infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Humans are the primary host of the virus, but it also circulates in nonhuman primates.
Subsequent infection with a different type increases the risk of severe complications (4).
In clean and unfavorable environment for Aides mosquito to reproduce, the infection of Dengue fever is rare. As there is no commercially available vaccine, prevention is sought by reducing the habitat and the number of mosquitoes and limiting exposure to bites.
Several factors have combined effect to produce favorable epidemiological conditions for Dengue fever in developing countries such as rapid population growth, rural-urban migration, inadequate basic urban infrastructure, unreliable water supply leading householders to store water in containers close to homes and increase in volume of solid waste, such as discarded plastic containers and other abandoned items which provide larval habitats in urban areas. Increased air travel and breakdown of vector control measures have also contributed greatly to the global burden of Dengue fever and Dengue Hemorrhagic Fever (DHF) (2).
In Godey town acute febrile illness cases become increased started from May 27, 2015 and serum sample from one suspected Dengue fever cases become positive. A team from EPHI, WHO and Somali regional health bureau deployed to Godey town to investigate the outbreak.
We investigated to identify risk factors of Dengue fever outbreak in order emphasize and commence both short-term long-term control and preventive measures.

Literature Review
An estimated 50 million Dengue infections occur annually and approximately 2.5 billion people live in Dengue endemic countries both tropical and subtropical areas. Although Dengue fever exists in the WHO African Region, surveillance data are poor. Outbreak reports exist, although they are not complete, and there is evidence that Dengue outbreaks are increasing in size and frequency. It has mostly been documented in Africa from published reports of sero-surveys or from diagnosis in travelers returning from Africa, and Dengue fever cases from countries in Sub-Saharan Africa. For eastern Africa, the available evidence so far indicates that DEN-1, -2 and -3 appear to be common causes of acute fever. Examples of this are outbreaks in the Comoros in various years (1948,1984 and 1993, DEN-1 and -2) and Mozambique (1984-1985, DEN-3) (5).
A cases control study to assess risk factors associated with an outbreak of Dengue fever in Brazil in 2001 showed the topographic location of the house was an important risk factor: Other risk factors associated with Dengue fever were plants with temporary water pools on the property, a gutter to collect rainwater, water storage in the house, uncovered water storage container, absence of waste collection and empty glass or plastic containers suitable as putative breeding sites for Aides aegypti (5) According to study conducted on factors associated with spread of Dengue fever in urban.
Lahore, Punjab, Pakistan, 2013, the presence of indoor stagnant water, presence of indoor larvae and non-use of repellents were found to be independent determinants of Dengue fever infection.On this study more men than women and younger rather than older people were affected which is consistent with other findings and may be because these groups are more likely to be Outdoors and, therefore, be exposed to mosquitoes (6).
The other study onrisk factors associated with an outbreak of Dengue fever/Dengue hemorrhagic fever in Hanoi, Vietnam 2014, indicated that living in rented housing, living near uncovered sewers, and living in a house discharging sewage directly into ponds were all significantly associated with DF/DHF (7).
A survey conducted in India showed Dengue cases were more during September to November only, which is similar to most of the previous outbreaks in India. It may be because this season is very favorable for high breeding of the vector, i.e., Aides aegypti.
This seasonal outbreak of disease transmission is very important at local level for effective control measures. The study draws attention toward the male, young adult age group (8).
Also a study done in Zambia reveled that Aides aegypti commonly bites during the day and therefore the use of Long Lasting Insecticidal Nets (LLINs) would not be expected to provide a barrier between the humans and this Dengue fever transmitting vector.
Considering the outdoor activities participated in during the day including farming, fishing, and socializing, the population may be at risk of being bitten by the vector (4).
Vector control is known to be a good method for prevention of vector borne diseases.
There are several reports from India which have demonstrated resistance of mosquito vector with anti larval substances like DDT and dihedron but susceptibility to malathione is reported. Temephos is relatively more effective in controlling Aides aegypti, followed by function, Malathion and DDT. Per domestic thermal fogging reduced the resting and biting for the 3 days after treatment, whereas indoor fogging suppressed adult populations for 5 days (8).

General Objective
To investigate Dengue fever outbreak and commence outbreak prevention and control measures, in Godey town, Somali Region, Ethiopia July 2015.

Specific Objectives
To describe the magnitude of the outbreak by person, place, and time Study population:aperson who fulfills inclusion criteria for either a case or control.

Inclusion Criteria
Cases: any person living in Godey town who fulfilled the case definition of Dengue fever or reactive for Dengue fever by either RDT or PCR and who are voluntary to participate in the study were included.
Controls: any person living in Godey town neighbor to the cases and who hadn't developed sign and symptoms of Dengue fever living in the Godey town during the study.

Exclusions Criteria
Cases and Control: For both cases and controls that refused to participate in the study were excluded.

Study design
We conducted unmatched case control study to identify risk factors associated with dengue fever. For each case, two controls were selected from the general population of the same kebele.

Sampling methods
Cases were selected randomly using the lottery method where each name on the line list was allocated a number on pieces of paper which were put in a box and randomly picked and the name corresponding to that number was recruited into the study.

Sample size determination
For each case, two controls were selected from the general population of the same kebele.
Accordingly, a total of 150 study subjects (50 cases and 100 controls) were included in the study.

Dependent variable
Occurrence of Dengue fever

Data Collection Tools and Procedure
We reviewed medical records and line lists from Hospital and private clinics and structured questionnaires were used to collect data on exposure status of study participants at household's levels. Data were collected from a total of 50 cases and 100 controls to obtain information about the socio-economic status, behavioral and environmental risk variables of cases and controls. Observation on Aides mosquito breeding sites at water sources, and household levels was made.

Definitions
A case patient was defined as a case when she/he fulfills the clinical criteria of acute dengue fever as set by Dengue Fever Guideline: The presence of an acute febrile illness lasting no more than 7 days in combination with the presence any of the following symptoms: headache, retro-orbital pain, myalgia, arthralgia, and or rash.
LLINs utilization: Using LLINs during sleeping by all family members Water containers: Any water containers found in the household level either useable or not but can accumulate water.
Laboratory Investigation: A total of 25 blood serum samples were collected by skilled laboratory professional from ill persons as per the case definition at Godey Hospital and during house to house case searches. The blood sample was tested by RDT at field (6 samples) and by PCR at national laboratory.

Bias control
To minimize recall bias, we used a pre-tested standardized questionnaire and limited the recall period to 12 weeks. Physical examinations and interviews were always performed by the same investigators (D.S and A.A). Thus, inter-observer bias can be neglected. As the epidemiological investigations took place within a period of 2 weeks, intra-observer bias presumably also was very low. All heads of families (cases, controls and the respective neighbors) who were asked to participate in the study permitted inspection of their houses, courtyards and gardens and voluntarily gave all information requested. Hence, non-participation bias can be excluded.

Data Processing and Analysis
Data was entered in to SPSS version 20 and we used SPSS and excel for calculating frequency, ratio, proportion, rate, odds ratio. Bi-variate analysis was used to assess the association between dependent and independent variables. Crude and adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated. Odds ratios were calculated for IgM + cases as well as for cases fulfilling the clinical case definition. All variables that showed a P-value < 0.25 underwent logistic regression and variable that had p-value less than 0.05 were declared to have significant association.

Ethical Considerations
Before interview respondents, observation of household level water containers and take sample from cases and/or controls, we explained the objective of the study and volunteer participation was requested. Then informed verbal consent was taken informally from all respondents and included all those agreed to take part. Specifically, for participants under the age of 16 years old the informed verbal consent was obtained from their parent or guardian.
As the purpose of this study was to timely investigate and respond to the outbreaks the approval by Scientific and Ethical Review Office is deemed unnecessary.

Descriptive Analysis
We identified 223 Dengue fever cases with no deaths. From this 116 (52%) were female.
All cases were resident of Godey town, and there no case reported from adjacent rural Woredas and majority of cases were from kebele one and kebele two of Godey town.
Majority of cases (154 = 69.1%) were in the age range 15-45 years, followed by the age   Analytical Study (A Case Control) A total of 150 people (50 cases and 100 controls) included in the case control study. Of the total included respondents, 42 (28%) were males and 108 (72%) were females (Table   1). Of the total 50 cases, 16(32%) and 34(68%) were males and females, respectively, while of the controls 26(26%) and 74(74%) were males and females, respectively. The mean ages of cases and controls were found to be 25.8 and 29.6 years respectively.
Based on the findings, the age group most affected was 15-44 years, in which 37 (74%) of the total 50 cases occurred in this age group. The proportion of cases were higher among married 34(68%), Somali ethnicity 28(56%), and housewives 20(40%), compared to their counterpart contributors (Table 1).  Regarding awareness of the respondents, only 49 (33%) of all respondents were aware/heard of Dengue Fever. Of those who heard of Dengue Fever, 55%, 74%, and 69% knew mode of transmission, symptoms, and methods of prevention of Dengue Fever respectively.
The main difference observed between cases and controls was the knowledge that how to prevent the disease, which is 61% for cases versus 74% for controls. Among study subjects who have awareness of Dengue fever 34 (72.3%) of them says water is required for mosquito to breed and there is deference within cases 11 (64.7%) and controls 23 (76.6%). Overall, awareness and knowledge of the respondents about Dengue Fever was observed to be low (Table 3).  (Table   4). Ethics approval and consent to participate Before interview respondents, observation of household level water containers and take sample from cases and/or controls, we explained the objective of the study and volunteer participation was requested. Then informed verbal consent was taken informally from all respondents and included all those agreed to take part. Specifically, for participants under the age of 16 years old the informed verbal consent was obtained from their parent or guardian.
As the purpose of this study was to timely investigate and respond to the outbreaks the approval by Scientific and Ethical Review Office is deemed unnecessary.

Consent for publication
Informed consent for publication was obtained from all participants verbally.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.