Factors associated with cholera outbreaks, Nairobi County, July 2017: a case control study

Background Cholera affects 1.3-4 million people globally and causes 21000-143,000 deaths annually. Nairobi County in Kenya reported cholera cases since April 2017. We investigated to identify associated factors and institute control measures. Methods We reviewed the line-list of patients admitted at the Kenyatta National referral Hospital, Nairobi and performed descriptive epidemiology. We carried out a frequency-matched case control study, using facility-based cases and community controls. We defined a case as acute onset of watery diarrhoea of at least >3 stools/24hours with or without vomiting in person of any age, admitted in Kenyatta National Hospital as from July 1st, 2017. We calculated odds ratios and their respective 95% confidence intervals. We also took water samples at water reservoirs, distribution and consumer points, and made observation on hygiene and sanitation conditions in the community. Results We reviewed 71 line-listed cases; median age 30 years (range 2-86 years); 45 (63%) were male. First case was admitted on 14th April 2017. Culture was performed on 44 cases, 30 (68%) was positive for Vibrio cholerae, biotype El-Tor, serotype Ogawa. There were 2 deaths (case fatality ratio 2.8%). Age-group ≥25 years was most affected. Drinking unchlorinated water (aOR 14.57, 95% CI 4.44-47.83), eating in public places (aOR 9.45, 95% CI 3.07-29.12) sourcing water from non-Nairobi city water company source (aOR 4.92, 95% CI 1.56-15.52) and having drank untreated water in the previous week before the outbreak (aOR 3.21, 95% CI 1.12-9.24) were independently associated with being a case in the outbreak. Out of 28 water samples, 4 (14%) had >180 coliforms/100mls; all were at consumer points. Conclusion Poor water quality and sanitation were responsible for this outbreak. We recommended adequate, clean water supply to unplanned settlements in Nairobi County, as well education of residents on water treatment at the household level. Author summary Cholera, a disease causing outbreaks in areas with low standards of hygiene and sanitation has afflicted humans for millennia. It is caused by a bacterium, Vibrio Cholerae, transmitted mainly through water contaminated by faecal matter. The resultant disease is acute watery diarrhoea, which causes death rapidly due to dehydration and shock. Virtually brought under control in the developed world due to improvements in hygiene, the disease still ravages many communities in low and middle income countries, as well as regions affected by conflict or natural disasters. In outbreak situations, rapid response in water treatment, sanitation improvement and setting up of cholera treatment centres for rehydration therapy reduces impact and saves lives. Long-term control can only be achieved through sustainable improvements in sanitation and standards of living. Case control studies in outbreak situations provide quick, actionable information to public health specialists during outbreak response. This study provides a cholera outbreak investigation in an urban informal settlement setting; the approach reported here can guide in outbreak investigations and response in similar settings globally.


54
Cholera is an enteric infection caused by toxigenic Vibrio cholerae serogroup O1 and 55 O139 [1]. Cholera is endemic in more than 50 countries globally and causes large epidemics 56 in countries or regions facing complex emergencies including conflict, natural disasters like 57 flooding or drought or massive displacement of persons [2]. It is estimated that every year, 1.3 58 billion people are at risk, 1.3 to 4 million get infected and 21000 to 143000 deaths occur 59 globally [3]. Up to 90% of infected people continue shedding the bacterium up to 14 days 60 without or with mild symptoms making cholera outbreaks difficult to control [4]. 61 Most cholera outbreaks occur in areas with inadequate supply of potable water and poor 62 sanitation facilities, especially during rainy seasons [5]. Other factors identified as risk factors 63 in previous epidemiological studies done in Kenya include lack of knowledge about cholera, 64 proximity to a large water body, living in a refugee camp and eating food outside the home [6][7][8][9][10]. A cross-district analysis of cholera occurrence also identified open defaecation as a risk 66 factor [11]. 67 Increase in acute watery diarrhoea cases, confirmed to be cholera by culture, was 68 reported in Nairobi County from April 2017 through the Integrated Disease Surveillance and 69 Reporting (IDSR) system. Sporadic cases were reported in May and early June but an upsurge 70 was observed in late June and July 2017. The epicentre of the outbreak was unplanned 71 settlements from the Eastern suburbs of the city; however, cases were also reported in high end 72 hotels and restaurants. Most of the cases were admitted at Kenyatta National Referral Hospital, 73 since an ongoing nurses' industrial action had paralyzed tier one, two and three facilities [12].    Case control 96 We then carried out a frequency matched case control study using facility cases from 97 KNH and community controls from the most affected sub-counties. Cases were matched to 98 controls using age groups (2-4, 5-14, 15-24, >24) years on a ratio of one case to two controls.

99
Two years is the cut-off for cholera case definition in areas with active outbreaks as per the 100 IDSR guidelines [14].
was defined as acute onset of watery diarrhoea of at least >3 stools/24hours with or without 105 vomiting in a person ≥2 years, admitted in Kenyatta National Hospital as from July 1 st , 2017. A 106 confirmed case was culture positive.

107
Controls were defined as absence of diarrhoea in the preceding 30 days in any randomly 108 selected person of the same age group as a particular case and came from the same Nairobi Sub-109 counties as cases. We administered verbal screening for symptom and admission questions to 110 any control prior to enrolment into the study.  We made the following assumptions while calculating the sample size for the study:

116
Power 80%, 21.6% prevalence of exposure for hand washing before meals among controls [15] 117 to detect a least an exposure odds ratio of 3.0, desired two-sided confidence intervals of 95% 118 and a case: control ratio of 1:2. A minimum sample size of 132 (44 cases and 88 controls) was 119 calculated using the Fleiss method [16].

130
For each case we selected two population controls, distributed into five sub-counties.

131
The sub-counties were selected on the basis of the number of cases reported, with the three with 132 the most number of cases and two with the least number of cases. We visited the selected sub-133 counties, and used the administrative offices of the Sub-counties at as our starting point.  Environmental testing 144 We collected water samples for testing from the Nairobi city water company pipeline 145 system and households, using sterile containers. For the water company system, the testing was 146 done at the water treatment sites/ reservoirs, during piping and selected consumer points.

147
Samples were also collected from conveniently selected control households, from the affected 148 sub-counties, as well as from some public establishments like schools in the affected sub-   independently associated with being a case in the outbreak (Table 3).  Water and sanitation is a major factor in cholera transmission in most outbreaks globally [20].

221
The current outbreak affected relatively younger individuals and males more than females.

222
Males are likely to consume different types of meals regarded as 'high risk' outside the home 223 during occupational ventures, hence predisposing them to higher risk of contracting food borne 224 diseases [21]. The case fatality of 3% for the patients admitted at the referral facility (KNH) is 225 unexpectedly high, with CFR expected to be less than 1% if proper treatment is instituted 226 promptly [22]. This can be explained by several contextual realities affecting both the Nairobi  [25]. 248 We found several gaps in response to the outbreak. First, the initial cases were not fully 249 investigated till the peaks in June and July occurred; this was a lost opportunity since promptly 250 investigating and instituting control measures reduces extent, scope and possibility of 251 propagation of outbreaks [26]. No cholera treatment centres (CTCs) were set up in the affected 252 Sub-counties; patients had to be ferried to the referral facility likely aiding disease transmission.

253
The best practice would have been to treat cholera at the sites of the outbreak. The nurses' strike 254 reduced the effectiveness of the response, and likely contributed to the protracted course of the 255 outbreak. Provision of water to most informal settlements in Nairobi is inadequate; water 256 vendors and illegal connections fill in the gap but expose residents to unpotable water for 257 human consumption.
Cholera control and prevention can be achieved in various ways. Of these, water, 259 sanitation and hygiene improvement are the most effective, with water treatment preventing up 260 to 90% of water borne diseases [27]. Cholera vaccination has only been effective in outbreak 261 situations when offered together with provision of safe water and improving environmental 262 hygiene [28]. Primary prevention in form of sanitizing the environment and provision of safe 263 water are also effective against cholera and other water and food borne diseases.

264
Our investigation had limitations. The sampling of the water was not random, as advised 265 by the WHO [29] therefore may not be representative to the water in use in the settlements from 266 which the cases and controls came from. We also did not manage to tests the water samples for