Background: Uganda is among the 51 countries where cholera outbreaks are common with epidemics occurring predominantly along the western border with Democratic Republic of Congo (DRC), Kampala city slums, Busia district which is a border town with Western Kenya, Mbale district and the Karamoja Sub-region. This report summarizes findings from the epidemiologic investigation, which aimed at identifying the mode of transmission and antibiotic susceptibility patterns of the Vibrio cholerae isolated in Kasese district, Uganda. Methods: A descriptive cross-sectional study was carried out between 2017 and 2018 to describe the epidemiology of the cholera epidemic in Kasese district, Uganda. Rectal swabs were collected from 69 suspected case-persons and cultured on Thiosulphate-Citrate-Bile-Salts Sucrose (TCBS™; SEIKEN Japan) agar and incubated at 37 °C for 18–24 h. The isolates were serotyped with polyvalent 01 antiserum and monovalent serotype Inaba and Ogawa antisera (Denka Seiken, Tokyo, Japan) to determine which serotype was responsible for the outbreak. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. A list of discharged patients was obtained from the isolation units of Bwera hospital and Kagando hospital and the individuals were followed to the community where they live. Questionnaires were administered to a total of 75 participants who were either the cases or relatives to the case. GPS points of the homes of the cases and pictures of potential source infection were also taken and cases were mapped. Results: A total of 222 cases were recorded in the Kasese District outbreak between the month of September 2017 and January 2018 with the case fatality rate (CFR) of 1.4%. Children below the age of 14 years contributed the biggest proportion of the cases (70%) and out of these, 33% were aged below 5 years. Culture isolated 69 V. cholerae 01 serotype Inaba from the total of 71 samples. Salmonella typhi was Isolated from the other two samples which were negative for V. cholerae. Antibiotic susceptibility using Kirby-Bauer disc diffusion method was done on isolates from 69 participants and showed 100% resistance to Ampicillin and over 50% were resistant to trimethoprim/Sulfamethoxazole whereas gentamicin showed 100% susceptibility. Environmental assessment revealed rampant cases of open defecation. Conclusion: Though we did not culture water to confirm contamination with Vibrio cholerae, we hypothesize that the cholera epidemic in Kasese 2017 was sparked off by consumption of contaminated water following the heavy floods that washed away latrines into water sources in Bwera, Isango and Nakiyumbu sub-counties. V. cholerae was also highly resistant to the commonly used antibiotics.
Keywords: Cholera; Antibiotic resistance; Epidemiology; Environment
Cholera has continued to be a major threat to the wellbeing of communities globally and an important indicator for poor social progress [[
Uganda is among the 51 countries where cholera outbreaks are common with epidemics occurring predominantly in Kasese, Kampala city slums, Busia district which is a border town with Western Kenya, Mbale district and the Karamoja Sub-region [[
A descriptive cross-sectional study was carried out between 2017 and 2018 to describe the epidemiology of the cholera epidemic in Kasese district, Uganda (Fig. 1). Kasese district lies along the equator and it is bordered by the districts of Kabarole to the north, Rubirizi to the south, Kamwenge to the east and the Democratic Republic of Congo to the West. The biggest population of the district live in rural areas and practicing subsistence farming. With a population of 757,269 people and 134,037 being children below 5 years the leading cause of morbidity was malaria and acute diarrhea; which is also a major presenting symptom for cholera was the second leading cause of morbidity. Cholera ranked as the third most important cause of Morbidity [[
Graph: Fig. 1 Map of Kasese district showing the study area and distribution of cases. Figure 1 is our own, drawn from the GPS coordinates taken using a hand held GPS during the study and analyzed using ARC GIS software
The study population comprised of both adults and children suspected to be suffering from cholera admitted in the isolation wards in Kagando hospital and Bwera hospital. According to the World Health Organization's standard case definition: if cholera is not known to be present in the area, a case is a patient ≥5 years with severe dehydration or death from acute watery diarrhea, while during the epidemic, every patient ≥5 years with acute watery diarrhea and/or vomiting is considered a case [[
A list of discharged patients was obtained from the isolation units of Bwera hospital and Kagando hospital and the individuals were followed to the community where they live. A total of 222 patients were recorded in the discharge book some of whom were children and these were followed to the community. We obtained telephone contacts of the care takers and worked with community health workers to locate the cases. Key questions on symptomatology and environment were asked. Major symptoms looked out for included acute diarrhea, vomiting and abdominal cramps. Environmental assessment was carried out using an environmental checklist. The key elements of the environmental checklist included; safe water, food safety, sanitation and hygiene, personal, family and school hygiene, municipal water supplies, other water supplies, solid waste disposal, disposal of excreta and treatment of waste water. We also took GPS points of the homes of the cases and pictures of potential source infection (Fig. 1).
Self-collected rectal swabs from suspected case-persons were transported to the laboratory in alkaline peptone water medium for culture and sensitivity. 'Case-persons' is used in this study to mean persons with signs and symptoms matching the standard definition for the cholera case [[
Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. The Escherichia coli reference strain ATCC 25922 was used as a control. Isolates were tested against 7 antimicrobial drugs as follows: ampicillin (10 μg), ciprofloxacin (5 μg), chloramphenicol (30 μg), gentamycin (30 μg), nalidixic acid (30 μg), Sulfamethoxazole/trimethoprim (1.25 μg + 23.75 μg) and tetracycline (30 μg) (all Oxoid, United Kingdom). Zones of inhibition were interpreted according to the 2014 Clinical and Laboratory Standards Institute (CLSI) guidelines as resistant and susceptible [[
Recall bias was the most common potential confounder as recollection of previous events might have been difficult for our respondents. However, the authors tried to minimize this by administering the questionnaires during the outbreak season to benefit from fresh memories.
Ethical approval was obtained from the Makerere University School of Biomedical Sciences Higher Degrees Research and Ethics committee (SBS-292). Written informed consent was obtained from all study participants. Consent from parents/guardians of participants below 18 years was sought and ascent was obtained from all minors who took part in this study. Participation was voluntary.
Data was checked for completeness to avoid cases of missing data and entered in Microsoft Excel. The variables of interest collected include; age sex, date of onset of symptoms, date of admission, duration of hospitalization, outcome and laboratory results, recovery and death. Cleaned data was exported to STATA v14 for analysis in time, place and person and presented in form of Tables and Figures.
A total of 222 cases were recorded in the Kasese District outbreak between the month of September 2017 and January 2018 with the case fatality rate (CFR) of 1.4%. By the time the outbreak started, the laboratory lacked necessary supplies to confirm the cases. The patients who died were two females aged 17 and 30 years and one male aged 60 years. The index case reported onset of symptoms on 23rd September was admitted on 24th September, the number of cases came to a peak at 87 in the epidemiologic week 39 and the last case was admitted in the epidemiologic week 49 (Fig. 2) before a drastic reduction in the epidemiologic week 41 due to initiation of the interventions to control the disease by the district response team. The key components of the response included; coordination, epidemiology and surveillance, laboratory identification, risk communication and social mobilization. The response strategy was adopted from the logic model for Uganda's health sector preparedness for public health threats and emergencies [[
Graph: Fig. 2 Kasese Cholera 2017 epidemic curve showing weekly notification of suspected cholera cases
Questionnaires were administered to a total of 75 participants who were either the cases or a relative to the case. In instances where the case was found dead or when the case was still recovering we opted to interview a relative who was a care taker. For the cases that were clustered in one place, only one case or relative of the case was selected randomly and considered for interviews because we were likely to get similar responses since they shared common water sources, toilets etc. There was no other scientific rational for the selection criteria.
The greatest proportion of the cases (92%) were clinically diagnosed and managed without laboratory confirmation for Cholera. All the cases in this out break presented with diarrhea as the most common symptom (
Distribution of cholera cases by person, place, time and diagnosis in Kasese district, 2017
Characteristics No. cases percentage Age group (Years) <5 25 33 5–14 28 37 15–24 5 7 25–34 6 8 ≥35 11 15 Sex Male 41 55 Female 34 45 Source of Drinking water Untreated open water source/river 37 49 Municipal tap water 12 16 Borehole water 26 35 Duration in isolation unit (days) 1–3 43 57 4–6 28 37 Above 6 4 5 Symptoms Diarrhea 75 100 Vomiting 69 92 Abdominal cramps 29 39 Type of diagnosis Clinical 69 92 Laboratory confirmation 6 8
Environmental assessment of the residences of the cases indicated inadequate water supply, poor sanitary conditions and unsafe disposal of solid waste (Fig. 3). All the three case fatalities were reported to consume untreated surface water with no methods employed to make the water safe for human consumption. Though we were not able to culture water samples to confirm the source of infection, we hypothesize that the cholera epidemic in Kasese 2017 was sparked off by consumption of contaminated water following the heavy floods that washed away latrines into water sources in Bwera, Isango and Nakiyumbu sub-counties.
Graph: Fig. 3 Common sources of drinking water in the affected area
Drinking safe water was not a concern until the time of the outbreak with 49% (37/75) of the homesteads consuming untreated surface water. Only 16% (12/75) of the homesteads reported consuming municipal tap water while the rest, 35% (26/75) consumed borehole water. None of the participants reported boiling drinking water or use of chemi-sterilants before the outbreak period. During the mapping exercise, we did not find any piped (tap) water in the entire outbreak zone and there was only one borehole sited in the whole community. The main source of water was river Kiyanzi which is untreated surface water, visibly turbid with on-going sand mining activities.
Whereas most households in the outbreak area had poor pit latrines, there were rampant cases of open defecation. Most of the pit latrines were unimproved (Fig.4) and some were washed away by heavy floods into the river and this is what sparked of the outbreak. Hand washing facilities were not observed at the pit latrine area, a good indication for poor hand hygiene. Most of the toilets and kitchens were built as temporary structures using mad, banana fiber or grass which compromises food hygiene.
Graph: Fig. 4 Example of sanitary conditions in the homesteads of the cases
Besides the poor management of the human excreta, there was generally poor management of solid waste in the entire community. River banks were the dumping sites for garbage. The cooking areas were not safe for preparation of food and when it rained, the whole area was covered by mud. Most houses of the cases were made of mud walls and most times, especially during flooding, rain water entered the houses.
The most affected people were from Bukonzo West constituency, an area that neighbors the Democratic Republic of Congo. This V. cholerae outbreak was epidemiologically linked to consumption of untreated surface water after heavy flooding leading to a number of pit latrines washing away into the water according to our environmental assessment report and case and/ care taker interviews. Water from this river is consumed without treatment and therefore exposing people to cholera and other water borne diseases.
Antibiotic susceptibility using Kirby-Bauer disc diffusion method showed 100% resistance to Ampicillin and over 50% were resistant to Trimethoprim/Sulfamethoxazole. Drugs like tetracycline which is among the recommended drugs in the clinical guidelines had close to 50% resistance whereas gentamicin showed 100% susceptibility. In addition, drugs like chloramphenicol and ciprofloxacin showed low resistance rates (11.76 and 5.9%) respectively. The general trend also showed increased susceptibility to combination therapy as opposed to mono-therapy (Fig. 5).
Graph: Fig. 5 Antibiotic Resistance Patterns for Vibrio cholerae in Kasese District
There was a high case fatality rate (CFR) of 1.4% recorded in this outbreak. The high CFR is probably because in Uganda, death of a case or two is usually a common trigger to intervention and surveillance activities. The persistently high number of cases reported in the frequent cholera outbreaks in Kasese district with some deaths at least reported during each outbreak may reflect more general problems in access to effective health care [[
Graph: Fig. 6 Accessibility to cases
Even with the poor road infrastructure, the local district team with the benefit of the previous experience of managing cholera outbreaks quickly and effective responded with awareness messages and active identification of cases. At the time of the outbreak, the laboratory lacked culture media and other necessary supplies necessary to detect and confirm the Cholera cases, at that point, anybody who presented with diarrhea was considered a case. A similar study in Kenya also pointed out similar challenges of supply chain and non-preparedness to respond to cholera outbreaks [[
Similarly, over 100 people were affected by cholera in the same district in the year 2015 [[
Kasese District is a hilly area with vast low lands that suffer frequent flooding. The outbreak of 2017 proceeded heavy flooding that washed toilets into the river in the low land. Consumption of contaminated water has been repeatedly implicated in a similar cholera outbreaks in Kasese [[
In this study, we report a high resistance to Ampicillin and trimethoprim/Sulfamethoxazole and this compares with the findings of other studies [[
Though we did not culture water to confirm contamination with Vibrio cholerae, we hypothesize that the cholera epidemic in Kasese 2017 was sparked off by consumption of contaminated water, following the heavy floods that washed away latines into water sources in Bwera, Isango and Nakiyumbu sub-counties.
V. cholerae was also highly resistant to the commonly used antibiotics.
Laboratory capacity to detect and monitor the rapidly emerging drug resistance among V. cholerae Isolates needs to be improved to effectively handle the dual challenge of treatment and prevention of Cholera. We also recommend proactive surveillance other than reactive surveillance to reduce the case fatality rate and to prevent future outbreaks. Both latrine and safe water coverage need to be improved.
Our findings can be generalized to similar settings in Uganda and other developing countries.
The International Development Research Centre-Canada (IDRC) grant to One Health Central and Eastern Africa (OHCEA) and the DELTAS Africa Initiative [grant107743/Z/15/Z] funded this study. The funding only covered data collection.
We gratefully acknowledge our respondents both the cases and non-case who provided useful information for this work. Heartfelt thanks to Bwera hospital and Kagando hospital laboratories for supporting the isolation and susceptibility testing during the time of the cholera outbreak. We also thank Stallone Kisembo for the great work he did as a research assistant.
IJS participated in conception of the research idea, study design and drafting the first manuscript; CK participated in analysis and interpretation of the data, IBR conducted critical reviews and through his International Development Research Centre IDRC-Canada Ecohealth project partially funded the project and BBA conducted critical reviews and supervised the study. All authors have read and approved the final version of the manuscript.
All data on which the conclusions of this manuscript are drawn is available on request from the corresponding author.
Ethical clearance was acquired from the School of Biomedical Sciences Higher degree's research and Ethics committee (SBS-292) of Makerere University and written informed consent was obtained from all study participants. Consent from parents/guardians of participants below 18 years was sought and written assent was provided by all minors who were able to read and write voluntarily participated in this study while those who were not able to read and write provided verbal assent. The pictures in Figs. 3, 4 and 6 were taken by the authors after obtaining written informed consent and are not under any copy right.
Not applicable.
The authors declare that they have no competing interests.
• Amp
- Ampicillin
• CFR
- case fatality rate
• Chl
- Chloramphenicol
• Cip
- Ciprofloxacin
• CLSI
- Clinical and Laboratory Standards Institute
• Gen
- Gentamycin
• GPS
- Global Positioning System
• GWFS
- Gravitational Water Flow Schemes
• SDG
- Sustainable Development Goals
• IDRC
- International Development Research Centre Canada
• Nal
- Nalidixic acid
• OHCEA
- One Health Central and East Africa
• SXT
- Trimethoprim/Sulfamethoxazole
• Tet
- Tetracycline
• WHO
- World Health Organization
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By Jacob Stanley Iramiot; Innocent B. Rwego; Catherine Kansiime and Benon B. Asiimwe
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