**4. Epidemiology of cholera**

Cholera is said to be a 'forgotten disease' which mainly affects 'forgotten people' of the world. It comes into limelight when an extensive cholera outbreak occurs, although some neglected populations continually suffer from the recurrent episodes of cholera [10]. Cholera is the main cause of epidemic diarrhea in the developing countries. For the last four decades, there is an ongoing global pandemic in Asia, Africa, and Latin America [9].

#### **4.1. Person distribution**

In endemic regions, the majority of cases occur among children less than 5 years of age and in reproductive-age women [3]. However, various studies conducted in different parts of the world have reported varying age distribution for cholera patients. A study conducted in Pakistan during the period 2000–2001 found the mean age of patients infected with *V. cholerae* O139 as 40 years as compared to those infected with *V. cholerae* O1 strains where the mean age was 23 years [18]. Tamang et al (2005) conducted a study in a teaching hospital in Nepal between May 1, 2004 and October 31, 2004. They investigated 148 stool samples from patients with acute diarrhea and found out that 46 cases (31%) were positive for *V. cholerae* serogroup O1, biotype El Tor, serotype Ogawa. In their study, younger age group of less than 30 years was mostly affected. Males and females were equally affected [19]. During a cholera outbreak in southwestern Nigeria from November 20, 2005 to January 1, 2006, a total of 115 cases and 11 deaths were reported. Overall case fatality rate was 9.6% with a case fatality rate in males of 11.9% as compared to 7.1% in females. During this outbreak, the age group of 15 years and above was the most affected comprising of 68.3% cases and 90.9% deaths [20]. A study conducted in southeast of Iran examined 3,178 patients with watery diarrhea, referred to a teaching hospital over a period of 4 years. A total of 362 (11.4%) samples contained *V. cholerae* strains; 336 (92.8%) were *V. cholerae* O1 Ogawa strain. A majority of the cases (270) were referred from rural areas. In this study, the patients ranged in age from 1 to 65 years. Approx‐ imately one-fourth (26%) were children under the age of 5 years [21]. In Mexico, the distribution of cholera cases by gender was reported to be similar. Individuals aged 25–44 years had the greatest proportion of cases while individuals aged over 65 years had the highest rates of infection. The authors state that this distribution differs from the distribution of cholera cases in endemic regions. The authors interpret this difference because of the occupational exposure and eating habits of the older individuals [3]. Most of the studies have mentioned a pattern of disparities between richer and poorer people with a higher incidence of cholera in lower socioeconomic groups [22]. Malnourished children and people with low immunity, such as HIV cases, have a higher mortality risk from cholera infection as compared to the normal population [8].

#### **4.2. Place distribution**

The frequency, severity, and duration of cholera infections vary and keep on changing in different parts of the world [13]. Cholera is endemic in Africa, south and southeast Asia [23]. In contrast, cholera is almost eradicated from most of the developed countries [5]. Incidence is as low as 0–5 cases per year in the United States [9].

In some countries such as Bangladesh and India, cholera infections occur every year [13]. Cholera reached West Africa and Ghana during the seventh pandemic [24]. In East Africa, cholera epidemic was first reported in 1836 but no cases were reported across Africa between 1870 and 1970. Cholera returned to Africa in 1970 as a result of seventh cholera pandemic. In 1974, cholera cases were reported for the first time in Tanzania, and then reported each year since 1977 [12]. In 1970, the first cholera case was reported in Ghana, after which cholera has been endemic in Ghana. Between 1999 and 2005, Africa accounted for about 90% of the cholera cases and 96% of the cholera-related deaths worldwide [24]. In contrast, other regions such as parts of South America have historically had only sporadic epidemics [13].

During 2013, a total of 56,329 cases were reported from Africa, which shows a decrease of 52% as compared to 2012 when 117,570 cases were reported. Africa accounted for 43.6% of the total cases in 2013 as compared to 93–98% of the total cases during the period 2001–2009. In contrast, 11,576 cases were reported from Asia, representing an increase of 57% as compared to 2012 when 7367 cases were reported from Asia [11].

In 2013, a total of 26 countries reported deaths due to cholera; 17 of these countries belonged to Africa. The case fatality rate was <1% in 4 countries, 1–5% in 17 countries, and >5% in 5 countries. In 2013, a majority (65%) of the deaths were reported from the African continent. A total of 1366 deaths were reported with a case fatality rate of 2.43% [11].

Various studies have reported differences in incidence of cholera in rural and urban areas. Sepúlveda et al (2006) reported high incidence of cholera in rural and suburban areas due to lack of basic sanitation infrastructure [3]. Other studies have reported cholera predominance in the urban areas, due to overcrowding and unsanitary living conditions. In urban commun‐ ities in Ghana, intermittent water supply along with indiscriminate sanitation practices increases the risk of cholera. Urban slum areas are also at high risk of cholera infection as a lack of safe drinking water, poor sanitation, high population density, and crowding are common features in these areas; all of which are the risk factors for cholera [12, 24].

Bompangue et al. (2008) explored geographic proximity of the cholera cases [25]. The number of cases was found to be statistically significantly higher in the presence of a lake, a main road, or a harbor. Proximity to surface water, high population density, and low educational status were also identified as the predictors of cholera in an endemic area of Bangladesh. Poverty, urbanization, and proximity to coastal areas were important geographic predictors of cholera in Mexico. Proximity and density of refuse dumps also play a significant role in cholera transmission [6]. Epidemiological studies have demonstrated an inverse relationship between diarrhea and access to tube well water, and positive associations with canal water compared with river or pond water [13].

#### **4.3. Time distribution**

*Vibrio cholerae* are found in seas, rivers, and ponds of coastal areas of the tropical countries. It is postulated that environmental factors such as climate variability, temperature, and salinity play an important role in cholera transmission. Cholera is also associated with rainfall patterns. Recurrence of epidemic cholera has also been related to climatic factors [6, 13, 14].

Even in endemic areas, the magnitude of cholera incidence varies from year to year. In rural Bangladesh, there is a premonsoon epidemic almost every year. Cholera is rare during the winter as the temperature is low and there is little rainfall. Gradually, the temperature gets hotter till the monsoon arrives. The incidence of cholera is low in the actual monsoon period as compared to premonsoon period. This lower incidence in the monsoon period is explained by the dilution effect reducing the amount of bacteria in the aquatic environment. However, postmonsoon epidemics are much larger than the premonsoon epidemics [22].

A regular seasonal cycle for cholera outbreaks related to the different strains: classical, El Tor and O139, is described for Bangladesh. El Tor is reported to be most incident from September to November. Some studies have reported two annual El Tor cholera peaks; smaller peak in April followed by a larger outbreak from September to December. *Vibrio cholerae* O139 has a similar seasonal pattern [13].

In Pakistan, the incidence of cholera increases from November to January and from April to May, while in India, cholera cases peak in April, May, and June. In South America, cholera peaks in summer months, January to February and in the rainy season. In eastern African countries such as Kenya, Somalia, Uganda, and Tanzania, cholera outbreaks occur following summer rainfall. From 1979 to 1983, two cholera peaks were reported from Tanzania; from October to December; and from March to May. Both of these peaks coincide with increased rainfall. In southern Tanzania, the highest incidence of cholera is reported in June and July, while during 2002 the northern parts of southern Africa reported maximum cholera cases from the last week of January to mid-March. In Mozambique, peak of cholera cases occurs from December to May [13].

Cholera outbreaks occur more commonly closer to the equator than at higher latitudes and do not follow a clear seasonal pattern near the equator. Although annual peaks are evident, it is difficult to determine distinct seasonal patterns in cholera outbreaks across regions. However, grouping countries by latitude range, rather than region, makes these seasonal peaks more obvious. Countries near the equator have higher and more constant temperatures, and have a greater incidence of cholera outbreaks [13].

The seasonality of cholera outbreaks may also be explained by secondary transmission. Several studies find that the severity of secondary transmission is associated with local environmental variables, predominantly water sources for household consumption. People who use conta‐ minated surface water for drinking, cooking, and bathing are more likely to contract cholera than those who do not [13].

#### **4.4. Social and behavioral epidemiology of cholera**

Cholera transmission is closely associated with the social and behavioral aspects of individuals as well as communities. There are many demographic factors which predispose an individual or community to cholera infection. An increase in population density can result in overbur‐ dening existing water supply and sanitation systems. Thus, population density, urbanization, and overcrowding influence intensity of the cholera outbreak [24].

With increasing world population, urbanization is expected to increase. Most of this urban growth will occur in the developing countries. Because of economic issues, most of urban growth in the developing countries is the expansion of squatter settlements. These settlements comprise of households that lack access to safe drinking water and sanitation facilities. These conditions are of particular concern in the spread of infectious diseases which have been associated with conditions prevalent in urban squatter settlements [12].

There are obvious socioeconomic disparities in the occurrence of cholera. Even in the devel‐ oping countries, the incidence of cholera is higher in socially deprived communities as compared to economically privileged class [13]. Among vulnerable groups living in areas at high risk for cholera, the case fatality rate is high. The secondary cases of cholera occur through fecal–oral transmission, and are related to poor hygiene, poor water, and sanitation environ‐ ment [6, 22]. The water and sanitation environment as well as proper hygiene and educational level are associated with socioeconomic status of individuals as well as communities. Indi‐ viduals with low socioeconomic status lack financial resources to install an appropriate sanitary system or obtain cleaner water sources. It is reported that cholera is more common in poorer households without safe water and proper sanitation system as compared to those having appropriate water and sanitation systems [22].

Surface water is contaminated with human excreta and sewage at place where rivers pass through overcrowded cities. In some African countries such as Ghana with multiethnic population, the traditional laws for protection of water bodies are no longer obeyed. Thus, waste dumps are a common sight at the banks of surface water bodies in urban communities. These urban inhabitants have to use such polluted water at the times of water shortage. The urban slums and squatter settlers have lack of accessibility and affordability to safe drinking water and sanitation. Sometimes, public utility providers are not bound legally to serve the urban slums because of technical and service regulations. In addition, many urban slums are located at low lying areas leading to higher vulnerability to floods, making them more prone to cholera infection. Once the disease is introduced in a population, these demographic and social variables further aggravate the situation [6, 24].

Rapid urbanization can lead to overcrowding, unprotected water sources, and improper disposal of solid waste, liquid waste, and human feces. All these conditions make the envi‐ ronment conducive for cholera transmission. In urban communities, cholera outbreaks have been attributed to poor waste management and sanitation systems [24].

The behavioral aspects of community regarding cholera are important because if cholera is recognized as a serious and life threatening condition by the community, it will be more receptive to community health education program. Human behavior is also important in the acceptance of vaccine program [2].

A humanitarian crisis in a country or region can result in cholera outbreaks. The risk of cholera epidemics also increases after large-scale natural disasters. Some areas of Democratic Republic of Congo have been the site of large scale disasters including invasion and occupation by foreign forces, civil war, population displacements, and earthquakes. These areas have also shown high incidence of cholera [26].

Outbreaks of cholera have negative impact on social and economic conditions of the country as it leads to widespread fear and travel sanctions. Moreover, within the cholera-affected countries, resources are diverted to the care of cholera patients. Certain countries such as Peru and Mexico suffered economically as a result of cholera outbreaks, because of a decrease in tourism and decreased exports by other countries [3].
