Study identification and selection

A total of 49 records were identified that investigated cholera and Zambia from January 2013 to June 2024 from PubMed, including one previous article exploring the epidemiology of cholera in Zambia from 2000 to 2010 [12]. An additional 23 unique records from a total of 76 were identified from Embase, and 13 more were found on Google Scholar, of which three were unique. Four additional titles were identified from alternative sources, such as preprints, in local journals or otherwise not listed on PubMed, and were included for analysis [13–16]. Full texts were available for all the studies and reported according to the PRISMA-Scoping Review (Scr) guidelines to ensure a systematic and transparent approach to study selection and data extraction, thereby enhancing the reliability, reproducibility and comprehensiveness of the review process [17]. After excluding 22 articles based on the set criteria, the total number of articles included was 53 (Fig 1). Fig 2 shows how the analysed publications were evaluated considering the different pillars they represent. The completed PRISMA-Scr checklist is included in the S1 Table.

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Fig 1. Study flow diagram showing the selection processes in line with the PRISMA-Scoping Review (Scr) Guidelines:

Fig 1 shows the flow diagram illustrating the scoping review process according to PRISMA guidelines, highlighting selection and inclusion criteria, search strategy, screening, eligibility assessment, and final included studies.

https://doi.org/10.1371/journal.pntd.0012422.g001

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Fig 2. Frequency of Cholera Publications in Zambia by theme from 2013–2024

Fig 2 illustrates the distribution of cholera-related publications in Zambia from 2013 to 2024 categorised by thematic focus. Themes include epidemiology, public health interventions, water, sanitation, and hygiene (WASH), healthcare infrastructure, and community engagement. The data provides insights into the evolving research priorities and strategies aimed at combating cholera within the Zambian context over the past decade.

https://doi.org/10.1371/journal.pntd.0012422.g002

Cholera epidemiology and burden

Table 1 shows studies exploring the epidemiology of cholera in Zambia. Consistently, the definition of an outbreak, based on the national Integrated Disease Surveillance and Response (IDSR) guidelines, was the confirmation by stool culture of V. cholerae in at least one cholera suspect patient with three episodes of acute watery diarrhoea in a 24-hour period in each district [18]. Once an outbreak has been declared, the subsequent cholera suspected patients are included in the line list based on the clinical case definition, with or without culture confirmation [18]. Only three studies depict multiyear surveillance data and are represented in Table 1 [6,12,19]. From 2000 to 2010, 39,285 cases in total over the ten years, with 80% of these cases occurring in Lusaka, the capital [12]. Overlapping slightly in years, Mwaba et al described the spatial distribution of cholera cases from 2008-2017 and again found that cases were primarily from Lusaka [19]. They identified 16 other cholera hotspots and noted that outside of Lusaka, cases were mostly identified in districts bordering Tanzania, Mozambique, Malawi or the DRC – suggesting a linkage to the movement of people to and from neighbouring countries [19]. However, at the peak of the 2024 outbreak, 70 of the 116 districts in the country reported confirmed cholera cases with evidence of local transmission [20]. In describing the 2024 outbreak response in Lusaka – the most affected province, Kateule and colleagues depict the epidemiological trends over time since the first outbreak in 1977 and demonstrate an increasing magnitude of cases but a reduction in the case fatality rate from close to 10% in 1978 to about 3% in 2024 [6]. Before 2013, the largest outbreaks had encompassed 13500 cases in 1991 and 1999. There were no large-scale outbreaks recorded after the launch of the MCEP in 2018 until the 2024 outbreak, which was the largest [6]. A limit may be that cholera cases were only reported in the IDSR system when an outbreak is confirmed by culture. Consequently, as documented by Wiens and colleagues, in endemic areas where suspected cases are not routinely subjected to laboratory confirmation, the true incidence and overall disease burden may be significantly underestimated, particularly outside of outbreak season [21]. Additional studies attempted to explore risk factors of the outbreaks, the regions and age groups of affected individuals, but were limited in size and scope [7,13,15,22–24]. Fig 2 shows the bias towards descriptive analyses of each localised outbreak.

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Table 1. Cholera Epidemiology and Burden in Zambia (2013–2024).

https://doi.org/10.1371/journal.pntd.0012422.t001

Risk factors and determinants of transmission

Male sex, close contact with a cholera case and the use of borehole water were found to be risk factors for cholera infection [14,23–28]. Drinking water sources were found to have inadequately low free-residual chlorine (FRC) in up to 71% of households surveyed [14,25,28]. Thirty-one per cent of those households with inadequate FRC had evidence of faecal contamination. Low latrine coverage, poor drainage systems, and sharing latrines [14,24] were also documented vulnerability factors that allowed for the perennial occurrence of cholera in some localities, particularly unplanned settlements such as the fishing villages in many of the areas bordering lakes and in high-density, peri-urban communities of Lusaka and the Copperbelt [19,22,26–28]. Whilst poor hygiene practices (mostly superimposed on people due to lack of facilities) were a notable risk factor, consumption of food products, particularly fresh fish, was not associated with an increased risk [16].

The availability and quality of drinking water in the peri-urban areas of Lusaka were assessed [28]. It was found that in areas underserved by the municipal utility companies, private borehole companies known as ‘Water Trusts’ would operate small shops known as ‘kiosks’ where community members could go and draw small quantities of water in buckets at a minimal cost to cover the fees only, and not for profit [28]. These trusts treated and provided water to the communities in these water-stressed unplanned settlements as an adjunct to the provincial utility company, and yet they were found to serve less than 60% of the communities in need of their services [12,24]. Despite this limitation, they were noted to present a safer alternative than privately owned consumer boreholes and shallow wells in terms of faecal contamination with Escherichia coli and nitrite content of the water [28]. Those unable to afford the kiosk water tended to use unsafe surface water sources such as shallow wells in their locality [24,25]. These presented the highest risk of contamination, particularly due to topographical features such as the high-water table in Lusaka Province, leading to a high risk of contamination of these shallow wells from nearby pit latrines [27,28].

The smallest surveillance unit of population reported was the ward level. It was found that the greatest risk for cholera was in the wards with the densest populations, unimproved sanitation and evidence of E. coli contamination of piped sources [14]. Elsewhere, as was seen in Kabwe, through an environmental sampling of groundwater using polymerase chain reactions (PCR) tracers, there was evidence of groundwater contamination with environmental vibrio [27]. The authors postulated that private boreholes are vulnerable to contamination, possibly due to incompetent casing, which may provide an artificial pathway for the Vibrio from contaminated ground sources and pose an even greater risk. Supporting this was the rapid decrease in cases seen during outbreaks, when there was an increased provision in WASH services, such as hyper-chlorination of the water utility lines, provision of safe water through emergency tanks in the hotspot areas [29] and with the use of reactive OCV campaigns [30].

Inter-district and inter-country spread of outbreaks

Risk factors for continued outbreaks between the peak years included increased poverty and inadequacies of social services due to rural-urban migration [12,24,31]. Similarly, movement between neighbouring districts [15,29] and neighbouring countries [32–35] was identified as a factor associated with epidemic cholera in Zambia. Chirabombo and colleagues documented how naïve districts neighbouring traditional hotspots such as Lusaka can present with outbreaks of their own, with evidence of local transmission [15]. The question of environmental persistence versus reintroduction into the district from neighbouring countries such as the DRC and Tanzania, which equally have continuous outbreaks, has been documented [33–37]. This is reaffirmed by laboratory studies and descriptive analyses of genomic sequencing isolates that showed a wide genetic diversity [33–34] and close linkage with isolates from other parts of the Great Lakes region [35–37]. This underscores the need for both a decentralised approach at the district and ward levels, but also shows a need for enhanced cross-border surveillance and possible cross-border joint responses [25–38].

Clinical characteristics and host predisposition

Globally, there is a dearth of information on the clinical characteristics of patients affected by outbreaks beyond general case counts and case fatality rates [39]. Little is known about the proportion of pregnant women, elderly or paediatric patients affected by cholera, nor the number of patients presenting with co-morbid conditions or other complications of care. What was seen is that having received limited education and being older than 55 years constituted one risk factor for increased mortality [23]. There was a slightly higher proportion of patients documented to have died before arrival at the treatment facilities (i.e., at home or community deaths) versus in the facility in the 2024 outbreak in Lusaka (60% community deaths) [6], proportionately more than the community deaths reported in the 2018 outbreak (45%) [23]. Intravenous fluids were not available beyond Cholera Treatment Centres (CTC), and there was no documented use of Community Oral Rehydration Points before the 2023/2024 outbreak [6]. Adequate Oral Rehydration Solutions (ORS) was protective [23], yet it was clear that there were disparities in the availability of ORS, particularly in rural communities [40]. Rising antimicrobial resistance was found to have direct implications on patient management in cholera treatment settings [1]. Specifically, it can compromise the effectiveness of antibiotics used for managing severe cases, potentially leading to prolonged illness, increased risk of complications and greater strain on clinical resources [38]. Prior antibiotic use was not found to be protective, although noted that patients often took metronidazole, which is not one of the recommended agents [23]. In younger patients, cholera was noted to be an important cause of morbidity and mortality in the under-five age group, with increasing antimicrobial resistance over the years [32,41,42]. For example, earlier studies showed low-level resistance to tetracyclines but as high as 95% in subsequent outbreaks due to its use as drug of choice for first-line treatment of severe patients [38,42]. Case management was reported to have improved, with reductions in the case fatality rate (CFR) decreasing from 6.7% in 2000 to 1.7% in 2010 [12]. However, as of the 2018 outbreak, the case fatality rate hovered around 2.5% [25]. The case fatality rate of the 2023/2024 outbreak was 1.3%, with increased documentation of community deaths [3]. For inpatient fatalities, there were higher odds of dying for those with pre-existing comorbid conditions [7].

Vaccine availability and effectiveness

Vaccines are known to be a useful tool for community-level interventions for controlling waterborne diseases such as cholera, in places where access to water, sanitation and hygiene remains limited [43,44]. Recent studies have used the new Euvichol Plus, which is the Eubiologics bivalent vaccine of El Tor and Ogawa, presented in glass containers as opposed to plastic vials to improve cold chain in humanitarian crises [45]. They have shown a higher vaccine efficacy in the two-dose strategy than the single dose (at 74% and 81%, respectively [46,47]; and that reported OCV administrative coverage is often much higher than the actual coverage which was found to be 66% of people getting both doses, which may further lower efficacy rates [48]. Questions persist about the very high dropout rate of 18% between the two doses [48]. Similarly, it remains to be seen the effect of previous preventative campaigns, as a lead-up to future multi-year preventative vaccination campaigns, or if delaying the second dose post outbreak can be used to time subsequent campaigns before the rainy season, which is a high-risk period for cholera transmission [49].

Pugliese-Garcia and colleagues attempted to explore the factors influencing vaccine acceptance and hesitancy in the hotspot districts of Lusaka. They found that traditional remedies, religious beliefs and alcohol use persist as impediments [50], as does a background mistrust towards Western medicine [51]. There was an overarching sense of helplessness or ‘fate’ as the participants were aware they could not change their living conditions and did not realise their ability to use safer water practices to protect themselves [51].

Investigation of the immunogenicity of the vaccines in a controlled population in one of the high-risk fishing villages found no significant difference in vibriocidal antibodies at two weeks or six months and provided evidence for the delayed dosing schedule [52] but also waning immunity beyond 12 months [53]. The group found no influence of ABO blood groupings on vaccine response [54]. HIV-positivity was found to reduce immunogenicity in these individuals regardless of the CD4 count, whilst serum vitamin A levels had no effect positive or negative [55]. Elsewhere, there was a suggestion of vitamin A supplementation as a possible adjuvant to improve T-cell expression following vaccination, particularly in children [56], which may offer a gateway into host-specific factors for improved immunity and transmission dynamics. There was no work yet published on the role of the gut microbiome in cholera vaccine responsiveness or protection in the face of household exposure. However, a review article describing environmental enteric dysfunction (EDD), a subclinical disorder of intestinal function in settings of poverty that affects vaccine uptake, concluded that the immunogenicity and efficacy of oral vaccines in developing countries was less in developing countries than developed countries based on pathology findings [57] The evidence surrounding EDD in Zambian cohorts is limited but also points towards a potential role of Immunoglobulin A supplementation to improve uptake of vaccines through improved nutritional status [58]. Most recently, a comparison of vibriocidal antibodies in naturally infected vs vaccinated individuals was found to be comparable, with peak immunity seen around day 19 post-infection and waning after day 30–39 [42] . The group explored waning immunity beyond 90 days in revaccinated individuals compared to naïve and found that repeated use of a single dose strategy was unprotective and probably contributing to more explosive future outbreaks following such campaigns [59]. suggested the need for booster vaccinations, particularly in high-risk areas, as a possible public health protective strategy. Additionally, ongoing work is being done to explore Zambian Vibrio cholerae strains for human challenge studies, to explore future vaccine candidate efficacy [60].

The use of a single-dose campaign of Sanchol was found to be cost-effective, amounting to just under $ 1 million to vaccinate 500,000 people [30]. A further evaluation of the cost of cholera illness and the cost-effectiveness of the single-dose campaign in Lusaka was close to $1000 per disability-adjusted-life year (DALY) averted, especially in those above the age of 15 years [61]. The social implications for affected communities have not been deeply studied, nor the cost-benefit analysis of community-based interventions and health education initiatives in the hotspot districts. With the increasing size of the outbreaks, it remains to be seen the cost-effectiveness of reactive campaigns, and also the macro-economic effects of the overall cholera responses.

Climate variability

The role of climate variability and extreme weather events cannot be ignored, with a strong association between the onset of rainfall and epidemic outbreaks [25]. Cholera outbreaks in Zambia, like many other African countries, are seasonal [25,36], differing from the Ganges Delta, where it occurs perennially [36]. The outbreaks start with the onset of the rainy season in 71% of cases and have been associated with 50% of all recorded drought years. Outbreaks are expected to increase in frequency by 300% in the near future with recurrent El Niño events [62]. El Nino events are associated with increased rainfall and flooding, which would lead to contamination of water sources, whilst the warmer temperatures will allow the growth and persistence of Vibrio cholerae in the environment. These conditions together create a conducive setting for the spread of cholera in vulnerable communities [62]. Following seasonal rains, the larger outbreaks are often heralded by flooding, which is a specific sequel of torrential rains possibly enhanced by climate change. Flooding has been associated with damage to WASH infrastructure, and the decay of flooding countermeasures, such as clogged-up drainage canals and sealing of ground passages for water, particularly when big cities such as Lusaka are afflicted [25,62], further compounding the problem. Reduced rainfall (i.e., drought periods) may also increase cholera outbreaks as seen in the U-shaped occurrence of diarrhoeagenic bacteria such as V. cholerae with rainfall and pathogen proliferation, meaning an increase in both ends of the spectrum – very dry and then very flooded – can contribute to increased cholera incidence [63]. Groundwater drilling during the drought years, if not carefully planned, will worsen the already water-stressed situation in certain parts of the country [62]. The anticipated periods of droughts in the near future are expected to exacerbate rural-urban migration into the peri-urban slums, further compounding the water-stressed situations and the likelihood of larger cholera outbreaks [62].

Mathematical modelling was used to predict the expected time to extinction of cholera in Lusaka, and based on previous estimates of a second wave in each outbreak found that heavy rains were associated with an increased environment-to-human transmission [31]. They warned that environmental vibrio could persist for eight months to six years in the environment, especially the shallow wells and areas with poor drainage, hence future outbreaks would be longer and more severe. They also recommended enforcement of the multisectoral cholera elimination plan, which sought the combination of WASH interventions with periodic oral cholera vaccinations [31]. A study exploring microbiological screening of plankton and meteorological monitoring of Uvira in DRC and Mpulungu in Zambia between 2000–2014 to better understand environmental factors that trigger cholera outbreaks in the region, concluded that whilst climate dynamics play a part in cholera transmission, most outbreaks in Africa region are due to genetically diverse strains that spread into non endemic areas and cause explosive outbreak [64] They suggested the need for localised prevention efforts to protect communities from introduction of new outbreaks, a nod to decentralisation of cholera control and prevention efforts. Chota and colleagues attempted to draw lessons from the cholera outbreak of 2017–2018 when responding to the COVID-19 pandemic in 2020–21. They engaged health care professionals and community leaders in focus group discussions around the successes and pitfalls of multisectoral response strategies. They concluded that challenges in the partnership collaboration included inadequate resources, poor communication, poor coordination, lack of clear shared vision, reactive response, poor involvement of the community, hegemonic powers and mistrust of each other [65]: “Despite the attempts at co-ordination, ministries have a tendency of operating in isolation, this has resulted in lack of a clear shared vision. This also contributes to duplications of tasks in trying to prevent an outbreak of cholera” [65]. It has been proposed that the key to success in cholera elimination would be greater community participation in developmental activities and empowering the communities to take ownership of their health by addressing underlying economic challenges [66]. All the reviewed articles are listed in Table 2 with their key findings and possible mitigating factors that can contribute to cholera control and elimination in Zambia.

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Table 2. Comprehensive Review of Cholera Research in Zambia (2013-2024): Aims, study design, population, identified risk factors and mitigative measures.

https://doi.org/10.1371/journal.pntd.0012422.t002