Towards a Cholera-Free Nigeria: Epidemiological Profile, Diagnostic Approaches, Vaccine Implementation, Challenges and Strategic Framework for Enhanced Coverage

• Improving water supply and sanitation infrastructure is essential for cholera prevention. Community-led initiatives that promote sustainable practices can effectively reduce transmission risks, highlighting the importance of engaging local populations in public health efforts.
• Expanding access to cholera vaccines in high-risk areas, combined with robust public awareness campaigns, is vital for increasing vaccination coverage. Fostering community engagement and addressing vaccine hesitancy are key to enhancing the overall effectiveness of cholera prevention strategies.
• Effective cholera control requires collaboration among government agencies, non-governmental organizations, and international partners. A coordinated response that integrates health, water, sanitation, and community engagement efforts can leverage resources and expertise, leading to more comprehensive and sustainable interventions against cholera outbreaks in Nigeria.

METHODS

This narrative review aims to synthesize existing literature on cholera in Nigeria, focusing on epidemiological profiles, diagnostic approaches, vaccine implementation, challenges, and strategic framework for enhanced coverage. The methodology involved a systematic search and selection of relevant articles from three major databases: Scopus, PubMed, and Google Scholar. These databases were selected for their extensive coverage of public health research and their reputable collections of peer-reviewed articles. The search was limited to studies published between 2011 and 2024 to ensure the inclusion of the most recent and pertinent data.

Search Strategy

A systematic search strategy was employed to identify relevant studies and articles. The search was conducted using Boolean operators (AND, OR) to combine keywords effectively. The search was limited to English-language articles to ensure accessibility and understanding of the content. The following keywords and phrases were used in the search: "Cholera", "Vibrio cholerae", "Epidemiology", "Nigeria", "Diagnostic Approaches", "Vaccination", "Public Health Policy", "Cholera Control" and "Water and Sanitation". These keywords were combined in various configurations to capture a wide range of relevant literature.

Inclusion and Exclusion Criteria

Articles were included in this review based on the following criteria:

Inclusion Criteria:

- Studies published between 2011 and 2024.

- Articles focusing on cholera epidemiology, diagnostics, vaccination, and policy in Nigeria.

- Peer-reviewed journal articles, reviews, and reports from reputable organizations.

Exclusion Criteria:

- Articles not available in English.

- Studies focusing on cholera in countries other than Nigeria.

- Non-peer-reviewed articles, opinion pieces, or editorials.

Data Extraction and Analysis

Data extraction was performed systematically using a pre-defined template. Relevant information was extracted from each selected article, including Study design and methodology, Key findings related to cholera epidemiology, diagnostics, and vaccination efforts, Identified challenges and policy recommendations, and Author and publication details. The extracted data were synthesized narratively to identify common themes, trends, and gaps in the literature. A comparative analysis was conducted to evaluate the effectiveness of different diagnostic approaches and vaccination strategies reported in the studies. The findings were then contextualized within the broader public health framework to provide insights into cholera control efforts in Nigeria. This methodology ensured a comprehensive and systematic review of the existing literature, paving the way for a thorough understanding of the current state of cholera in Nigeria and the challenges faced in its control.

RESULTS and DISCUSSION

Epidemiological Profile of Cholera in Nigeria

Cholera has a long-standing history in Nigeria, with numerous outbreaks reported since the first recorded case in the country in the 19th century. The disease has persisted in various regions, particularly in the northern and coastal areas, where access to clean water is limited. Cholera presents a complex epidemiological pattern in Nigeria, manifesting as both endemic disease and periodic epidemics. Endemic cholera persists year-round in coastal regions and riverine communities, while epidemic outbreaks typically coincide with the rainy season (June-September) [8, 9].

Since Nigeria's first documented outbreak in 1972, cholera has maintained endemic-epidemic cycles, with the country experiencing outbreaks during six of the seven cholera pandemics that have occurred globally. Recent data indicate that Nigeria has experienced a resurgence of cholera outbreaks, particularly from 2017 to 2021. The Nigeria Centre for Disease Control (NCDC) reported thousands of cases annually, with significant mortality rates. The cyclical nature of cholera outbreaks in Nigeria is linked to seasonal flooding, urbanization, and population displacement due to conflict and economic challenges [8].

The disease burden has shown significant escalation in recent years. During the 2022 outbreak, Nigeria reported over 7,700 cases across the northeastern states, with Borno accounting for 70% of cases. In 2023, 2,309 suspected cases and 57 deaths were documented across 26 states (Figure 1), yielding a case fatality rate (CFR) of 2.5% [9]. The situation intensified in 2024, with 10,837 suspected cases and 359 deaths (CFR 3.3%) reported across all 36 states (Figure 2) by September. Lagos State emerged as the epicenter, contributing 43% of total cases, followed by Jigawa (870 cases), Kano (809), and Borno (588). Demographic analysis reveals heightened vulnerability among children under 14 years old, with a slight male predominance (52%) [10].

Table (1): Characteristics of cholera vaccines

Table (2):    Challenges and Prospects of Cholera vaccine implementation

Risk Factors Driving Cholera Transmission in Nigeria

Key risk factors contributing to cholera transmission in Nigeria include [11, 12]:

Inadequate Water Supply: Poor access to clean and safe drinking water increases the risk of cholera outbreaks.

Poor Sanitation: Open defecation and inadequate sewage disposal systems facilitate the spread of Vibrio cholerae.

Crowded Living Conditions: Urban slums and overcrowded communities are hotspots for cholera transmission.

Climate Change: Flooding and changes in rainfall patterns have been linked to increased cholera cases [13].

Clinical Characteristics and Complications associated with Cholera

The incubation period typically ranges from 12 hours to 5 days, with most patients developing symptoms within 2-3 days of exposure. While mild cases often resolve spontaneously, severe cholera can lead to critical complications including acute renal failure (15-20% of severe cases), electrolyte imbalances, severe dehydration leading to hypovolemic shock, metabolic acidosis, and cardiac arrhythmias in advanced cases [14].

Current Diagnostic Approaches for Cholera Detection in Nigeria

Nigeria employs a hierarchical diagnostic network comprising primary healthcare centers, secondary hospitals, and tertiary reference laboratories. The Nigeria Centre for Disease Control (NCDC) coordinates this network, implementing standardized protocols aligned with WHO guidelines. The diagnostic landscape encompasses microscopy, traditional culture-based methods, rapid diagnostics, and advanced molecular techniques, with varying accessibility across different healthcare tiers [15].

Clinical Diagnosis

Primary diagnostic approaches begin with clinical assessment based on WHO case definitions:

1. Suspected Case:

Suspected cases are defined by acute watery diarrhea with or without vomiting, severe dehydration in patients aged 5 years or older, and occurrence in areas with confirmed cholera outbreak

2. Confirmed Case:

Confirmed cases are defined by laboratory isolation of Vibrio cholerae O1 or O139 from stool samples and epidemiological linkage to confirmed cases during outbreaks.

Clinical evaluation includes: 1) Assessment of dehydration severity using WHO criteria, 2) Evaluation of vital signs and mental status, 3) Documentation of characteristic rice-water stools, and 4) Recording of epidemiological links in outbreak settings. Cholera is primarily diagnosed based on clinical symptoms, including profuse watery diarrhea and dehydration. However, clinical diagnosis alone is insufficient for effective outbreak management [16].

Laboratory Diagnosis

1. Microscopic Examination

Direct microscopy remains a fundamental first-line tool in Nigerian laboratories. This includes: Wet mount preparation examination, Gram staining for curved gram-negative bacilli, and Dark-field microscopy where available. Limitations include: 1) Low specificity and sensitivity, 2) Requirement for skilled microscopists, and 3) Inability to differentiate V. cholerae serotypes [17].

2. Culture Methods

Traditional cultural techniques serve as the gold standard. Primary isolation deploys the use of Alkaline peptone water (APW) enrichment, Thiosulfate-citrate-bile salts-sucrose (TCBS) agar, and Modified TCBS formulations for enhanced selectivity. Identification procedures consist of colony morphology assessment, biochemical characterization, Triple Sugar Iron (TSI) agar reactions, oxidase testing, and string test for identification. On TCBS Agar, it forms yellow colonies 2-3 mm in diameter, smooth and slightly flattened. In contrast, on Blood Agar, colonies appear gray to off-white and exhibit beta-hemolytic activity. Biochemically, V. cholerae ferments glucose, sucrose, and mannitol, while being negative for lactose fermentation. It shows positive results for indole production and the Methyl Red test, with variable citrate utilization. When placed on TSI Agar, it presents an alkaline slant and acid butt (K/A), indicating glucose fermentation without gas or Hydrogen sulfide (H₂S). The oxidase test yields a strong positive result, evidenced by a deep purple color change within ten seconds. The string test also confirms its identity, producing mucoid strings in the presence of sodium deoxycholate. V. cholerae thrives optimally at 37°C and a pH of 7.6-8.6, displaying darting motility due to a single polar flagellum. Its halophilic nature allows growth at 1-3% NaCl, with minimal tolerance above this range. Collectively, these characteristics enable accurate identification and differentiation from other Vibrio species [18].

3. Serological Methods

Serological assays can be used to identify specific serogroups of V. cholerae, aiding in epidemiological studies and outbreak investigations. These methods enable public health officials to track the spread of the disease and determine its origin, thereby informing effective intervention strategies [19]. Serological confirmation involves several techniques, including:

i) Slide Agglutination with Polyvalent Antisera: This method utilizes a mixture of antisera that can react with different serogroups of V. cholerae. By mixing a bacterial isolate with these antisera on a slide, agglutination indicates the presence of specific serogroups, providing rapid results that help in preliminary identification.

ii) Specific O1 and O139 Serotyping: This technique is employed to differentiate between the major pathogenic serogroups of V. cholerae, namely O1 and O139. These serogroups are the most commonly associated with cholera outbreaks, and their identification is critical for understanding the epidemiology of the disease and for targeted vaccination efforts.

iii) Inaba and Ogawa Subtype Determination: Further classification of serogroup O1 into Inaba and Ogawa biotypes is essential for epidemiological tracking. These subtypes can exhibit variations in virulence and transmission dynamics, which can influence outbreak patterns. Their identification aids in monitoring changes in circulating strains, thus enhancing outbreak preparedness and response. By employing these serological methods, public health authorities can gain valuable insights into cholera transmission dynamics, facilitating timely and effective public health interventions.

4) Rapid Diagnostic Tests (RDTs)

In recent years, Nigeria has increasingly adopted Rapid Diagnostic Tests (RDTs) to facilitate quick and efficient field diagnosis of cholera, significantly enhancing outbreak response efforts. Among the various RDT platforms available, "Crystal VC Dipsticks" has emerged as the most commonly utilized tool in the country.

Crystal VC Dipsticks allow for the rapid detection of V. cholerae serogroups O1 and O139, which are responsible for the majority of cholera outbreaks. The test provides results within a remarkably short timeframe of 15-20 minutes, enabling health workers to make prompt decisions regarding treatment and containment measures. The sensitivity of these dipsticks ranges from 90-95%, while specificity is reported at 85-90%, making them a reliable option for field testing.

The implementation strategy for RDTs emphasizes their primary use in outbreak investigations, where rapid identification of cases is critical. They are particularly beneficial for screening in resource-limited settings, where access to sophisticated laboratory facilities may be restricted. Additionally, RDTs support point-of-care testing in remote areas, ensuring that even the most underserved populations can receive timely diagnostic services. During epidemics, these tests play a crucial role in enhancing surveillance efforts, enabling health authorities to monitor the spread and control of the disease effectively. Overall, the integration of RDTs into Nigeria's cholera response strategy represents a significant advancement in public health initiatives [20].

5. Molecular Techniques

Molecular methods have revolutionized the diagnostic landscape for cholera, with techniques such as Polymerase Chain Reaction (PCR) emerging as essential tools for rapid and accurate diagnosis. These molecular approaches allow for the direct detection of cholera toxin genes, significantly streamlining the diagnostic process compared to traditional culture methods, which can be time-consuming and less reliable [21].

a) Polymerase Chain Reaction (PCR) is a foundational molecular technique employed in various forms:

i) Conventional PCR focuses on detecting specific toxin genes, making it a valuable tool for confirming cholera infections.

ii) Multiplex PCR enables the simultaneous detection of multiple genetic targets within a single reaction, enhancing efficiency in identifying various V. cholerae strains.

iii) Real-time PCR provides quantitative analysis, allowing for the measurement of gene expression levels and the precise quantification of bacterial load, thereby aiding in severity assessments [22].

Key target genes in cholera diagnostics include:

“ctxA”, which encodes for cholera toxin, a critical virulence factor.

“tcpA”, associated with the toxin-coregulated pilus, facilitating bacterial adhesion.

"rfb", is involved in O-antigen biosynthesis, helping to identify specific serogroups.

“toxR”, a transcriptional activator that regulates virulence gene expression.

b) Advanced Molecular Applications available at reference laboratories further enhance the understanding of cholera dynamics:

i) Whole Genome Sequencing (WGS) provides comprehensive insights into the genetic makeup of V. cholerae, enabling precise strain characterization.

ii) Multi-locus Sequence Typing (MLST) allows for the differentiation of bacterial strains based on variations in several housekeeping genes, facilitating epidemiological studies.

iii) Pulse-field Gel Electrophoresis (PFGE) is used to analyze the genetic fingerprints of bacterial isolates, assisting in outbreak investigations.

These advanced techniques enable public health officials to conduct thorough strain characterization, monitor antimicrobial resistance, and perform evolutionary analyses, thus strengthening cholera surveillance and control efforts. Together, molecular methods represent a critical advancement in the fight against cholera, providing essential tools for timely diagnosis and effective public health interventions [23].

Surveillance and Reporting Systems for Cholera

Effective surveillance and reporting systems are vital for the timely detection and control of cholera outbreaks in Nigeria. The country has developed a structured surveillance network that integrates various laboratory and public health resources to enhance disease monitoring and response [24].

1. Laboratory-Based Surveillance

Nigeria maintains a robust laboratory-based surveillance system characterized by a tiered structure. This structure comprises:

Local Health Facility Laboratories: These serve as the first point of contact for cholera diagnosis. They are equipped to conduct preliminary tests and identify suspected cases, ensuring that immediate action can be taken at the community level.

State Public Health Laboratories: These laboratories provide more advanced diagnostic services, supporting local health facilities by confirming preliminary results and conducting further testing as needed. They play a crucial role in monitoring regional trends and facilitating data collection.

Regional Reference Laboratories: These facilities serve multiple states and are equipped with more sophisticated diagnostic technologies. They specialize in complex testing, outbreak investigations, and quality assurance for lower-tier laboratories.

National Reference Laboratory: This laboratory oversees the entire surveillance network, ensuring consistency and reliability in diagnostic processes. It serves as a hub for advanced research, training, and coordination of national health responses [25].

Cholera Diagnostic and Surveillance Challenges in Nigeria

Nigeria faces significant challenges in its efforts to diagnose and control cholera outbreaks effectively. These challenges can be categorized into infrastructure constraints, technical hurdles, and resource limitations, each contributing to the overall difficulty in managing this public health threat [26].

1. Infrastructure Constraints

Infrastructure deficits are a major barrier to effective cholera diagnosis and surveillance in Nigeria:

a) Limited Laboratory Facilities in Rural Areas: Many rural health facilities lack the necessary laboratory infrastructure to conduct reliable cholera diagnostics. This limitation means that patients in remote areas often do not receive timely diagnoses, leading to delayed treatment and increased transmission risks [27].

b) Inconsistent Power Supply: Frequent power outages hinder the operation of laboratory equipment, affecting testing capabilities. Without a stable power supply, laboratories cannot maintain optimal conditions for diagnostic testing, leading to compromised results.

c) Inadequate Cold Chain Maintenance: Maintaining a proper cold chain is essential for preserving the viability of specimens and reagents. Inadequate cold chain systems in many laboratories result in the degradation of samples, further complicating accurate diagnosis.

d) Transportation Difficulties for Specimens: Transportation of specimens from remote health facilities to laboratories is often hampered by poor road infrastructure and logistical challenges. These difficulties can delay the testing process, which is critical for a timely outbreak response.

2. Technical Challenges

Technical issues also impede effective cholera surveillance and diagnosis:

a) Shortage of Trained Laboratory Personnel: A significant gap exists in the availability of trained laboratory personnel skilled in cholera diagnostics. This shortage limits the capacity of laboratories to conduct accurate testing and hampers overall surveillance efforts [28].

b) Limited Access to Advanced Diagnostic Platforms: Many laboratories, especially in rural areas, lack access to advanced diagnostic technologies such as molecular testing platforms. This limitation restricts the ability to perform rapid and accurate diagnoses, which are crucial during outbreaks.

c) Quality Control Inconsistencies: The lack of standardized quality control procedures across laboratories leads to inconsistencies in test results. These discrepancies can undermine the reliability of data collected for surveillance and outbreak management.

d) Reagent Supply Chain Issues: Frequent shortages of essential reagents necessary for diagnostic testing disrupt laboratory operations, leading to delays in case identification and reporting.

3. Resource Limitations

Resource constraints further exacerbate the challenges faced in cholera diagnostics and surveillance:

a) Financial Constraints: Limited funding for public health initiatives restricts the ability to upgrade laboratory facilities, procure necessary equipment, and implement comprehensive training programs for laboratory personnel.

b) Equipment Maintenance Challenges: Ongoing maintenance of laboratory equipment is often overlooked due to budget limitations, leading to equipment malfunctions and reduced diagnostic capacity.

c) Consumable Availability: The unavailability of essential consumables, such as test kits and laboratory supplies, can cause interruptions in diagnostic services, delaying case identification.

d) Training Program Sustainability: Sustaining effective training programs for laboratory personnel is challenging due to financial and logistical constraints, hindering the development of a skilled workforce [29].

4) Delayed Reporting:

Delay reporting is another critical issue that hampers effective cholera management in Nigeria. Slow laboratory turnaround times can significantly hinder timely outbreak response efforts. In many cases, the diagnostic process may take several days or even weeks, delaying the identification of cholera cases and the implementation of necessary public health interventions. This delay can lead to a rapid spread of the disease, particularly in densely populated areas where cholera can thrive due to inadequate sanitation and water supply. Additionally, slow reporting can undermine the effectiveness of surveillance systems meant to monitor and control cholera outbreaks [30].

Key Strategies for overcoming cholera diagnostics and surveillance challenges

To address these challenges and enhance cholera diagnostics and surveillance in Nigeria, several key strategies can be implemented [31]:

1. Diagnostic Capacity Enhancement

i. Expansion of Molecular Testing Facilities: Increasing the number of laboratories equipped for molecular testing will improve the accuracy and speed of cholera diagnoses. This expansion can significantly enhance outbreak response capabilities.

ii. Implementation of Automated Systems: Introducing automated diagnostic systems can streamline laboratory workflows, increase throughput, and reduce human error, leading to more reliable results.

iii. Integration of Point-of-Care Technologies: Developing and distributing point-of-care testing technologies will enable rapid diagnosis in remote areas, allowing for quicker treatment and containment of outbreaks.

iv. Development of Mobile Laboratory Units: Creating mobile laboratories can facilitate on-site testing during outbreaks, ensuring timely diagnosis and response, especially in hard-to-reach areas [32].

2. Quality Management

i. Strengthening Quality Assurance Programs: Implementing robust quality assurance measures will enhance the reliability of laboratory testing and ensure adherence to established protocols.

ii. Standardization of Diagnostic Protocols: Developing standardized diagnostic protocols across all laboratories will ensure consistency in testing and reporting, improving the overall quality of data collected.

iii. Regular Proficiency Testing: Establishing routine proficiency testing will help laboratories benchmark their performance, identify areas for improvement, and maintain high standards of practice.

iv. Documentation System Improvement: Enhancing documentation practices within laboratories will ensure better tracking of diagnostic processes and facilitate data sharing for surveillance purposes [33].

3. Surveillance Integration

i. Enhanced Data Management Systems: Investing in advanced data management systems will streamline data collection, analysis, and reporting, making it easier to monitor cholera trends and outbreaks.

ii. Real-time Reporting Capabilities: Implementing real-time reporting systems will enable health authorities to respond swiftly to emerging outbreaks, minimizing the impact on public health.

iii. Cross-Border Surveillance Coordination: Strengthening collaboration with neighboring countries will enhance regional surveillance efforts, facilitating the tracking of cholera across borders.

iv. Advanced Analytical Tools Implementation: Utilizing advanced analytical tools will improve data interpretation and support evidence-based decision-making for cholera control [34].

4. Capacity Building

i. Training Program Development: Establishing comprehensive training programs for laboratory personnel will enhance their skills and knowledge, improving diagnostic accuracy and efficiency.

ii. Technical Skill Enhancement: Focused workshops and training sessions will address specific technical skills needed for cholera diagnostics, ensuring that personnel are well-equipped to handle the challenges they face.

iii. Quality Management Education: Educating laboratory staff on quality management principles will foster a culture of excellence and accountability within laboratories.

iv. Research Capability Strengthening: Investing in research initiatives will promote innovation in cholera diagnostics and surveillance, leading to the development of novel approaches tailored to local contexts [35].

5. Innovation and Research

i. Novel Diagnostic Tool Evaluation: Evaluating new and innovative diagnostic tools will help identify cost-effective and efficient solutions for cholera detection.

ii. Local Technology Adaptation: Fostering the adaptation of existing technologies to local contexts will enhance accessibility and affordability, ensuring that diagnostic tools are suitable for the Nigerian healthcare environment.

iii. Cost-Effective Method Development: Prioritizing the development of cost-effective diagnostic methods will make cholera testing more accessible, particularly in resource-limited settings.

iv. Validation Studies Conduct: Conducting validation studies on new diagnostic methods will ensure their reliability and effectiveness before widespread implementation [36].

Overall, addressing the diagnostic and surveillance challenges facing Nigeria requires a multi-faceted approach that enhances infrastructure, builds technical capacity, and fosters innovation. By investing in these areas, Nigeria can significantly improve its cholera response efforts, ultimately reducing the burden of this preventable disease on public health.

Cholera Vaccine Implementation

There are two main types of cholera vaccines:

1) Inactivated Whole-Cell Vaccines: These vaccines provide short-term immunity and require multiple doses.

2) Oral Cholera Vaccines (OCVs): OCVs are easier to administer and are effective in endemic areas [37].

In the past year, the demand for the Oral Cholera Vaccine (OCV) has significantly increased, with the World Health Organization (WHO) reporting ongoing cholera cases in at least 24 countries by March 2023. The Global OCV Stockpile, established in 2013 and supported by Gavi since 2014, has distributed 73 million doses across 23 countries, yet this number falls short of the estimated annual need for over 75 million doses [38].

The severity of outbreaks in 2022, coupled with OCV shortages, prompted the International Coordinating Group (ICG) to temporarily modify the vaccination strategy from a two-dose to a one-dose regimen. This approach has shown effectiveness in outbreak management, although the duration of protection remains uncertain. The second dose, typically given within six months, provides three years of immunity, but the one-dose strategy is intended as a short-term measure [39].

Currently, three WHO-prequalified oral cholera vaccines—Dukoral®, Euvichol®, and Shanchol™—are available (Table 1), with Euvichol and Shanchol distributed through Gavi. Dukoral® requires a buffer solution and is intended for travelers, offering two years of protection after two doses. In contrast, Shanchol™ and Euvichol® do not require a buffer and provide three years of immunity after two doses. As of now, about 142 million doses have been shipped through the ICG to 31 countries, especially in outbreak-prone and high-risk areas. Ongoing research aims to develop new vaccines that provide extended protection with more convenient dosing schedules [40, 41].

Timeline of vaccines emergence

The timeline of cholera vaccine emergence began in 1885 when Spanish bacteriologist Jaume Ferran I Clua developed the first cholera vaccine from live whole cells, using samples from patients in Marseille [45]. Waldemar Haffkine later improved this vaccine between 1893 and 1896, testing it on over 40,000 individuals in Calcutta, marking it as the first widely accepted human cholera vaccine [46]. Although numerous formulations emerged in the 20th century, none met WHO recommendations due to efficacy and safety issues. A landmark achievement occurred in 2001 when the first internationally licensed whole-cell oral cholera vaccine received WHO pre-qualification [44, 48].

Types and efficacy of cholera vaccines

Cholera vaccines are crucial for controlling outbreaks, especially in endemic regions. The World Health Organization (WHO) endorses three prequalified oral cholera vaccines (OCVs) and recommends their use in high-risk areas, supported by a global stockpile established in 2013. This initiative, backed by Gavi and the Global Task Force on Cholera Control, has facilitated over 25 million doses administered in mass vaccination campaigns across 19 countries [49, 50].

Dukoral, approved in 1991, contains inactivated Vibrio cholerae O1 strains and the recombinant cholera toxin B subunit (WC-rBS). It generates antibodies that prevent bacterial colonization in the intestine, reducing diarrhea symptoms. Real-world trials have shown its efficacy ranging from 79% to 86% across various countries [51, 52].

Shanchol, unlike Dukoral, does not contain the cholera toxin B subunit but consists of inactivated strains of Vibrio cholerae O1 and O139. It effectively immunizes children aged one year and older, demonstrating a protective efficacy of 67% in India and 66% in Vietnam [38-41].

Vaxchora (CVD 103-HgR), originally for U.S. travelers, is now globally available for individuals aged 6 to 64. This single-dose vaccine uses a live attenuated strain, achieving a 90.3% efficacy against both mild and severe diarrhea, with 79.5% effectiveness lasting up to three months [28, 29]. Collectively, these vaccines play a vital role in cholera prevention, with varying efficacies that reflect their different mechanisms and formulations.

Current Cholera Vaccination Strategies in Nigeria

The introduction of OCVs has been a significant step towards cholera control in Nigeria. Mass vaccination campaigns have been implemented in high-risk areas, particularly during outbreaks [53].

1. Target Population

Efforts are focused on vaccinating vulnerable populations, including children under five, pregnant women, and those living in cholera-prone regions.

2. Delivery Mechanisms

Vaccination campaigns are typically conducted through:

i)                    Routine Immunization Programs: Integrating cholera vaccines into existing immunization schedules.

ii)                  Emergency Vaccination Campaigns: Rapid response campaigns during outbreaks to curtail transmission [54].

Cholera Vaccine Campaigns and Impact in Nigeria

Nigeria has implemented various cholera vaccination campaigns to combat outbreaks and prevent future epidemics, particularly targeting vulnerable populations like internally displaced persons (IDPs) and communities lacking access to clean water. The initial deployment of the oral cholera vaccine (OCV) occurred in Maiduguri, Borno State, in September 2017, in response to an outbreak among IDPs. Subsequently, preventive OCV campaigns were organized by the National Primary Health Care Development Agency (NPHCDA) from November 2018 to September 2019 across ten high-risk local government areas (LGAs) [55].

Following a significant cholera outbreak in July 2018, which affected 16 states and resulted in over 16,000 suspected cases and 186 deaths, OCV was deployed in impacted areas, including Yobe, Bauchi, Adamawa, and Zamfara [56]. Adamawa received over 700,000 doses of emergency vaccination [57]. The International Coordinating Group (ICG) also approved over five million OCV doses for a 2021 outbreak response across seven high-burden LGAs in four states [58]. These vaccination efforts have led to a marked decrease in cholera incidence and mortality rates in targeted areas, while also enhancing community awareness of cholera prevention measures. However, challenges such as logistical issues, vaccine hesitancy, and funding constraints persist [59]. The overall impact demonstrates significant progress in controlling cholera through robust vaccination initiatives.

The impact of cholera vaccine campaigns in Nigeria has been substantial, evidenced by a notable decrease in cholera incidence and mortality rates in vaccinated areas. Moreover, vaccine campaigns have contributed to raising awareness about cholera prevention and control measures among communities, leading to improved hygiene practices and increased demand for clean water sources. Measuring the impact of cholera vaccine campaigns involves evaluating various indicators, including vaccine coverage, reduction in cholera cases and deaths, and cost-effectiveness. While challenges such as logistical constraints, vaccine hesitancy, and funding shortages may affect campaign outcomes, studies have shown promising results in reducing the burden of cholera in vaccinated populations.

Cholera Vaccine Awareness

Despite the ongoing threat of cholera, awareness of vaccination as a preventive measure remains low in Nigeria. Factors such as limited health literacy, cultural beliefs, and vaccine mistrust contribute to the low uptake of cholera vaccination campaigns. To enhance vaccine acceptance and coverage, it is crucial to raise awareness and educate communities about the benefits of cholera vaccination [60].

Understanding vaccine awareness involves assessing knowledge, attitudes, and usage of vaccines within a specific context. However, existing studies often focus on raising awareness about cholera infection rather than comprehensively exploring individuals' knowledge and attitudes regarding the oral cholera vaccine (OCV). For instance, research indicates a significant variance in awareness levels. In Bangladesh, only 16% of participants knew about the cholera vaccine [61], while 28% in Congo viewed it as a treatment option [62]. Conversely, a study in Uganda revealed that 77% understood the vaccine's preventive role against cholera [63].

In Nigeria, during the 2017 outbreak in Maiduguri, an OCV campaign achieved a coverage rate of 90%, indicating strong participation despite overall awareness levels being uncertain [38]. Nonetheless, an evaluation of understanding and utilization of the OCV was lacking. A study in Makurdi found that only 27% accurately identified cholera, highlighting the need for targeted health education initiatives to improve knowledge of cholera and the OCV. Efforts should particularly focus on low-literacy populations to enhance proactive measures against cholera [39, 40].

Cholera Vaccine Policies

To effectively manage cholera control through vaccination, several policies have been established, focusing on the procurement, storage, and distribution of the Oral Cholera Vaccine (OCV). In response to WHO recommendations, the Nigeria Center for Disease Control (NCDC) held a workshop in June 2017, officially endorsing OCV as a crucial intervention tool against cholera [41]. A key requirement for deploying the OCV is obtaining authorization from the National Agency for Food and Drug Administration and Control, which allowed its initial use during the 2017 outbreak in Borno. Acquiring cholera vaccines involves a structured application process directed to the International Coordinating Group (ICG), responsible for the global vaccine stockpile. The application undergoes rapid evaluation based on factors such as vaccination methods and current outbreak situations. Since 2013, over 5 million doses of approved vaccines (Shanchol, Dukoral, Euvichol) have been distributed [23]. The vaccine is deployed in response to outbreaks or high-risk areas, rather than as part of routine immunizations [42, 43].

Challenges and Prospects of Cholera Vaccine Implementation

Implementing cholera vaccination in Nigeria faces multiple challenges but holds promising prospects. Key obstacles include inadequate infrastructure and logistics, such as cold chain storage and transportation, which hinder vaccine distribution, especially in remote areas. Vaccine hesitancy, driven by misinformation and mistrust in healthcare, further complicates uptake. Limited healthcare workforce also affects vaccine administration and post-vaccination monitoring [43, 65].

Socioeconomic disparities exacerbate unequal access to vaccines, particularly in underserved or conflict-affected regions. Enhanced surveillance and monitoring are crucial to track coverage and identify outbreaks early. Partnerships with international organizations, NGOs, and philanthropic groups can alleviate funding and logistical barriers [44].

Promising prospects involve integrating cholera vaccination with existing public health initiatives, including water, sanitation, and hygiene (WASH) programs, to maximize impact. Strong policy advocacy and sustainable funding are critical for long-term success, ensuring cholera vaccination becomes a public health priority [41-43]. The challenges and prospects of cholera vaccine implementation are summarized in Table 2 below. 

Unanswered Questions on Cholera Vaccination Seeking answers

1. What is the long-term efficacy of oral cholera vaccines (OCVs) beyond five years? Longitudinal studies are needed to assess the duration of immunity provided by OCVs beyond the current five-year protection period. These studies should track vaccinated individuals over time to observe waning immunity and determine the need for booster doses.
2. What are the optimal strategies for integrating OCVs into national immunization programs? Operational research is needed to evaluate how best to incorporate cholera vaccines into routine immunization schedules alongside existing vaccines.
3. How effective are OCVs in controlling cholera outbreaks in diverse environmental settings? Comparative studies across different ecological and socio-economic environments (e.g., urban slums, rural areas, coastal regions) are necessary to understand how vaccine efficacy and outbreak control differ by setting.
4. What are the barriers to vaccine uptake in high-risk populations, and how can they be overcome? Social science research focused on understanding the cultural, economic, and logistical factors that influence vaccine acceptance and uptake is critical. Community-based studies can explore perceptions of cholera risk, trust in vaccines, and access to vaccination services.
5. Can combining OCVs with water, sanitation, and hygiene (WASH) interventions provide synergistic benefits in cholera control? Interdisciplinary research should assess the combined impact of OCVs and WASH interventions in cholera-endemic regions.
6. How can we ensure equitable access to cholera vaccines during emergencies and outbreaks? Policy and health systems research should focus on improving vaccine distribution mechanisms, especially in conflict zones, refugee camps, and areas affected by natural disasters.
7. What is the impact of large-scale cholera vaccination campaigns on antimicrobial resistance (AMR)? Research is needed to explore the potential indirect effects of mass cholera vaccination on AMR patterns, particularly in regions where cholera outbreaks often lead to the widespread use of antibiotics.

By addressing these questions through targeted research, future cholera control efforts can be optimized, improving both vaccine implementation strategies and overall public health outcomes.

1. Strengthening Surveillance Systems

Enhancing disease surveillance systems is crucial for the early detection and rapid response to cholera outbreaks. This involves upgrading laboratory capacities, implementing real-time reporting mechanisms, and establishing a robust network of health facilities equipped to monitor cholera cases effectively. By investing in training for healthcare workers and employing advanced data management systems, Nigeria can ensure the timely identification of outbreaks, allowing for swift interventions that can significantly reduce morbidity and mortality. A comprehensive surveillance strategy should also include community-based reporting systems to capture data from remote areas [63].

2. Improving Water and Sanitation Facilities

Investing in water supply and sanitation infrastructure is critical for preventing cholera transmission. Access to clean drinking water and adequate sanitation facilities directly influences the incidence of cholera. The strategic framework should prioritize the development and rehabilitation of water supply systems, sewage management, and proper waste disposal. Community-led initiatives should be encouraged to promote sustainable practices, such as rainwater harvesting and the construction of household latrines. Engaging communities in the planning and implementation of these projects ensures that solutions are culturally appropriate and more likely to be maintained over the long term [64].

3. Expanding Vaccination Coverage

Increasing access to cholera vaccines, particularly in high-risk areas, is a vital component of the strategic framework. This includes improving vaccine supply chains to ensure that doses are available when needed and fostering community engagement to increase vaccine acceptance. Targeted vaccination campaigns should be organized during peak transmission seasons, and outreach efforts must be tailored to address specific community concerns and misconceptions about vaccination [65].

4. Enhancing Community Awareness and Education

Public awareness campaigns must be implemented to educate communities about cholera prevention, hygiene practices, and the importance of vaccination. These campaigns should utilize various channels, including social media, community meetings, and school programs, to reach diverse audiences. Empowering community leaders and health workers as advocates for cholera prevention can enhance trust and participation. Educational materials should be culturally sensitive and available in local languages to maximize understanding and impact [66].

5. Collaborating with Stakeholders

Collaboration among government agencies, non-governmental organizations, and international partners is essential for a coordinated cholera response. Establishing partnerships can facilitate resource sharing, knowledge exchange, and logistical support. A multi-sectoral approach that involves health, water, sanitation, and education sectors will enhance the effectiveness of interventions. Regular stakeholder meetings and joint planning sessions can ensure that all parties are aligned in their efforts to combat cholera, fostering a unified response that leverages the strengths of each partner [66].

CONCLUSION

In conclusion, cholera presents a significant worldwide health concern, particularly in developing nations like Nigeria where overcrowding and inadequate sanitation create favorable conditions for its rapid transmission. The utilization of oral cholera vaccines has emerged as a pivotal strategy in addressing this ailment. These vaccines have shown effectiveness in preventing and managing cholera outbreaks, aided by endeavors like the Global Task Force on Cholera Control and the establishment of a worldwide vaccine reserve. Enhancing accessibility and adoption of these vaccines during epidemics and humanitarian emergencies represents a noteworthy accomplishment. Prioritizing vaccine access, education, and distribution in vulnerable areas is crucial. While progress has been made, long-term solutions, including improved water and sanitation, are essential. Continued efforts in vaccination, education, and research are vital to reducing cholera's global impact. Achieving a cholera-free Nigeria requires a multifaceted approach that combines epidemiological surveillance, effective diagnostic methods, robust vaccination strategies, and strong policy frameworks. By addressing the underlying determinants of cholera and fostering community engagement, Nigeria can significantly reduce the burden of this preventable disease and promote public health resilience.

Recommendations

It is crucial to design comprehensive education campaigns that raise awareness about the importance of blood donation, address misconceptions, provide clear information on donation procedures, and actively engage communities. Utilizing multiple channels such as radio, television, social media, and community outreach programs can help reach diverse audiences and maximize the impact of education efforts. Additionally, partnerships with healthcare institutions, local organizations, and government agencies can strengthen the reach and effectiveness of blood donation campaigns.

Acknowledgement:

Not applicable.

Ethical approval:

Not applicable.

Conflict of Interest Statement: No conflict of interest in this study.

Funding Sources:  No funding support in this review.

Author Contributions: Research concept: EOO, MOJ, SSE & PEF; Literature search: EOO, MOJ, SSE, PEF, EOD & RAO; Writing the manuscript: EOO, MOJ, SSE, PEF, EOD & RAO; Critical revision of the manuscript: EOO, MOJ, SSE & EOD; Final approval of the uploaded manuscript: EOO, MOJ, SSE, PEF, EOD & RAO