Systematic Study and Meta-Analysis of Risk Factors Associated with Cholera Outbreaks in Africa: A Review

In Sub-Saharan Africa, cholera is a persistent public health problem. Various methods are now being applied to reduce the mobility and mortality that these diseases cause. Because of the implemented policies, there seem to have been several improvements. However, the constraints suggest inefficiency in eliminating the burden, necessitating a straightforward explanation. The systematic review and meta-analysis aimed are to investigate the reasons for the incomplete eradication of cholera disease in Sub-Saharan Africa. We were able to obtain pooled estimates using random effect models. Four experiments were excluded from the study because they were duplicated in the studies, 13 because of an outbreak did not occur, 13 publications did not include risk factors and odds ratios in their outcome analysis, and an outbreak occurred before 2013. The review points out that drinking contaminated water, consuming unwashed vegetables, and the use of poor publish toilet facilities enhance cholera in Africa. PubMed, Web of Science, EMBASE, and EBSCO were among the four meticulously and systematically searched databases using predetermined criteria or search strategies. Two independent reviewers recognized studies that met the selection criteria, and data was collected using validated methods.

The data tabulated from the national study is insufficient. The best deciding factors are steady estimates of infant mortality rates and patterns at the subnational level [8]. Within 99 low-and middle-income countries, the sub-national difference in mortality rates and the number of deaths of neonates and children below five years is not examined [8]. In 2018, a cholera outbreak in Nigeria's northern region signaled an increased burden. It emphasizes the strategic importance of a multi-sectoral strategy in developing and implementing public health strategies [17].  [18] [19]. Cholera outbreaks across borders are a significant public health concern in Sub-Saharan Africa. It leads to the high number of cholera cases and deaths recorded every year. Both people's lives and livelihoods are impacted, making prevention and regulation more complex [20]. The most vulnerable age ranges are children under the age of five who are in kindergarten. As a result, guidelines and procedures should be checked to delegate specific roles and obligations to children under eighteen. It will ensure that these epidemics are effectively prevented, detected, monitored, and controlled [20] [21].
Prevention by better water, sanitation, hygiene facilities, and the use of oral cholera vaccines (OCVs) [22] [23] are only a few of the methods that have been used.
In Sub-Saharan Africa, however, there are outbreaks and occasional cases of cholera.
We were unable to locate a report that attempted to quantify the global prevalence of the burden to the best of our knowledge. Subsequently, we conducted a systematic review and meta-study to investigate why the incomplete eradication of cholera diseases in Sub-Saharan Africa.

Materials and Method
The current research was conducted between December 2020 and February 2021 as a systematic overview and meta-analysis. This study supported the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The goal was to find a pooled estimate of the odds ratio of risk factors linked to African cholera outbreaks. In addition, the research also looked at the most common risk factor associated with cholera outbreaks in the general population in Africa.

The Search Strategy
A thorough and systematic search of four databases (PubMed, EMBASE, Web of Science, and EBSCO) was conducted. The search was restricted to 1990 through 2020, with the most recent search taking place on January 25, 2021. Using the following search technique, we conducted advanced searches in all databases using MeSH (Medical Subject Headings) on PubMed ((("Risk Factors" [Mesh]) and "Cholera" [Mesh]) "Africa South of the Sahara" [Mesh]). Moreover, TS = Risk factors AND TS = cholera AND TS = Africa are used for Web of Science, ("risk factor"/exp OR "risk factor") AND ("cholera"/exp OR cholera) AND ('Africa south of the site For studies conducted in English, the researcher also included keywords such as "cholera," "outbreaks," "risk factors," "Vibrio cholera," and "Africa."

Requirement for Eligibility and Exclusion
The following criteria were used to select inclusion criteria: observational epidemiological studies, including case management, cohort studies, cross-sectional (retrospective or prospective studies) with a population-based design that quantifies or defines risk factors associated with cholera outbreaks in any age group [24]. A risk factor is characterized as an aspect of personal behavior or lifestyle, environmental exposure, an inborn or hereditary trait known to be correlated with a health-related condition that is important to avoid based on epidemiological evidence (MeSH definition). Participants in the study must be from Africa, and the research must be performed or published in English. The risk factors that are included in the study must be listed as odds ratios. Studies were excluded if the study's result did not match the study's goal, and studies that used mixed methods were also excluded. The risk factor identified in the studies was used to test them.

Extraction of Information
Two investigators (S.F.M. and UB) carried out retrieving studies, who worked independently on the searches and handled the findings using EndNote X9 (Build 12 062). After eliminating duplicates, the reviewers looked at the titles of the retrieved papers to see if they were necessary. In addition, for full-text articles, specific articles were sought and screened for inclusion based on the inclusion criteria. When inconsistencies arose during the selection process, the third author resolved them. Author's name, year of publication, country, age range, study design, sample size, cases, controls, odds ratio, and confidence intervals of risk factors were all extracted from each paper using a standardized form with the following domains: author's name, year of publication, country, age range, study design, sample size, cases, controls, odds ratio and confidence intervals of risk factors.

Statistical Analysis
The risk factors associated with cholera outbreaks were the only outcome of this research. The established risk factors are examined individually, with subgroup analysis by region. The impact sizes and standard errors were calculated using StataCorp. 16.0 commands for meta-analysis, using the risk factors' odds ratios and confidence gaps. The odds ratios for the individual hazard factors were cal-culated using a pooled calculation. The standard error, confidence interval, and forest plots were calculated using STATA version 16 software. Depending on the heterogeneity, the random-effects model was used. The Cochran Q-test of heterogeneity was used to assess statistical heterogeneity in the studies at a significance level of 5%, and I2 was used to assess quantitative heterogeneity among the findings according to the Higgins classification, with an I2 value above 75% indicating significant heterogeneity. Furthermore, the Begg and Egger experiments were used to look at publication bias. In the case of high heterogeneity, the cause of heterogeneity was investigated, and sensitivity analysis was carried out by eliminating one study from the analysis and studies of inadequate consistency.

Evaluation of the Included Study Quality
The methodological authenticity of the included studies was determined using the JBI. Critical Appraisal Checklist for Cohort Studies and the JBI, Critical Appraisal Checklist for Case-Control Studies. The studies' nature, execution, and interpretation were scrutinized for the possibility of bias. The checklist had ten questions with yes, no, ambiguous, and not applicable answers. The frequency of yes and no responses determines high and low quality, respectively. Uncertain answers necessitate contacting the relevant author for clarification. The papers that were included were evaluated using the following questions: Are the groups comparable except for the presence of disease in cases of the absence of disease in controls, were cases and controls appropriately matched, were the same criteria used for case and control identification, was exposure measured in a standard, valid, and reliable manner, was exposure measured in the same manner for cases and controls, where confounding factors identified, and were strategies implemented? Participant recruitment, study design, and sample size were carefully examined for potential bias in the papers. The ten included studies all used a case-control study design. However, one of the ten trials did not have enough participants (Table 1).

Result
Our quest yielded 460 papers found using electronic search engines and strategies. Out of these, 97 were eliminated as duplicates, leaving 363 articles for further screening by title, full text, and abstract, which resulted in the exclusion of 321 more articles. As a result, 42 full-text studies were screened for inclusion criteria and other parameters aligned with the review objectives. Four findings were omitted from the research because they were not English studies, 14 were outside of the study environment, and thirteen papers did not include risk factors and odds ratios in Figure 1.

Result Characteristic
Eleven papers were included in the final systematic review and meta-analysis, Note: 1 = were groups comparable, 2 = were cases and controls matched, and 3 = were the same criteria used to identify cases and controls. 4 = were exposure measured in a standard way, 5 = were exposure restrained in the same way for cases and controls, 6 = were bewildering factors recognized, 7 were approaches to deal with confounding factors mentioned, 8 = were outcomes assessed in a standard way in addition, = Yes and = No, UC = undefined, and NA. = not available are used.  Furthermore, most studies, cases, and controls were not equivalent, and data collection was done in the neighborhood Table 2. Drinking untreated water (7 studies), consuming raw vegetables (4 studies), interaction with an infected person(s) (7 studies), eating outside of the home (4 studies), sharing toilet facilities with more than one household (4 studies), a lack of health education on preventive measures/intervention (3 studies), and poor hand hygiene before eating was established as risk factors (2 studies).

Drinking Untreated Water
Seven included studies identified the connection between drinking untreated water and cholera outbreaks. The research was carried out in Nigeria [36], Ethiopia [37], Cameroon [38], Kenya [39], and Zambia [40]. This risk factor for a cholera outbreak was correlated with a pooled odds ratio calculation shown in Figure 2 and Figure 3 [OR = 1.83; 95 percent CI: (1.23, 2.44)]. The heterogeneity (I2 = 62.78%) between studies was less than 75%.

Eating Raw Vegetables
Eating raw vegetables was the second risk factor associated with the cholera outbreak. This risk factor was the subject of four reports. The analysis has pooled odds ratio calculation [OR = 1.92; 95 percent CI: (0.88 -2.97)], the probability of cholera outbreak was nearly two times higher among people who consumed raw vegetables Figure 4.

Contact with an Infected Individual
Communication with an infected individual was classified as the third risk factor identified in the included articles. It was reported in seven papers as a risk factor associated with cholera outbreaks. The pooled odds ratio calculation [OR = 1.78; 95 percent CI: (1.20 -2.36)] revealed that individuals who come into contact with sick people are nearly twice as likely to catch the disease, shown in Figure  5.

Sharing Toilet Facilities with More Than One Person
Sharing toilet facilities with more than one household was the fourth risk factor associated with cholera outbreaks. The pooled odds ratio calculation [OR = 1.09; 95 percent CI: (0.62 -1.55)] was correlated with this risk factor for cholera outbreaks in four articles from four different countries Figure 6.

Inadequate Health Education
The fifth factor linked to cholera outbreaks among African populations was a lack of health education on preventive measures/interventions: three of the eleven studies published on this risk factor. The pooled odds ratio in Figure 7 calculation [OR = 1.18; 95 percent CI: (0.72 -1.64)] was correlated with cholera outbreak health education.

Eating Outside of the Home
Four researches looked at eating outside the home as a potential factor for cholera outbreaks. According to the pooled odds ratio calculation shown in Figure 8, [OR = 2.02; 95 percent CI: (1.28 -3.18)], people who eat out are more expected to catch the disease than those at home. The heterogeneity between studies was 62.7 percent less than the threshold of significant heterogeneity of 75 percent. which are shown in Figure 9. There was much variation between the studies (91 percent).

Bias in Publication
The funnel plot and Egger's test were used to screen for publication bias among the included studies for the meta-analysis [41]. According to Egger's test (P = 0.25), the publication bias was shallow, which was not significant to the current data, and funnel plots were symmetrical.

Discussion
Sporadic cholera outbreaks continue to occur, especially in Sub-Saharan Africa, and are unchecked [42]. Inadequate health literacy, inadequate water and sanitation services, community mobilization, and the absence of national plans, cross-border partnerships, and overcrowding are all risk factors for cholera [43] [44].
In addition to the current preventive steps, improved water, sanitation, and hygiene facilities and the use of OCVs are prominent. In Sub-Saharan Africa, however, there are outbreaks and occasional cases of cholera [45]. To the best of our understanding, no surveys have attempted to quantify the global prevalence of the burden. Therefore, we used a systematic study and meta-analysis to investigate why the incomplete eradication of cholera diseases in Sub-Saharan Africa. Our report screened 42 full-text studies after eliminating duplicates and searched for eligibility requirements in the papers we collected from databases applied to the review objectives [46] [47]. Finally, 11 papers from three different research designs were included in the final systematic review and meta-analysis. Many studies [43] [48] used an unmatched case-control design, while three used matched case-control, one retrospective matched case-control, and one case-control design. The sample size for the participants ranged from 47 to 300, and all of the studies included case and control groups. Drinking untreated water, consuming raw vegetables, interacting with infectious people, eating outside of the home, sharing toilet facilities with more than one household, a lack of health education on preventive measures/intervention, and poor hand hygiene before eating were the risk factors found in the studies. implementation [50]. The correlation between untreated drinking water and cholera outbreaks was identified in seven studies for meta-analyses, and five countries share it. Nigeria, Ethiopia, Cameroon, Kenya, and Zambia are among them. Although the pooled odds ratio estimate is 1.83, the variability associated with this risk factor for a cholera outbreak was less than 75%. With a long-term solution to water WASH, a report on climate change as a negative or positive related factor for cholera transmission. Drought, for example, can increase pathogen desiccation and reduce rainwater harvesting [51]. Finally, we have four studies that point to consuming raw vegetables as a risk factor for cholera outbreaks. The pooled odds ratio was 1.92, and the study revealed that the risk of the cholera outbreak was nearly twice as high among people who consumed raw vegetables.
A positive correlation was found in a study to evaluate and synthesize established evidence of OCV efficacy when used reactively in real-world conditions [52]. Another risk factor for cholera is fetal, neonatal, and maternal mortality caused by cholera during pregnancy. One research, however, found no difference in fetal death rates by trimester [52]. Contact with an infected individual was listed as a risk factor associated with cholera outbreaks in seven articles in

Minimizing Cholera in Sub-Saharan Africa
Cholera typically causes significant outbreaks and epidemics in Sub-Saharan Africa, owing to a lack of safe water and sanitation and insufficient case care.
When symptomatic or asymptomatic carrier enters a vulnerable community or when an individual meets contaminated environmental sources, an outbreak might begin in a new place [53]. ing contaminated water from lakes, rivers, estuaries, irrigation canals. In Africa, cholera transmission has been linked to river bathing and residential water consumption [58]. However, when stored in open containers within households or during transportation, clean water may get contaminated. Vendors may pollute drinking water during the extraction of water from wells and the transfer to containers purchased. Shallow, uncovered hand-dug wells, which are the primary source of drinking water for many people in Africa, have been implicated with cholera epidemics across Sub-Saharan Africa on multiple occasions [59]. For instance, in the Douala slum region of Cameroon, over 70,000 wells are less than 1.5 meters deep and frequently become contaminated by shallow groundwater, which is polluted by sewage and latrine discharge drains. Food can become infected with Vibrio cholera in the natural environment while being prepared or stored. Due to the concentration of vibrios in the gastrointestinal tracts of mollusks, crabs, these kinds of seafood have been consumed linked to cholera outbreaks. Transmission of V. cholera O1 has been linked to the consumption of unwashed raw vegetables and fruits and poor hygiene practices during meal preparation, as observed during fish gutting processes. Food that has been improperly stored and reheated has been proved to carry cholera. In Africa, cooked rice in Guinea, millet gruel in Mali, and pigeon peas in Malawi have been discovered.

Limitation and Strength
The analysis has many advantages: To begin, we used a pre-specified protocol for search and data extraction, as well as a quality evaluation of two independent investigators to reduce assessor bias. The pooled estimate was then subjected to sensitivity analysis to assess its robustness. Nevertheless, our systematic review and meta-analysis have some shortcomings: First, subgroup analysis revealed no substantial difference in heterogeneity compared to the overall outcome.

Practices Implication
Periodic surveillance commitments necessitate disaggregated data, which would be made available weekly or monthly from local settings, to provide analytical data for the cholera control roadmap. Since most cholera outbreaks are periodic, the existence of cholera can provide annual windows of opportunity for regulatory cholera preparedness activities. Surveys are necessary to establish the effec-tiveness of intervention in Sub-Saharan Africa and the mode and study selection. There were no variations in terms of other outcomes when comparing the safety and effectiveness of different ranges of ORS for treating dehydration due to cholera. We suggest that mothers have adequate sanitation and water quality knowledge, diarrheal complications such as dehydration be recognized early, and oral rehydration solution (ORS) be used immediately at home. These are useful in the treatment and prevention of cholera and its complications. Mothers' healthy feeding habits for young children will help reduce more than 10% of childhood diarrheal mortality. Furthermore, good hygienic practices, especially proper hand washing and waste disposal, may help reduce the prevalence of cholera.

Conclusion
In Sub-Saharan Africa, a novel behavioral change and these techniques are the last line of protection in improving general wellbeing or health by reducing the burden of cholera disease. The cost-effectiveness of the available approaches must be examined. Improved water, sanitation, and hygiene systems and the use of OCVs can help prevent cholera transmission. Analytical data for the cholera control roadmap provides periodic surveillance commitments that necessitate disaggregated data, which would be made available weekly or monthly from local settings. Since cholera outbreaks are usually seasonal, the regulatory community should plan for cholera preparedness measures annually.