Patients infected with JE typically show nonspecific febrile fever, including diarrhoea, coryza, and rigors after a few days of infection. This can be followed by headache, vomiting, and low levels of unconsciousness, especially in older children and adults; inappropriate behavior may be the only presenting symptom of mental disease, leading to an initial diagnosis. Other patients manifest aseptic meningitis without encephalopathy symptoms. As mentioned in the previous response, reports indicate that as many as 85% of adults with Japanese encephalitis have experienced convulsions [16]. Furthermore, some subgroups of individuals infected with Japanese encephalitis virus who exhibited acute flaccid paralysis resembled poliomyelitis. Here, following a long session of febrile fever, the patient suddenly acquired flaccid paralysis in one or more limbs. The legs were typically affected first, followed by the arms, and the weakness was typically asymmetrical[17]. Similarly, there are many clinical features assisted to diagnose the disease and help it to prevent severe condition. Here, 29 studies were analysed to determine which clinical characteristics are most strongly associated with the ability to predict the disease.
3.2. Characteristics of the studies
The majority of included studies were conducted on a national scale, and the duration of data collection was between 4 and 5 years. The selected studies contains clinical factor those are associated with JE and their outcomes. Only a few studies shown that genetic factors were also connected with clinical predictors, and that the level of existence of these predictors affected the individuals and their diagnosis. A total of 38 studies were chosen, with n = 13 from India, n = 5 from Taiwan, n = 9 from China, n = 5 from Thailand, n = 1 from Malaysia, n = 1 from Laos, n = 2 from Bali, Bangladesh, n = 1, japan n = 1 Nepal, and, n = 1 from South Korea. This constituted 1062 female patients, 3239 males where 14 studies included children and adults both while 5 studies included only adults, and 14 studies included only children. The clinical predictors and their results were able to be accessed in the majority of the investigations. Sociodemographic data with clinical predictors include headache, vomiting, fever, seizures, stiff neck, muscle tone, parkinsonism, limb weakness/paralysis, diarrhoea, meningitis irritation, coma, confusion, IgM and IgG antibody presence in CSF and serum were observed in the selected studies[9, 12, 18–27]. Moreover, remaining studies were cited in the meta-analysis. According to the findings of these studies, the most important clinical variables were fever that include 22 studies, 21 of the studies reported headaches, 18 of the studies reported vomiting, 26 of the studies reported seizures, 14 of the studies reported stiff neck, 7 of the studies reported muscle tone rigidity, 4 of the studies showed parkinsonism, 10 of the studies reported coma, 6 of the studies reported limb weakness, 4 studies showed altered sensorium, and 3 of the studies reported diarrhoea. Furthermore, 12 reports showed IgM and IgG antibody presence in serum and CSF to diagnose the JE cases, neurological sequelae observed in 3 studies, 2 studies observed stroke in severe condition, 2 studies showed the data of co-morbidity that include diabetes, coronary heart disease, hypertension, and 3 studies showed meningitis irritation.
3.4. Clinical predictors
Fever: Here, seventeen (17) studies were analysed to understand the relationship between fever and JE[13, 15, 28–42]. The meta-analysis was performed using random model in RevMan 5.4.1, the generated outcome for fever were shown in Fig. 3(a), that include odd ratio 6.64 [2.25, 19.58] Heterogeneity: Tau2 = 4.02; Chi2 = 429.25, df = 15 (P < 0.00001); I2 = 97%, and overall effect: Z = 3.43 (P = 0.0006). The odd ratio values showed positive correlation between fever and JE, The value 6.64 represents the point estimate of the effect size, while the interval of 2.25 to 19.58 reflects the 95% confidence interval adjacent the value. The analysis suggests that there is a significant association between fever and Japanese encephalitis, with an overall odds ratio of 6.64 (95% confidence interval: 2.25–19.58). This indicates that individuals with fever are over six times more likely to have Japanese encephalitis than those without fever. Tau2 = 4.02 and Chi2 = 429.25 (df = 15, P 0.00001) show that there is a lot of difference between the studies that were included. Moreover, the overall effect Z = 3.43 (P = 0.0006) indicated a significant relation between fever and JE. It was also observed that all JE-infected patients had fever.
Headache: Seventeen studies were analysed to understand the relationship between headache and JE[13, 15, 28–34, 36, 37, 39–44]. The meta-analysis was performed using random model in RevMan 5.4.1, the generated outcome for fever were shown in Fig. 3(b) that include odd ratio 1.25 [0.74, 2.12] there is a positive relationship between headache and JE, with an overall effect size of 1.25 (95% confidence interval: 0.74–2.12). This indicates that individuals with headache are 1.25 times more likely to have Japanese encephalitis than those without headache. However, the wide confidence interval indicates that the effect size is not precisely estimated, and further studies are needed to confirm this relationship. Nevertheless, the analysis showed significant heterogeneity Tau2 = 0.97; Chi2 = 270.59, df = 16 (P < 0.00001); I2 = 94% that indicating substantial variability in selected studies. Moreover the overall effect: Z = 0.84 (P = 0.41) indicated no significant correlation between headache and JE. Overall, these findings suggested that further investigation with more studies may be necessary to clarify the true relationship between headache and Japanese encephalitis.
Vomiting: Fourteen studies were analysed to understand the relationship between vomiting and JE[15, 28–34, 36, 40–44]. The meta-analysis was performed using random model in RevMan 5.4.1, the generated outcome for vomiting include 0.45 [0.25, 0.79], Heterogeneity: Tau2 = 0.95; Chi2 = 142.94, df = 13 (P < 0.00001); I2 = 91% and, test for overall effect: Z = 2.75 (P = 0.006). The analysis suggests that there is a negative relationship between vomiting and JE, with an overall odd ratio of 0.45 (95% confidence interval: 0.25–0.79). This indicates that individuals with vomiting are less likely to have JE than those without vomiting. However, there is significant heterogeneity among the included studies, with a Tau2 value of 0.95 and a Chi2 value of 142.94 (df = 13, P < 0.00001), and an I2 value of 91%. This suggests that there is considerable variability among the studies in terms of their effect sizes. Moreover, the Z-score for the overall effect size is 2.75 and P-value of 0.006, indicating statistically significant relationship between vomiting and JE. Overall, the meta-analysis indicates a negative relationship between vomiting and JE, but the heterogeneity among the studies suggests that further research is needed to better understand the nature of this relationship and the factors that may contribute to the observed variability. Nonetheless, the statistically significant overall effect size suggested that vomiting may have a protective effect against JE, and this finding could be used to inform public health strategies aimed at preventing the spread of the disease.Top of Form.
Seizures: Eighteen studies were analysed to understand the relationship between seizures and JE[13, 15, 28, 30–38, 41–46]. The meta-analysis was performed using random model in RevMan 5.4.1, the generated outcome for seizures were shown in Fig. 3(d), that include 0.60 [0.33, 1.09], Heterogeneity: Tau2 = 1.41; Chi2 = 332.94, df = 17 (P < 0.00001); I2 = 95% and, test for overall effect: Z = 1.67 (P = 0.10). The analysis suggested that there may be a positive relationship between seizures and JE, with an odd ratio of 0.60 (95% confidence interval: 0.33–1.09). This indicated that individuals with seizures may be more likely to have JE than those without seizures. Since the confidence interval includes 1 the exposure must be the risk factor for the Japanese encephalitis. The heterogeneity among the included studies is significant, with a Tau2 value of 1.41 and a Chi2 value of 332.94 (df = 17, P < 0.00001), and an I2 value of 95%. This suggests that there is considerable variability among the studies in terms of their effect sizes. Moreover, the overall effect size z-value, is 1.67, with a corresponding P-value of 0.10. This showed that there is no statistically significant association between seizures and Japanese encephalitis.
Stiff neck/neck rigidity: Eleven studies were analysed to understand the relationship between stiff neck and JE[13, 15, 28, 31–33, 35, 42–45]. Here also the meta-analysis was performed using random model in in RevMan 5.4.1, the generated outcome for seizures were shown in Fig. 3(e), that include odd ratio 0.45 [0.23, 0.87], Heterogeneity: Tau2 = 1.06; Chi2 = 102.61, df = 10 (P < 0.00001); I2 = 90% and test for overall effect: Z = 2.39 (P = 0.02). The value 0.45 [0.23, 0.87], represent the odds ratio and its corresponding 95% confidence interval for the association between stiff neck and Japanese encephalitis (JE). The odd ratio suggests negative association between JE and stiff neck and confidence intervals does not include 1 that suggest exposure might be protective factor against JE. I2 = 90% suggested substantial variability in the selected studies. However, the presence of heterogeneity (Tau2 = 1.06; Chi2 = 102.61, df = 10, P < 0.00001; I2 = 90%) indicated that the studies included in the analysis were not entirely consistent in their findings. The test for overall effect (Z = 2.39, P = 0.02) suggested that there is a statistically significant relationship between stiff neck and JE.
Muscle tone: Six were analysed to understand the relationship between muscle tone and JE[13, 31, 33, 35, 42, 45]. Finally, the meta-analysis for muscle toning was performed using random model RevMan 5.4.1, the generated outcome for seizures were shown in Fig. 3(f), that include 0.66 [0.35, 1.24], Heterogeneity: Tau2 = 0.47; Chi2 = 26.92, df = 5 (P < 0.0001); I2 = 81% and, overall effect: Z = 1.30 (P = 0.19). The outcome of the odds ratio indicates a moderately positive association, and the confidence interval suggested that the exposure may act as a risk factor for JE. The I2 value of 81% indicates a significant degree of variability in the selected studies, with Tau2 of 0.47, Chi2 value of 26.92, degrees of freedom of 5, and P-value less than 0.0001. These findings showed that the differences between the studies included in the analysis may contribute to the heterogeneity of effect sizes and reflect systematic differences in their outcomes. The overall effect Z = 1.34 wit P-value 0.19 indicated there were no significant correlation between muscle tone and JE.