Magnitude of Antibody Cross-Reactivity in Medically Important Mosquito-Borne Flaviviruses: A Systematic Review.

INTRODUCTION: Flaviviruses are a genus of enveloped single-stranded RNA viruses that include dengue virus (DENV), yellow fever virus, West Nile virus (WNV), Japanese encephalitis virus, and Zika virus. Nowadays, diverse serological assays are available to diagnose flaviviruses. However, infection with flaviviruses induces cross-reactive antibodies, which are a challenge for serological diagnosis. OBJECTIVE: This systematic review aimed to assess the magnitude of medically important mosquito-borne flavivirus-induced antibody cross-reactivity and its influence on serological test outcomes. METHODS: This study was designed based on the PRISMA guidelines. It includes original research articles published between 1994 and 2019 that reported serological cross-reactions between medically important mosquito-borne flaviviruses. Articles were searched on PubMed using controlled vocabulary. Eligibility was assessed by title, abstract, and finally by reading the full paper. The articles included are compared, evaluated, and summarized narratively. RESULTS: A total of 2,911 articles were identified, and finally 14 were included. About 15.4%-84% of antibodies produced against non-DENV flaviviruses were cross-reactive with DENV on different assays. Up to 30% IgM and up to 60% IgG antibodies produced against non-WNV flaviviruses were cross-reactive with WNV on EIA assays. The magnitude of antibodies produced against flaviviruses that are cross-reactive with chikungunya virus (Alphavirus) was minimal (only about 7%). The highest antibody cross-reactivity of flaviviruses was reported in IgG-based assays compared to IgM-based assays and assays based on E-specific immunoglobulin compared to NS1-specific immunoglobulin. It was found that preexisting immunity due to vaccination or prior flavivirus exposure to antigenetically related species enhanced the cross-reactive antibody titer. CONCLUSION: This review found the highest cross-reaction between DENV and non-DENV flaviviruses, especially yellow fever virus, and the least between chikungunya virus and DENV. Moreover, cross-reaction was higher on IgG assays than IgM ones and assays based on Eprotein compared to NS1protein. This implies that the reliability of serological test results in areas where more than one flavivirus exists is questionable. Therefore, interpretation of the existing serological assays should be undertaken with a great caution. Furthermore, research on novel diagnostic signatures for differential diagnosis of flaviviruses is needed.

Seroprevalence of Yellow fever, Chikungunya, and Zika virus at a community level in the Gambella Region, South West Ethiopia.

Yellow fever (YF), Chikungunya (CHIK), and Zika(ZIK) are among re-emerging arboviral diseases of major public health concern. Despite the proximity of the Gambella Region to South Sudan where arboviral cases have been recorded repeatedly the current epidemiological situation is unclear in this part of southwest Ethiopia. Therefore, we conducted a community-based seroprevalence survey of YF virus (YFV), CHIK virus (CHIKV), and ZIK virus (ZIKV) infections in two selected districts. A cross-sectional study was conducted in two locations of the Gambella region (Lare and Itang) to investigate the seroprevalence of these viruses' infections. Blood samples were collected from the study participants and screened for IgG antibodies specific to YFV and CHIKV infections using enzyme-linked immunosorbent assays (ELISA). For the detection of ZIKV specific IgG antibodies, Blockade-of-binding ELISA was used. Data were analyzed using the STATA version 13.1 Softwares. A total of 150 individuals (96 males and 54 females, age ranging from 18 to 65 years, mean age ± SD = 35.92 ± 10.99) participated and provided blood samples. Among the 150 samples 135, 90, and 150 were screened for YFV, CHIKV, and ZIKV, respectively. Hence, 2.9% (95% CI: 1.1-7.7%), 15.6% (95% CI: 9.3-24.8%), and 27.3% (95% CI: 20.7-35.3%) of samples tested positive for IgG antibodies to YFV, CHIKV, and ZIKV infections, respectively. Among the individual seropositive for ZIKV, YFV and CHIKV, only six, one and three had a history of residence outside the Gambella region respectively. Agro-pastoral occupation was significantly associated with a higher prevalence of IgG against CHIKV (AOR = 14.17; 95%CI: 2.30, 87.30) and residency in the Lare district (AOR = 11; 95%CI: 3.31, 39.81) was found to be significantly associated with a higher prevalence of IgG against ZIKV. Our findings revealed the occurrence of YFV, CHIKV and ZIKV infections in the study locations.

Sero-prevalence of West Nile virus and Rift Valley fever virus infections among cattle under extensive production system in South Omo area, southern Ethiopia.

West Nile fever (WNF) and Rift Valley fever (RVF) are emerging and re-emerging zoonotic diseases of veterinary and public health importance in Africa. Despite the existence of potential vectors and a wide range of hosts, the transmission of these diseases in domestic animals has not been well documented in the South Omo area of Ethiopia. This study aimed to estimate the sero-prevalence of IgG antibodies produced against West Nile virus (WNV) and Rift Valley fever virus (RVFV) infections among cattle in the South Omo area. Between May and June 2019, blood samples were collected from 397 cattle and screened for IgG antibodies against WNV and RVFV infections using enzyme-linked immunosorbent assay (ELISA). The overall sero-prevalence of IgG antibody to WNV infection was 4.8% (95% CI: 2.67-6.88%), while it was 5.0% to RVFV infection (95% CI: 2.87-7.18). Compared to 1-3 years old cattle, those in the age group ≥ 7 years had significantly higher odds of being positive for WNV (AOR = 6.82; 95% CI: 1.72-26.99) and RVFV (AOR = 4.38; 95% CI: 1.08-17.88) infections. The occurrence of WNV and RVFV infections in cattle population in the present study area indicates the risk of transmission to humans. Strengthening the surveillance system and conducting further studies to identify active cases in domestic and wild animals as well as in humans is crucial to reduce the risk of possible outbreaks.

Seroprevalence of Rift Valley Fever and West Nile Fever in Cattle in Gambella Region, South West Ethiopia.

INTRODUCTION: Rift Valley fever (RVF) and West Nile fever (WNF) are re-emerging mosquito-borne zoonotic diseases that cause public health and economic crises. Ethiopia shares borders with South Sudan and Kenya, where these diseases are often documented. The free movement of animals and humans across these borders expects to increase the spread of these diseases. The current study was conducted to assess the occurrence of these diseases in the Gambella region of Ethiopia. METHODOLOGY: We collected a total of 368 cattle serum samples from the Lare district on the border of South Sudan and measured the presence of IgG antibody against RVF and WNF virus infections using enzyme-linked immunosorbent assays (ELISA). RESULTS: The prevalence of anti-RVF virus IgG antibody was 7.6% (95% CI: 5.3-10.82%), while that of anti-WNF virus IgG antibody was 5.4% (95% CI: 3.52-8.29%). In this study higher seroprevalence of IgG antibodies to RVF virus infection was observed comparing to the WNF virus in cattle. There was no significant association between the prevalence and the cattle age, sex or sampled locations. CONCLUSION: The detection of IgG antibody to RVF and WNF virus infections in the Gambella region warrants further study of active case findings and the dynamics of transmission.

Community-based sero-prevalence of chikungunya and yellow fever in the South Omo Valley of Southern Ethiopia.

BACKGROUND: Chikungunya (CHIK) and yellow fever (YF) are becoming major public health threats in East African countries including Ethiopia. In Ethiopia, there is no reliable information about the epidemiology of CHIK. This study aimed to assess a community-based sero-prevalence of CHIK and YF in the South Omo Valley, an endemic area for YF. METHODS: Between February and June 2018, blood samples were collected from study participants and screened for IgG antibody against CHIK virus (CHIKV) and YF virus (YFV) infections using ELISA. Data were computerized using Epi Data Software v.3.1 and analyzed using SPSS. RESULTS: A total of 360 participants (51.7% males, age range from 6 to 80, mean age ± SD = 31.95 ± 14.05 years) participated in this study. The overall sero-prevalence of IgG antibody was 43.6% (157/360) against CHIKV, while it was 49.5% (155/313) against YFV. Out of 155 samples which were positive for IgG antibody to YFV, 93 (60.0%) were positive for IgG antibody to CHIKV. Out of 158 samples which were negative for IgG antibody to YFV, 64(40.5%) were positive for IgG antibody to CHIKV. There was a significant positive correlation between IgG antibodies to CHIKV and YFV (sr = 0.82; P<0.01). Residency in the Debub Ari district (AOR = 8.47; 95% CI: 1.50, 47.74) and travel history to sylvatic areas (AOR = 2.21; 95% CI: 1.02, 4.81) were significantly and positively associated with high sero-prevalence of IgG antibody to CHIKV and YFV, respectively. CONCLUSION: High sero-prevalence of IgG antibody to CHIKV shows the circulation of the virus in the present study area. A low sero-prevalence of IgG antibody to YFV in YF vaccine received individuals is highly concerning from a public health point of view as waning of immune response to YFV infection could result in a periodic outbreaks of YF in endemic areas.Nevertheless, the present study has not investigated for possible cross-reactivity of antibody to CHIKV with other alphaviruses like O'nyong-nyong virus and antibody to YFV with other flaviviruses like Dengue fever virus and this warrants further studies in the present study area.

Knowledge, Attitude, and Practice of Jinka University Students About Yellow Fever, Ethiopia: A Cross-Sectional Study.

BACKGROUND: Yellow fever (YF) is endemic in South Omo area of Ethiopia. Although Jinka University (JKU) is located in South Omo Zone, there is no information regarding the level of knowledge, attitude, and practice of students toward YF. The current study aimed to assess knowledge, attitude, and practice of JKU students toward YF and factors associated with the overall knowledge and attitude about the disease. METHODS: In this cross-sectional study, a semi-structured self-administered questionnaire was used to collect data from randomly selected regular program JNU students. Data were analyzed using SPSS. Bivariate and multivariable logistic regression analyses were performed to investigate associations of socio-demographic factors with overall knowledge and attitude scores. RESULTS: A total of 322 students (61.2% males, mean age of 20.7 years) participated in this study. Of these, 94.1% joined the University from places other than South Omo area and 86.0% (277/322) ever heard about YF. 9.6% were found to have a high level of overall knowledge about YF. High overall knowledge of YF was associated with being born and grown up in South Omo area (AOR=3.91; 95% CI: 1.28, 11.98) and being a student of a social science discipline (AOR=3.52; 95% CI: 1.22, 10.13). 48.8% of the participants had favorable overall attitude toward YF. Being a second-year student (AOR=1.96; 95% CI: 1.14-3.37), being born and grown up in South Omo area (AOR=5.13; 95% CI: 1.32-19.98), and having high overall knowledge of YF (AOR=13.24; 95% CI: 3.69, 47.44) were associated with favorable overall attitude toward YF. On the other hand, only 5.8% of the participants reported that they were vaccinated for YF. CONCLUSION: The low level of knowledge and low vaccination coverage of JKU students to YF, especially among those students from other parts of the country, calls for urgent awareness creation during admission and making vaccination available.

Community knowledge, attitudes and practices on Yellow fever in South Omo area, Southern Ethiopia.

BACKGROUND: Yellow fever (Yf) outbreak was recently reported in South Omo of Southern Ethiopia. This area was also highly affected by Yf outbreak in the 1960s. However, there is no reliable information on the level of community knowledge attitudes and practices about the disease in the area. The objective of the current study was to assess level of community knowledge, attitudes and practices about Yf. METHODS: Between March and May 2017, a community-based cross-sectional survey was conducted in two districts of the South Omo area. During the survey, 612 randomly selected adults were interviewed about Yf using structured questionnaire. RESULTS: Out of the 612 study participants, 508 (83.0%) reported that they heard about Yf which is locally known as "a disease that causes vomiting blood". Most (90.4%) of the study participants also said that Yf is different from malaria. Two hundred thirteen (41.9%) participants said that Yf can be transmitted from a patient to another person, while only 80 (37.6%) mentioned that the disease is transmitted through mosquitoes bite. Out of 333 (65.7%) study participants who believed that Yf is a preventable disease, 280 (84.1%) mentioned vaccine as a preventive method. The majority believed that the disease is a killer (97.2%) and a newly emerging (69.4%). Among the total of 612 study participants, 221(36.1%) were considered as having a high level of overall knowledge of Yf. Having educational level above 7th grade (AOR = 3.25, 95% CI: 1.39, 7.57, p = 0.006) and being resident of Bena-Tsemay district (AOR = 1.77, 95% CI: 1.12, 2.78, P = 0.014) were significantly associated with having a high level of overall knowledge of Yf. Agro-pastoralism as an occupation compared to farming was associated with having a low level of overall knowledge of Yf (AOR = 0.51, 95% CI, 0.33, 0.79, P = 0.003). CONCLUSION: The findings indicate that most of the study community members had a low level of overall knowledge of Yf, especially about its cause, mode of transmission and preventive methods. Thus, there is a need to increase people's knowledge and practices regarding the cause, mode of transmission and preventive methods like avoiding mosquitoe breeding sites beside vaccination through various strategies like disseminating information through community health extension workers and community leaders in the study area.

Paramedical staffs knowledge and attitudes towards antimicrobial resistance in Dire Dawa, Ethiopia: a cross sectional study.

BACKGROUND: The continuing emergence, development and spread of pathogenic organisms that are resistant to antimicrobials are a cause of increasing concern. The control of antimicrobial resistance requires knowledge of factors causing antimicrobial resistance, good attitudes towards the intervention strategies as well as changes in antibiotic prescribing behavior of health workers. Hence, this study was aimed to assess paramedical staffs' knowledge and attitudes towards antimicrobial resistance and their antibiotics prescription practices in Dire Dawa, Ethiopia. METHODS: A cross-sectional survey was conducted among paramedical staffs working in hospitals and health centers. A total of 218 paramedical staffs were participated and a self-administered questionnaire was used to collect data. Data was analyzed using SPSS version 20. Chi square/Fisher's exact tests were used for comparison of data and a p value of less than 0.05 was considered statistically significant. RESULTS: Out of the total, 137 (62.8%) of paramedical staffs had good knowledge on the factors causing antimicrobial resistance. The most common causes of antimicrobial resistance reported were patients' poor adherence (96.5%), self prescription (95%), and empiric choice of antibiotics (94.5%). In general, more than 80% of the respondents had positive attitudes towards the antimicrobials resistance intervention strategies. Relatively less proportion of participants recognized that antimicrobial resistance as a problem in their local institutions. The most perceived driving forces for unnecessary antibiotics prescriptions were treatment failure (67.7%) and patient push (53.3%). The majority, 76.9% of the prescribers mentioned that standard treatment guidelines were available in their institutions though only 15.7% of them reported referring the guidelines on the daily basis. Among the prescribers, 85.8% never attended formal trainings on antibiotics prescriptions. CONCLUSIONS: As this study generated important information on knowledge and attitudes of paramedical staffs about antimicrobial resistance, it identified areas of misconceptions and specific groups to be targeted for educational interventions regarding antimicrobial resistance. It is, therefore, suggested that a well-planned, organized and structured training programs should be undertaken to improve the appropriate use of antibiotics.

Predictors of compliance with community-directed treatment with ivermectin for onchocerciasis control in Kabo area, southwestern Ethiopia.

BACKGROUND: Compliance with annual ivermectin treatment is a major challenge in community-directed treatment with ivermectin (CDTI) implementation. There are individuals who do not comply with the annual mass treatment, which contributes to the continuity for disease transmission. Hence, ensuring high treatment coverage and sustained compliance should be given due emphasis in the control of onchocerciasis. The aim of this study was to determine CDTI compliance rate and predictors of compliance where the CDTI was in its 9(th) round in Kabo area, southwestern Ethiopia. METHODS: Community-based cross-sectional study was conducted in Kabo area, three weeks after the 9th round of annual ivermectin distribution. Systematic random sampling was used to select head of households and structured, pre-tested questionnaire was used to interview the study participants. Data was analyzed using SPSS version 16. Descriptive statistics was used to compute mean and standard deviation of continuous variables and frequency for categorical variables, while bivariate and multivariate logistic regressions were used to assess the effects of independent variables on the outcome variable. Variables which showed association in multivariate analysis were considered as final predictors of compliance and strength of association was measured through adjusted odds ratio (AOR). RESULTS: A total of 308 respondents (age range 18-70, mean age ± SD, 32.21 ± 9.64) participated in the study. Of these, 249 (80.8%) reported that they took ivermectin during the 9th round annual treatment. Significantly higher rate of treatment compliance was reported by participants age ≥35 years (AOR = 5.48, 95% CI; 1.97 - 15.23), participants who stayed in the area for more than ten years (AOR = 3.86, 95% CI; 1.83- 8.11), participants who perceive that they are at risk of contracting the disease(AOR = 7.05, 2.70- 18.43), participants who perceive community drug distributors (CDDs) are doing their work well (AOR = 2.35 95% CI; 1.15- 4.83) and participants who know at least one CDD in their village (AOR = 2.83, 95% CI; 1.26- 6.40). CONCLUSION: The majority of the study participants in the present study area complied with ivermectin treatment. Nevertheless, intervention packages should consider factors such as age, residence duration and community's perception of the disease to improve compliance and make drug distribution sustainable.