Prevalence of Lumpy Skin Disease in Africa: A Systematic Review and Meta-Analysis from 2007 to 2023

Background Lumpy skin disease (LSD) is an economically important, transboundary viral disease of cattle caused by LSD virus. This systematic review and meta-analysis are concerned with summarizing the status of lumpy skin disease in Africa. Methods Literature searches between 2007 and 2023 were conducted using different database searches: Google, Google Scholar, PubMed, and Science Direct, and then the required information were extracted. A random effect model was used to pool estimates of prevalence at 95% CI. Publication bias was assessed by applying funnel plots. Results The pooled estimated prevalence of LSD was 54% (95% CI: −0.09–1.18), with individual study prevalence ranging from 6 to 89%. Subgroup analysis showed that the random pooled prevalence of LSD was 28% (95% CI: −1.48–2.03) in Ethiopia, 37% (95% CI: −3.79–4.52) in Uganda, 88% (95% CI: −0.11–1.28) in Zimbabwe, and 58% (95% CI: −6.96–8.72) in Egypt. No single study was documented from western and northern Africa. Conclusion The estimated pooled LSD prevalence was investigated as high and indicated nonsignificant variation among study countries. Thus, vaccination of cattle, quarantine, and biting insect control should be applied to control the disease.


Introduction
Lumpy skin disease (LSD) is an economically important, transboundary viral disease of cattle caused by LSD virus or prototype strain of Neethling virus in the genus Capripoxvirus, family Poxviridae [1,2].Lumpy skin disease viruses (LSDVs) have deoxyribose nucleic acid (DNA) of about 151 kb in size, consists of a central coding region connected by 2.4 kb similar inverted terminal repeats, and contains 156 putative genes [3,4].Te hosts of LSDV are cattle and bufalo.Te transmission occurs mechanically via bloodfeeding insects or fies such as Stomoxys calcitrans and Biomyia fasciata [5,6].Rhipicephalus appendiculatus ticks can also transmit mechanically LSDV [7].Warm humid agro-climate, watering, and introduction of new animals in a herd are risk factors for the spread of LSDV [8].Rainy seasons and cow grazing along water areas lead to outbreaks of LSD.Te herd size and low immunity were linked to the development of disease [9].Te temporal pattern of LSD disease occurrence can be explained with short-term, cyclical seasonal, and long-term trends [10].LSD was announced for the frst time in Zambia in 1929 [11][12][13].It was described at the time due to its panzootic occurrence in Botswana, Zimbabwe, and the Republic of South Africa in 1943 and 1945 [14,15].Te distribution of LSDV has reached from sub-Saharan countries to Egypt, and Western Africa [14].It occurred in Kenya and was associated with an outbreak of sheep pox in 1957 [4,8,16].LSDV was frst indicated in Nigeria in 1974 and 1976 [17].LSD was frst explained in Egypt at the Suez and Ismailia provinces in May 1989 due to imported cattle from Africa [2,5,18].LSD was reported for the frst time in 1983 in the western part of Ethiopia.It has now spread to all regions and agro-climatic zones in the country [14,19].Te frst appearance of LSD outside Africa was reported in Kuwait in 1986 [16].LSDV infection had been reported in Saudi Arabia in 1992 [20].LSDV has spread since 2000 to the Middle East countries including Iran, Syria, and Israel [19].In European countries, many outbreaks have been reported recently: in Croatia in 2016, the Balkan Area, Serbia in 2016, and Greece in 2015 [21].
LSD can be found in acute, subacute, or chronic forms with varying severity depending on the host breed and immunity of the host [13,22].LSD is identifed by fever, nodular eruption all over the body, keratitis, conjunctivitis, and enlarged superfcial lymph nodes [19,23].Diagnosis of LSDV is carried out based on clinical signs, virus neutralization test (VNT), indirect fuorescent antibody test (IFAT), virus isolation, and molecular techniques [1,9].IFAT has good sensitivity, but some rarely occurring Parapox and Orthopox virus antibodies may cross-react and infuence its specifcity during low serum dilution [14,24].Te VNT is used mostly for detecting Capripox-specifc antibodies.It has high specifcity, which is useful to exclude false positives, but its sensitivity may be lower [9,14].Terefore, the most suggestive method for identifying such viruses is the polymerase chain reaction (PCR) technique [25].Most of the molecular methods target Gprotein-coupled chemokine receptor (GPCR), P32, and RPO30 genes to distinguish and characterize LSDV and other Capri poxviruses.Te GPCR gene is a suitable target for genetic identifcation between Capripoxviruses [19,26].Te economic signifcance of LSD concerns production losses [14,27].LSD afects the African country's growth by causing decreases in milk yield, loss of draught power from lameness, abortion, and infertility in cows [22,25].Milk yield can be reduced by > 50% in infected herds and secondary infections can lead to mastitis.LSD can cause skin lesions and result in permanent scars on the hide, decreasing its value [7,28].LSD has low mortality <10% and varying morbidity [19,29].Te morbidity and mortality of LSD vary considerably, depending on the type of breed, immunological status of the host, and the insect vectors [19,25].
Te control and prevention strategies for LSD include livestock movement controls, vaccination, vector control, quarantines, and the slaughter of infected and exposed animals [17,25].Vaccination is an appropriate strategy for preventing LSD [6,20,25].Several live-attenuated capripoxvirus (CaPV) vaccine strains including the Neethling strain of LSDV, Kenyan sheep pox viruses (SPPV) and goat pox viruses (GTPV), Yugoslavian strain of SPPV, Romanian strain of SPPV, and Gorgan strain of GTPV are practiced for the prevention and control of LSD [1,20].LSD has been reported in diferent African countries with various prevalence rates due to the availability of warm humid agroclimate, watering, and the presence of vector and introduction of new animals in a herd as risk factors for the spread of LSDV [19,28].However, there has been no systematic review and pooled quantitative presentation of the status of LSD in Africa, which are essential in making strategies for preventing and controlling LSD to decrease its prevalence.Terefore, the objective of this systematic review and meta-analysis will be to determine the pooled prevalence of LSD in cattle in Africa.

Study Protocols.
Tis systematic review and metaanalysis study was done by observing the PRISMA guideline [21].Te PRISMA checklist indicates the inclusion criteria for relevant information to this study.Te objective of this study is to estimate the pooled prevalence of LSD in Africa.Te study protocol had been registered on PROS-PERO with reference number ID: CRD513988 and is available from: https://www.crd.york.ac.uk/ID=CRD513988.

Selection of Studies.
Te database search was carried out by using Science Direct, Scopus, Google Scholar, and PubMed/PubMed Central until June 29, 2023.Te article search was done by using scientifc terms.Te keywords were "Lumpy Skin Disease" or "LSD," "Sero-prevalence" or "Prevalence," "Cattle" or "Bovine," and "Africa."We used "or" and "Boolean operators to identify studies with any of the keywords in their titles, abstracts, and full texts."

Eligibility Criteria.
Te inclusion criteria to assure the eligibility of the searched articles includes: (1) research articles published in a reputable journal, which were conducted in Africa; (2) retrospective, prospective, and crosssectional studies that presented the prevalence of LSD with endemic or outbreak occurrence; (3) articles with full information; (4) studies were carried out by using ELISA, IFAT, PCR, VNT, and SNT; (5) studies explained the total sample size and number of positive samples; (6) articles published in the English language, and (7) Articles published between 2007 and June 29, 2023.Articles that did not meet the above criteria were excluded.

Selection of Study and Data Extraction.
Articles collected from diferent databases were exported to Mendeley software version 1.19.Repeated documents were identifed and removed with Mendeley.Te authors screened the titles and abstracts based on the predefned inclusion criteria.Similarly, the data extraction format was carried out concerning author, publication year, study year, study country, study design, disease occurrences, total sample, diagnostic test, and positive samples, individual-level prevalence.
Te efect size and confdence intervals were calculated from the extracted data.Mendeley version 1.19.8 was used to manage citations.Microsoft Excel was used to code and manage all extracted data.2.5.Quality Assessment.Independent researchers assessed the quality of the included articles using an assessment checklist.Te checklist contained items assessing objectives and the methods parts (study design, sample size, disease occurrence, and statistical methods).

Statistical Analysis.
Te random-efects model metaanalysis was used to estimate the pooled prevalence of LSD at 95% CI [10,30].Heterogeneity (I 2 ) among studies were evaluated.Te I 2 values of 25, 50, and 75% were classifed as low, moderate, and high heterogeneity [15].Te I 2 values (0%) tell us the absence of heterogeneity [15].Subgroup analysis was calculated associated with country, study design, disease occurrence, and type of diagnostic method.

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Veterinary Medicine International Publication bias was evaluated using Begg and Egger's test [11] and by observing the funnel plot.Heterogeneity among studies also was evaluated using meta-regression.Country, study design, disease occurrence, event, and sample were evaluated by using multivariable meta-regression analysis.All statistical analyses were performed by using Stata/ MP 17.0.

Descriptive Results.
Among the 188 studies that were assembled, 16 articles met the inclusion criteria (Figure 1).Te total sample size was 10090, and 1874 were identifed as positive cases for the LSD virus.Te pooled prevalence of LSD was 54% (95% CI: −0.09-1.18).Te largest sample size is 2368 while the smallest sample size is 20 (Table 1).Te LSD was identifed in Egypt, Ethiopia, Uganda, and Zimbabwe.

Meta-Analysis.
Te pooled estimated prevalence of LSD in Africa was 54% (95% CI: −0.09-1.18).Te individual studies prevalence were ranged from 6.4 to 100%.Studies were approximately weighted nearly equal with an individual weight ranging from 1.17 to 10.49%.Te forest plot describes the pooled prevalence of LSD in Africa as shown in Figure 2.

Subgroup Meta-Analysis.
A subgroup meta-analysis was calculated for the country, disease occurrence, study design, and diagnostic methods (Figure 3).Te sub-total estimated pooled prevalence of LSD by disease occurrence was 43.6% (95% CI: −0.364-1.236) in the endemic area and 71.9% (95% CI: −0.324-1.761) in the outbreak condition (  Veterinary Medicine International 4 Veterinary Medicine International methods were applied for the examination of the LSD virus of which PCR was mostly applied having pooled prevalence at 72.6% (95% CI: −0.604-2.055).

Meta-Regression.
Country, study design, disease occurrence, event, and sample were evaluated by using meta-regression analysis.None of the above variables was signifcantly related to the prevalence of LSD during multivariable meta-regression analysis (Table 3).

Publication Bias.
Tere is a publication bias for the prevalence of LSD based on the analysis of efect sizes against standard errors.So, the funnel plot indicated that there are asymmetry patterns in studies assessing the presence of publication bias (Figure 4).

Discussion
Tis type of systematic review and meta-analysis has not been done on the prevalence of LSD in Africa until now.Te results illustrated in this meta-analysis were from studies of LSD prevalence at diferent country levels between the years 2007 and 2023.
Te meta-analysis of the pooled prevalence of LSD was estimated by using sixteen articles, which were published in diferent African countries.Among them, eight records were from Egypt, fve from Ethiopia, two from Uganda, and one from Zimbabwe.Relatively higher studies were from Egypt.On the other hand, lower studies were from Uganda and Zimbabwe.Among the number of studies conducted, the cross-sectional study design type was used at the highest rate with a pooled prevalence of ffty-four percent (Table 2).Retrospective study designs were used at a lower rate with an efect size of eight percent.Most studies indicated that the LSD disease occurrence was due to endemic with a pooled prevalence of forty-four percent.Diferent types of diagnostic techniques were applied for LSD detection in this meta-analysis from which PCR was used at the highest rate and SNT, IFAT, and RT-PCR were used at the lowest rate.
LSD may be introduced to diferent countries by the movement of infected animals, biting insects that have fed on infected cattle, and importation of contaminated hides.
Te random-efects model meta-analysis illustrated that there is no signifcant diference among studies with heterogeneity (I 2 ), which tells us the existence of the LSD virus in diferent countries due to the movement of biting insects.Even though there was considerable homogeneity among        Veterinary Medicine International studies, the weight of studies was not nearly equal.No variables, that were presented in the meta-regression, were statistically signifcant in describing the study's homogeneity.
Tere is a higher prevalence of LSD in and Egypt while the lowest prevalence of LSD is in Ethiopia and Uganda (Figure 5).Te pooled prevalence of LSD at all country level is 54%.Te prevalence of LSD difers signifcantly among countries, which might be presented by the number of articles.Tis signifcant variation in the prevalence of LSD among African countries are based on the following reason: the availability of warm humid agro-climate, rainy season immunological status of the host, and the presence of vector and introduction of new animals in a herd as risk factors for the spread of LSDV [28,30,31].Type of diagnostic method used, study design, disease occurrence and the number of studies reported are also the other the main determinant.Based on the current fndings, LSD studies have been mostly done in Egypt [16,20,26].In addition to this, a higher number of articles were documented in Ethiopia [14,18].A higher number of reports were presented from Egypt; the lowest prevalence was documented in Ethiopia.Te highest prevalence of LSD was indicated in Zimbabwe.On the opposite side, no study was carried out from the western and northern parts of Africa.
Tere is a publication bias for the prevalence of LSD based on the analysis of efect sizes against standard errors (Figure 4).Tis review is an indicator of more task requirements for LSD studies in Africa.LSD afects the country's growth by causing decreases in milk yield, loss of draught power from lameness, abortion, and infertility in cows [10,25,29].Milk yield can be reduced by > 50% in infected herds and secondary infections [14,30,31].

Limitations of the Study.
A few numbers of published articles were selected from the countries involved in this study, and published articles from the North Africa and West Africa countries were not included about the prevalence of LSD in Africa.

Conclusions
Tis type of systematic review and meta-analysis has not been done on the prevalence of LSD in Africa until now.It indicated the existence of a high-pooled prevalence of LSD in Africa, and this disease had indicated nonsignifcant variation among study countries.A higher number of reports were registered in Egypt and Ethiopia.Te number of studies is limited about the prevalence of LSDV in Africa.Terefore, a further investigation had better to be carried out for LSD.Special strategies and policies are needed from each country's responsible bodies concerning Introduction of new cattle, the vaccination of cattle, and biting insects controlling to reduce the risk of LSD transmissions.

Figure 1 :
Figure 1: PRISMA 2020 fow diagram of the selection of eligible studies for quantitative analysis.

Figure 2 :
Figure 2: Forest plot illustrating the estimated pooled prevalence of LSD in Africa in diferent studies from 2007 to 2023.

Figure 4 :
Figure 4: A funnel plot was used to illustrate the presence of publication bias in diferent studies.

Figure 5 :
Figure 5: Pooled countries with the highest and lowest prevalence of LSD in Africa.

Table 1 :
Summary of metadata of LSD from 2007 to 2023 published studies in Africa.
RT-PCR means real-time PCR; c PCR means conventional PCR.

Table 2 :
Subgroup meta-analysis was done in diferent variables like country, study design, disease occurrence, and type of diagnostic method.

Table 3 :
Multivariable meta-regression analysis was calculated in diferent variables.