High Levels of Genetic Diversity within Nilo-Saharan Populations: Implications for Human Adaptation.

Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5, SNX13, TYRP1, and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.

Tick populations and molecular detection of selected tick-borne pathogens in questing ticks from northern and central Tanzania.

Ticks are vectors and reservoirs of a variety of pathogens including protozoa, bacteria and viruses which cause tick-borne diseases (TBDs) in humans and livestock. TBDs pose serious constraints to the improvement of livestock production in tropical and subtropical regions of the world. Despite their wide distribution, information on the tick and pathogen relationship is scarce in Tanzania. We used nested PCR and sequencing to screen pathogens of public and veterinary health importance in ticks collected by flagging from four districts of Tanzania. In total, 2021 ticks comprising nine species were identified. DNA from ticks was pooled according to tick species, developmental stage, and location, then screened for Babesia bigemina, Babesia bovis, Theileria parva and Coxiella burnetii. Out of 377 pools, 34.7% were positive for at least one pathogen. Theileria parva was the most abundant with a minimum infection rate (MIR) of 2.8%, followed by B. bigemina (MIR = 1.8%) and B. bovis (MIR = 0.8%). Multiple pathogens detection was observed in 7.2% of the tested pools. However, PCR screening of individual tick DNA revealed that only 0.3% of the examined pools had co-infection. DNA of C. burnetii was never detected in any tick DNA pool. The MIR of tick-borne pathogens (TBPs) differed significantly among districts, seasons, tick species, and tick developmental stages. Sequence analysis showed that B. bigemina RAP-1a, B. bovis SBP-4, and T. parva p104 genes were conserved among pathogens in the four districts. Despite the absence of C. burnetii in ticks, considering its pathogenic potential, it is essential to continue monitoring for its possible recurrence in ticks. This information adds to the knowledge of TBPs epidemiology and will contribute to the scientific basis for planning future control strategies.

Copy number variation in human genomes from three major ethno-linguistic groups in Africa.

BACKGROUND: Copy number variation is an important class of genomic variation that has been reported in 75% of the human genome. However, it is underreported in African populations. Copy number variants (CNVs) could have important impacts on disease susceptibility and environmental adaptation. To describe CNVs and their possible impacts in Africans, we sequenced genomes of 232 individuals from three major African ethno-linguistic groups: (1) Niger Congo A from Guinea and Côte d'Ivoire, (2) Niger Congo B from Uganda and the Democratic Republic of Congo and (3) Nilo-Saharans from Uganda. We used GenomeSTRiP and cn.MOPS to identify copy number variant regions (CNVRs). RESULTS: We detected 7608 CNVRs, of which 2172 were only deletions, 2384 were only insertions and 3052 had both. We detected 224 previously un-described CNVRs. The majority of novel CNVRs were present at low frequency and were not shared between populations. We tested for evidence of selection associated with CNVs and also for population structure. Signatures of selection identified previously, using SNPs from the same populations, were overrepresented in CNVRs. When CNVs were tagged with SNP haplotypes to identify SNPs that could predict the presence of CNVs, we identified haplotypes tagging 3096 CNVRs, 372 CNVRs had SNPs with evidence of selection (iHS > 3) and 222 CNVRs had both. This was more than expected (p < 0.0001) and included loci where CNVs have previously been associated with HIV, Rhesus D and preeclampsia. When integrated with 1000 Genomes CNV data, we replicated their observation of population stratification by continent but no clustering by populations within Africa, despite inclusion of Nilo-Saharans and Niger-Congo populations within our dataset. CONCLUSIONS: Novel CNVRs in the current study increase representation of African diversity in the database of genomic variants. Over-representation of CNVRs in SNP signatures of selection and an excess of SNPs that both tag CNVs and are subject to selection show that CNVs may be the actual targets of selection at some loci. However, unlike SNPs, CNVs alone do not resolve African ethno-linguistic groups. Tag haplotypes for CNVs identified may be useful in predicting African CNVs in future studies where only SNP data is available.

First genetic detection and characterization of canine parvovirus from diarrheic dogs in Zambia.

Although canine parvovirus (CPV) causes severe gastroenteritis in dogs globally, information on the molecular epidemiology of the virus is lacking in many African countries. Here, 32 fecal samples collected from diarrheic dogs in Zambia were tested for CPV infection using molecular assays. CPV was detected in 23 samples (71.9%). Genetic characterization revealed the predominance of CPV-2c (91.3%). This finding differs from previous reports in Africa, which indicated that CPV-2a and CPV-2b were most prevalent. Phylogenetically, most Zambian CPVs formed a distinct cluster. This is the first report on the molecular characterization of CPV in Zambia.

Molecular detection and characterization of genotype 1 bovine leukemia virus from beef cattle in the traditional sector in Zambia.

Whilst bovine leukemia virus (BLV) causes considerable economic losses to the dairy industry worldwide, information on its molecular epidemiology and economic impact in beef cattle is limited. Here, blood from 880 animals from Zambia's major cattle-rearing provinces was screened for BLV by nested PCR. Positive pools were sequenced and phylogenetically analyzed. The estimated pooled prevalence was 2.1%. All strains belonged to genotype 1 and formed a distinct phylogenetic cluster. The study suggests circulation of genotype 1 BLV in beef cattle in these regions. This is the first report on molecular detection and characterization of BLV from beef cattle in Africa.

Prevalence and risk factors associated with Theileria parva infection in cattle in three regions of Tanzania.

Ticks and tickborne diseases (TBDs) are serious constraints to cattle production in Tanzania and other tropical and subtropical countries. Among the TBDs, East Coast fever (ECF) is the most important as it causes significant economic losses to the cattle industry in Tanzania. However, control of ECF in Tanzania has continued to be a challenge due to inadequate epidemiological information. The main objective of this study was to determine the epidemiological situation of Theileria parva infections in cattle kept under pastoral and agro-pastoral farming systems in Mara, Singida, and Mbeya regions of Tanzania. Blood samples were collected from 648 cattle in the three regions. Genomic DNA was extracted and amplified in a polymerase chain reaction (PCR) using T. parva-specific primers targeting the 104-kD antigen (P104) gene. In addition, information was collected on the possible risk factors of T. parva infection (animal age, region, animal sex, tick burden, tick control method, and frequency of acaricide application). The prevalence of T. parva across the three regions was 14.2%. There was variation in prevalence among the three regions with Mara (21.8%) having a significantly higher (p = 0.001) prevalence than the other regions. Moreover, Mbeya exhibited relatively lower prevalence (7.4%) compared to the other regions. Factors found to be significantly associated with an animal being PCR positive for T. parva were region (p = 0.001) and tick burden (p = 0.003). Other factors were not found to be significant predictors of being PCR positive for T. parva. The present study showed high variation in tick burden and T. parva prevalence across the regions. Therefore, different strategic planning and cost-effective control measures for ticks and T. parva infection should be implemented region by region in order to reduce losses caused by ticks and ECF in the study area.

Comprehensive molecular detection of tick-borne phleboviruses leads to the retrospective identification of taxonomically unassigned bunyaviruses and the discovery of a novel member of the genus phlebovirus.

UNLABELLED: Until the recent emergence of two human-pathogenic tick-borne phleboviruses (TBPVs) (severe fever with thrombocytopenia syndrome virus [SFTSV] and Heartland virus), TBPVs have been neglected as causative agents of human disease. In particular, no studies have addressed the global distribution of TBPVs, and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. In order to provide a useful tool for the ecological and epidemiological study of TBPVs, we have established a simple system that can detect all known TBPVs, based on conventional reverse transcription-PCR (RT-PCR) with degenerate primer sets targeting conserved regions of the viral L genome segment. Using this system, we have determined that several viruses that had been isolated from ticks decades ago but had not been taxonomically identified are novel TBPVs. Full-genome sequencing of these viruses revealed a novel fourth TBPV cluster distinct from the three known TBPV clusters (i.e., the SFTS, Bhanja, and Uukuniemi groups) and from the mosquito/sandfly-borne phleboviruses. Furthermore, by using tick samples collected in Zambia, we confirmed that our system had enough sensitivity to detect a new TBPV in a single tick homogenate. This virus, tentatively designated Shibuyunji virus after the region of tick collection, grouped into a novel fourth TBPV cluster. These results indicate that our system can be used as a first-line screening approach for TBPVs and that this kind of work will undoubtedly lead to the discovery of additional novel tick viruses and will expand our knowledge of the evolution and epidemiology of TBPVs. IMPORTANCE: Tick-borne phleboviruses (TBPVs) have been largely neglected until the recent emergence of two virulent viruses, severe fever with thrombocytopenia syndrome virus and Heartland virus. Little is known about the global distribution of TBPVs or how these viruses evolved and emerged. A major hurdle to study the distribution of TBPVs is the lack of tools to detect these genetically divergent phleboviruses. In order to address this issue, we have developed a simple, rapid, and cheap RT-PCR system that can detect all known TBPVs and which led to the identification of several novel phleboviruses from previously uncharacterized tick-associated virus isolates. Our system can detect virus in a single tick sample and novel TBPVs that are genetically distinct from any of the known TBPVs. These results indicate that our system will be a useful tool for the surveillance of TBPVs and will facilitate understanding of the ecology of TBPVs.

Development of a One Health National Capacity in Africa : the Southern African Centre for Infectious Disease Surveillance (SACIDS) One Health Virtual Centre Model.

Among the many challenges to health, infectious diseases stand out for their ability to have a profound impact on humans and animals. The recent years have witnessed an increasing number of novel infectious diseases. The numerous examples of infections which originated from animals suggest that the zoonotic pool is an important and potentially rich source of emerging diseases. Since emergence and re-emergence of pathogens, and particularly zoonotic agents, occur at unpredictable rates in animal and human populations, infectious diseases will constitute a significant challenge for the public health and animal health communities in the twenty-first century. The African continent suffers from one of the highest burdens of infectious diseases of humans and animals in the world but has the least capacity for their detection, identification and monitoring. Lessons learnt from recent zoonotic epidemics in Africa and elsewhere clearly indicate the need for coordinated research, interdisciplinary centres, response systems and infrastructures, integrated surveillance systems and workforce development strategies. More and stronger partnerships across national and international sectors (human health, animal health, environment) and disciplines (natural and social sciences) involving public, academic and private organisations and institutions will be required to meet the present and future challenges of infectious diseases. In order to strengthen the efficiency of early warning systems, monitoring trends and disease prediction and timely outbreak interventions for the benefit of the national and international community, it is essential that each nation improves its own capacity in disease recognition and laboratory competence. The SACIDS, a One Health African initiative linking southern African academic and research institutions in smart partnership with centres of science excellence in industrialised countries as well as international research centres, strives to strengthen Africa's capacity to detect, identify and monitor infectious diseases of humans and animals, to better manage health and socio-economic risks posed by them, and to improve research capacity in investigating the biologic, socio-economic, ecologic and anthropogenic factors responsible for emergence and re-emergence of infectious diseases.

Knowledge, Attitudes, Practices, and Risk Perception of Antimicrobial Use and Antimicrobial Resistance Among Dairy Farm Owners/Workers in Addis Ababa, Ethiopia.

Introduction: Antimicrobial resistance (AMR) is one of the most significant global health threats to the public, animals, and the ecosystem. Inappropriate use of antibiotics in food animals is considered a major driver of AMR in humans. This study was conducted to assess the knowledge, attitude, practices, and risk perception (KAPP) of dairy farm owners/workers in Addis Ababa about antibiotic use and resistance. Methods: A face-to-face interview using a structured questionnaire was conducted with 281 respondents in four selected subcities of Addis Ababa. The responses provided by each participant were recoded into a binary scale based on the mean score of each domain. Pearson chi-square was used to check the association between the KAPP and sociodemographic characteristics of the respondents and logistic regression analysis was done to explore the factors associated with KAPP. Results: Overall, more than half of the surveyed dairy farm owners/workers had good knowledge (57.7%) and appropriate practice (53.0%), while less than half of the respondents showed desirable attitudes (47.7%) and positive risk perceptions (42.7%). The findings revealed a strong association between the respondents' KAPP and education and between knowledge and risk perception and farming experience. Conclusion: This study found that continuous education of dairy farm owners/workers regarding antimicrobial usage and antimicrobial resistance in dairy farms will increase their awareness and perception of risk as well as motivate them to adopt desirable attitudes and appropriate practices, and consequently limit inappropriate use of antimicrobials leading to mitigating emergence of AMR.

Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0-6%, 3-10%, and 6-20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent.

Rabies Realities: Navigating Barriers to Rabies Control in Rural Zambia-A Case Study of Manyinga and Mwansabombwe Districts.

Rabies persists as a longstanding issue in Zambia, despite being preventable. The current control measures, including dog vaccination, population control, and movement restriction, guided by 'The Control of Dogs Act Chapter 247 of the Laws of Zambia', have not yielded the desired impact in many areas of the country including Manyinga and Mwansabombwe districts. These two districts continue to report low dog vaccination rates, unrestricted dog movements, and escalating cases of animal and human rabies, along with dog bites. Aligned with global aspirations to achieve zero human rabies cases by 2030, this study scrutinizes the determinants and obstacles hampering the execution of rabies control initiatives in Manyinga and Mwansabombwe. Spanning approximately 11 months, this cross-sectional study gathered pre- and post-vaccination data from 301 households in Manyinga and 100 households in Mwansabombwe. Questionnaires probed knowledge, attitudes, and practices related to rabies prevention and control. A transect survey, key informant interviews, and assessment of rabies vaccination and dog bite records complemented the data collection. Findings revealed that 88.0% of respondents from both districts possessed knowledge about rabies, confirming affected species and transmission. Moreover, 76.8% in Manyinga and 88.6% in Mwansabombwe were acquainted with rabies prevention and control methods. Concerning dog owners, 89.0% were aware of rabies, 66.0% understood its prevention and control, and the majority identified bites as the primary mode of transmission. Despite the high level of knowledge recorded during the survey, the implementation of preventive measures was low, which was attributed to low levels of law enforcement by the local government authority, inadequate staffing in the veterinary department, unwillingness to pay for dog vaccinations, and unavailability of rabies vaccine at the veterinary office in both districts. Vaccination coverage stood at 64.0% in Manyinga and 21.0% in Mwansabombwe. Notably, education and occupation exhibited a positive significant association with rabies knowledge. In terms of dog bite cases, Manyinga recorded 538 dog bite cases from 2017 to June 2022, while Mwansabombwe recorded 81 dog bite and 23 jackal bite cases from 2021 to June 2022. The study underscores critical knowledge gaps in rural areas and emphasizes the imperative for enhanced public education and awareness programs, improved rabies surveillance, free mass vaccination campaigns, and community engagement to augment vaccination coverage and knowledge about rabies.

An assessment of the genomic structural variation landscape in Sub-Saharan African populations.

Structural variants are responsible for a large part of genomic variation between individuals and play a role in both common and rare diseases. Databases cataloguing structural variants notably do not represent the full spectrum of global diversity, particularly missing information from most African populations. To address this representation gap, we analysed 1,091 high-coverage African genomes, 545 of which are public data sets, and 546 which have been analysed for structural variants for the first time. Variants were called using five different tools and datasets merged and jointly called using SURVIVOR. We identified 67,795 structural variants throughout the genome, with 10,421 genes having at least one variant. Using a conservative overlap in merged data, 6,414 of the structural variants (9.5%) are novel compared to the Database of Genomic Variants. This study contributes to knowledge of the landscape of structural variant diversity in Africa and presents a reliable dataset for potential applications in population genetics and health-related research.

Development of a multiplex PCR assay for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle.

Tropical theileriosis, bovine babesiosis and anaplasmosis are tick-borne protozoan diseases that impose serious constraints on the health and productivity of domestic cattle in tropical and sub-tropical regions of the world. A common feature of these diseases is that, following recovery from primary infection, animals become persistent carriers of the pathogen and continue to play a critical role in disease epidemiology, acting as reservoirs of infection. This study describes development and evaluation of multiplex and single PCR assays for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle. Following in silico screening for candidate target genes representing each of the pathogens, an optimised multiplex PCR assay was established using three primer sets, cytob1, MAR1bB2 and bovar2A, for amplification of genomic DNA of T. annulata, A. marginale and B. bovis respectively. The designed primer sets were found to be species-specific, generating amplicons of 312, 265 and 166 base pairs, respectively and were deemed suitable for the development of a multiplex assay. The sensitivity of each primer pair was evaluated using serial dilutions of parasite DNA, while specificity was confirmed by testing for amplification from DNA of different stocks of each pathogen and other Theileria, Babesia and Anaplasma species. Additionally, DNA preparations derived from field samples were used to evaluate the utility of the single and multiplex PCRs for determination of infection status. The multiplex PCR was found to detect each pathogen species with the same level of sensitivity, irrespective of whether its DNA was amplified in isolation or together with DNA representing the other pathogens. Moreover, single and multiplex PCRs were able to detect each species with equal sensitivity in serially diluted DNA representing mixtures of T. annulata, B. bovis and A. marginale, and no evidence of non-specific amplification from non-target species was observed. Validation that the multiplex PCR efficiently detects single and mixed infections from field samples was demonstrated. The developed assay represents a simple and efficient diagnostic for co-detection of tropical theileriosis, bovine babesiosis and anaplasmosis, and may be a valuable tool for epidemiological studies aimed at assessing the burden of multiple infection with tick-borne pathogens and improving control of the associated diseases in endemic regions.

Prevalence and Association of Trypanosomes and Sodalis glossinidius in Tsetse Flies from the Kafue National Park in Zambia.

Tsetse flies are obligate hematophagous vectors of animal and human African trypanosomosis. They cyclically transmit pathogenic Trypanosoma species. The endosymbiont Sodalis glossinidius is suggested to play a role in facilitating the susceptibility of tsetse flies to trypanosome infections. Therefore, this study was aimed at determining the prevalence of S. glossinidius and trypanosomes circulating in tsetse flies and checking whether an association exists between trypanosomes and Sodalis infections in tsetse flies from Kafue National Park in Zambia. A total of 326 tsetse flies were sampled from the Chunga and Ngoma areas of the national park. After DNA extraction was conducted, the presence of S. glossinidius and trypanosome DNA was checked using PCR. The Chi-square test was carried out to determine whether there was an association between the presence of S. glossinidius and trypanosome infections. Out of the total tsetse flies collected, the prevalence of S. glossinidius and trypanosomes was 21.8% and 19.3%, respectively. The prevalence of S. glossinidius was 22.2% in Glossina morsitans and 19.6% in Glossina pallidipes. In relation to sampling sites, the prevalence of S. glossinidius was 26.0% in Chunga and 21.0% in Ngoma. DNA of trypanosomes was detected in 18.9% of G. morsitans and 21.4% of G. pallidipes. The prevalence of trypanosomes was 21.7% and 6.0% for Ngoma and Chunga, respectively. The prevalences of trypanosome species detected in this study were 6.4%, 4.6%, 4.0%, 3.7%, 3.1%, and 2.5% for T. vivax, T. simiae, T. congolense, T. godfreyi, T. simiae Tsavo, and T. b. brucei, respectively. Out of 63 trypanosome infected tsetse flies, 47.6% of the flies also carried S. glossinidius, and the remaining flies were devoid of S. glossinidius. A statistically significant association was found between S. glossinidius and trypanosomes (p < 0.001) infections in tsetse flies. Our findings indicated that presence of S. glossinidius increases the susceptibility of tsetse flies to trypanosome infections and S. glossinidius could be a potential candidate for symbiont-mediated vector control in these tsetse species.

High throughput analysis of MHC class I and class II diversity of Zambian indigenous cattle populations.

The classical MHC class I and class II molecules play key roles in determining the antigenic-specificity of CD8+ and CD4+ T-cell responses-as such characterisation of the repertoire of MHCI and MHCII allelic diversity is fundamental to our ability to understand, and potentially, exploit how genetic diversity influences the outcome of immune responses. Cattle remain one of the most economically livestock species, with particular importance to many small-holder farmers in low-and-middle income countries (LMICs). However, our knowledge of MHC (BoLA) diversity in the indigenous breeds that form the mainstay of cattle populations in many LMICs remains very limited. In this study we develop a MiSeq-based platform to enable the rapid analysis of BoLA-DQA and BoLA-DQB, and combine this with similar platforms to analyse BoLA-I and BoLA-DRB repertoires, to study a large cohort of cattle (~800 animals) representing the 3 major indigenous breeds (Angoni, Barotse, Tonga) in Zambia. The data presented confirms the capacity of this high-throughput and high-resolution approach to provide a full characterisation of the MHCI-MHCII genotypes of cattle for which little previous MHC sequence data has been obtained. The cattle in Zambia were found to express a diverse range of MHCI, MHCII and extended MHCI-MHCII haplotypes. The combined MHCI-MHCII genotyping now possible opens new opportunities to rapidly expand our knowledge of MHC diversity in cattle that could find applications in a related translational disciplines such as vaccine development.

Financial Losses Arising from Cattle Organ and Carcass Condemnation at Lokoloko Abattoir in Wau, South Sudan.

Slaughterhouses in South Sudan mirror the economic losses resulting from cattle organs and carcass condemnation due to zoonotic and epizootic diseases of livestock, such as tuberculosis, cysticercosis, and hydatidosis in cattle. However, due to the war, slaughterhouse record keeping has been inconsistent in South Sudan, and thus the estimation of diseases in cattle and their impact may be underestimated. Therefore, this study was conducted to estimate the major causes of carcasses and organ condemnation of cattle slaughtered at Lokoloko abattoir and the resulting financial losses. A cross-sectional active abattoir survey involving antemortem and postmortem examinations was conducted on 310 cattle between January 2021 and March 2021. Furthermore, five-year (September 2015-September 2020) retrospective data on meat inspection records were also collected and analyzed. During the antemortem inspection of the active abattoir survey, 103 (33.2%) cattle had signs of disease. These signs included herniam 17 (5.5%), local swelling 16 (5.2%), lameness 15 (4.8%), emaciation 13 (4.2%), blindness 12 (3.9%), depression 11 (3.5%), pale mucus membrane 7 (2.3%), nasal discharge 5 (1.6%), lacrimation 4 (1.3%), and salivation 03 (0.97%). Postmortem inspection revealed gross pathological findings on 180 (58.6%) carcasses, out of which 47 (26.1%) livers and 31 (17.2%) hearts were condemned due to various causes. The active abattoir survey and the retrospective data revealed that tuberculosis, fascioliasis, hydatidosis, and heart cysticercosis were the leading causes of condemnation of carcasses and organs. In the active abattoir survey, a total of 19,592,508 South Sudanese Pounds, equivalent to US$29,686 was lost from organ condemnation, while in the retrospective data; the overall direct financial loss during the five years was estimated to be 299,225,807 South Sudanese Pounds equivalent to US$453,372. This study revealed that bacterial and parasitic diseases were the common causes of carcass and organ condemnations and caused significant financial losses at Lokoloko abattoir in Wau, South Sudan. Therefore, there is a need for training farmers on cattle disease management, heightened meat inspections, and proper disposal of condemned meat.

Characterization of CYP2D6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes-derived from activity scores-were examined across multiple sub-Saharan African populations based on bioinformatics analysis of 961 high-depth whole genome sequences. This was followed by characterization of novel star alleles and suballeles in a subset of the participants via targeted high-fidelity Single-Molecule Real-Time resequencing (Pacific Biosciences). This study revealed varying frequencies of known CYP2D6 alleles and predicted phenotypes across different African ethnolinguistic groups. Twenty-seven novel CYP2D6 star alleles were predicted computationally and two of them were further validated. This study highlights the importance of studying variation in key pharmacogenes such as CYP2D6 in the African context to better understand population-specific allele frequencies. This will aid in the development of better genotyping panels and star allele detection approaches with a view toward supporting effective implementation of precision medicine strategies in Africa and across the African diaspora.

Epidemiology of intestinal helminthiasis with an emphasis on taeniasis in Chipata district of the Eastern province of Zambia.

BACKGROUND: Intestinal helminth infections are among the most common infections worldwide and have a negative impact on the health, education, nutrition and economic development of affected populations. This study aimed to estimate the prevalence of intestinal helminthiasis, including T. solium taeniasis, using a large-scale community-based study in Chiparamba area of Chipata District in the Eastern province of Zambia. METHODS/PRINCIPAL FINDINGS: A cross-sectional study was conducted between June 2019 and December 2022 in a rural community of 25 randomly selected villages known to be at risk for T. solium infection. Stool samples were examined for intestinal helminths using the formol-ether concentration technique and further tested for taeniasis by copro antigen-ELISA (copro Ag-ELISA). Descriptive statistical analyses were conducted, and associations between the disease prevalence of active infections and individual- and village-level variables were determined using the chi-square or Fisher's exact test. Predictors of an individual being positive for either taeniasis or other soil-transmitted helminths were determined using binary logistic regression. A total of 2762 stool samples were examined. One hundred ninety-five (7.1%) tested positive for at least one helminthic parasite on microscopy, with hookworm being the most frequent 84 (3.0%), followed by S. mansoni, 66 (2.4%). For taeniasis, 11 (0.4%) participants were positive for Taenia spp. microscopically, while 241 (8.7%) tested positive via copro Ag-ELISA. On bivariate analysis, male sex was significantly associated with the prevalence of intestinal parasites (p = 0.012) but not with that of taeniasis based on copro Ag-ELISA results. Village level differences were significant for infection with intestinal helminths as well as for taeniasis positivity on copro Ag-ELISA (p <0.001). CONCLUSION: Intestinal helminths, including T. solium taeniasis, are prevalent in Chiparamba area of Chipata district in the eastern province of Zambia, supporting the clear need for further targeted public health interventions for surveillance and control.

Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts.

Community knowledge, attitudes and practices related to Taenia solium taeniosis and cysticercosis in Zambia.

BACKGROUND: Several studies on Taenia solium taeniosis / cysticercosis (TSTC) have been conducted in Zambia. However, none has assessed community knowledge, attitudes and practices related to TSTC and epilepsy. METHODS: A community-based cross-sectional study was conducted between November and December 2022. The design consisted of a questionnaire-based survey conducted in each of the 25 purposely selected villages in Chiparamba Rural Health Centre (RHC) catchment area in Chipata district of the Eastern Province. RESULTS: A total of 588 participants comprising 259 (44%) males and 329 (56%) females with median age of 42 years (range 17 to 92 years) were interviewed. Awareness of the signs and symptoms of taeniosis and human cysticercosis (HCC), including transmission and prevention measures was very low. Whilst the majority had heard about epilepsy, they were not able to link HCC to epilepsy. Most participants were aware of cysticerci in pigs (PCC) including its predilection sites but were not aware of mode of transmission and prevention measures. The pork meat inspection by trained professionals was also not a common practice in the area. Risk perception of T. solium infections was thus very low. Overall knowledge, attitude and practice scores related to T. solium infections and to epilepsy were very low with median scores of 0.38 (IQR 0.25-0.54) for knowledge, 0.25 (0.25-0.50) for attitudes, and 0.31 (0.25-0.44) for practices. Males had better knowledge on TSTC (median = 0.42, p = 0.017, r = 0.098) and better practice scores (median = 0.38, p = < 0.001, r = 0.154) compared to females though the effect size was small. With regards to sanitation and hygiene washing with soap and water was reported by many but only few had a hand washing facility near their latrines. CONCLUSION: The study shows overall poor knowledge, attitudes and practices related to TSTC among the community of Chiparamba RHC in Chipata district of the Eastern Province of Zambia. This poses a serious challenge for control and elimination of T. solium infections and thus efforts to improve knowledge, attitudes and practices should be made using a One Health approach for the control and elimination of TSTC. Educational programs about TSTC transmission, signs and symptoms, prevention, management and control need to be scaled up in the study area and Zambia as a whole.