The epidemiology of human Taenia solium infections: A systematic review of the distribution in Eastern and Southern Africa

Background Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence of human taeniosis and cysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in ESA. Methods/Principle findings Scientific literature published between 1st January 2000 and 20th June 2022 in international databases [MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey] was systematically reviewed for ESA. The study area included 27 countries that make up the ESA region. Information on either taeniosis, cysticercosis or NCC was available for 16 of 27 countries within the region and a total of 113 reports were retained for the review. Most case reports for cysticercosis and NCC were from South Africa, while Tanzania had the most aggregated cysticercosis reports. Eleven countries reported on NCC with seven countries reporting data on NCC and epilepsy. Unconfirmed human T. solium taeniosis cases were reported in nine countries while two countries (Madagascar and Zambia) reported confirmed T. solium cases. The cysticercosis seroprevalence ranged between 0.7–40.8% on antigen (Ag) ELISA and between 13.1–45.3% on antibody (Ab) ELISA. Based on immunoblot tests the Ab seroprevalence was between 1.7–39.3%, while the proportion of NCC-suggestive lesions on brain CT scans was between 1.0–76% depending on the study population. The human taeniosis prevalence based on microscopy ranged between 0.1–14.7%. Based on Copro Ag-ELISA studies conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence of 19.7% was reported in Kenya. Conclusions Despite the public health and economic impact of T. solium in ESA, there are still large gaps in knowledge about the occurrence of the parasite, and the resulting One Health disease complex, and monitoring of T. solium taeniosis and cysticercosis is mostly not in place.

Introduction Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. The life cycle of T. solium involves pigs as intermediate hosts (cysticercosis) while humans are definitive hosts (taeniosis). Humans may also act as accidental intermediate hosts when larvae of the parasite settle in muscles, subcutaneous or organ tissues causing human cysticercosis (HC). If they lodge in the central nervous system (CNS), including the brain and the spinal cord, the disease is called neurocysticercosis (NCC) [1,2]. An individual may also have cysticerci in the CNS as well as in other parts of the body, which is referred to as (neuro) cysticercosis. NCC may be asymptomatic, but it can also cause various neurological signs/symptoms such as epileptic seizures and epilepsy, chronic progressive headache, focal neurological deficits, signs and symptoms of increased intracranial pressure and in rare cases, death [3][4][5]. Globally, NCC is estimated to be responsible for 30% of cases of acquired epilepsy in endemic areas [6] and 22% in sub-Saharan Africa [7]. However, this proportion depends on the infection pressure of T. solium and thus may vary considerably.
T. solium is endemic in Africa, Asia and Latin America, especially in areas where pigs are reared under free-ranging conditions, where pork is eaten and where hygiene is limited [8][9][10]. Nevertheless, information on the endemicity of T. solium is limited and there are many countries from which no published information is available for either human or porcine cysticercosis. Within the Eastern and Southern African region, information on porcine cysticercosis was recently published [11]. However, not much is known about the epidemiology of T. solium infections in humans. The purpose of this review was to gather all published information on human T. solium infections (T. solium taeniosis/(neuro)cysticercosis (TSTC)) in Eastern and Southern Africa (ESA) within the period 1st January 2000 and 20th June 2022 and describe the gaps in the epidemiology of TSTC in this area.

Methods
The systematic review was conducted following a pre-registered protocol and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [12] (S1 Table). The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD 42022343072).

Search strategy
All published articles were searched using the electronic databases, MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey. The reference lists of included studies were also scanned to identify further eligible documents. The searches were conducted on 20 th June 2022. For all questions subject headings (where applicable) and text words describing T. solium taeniosis/cysticercosis/neurocysticercosis and prevalence, epidemiology, control, elimination, or eradication were searched. The search strategy was intended to obtain all available literature on human taeniosis, cysticercosis and neurocysticercosis in ESA conducted and published in the last 22 years. Grey literature was also searched for any relevant publications. The search terms for all databases can be found in (S1 File).
Comoros, Djibouti, Eritrea, Ethiopia, Kenya, Lesotho, Madagascar, Malawi, Mauritius, Mayotte, Mozambique, Namibia, Reunion, Rwanda, Seychelles, Socotra, Somalia, Somaliland, South Africa, Eswatini (former Kingdom of Swaziland), Tanzania, Uganda, Zambia and Zimbabwe. Included in this review were studies that describe the epidemiology, disease occurrence, burden, prevalence, incidence, prevention and control of TSTC in any of the twentyseven countries of ESA. All observational studies including case series and case reports and systematic reviews of such studies were included. Only studies conducted between 1 st January 2000 and 20 th June 2022 were considered. No language limits were imposed on the search, although studies in languages other than English were only included if they could be adequately translated by using Google Translate.
Exclusion criteria. We excluded studies that did not concern T. solium, did not concern humans, did not report data from within ESA and studies conducted before 1 st January 2000.

Risk of bias assessment
The risk of bias in the studies was assessed using items recommended by the Agency for Health Care Research and Quality (AHRQ) [13]. This assessment covered baseline characteristics, inclusion-exclusion criteria, confounding and modifying variables, performance bias, attrition bias, detection bias and reporting bias. Each of these factors was rated and categorized as low, or high risk of bias. If the information available was insufficient, the risk of bias was considered 'unsure'.

Statistical analyses
No statistical pooling of results was conducted and the findings of the review are presented in a narrative synthesis with tables and figures to aid data presentation. Prevalence data if not already provided were calculated using the numerator and denominator of the study sample. Data were analyzed separately for taeniosis, cysticercosis, and neurocysticercosis. For the latter two, data were also presented separately for the general population and people with epilepsy.

Ethical considerations
Ethical recommendation was not required for this review.

Study selection
Our search yielded 2114 records of which 1198 were duplicates. Through screening of titles and abstracts, 776 (85%) records were excluded and for a further 8, no full text was found. Full-text assessment with respect to the inclusion criteria was performed on 132 records of which 19 (14%) were excluded (17 reported data described in other included studies, one did not concern T. solium, and one reported results outside the scope of the study). One hundred and thirteen (113) studies were finally included in the review. Of those, 49 were concerned with only (neuro) cysticercosis, 57 with taeniosis, and 7 with both cysticercosis and taeniosis. Of the 113 reports reviewed, 25 were case reports, 82 were cross-sectional, 3 cohort and 3 casecontrol studies. The flow diagram for the search is shown in (Fig 1). The reference for included studies is shown in (S2 Table). a high risk of bias due to inadequate inclusion and exclusion criteria, and 45 articles had a high risk of bias due to confounding and modifying variables.

Results of individual studies
Human (neuro) cysticercosis. Information on human (neuro) cysticercosis was obtained from 62 sources. In total, 25 (40%) records provided individual information on NCC and CC. Twelve (48%) of these records were on NCC only, seven (28%) on CC and six (24%) on both NCC and CC. Thirty-seven (60%) records reported aggregated information on NCC and CC. Ten (27%) of these records were on NCC only, twenty-one (57%) on CC only, and six (16%) on both NCC and CC. Information on human neuro(cysticercosis) was available for 14 of 27 ESA countries. No reports were available for Angola, Botswana, Comoros, Djibouti, Eritrea, Ethiopia, Lesotho, Mayotte, Reunion, Seychelles, Socotra, Somaliland and Somalia.
Human cysticercosis case reports. Individual human CC cases during the period 2000 to 2022 were reported in 13 hospital case records from six of the ESA countries with, South Africa reporting four cases; Madagascar, Malawi, Rwanda and Tanzania reporting two cases each and Mauritius reporting one case (Table 1). Individual NCC cases were reported in 18 hospital records from eight of the ESA countries with South Africa reporting eight cases while Madagascar, Malawi and Zambia reported two cases each. Mozambique, Eswatini, Tanzania and Zimbabwe reported one case each ( Table 2). All reports were based on individual patients presenting with various signs/symptoms, and investigations leading to their diagnosis of either   (Table 3). These were reports from nine countries, the majority of which were conducted in Tanzania (n = 7) followed by Madagascar (n = 6) and Zambia (n = 4). South Africa, Mozambique, Rwanda and Kenya had two reports each. For Burundi and Uganda one report each was available. There was great variation in the aggregated number of human CC cases across countries with over 2307 cases reported from Madagascar alone. The number of human CC cases identified in other ESA countries in documents published between 2000 and 2022 is shown in (Fig  2) below.
To ascertain cases of aggregated human CC, various diagnostic methods were utilized in the included reports with nine (33%) studies employing a combination of antibody and antigen based serologic tests. Seven (26%) studies employed only the Ag-ELISA, while eight (30%) utilized only the immunoblot methods. One report (4%) utilized only the electroimmunotransfer blot assay (EITB) and one report (4%) was based on postmortem findings of CC through full-body dissection [65]. One report did not specify the type of serologic test used. The methods used for CC diagnosis are shown in (Fig 3).
The prevalence of human CC in ESA in different study populations showed wide variation within and between countries (Fig 4 and Table 3). The CC seroprevalence ranged between 0.7-40.8% on Ag-ELISA and between 13.1-45.3% on Ab-ELISA tests. Based on Ab-tests using the immunoblot the CC seroprevalence ranged between 1.7-39.3%. The highest point prevalence based on serum Ab-ELISA was reported in Tanzania (45.3%) from a study conducted in the Mbozi area of Mbeya District [55].
For the studies conducted within Tanzania, this was an outlier value. High prevalence variation was also observed within countries as seen in Madagascar, Rwanda and Zambia (Fig 5).

Gender Location of pathogen Comment Reference
Zimbabwe 35 Male A Suprasellar cystic lesion compressing the optic nerve #$ A 35-year-old man presenting with pain accompanied by mild vision loss in the right eye due to a cystic mass compressing the optic nerve. [38] ARVs, Antiretroviral medication; HIV, Human immunodeficiency virus; NCC, Neurocysticercosis; Yrs., Years. * Serology with Ag-ELISA and EITB also used for diagnosis ¶ CSF Ag-ELISA also used for diagnosis [39] Kenya 2113 122 (5.8) Ag-ELISA A cross-sectional survey around the Lake Victoria region to evaluate human and animal zoonotic and non-zoonotic disease in a rural farming community. [40] 17 12 Ag-ELISA A cross-sectional study to determine the prevalence of cysticercosis and NCC among PWE (17) and PWOE (12) in a pig keeping community in Western Kenya.
[41] The lowest point prevalence (0.7%) was also reported from Tanzania. For details on sources refer to Table 3. Aggregated human neurocysticercosis. For reports presenting aggregated NCC cases (Table 4), 16 records were available. Four (25%) employed imaging (brain CT or MRI) only, whereas 11 (69%) incorporated both imaging and serological tests, and one (6%) was based on postmortem full-body dissection. The NCC-suggestive lesions on brain CT scans showed a   Table 4). One report utilized MRI to identify lesions suggestive of NCC in HIV+ children. In this report, four children (8.5% of the total) were found to have NCC, with imaging suggesting the vesicular (active) stage of NCC in all of them [66].
Neurocysticercosis and epilepsy. Among the 16 records reporting aggregated NCC, eight (50%) reported data linking NCC and epilepsy ( Table 5). Three of these records were reported from South Africa whereas one record each was reported from Kenya, Mozambique, Rwanda, Tanzania and Zambia. Three (33%) of these NCC epilepsy studies were community-based studies and six (67%) were conducted in hospital/health facility settings. The prevalence of NCC among people with epilepsy ranged between 0-61%. One study in Kenya in a T. solium endemic area found none of the participants with epilepsy had serological evidence of cysticercosis and none had radiographic findings consistent with NCC [41]. Whereas at St Elizabeth's Hospital, Lusikisiki, Eastern Cape, 61% of the patients presenting with epilepsy had NCC associated epilepsy, the prevalence being highest in the 10-19-year-old age group [52]. For details on sources refer to Table 5.
Human taeniosis. A total of 64 records were identified providing information on taeniosis cases in ESA for the period 2000 to 2022 (Table 6). These records were reported in 11 out of 27 ESA countries (Fig 7) with Ethiopia reporting the most records (n = 38) followed by Tanzania (n = 6) and Zambia (n = 5). Kenya and Uganda had three records each while Angola, Mozambique, and South Africa had two records each. Malawi, Madagascar and Rwanda had one record each. There were no cases reported from Botswana, Burundi, Comoros, Djibouti, Eritrea, Lesotho, Mauritius, Mayotte, Namibia, Reunion, Seychelles, Socotra, Somalia, Somaliland, Swaziland, and Zimbabwe.
Several groups of people were studied for human taeniosis with 25 records reporting taeniosis cases in school children, 18 records on patients presenting at health facilities, 15 on consenting community volunteers, and six on food handlers. There was great variation in aggregated numbers of human taeniosis cases across countries with 595 cases reported from Ethiopia alone and even more (4834) reported from Mozambique. The number of human taeniosis cases identified for the other nine countries in ESA is shown in (Fig 8).
The largest number of cases were reported as Taenia spp. (Table 6) without specifying the type of species. One record from Madagascar and another from Zambia, reported confirmed T. solium using PCR; [62,70]. Microscopy alone was employed for 53 studies, and copro Ag-ELISA alone in three studies. Five studies used both copro Ag-ELISA and microscopy for taeniosis diagnosis. Three studies used the rES33 EITB for the presence of a tapeworm antibodies in the body. Immunological data (copro Ag-ELISA or rES33 EITB) on taeniosis was only available from Kenya, Rwanda, Tanzania, and Zambia. Within the ESA region, the prevalence of human taeniosis based on microscopy ranged between 0.1-14.7% with the highest prevalence reported in a study conducted among food handlers at Wolkite University in Ethiopia [71] (Figs 7 and 9). Among studies based on copro Ag-ELISA conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence was reported in Kenya at 19.7% [40]. Rwanda had a taeniosis prevalence of 1.4% [51], Tanzania ranged between 0.5 to 5.2% [55,72] [16], [22] and Zambia ranged between 0.3 to 13.8% [62,73] (Fig 10). For details on sources refer to Table 6.

Discussion
This study aimed at collecting epidemiological data on T. solium infections in humans in the ESA region for the period 2000 to 2022. For both cysticercosis and taeniosis, there was no data from Comoros, Djibouti, Eritrea, Mayotte, Reunion, Seychelles, Socotra, Somalia and Somaliland that could be retrieved. Seventy per cent of the Somali human population subsists in pastoralism with sheep and goats being the dominant animals. Camels are primarily raised for milk production and small ruminants are for generating cash income for the family [126]. Somalia has for some time now experienced internal conflicts and this may have a bearing on the diagnosis and reporting of human cysticercosis and taeniosis cases. In addition, Somaliland and Somalia are predominantly Muslim communities where pig rearing and pork consumption is prohibited [127]. For the other six island states and territories, a lack of T. solium research in reporting cases has been cited [128]. The same can be said about Botswana and Lesotho from which data on cysticercosis and taeniosis was also lacking. Cysticercosis data was lacking in even more countries.
According to the World Bank IBRD-IDA report of 2022 [129] the population using safely managed sanitation services for both Comoros and Djibouti only stood at 37% with no data for other island states. People practicing open defecation were higher in Eritrea (67%) with Somalia reporting (23%) and Djibouti (16%). On the Réunion island, pork is said to be the most popular meat with a total annual pork consumption of about 20 000 tones. Half of this is produced on the island and the rest is imported frozen from Europe [130]. Comoros on the other hand has a small livestock sector with most of its meat including pork imported from Tanzania, Madagascar and France [131]. For Mayotte, Eritrea and Djibouti, information on

PLOS NEGLECTED TROPICAL DISEASES
Epidemiology of human T. solium infections in Eastern and Southern Africa pig rearing could not be found as these countries focus mostly on cattle, sheep, goats, and camels [132]. However, for Eritrea, pig breeding has recently begun to be promoted [133] and so is the case for Seychelles whose 2011 census of agriculture showed that 2% (483/24770) of the households were raising pigs in small holdings [134]. While it is not possible to ascertain the presence or absence of human T. solium infections in these countries, there is a possibility that these infections do exist as pork consumption seems to be practiced and risk factors are present. Therefore, the numbers collected for this review represent an underestimation of the T. solium epidemiology for human disease in ESA.
Regarding human cysticercosis cases, T. solium tapeworm carriers being the source of T. solium eggs are the sole cause of infection in both rural and urban areas of the ESA region [10,135]. T. solium tapeworm carriers, if not treated, pose a risk to themselves if they ingest infective eggs leading to cysticercosis but can also pose a risk to other people in contact [70,136]. A study in Madagascar found that the overall prevalence of cysticercosis at a household level was 46% and 34% detected by Ab-ELISA and EITB respectively, in the same household where a tapeworm carrier was found [70]. Individual human cysticercosis cases were identified from a third of the 27 ESA countries. South Africa reported the highest number of

PLOS NEGLECTED TROPICAL DISEASES
individual human cysticercosis cases followed by Madagascar. This could be due to increased awareness of cysticercosis as a possible diagnosis in, for example, people with epilepsy in these countries compared to other countries within the region. South Africa also has more resources to carry out testing compared to the other countries within the region. For example, as early as 2003 South Africa already had 214 CT scanners and 111 neurologists. This is an advantage in terms of diagnosis and management of particularly NCC that is not present in other countries within the region [137]. With poor pig management, poor meat inspection, and poor sanitation those who do not eat pork are equally at risk of infection with cysticercosis as those eating pork [138][139][140]. Additionally, certain cultural practices within the region have also been cited as contributing factors to cysticercosis. For example, in South Africa, it has been reported that

PLOS NEGLECTED TROPICAL DISEASES
Epidemiology of human T. solium infections in Eastern and Southern Africa some unqualified traditional healers "baloi" used Taenia segments and added them to medicinal mixtures as strengthening ingredients. There are also reports of T. solium segments being added to the beer of unfaithful husbands or lovers as punishment [137]. NCC has been associated with up to 57% of epilepsy cases in sub-Saharan Africa to which the region under consideration belongs [7,64]. This is higher than the global average of 30% of NCC among PWE [6]. For most countries within ESA, the diagnosis of NCC is problematic due to the scarcity of neuroimaging, serology and trained neurologists [141,142]. This diagnostic challenge is not only present in ESA but also in Europe where a lack of awareness of NCC leads to underdiagnoses [143]. Only a quarter of the countries within the ESA reported data on NCC and epilepsy. Epilepsy is one of the most common neurological disorders in many parts of sub-Saharan Africa and NCC seems to be a major cause of it in T. solium cysticercosis endemic areas. Diagnosing NCC among people with epilepsy is vital to prevent further morbidity and mortality from the disease as well as to reduce the social stigma associated with epilepsy in the region [141,[144][145][146].
Regarding human T. solium taeniosis in ESA, only Kenya, Madagascar, Rwanda, Tanzania, and Zambia conducted community-based studies and employed serological tests that specifically aimed at determining the burden of infection. The other countries reported data on taeniosis as incidental findings following microscopic examinations of stool samples conducted for soil-transmitted helminths. The reported human taeniosis cases were also reported on an aggregated level without evidence of species determination. Thus, cases reported as either taeniosis or Taenia spp. could not for instance be differentiated from cases due to Taenia saginata which is also widely distributed in ESA [128]. Only two studies, one from Madagascar and another from Zambia were able to confirm the T. solium species after collecting tapeworm proglottids [62,70].
This lack of species differentiation creates uncertainty regarding the epidemiology of T. solium infections in ESA. Therefore, the prevalence of T. solium taeniosis in the region may be overestimated as most Taenia spp. diagnoses could be T. saginata as beef is consumed in most countries, while in some regions, the consumption of pork is prohibited for religious reasons. This is worsened by the fact that T. solium taeniosis is not even a notifiable disease in most of these countries. Application of molecular methods to differentiate T. solium species on stool

PLOS NEGLECTED TROPICAL DISEASES
Epidemiology of human T. solium infections in Eastern and Southern Africa A cross-sectional study in three primary schools in Sululta after deworming. [112] (Continued ) examination is not widely practiced and it is not possible to differentiate Taenia eggs based on microscopy [135,147]. More sensitive and specific diagnostic tools need to be used to identify the true prevalence and outline the epidemiology of T. solium. Human taeniosis in the region is due to the high prevalence of porcine cysticercosis in ESA countries which is ranked amongst the highest in the world [10]. The pooled prevalence for porcine cysticercosis within the region was recently estimated to be as high as 27% by carcass dissection which is a gold standard technique for porcine cysticercosis diagnosis [11]. Over the last decade, pig production as a risk factor for human taeniosis in the rural communities of A cross-sectional survey around the Lake Victoria region to evaluate human and animal zoonotic and non-zoonotic disease in a rural farming community. [

PLOS NEGLECTED TROPICAL DISEASES
Epidemiology of human T. solium infections in Eastern and Southern Africa ESA countries has increased mainly because pig raising is an attractive alternative to other animals as it does not require grazing land compared to ruminants. Free-range pig keeping is popular, especially in rural areas of the region as it is easy and cheap. This coupled with the general lack of slaughterhouses and inspection of pork with a lack of sanitation facilities has contributed to the risk for people to acquire taeniosis and cysticercosis [3,10,148].

Study limitation
Our study is limited by the fact that search platforms were used only for online publications. Thus, unpublished data which could have contributed significantly to a more nuanced picture

Conclusion
In this review on human T. solium taeniosis and (neuro) cysticercosis within ESA, we found wide variations in the prevailing prevalence estimates depending on the quality of the study and the diagnostic methods used. There remain large gaps with regards to T. solium infections within the ESA region with 11 countries without any information on human taeniosis and cysticercosis, and even more countries [18] without any information for cysticercosis. Considering the public health and economic impact that T. solium infections have, it is important to understand its epidemiology in humans. Human taeniosis, cysticercosis and