Microbial networks and pathogen detection: Insights from ticks and patients with acute febrile illness.

Background: The Delta variant of SARS-CoV-2 virus, one of the alarming variants of concern (VOC) with a distinct mutation characteristic, was immensely detrimental and a significant cause of the prolonged pandemic waves. This study aimed to analyze the genetic characteristics of the predominant Delta variant in acute febrile illness (AFI) patients in Ethiopia. Method: Nasopharyngeal swab samples were collected from AFI patients in four hospitals from February 2021 to June 2022 and tested for SARS-CoV-2 by using RT-qPCR. Of 101 positive samples, 48 stored specimens were re-tested, and 26 with sufficient RNA quality (Ct < 30) were sequenced using whole-genome sequencing to identify variants of concern, specific virus lineages and mutation features. Result: Delta variants (21J clade) were found predominant among all the sequenced SARS-CoV-2 isolate (80.8%, 21/26). AY.120 (46.2%) and B.1.617.2 (26.9%) were the predominant sub-lineages of the Delta variant. Omicron (21k, Pango BA.1.1/BA.1.17/BA.1) and Alpha (20I, Pango B.1.1.7) variants accounted for 11.5% and 7.7% of the total sequenced samples. Phylogenetic analysis showed evidence of local transmission and possible multiple introductions of SARS-CoV-2 VOCs in Ethiopia. The number of mutations increases dramatically from Alpha (~35 avg) to Delta (~42 avg) to Omicron (~56 avg). The Delta variant revealed a spike mutation on L452R and T478K and P681R, and was characterized by the double deletion E156-F157- in Spike protein. Conclusions: The findings are indicative of a gradual change in the genetic coding of the virus underscoring the importance of ongoing genomic surveillance to track the evolution and spread of SARS-CoV-2 and other emerging virus.

Background: Clinicians across the globe refer to the published KDIGO definition of Acute Kidney Injury (AKI) as one of the following: • An increase in serum creatinine by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hrs • An increase in serum creatinine to ≥1.5 times baseline within the previous 7 days • Urine volume &lt;0.5 ml/kg/h for 6 hrs Acute febrile illnesses are a common cause of AKI in hospitalized patients. The present study was undertaken to evaluate the incidence of AKI in patients presenting with acute febrile illness and also study the different etiological factors responsible for acute febrile illness. Materials and Methods: The study included 200 patients of acute febrile illness admitted in Silchar Medical College And Hospital in the Department of Medicine over a period of 24 months. The data regarding the various causes such as the etiology of fever, kidney function tests and other parameters of the cases were obtained and analyzed using simple statistical methods. Results and Observations: A total of 52 patients (26%) with acute febrile illness due to etiologies like Leptospirosis, Falciparum Malaria, Enteric fever, Dengue, Scrub Typhus, and mixed Malaria, etc developed AKI out of the 200 admitted cases presenting with acute febrile illness. Conclusion: The incidence of AKI is common in hospitalized patients of acute febrile illness and a thorough evaluation and detailed clinicobiochemical monitoring of the patients are necessary as it has varied etiology and often lead to an unfavorable or even unexpected outcome.

Fever accounts for around 15% of emergency visits in elderly age group and around 5% in adults. The spectrum of etiologies ranges from non-infectious to infectious etiologies. There are very few studies done in the past highlighting the approach of patients with acute febrile illness without any localizing signs and symptoms. Objectives:The aim of the study was to formulate a targeted approach for evaluation and treatment of patients with acute undifferentiated febrile illness without evidence of localizing symptoms and signs. The secondary objective was to study the etiology and final outcome of patients with acute undifferentiated febrile illness.Materials and Methods:A protocol was devised for patients aged more than 18 years, who presented in emergency department with complaints of fever without localizing symptoms or signs of sepsis over a period of 6 months from April 2018 to September 2018. Patient's data were collected retrospectively from the hospital record section.Results:A total of 212 patients of undifferentiated acute febrile illness were enrolled in the study. Maximum number of patients [n = 69 (32.5%)], presented on second day of illness. All the patients presenting within 1 or 2 days of fever experienced defervescence. Out of these 69 patients, 35 (36.4%) were investigated of which in 29 (82.2%) investigations were not found to be useful; 75 (78.1%) patients with 1 or 2 days history of fever improved without investigations. Surprisingly, 54 patients (72%) with 1 or 2 days' history of acute febrile illness experienced defervescence without the need of antibiotics.Conclusion:There is an urgent need to devise a standardized protocol for diagnosis and treatment of patients with acute undifferentiated febrile illness in order to avoid unnecessary investigations and antimicrobial use.

Acute febrile illness (AFI) patients present to the emergency department (ED), with fever to multi-organ dysfunction. There is a lack of early point-of-care-based disposition criteria in AFI patients regarding the need for intensive care unit (ICU) or high dependency unit (HDU) care. We enrolled 100 patients with AFI presenting to the ED and evaluated using point-of-care ultrasound with two-dimensional echocardiography (ECHO), lung ultrasound score (LUS), renal arterial resistive index (RRI), and arterial blood gas. The need for ICU/HDU admission, ventilation (either noninvasive or invasive), and renal-replacement therapy (RRT) within 48 h of hospitalization was noted. Ninety-five patients were included in the analysis. 72 (75.8%) patients required either ICU or HDU admission, 45 (47.4%) required ventilatory support (either noninvasive or invasive), and 32 (33.7%) required RRT. After logistic regression, LUS ≥16, and arterial lactate ≥12 mg/dL were independent predictors of the need for ICU or HDU admission. The respiratory rate (RR) ≥28/minute, LUS ≥16 and RRI ≥61 were the independent predictors of the need for ventilation. The MAP ≤73 mmHg, LUS (≥16), and RRI (≥67) were the predictors of the need for RRT. In AFI patients presenting to the ED, the MAP, LUS, and lactate are predictors of the need for ICU/HDU admission. The LUS and RRI were predictors of the need for RRT whereas the RR, LUS, and RRI were the predictors of the need for ventilation.

Research has not been conducted on physical activity in early child education and care (ECEC) settings in low-income, rural communities in South Africa. This study aimed to describe the physical activity environment of these settings and identify child and contextual factors associated with physical activity in these settings. By understanding physical activity in this environment, it will be possible to identify context-specific opportunities, including with teachers, to overcome potential challenges and maximise physical activity in a low- and middle-income country setting. The study was conducted in rural Bushbuckridge, Mpumalanga in 2014. Preschool-aged children (n=55) were recruited from five ECEC settings, including three preschools and two primary schools, where preschool-aged children are in their reception year, grade R. Preschool environment characteristics were assessed using an observational tool adapted from existing tools. Children's physical activity was assessed using the Observational System for Recording Physical Activity in Children - Preschool Version. Differences between preschool and grade R settings were assessed using χ2 analyses, and multinomial logistic regression analysis was used to determine factors associated with physical activity in the ECEC settings. The physical activity environment differed between preschool and grade R ECEC settings in terms of space (preschoolpgrade R, p<0.001). On average, children spent 28.7% of their day in the ECEC settings engaged in physical activity, of which 22.3% was moderate- to vigorous-intensity physical activity (MVPA). Children spent the greatest proportion of the day in sedentary activities (69.9%) and this differed significantly between preschool (63.2%) and grade R children (81.3%, p<0.001). Preschool children were significantly more active than grade R children, and spent greater proportions of time in light-intensity physical activity (8.6% v 2.7%, p<0.001) and MVPA (25.4% v 15.3%, p<0.001). Irrespective of ECEC setting, children were significantly more likely to participate in MVPA if they were outdoors (p=0.001), and significantly less likely to do MVPA if they were overweight/obese (p=0.006). These findings provide insight into child-level and contextual factors associated with preschool-aged children's physical activity within ECEC settings in a low-income, rural community in South Africa. Particularly, the physical and social features of ECEC settings are important in the promotion of physical activity. Findings from this study suggest that it is necessary to upskill and encourage teachers in ECEC settings to maximise opportunities for physical activity in rural low-income communities in South Africa.

BackgroundFew studies of dengue have shown group-level associations between demographic, socioeconomic, or geographic characteristics and the spatial distribution of dengue within small urban areas. This study aimed to examine whether specific characteristics of an urban slum community were associated with the risk of dengue disease.Methodology/Principal FindingsFrom 01/2009 to 12/2010, we conducted enhanced, community-based surveillance in the only public emergency unit in a slum in Salvador, Brazil to identify acute febrile illness (AFI) patients with laboratory evidence of dengue infection. Patient households were geocoded within census tracts (CTs). Demographic, socioeconomic, and geographical data were obtained from the 2010 national census. Associations between CTs characteristics and the spatial risk of both dengue and non-dengue AFI were assessed by Poisson log-normal and conditional auto-regressive models (CAR). We identified 651 (22.0%) dengue cases among 2,962 AFI patients. Estimated risk of symptomatic dengue was 21.3 and 70.2 cases per 10,000 inhabitants in 2009 and 2010, respectively. All the four dengue serotypes were identified, but DENV2 predominated (DENV1: 8.1%; DENV2: 90.7%; DENV3: 0.4%; DENV4: 0.8%). Multivariable CAR regression analysis showed increased dengue risk in CTs with poorer inhabitants (RR: 1.02 for each percent increase in the frequency of families earning ≤1 times the minimum wage; 95% CI: 1.01-1.04), and decreased risk in CTs located farther from the health unit (RR: 0.87 for each 100 meter increase; 95% CI: 0.80-0.94). The same CTs characteristics were also associated with non-dengue AFI risk.Conclusions/SignificanceThis study highlights the large burden of symptomatic dengue on individuals living in urban slums in Brazil. Lower neighborhood socioeconomic status was independently associated with increased risk of dengue, indicating that within slum communities with high levels of absolute poverty, factors associated with the social gradient influence dengue transmission. In addition, poor geographic access to health services may be a barrier to identifying both dengue and non-dengue AFI cases. Therefore, further spatial studies should account for this potential source of bias.

Acute febrile illness (AFI) is a sudden fever which can be caused by various viruses such as dengue, Zika, and chikungunya viruses. This study aimed to identify viruses present in AFI patients via metagenomic next-generation sequencing (mNGS) through meta-analysis, and to compare the prevalence and viral load of the common viruses between AFI patients and healthy blood donors in northeastern Thailand. Our meta-analysis revealed that human anelloviruses-including torque teno virus (TTV), torque teno mini virus (TTMV), and torque teno midi virus (TTMDV)-were the most prevalent viruses detected. We confirmed their presence in peripheral blood mononuclear cells from 203 AFI patients and 100 healthy blood donors using real-time PCR. TTV was the most identified anellovirus, detected in 84% of healthy donors and 61.08% of AFI patients. The mean TTV load was significantly lower in AFI patients compared to healthy donors. In AFI patients, TTV load increased in those with higher total white blood cell and neutrophil counts but decreased in those with higher lymphocyte counts. Our findings demonstrate high prevalence of anelloviruses, particularly TTV, in both AFI patients and healthy donors, and highlight the potential value of the TTV load in blood as an immune status biomarker in AFI patients.

South Africa has many developmental challenges but three have been identified as affecting each other. The three challenges are unemployment, poverty and inequality. The Second Quarter Report by Statistics South Africa (STATSSA) confirms that poverty, unemployment and inequality are highest in rural areas and most especially among people with no or little education. Meanwhile, many people in rural South Africa have access to land which can be used to produce food for the ever increasing population in both the rural and urban areas, as well as for export and other value adding agribusinesses. The task of addressing the challenges of poor communities calls for a multi-stakeholder approach which can include the private sector, NGOs, communities, traditional leaders and the state coming together to pursue economic transformation in rural South Africa by tapping into the natural resources nature has provided for the communities. This article reports on how some stakeholders have come together to transform a rural community in South Africa. The paper uses qualitative data from personal and focus group interviews and observations as the main data collection instruments. The findings indicate that the stakeholders have been able to empower a community by tapping into and effectively using the natural resources in an area to transform it through collaborations and partnerships. The model is recommended to the government and development practitioners for adoption on how the natural resources that exist within communities can be exploited and effectively managed to transform rural economies to ensure inclusive growth and development.

Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Several dengue diagnosis methods are recommended by WHO. The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity. Therefore, clinical diagnosis remains a common practice especially in resource limited settings. Bayesian networks have been shown to be a useful tool for diagnostic decision support. This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue. Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation. The two best final models were selected: one with and one without NS1 rapid test result. The diagnostic accuracy of the models was compared with that of physicians on the same set of patients. The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively. The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital’s fellows in infectious disease. Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses. The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.

IntroductionA wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro.MethodsA total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants.ResultsThe median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients.ConclusionThese results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.

Fever is a common symptom of infectious diseases including for those with epidemic potential. Beyond malaria, the causes of undifferentiated (i.e., non-respiratory, non-diarrheal) acute febrile illnesses are not well characterized in Liberia. From December 2018 through March 2020, we established two acute febrile illness (AFI) sentinel surveillance sites in urban Monrovia at Redemption Hospital and Star of the Sea Health Centre, health facilities that were among the first to have Ebola cases during the 2014-2015 West Africa epidemic. Enrolled AFI patients were two (2) years of age or greater, had a measured fever of ≥37.5oC or history of fever within the past week, and without a known cause of fever. A standardized survey was administered to collect demographic, clinical characteristics, and risk factors. Whole blood was taken, nucleic acid material was extracted and ran on TaqMan Array Cards (TAC), a real-time polymerase chain reaction (RT-PCR) testing platform for 28 pathogens. Data were analyzed using descriptive statistics, and multivariate regression models of any TAC detections stratified by site and age. We enrolled 1506 AFI patients, 1206 (80%) from Redemption Hospital and 300 (20%) from Star of the Sea. AFI patients were predominantly female (69%) and had a median (interquartile range) age of 18 (7-27) years. Among the 699 (46%) that were TAC positive, 627 were detected from Redemption Hospital and 72 were detected from Star of the Sea Health Centre. Overall Plasmodium spp. (malaria) (96%) were the majority of detections followed by dengue virus (2%), Streptococcus pneumoniae (2%), and Rickettsia spp. (1%). We detected 19 co-infections [malaria co-infections (84%) being the most common]. Two pathogens with epidemic potential, Neisseria meningitidis (detected at Star of the Sea Health Centre) and Lassa virus (detected at Redemption Hospital), were also found. Patients with non-malaria TAC detections (n = 29) were higher at Star of the Sea Health Centre than Redemption Hospital (4% versus 1% respectively, p < 0.05). In multivariate regression for those ages 15 years and older at Redemption Hospital (adjusting for sex, age, pregnancy status, education, occupation, any medication use, measured fever at enrollment, headache, abdominal pain, vomiting/nausea and joint pain), any medication use (aOR=0.6, 95% CI = 0.4-0.9), measured fever at enrollment (aOR=3.5, 95% CI = 1.1-12.0), headache (aOR=1.7, 95% CI = 1.1-2.6 were statistically significant with any TAC detection. In multivariate regression for those ages 2-14 years at Redemption Hospital (adjusting for sex, age, abdominal pain, cough, vomiting/nausea, runny nose, and any animal exposure), having abdominal pain (aOR=1.9, 95% CI = 1.3-2.8), vomiting/nausea (aOR=0.6, 95% CI = 0.4-1.0), and any animal exposure (aOR=1.5, 95% CI = 1.0-2.3) were statistically significant with any TAC detection. This is the first laboratory evidence of dengue and rickettsial disease in humans in Liberia. Liberia's incipient AFI platform was successful exploring causes of fever in emerging infections and detected circulating pathogens beyond malaria. AFI surveillance data can assist in the prioritization of public health diagnostic and clinical capabilities to prevent, detect, and respond to emerging infectious disease threats in Liberia.

IntroductionFever is a common symptom of infectious diseases including for those with epidemic potential. Beyond malaria, the causes of undifferentiated (i.e., non-respiratory, non-diarrheal) acute febrile illnesses are not well characterized in Liberia.MethodsFrom December 2018 through March 2020, we established two acute febrile illness (AFI) sentinel surveillance sites in urban Monrovia at Redemption Hospital and Star of the Sea Health Centre, health facilities that were among the first to have Ebola cases during the 2014–2015 West Africa epidemic. Enrolled AFI patients were two (2) years of age or greater, had a measured fever of ≥37.5oC or history of fever within the past week, and without a known cause of fever. A standardized survey was administered to collect demographic, clinical characteristics, and risk factors. Whole blood was taken, nucleic acid material was extracted and ran on TaqMan Array Cards (TAC), a real-time polymerase chain reaction (RT-PCR) testing platform for 28 pathogens. Data were analyzed using descriptive statistics, and multivariate regression models of any TAC detections stratified by site and age.ResultsWe enrolled 1506 AFI patients, 1206 (80%) from Redemption Hospital and 300 (20%) from Star of the Sea. AFI patients were predominantly female (69%) and had a median (interquartile range) age of 18 (7–27) years. Among the 699 (46%) that were TAC positive, 627 were detected from Redemption Hospital and 72 were detected from Star of the Sea Health Centre. Overall Plasmodium spp. (malaria) (96%) were the majority of detections followed by dengue virus (2%), Streptococcus pneumoniae (2%), and Rickettsia spp. (1%). We detected 19 co-infections [malaria co-infections (84%) being the most common]. Two pathogens with epidemic potential, Neisseria meningitidis (detected at Star of the Sea Health Centre) and Lassa virus (detected at Redemption Hospital), were also found. Patients with non-malaria TAC detections (n = 29) were higher at Star of the Sea Health Centre than Redemption Hospital (4% versus 1% respectively, p < 0.05). In multivariate regression for those ages 15 years and older at Redemption Hospital (adjusting for sex, age, pregnancy status, education, occupation, any medication use, measured fever at enrollment, headache, abdominal pain, vomiting/nausea and joint pain), any medication use (aOR=0.6, 95% CI = 0.4–0.9), measured fever at enrollment (aOR=3.5, 95% CI = 1.1–12.0), headache (aOR=1.7, 95% CI = 1.1–2.6 were statistically significant with any TAC detection. In multivariate regression for those ages 2–14 years at Redemption Hospital (adjusting for sex, age, abdominal pain, cough, vomiting/nausea, runny nose, and any animal exposure), having abdominal pain (aOR=1.9, 95% CI = 1.3–2.8), vomiting/nausea (aOR=0.6, 95% CI = 0.4–1.0), and any animal exposure (aOR=1.5, 95% CI = 1.0–2.3) were statistically significant with any TAC detection.ConclusionThis is the first laboratory evidence of dengue and rickettsial disease in humans in Liberia. Liberia’s incipient AFI platform was successful exploring causes of fever in emerging infections and detected circulating pathogens beyond malaria. AFI surveillance data can assist in the prioritization of public health diagnostic and clinical capabilities to prevent, detect, and respond to emerging infectious disease threats in Liberia.

BackgroundThe breast cancer burden on the South African healthcare system is severe, with rural South African women often diagnosed at an advanced stage of the disease. South Africa’s rural areas are classified as low-resource settings with limited medical services and infrastructure. The impact of breast cancer on rural communities in South Africa requires ongoing research to better understand the severity of this disease among one of the most vulnerable populations.ObjectivesThis study aimed to explore the barriers and enablers of breast cancer screening among rural South African women.MethodAn exploratory qualitative study was utilised. A semi-structured interview was conducted with 22 rural South African women. Data were analysed using thematic analysis. This study utilised the care-seeking behaviour theory as its theoretical framework.ResultsParticipants identified many barriers to breast cancer screening, including individual affordability, transportation, rural services, infrastructure, health professional behaviour, and the lack of educational materials. Several factors are suggested to enable the screening of breast cancer in rural South Africa, including breast cancer campaigns, health education, the involvement of key stakeholders, and promotional materials.ConclusionDespite the many barriers to breast cancer screening among rural South African women, there is still hope in implementing the various promotional tools outlined in this study and ensuring that breast self-examination is an alternative, affordable screening method.ContributionThe purpose of this article is to contribute to the attainment of the Sustainable Development Goal (SDG) 3, which focusses reducing premature mortality from non-communicable diseases, including cancer.

There is a known shortage of rehabilitation staff in rural settings and a sharp increase in the number of lower limb amputations being performed. A lack of adequate pre-prosthetic rehabilitation will result in worse physical and psychological outcomes for a person with a lower limb amputation, and they will not be eligible to be fitted with a prosthesis. To explore therapists' experiences with providing pre-prosthetic rehabilitation in a rural setting. A qualitative descriptive approach was used to collect and analyse data. Data were collected from 17 purposively sampled therapists in five district hospitals in a rural community in South Africa. Data were collected in two rounds of focus groups to explore the challenges of providing pre-prosthetic rehabilitation in rural South Africa. The main themes identified in the study were (1) a lack of government health system support, (2) poor socioeconomic circumstances of patients and (3) cultural factors that influence rehabilitation. These themes all negatively influence the therapists' ability to follow up patients for pre-prosthetic rehabilitation after discharge from hospital. A lack of adequate pre-prosthetic rehabilitation is a substantial barrier to prosthetic fitting in rural South Africa. Patients who do not receive pre-prosthetic rehabilitation have a poorly shaped residuum or other complications such as knee or hip joint contractures which disqualifies them from being referred to prosthetic services. Therapists involved in this study identified the most important barriers to patients having access to prosthetic services. Clinical relevance Pre-prosthetic rehabilitation provides care of the residuum; maintenance or improvement of physical strength, joint range of motion and referral to a prosthetist. By exploring the challenges known to exist in this service, we can identify potential ways to reduce these barriers and improve the lives of those who use it.