Evaluation of a point-of-care test for the diagnosis of Taenia solium neurocysticercosis in rural southern Tanzania: a diagnostic accuracy study.

BACKGROUND: Neurocysticercosis is a common cause of epilepsy in Taenia solium-endemic areas in sub-Saharan Africa but is often undiagnosed because of an absence of affordable diagnostic tools. This study evaluated the diagnostic accuracy of a T solium cysticercosis antibody-detecting lateral-flow point-of-care assay (TS POC test) for the neuroimaging-based diagnosis of neurocysticercosis. METHODS: Patients with epileptic seizures or severe progressive headache were recruited consecutively from three hospitals in southern Tanzania. All patients were tested with the TS POC test. All patients positive for cysticercosis on the TS POC test and every tenth patient who was negative for cysticercosis received a brain CT examination and underwent reference testing for T solium cysticercosis (ie, rT24H-EITB, LLGP-EITB, and antigen ELISA). The primary outcome of the study was the sensitivity of the TS POC test for the diagnosis of neurocysticercosis. FINDINGS: Of the 601 recruited participants, 102 (17%) tested positive for cysticercosis with the TS POC test. Overall, 48 (62%) of the 77 patients positive for cysticercosis and five (17%) of the 29 patients negative for cysticercosis on the TS POC test had CT-confirmed neurocysticercosis. The TS POC test yielded a sensitivity of 49% (uncertainty interval [UI] 41-58) for neurocysticercosis. Sensitivity was similar to that of the rT24H-EITB (44%, UI 37-51) and the antigen ELISA (50%, 43-56). For the subset of neurocysticercosis cases with at least one active (ie, vesicular) lesion, sensitivity was above 98% for the TS POC test, the rT24H-ETIB, and the antigen ELISA. INTERPRETATION: The TS POC test showed promising results for the diagnosis of neurocysticercosis in patients with vesicular lesions, which need to be confirmed in a larger study. This test could be considered to support policies on screening patients with suspected neurocysticercosis in clinical settings, which would allow appropriate referral for neuroimaging and early treatment. FUNDING: German Federal Ministry of Education and Research and the European & Developing Countries Clinical Trials Partnership. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Knowledge and misconceptions about epilepsy among people with epilepsy and their caregivers attending mental health clinics: A qualitative study in Taenia solium endemic pig-keeping communities in Tanzania.

OBJECTIVE: Taenia solium (T. solium) neurocysticercosis (NCC) affects the central nervous system and is associated with 30% of acquired epilepsy in some endemic areas. Epilepsy is a stigmatizing disease in many societies and people with epilepsy (PWE) and their families experience discrimination. This study aimed to explore the knowledge, perceptions, and experiences of epilepsy among PWE and their caregivers attending mental health clinics. METHODS: In T. solium endemic areas of Tanzania, PWE and their caregivers attending mental health clinics were identified and their informed consent was sought prior to study participation. In-depth interviews were conducted in Swahili language and analyzed thematically. The coding was undertaken by two independent researchers using NVivo (Version 12, QSR International). RESULTS: Thirty-eight participants were interviewed. Three themes were identified during the analysis, namely, knowledge about epilepsy; perception of epilepsy; and experience with epilepsy among PWE and their caregivers. Participants commonly defined epilepsy as a "falling disease," perceived to be caused by witchcraft, and were unaware of the association between T. solium and epilepsy. Stigmatization of epilepsy was reported as a problem. Reported treatment patterns after the initial onset of epilepsy varied widely; however, patients usually began treatment with traditional healing methods, and only later opted for biomedical treatment. Patients had generally poor adherence to antiseizure medication, which could be caused by inadequate knowledge or irregular supply. SIGNIFICANCE: Level of knowledge about epilepsy was low, and NCC was not mentioned as a cause of epilepsy among participants. Epilepsy was generally perceived to be the result of witchcraft, evil spirits, or curses. Health education is needed, including an explanation of the model of T. solium transmission and the insistence on hygiene measures. This could reduce the number of new infections with T. solium, improve access to prompt biomedical treatment, and improve the lives of PWE.

Implementing tuberculosis patient cost surveys in resource-constrained settings: lessons from Tanzania.

Tuberculosis (TB) disproportionally affects persons and families who are economically and socially disadvantaged. Therefore, a patient cost survey was conducted in Tanzania to evaluate the costs incurred by patients and their households before and after the diagnosis of TB. It was the first survey in Tanzania to ascertain baseline information and experience for subsequent surveys. This paper aims to share the experience encountered during the survey to ensure a standardized approach and elimination of potential barriers for the implementation of future surveys. A total of 777 TB patients from 30 clusters selected based on probability proportional to the size were interviewed during the study period. As the sample size was calculated based on notification data from the previous year, some health facilities experienced an inadequate number of TB patients during the study to meet the allocated cluster size for the survey. Most facilities had poor recording and recordkeeping in TB registers where deaths were not registered, and some patients had not been assigned district identification numbers. Fixed days for TB drug refills in health facilities affected the routine implementation of the survey as the interviews were conducted when patients visited the facility to pick up the drugs. Tablets used to collect data failed to capture the geographic location in some areas. The households of TB patients lost to follow-up and those who had died during TB treatment were not included in the survey. When planning and preparing for patient costs surveys, it is important to consider unforeseen factors which may affect planned activities and findings. During the survey in Tanzania, the identified challenges included survey logistics, communications, patient enrollment, and data management issues. To improve the quality of the findings of future surveys, it may be reasonable to revise survey procedures to include households of TB patients who were lost to follow-up and those who died during TB treatment; the households of such patients may have incurred higher direct and indirect costs than households whose patient was cured as a result of receiving TB treatment.

Epidemiological, clinical and radiological characteristics of people with neurocysticercosis in Tanzania-A cross-sectional study.

BACKGROUND: Neurocysticercosis (NCC) is common among people with epilepsy in low-resource settings. Prevalence of NCC and radiological characteristics of patients with NCC vary considerably even within small areas but differences have been poorly characterized so far. METHODS: We conducted a cross-sectional study between August 2018 and April 2020 in three district hospitals in southern Tanzania (Ifisi, Tukuyu and Vwawa). Patients with and without epileptic seizures were included in this study. All patients were tested with a novel antibody-detecting point-of-care test for the diagnosis of Taenia solium cysticercosis. All test positives and a subset of test negatives had a further clinical work-up including medical examination and computed tomography of the brain. NCC was defined according to the Del Brutto criteria. We assessed epidemiological, clinical and radiological characteristics of patients with NCC by presence of epileptic seizures and by serology status. RESULTS: In all three district hospitals, more than 30% of all people with epileptic seizures (PWE) had NCC lesions in their brain (38% in Vwawa, 32% in Tukuyu and 31% in Ifisi). Most PWE with NCC had multiple lesions and mostly parenchymal lesions (at least 85%). If patients were serologically positive, they had in the median more lesions than serologically negative patients (15 [interquartile range 8-29] versus 5 [1.8-11]), and only serologically positive patients had active stage lesions. Furthermore, serologically positive PWE had more lesions than serologically positive people without epileptic seizures (10.5 [7-23]), and more often had active lesions. PWE diagnosed with NCC (n = 53) were older, and more commonly had focal onset seizures (68% versus 44%, p = 0.03) and headache episodes (34% versus 14%, p = 0.06), which were also stronger than in PWE without NCC (p = 0.04). CONCLUSION: NCC is common among PWE. A combination of clinical and serological factors could help to establish an algorithm to identify patients potentially suffering from active NCC, who benefit from further clinical investigation including neuroimaging.

Daily Life and Challenges Faced By Households With Permanent Childhood Developmental Disability in Rural Tanzania - A Qualitative Study.

Severe developmental disability in children affects the life of the child and entire household. We conducted a qualitative study to understand how caregivers manage severe developmental disabilities in children in rural Africa. Families and six children (out of 15 children) who had serious permanent sequelae from a cerebral infection in Handeni, Tanzania, were contacted and invited to a workshop to recount their experience living with severe developmental disabilities. After consent, individual interviews were conducted first through recording of individual digital stories and then through individual semi-structured interviews. Pre-determined key categories were used to analyse the data. Our results showed that developmental disabilities required constant care and reduced the autonomy of the children. Schooling had not been attempted or was halted because of learning problems or inability to meet specialized school costs. Parents were under constant physical, emotional and financial stress. Their occupational earnings decreased. Some families sold their assets to survive. Others began to rely on relatives. Understanding the consequences of developmental disability helps to identify where social support should be focused and improved.

Economic burden of tuberculosis in Tanzania: a national survey of costs faced by tuberculosis-affected households.

BACKGROUND: Although tuberculosis (TB) care is free in Tanzania, TB-associated costs may compromise access to services and treatment adherence resulting in poor outcomes and increased risk of transmission in the community. TB can impact economically patients and their households. We assessed the economic burden of TB on patients and their households in Tanzania and identified cost drivers to inform policies and programs for potential interventions to mitigate costs. METHODS: We conducted a nationally representative cross-sectional survey using a standard methodology recommended by World Health Organization. TB patients of all ages and with all types of TB from 30 clusters across Tanzania were interviewed during July - September 2019. We used the human capital approach to assess the indirect costs and a threshold of 20% of the household annual expenditure to determine the proportion of TB-affected households experiencing catastrophic cost. We descriptively analyzed the cost data and fitted multivariable logistic regression models to identify potential predictors of catastrophic costs. RESULTS: Of the 777 TB-affected households, 44.9% faced catastrophic costs due to TB. This proportion was higher (80.0%) among households of patients with multi-drug resistant TB (MDR-TB). Overall, cost was driven by income loss while accessing TB services (33.7%), nutritional supplements (32.6%), and medical costs (15.1%). Most income loss was associated with hospitalization and time for picking up TB drugs. Most TB patients (85.9%) reported worsening financial situations due to TB, and over fifty percent (53.0%) borrowed money or sold assets to finance TB treatment. In multivariable analysis, the factors associated with catastrophic costs included hospitalization (adjusted odds ratio [aOR] = 34.9; 95% confidence interval (CI):12.5-146.17), living in semi-urban (aOR = 1.6; 95% CI:1.0-2.5) or rural areas (aOR = 2.6; 95% CI:1.8-3.7), having MDR-TB (aOR = 3.4; 95% CI:1.2-10.9), and facility-based directly-observed treatment (DOT) (aOR = 7.2; 95% CI:2.4-26.6). CONCLUSION: We found that the cost of TB care is catastrophic for almost half of the TB-affected households in Tanzania; our findings support the results from other surveys recently conducted in sub-Saharan Africa. Collaborative efforts across health, employment and social welfare sectors are imperative to minimize household costs due to TB disease and improve access to care, patient adherence and outcomes.

Trial Design of a Prospective Multicenter Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and Neurocysticercosis in Hospital-Based Settings in Tanzania.

Taenia solium diagnosis is challenging as trained personnel, good diagnostic tools, and infrastructure is lacking in resource-poor areas. This paper aims to describe the study trial design adopted to evaluate a newly developed rapid point-of-care test that simultaneously detects taeniosis and neurocysticercosis (TS POC) in three district hospitals in Tanzania. The two-stage design included three types of patients: patients with specific neurological signs and symptoms (group 1); patients with complaints compatible with intestinal worm infections (group 2); patients with other symptom(s) (group 3). For group 1, all patients were tested using the TS POC test (stage 1), after which all positive, and a subset of negative, patients were selected for laboratory reference tests, clinical examination, and a brain computed tomography (CT) scan (stage 2). For groups 2 and 3, a similar design was adopted, but clinical examination and a brain CT scan (stage 2) were only performed in patients who were TS POC test-positive for cysticercosis. Due to the lack of a gold standard, a Bayesian approach was used to determine test accuracy for taeniosis and cysticercosis. For neurocysticercosis, a composite case definition was used as the reference standard. If successful, this study will help the future developments (commercialization and implementation) of the rapid test and improve patient management and disease prevention.

Post-Ebola Awakening: Urgent Call for Investing in Maintaining Effective Preparedness Capacities at the National and Regional Levels in Sub-Saharan Africa.

BACKGROUND: The 2014 Ebola outbreak reminded us of the importance of preparedness for addressing health security threats. Learning from this experience, we aim to (1) enhance the understanding of preparedness by policy and decision makers, (2) discuss opportunities for Africa to invest in the prevention of health security threats, (3) highlight the value of investing in preventing health security threats, and (4) propose innovations to enhance investments for the prevention or containment of health security threats at the source. METHODS: We used observations of governments' attitudes towards investing in preparedness for health security prevention or containment at the source. We conducted a literature review through PubMed, the World Wide Web, and Mendeley using the keywords: "health emergency financing", "investing in health threats prevention", and "stopping outbreaks at the source". RESULTS: Countries in sub-Saharan Africa invest inadequately towards building and maintaining critical capacities for preventing, detecting, and containing outbreaks at the source. Global health security emergency funding schemes target responses to outbreaks but neglect their prevention. Governments are not absorbing and maintaining adequately capacity built through GHS, World Bank, and development aid projects - a lost opportunity for building and retaining outbreak prevention capacity. RECOMMENDATIONS: Governments should (1) allocate adequate national budgets for health honouring the Abuja and related commitments; (2) own and maintain capacities developed through International Development Aids, OH networks, research consortia and projects; (3) establish a regional health security threats prevention fund. The global community and scientists should (1) consider broadening existing health emergency funds to finance the prevention and containment outbreaks at the source and (2) Strengthen economic analyses and case studies as incentives for governments' budget allocations to prevent health security threats.

Can we measure cognitive constructs consistently within and across cultures? Evidence from a test battery in Bangladesh, Ghana, and Tanzania.

We developed a test battery for use among children in Bangladesh, Ghana, and Tanzania, assessing general intelligence, executive functioning, and school achievement. The instruments were drawn from previously published materials and tests. The instruments were adapted and translated in a systematic way to meet the needs of the three assessment contexts. The instruments were administered by a total of 43 trained assessors to 786 children in Bangladesh, Ghana, and Tanzania with a mean age of about 13 years (range: 7-18 years). The battery provides a psychometrically solid basis for evaluating intervention studies in multiple settings. Within-group variation was adequate in each group. The expected positive correlations between test performance and age were found and reliability indices yielded adequate values. A confirmatory factor analysis (not including the literacy and numeracy tests) showed a good fit for a model, merging the intelligence and executive tests in a single factor labeled general intelligence. Measurement weights invariance was found, supporting conceptual equivalence across the three country groups, but not supporting full score comparability across the three countries.

The use of placebo in a trial of rectal artesunate as initial treatment for severe malaria patients en route to referral clinics: ethical issues.

Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere.