The Good Wishes Project: An End-of-Life Intervention for Individuals Experiencing Homelessness.

Background: Individuals experiencing homelessness face marginalization, dehumanization, and barriers to accessing quality palliative care. Inspired by the 3 Wishes Project, the Good Wishes Project (GWP) facilitates granting wishes to individuals experiencing homelessness and receiving palliative care with a goal of enhancing comfort and personalizing the end-of-life experience. Objective: The main objective of this study was to elicit provider perspectives on the utility of the GWP in the delivery of end-of-life care to a population of homeless and vulnerably housed individuals. Design: For this qualitative study, GWP client information and wish data were collected anonymously and analyzed quantitatively and descriptively. Semistructured interviews were conducted with health and social service professionals who cared for GWP clients. Interviews were recorded, transcribed, and analyzed through qualitative content analysis. Results: At the time of evaluation, there were a total of 27 clients in the GWP. At 14 months after the project's launch, 40 wishes had been made, 24 of which had been granted. Wishes were classified into five categories: basic necessities, end-of-life preparations, personal connections, paying-it-forward, and leisure. From the provider perspective (n = 7), the project was found to have utility in three main domains: establishing and enhancing connection, satisfying basic needs, and promoting person-centered care. Conclusions: The GWP is a promising psychosocial intervention in providing quality palliative care to individuals experiencing homelessness, whose lives have largely been burdened with hardship and marginalization.

Outcomes of an individual counselling programme in Grozny, Chechnya: a randomised controlled study.

OBJECTIVES: To evaluate the effectiveness of individual counselling on functioning of clients participating in a mental health intervention in a humanitarian setting. DESIGN: Randomised controlled trial. SETTING: Mental health programme implemented by Médecins Sans Frontières in Grozny, Republic of Chechnya. PARTICIPANTS: 168 eligible clients were randomly assigned to the intervention and waitlisted (2 months) arms between November 2014 and February 2015. INTERVENTION: Individual counselling sessions. MAIN OUTCOME MEASURES: Change in functioning was measured using the Short Form 6 (SF6) and gender-specific locally adapted Chechen functioning instruments in the intervention group at the end of counselling and the waitlisted group after their waitlisted period. Unadjusted differences in gain scores (DGSs) between intervention and waitlisted groups were calculated with effect size (Cohen's d) for both tools. Linear regression compared the mean DGS in both groups. RESULTS: The intervention group (n=78) improved compared with waitlisted controls (n=80) on the SF6 measures with moderate to large effect sizes: general health (DGS 12.14, d=0.52), body pain (DGS 10.26, d=0.35), social support (DGS 16.07, d=0.69) and emotional functioning (DGS 16.87, d=0.91). Similar improvement was seen using the Chechen functioning instrument score (female DGS -0.33, d=0.55; male DGS -0.40, d=0.99). Adjusted analysis showed significant improvement (p<0.05) in the intervention group for all SF6 measures and for the Chechen functioning instrument score in women but not men (p=0.07). CONCLUSIONS: Individual counselling significantly improved participants' ability to function in the intervention group compared with the waitlisted group. Further research is needed to determine whether similar positive results can be shown in other settings and further exploring the impact in male clients' population. TRIAL REGISTRATION NUMBER: NTR4689.

Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa.

Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites.

INTRODUCTION: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. METHODS: In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. RESULTS: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. CONCLUSIONS: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.

Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives.

INTRODUCTION: Although individual HIV rapid diagnostic tests (RDTs) show good performance in evaluations conducted by WHO, reports from several African countries highlight potentially significant performance issues. Despite widespread use of RDTs for HIV diagnosis in resource-constrained settings, there has been no systematic, head-to-head evaluation of their accuracy with specimens from diverse settings across sub-Saharan Africa. We conducted a standardized, centralized evaluation of eight HIV RDTs and two simple confirmatory assays at a WHO collaborating centre for evaluation of HIV diagnostics using specimens from six sites in five sub-Saharan African countries. METHODS: Specimens were transported to the Institute of Tropical Medicine (ITM), Antwerp, Belgium for testing. The tests were evaluated by comparing their results to a state-of-the-art reference algorithm to estimate sensitivity, specificity and predictive values. RESULTS: 2785 samples collected from August 2011 to January 2015 were tested at ITM. All RDTs showed very high sensitivity, from 98.8% for First Response HIV Card Test 1-2.0 to 100% for Determine HIV 1/2, Genie Fast, SD Bioline HIV 1/2 3.0 and INSTI HIV-1/HIV-2 Antibody Test kit. Specificity ranged from 90.4% for First Response to 99.7% for HIV 1/2 STAT-PAK with wide variation based on the geographical origin of specimens. Multivariate analysis showed several factors were associated with false-positive results, including gender, provider-initiated testing and the geographical origin of specimens. For simple confirmatory assays, the total sensitivity and specificity was 100% and 98.8% for ImmunoComb II HIV 12 CombFirm (ImmunoComb) and 99.7% and 98.4% for Geenius HIV 1/2 with indeterminate rates of 8.9% and 9.4%. CONCLUSION: In this first systematic head-to-head evaluation of the most widely used RDTs, individual RDTs performed more poorly than in the WHO evaluations: only one test met the recommended thresholds for RDTs of ≥99% sensitivity and ≥98% specificity. By performing all tests in a centralized setting, we show that these differences in performance cannot be attributed to study procedure, end-user variation, storage conditions, or other methodological factors. These results highlight the existence of geographical and population differences in individual HIV RDT performance and underscore the challenges of designing locally validated algorithms that meet the latest WHO-recommended thresholds.

Monitoring and Evaluating Psychosocial Intervention Outcomes in Humanitarian Aid.

Existing tools for evaluating psychosocial interventions (un-validated self-reporting questionnaires) are not ideal for use in non-Western conflict settings. We implement a generic method of treatment evaluation, using client and counsellor feedback, in 18 projects in non-Western humanitarian settings. We discuss our findings from the perspective of validity and suggestions for future research. A retrospective analysis is executed using data gathered from psychosocial projects. Clients (n = 7,058) complete two (complaints and functioning) rating scales each session and counsellors rate the client's status at exit. The client-completed pre- and post-intervention rating scales show substantial changes. Counsellor evaluation of the clients' status shows a similar trend in improvement. All three multivariable models for each separate scale have similar associations between the scales and the investigated variables despite different cultural settings. The validity is good. Limitations are: ratings give only a general impression and clinical risk factors are not measured. Potential ceiling effects may influence change of scales. The intra and inter-rater reliability of the counsellors' rating is not assessed. The focus on client and counsellor perspectives to evaluate treatment outcome seems a strong alternative for evaluation instruments frequently used in psychosocial programming. The session client rated scales helps client and counsellor to set mutual treatment objectives and reduce drop-out risk. Further research should test the scales against a cross-cultural valid gold standard to obtain insight into their clinical relevance.

Effect of Short-Term Supplementation with Ready-to-Use Therapeutic Food or Micronutrients for Children after Illness for Prevention of Malnutrition: A Randomised Controlled Trial in Uganda.

BACKGROUND: Globally, Médecins Sans Frontières (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food but also by illnesses and by poor infant and child feeding practices. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2-wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here, we report on the trial that took place in Kaabong, a poor agropastoral region of Karamoja, in east Uganda. While the region of Karamoja shows an acute malnutrition rate between 8.4% and 11.5% of which 2% to 3% severe malnutrition, more than half (58%) of the population in the district of Kaabong is considered food insecure. METHODS AND FINDINGS: We investigated the effect of two types of nutritional supplementation on the incidence of malnutrition in ill children presenting at outpatient clinics during March 2011 to April 2012 in Kaabong, Karamoja region, Uganda, a resource-poor region where malnutrition is a chronic problem for its seminomadic population. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed with malaria, diarrhoea, or lower respiratory tract infection. Non-malnourished children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of ready-to-use therapeutic food (RUTF), two sachets/d of micronutrient powder (MNP), or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate progression to moderate or severe acute malnutrition; it was defined as weight-for-height z-score <-2, mid-upper arm circumference (MUAC) <115 mm, or oedema, whichever came first. Of the 2,202 randomised participants, 51.2% were girls, and the mean age was 25.2 (±13.8) mo; 148 (6.7%) participants were lost to follow-up, 9 (0.4%) died, and 14 (0.6%) were admitted to hospital. The incidence rates of NNO (first event/year) for the RUTF, MNP, and control groups were 0.143 (95% confidence interval [CI], 0.107-0.191), 0.185 (0.141-0.239), and 0.213 (0.167-0.272), respectively. The incidence rate ratio was 0.67 (95% CI, 0.46-0.98; p = 0.037) for RUTF versus control; a reduction of 33.3%. The incidence rate ratio was 0.86 (0.61-1.23; p = 0.413) for MNP versus control and 0.77 for RUTF versus MNP (95% CI 0.52-1.15; p = 0.200). The average numbers of study illnesses for the RUTF, MNP, and control groups were 2.3 (95% CI, 2.2-2.4), 2.1 (2.0-2.3), and 2.3 (2.2-2.5). The proportions of children who died in the RUTF, MNP, and control groups were 0%, 0.8%, and 0.4%. The findings apply to ill but not malnourished children and cannot be generalised to a general population including children who are not necessarily ill or who are already malnourished. CONCLUSIONS: A 2-wk nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, LRTI, or diarrhoea proved effective in preventing malnutrition in eastern Uganda. The low incidence of malnutrition in this population may warrant a more targeted intervention to improve cost effectiveness. TRIAL REGISTRATION: clinicaltrials.gov NCT01497236.

Effect of Short-Term Supplementation with Ready-to-Use Therapeutic Food or Micronutrients for Children after Illness for Prevention of Malnutrition: A Randomised Controlled Trial in Nigeria.

BACKGROUND: Globally, Médecins Sans Frontières (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food and poor infant and child feeding practices but also by illnesses. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2-wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here we report on the trial that took place in Goronyo, a rural region of northwest Nigeria with high morbidity and malnutrition rates. METHODS AND FINDINGS: We investigated the effect of supplementation with ready-to-use therapeutic food (RUTF) and a micronutrient powder (MNP) on the incidence of malnutrition in ill children presenting at an outpatient clinic in Goronyo during February to September 2012. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed as having malaria, diarrhoea, or lower respiratory tract infection. Children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of RUTF; two sachets/d of micronutrients or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate occurrence of malnutrition; it was defined as low weight-for-height z-score (<-2 for non-malnourished and <-3 for moderately malnourished children), mid-upper arm circumference <115 mm, or oedema, whichever came first. Of the 2,213 randomised participants, 50.0% were female and the mean age was 20.2 (standard deviation 11.2) months; 160 (7.2%) were lost to follow-up, 54 (2.4%) were admitted to hospital, and 29 (1.3%) died. The incidence rates of NNO for the RUTF, MNP, and control groups were 0.522 (95% confidence interval (95% CI), 0.442-0.617), 0.495 (0.415-0.589), and 0.566 (0.479-0.668) first events/y, respectively. The incidence rate ratio was 0.92 (95% CI, 0.74-1.15; p = 0.471) for RUTF versus control; 0.87 (0.70-1.10; p = 0.242) for MNP versus control and 1.06 (0.84-1.33, p = 0.642) for RUTF versus MNP. A subgroup analysis showed no interaction nor confounding, nor a different effectiveness of supplementation, among children who were moderately malnourished compared with non-malnourished at enrollment. The average number of study illnesses for the RUTF, MNP, and control groups were 4.2 (95% CI, 4.0-4.3), 3.4 (3.2-3.6), and 3.6 (3.4-3.7). The proportion of children who died in the RUTF, MNP, and control groups were 0.8% (95% CI, 0.3-1.8), 1.8% (1.0-3.3), and 1.4% (0.7-2.8). CONCLUSIONS: A 2-wk supplementation with RUTF or MNP to ill children as part of routine primary medical care did not reduce the incidence of malnutrition. The lack of effect in Goronyo may be due to a high frequency of morbidity, which probably further affects a child's nutritional status and children's ability to escape from the illness-malnutrition cycle. The duration of the supplementation may have been too short or the doses of the supplements may have been too low to mitigate the effects of high morbidity and pre-existing malnutrition. An integrated approach combining prevention and treatment of diseases and treatment of moderate malnutrition, rather than prevention of malnutrition by nutritional supplementation alone, might be more effective in reducing the incidence of acute malnutrition in ill children. TRIAL REGISTRATION: clinicaltrials.gov NCT01154803.

Learning without Borders: A Review of the Implementation of Medical Error Reporting in Médecins Sans Frontières.

OBJECTIVE: To analyse the results from the first 3 years of implementation of a medical error reporting system in Médecins Sans Frontières-Operational Centre Amsterdam (MSF) programs. METHODOLOGY: A medical error reporting policy was developed with input from frontline workers and introduced to the organisation in June 2010. The definition of medical error used was "the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim." All confirmed error reports were entered into a database without the use of personal identifiers. RESULTS: 179 errors were reported from 38 projects in 18 countries over the period of June 2010 to May 2013. The rate of reporting was 31, 42, and 106 incidents/year for reporting year 1, 2 and 3 respectively. The majority of errors were categorized as dispensing errors (62 cases or 34.6%), errors or delays in diagnosis (24 cases or 13.4%) and inappropriate treatment (19 cases or 10.6%). The impact of the error was categorized as no harm (58, 32.4%), harm (70, 39.1%), death (42, 23.5%) and unknown in 9 (5.0%) reports. Disclosure to the patient took place in 34 cases (19.0%), did not take place in 46 (25.7%), was not applicable for 5 (2.8%) cases and not reported for 94 (52.5%). Remedial actions introduced at headquarters level included guideline revisions and changes to medical supply procedures. At field level improvements included increased training and supervision, adjustments in staffing levels, and adaptations to the organization of the pharmacy. CONCLUSION: It was feasible to implement a voluntary reporting system for medical errors despite the complex contexts in which MSF intervenes. The reporting policy led to system changes that improved patient safety and accountability to patients. Challenges remain in achieving widespread acceptance of the policy as evidenced by the low reporting and disclosure rates.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

BACKGROUND: Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. METHODOLOGY/PRINCIPAL FINDINGS: Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). CONCLUSION: The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

"Losing the tombola": a case study describing the use of community consultation in designing the study protocol for a randomised controlled trial of a mental health intervention in two conflict-affected regions.

BACKGROUND: Community consultation is increasingly recommended, and in some cases, required by ethical review boards for research that involves higher levels of ethical risk such as international research and research with vulnerable populations. In designing a randomised control trial of a mental health intervention using a wait list control, we consulted the community where the research would be undertaken prior to finalising the study protocol. The study sites were two conflict-affected locations: Grozny in the Chechen Republic and Kitchanga in eastern Democratic Republic of Congo. METHODS: Group discussions with a range of community members were held in both study sites. Facilitators used a prepared set of questions to guide the discussions and to solicit feedback on the value of the research as well as on the study design. Specific questions were asked about enablers and barriers to participation in the research. RESULTS: Six groups were held in Grozny and thirteen in Kitchanga. The majority of individuals and groups consulted supported the research, and understood the purpose. In Grozny, the main concern raised was the length of the waiting period. Barriers to both waiting and returning for follow up were identified. In Kitchanga, there was a strong reaction against the wait list control and against randomisation. The consultations provided information on unanticipated harms to the community, allowing changes to the study design to mitigate these harms and increase acceptability of the study. It also served to inform the community of the study, and through engaging with them early, helped promote legitimacy and joint responsibility. CONCLUSION: Community consultation prior to finalising the study design for a mental health intervention trial in two humanitarian settings proved feasible. Our experience reinforces the importance of community consultation before the study design is finalised and the importance of broad consultation that includes both community leaders and the potential study participants.

Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings.

BACKGROUND: Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results. METHODS: Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result. RESULTS: 2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %. CONCLUSION: This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01716299 .

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses.

BACKGROUND: In Ethiopia a tiebreaker algorithm using 3 rapid diagnostic tests (RDTs) in series is used to diagnose HIV. Discordant results between the first 2 RDTs are resolved by a third 'tiebreaker' RDT. Médecins Sans Frontières uses an alternate serial algorithm of 2 RDTs followed by a confirmation test for all double positive RDT results. The primary objective was to compare the performance of the tiebreaker algorithm with a serial algorithm, and to evaluate the addition of a confirmation test to both algorithms. A secondary objective looked at the positive predictive value (PPV) of weakly reactive test lines. METHODS: The study was conducted in two HIV testing sites in Ethiopia. Study participants were recruited sequentially until 200 positive samples were reached. Each sample was re-tested in the laboratory on the 3 RDTs and on a simple to use confirmation test, the Orgenics Immunocomb Combfirm® (OIC). The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. RESULTS: 2620 subjects were included with a HIV prevalence of 7.7%. Each of the 3 RDTs had an individual specificity of at least 99%. The serial algorithm with 2 RDTs had a single false positive result (1 out of 204) to give a PPV of 99.5% (95% CI 97.3%-100%). The tiebreaker algorithm resulted in 16 false positive results (PPV 92.7%, 95% CI: 88.4%-95.8%). Adding the OIC confirmation test to either algorithm eliminated the false positives. All the false positives had at least one weakly reactive test line in the algorithm. The PPV of weakly reacting RDTs was significantly lower than those with strongly positive test lines. CONCLUSION: The risk of false positive HIV diagnosis in a tiebreaker algorithm is significant. We recommend abandoning the tie-breaker algorithm in favour of WHO recommended serial or parallel algorithms, interpreting weakly reactive test lines as indeterminate results requiring further testing except in the setting of blood transfusion, and most importantly, adding a confirmation test to the RDT algorithm. It is now time to focus research efforts on how best to translate this knowledge into practice at the field level. TRIAL REGISTRATION: Clinical Trial registration #: NCT01716299.

Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. METHODS AND FINDINGS: In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. CONCLUSIONS: Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.

Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. METHODS AND FINDINGS: We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 µg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. INTERPRETATION: Increasing VBLL (from ≥80 µg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols.

Diagnostic accuracy evaluation of the ImmunoFlow HCV rapid immunochromatographic test for the detection of hepatitis C antibodies.

2% of the world's population lives with a hepatitis C virus (HCV) infection with highest rates in developing countries. The most common mode of transmission takes place via unsafe blood transfusions and unsafe therapeutic injections. Thus, screening potential blood donors for hepatitis C infection is a must to ensure safe blood transfusions. Rapid immunochromatographic tests are the best suitable test format to be used for screening for blood donors in resource-limited settings. The ImmunoFlow HCV from Core Diagnostics was evaluated at the Paul-Ehrlich-Institute, Germany for its test accuracy on three seropanels. Panel 1 consisted of 26 HCV positive and 55 negative samples, panel 2 of 193 HCV positive samples. Panel 3 contained 116 samples of 10 patients during seroconversion period. 39 of these 116 samples were characterized as HCV positive. The HCV ImmunoFlow had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.8-100) when samples of panel 1 were tested. 191 samples of the 193 samples in panel 2 were correctly by the HCV Immunoflow, resulting in a sensitivity of 99.0%. 9 of 10 HCV infections were detected by the HCV ImmunoFlow when panel 3 was used. This evaluation revealed good sensitivity of the HCV ImmunoFlow test from and compares favorably with the results from the WHO evaluation and a systematic review conducted of field evaluations of Hepatitis C rapid diagnostic and other point of care tests.

Spinal cord injury in the emergency context: review of program outcomes of a spinal cord injury rehabilitation program in Sri Lanka.

BACKGROUND: The final months of the conflict in Sri Lanka in 2009 resulted in massive displacement of the civilian population and a high volume of orthopedic trauma including spinal cord injury. In response to this need, Médecins Sans Frontières implemented a multidisciplinary rehabilitation program. METHODS: Patients were admitted to the program if they had a spinal cord injury, a stable spine and absence of a high-grade pressure ulcer. All patients were assessed on admission with a standardized functional scale the Spinal Cord Independence Measure II (SCIM) and the American Spinal Injury Association Impairment Scale (ASIA). A multidisciplinary team provided nursing care, physiotherapy, bowel and bladder training, mental health care, and vocational rehabilitation. Patients were discharged from the program when medically stable and able to perform activities of daily living independently or with assistance of a caregiver. The primary outcome measures were discharge to the community, and change in SCIM score on discharge. Secondary outcome measures were measured at 6-12 weeks post-discharge, and included SCIM score and presence of complications (pressure ulcers, urinary tract infections and bowel problems). RESULTS: 89 patients were admitted. The majority of injuries were to the thoracic region or higher (89%). The injuries were classified as ASIA grade A in 37 (43%), grade B in 17(20%), grade C in 15 (17%) and grade D in 17(20%). 83.2% met the criteria for discharge, with a further 7.9% patients requiring transfer to hospital for surgical care of pressure ulcers. There was a significant change in SCIM score from 55 on admission to 71 on discharge (p < 0.01). 79.8% and 66.7% achieved a clinically significant and substantially significant SCIM score improvement, respectively. Amongst those with follow up data, there was a reduction in post spinal cord injury complications from those experienced either at or during admission. A further 79% of SCIM scores were stable or improved compared to the score on discharge. CONCLUSIONS: Provision of effective rehabilitation for spinal cord injury is possible in complex humanitarian emergency situations. A multidisciplinary approach, including psychological support along with partnerships with local and international organizations with specialized expertise, was key to the program's success.

Causes of false-positive HIV rapid diagnostic test results.

HIV rapid diagnostic tests have enabled widespread implementation of HIV programs in resource-limited settings. If the tests used in the diagnostic algorithm are susceptible to the same cause for false positivity, a false-positive diagnosis may result in devastating consequences. In resource-limited settings, the lack of routine confirmatory testing, compounded by incorrect interpretation of weak positive test lines and use of tie-breaker algorithms, can leave a false-positive diagnosis undetected. We propose that heightened CD5+ and early B-lymphocyte response polyclonal cross-reactivity are a major cause of HIV false positivity in certain settings; thus, test performance may vary significantly in different geographical areas and populations. There is an urgent need for policy makers to recognize that HIV rapid diagnostic tests are screening tests and mandate confirmatory testing before reporting an HIV-positive result. In addition, weak positive results should not be recognized as valid except in the screening of blood donors.

Variation in specificity of HIV rapid diagnostic tests over place and time: an analysis of discordancy data using a Bayesian approach.

BACKGROUND: Recent trends to earlier access to anti-retroviral treatment underline the importance of accurate HIV diagnosis. The WHO HIV testing strategy recommends the use of two or three rapid diagnostic tests (RDTs) combined in an algorithm and assume a population is serologically stable over time. Yet RDTs are prone to cross reactivity which can lead to false positive or discordant results. This paper uses discordancy data from Médecins Sans Frontières (MSF) programmes to test the hypothesis that the specificity of RDTs change over place and time. METHODS: Data was drawn from all MSF test centres in 2007-8 using a parallel testing algorithm. A Bayesian approach was used to derive estimates of disease prevalence, and of test sensitivity and specificity using the software WinBUGS. A comparison of models with different levels of complexity was performed to assess the evidence for changes in test characteristics by location and over time. RESULTS: 106, 035 individuals were included from 51 centres in 10 countries using 7 different RDTs. Discordancy patterns were found to vary by location and time. Model fit statistics confirmed this, with improved fit to the data when test specificity and sensitivity were allowed to vary by centre and over time. Two examples show evidence of variation in specificity between different testing locations within a single country. Finally, within a single test centre, variation in specificity was seen over time with one test becoming more specific and the other less specific. CONCLUSION: This analysis demonstrates the variable specificity of multiple HIV RDTs over geographic location and time. This variability suggests that cross reactivity is occurring and indicates a higher than previously appreciated risk of false positive HIV results using the current WHO testing guidelines. Given the significant consequences of false HIV diagnosis, we suggest that current testing and evaluation strategies be reviewed.