'SILVAMP TB LAM' rapid urine tuberculosis test predicts mortality in hospitalized HIV patients in South Africa. Sossen, B; Broger, T; Kerkhoff, AD; Schutz, C; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Wilkinson, RJ; Barr, DA; Nicol, MP; Denkinger, CM; Meintjes, G Reducing diagnostic delay is key towards decreasing tuberculosis-associated deaths in people living with HIV. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.
Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger Coldiron, M; Assao, B; Langendorf, C; Sayinzoga-Makombe, N; de la Tour, R; Piriou, E; Ciglenecki, I; Mumina, A; Guindo, O; Page, A-L; Yarima Bako, M; Grais, R Background Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. Methods A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. Results In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. Conclusions The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India Isaakidis, P; Ferlazzo, G; Das, M; Pasupuleti, D; Sloan, S; Hossain, F; Kalon, S; Mansoor, H; Rao, S Abstract: Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
“To die is better for me”, social suffering among Syrian refugees at a noncommunicable disease clinic in Jordan: A Qualitative Study Ansbro, E; Maconick, L; Ellithy, S; Jobanputra, K; Tarawneh, M; Roberts, B Background The conflict in Syria has required humanitarian agencies to implement primary-level services for non-communicable diseases (NCDs) in Jordan, given the high NCD burden amongst Syrian refugees; and to integrate mental health and psychosocial support into NCD services given their comorbidity and treatment interactions. However, no studies have explored the mental health needs of Syrian NCD patients. This paper aims to examine the interaction between physical and mental health of patients with NCDs at a Médecins Sans Frontières (MSF) clinic in Irbid, Jordan, in the context of social suffering. Methods This qualitative study involved sixteen semi-structured interviews with Syrian refugee and Jordanian patients and two focus groups with Syrian refugees attending MSF’s NCD services in Irbid, and eighteen semi-structured interviews with MSF clinical, managerial and administrative staff. These were conducted by research staff in August 2017 in Irbid, Amman and via Skype. Thematic analysis was used. Results Respondents describe immense suffering and clearly perceived the interconnectedness of their physical wellbeing, mental health and social circumstances, in keeping with Kleinman’s theory of social suffering. There was a ‘disconnect’ between staff and patients’ perceptions of the potential role of the NCD and mental health service in alleviating this suffering. Possible explanations identified included respondent’s low expectations of the ability of the service to impact on the root causes of their suffering, normalisation of distress, the prevailing biomedical view of mental ill-health among national clinicians and patients, and humanitarian actors’ own cultural standpoints. Conclusion NCD patients recognised the psychological dimensions of their illness but may not utilize clinic-based humanitarian mental health and psychosocial support services. Humanitarian agencies must engage with NCD patients to elicit their needs and design culturally relevant services.
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention van Lenthe, M; van der Meulen, R; Okell, L; Piriou, E; Lassovski, M; Bakula, E; Badio, C; Roper, C; Bousema, T; Ouabo, A; Cibenda, D; Grignard, L; Lanke, Kjerstin; Rao, B Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample. Conclusions The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
Trauma in the Kashmir Valley and the mediating effect of stressors of daily life on symptoms of posttraumatic stress disorder, depression and anxiety Housen, T; Lenglet, A; Shah, S; Sha, H; Richardson, A; Pintaldi, G; Shabnum, A Background The negative psychological impact of living in a setting of protracted conflict has been well studied, however there is a recognized need to understand the role that non-conflict related factors have on mediating exposure to trauma and signs of psychological distress. Methods We used data from the 2015 Kashmir Mental Health Survey and conducted mediation analysis to assess the extent to which daily stressors mediated the effect of traumatic experiences on poor mental health outcomes. Outcomes of interest were probable diagnosis of anxiety, depression, or PTSD; measured using the pre-validated Hopkins Symptoms Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ). Results Total effect mediated were statistically significant but the proportions of effect mediated were found to be small in practical terms. Financial stress mediated 6.8% [95% Confidence Interval (CI) 6∙0–8∙4], 6.7% [CI 6.2–7∙7] and 3.6% [CI 3∙4–4∙0] of the effect of experiencing multiple traumaticogenic events on symptoms of anxiety, depression and PTSD, respectively. Family stress mediated 11.3% [CI 10.3–13.8], 10.3% [CI 9.5–11.9] and 6.1% [CI 5.7–6.7] of the effect of experiencing multiple traumatogenic events on symptoms of anxiety, depression and PTSD, respectively. Poor physical health mediated 10.0% [CI 9.1–12∙0], 7.2% [CI 6.6–8.2] and 4.0% [CI 3.8,4.4] of the effect of experiencing more than seven traumatic events on symptoms of anxiety, depression and PTSD, respectively. Conclusion Our findings highlight that not only do we need to move beyond a trauma-focussed approach to addressing psychological distress in populations affected by protracted conflict but we must also move beyond focussing on daily stressors as explanatory mediators.
Increased risk of acquisition and transmission of ESBL-producing Enterobacteriaceae in malnourished children exposed to amoxicillin Maataoui, N; Langendorf, C; Berthe, F; Grais, R; van Schaik, W; Isanaka, S; Clermont, O; Bayjanov, J; Andremont, A; Armand-Lefevre, Laurence; Woerther, P-L OBJECTIVES: Routine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition. METHODS: We screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547. RESULTS: Carriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04]. CONCLUSIONS: Among children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.
Paediatric Buruli ulcer in Australia Walker, G; Friedman, D; Cooper, C; O'Brien, M; McDonald, A; Callan, P; O'Brien, D AIM: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. METHODS: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. RESULTS: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. CONCLUSIONS: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
A reflection on case reporting in resource-limited settings Wind, A In 2015, I was in the Democratic Republic of the Congo (DRC), working as a pediatrician with Médecins Sans Frontières (MSF). As had been the case in my two previous assignments with MSF, I encountered many interesting and challenging cases—cases that I had never experienced prior to working in resource limited settings. Contrary to when I work in the USA and have access to extensive laboratory exams and diagnostic testing, in our hospital in the DRC, no such tools were available, and thus I needed to use a whole new level of clinical skills and deductive reasoning. To make clinical management even more challenging, I rarely saw these types of cases written about or published in the medical literature. I was discouraged that although these clinical examples were perfect fodder for medical case discussions, they did not have the ‘components’ required for a traditional case report. In frustration, I wrote the following: ‘The reason why we, those working in “resource limited settings”, do not often attempt to publish case reports is because we don’t often find an answer. We think that published articles and case reports should be neat and clean. That students or colleagues should be able to read a mystery case, try to solve the puzzle, and at the end be rewarded with an answer brought about by some obscure lab or radiology report. But that’s not what happens. The world of medicine in resource limited settings isn’t neat and clean. It’s frustrating and messy. Mystifying and sad. You can come up with a million differentials but ultimately the child, because of, or in despite of, your chosen treatment, makes it. Or doesn’t make it. And you never get an answer. You don’t learn. And you can try to look in the literature, but the research will talk about IGF1 and MRI and calcium. I can’t even get a cal.ci.um. And so, the mystery disease leads to a mystery death and you are left feeling powerless. And there is not even a take home message.’ I am excited that now with the Oxford Medical Case Reports collaboration, there is a platform to start regaining some power, to start creating a take-home message. There is a platform for collaboration amongst all of us medical professionals working in resource limited settings—a platform to share these unique cases to perhaps discover that they are not so unique at all. They are just not published.
Ensuring On-site Ebola Patient Monitoring and Follow-up: Development of a Laboratory Structure Embedded in an Ebola Treatment Center. Williams, A; Amand, M; Van den Bergh, R; De Clerck, H; Antierens, A; Chaillet, P The capacity to rapidly distinguish Ebola virus disease from other infectious diseases and to monitor biochemistry and viremia levels is crucial to the clinical management of suspected Ebola virus disease cases. This article describes the design and practical considerations of a laboratory straddling the high- and low-risk zones of an Ebola treatment center to produce timely diagnostic and clinical results for informed case management of Ebola virus disease in real-life conditions. This innovation may be of relevance for actors requiring flexible laboratory implementation in contexts of high-communicability, high-lethality disease outbreaks. We regret that this article is behind a paywall.
Feasibility of antiretroviral therapy initiation under the treat‐all policy under routine conditions: a prospective cohort study from Eswatini Kerschberger, B; Jobanputra, K; Schomaker, M; Kabore, SM; Teck, R; Mabhena, E; Lukhele, N; Rusch, B; Boulle, A; Ciglenecki, I Introduction The World Health Organization recommends the Treat‐All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource‐poor settings. We assessed the feasibility of Treat‐All compared with standard of care (SOC) under routine conditions. Methods This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat‐All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan–Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. Results Of the 1726 (57.3%) patients enrolled under Treat‐All and 1287 (42.7%) under SOC, cumulative three‐month ART initiation was higher under Treat‐All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat‐All, ART initiation was higher in pregnant women (vs. non‐pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV‐positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3‐month ART initiation was similar in both interventions (91% to 92%) although Treat‐All initiated patients more quickly during the first month after HIV care enrolment. Conclusions ART initiation was high under Treat‐All and without evidence of de‐prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long‐term impact of Treat‐All on patient outcomes.
Who is telling the story? A systematic review of authorship for infectious disease research conducted in Africa, 1980-2016 Introduction Africa contributes little to the biomedical literature despite its high burden of infectious diseases. Global health research partnerships aimed at addressing Africa-endemic disease may be polarised. Therefore, we assessed the contribution of researchers in Africa to research on six infectious diseases. METHODS: We reviewed publications on HIV and malaria (2013-2016), tuberculosis (2014-2016), salmonellosis, Ebola haemorrhagic fever and Buruli ulcer disease (1980-2016) conducted in Africa and indexed in the PubMed database using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Papers reporting original research done in Africa with at least one laboratory test performed on biological samples were included. We studied African author proportion and placement per study type, disease, funding, study country and lingua franca. RESULTS: We included 1182 of 2871 retrieved articles that met the inclusion criteria. Of these, 1109 (93.2%) had at least one Africa-based author, 552 (49.8%) had an African first author and 41.3% (n=458) an African last author. Papers on salmonellosis and tuberculosis had a higher proportion of African last authors (p<0.001) compared with the other diseases. Most of African first and last authors had an affiliation from an Anglophone country. HIV, malaria, tuberculosis and Ebola had the most extramurally funded studies (≥70%), but less than 10% of the acknowledged funding was from an African funder. CONCLUSION: African researchers are under-represented in first and last authorship positions in papers published from research done in Africa. This calls for greater investment in capacity building and equitable research partnerships at every level of the global health community.