Journal Article > CommentaryFull Text
PLOS Med. 2014 April 22; Volume 11 (Issue 4); DOI:10.1371/journal.pmed.1001632
Gerdin M, Clarke M, Allen C, Kayabu B, Summerskill W, et al.
PLOS Med. 2014 April 22; Volume 11 (Issue 4); DOI:10.1371/journal.pmed.1001632
Journal Article > CommentaryFull Text
PLOS Med. 2020 February 14; Volume 17 (Issue 2); e1003028.; DOI:10.1371/journal.pmed.1003028.
Ford NP, Geng EH, Ellman T, Orrell C, Ehrenkranz PD, et al.
PLOS Med. 2020 February 14; Volume 17 (Issue 2); e1003028.; DOI:10.1371/journal.pmed.1003028.
Journal Article > ResearchFull Text
PLOS Med. 2005 February 1; Volume 2 (Issue 2); DOI:10.1371/journal.pmed.0020014
Dentico N, Ford NP
PLOS Med. 2005 February 1; Volume 2 (Issue 2); DOI:10.1371/journal.pmed.0020014
Journal Article > CommentaryFull Text
PLOS Med. 2013 November 5; Volume 10 (Issue 11); DOI:10.1371/journal.pmed.1001544
Minetti A, Bopp C, Fermon F, Francois G, Grais RF, et al.
PLOS Med. 2013 November 5; Volume 10 (Issue 11); DOI:10.1371/journal.pmed.1001544
Andrea Minetti and colleagues compare measles outbreak responses from the Democratic Republic of the Congo and Malawi and argue that outbreak response strategies should be tailored to local measles epidemiology. Please see later in the article for the Editors' Summary.
Journal Article > CommentaryFull Text
PLOS Med. 2019 May 29; Volume 16 (Issue 5); e1002820.; DOI:10.1371/journal.pmed.1002820
Ehrenkranz PD, Baptiste SL, Bygrave H, Ellman T, Doi N, et al.
PLOS Med. 2019 May 29; Volume 16 (Issue 5); e1002820.; DOI:10.1371/journal.pmed.1002820
Journal Article > CommentaryFull Text
PLOS Med. 2016 September 6; Volume 13 (Issue 9); e1002111.; DOI:10.1371/journal.pmed.1002111
Sheather J, Jobanputra K, Schopper D, Pringle J, Venis S, et al.
PLOS Med. 2016 September 6; Volume 13 (Issue 9); e1002111.; DOI:10.1371/journal.pmed.1002111
SUMMARY POINTS
• Humanitarian organisations often have to innovate to deliver health care and aid to populations in complex and volatile contexts.
• Innovation projects can involve ethical risks and have consequences for populations even if human participants are not directly involved. While high-level principles have been developed for humanitarian innovation, there is a lack of guidance for how these should be applied in practice.
• Médecins sans Frontières (MSF) has well-established research ethics frameworks, but application of such frameworks to innovation projects could stifle innovation by introducing regulation disproportionate to the risks involved. In addition, the dynamic processes of innovation do not fit within conventional ethics frameworks.
• MSF developed and is piloting an ethics framework for humanitarian innovation that is intended for self-guided use by innovators or project owners to enable them to identify and weigh the harms and benefits of such work and be attentive towards a plurality of ethical considerations.
• Humanitarian organisations often have to innovate to deliver health care and aid to populations in complex and volatile contexts.
• Innovation projects can involve ethical risks and have consequences for populations even if human participants are not directly involved. While high-level principles have been developed for humanitarian innovation, there is a lack of guidance for how these should be applied in practice.
• Médecins sans Frontières (MSF) has well-established research ethics frameworks, but application of such frameworks to innovation projects could stifle innovation by introducing regulation disproportionate to the risks involved. In addition, the dynamic processes of innovation do not fit within conventional ethics frameworks.
• MSF developed and is piloting an ethics framework for humanitarian innovation that is intended for self-guided use by innovators or project owners to enable them to identify and weigh the harms and benefits of such work and be attentive towards a plurality of ethical considerations.
Journal Article > ResearchFull Text
PLOS Med. 2017 October 23; Volume 14 (Issue 10); DOI:10.1371/journal.pmed.1002411
Keitel K, Kagoro F, Samaka J, Masimba J, Said Z, et al.
PLOS Med. 2017 October 23; Volume 14 (Issue 10); DOI:10.1371/journal.pmed.1002411
The management of childhood infections remains inadequate in resource-limited countries, resulting in high mortality and irrational use of antimicrobials. Current disease management tools, such as the Integrated Management of Childhood Illness (IMCI) algorithm, rely solely on clinical signs and have not made use of available point-of-care tests (POCTs) that can help to identify children with severe infections and children in need of antibiotic treatment. e-POCT is a novel electronic algorithm based on current evidence; it guides clinicians through the entire consultation and recommends treatment based on a few clinical signs and POCT results, some performed in all patients (malaria rapid diagnostic test, hemoglobin, oximeter) and others in selected subgroups only (C-reactive protein, procalcitonin, glucometer). The objective of this trial was to determine whether the clinical outcome of febrile children managed by the e-POCT tool was non-inferior to that of febrile children managed by a validated electronic algorithm derived from IMCI (ALMANACH), while reducing the proportion with antibiotic prescription.
Journal Article > ResearchFull Text
PLOS Med. 2021 August 10; Volume 18 (Issue 8); e1003720.; DOI:10.1371/journal.pmed.1003720
Isanaka S, Garba S, Plikaytis BD, McNeal MM, Guindo O, et al.
PLOS Med. 2021 August 10; Volume 18 (Issue 8); e1003720.; DOI:10.1371/journal.pmed.1003720
BACKGROUND
Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine.
METHODS AND FINDINGS
We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear.
CONCLUSIONS
This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.
Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine.
METHODS AND FINDINGS
We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear.
CONCLUSIONS
This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.
Journal Article > ResearchFull Text
PLOS Med. 2019 April 5; Volume 16 (Issue 4); DOI:10.1371/journal.pmed.1002776
Gupta-Wright A, Corbett EL, Wilson D, van Oosterhout JJ, Dheda K, et al.
PLOS Med. 2019 April 5; Volume 16 (Issue 4); DOI:10.1371/journal.pmed.1002776
The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings. A cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30-43), 45.4% were female, median CD4 cell count at admission was 76 cells/μl (IQR 23-206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%-55.2%) mortality risk in the high-risk group compared to 12.5% (95% CI 5.7%-25.4%) in the low-risk group (p < 0.001). The odds ratio (OR) for mortality was 6.1 (95% CI 2.4-15.2) in high-risk patients compared to low-risk patients (p < 0.001). Discrimination (c-statistic 0.70, 95% CI 0.63-0.76) and calibration (Hosmer-Lemeshow statistic, p = 0.78) were good in the derivation cohort, and similar in the external validation cohort (complete cases n = 372, c-statistic 0.68 [95% CI 0.61-0.74]). The validation cohort included 644 patients between January 2013 and August 2015. Median age was 36 years, 48.9% were female, and median CD4 count at admission was 61 (IQR 21-145). OR for mortality was 5.3 (95% CI 2.2-9.5) for high compared to low-risk patients (complete cases n = 372, p < 0.001). The score also predicted patients at higher risk of death both pre- and post-discharge. A simplified score (any 3 or more of the predictors) performed equally well. The main limitations of the scores were their imperfect accuracy, the need for access to urine LAM testing, modest study size, and not measuring all potential predictors of mortality (e.g., tuberculosis drug resistance). This risk score is capable of identifying patients who could benefit from enhanced clinical care, follow-up, and/or adjunctive interventions, although further prospective validation studies are necessary. Given the scale of HIV/TB morbidity and mortality in African hospitals, better prognostic tools along with interventions could contribute towards global targets to reduce tuberculosis mortality.
Journal Article > ResearchFull Text
PLOS Med. 2014 September 9; Volume 11 (Issue 9); e1001718.; DOI:10.1371/journal.pmed.1001718
Boulle AM, Schomaker M, May MT, Hogg RS, Shepherd B, et al.
PLOS Med. 2014 September 9; Volume 11 (Issue 9); e1001718.; DOI:10.1371/journal.pmed.1001718
BACKGROUND
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
METHODS AND FINDINGS
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
CONCLUSIONS
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
METHODS AND FINDINGS
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
CONCLUSIONS
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.