Now showing items 1-20 of 3200

    • Measuring the unknown: an estimator and simulation study for assessing case reporting during epidemics

      Jarvis, CI; Gimma, A; Finger, F; Morris, TP; Thompson, JA; de Waroux, OlP; Edmunds, WJ; Funk, S; Jombart, T (bioRxiv, 2021-12-17)
      The fraction of cases reported, known as ‘reporting’, is a key performance indicator in an outbreak response, and an essential factor to consider when modelling epidemics and assessing their impact on populations. Unfortunately, its estimation is inherently difficult, as it relates to the part of an epidemic which is, by definition, not observed. We introduce a simple statistical method for estimating reporting, initially developed for the response to Ebola in Eastern Democratic Republic of the Congo (DRC), 2018-2020. This approach uses transmission chain data typically gathered through case investigation and contact tracing, and uses the proportion of investigated cases with a known, reported infector as a proxy for reporting. Using simulated epidemics, we study how this method performs for different outbreak sizes and reporting levels. Results suggest that our method has low bias, reasonable precision, and despite sub-optimal coverage, usually provides estimates within close range (5-10%) of the true value. Being fast and simple, this method could be useful for estimating reporting in real-time in settings where person-to-person transmission is the main driver of the epidemic, and where case investigation is routinely performed as part of surveillance and contact tracing activities.
    • Pneumococcal Meningitis Outbreaks in Africa, 2000-2018: Systematic Literature Review and Meningitis Surveillance Database Analyses.

      Franklin, K; Kwambana-Adams, B; Lessa, FC; Soeters, HM; Cooper, L; Coldiron, ME; Mwenda, J; Antonio, M; Nakamura, T; Novak, R; et al. (Oxford University Press, 2021-09-01)
      Background The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. Methods Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. Results A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. Conclusions Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.
    • Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger.

      Platts-Mills, JA; Houpt, ER; Liu, J; Zhang, J; Guindo, O; Sayingoza-Makombe, N; McMurry, TL; Elwood, S; Langendorf, C; Grais, RF; et al. (Oxford University Press, 2021-09-01)
      Background High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. Methods We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. Results The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. Conclusions In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.
    • Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response.

      Azam, JM; Saitta, B; Bonner, K; Ferrari, MJ; Pulliam, JRC (Elsevier, 2021-09-01)
      Introduction: Rapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits. Methods: We developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes. Results: The OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases. Discussion: The OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.
    • Public investments in the development of GeneXpert molecular diagnostic technology.

      Gotham, D; McKenna, L; Deborggraeve, S; Madoori, S; Branigan, D (Public Library of Science, 2021-08-31)
      Background: The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid's suite of cartridge-based assays. Methods: Public funding data were collected from the proprietor company's financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology's development. The value of research and development (R&D) tax credits was estimated based on financial filings. Results: Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business 'springboard' grants. Conclusion: The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance
    • Slipping through the cracks: a qualitative study to explore pathways of HIV care and treatment amongst hospitalised patients with advanced HIV in Kenya and the Democratic Republic of the Congo.

      Burns, R; Venables, E; Odhoch, L; Kocholla, L; Wanjala, S; Mucinya, G; Bossard, C; Wringe, A (Taylor and Francis, 2021-08-26)
      Advanced HIV causes substantial mortality in sub-Saharan Africa despite widespread antiretroviral therapy coverage. This paper explores pathways of care amongst hospitalised patients with advanced HIV in rural Kenya and urban Democratic Republic of the Congo, with a view to understanding their care-seeking trajectories and poor health outcomes. Thirty in-depth interviews were conducted with hospitalised patients with advanced HIV who had previously initiated first-line antiretroviral therapy, covering their experiences of living with HIV and care-seeking. Interviews were audio-recorded, transcribed and translated before being coded inductively and analysed thematically. In both settings, participants' health journeys were defined by recurrent, severe symptoms and complex pathways of care before hospitalisation. Patients were often hospitalised after multiple failed attempts to obtain adequate care at health centres. Most participants managed their ill-health with limited support networks, lived in fragile economic situations and often experienced stress and other mental health concerns. Treatment-taking was sometimes undermined by strict messaging around adherence that was delivered in health facilities. These findings reveal a group of patients who had "slipped through the cracks" of health systems and social support structures, indicating both missed opportunities for timely management of advanced HIV and the need for interventions beyond hospital and clinical settings.
    • How COVID-19 highlighted the need for infection prevention and control measures to become central to the global conversation: experience from the conflict settings of the Middle-East.

      Mouallem, RE; Moussally, K; Williams, A; Repetto, E; Menassa, M; Martino, C; Sittah, GA (Elsevier, 2021-08-19)
      The COVID-19 pandemic has managed to bring to the foreground, in just few months, the conversation around what Infection Prevention and Control (IPC) experts have been pushing for decades to control the spread of infections. Implementing the basics of IPC has been a challenge for all affected countries battling with an exponential COVID-19 curve of infection, preventing nosocomial transmission of the disease in highly-resourced and stable contexts but more so in the conflict context of the Middle-East. COVID-19 has created additional challenges to a long list of existing ones hindering the implementation of optimal IPC measures, necessary to break the chain of infection of both respiratory and non-respiratory infections, in those settings. This paper outlines and gives examples of the challenges faced across the Middle East conflict setting and serves as a call for action for IPC to be prioritized, given the needed resources, and fed with contextualized evidence.
    • International migration of unaccompanied minors: trends, health risks, and legal protection.

      Corona Maioli, S; Bhabha, J; Wickramage, K; Wood, LCN; Erragne, L; Ortega Garcia, O; Burgess, R; Digidiki, V; Aldirdge, RW; Devakumar, D (Elsevier, 2021-08-17)
      The global population of unaccompanied minors-children and adolescents younger than 18 years who migrate without their legal guardians-is increasing. However, as data are not systematically collected in any region, if collected at all, little is known about this diverse group of young people. Compared with adult migrants, unaccompanied minors are at greater risk of harm to their health and integrity because they do not have the protection provided by a family, which can affect their short-term and long-term health. This Review summarises evidence regarding the international migration and health of unaccompanied minors. Unaccompanied minors are entitled to protection that should follow their best interests as a primary consideration; however, detention, sometimes under the guise of protection, is a widespread practice. If these minors are provided with appropriate forms of protection, including health and psychosocial care, they can thrive and have good long-term outcomes. Instead, hostile immigration practices persist, which are not in the best interests of the child.
    • A feasibility study using mid-upper arm circumference as the sole anthropometric criterion for admission and discharge in the outpatient treatment for severe acute malnutrition.

      Garba, S; Salou, H; Nackers, F; Ayouba, A; Escruela, M; Guindo, O; Rocaspana, M; Grais, RF; Isanaka, S (BioMed Central, 2021-08-12)
      Background: The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage. Methods: This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger. Results: Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program. Conclusions: The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent.
    • A feasibility study using mid-upper arm circumference as the sole anthropometric criterion for admission and discharge in the outpatient treatment for severe acute malnutrition.

      Garba, S; Salou, H; Nackers, F; Ayouba, A; Escruela, M; Guindo, O; Rocaspana, M; Grais, RF; Isanaka, S (BioMed Central, 2021-08-12)
      Background: The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage. Methods: This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger. Results: Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program. Conclusions: The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent.
    • Visceral Leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans.

      Dahal, P; Singh-Phulgenda, S; Maguire, BJ; Harriss, E; Ritmeijer, K; Alves, F; Guerin, PJ; Olliaro, Pl (Public Library of Science, 2021-08-10)
      Background: Reports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the mother and foetus. Methods: A review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; World Health Organization Global Index Medicus: LILACS (Americas); IMSEAR (South-East Asia); IMEMR (Eastern Mediterranean); WPRIM (Western Pacific); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform. Selection criteria included any clinical reports describing the disease in pregnancy or vertical transmission of the disease in humans. Articles meeting pre-specified inclusion criteria and non-primary research articles such as textbook, chapters, letters, retrospective case description, or reports of accidental inclusion in trials were also considered. Results: The systematic literature search identified 272 unique articles of which 54 records were included in this review; a further 18 records were identified from additional search of the references of the included studies or from personal communication leading to a total of 72 records (71 case reports/case series; 1 retrospective cohort study; 1926-2020) describing 451 cases of VL in pregnant women. The disease was detected during pregnancy in 398 (88.2%), retrospectively confirmed after giving birth in 52 (11.5%), and the time of identification was not clear in 1 (0.2%). Of the 398 mothers whose infection was identified during pregnancy, 346 (86.9%) received a treatment, 3 (0.8%) were untreated, and the treatment status was not clear in the remaining 49 (12.3%). Of 346 mothers, Liposomal amphotericin B (L-AmB) was administered in 202 (58.4%) and pentavalent antimony (PA) in 93 (26.9%). Outcomes were reported in 176 mothers treated with L-AmB with 4 (2.3%) reports of maternal deaths, 5 (2.8%) miscarriages, and 2 (1.1%) foetal death/stillbirth. For PA, outcomes were reported in 88 mothers of whom 4 (4.5%) died, 24 (27.3%) had spontaneous abortion, 2 (2.3%) had miscarriages. A total of 26 cases of confirmed, probable or suspected cases of vertical transmission were identified with a median detection time of 6 months (range: 0-18 months). Conclusions: Outcomes of VL treatment during pregnancy is rarely reported and under-researched. The reported articles were mainly case reports and case series and the reported information was often incomplete. From the studies identified, it is difficult to derive a generalisable information on outcomes for mothers and babies, although reported data favours the usage of liposomal amphotericin B for the treatment of VL in pregnant women.
    • Visceral Leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans.

      Dahal, P; Singh-Phulgenda, S; Maguire, BJ; Harriss, E; Ritmeijer, K; Alves, F; Guerin, PJ; Olliaro, Pl (Public Library of Science, 2021-08-10)
      Background: Reports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the mother and foetus. Methods: A review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; World Health Organization Global Index Medicus: LILACS (Americas); IMSEAR (South-East Asia); IMEMR (Eastern Mediterranean); WPRIM (Western Pacific); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform. Selection criteria included any clinical reports describing the disease in pregnancy or vertical transmission of the disease in humans. Articles meeting pre-specified inclusion criteria and non-primary research articles such as textbook, chapters, letters, retrospective case description, or reports of accidental inclusion in trials were also considered. Results: The systematic literature search identified 272 unique articles of which 54 records were included in this review; a further 18 records were identified from additional search of the references of the included studies or from personal communication leading to a total of 72 records (71 case reports/case series; 1 retrospective cohort study; 1926-2020) describing 451 cases of VL in pregnant women. The disease was detected during pregnancy in 398 (88.2%), retrospectively confirmed after giving birth in 52 (11.5%), and the time of identification was not clear in 1 (0.2%). Of the 398 mothers whose infection was identified during pregnancy, 346 (86.9%) received a treatment, 3 (0.8%) were untreated, and the treatment status was not clear in the remaining 49 (12.3%). Of 346 mothers, Liposomal amphotericin B (L-AmB) was administered in 202 (58.4%) and pentavalent antimony (PA) in 93 (26.9%). Outcomes were reported in 176 mothers treated with L-AmB with 4 (2.3%) reports of maternal deaths, 5 (2.8%) miscarriages, and 2 (1.1%) foetal death/stillbirth. For PA, outcomes were reported in 88 mothers of whom 4 (4.5%) died, 24 (27.3%) had spontaneous abortion, 2 (2.3%) had miscarriages. A total of 26 cases of confirmed, probable or suspected cases of vertical transmission were identified with a median detection time of 6 months (range: 0-18 months). Conclusions: Outcomes of VL treatment during pregnancy is rarely reported and under-researched. The reported articles were mainly case reports and case series and the reported information was often incomplete. From the studies identified, it is difficult to derive a generalisable information on outcomes for mothers and babies, although reported data favours the usage of liposomal amphotericin B for the treatment of VL in pregnant women.
    • Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

      Isanaka, S; Garba, S; Plikaytis, B; McNeal, MM; Guindo, O; Langendorf, C; Adehossi, E; Ciglenecki, I; Grais, RF (Public Library of Science, 2021-08-10)
      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.
    • Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

      Isanaka, S; Garba, S; Plikaytis, B; McNeal, MM; Guindo, O; Langendorf, C; Adehossi, E; Ciglenecki, I; Grais, RF (Public Library of Science, 2021-08-10)
      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.
    • Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

      Hotez, PJ; Batista, C; Amor, YB; Ergonul, O; Figueroa, JP; Gilbert, S; Gursel, M; Hassanain, M; Kang, G; Kaslow, DC; et al. (The Lancet, 2021-08-03)
      A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.
    • CommunityFirst solutions for COVID-19: decolonising health crises responses.

      Kiddell-Monroe, R; Farber, J; Devine, C; Orbinski, J (The Lancet, 2021-08-01)
    • How to improve outbreak response: a case study of integrated outbreak analytics from Ebola in Eastern Democratic Republic of the Congo.

      Carter, SE; Ahuka-Mundeke, S; Pfaffman Zambruni, J; Navarro Colorado, C; van Kleef, E; Lissouba, P; Meakin, S; le Polain de Waroux, O; Jombart, T; Mossoko, M; et al. (BMJ Publishing Group, 2021-08-01)
      The emerging field of outbreak analytics calls attention to the need for data from multiple sources to inform evidence-based decision making in managing infectious diseases outbreaks. To date, these approaches have not systematically integrated evidence from social and behavioural sciences. During the 2018-2020 Ebola outbreak in Eastern Democratic Republic of the Congo, an innovative solution to systematic and timely generation of integrated and actionable social science evidence emerged in the form of the Cellulle d'Analyse en Sciences Sociales (Social Sciences Analytics Cell) (CASS), a social science analytical cell. CASS worked closely with data scientists and epidemiologists operating under the Epidemiological Cell to produce integrated outbreak analytics (IOA), where quantitative epidemiological analyses were complemented by behavioural field studies and social science analyses to help better explain and understand drivers and barriers to outbreak dynamics. The primary activity of the CASS was to conduct operational social science analyses that were useful to decision makers. This included ensuring that research questions were relevant, driven by epidemiological data from the field, that research could be conducted rapidly (ie, often within days), that findings were regularly and systematically presented to partners and that recommendations were co-developed with response actors. The implementation of the recommendations based on CASS analytics was also monitored over time, to measure their impact on response operations. This practice paper presents the CASS logic model, developed through a field-based externally led consultation, and documents key factors contributing to the usefulness and adaption of CASS and IOA to guide replication for future outbreaks.
    • Control of visceral leishmaniasis in East Africa: fragile progress, new threats.

      Dahl, EH; Hamdan, HM; Mabrouk, L; Matendechero, SH; Mengistie, TB; Elhag, MS; Lado, M; Adera, C; Atia, AA; Potet, J; et al. (BMJ Publishing Group, 2021-08-01)
    • Performance of six rapid diagnostic tests for SARS-CoV-2 antigen detection and implications for practical use.

      Fourati, S; Langendorf, C; Audureau, E; Challine, D; Michel, J; Soulier, A; Ahnou, N; Desveaux, I; Picard, O; Ortonne, V; et al. (Elsevier, 2021-07-25)
      Background: Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection. Aims and methods: The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative. Results: The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25. Conclusions: The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.
    • Model of care, Noma Children's Hospital, northwest Nigeria.

      Isah, S; Amirtharajah, M; Farley, E; Semiyu Adetunji, A; Samuel, J; Oluyide, B; Bil, K; Shoaib, M; Abubakar, N; de Jong, A; et al. (Wiley Online, 2021-07-22)
      The Nigerian Ministry of Health has been offering care for noma patients for many years at the Noma Children's Hospital (NCH) in Sokoto, northwest Nigeria, and Médecins Sans Frontières has supported these initiatives since 2014. The comprehensive model of care consists of four main components: acute care, care for noma sequelae, integrated hospital-based services and community-based services. The model of care is based on the limited evidence available for prevention and treatment of noma and follows WHO's protocols for acute patients and best practice guidelines for the surgical treatment of noma survivors. The model is updated continually as new evidence becomes available, including evidence generated through the operational research studies performed at NCH. By describing the model of care, we wish to share the lessons learned with other actors working in the noma and neglected tropical disease sphere in the hope of guiding programme development.