In The Lancet Infectious Diseases, Eddy Fadlyana and colleagues report an important, pragmatic vaccine trial done amid difficult pandemic circumstances that set about addressing questions of direct ...and immediate national, regional, and even global policy relevance.1 Examining adult previous recipients of two-doses of inactivated COVID-19 vaccine, the masked investigators randomly assigned them to receive a booster in one of five groups: either homologous inactivated vaccine at full-dose or to receive heterologous boosting, being either mRNA or adenovirus-vectored vaccine, each in either full-dose or fractionated intramuscular half-dose. Fractional vaccine dosing involves the use of a lower dose than that recommended by the manufacturer or regulator.2 It is not uncommon for immunisation programmes in low resource settings to use fractional doses to extend the supplies of vaccine doses for maximal vaccine coverage.3 In addition, fractionated doses have been used to minimise adverse events following immunisation while maintaining the minimum acceptable concentration of antibodies required for protection.4 Dose sparing through fractionation is a sometimes controversial practice, and should not be done without specific supportive evidence of individual efficacy, even when the objective is to maximise efficiently the total good. ...generation vaccines are in development that aim to broaden protection in variant-independent ways, or to target mucosal immunity and hopefully reduce transmission (although the methodological challenges are far from trivial), and that provide sustained defence against severe disease and prolonged protection from infection.
In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus ...spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Globally, over four million deaths are attributed to exposure to household air pollution (HAP) annually. Evidence of the association between exposure to HAP and under-five ...mortality in sub-Saharan Africa (SSA) is insufficient. We assessed the association between exposure to HAP and under-five mortality risk in 14 SSA countries.
Methods
We pooled Demographic and Health Survey (DHS) data from 14 SSA countries (
N
= 164376) collected between 2015 and 2018. We defined exposure to HAP as the use of biomass fuel for cooking in the household. Under-five mortality was defined as deaths before age five. Data were analyzed using mixed effects logistic regression models.
Results
Of the study population, 73% were exposed to HAP and under-five mortality was observed in 5%. HAP exposure was associated with under-five mortality, adjusted odds ratio (OR) 1.33 (95% confidence interval (CI) 1.03–1.71). Children from households who cooked inside the home had higher risk of under-five mortality compared to households that cooked in separate buildings 0.85 (0.73–0.98) or outside 0.75 (0.64–0.87). Lower risk of under-five mortality was also observed in breastfed children 0.09 (0.05-0.18) compared to non-breastfed children.
Conclusions
HAP exposure may be associated with an increased risk of under-five mortality in sub-Saharan Africa. More carefully designed longitudinal studies are required to contribute to these findings. In addition, awareness campaigns on the effects of HAP exposure and interventions to reduce the use of biomass fuels are required in SSA.
Abstract
Background
Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or ...suspected cholera.
Methods
AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2–23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies.
Results
Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 28.3%) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference RDlikely, −11.6 95% confidence interval {CI}, −15.6 to −7.6) and possible bacterial etiology (RDpossible, −8.7 95% CI, −13.0 to −4.4) but not in other children (RDunlikely, −0.3% 95% CI, −2.9% to 2.3%). A similar association was observed for 90-day hospitalization or death (RDlikely, −3.1 95% CI, −5.3 to −1.0; RDpossible, −2.3 95% CI, −4.5 to −.01; RDunlikely, −0.6 95% CI, −1.9 to .6). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella.
Conclusions
Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.
Clinical Trials Registration
NCT03130114.
Improved clinical outcomes among children with acute watery diarrhea of bacterial etiology in this reanalysis of the ABCD trial suggest that a short course of azithromycin may be warranted if bacterial etiologies could be identified at the point of care.
Malaria remains a significant cause of morbidity and mortality in the paediatric population in Malawi. Insecticide-treated bed nets are a key vector malaria control intervention, however, advancement ...towards universal access is progressing slowly. Malawi Malaria indicator surveys (MMIS) show diverse user preferences of bed net shape and colour. The objective of this work was to understand if bed net shape and colour preferences affect usage.
This is a secondary analysis of data from households that participated in the 2016-2017 MMIS. The main outcome variable was net usage defined, at net level, whether someone slept under a particular net on the night before the survey. The main exposure variables were preference attributes, whether a particular net is of a preferred colour or shape as defined by the household respondent. Both bivariate and multivariate logistic regression analyses were done to determine the association between the exposure and outcome variables.
A total of 3729 households with 16,755 individuals were included in this analysis. There were a total 7710 bed nets in households that participated in the survey of which 5435 (70.5%) of these nets had someone sleep under them the previous night before the survey. Bed nets that are of a preferred shape have 3.55 times higher odds of being used than those not preferred AOR 3.55 (95% CI 2.98, 4.23; p value < 0.001). Bed nets that are of a preferred colour have 1.61 times higher odds of being used than those that are not of a preferred colour AOR 1.61 (95% CI 1.41, 1.84; p value < 0.001.
The results indicate that if a bed net is of a preferred colour or shape, it is more likely to be used. Bed net purchase by malaria stakeholders need to balance more factors on top of preferences such as price and efficacy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Following a 30-year development process, RTS,S/AS01
E
(GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria ...Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01
E
through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on
Plasmodium falciparum
variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01
E
through active participant follow-up in the context of its real-life implementation.
Methods
EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the
P. falciparum
genetic diversity in the periods before and after vaccine implementation.
Conclusion
GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01
E
vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01
E
’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa.
Graphic abstract
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
The RTS,S/AS01
E
malaria vaccine is being assessed in Malawi, Ghana and Kenya as part of a large-scale pilot implementation programme. Even if impactful, its incorporation into ...immunisation programmes will depend on demonstrating cost-effectiveness. We analysed the cost-effectiveness and public health impact of the RTS,S/AS01
E
malaria vaccine use in Malawi.
Methods:
We calculated the Incremental Cost Effectiveness Ratio (ICER) per disability-adjusted life year (DALY) averted by vaccination and compared it to Malawi’s mean per capita Gross Domestic Product. We used a previously validated Markov model, which simulated malaria progression in a 2017 Malawian birth cohort for 15 years. We used a 46% vaccine efficacy, 75% vaccine coverage, USD5 estimated cost per vaccine dose, published local treatment costs for clinical malaria and Malawi specific malaria indicators for interventions such as bed net and antimalarial use. We took a healthcare provider, household and societal perspective. Costs were discounted at 3% per year, no discounting was applied to DALYs. For public health impact, we calculated the DALYs, and malaria events averted.
Results:
The ICER/DALY averted was USD115 and USD109 for the health system perspective and societal perspective respectively, lower than GDP per capita of USD398.6 for Malawi. Sensitivity analyses exploring the impact of variation in vaccine costs, vaccine coverage rate and coverage of four doses showed vaccine implementation would be cost-effective across a wide range of different outcomes. RTS,S/AS01 was predicted to avert a median of 93,940 (range 20,490–126,540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116,480 (31,450–160,410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children.
Conclusions:
We predict the introduction of the RTS,S/AS01 vaccine in the Malawian expanded programme of immunisation (EPI) likely to be highly cost effective.
Background:
The RTS,S/AS01
E
malaria vaccine is being assessed in Malawi, Ghana and Kenya as part of a large-scale pilot implementation programme. Even if impactful, its incorporation into ...immunisation programmes will depend on demonstrating cost-effectiveness. We analysed the cost-effectiveness and public health impact of the RTS,S/AS01
E
malaria vaccine use in Malawi.
Methods:
We calculated the Incremental Cost Effectiveness Ratio (ICER) per disability-adjusted life year (DALY) averted by vaccination and compared it to Malawi’s mean per capita Gross Domestic Product. We used a previously validated Markov model, which simulated malaria progression in a 2017 Malawian birth cohort for 15 years. We used a 46% vaccine efficacy, 75% vaccine coverage, USD5 estimated cost per vaccine dose, published local treatment costs for clinical malaria and Malawi specific malaria indicators for interventions such as bed net and antimalarial use. We took a healthcare provider, household and societal perspective. Costs were discounted at 3% per year, no discounting was applied to DALYs. For public health impact, we calculated the DALYs, and malaria events averted.
Results:
The ICER/DALY averted was USD115 and USD109 for the health system perspective and societal perspective respectively, lower than GDP per capita of USD398.6 for Malawi. Sensitivity analyses exploring the impact of variation in vaccine costs, vaccine coverage rate and coverage of four doses showed vaccine implementation would be cost-effective across a wide range of different outcomes. RTS,S/AS01 was predicted to avert a median of 93,940 (range 20,490–126,540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116,480 (31,450–160,410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children.
Conclusions:
We predict the introduction of the RTS,S/AS01 vaccine in the Malawian expanded programme of immunisation (EPI) likely to be highly cost effective.
ObjectiveThe objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children ...under 2 years of age with moderate to severe diarrhoea (MSD).DesignA secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114).PatientsChildren with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample.Study periodJune 2017–July 2019.InterventionsNone.Main outcome measuresLikely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology.ResultsA total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools.ConclusionThe presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.
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