A Systematic Review of the Incremental Costs of Implementing a New Vaccine in the Expanded Program of Immunization in Sub-Saharan Africa

Background. The World Health Organization is planning a pilot introduction of a new malaria vaccine in three sub-Saharan African countries. To inform considerations about including a new vaccine in the vaccination program of those and other countries, estimates from the scientific literature of the incremental costs of doing so are important. Methods. A systematic review of scientific studies reporting the costs of recent vaccine programs in sub-Saharan countries was performed. The focus was to obtain from each study an estimate of the cost per dose of vaccine administered excluding the acquisition cost of the vaccine and wastage. Studies published between 2000 and 2018 and indexed on PubMed could be included and results were standardized to 2015 US dollars (US$). Results. After successive screening of 2119 titles, and 941 abstracts, 58 studies with 80 data points (combinations of country, vaccine type, and vaccination approach–routine v. campaign) were retained. Most studies used the so-called ingredients approach as costing method combining field data collection with documented unit prices per cost item. The categorization of cost items and the extent of detailed reporting varied widely. Across the studies, the mean and median cost per dose administered was US$1.68 and US$0.88 with an interquartile range of US$0.54 to US$2.31. Routine vaccination was more costly than campaigns, with mean cost per dose of US$1.99 and US$0.88, respectively. Conclusion. Across the studies, there was huge variation in the cost per dose delivered, between and within countries, even in studies using consistent data collection tools and analysis methods, and including many health facilities. For planning purposes, the interquartile range of US$0.54 to US$2.31 may be a sufficiently precise estimate

Researchers' perceptions of malaria eradication: findings from a mixed-methods analysis of a large online survey.

The value of malaria eradication, the permanent reduction to zero of the worldwide incidence of malaria infection caused by human malaria parasites, would be enormous. However, the expected value of an investment in an intended, but uncertain, outcome hinges on the probability of, and time until, its fulfilment. Though the long-term benefits of global malaria eradication promise to be large, the upfront costs and uncertainty regarding feasibility and timeframe make it difficult for policymakers and researchers to forecast the return on investment. - Label: METHODS NlmCategory: METHODS content: A large online survey of 844 peer-reviewed malaria researchers of different scientific backgrounds administered in order to estimate the probability and time frame of eradication. Adjustments were made for potential selection bias, and thematic analysis of free text comments was carried out. - Label: RESULTS NlmCategory: RESULTS content: "The average perceived likelihood of global eradication among malaria researchers approximates the number of years into the future: approximately 10% of researchers believe that eradication will occur in the next 10\xC2\xA0years, 30% believe it will occur in the next 30\xC2\xA0years, and half believe eradication will require 50\xC2\xA0years or more. Researchers who gave free form comments highlighted systemic challenges and the need for innovation as chief among obstacles to achieving global malaria eradication." - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: The findings highlight the difficulty and complexity of malaria eradication, and can be used in prospective cost-benefit analyses to inform stakeholders regarding the likely return on eradication-specific investments

The impact of a malaria elimination initiative on school outcomes: Evidence from Southern Mozambique

Despite the significant improvements achieved over the last ten years, primary education attainment in Mozambique is still low. Potential reasons acting from the demand perspective include ill health, among other factors. In Mozambique, ill health is still largely linked to malaria, which is a leading cause of outpatient contacts, hospital admissions and death, particularly among under-five and school-aged children. Despite this, in Mozambique and more generally, in malaria endemic countries, the identification and measurement of how improved malaria indicators may contribute to better school outcomes remains largely unknown. In particular, there is a low understanding of the extent to which better health translates immediately into school indicators, such as absenteeism and grades. In this study, we exploit the first year of a malaria elimination initiative implemented in Magude district (Southern Mozambique) that started in 2015, as a quasi-experiment to estimate the impact of malaria on selected primary school outcomes. While malaria was not eliminated, its incidence drastically dropped. We use as control a neighbouring district (Manhiça) with similar socio-economic and epidemiological characteristics. By employing a difference-in-differences (DiD) approach, we examine whether the positive health shock translated into improved school outcomes. Using information from school registers, we generated a dataset on school attendance and grades for 9,848 primary-school students from 9 schools (4 in the treated district and 5 in the control district). In our main specification, a repeated cross-section analysis, we find that the elimination initiative led to a 28% decrease in school absenteeism and a 2% increase in students' grades. Our results are robust across different specifications, including a panel DiD individual fixed effects estimate on a sub-sample of students. These findings provide evidence on the negative impact of malaria on primary education attainment and suggest remarkable economic benefits consequent to its elimination

What is the true tuberculosis mortality burden? Differences in estimates by the World Health Organization and the Global Burden of Disease study

Background: The World Health Organization (WHO) and the Global Burden of Disease (GBD) study at the Institute for Health Metrics and Evaluation (IHME) periodically provide global estimates of tuberculosis (TB) mortality. We compared the 2015 WHO and GBD TB mortality estimates and explored which factors might drive the differences. Methods: We extracted the number of estimated TB-attributable deaths, disaggregated by age, HIV status, sex and country from publicly available WHO and GBD datasets for the year 2015. We ‘standardized’ differences between sources by adjusting each country’s difference in absolute number of deaths by the average number of deaths estimated by both sources. Results: For 195 countries with estimates from both institutions, WHO estimated 1 768 482 deaths attributable to TB, whereas GBD estimated 1 322 916 deaths, a difference of 445 566 deaths or 29% of the average of the two estimates. The countries with the largest absolute differences in deaths were Nigeria (216 621), Bangladesh (49 863) and Tanzania (38 272). The standardized difference was not associated with HIV prevalence, prevalence of multidrug resistance or global region, but did show correlation with the case detection rate as estimated by WHO [r ¼ 0.37, 95% confidence interval (CI): 049; 0.24] or, inversely, with case detection rate based on GBD data (r ¼ 0.44, 95% CI: 0.31; 0.54). Countries with a recent national prevalence survey had higher standardized differences (higher estimates by WHO) than those without (P ¼ 0.006). After exclusion of countries with recent prevalence surveys, the overall correlation between both estimates was r ¼ 0.991. Conclusions: A few countries account for the large global discrepancy in TB mortality estimates. The differences are due to the methodological approaches used by WHO and GBD. The use and interpretation of prevalence survey data and case detection rates seem to play a role in the observed differences

Evidence of high bed net usage from a list randomization experiments in rural Gambia.

Label: BACKGROUND NlmCategory: BACKGROUND content: Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly, and where respondents answer what they think the recorder may want to hear. Sleeping under a long-lasting insecticidal net (LLIN) is an important intervention for malaria prevention, yet it is difficult to gauge the extent to which coverage (how many nets are in the community) differs from usage (how many people actually sleep under a net). List randomization, a novel method which partially obscures respondents' answers to sensitive questions, was employed to estimate LLIN usage in The Gambia. - Label: METHODS NlmCategory: METHODS content: "802 heads-of-household from 15 villages were recruited into a randomized controlled trial assessing the effect of a housing intervention on malaria. These houses were randomly assigned to a housing intervention versus control, with stratification by village so as to ensure balance between arms. From these, 125 households (63 intervention, 52 control) were randomly selected for participation in the list randomization experiment, along with 68 households from the same villages but which were not part of the housing improvement study, resulting in a total of 196 households for the list randomization experiment. Approximately half (n\xE2\x80\x89=\xE2\x80\x8997) of the 196 study participants were randomly assigned to the control group and received a four-question list about non-sensitive behaviours; the intervention group (n\xE2\x80\x89=\xE2\x80\x8999) received the same list, with the addition of one question on a sensitive behaviour: whether or not they had used a bed net the previous night. Participants were read the list of questions and then said how many of the statements were true. Bed net usage was estimated by calculating the difference in means between the number of affirmative responses between the two groups." - Label: RESULTS NlmCategory: RESULTS content: The mean number of affirmative responses in the control group was 2.60 of four statements (95% confidence interval, 95% CI 2.50-2.70), compared with 3.68 (95% CI 3.59-3.78) in the intervention group. Such difference (1.08; 95% CI 94.9-100%) suggests near universal bed net usage. - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: Bed net usage by household heads in these rural villages was found to be high. Though not entirely unexpected given other studies' estimates of high bed net usage in the area, the list randomization method should be further validated in an area with lower coverage

Mapping the potential use of endectocide-treated cattle to reduce malaria transmission

Treating cattle with endectocide is a longstanding veterinary practice to reduce the load of endo and ectoparasites, but has the potential to be added to the malaria control and elimination toolbox, as it also kills malaria mosquitoes feeding on the animals. Here we used openly available data to map the areas of the African continent where high malaria prevalence in 2-10 year old children coincides with a high density of cattle and high density of the partly zoophilic malaria vector Anopheles arabiensis. That is, mapping the areas where treating cattle with endectocide would potentially have the greatest impact on reducing malaria transmission. In regions of Africa that are not dominated by rainforest nor desert, the map shows a scatter of areas in several countries where this intervention shows potential, including central and eastern sub-Saharan Africa. The savanna region underneath the Sahel in West Africa appears as the climatic block that would benefit to the largest extent from this intervention, encompassing several countries. West Africa currently presents the highest under-10 malaria prevalence and elimination within the next twenty years cannot be contemplated there with currently available interventions alone, making the use of endectocide treated cattle as a complementary intervention highly appealing

Monitoring the COVID-19 epidemic in the context of widespread local transmission.

Coronavirus disease 2019 (COVID-19) is a novel viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first detected in Wuhan, China, in December, 2019.1 Given the fast spread, the severity of disease, the increasing number of cases outside China, and the number of affected countries, WHO declared the rapid spread of SARS-CoV-2 a pandemic on March 11, 2020.2 The availability of reliable surveillance platforms is crucial to monitor the COVID-19 epidemic in a timely manner and to respond with adequate control measures. Since the beginning of the outbreak, different countries have used different testing approaches and criteria, depending on their resources and capacity

Mapping the potential use of endectocide-treated cattle to reduce malaria transmission

Treating cattle with endectocide is a longstanding veterinary practice to reduce the load of endo and ectoparasites, but has the potential to be added to the malaria control and elimination toolbox, as it also kills malaria mosquitoes feeding on the animals. Here we used openly available data to map the areas of the African continent where high malaria prevalence in 2-10 year old children coincides with a high density of cattle and high density of the partly zoophilic malaria vector Anopheles arabiensis. That is, mapping the areas where treating cattle with endectocide would potentially have the greatest impact on reducing malaria transmission. In regions of Africa that are not dominated by rainforest nor desert, the map shows a scatter of areas in several countries where this intervention shows potential, including central and eastern sub-Saharan Africa. The savanna region underneath the Sahel in West Africa appears as the climatic block that would benefit to the largest extent from this intervention, encompassing several countries. West Africa currently presents the highest under-10 malaria prevalence and elimination within the next twenty years cannot be contemplated there with currently available interventions alone, making the use of endectocide treated cattle as a complementary intervention highly appealing

The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission in low risk, non-severe COVID-19 patients in the first 48 hours after symptoms onset: A structured summary of a study protocol for a randomized control pilot trial

Objectives: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra