Search

ABSTRACT Background Antimicrobial resistance (AMR) presents a significant global mortality burden which particularly affects the low‐ and middle‐income countries (LMICs). Enhancing diagnostics to identify drug‐resistant infections and improving appropriate access to novel Reserve antibiotics in LMICs can address AMR‐related morbidity, mortality and healthcare costs. This article characterizes the AMR landscape across 14 LMICs and describes an introductory pathway for novel Reserve antibiotics. Methods This mixed‐method study was completed in 14 LMICs in Africa, the Americas, Asia and Europe through a combination of qualitative interviews with physicians and public health experts (PHEs), and a quantitative survey of physicians, supported by an assessment of secondary materials relating to antibiotic introduction and AMR burden. Results A total of 54 physicians and 17 PHEs were interviewed, and 209 physicians participated in the survey. Top unmet needs across public and private settings were as follows: access to new antibiotics to better manage drug‐resistant infections; affordability; adequate safety profile for prescribed antibiotics. Access to diagnostics and antibiotic susceptibility testing was noted as a barrier, with large tertiary and private centres experiencing better access. Implementation of antibiotic stewardship programmes was variable and limited by insufficient funding, shortage of infectious disease physicians, poor AMR education and lack of restrictions to limit antibiotic use. Antibiotic access varies by sector, centre type, location and strength of individual state procurement systems. In particular, private sector facilities have better access to Reserve products. In most countries, most Reserve antibiotics included in WHO's Essential Medicines List (EML) were not included in national EMLs or not registered in countries. Conclusion This study has helped to identify common barriers and pathways to Reserve antibiotic access, irrespective of the level of preparedness of countries. The data offer insights into possible solutions to improve access and highlight opportunities to strengthen access pathways and expedite access, for example, by identifying priority antibiotics based on national public health need. A six‐step introductory pathway for novel Reserve antibiotics is described.

In 2022, an estimated 1.25 million children 50% remained undiagnosed or unreported. WHO recently recommended integrated and decentralized models of care as an approach to improve access to TB services for children, but evidence remains limited. The Catalyzing Paediatric TB Innovation project (CaP-TB) implemented a multi-pronged intervention to improve TB case finding in children in nine sub-Saharan African countries. The intervention introduced systematic TB screening in different facility-based child-health entry-points, decentralisation of TB diagnosis and management, improved sample collection with access to Xpert® MTB/RIF or MTB/RIF Ultra testing, and implementation of contact investigation. Pre-intervention records were compared with those during intervention to assess effect on paediatric TB cascade of care. The intervention screened 1 991 401 children

# Background Tuberculosis preventive treatment (TPT) in child household contacts is recommended by World Health Organization (WHO) but limited data has been reported on the costs experienced by households with children receiving TPT. # Methods We evaluated the economic impact on households with children receiving TPT within a service-delivery model cluster-randomised controlled trial in Cameroon and Uganda. The intervention included community health worker-led home-based child-contact screening, TPT initiation and monitoring, and referral of children with presumptive tuberculosis or side effects, and was compared with each country's facility-based standard of care (control). We used a retrospective cross-sectional survey adapted from the WHO Global task force on tuberculosis patient cost surveys. All costs were collected between February 2021 and March 2021 and are presented in 2021 US\$. # Results The median household costs estimated using the human capital approach were higher in the control arm (\$62.96 \[interquartile range, IQR; \$19.78-239.74\] in Cameroon and \$35.95 \[IQR; \$29.03-91.26\] in Uganda) compared to the intervention arm (\$2.73 \[IQR; \$2.73-14.18\] in Cameroon and \$4.55 \[IQR; \$3.03-6.06\] in Uganda). Using a threshold of 20% of annual household income, 15% (95%CI; 5-31%) of households in Cameroon and 14% (95%CI; 4-26%) in Uganda experienced catastrophic costs in the control compared to 3% (95%CI; 1- 8%) in Cameroon and 3% (95%CI; 1-8%) in Uganda in the intervention. Using the output-based approach to estimate income losses increased costs by 14-32% in the control and 13-19% in the intervention across the two countries. The proportion of participants experiencing any dissaving was higher in the control, 53% (95%CI; 36-71%) in Cameroon and 50% (95%CI; 31-69%) in Uganda, compared to 18% (95%CI; 10-29%) in Cameroon and 17% (95%CI; 8-28%) in Uganda in the intervention. # Conclusions Households with child contacts initiated on TPT under a facility-based model incur significant costs. Community-based interventions help to reduce these costs but do not eliminate catastrophic expenditures. \ **Registration** https://clinicaltrials.gov/ct2/show/NCT03832023.

BackgroundOver 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention.Methods and findingsWe analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded.ConclusionsIn most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context.Trial registrationThis evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

Abstract Background The survival of HIV-infected infants depends on early identification and initiation on effective treatment. HIV-exposed infants are tested at 6 weeks of age; however, testing for HIV sooner (e.g., shortly after birth) can identify in utero infection, which is associated with rapid progression. Infant early diagnostic virologic tests often have long turnaround times, reducing the utility of early testing. Point-of-care (POC) testing allows neonates born in health facilities to get results prior to discharge. This study aimed to understand the views of mothers and health workers regarding the use and acceptability of POC birth testing. Methods Beginning in 2018, Zimbabwe offered standard HIV testing at birth to high-risk HIV-exposed infants; as part of a pilot program, at 10 selected hospitals, POC birth testing (BT) was offered to every HIV-exposed infant. In order to understand experiences at the selected sites, 48 interviews were held: 23 with mothers and 25 with health workers, including 6 nurses-in-charge. Participants were purposively sampled across the participating sites. Interviews were held in English, Shona, or Ndebele, and transcribed in English. Line-by-line coding was carried out, and the constant comparison method of analysis was used to identify key themes for each respondent type. Results Findings were organized under four themes: challenges with BT, acceptability of BT, benefits of BT, and recommendations for BT programs. Overall, BT was well accepted by mothers and health workers because it encouraged mothers to better care for their uninfected newborns or initiate treatment more rapidly for infected infants. While the benefits were well understood, mothers felt there were some challenges, namely that they should be informed in advance about testing procedures and tested in a more private setting. Mothers and HCWs also recommended improving awareness of BT, both among health care workers and in the community in general, as well as ensuring that facilities are well-stocked with supplies and can deliver results in a timely way before scaling up programs. Conclusions Mothers and health workers strongly support implementation and expansion of birth testing programs due to the benefits for newborns. The challenges noted should be taken as planning guidance, rather than reasons to delay or discontinue birth testing programs.

Objective Implement a user-centred digital health information system to facilitate rapidly and substantially increasing the number of patients treated for hypertension in low/middle-income countries.Methods User-centred design of Simple, an offline-first app for mobile devices to record patient clinical visits and a web-based dashboard to monitor programme performance.Results The Simple mobile application scaled rapidly over the past 4 years to reach more than 11 400 primary care facilities in four countries with over 3 million patients enrolled. Simple achieved median duration for new patient registration of 76 s (IQR 2 s) and follow-up visit entry of 13 s (IQR 1 s).Conclusions A fast, easy-to-use digital information system for hypertension programmes that accommodates healthcare worker time constraints by minimising data entry and focusing on key performance indicators can successfully reach scale in low-resource settings.

A doença cardiovascular (DCV) é a principal causa de morte nas Américas, e a pressão arterial elevada é responsável por mais de 50% dos casos de DCV. Nas Américas, mais de um quarto das mulheres adultas e quatro de cada dez homens adultos têm hipertensão arterial, sendo que diagnóstico, tratamento e controle estão abaixo do ideal. Em 2021, a Organização Mundial da Saúde (OMS) divulgou uma atualização das diretrizes para o tratamento medicamentoso da hipertensão arterial em adultos. Esta publicação ressalta o papel facilitador da iniciativa Global HEARTS da OMS e da iniciativa HEARTS nas Américas para catalisar a implementação dessas diretrizes, oferece recomendações específicas de políticas para sua implementação e enfatiza a necessidade de uma abordagem estratégica abrangente para o controle da hipertensão arterial. Os autores clamam para que tanto as pessoas que advogam pela Saúde, quanto as autoridades responsáveis, priorizem a prevenção e o controle da hipertensão arterial como forma de melhorar a saúde e o bem-estar das populações e reduzir as disparidades de saúde cardiovascular dentro das populações das Américas e entre elas.

Las enfermedades cardiovasculares son la principal causa de muerte en la Región de las Américas y la hipertensión es la causa de más del 50% de ellas. En la Región, más de una cuarta parte de las mujeres adultas y cuatro de cada diez hombres adultos tienen hipertensión y su diagnóstico, tratamiento y control son deficientes. En el 2021, la Organización Mundial de la Salud (OMS) publicó directrices actualizadas sobre el tratamiento farmacológico de la hipertensión en personas adultas. En este artículo se destaca el papel facilitador de la iniciativa mundial HEARTS de la OMS y la iniciativa HEARTS en las Américas para catalizar la implementación de estas directrices, a la vez que se proporciona asesoramiento específico sobre políticas para dicha implementación y se destaca la necesidad de adoptar un enfoque estratégico general para el control de la hipertensión. Los autores instan a quienes abogan por la salud y a los responsables de las políticas a priorizar la prevención y el control de la hipertensión para mejorar la salud y el bienestar de la población, y a reducir las disparidades de salud en relación con las enfermedades cardiovasculares dentro de la población y entre las poblaciones de la Región de las Américas.

The COVID-19 epidemic has once again highlighted the challenges to achieve equitable access to critical antimicrobials and vaccines. The problem is particularly acute for antimicrobials.Despite recent investments improving the pipeline for new treatments, most new treatments are not available to populations most in need, especially in low- and middle-income countries. Once a drug is approved a range of factors may hinder access, from lack incentives to register and commercialize products due to unattractive market potential to unfunded national action plans that can help improve the uptake and appropriate use of new tools to combat antibiotic resistance. Previous studies have shown that the majority of the 18 new antibacterials approved and launched between 2010-2020 were accessible in only 3 out of 14 high-income countries (Sweden, UK, and US). In low- and middle-income countries, the problem is even worse, with only 10 of the 25 new antibiotics that entered the market between 1999 and 2014 registered in more than ten countries.While lack of equitable access to life-saving medicines, diagnostics, and vaccines is not a new problem for infectious diseases, emerging opportunities and innovative approaches can help improve access globally. This talk will review promising recent developments in governance and collaborations, policies, economic models and initiatives that may help correct deadly inequities.For example, the objectives of the Access to COVID-19 Tools Accelerator may serve as model that convenes diverse actors to mount a coordinated access response which may be applied to access to other antimicrobials and vaccines. In addition, novel licensing agreements for access and stewardship to cefiderocol, an antimicrobial that is on the WHO Essential Medicines List can help serve as a pathfinder to accelerate equitable access to novel antimicrobials. The talk will also surface critiques of ongoing initiatives and raise questions for further study and discussion.

Abstract Background Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma. Methods Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle β, FEV1, FVC, FEV1/FVC, FEF50%, FEF25–75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified. Results A total of 2983 tests were analyzed in adults aged 18–40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p

Abstract Background There are major gaps in the management of pediatric tuberculosis (TB) contact investigation for rapid identification of active tuberculosis and initiation of preventive therapy. This study aims to evaluate the impact of a community-based intervention as compared to facility-based model for the management of children in contact with bacteriologically confirmed pulmonary TB adults in low-resource high-burden settings. Methods/design This multicenter parallel open-label cluster randomized controlled trial is composed of three phases: I, baseline phase in which retrospective data are collected, quality of data recording in facility registers is checked, and expected acceptability and feasibility of the intervention is assessed; II, intervention phase with enrolment of index cases and contact cases in either facility- or community-based models; and III, explanatory phase including endpoint data analysis, cost-effectiveness analysis, and post-intervention acceptability assessment by healthcare providers and beneficiaries. The study uses both quantitative and qualitative analysis methods. The community-based intervention includes identification and screening of all household contacts, referral of contacts with TB-suggestive symptoms to the facility for investigation, and household initiation of preventive therapy with follow-up of eligible child contacts by community healthcare workers, i.e., all young (

Abstract Background Testing for HIV at birth has the potential to identify infants infected in utero, and allows for the possibility of beginning treatment immediately after birth; point of care (POC) testing allows rapid return of results and faster initiation on treatment for positive infants. Eswatini piloted birth testing in three public maternities for over 2 years. Methods In order to assess the acceptability of POC birth testing in the pilot sites in Eswatini, interviews were held with caregivers of HIV-exposed infants who were offered birth testing (N = 28), health care workers (N = 14), and policymakers (N = 10). Participants were purposively sampled. Interviews were held in English or SiSwati, and transcribed in English. Transcripts were coded by line, and content analysis and constant comparison were used to identify key themes for each respondent type. Results Responses were categorized into: knowledge, experience, opinions, barriers and challenges, facilitators, and suggestions to improve POC birth testing. Preliminary findings reveal that point of care birth testing has been very well received but challenges were raised. Most caregivers appreciated testing the newborns at birth and getting results quickly, since it reduced anxiety of waiting for several weeks. However, having a favorable experience with testing was linked to having supportive and informed family members and receiving a negative result. Caregivers did not fully understand the need for blood draws as opposed to tests with saliva, and expressed the fears of seeing their newborns in pain. They were specifically grateful for supportive nursing staff who respected their confidentiality. Health care workers expressed strong support for the program but commented on the high demand for testing, increased workload, difficulty with errors in the testing machine itself, and struggles to implement the program without sufficient staffing, especially on evenings and weekends when phlebotomists were not available. Policymakers noted that there have been challenges within the program of losing mothers to follow up after they leave hospital, and recommended stronger linkages to community groups. Conclusions There is strong support for scale-up of POC birth testing, but countries should consider ways to optimize staffing and manage demand.

Abstract Background Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. Methods Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children

Summary: Cardiovascular disease (CVD) is the leading cause of death in the Americas and raised blood pressure accounts for over 50% of CVD. In the Americas over a quarter of adult women and four in ten adult men have hypertension and the diagnosis, treatment and control are suboptimal. In 2021, the World Health Organization (WHO) released an updated guideline for the pharmacological treatment of hypertension in adults. This policy paper highlights the facilitating role of the WHO Global HEARTS initiative and the HEARTS in the Americas initiative to catalyze the implementation of this guideline, provides specific policy advice for implementation, and emphasizes that an overarching strategic approach for hypertension control is needed. The authors urge health advocates and policymakers to prioritize the prevention and control of hypertension to improve the health and wellbeing of their populations and to reduce CVD health disparities within and between populations of the Americas.

Hypertension is the most important risk factor for cardiovascular diseases (CVDs), which are the leading global cause of death. Hypertension is under-diagnosed and under-treated in most low- and middle-income countries (LMICs). Current algorithms for hypertension treatment are complex for the healthcare worker, limit decentralization, complicate procurement and often translate to a large pill burden for the person with hypertension. We summarize evidence supporting implementation of simple, algorithmic, accessible, non-toxic and effective (SAANE) algorithms to provide a feasible way to access and maintain quality care for hypertension. Implementation of these algorithms will enable task shifting to less specialised health care workers and lay cadres, provision of fixed dose combinations, consolidation of the market while retaining generic competition, simplification of laboratory requirements, and lowering costs for health systems and people who incur out of pocket expenses.

Expanding hypertension services in low- and middle-income countries requires efficient and effective service delivery approaches that meet the needs and expectations of people living with hypertension within the resource constraints of existing national health systems. Ideally, a hypertension program will extend treatment coverage while maintaining service quality, maximizing efficient resource utilization and improving clinical outcomes. In this article, we discuss lessons learned from HIV differentiated service delivery initiatives, and make the case that the same approach should be adopted for hypertension programs.

Background: India has a high burden of hypertension. While the private sector provides 70% of out-patient care in the country, a significant proportion of patients seeking care from the public sector buy drugs from private markets. This study aimed to describe India’s private sector antihypertensive drugs market at the national and state levels over 2016–2018. Methods: Antihypertensive drugs sales in India from 2016–2018 were analysed using a large nationally representative dataset for the private pharmaceuticals market. In addition, data for five states (Punjab, Madhya Pradesh, Kerala, Telangana, and Maharashtra) that were the foci of a large hypertension control program were studied. Results: The Indian hypertension drug market grew at a rate of 6.9% from 2016 to 2018 with a total of 21,066 million pills sales in 2018. Single-pill combinations (SPCs) contributed to 39.1% of total sale volumes. The market comprised of 182 different antihypertensive drugs including 134 SPCs. Total volume of sales covered a maximum of 26% of treatment need for the estimated population with hypertension. Two-drug SPCs had the highest market share (36%), followed by calcium channel blockers (18%), beta-blockers (16%) and angiotensin receptor blockers (14%). Among SPCs, amlodipine+atenolol had highest sales (9.8%). Twenty-five drugs, a mix of single drugs and SPCs, accounted for 80% of total sales. There were large state-to-state variations in sales per capita, preferred therapeutic classes and drugs. Conclusions: Despite the large antihypertensive drugs market, there exists a high unmet need for treatment in India. Inter-state differences in product sales indicate variable treatment practices, underscoring the need for private sector engagement to improve hypertension care practices aligned with national and international guidelines. SPCs contributed to a large share of the private market and inclusion of select antihypertensive SPCs in the national list of essential medications should be considered for the public health system.

Hypertension remains the leading cause of cardiovascular disease worldwide and disproportionately impacts patients living in low- and middle-income countries (LMICs). Telemedicine offers a potential solution for improving access to health care for vulnerable patients in LMICs.ObjectivesThe purpose of this scoping review was to summarize the evidence for telemedicine interventions for blood pressure management in LMICs and assess the relationships between the telemedicine intervention characteristics and clinical outcomes.DesignPublished studies were identified from the following databases (from their inception to May 2020): PubMed, Scopus, and Embase. Search terms related to "Low and Middle Income Countries," "Telemedicine," and "Hypertension" were used, and clinical outcomes were extracted from the screened articles.ResultsOur search resulted in 530 unique articles, and 14 studies were included in this review. Five studies assessed telemedicine interventions for patient-provider behavioral counseling, four assessed patient-provider medical management, and five assessed provider-provider consultation technologies. Out of fourteen individual studies, eleven demonstrated a significant improvement in systolic or diastolic blood pressure in the intervention group. Of the eight studies that reported difference-in-differences changes in systolic blood pressure, between-arm differences ranged from 13.2 mmHg to 0.4 mmHg.ConclusionsThe majority of the studies in this review demonstrated a significant reduction in blood pressure with use of the telemedicine intervention, though the magnitude of benefit was not consistently large. Limitations of the studies included small sample sizes, short duration, and intervention heterogeneity. Current evidence suggests that telemedicine may provide a promising approach to increase access to care and improve outcomes for hypertension in LMICs, especially during events that limit access to in-person care, such as the COVID-19 pandemic. However, high-quality clinical trials of sufficient size and duration are needed to establish the impact and role of telemedicine in hypertension care. The protocol for this review was not registered.

Differentiated service delivery (DSD) models for HIV often exclude children and adolescents. Given that children and adolescents have lower rates of HIV diagnosis, treatment and viral load suppression, there is a need to use DSD to meet the needs of children and adolescents living with HIV. This commentary reviews the concept of DSD, examines the application of DSD to the care of children and adolescents living with HIV, and describes national guidance on use of DSD for children and adolescents and implementation of DSD for HIV care and treatment in children and adolescents in Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)–supported programmes in seven sub-Saharan countries between 2017 and 2019. Programme descriptions include eligibility criteria, location and frequency of care delivery, healthcare cadre delivering the care, as well as the number of EGPAF-supported facilities supporting each type of DSD model. A range of DSD models were identified. While facility-based models predominate, several countries support community-based models. Despite significant uptake of various DSD models for children and adolescents, there was variable coverage within countries and variability in age criteria for each model. While the recent uptake of DSD models for children and adolescents suggests feasibility, more can be done to optimise and extend the use of DSD models for children and adolescents living with HIV. Barriers to further DSD uptake are described and solutions proposed. DSD models for children and adolescents are a critical tool that can be optimised to improve the quality of HIV care and outcomes for children and adolescents.

Abstract Background The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. Methods We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. Results In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. Conclusions These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Abstract Background Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. Methods We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. Results For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. Conclusion HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

Introduction: We determine the level of adherence to the revised Kenya early infant diagnosis (EID) algorithm during implementation of a point-of-care (POC) EID project. Methods: Data before (August 2016 to July 2017) and after (August 2017 to July 2018) introduction of POC EID were collected retrospectively from the national EID database and registers for 33 health facilities. We assessed the number of HIV-infected infants who underwent confirmatory testing and received baseline viral load test and proportion of infants with an initial negative result who had a subsequent test. Results and Discussion: Significantly higher number of infants accessed confirmatory testing (94.2% versus 38.6%; P < .0001) with POC EID. Baseline viral load test and follow-up testing at 6 months, although higher with POC EID, were not significantly different from the pre-POC EID intervention period. Conclusion: The POC EID implementation has the potential to increase proportion of infants who receive confirmatory testing, thus reducing the risk of false-positive results.

Background: In 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs

Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization's routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries.An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes.Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2 ug/ml and 0.35 ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality.PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to effectively implement extended age vaccinations, access to affordably-priced PCV is critical.

BackgroundHIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including storage and transport limitations for whole blood and plasma. Data from various studies indicate that HIV RNA is stable beyond current recommendations. We conducted a systematic review to assess stability data of HIV RNA in whole blood and plasma across times and temperatures.Methods and findingsUsing a pre-defined protocol, five databases were searched for studies where blood samples from HIV patients were stored at time and temperature points that exceeded manufacturer recommendations. RNA stability, the primary outcome, was measured by the difference in means compared to samples stored within established thresholds. RNA stability was defined as ≤0.5 log degradation. The search identified 10,716 titles, of which nine full-text articles were included for review. HIV RNA maintained stability in EDTA whole blood and plasma at all measured time points up to 168 hours when stored at 4°C, while stability was detected at 72 hours (95% confidence) in whole blood at 25°C, with data points before and beyond 72 hours suggesting stability but not reaching statistical significance. For EDTA plasma stored at 30°C, stability was maintained up to 48 hours (95% confidence), with OLS linear regression estimates up to 127 hours, suggesting stability. Overall, quality of studies was moderate. Limitations included small sample sizes, few studies meeting inclusion criteria, and no studies examining RNA stability in low viremia (ConclusionsWhole blood and plasma samples in EDTA may remain stable under conditions exceeding current manufacturer recommendations for HIV VL testing. However, given the limited number of studies addressing this question, especially at low levels of viremia, additional evaluations on HIV RNA stability in EDTA tubes and PPT in field conditions are needed.

Most infections by genus Bartonella in immunocompromised patients are caused by B. henselae and B. quintana. Unlike immunocompetent hosts who usually develop milder diseases such as cat scratch disease and trench fever, immunocompromised patients, including those living with HIV/AIDS and posttransplant patients, are more likely to develop different and severe life-threatening disease. This paper will discuss Bartonella's manifestations in immunosuppressed patients and will examine Bartonella's interaction with the immune system including its mechanisms of establishing infection and immune escape. Gaps in current understanding of the immunology of Bartonella infection in immunocompromised hosts will be highlighted.