Vaccines and therapeutics for immunocompromised patients with COVID-19.

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.

Mental Health During the First Year of the COVID-19 Pandemic: A Review and Recommendations for Moving Forward.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

Institutional and behaviour-change interventions to support COVID-19 public health measures: a review by the Lancet Commission Task Force on public health measures to suppress the pandemic.

The Lancet COVID-19 Commission Task Force for Public Health Measures to Suppress the Pandemic was launched to identify critical points for consideration by governments on public health interventions to control coronavirus disease 2019 (COVID-19). Drawing on our review of published studies of data analytics and modelling, evidence synthesis and contextualisation, and behavioural science evidence and theory on public health interventions from a range of sources, we outline evidence for a range of institutional measures and behaviour-change measures. We cite examples of measures adopted by a range of countries, but especially jurisdictions that have, thus far, achieved low numbers of COVID-19 deaths and limited community transmission of severe acute respiratory syndrome coronavirus 2. Finally, we highlight gaps in knowledge where research should be undertaken. As countries consider long-term measures, there is an opportunity to learn, improve the response and prepare for future pandemics.

Comparative performance study of three Ebola rapid diagnostic tests in Guinea.

BACKGROUND: The 2014/15 Ebola outbreak in West Africa resulted in 11,000 deaths and massive strain on local health systems, and the ongoing outbreak in Democratic Republic of Congo has afflicted more than 3000 people. Accurate, rapid Ebola diagnostics suitable for field deployment would enable prompt identification and effective response to future outbreaks, yet remain largely unavailable. The purpose of this study was to assess the accuracy of three novel rapid diagnostic tests (RDTs): an Ebola, an Ebola-Malaria, and a Fever Panel test that includes Ebola, all from a single manufacturer. METHODS: We evaluated the three RDTs in 109 Ebola-positive and 96 Ebola-negative stored serum samples collected during the outbreak in Guinea in 2014/15, and tested by real-time polymerase chain reaction (RT-PCR). Sensitivity, specificity, and overall percent agreement were calculated for each RDT using RT-PCR as a reference standard, stratified by Ct value ranges. RESULTS: All tests performed with high accuracy on samples with low Ct value (high viral load). The Fever Panel test performed with the highest accuracy, with a sensitivity of 89.9% and specificity of 90.6%. The Ebola and Ebola-Malaria tests performed comparably to each other: sensitivity was 77.1 and 78% respectively, and specificity was 91.7% for the Ebola test and 95.8% for the Ebola-Malaria test. CONCLUSIONS: This study evaluated the accuracy of three novel rapid diagnostic tests for Ebola. The tests may have significant public health relevance, particularly the Fever Panel test, which detects seven pathogens including Ebola. Given limitations to the study resulting from uncertain sample quality, further evaluation is warranted. All tests performed with highest accuracy on samples with low Ct value (high viral load), and the data presented here suggests that these RDTs may be useful for point-of-care diagnosis of cases in the context of an outbreak. Restrictions to their use in non-severe Ebola cases or for longitudinal monitoring, when viral loads are lower, may be appropriate. Highlighting the challenge in developing and evaluating Ebola RDTs, there were concerns regarding sample integrity and reference testing, and there is a need for additional research to validate these assays.

Optimizing PMTCT efforts by repeat HIV testing during antenatal and perinatal care in resource-limited settings: A longitudinal assessment of HIV seroconversion.

BACKGROUND: Mother to child transmission (MTCT) of HIV remains a challenge in resource-limited settings. Central to elimination of MTCT is effective Provider Initiated HIV Counseling and Testing (PICT). Research has shown that conducting PICT only at the initial antenatal care (ANC) visit fails to benefit pregnant women who seroconvert later in their pregnancy. This study aimed to determine the most cost effective time to perform repeat HIV testing during ANC and perinatal care (PNC). METHODS: We studied the repeat HIV testing results of pregnant women ≥ 18 and adolescent girls aged 15-17 in the Sauri, Kenya Millennium Villages Project (MVP) site. Nurses provided HIV screening to 1,403 expectant women and 256 adolescent girls following the 1st, 2nd, 3rd and 4th ANC visits, at birth and 6 and 14 weeks postpartum. RESULTS: Five women seroconverted during the study period (incidence proportion 0.41%). One woman seroconverted at the 2nd ANC visit, another one at the 3rd, two at the 4th and one at 6 weeks post-partum. Of all the women who seroconverted, four reported an HIV negative primary partner, while one reported an unknown partner status. None of the participants reported condom use during pregnancy. Two of the seroconverters vertically transmitted HIV to their babies. The results did not suggest a clear pattern of seroconversion during ANC and PNC. CONCLUSIONS: The low rates of seroconversion suggest that testing pregnant women multiple times during ANC and PNC may not be cost effective, but a follow-up test during birth may be protective of the newborn.

The impact of "male clinics" on health-seeking behaviors of adult men in rural Kenya.

BACKGROUND: In most parts of the world, men access health services less frequently than women, and this trend is unrelated to differences in need for services. While male involvement in healthcare as partners or fathers has been extensively studied, less is known about the health-seeking behavior of men as clients themselves. This interventional research study aimed to determine how the introduction of male-friendly clinics impacted male care-seeking behavior and to describe the reasons for accessing services among men in rural Kenya. METHODS AND FINDINGS: We questioned men to assess utilization and perceptions of existing health clinics, then designed and evaluated a "male clinics" intervention where dedicated male health workers were hired for one year to offer routine, free services exclusively to men within existing healthcare facilities. Results were compared between data from Male Clinics in specific health facilities, the same facilities concurrently, nearby control facilities concurrently, and intervention facilities historically. Costs of services, distance to facilities, and quality of care were the main barriers to healthcare access reported. The number of total visits was significantly higher than control groups (p<0·0001). In the intervention group, 18·6% of visits were for a checkup compared to almost none in control groups. The most common diagnoses overall were upper respiratory tract infections, malaria and injury. A major limitation of this study is the non-comparability in information captured using the Male Clinic registers compared to control registers. CONCLUSIONS: Costs and quality of services deter men from seeking healthcare. The introduction of male-friendly health services could encourage men to seek preventive care and increase service uptake.

Tropical Laboratory Initiative: An innovative model for laboratory medicine in rural areas.

BACKGROUND: Communities in rural, low-resource settings often lack access to reliable diagnostics. This leads to missed and misdiagnosed cases of disease and contributes to morbidity and mortality. OBJECTIVE: This paper describes a model for providing local laboratory services to rural areas of Ghana, and provides suggestions on how it could be adapted and expanded to serve populations in a range of rural communities. METHODS: The Tropical Laboratory Initiative (TLI) system in Ghana comprises one central laboratory where samples delivered from clinics by motorbike riders are analysed. Test requests and results are communicated on a mHealth application, and the patient does not have to visit the laboratory or travel beyond the clinic to receive a test. The TLI also serves as a research base. The laboratory is accredited by the National Health Insurance Authority, and accepts the national health insurance. The TLI serves several communities in Amansie West, Ashanti region, and currently works with 10 clinics. The nearest hospital is a one-hour drive away and is the only other nearby facility for diagnostics beyond basic rapid tests. RESULTS: Demand for services has increased yearly since the launch in 2010, and the TLI currently provides over 1000 tests to approximately 350 patients monthly. The majority of patients are female, and the most common tests are for antenatal care. Our experience demonstrates that laboratory services can be affordable and most components already exist, even in rural areas. CONCLUSION: Ministries of health in low-resource settings should consider this model to complement the rapid tests available in clinics. Integrating with an insurance system promotes financial sustainability.

Performance of the BD-FACS Presto for CD4 count and hemoglobin measurement in a district hospital and rural laboratory in Ghana.

INTRODUCTION: In Ghana, initiation of Antiretroviral Therapy (ART) is recommended for all patients with an HIV diagnosis, regardless of CD4+ T-cell count. However, measurement of CD4 count remains an important metric for identifying patients with advanced HIV disease, and assessing a person's overall immune status, which informs the decision to offer opportunistic infection screening and prophylaxis. Access to CD4+ T cell count in rural health facilities remains a major challenge in Ghana and other resource-limited settings. This study aimed to validate the accuracy of the BD FACSPresto near-patient device for measurement of CD4 count and hemoglobin concentration against the FACSCount (CD4) and Sysmex (hemoglobin) diagnostic machines when operated in both a district hospital and rural laboratory, serving a network of health posts in Ashanti Region, Ghana. METHODOLOGY: In the first phase of the study, patients were recruited from a district hospital, and both venous and capillary blood samples were tested using the FACSCount and Sysmex as reference tests and compared to results of the FACSPresto performed in the clinic laboratory at the district hospital. In the second phase, patients were recruited from both the hospital and from rural health clinics, and samples were tested using the FACSPresto at a rural laboratory. Sensitivity and specificity among samples categorized into different clinically relevant CD4 count ranges were calculated, along with correlation between the Presto and the reference measurements, and mean and relative bias with limits of agreement. RESULTS: The FACSPresto was successfully operated in both clinical settings. A total of 59 samples in the first phase and 48 samples in the second phase were included. Positive bias was observed when comparing CD4 count measured by BD FACSPresto to FACSCount in the district hospital (bias = 44, LOA -72,160) and in the rural laboratory setting (bias = 74, LOA -96, 244). In addition, capillary blood samples were shown to give higher measures when compared to venous blood samples from the same participant. All results were statistically significant (p<0.05) apart from hemoglobin measurement in venous blood in the rural laboratory. Correlation coefficients were high for CD4 count measures and lower for hemoglobin measures. CONCLUSION: Overall, the Presto gave higher estimates of CD4 count compared to FACSCount, and hemoglobin measurements were higher than from Sysmex. Samples of capillary blood in turn gave higher results for both measurements compared to venous blood, consistent with previous analyses. These findings should be considered when selecting CD4 count machines for use at the point of care, especially in remote areas where capillary blood sampling may be preferable, but are likely balanced by device's ease of use, portability, and ability to expand access to services. These results are some of the first to demonstrate the accuracy of the FACSPresto in West Africa and show that this device can be successfully operated in a very rural lab setting and may therefore assist to provide CD4 count and hemoglobin concentration measurement to populations in need.

A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases.

Hemorrhagic fever outbreaks such as Ebola are difficult to detect and control because of the lack of low-cost, easily deployable diagnostics and because initial clinical symptoms mimic other endemic diseases such as malaria. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need. Although rapid tests such as lateral flow can be broadly deployed, they are typically not well-suited for differentiating among multiple diseases presenting with similar symptoms. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect and differentiate infection with Ebola virus from other more common febrile diseases. Here, we developed and tested an immunoassay technology that uses surface-enhanced Raman scattering (SERS) tags to simultaneously detect antigens from Ebola, Lassa, and malaria within a single blood sample. Results are provided in <30 min for individual or batched samples. Using 190 clinical samples collected from the 2014 West African Ebola outbreak, along with 163 malaria positives and 233 negative controls, we demonstrated Ebola detection with 90.0% sensitivity and 97.9% specificity and malaria detection with 100.0% sensitivity and 99.6% specificity. These results, along with corresponding live virus and nonhuman primate testing of an Ebola, Lassa, and malaria 3-plex assay, indicate the potential of the SERS technology as an important tool for outbreak detection and clinical triage in low-resource settings.

Global Introduction of New Multidrug-Resistant Tuberculosis Drugs-Balancing Regulation with Urgent Patient Needs.

New treatments for multidrug-resistant tuberculosis (MDR TB) are urgently needed. Two new drugs, bedaquiline and delamanid, have recently been released, and several new drugs and treatment regimens are in the pipeline. Misuse of TB drugs is a principal cause of drug resistance. As new drugs and regimens reach the market, the need to make them available to patients must be balanced with regulation of their use so that resistance to the new drugs can be prevented. To foster the rational use of new drugs, we propose 1) expanding/strengthening the capacity for drug susceptibility testing, beginning with countries with a high TB burden; 2) regulating prescribing practices by banning over-the-counter sale of TB drugs and enacting an accreditation system whereby providers must be certified to prescribe new drugs; and 3) decentralizing MDR TB care in rural communities by employing trained community health workers, using promising mobile technologies, and enlisting the aid of civil society organizations.

Use of eCompliance, an innovative biometric system for monitoring of tuberculosis treatment in rural Uganda.

Directly observed therapy short-course (DOTS) requires direct observation of tuberculosis (TB) patients and manual recording of doses taken. Programmatically, manual tracking is both time-consuming and prone to human error. Our project in western Uganda assessed the impact on TB treatment outcomes of a comprehensive patient support program including eCompliance, a biometric medical record device, with the aim of increasing TB patient retention. Through an observational study of 142 patients, DOTS outcomes of patients in the intervention group were compared with two control groups. Descriptive statistical comparisons, case-cohort analysis, and difference in change over time were used to assess the impact. Intervention patients had a higher cure rate than all other patients (55.6% versus 28.3% [P < 0.01]) and the odds of having a "cured" outcome were 3.17 higher (P < 0.05). The intervention group had a statistically significantly lower odds of having a negative outcome (0% versus.17% [P < 0.01]) than patients from the control groups. Additionally, the intervention group had a lost to follow-up rate lower than all other groups (0% versus 7%) that was trending on significant. In resource-limited settings, implementing comprehensive DOTS including eCompliance may reduce the occurrence of negative DOTS outcomes for patients.

Evaluation of the impact of a mobile health system on adherence to antenatal and postnatal care and prevention of mother-to-child transmission of HIV programs in Kenya.

BACKGROUND: The Millennium Villages Project (MVP) implemented in Western Kenya a mobile Health tool that uses text messages to coordinate Community Health Worker (CHW) activities around antenatal care (ANC) and Prevention of Mother-to-Child Transmission of HIV (PMTCT), named the ANC/PMTCT Adherence System (APAS). METHODS: End-user changes in health-seeking behavior in ANC and postnatal care (PNC) were investigated following registration of 800 women into APAS. These investigations employed interviews of pregnant women or new mothers (n = 67) and CHWs (n = 20). Ordinal logistic regressions and exact binomial tests were used in the routine data analyses (n = 650, health registers). RESULTS: All CHWs interviewed agreed that APAS helped them track pregnant woman efficiently, compared to paper-based tracking forms. Women registered in APAS reported that CHWs reminded them of appointments more regularly than before its inception. The routine data analysis showed that among women who had their 1(st) ANC visit in the 2(nd) trimester, women who resided in the MVP cluster and were in APAS had: 3 times the odds of going for more ANC visits compared to women who were not registered (but resided in the cluster), after adjusting for the mother's HIV status in the multivariate model (Adjusted OR = 2.58, 95% CI [1.10-6.01]); twice the odds of going for more ANC visits compared to women who were not registered and resided outside the cluster (Adjusted OR = 2.37, 95% CI [0.99-5.67]) Among women not registered, residence inside or outside the cluster did not affect the number of ANC visits made (Adjusted OR = 0.86, 95% CI [0.45-1.69]). The APAS also greatly increased the likelihood of women making the 6 recommended post-delivery baby follow-ups. For women registered in APAS, the MTCT rate at 18 months was significantly different from that of women not registered, and from the global rate of 30%. Women not registered had a 9% MTCT rate at 18 months regardless of residence, while women registered had a 0% transmission rate at both 9 and 18 months. CONCLUSIONS: The incorporation of mHealth tools in CHW programs can improve adherence to ANC and PNC and enhance PMTCT efforts.

Lessons from Africa: developing a global human rights framework for tuberculosis control and prevention.

BACKGROUND: Tuberculosis is a highly contagious disease, and there has been a rise in recent years of drug-resistant cases no longer responding to standard treatment. In order to address this threat and contain possible transmission of drug-resistant cases, some countries have taken strong action, including the compulsory detention of non-adherent drug-resistant patients. These measures have been strongly criticized by human rights advocates, and they raise the question of how to legally protect both citizens and the community. DISCUSSION: Following discussions with National Tuberculosis Programs in Africa (the continent with the highest incidence rates of tuberculosis worldwide), we show that of all the countries surveyed, all but one (Swaziland) had either no specific policy addressing tuberculosis, or only general policies regarding public health applicable to tuberculosis. Six countries also reported having policies that address non-adherence to treatment with containment (isolation in health facilities or incarceration), but laws are not adequately enforced. If the international community wants to effectively respond to the threat of tuberculosis transmission, there is a need to go beyond national tuberculosis policies and to implement an international framework for tuberculosis control, inspired by the Framework Convention on Tobacco Control, a key model for future public health treaties that address global burdens of disease. The framework, for which we clarify the conditions and procedures in this piece, would define the rights and responsibilities of the different stakeholders involved: patients, doctors, pharmaceutical firms and public authorities. To facilitate the governance of the national obligations under the Convention, a coordinating body should be set up, under the leadership of the World Health Organization and the Stop TB Partnership. Successfully implementing policies for tuberculosis that simultaneously address patients' rights and communities' wellbeing will have positive implications for those affected by the disease and serve as a basis for other global health conventions to truly ensure the global right to health.

Improved access to early infant diagnosis is a critical part of a child-centric prevention of mother-to-child transmission agenda.

BACKGROUND: Prevention-of-mother-to-child-transmission (PMTCT) programs have made it possible to achieve dramatic reductions in the rate of vertical HIV transmission. However, high attrition, particularly after delivery, has limited the impact of these interventions for HIV-exposed infants who remain at risk through the end of breastfeeding. DESIGN AND METHODS: A review of current literature on early infant diagnosis (EID) testing and country experience in low-and middle-income countries. RESULTS: While PMTCT programs report reduced rates of infection among infants tested at 2 months of age, too few services are focused on retention of HIV-exposed infants in care. An unacceptably large proportion of HIV-exposed and HIV-infected infants remain unidentified. While the complexities of EID have been simplified with the development of optimized commodities and tools to improve service delivery, the inaccessibility and inadequate uptake of EID services has resulted in lag of care for the millions of HIV-exposed infants who remain unidentified. Coverage of EID testing remains low and there are many HIV- infected infants or at risk of infection who may not enter the health system through PMTCT programs. Waiting for HIV-infected children to present sick is not an adequate strategy for identifying and linking infants to treatment. Several interventions suggest a potential to expand access to EID testing, while more aggressive testing strategies may ensure children can be captured at any point of contact with the health system. CONCLUSIONS: Programs focused on preventing vertical transmission need to increase their commitment to child-centric interventions and broaden their measure of success to reflect infants who test negative at the end of the exposure period. This paper argues that EID is a key strategy to retaining HIV-exposed infants through the end of the exposure period, as it provides an opportunity to offer early clinical care and continuous follow up. It is imperative that maternal and child survival programs become sensitized to the urgency of early identification of HIV in infants and their retention in care.

What's in a name? The future of drug-resistant tuberculosis classification.

Due to a recent resurgence in tuberculosis research focused on drug development, several new antituberculosis drugs are in the pipeline, and the standard of care for tuberculosis might soon change. If new drugs replace the current first-line treatment, then existing classifications of resistance, including multidrug-resistant and extensively drug-resistant tuberculosis, might become less relevant. When much needed new drugs reach the market, a new classification system for resistance might need to be devised to describe resistance to these novel agents. Many options for such a system exist, each with its own inherent benefits and challenges. The adoption of new terminology for resistance should be guided by outcomes data from clinical trials in progress, and should be accompanied by increased support for drug susceptibility testing in developing countries to be clinically useful. Consideration of these issues now will hopefully help foster an informed approach to the classification of drug-resistant tuberculosis in the era of new drugs.

The co-management of tuberculosis and diabetes: challenges and opportunities in the developing world.

Yanis Ben Amor and Timothy Sullivan call for more research to examine whether the diagnosis and treatment of diabetes in TB patients may improve TB outcomes and patient survival.