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Publications (284)
Background:
Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infectio...
This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required f...
World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respir...
Background
Multiple factors contribute to variation in disease burden, including the type and quality of data, and inherent properties of the models used. Understanding how these factors affect mortality estimates is crucial, especially in the context of public health decision making. We examine how the quality of the studies selected to provide mo...
Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables continual assessment to ensure the benefits outweigh the risks and, when safety problems arise, they are quickly identified, characterised and further problems prevented when possible. We...
Addressing social determinants of tuberculosis (TB) is essential to achieve elimination, including in low-incidence settings. We measured the association between socio-economic status and intermediate social determinants of health (SDHs, including drug misuse, tobacco smoking and alcohol), and TB, taking into account their clustering in individuals...
At the time of writing in 2019, there have been 754 confirmed cases of Lassa fever in Nigeria, 21% of whom have died. Lassa is on the priority pathogen list for WHO's R&D Blueprint for Action to Prevent Epidemics. In September 2019, WHO convened 67 scientists, regulators, ethicists, public health officials, funders and vaccine developers to discuss...
Background: Dengvaxia was used in the Philippines to vaccinate 9-10-year-old school children, living in areas highly endemic for dengue. After about 830,000 had received at least 1 of 3 recommended doses, risks of enhanced disease in dengue-naïve vaccinees were reported.
Methods: We used Phase 3 trial data to derive the proportions of cases of hosp...
The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct...
The Strategic Advisory Group of Experts (SAGE) on Immunization advises WHO on global policies for vaccines. In April, 2016, SAGE issued recommendations on the use of the first licenced dengue vaccine, CYD-TDV. In November, 2017, a retrospective analysis of clinical trial data, stratifying participants according to their dengue serostatus before the...
Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines o...
The respiratory syncytial virus causes a considerable respiratory disease burden globally, most markedly in young infants, in low and middle income countries. A diverse product pipeline illustrates the recent intensification of research and development activities for vaccines and monoclonal antibodies against RSV. With the aim to ensure that produc...
According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among causes of death for all ages, and fourth among children under 5 years old, accounting for an estimated 499,000 deaths in this young age group. It was also the second most common cause of years lived with disability (2.39 billion YLDs). The goal of the WHO/UNICEF Integ...
Background
Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s unive...
Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90days of life. Intrapartum antibiotic prophylaxis (IAP) for women at increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In...
SETTING: Greater Banjul and Upper River Regions, The Gambia.
OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia.
DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2–59 mon...
Background:
In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development...
Until 1986, transmissible spongiform encephalopathies (TSEs) were mainly of interest because of the unusual nature of the causative infectious agent—an infectious protein (prion) containing no deoxyribonucleic acid and with remarkable survival properties. However, following the large epidemic of bovine spongiform encephalopathy (BSE) in the United...
Infectious disease epidemiology is the application of methods and approaches used to understand the distribution and determinants of health and disease to the study of infections. This handbook provides a comprehensive and succinct overview of the subject and covers related specialist areas needed to understand the epidemiology of infections. The b...
The Ebola virus disease outbreak in 2014-2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emerg...
Background
In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Gui...
There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx.
A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were...
The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola Virus Disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, non-randomized comparative clinical trials were initiated. The Ebola-Tx...
Respiratory syncytial virus (RSV) is a globally prevalent, common cause of lower respiratory infection in neonates and infants. Despite its disease burden, a safe and effective RSV vaccine has remained elusive. In recent years, improved understanding of RSV biology and innovations in immunogen design has resulted in the advancement of multiple vacc...
The World Health Organization recommends artemisinin-based combination (ACT) for the treatment of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eurartesim®, following its introducti...
This Lancet commentary aims at explaining some of the nuances behind such estimates and suggests some constructive ways going forward.
Before new interventions can be used in disease control programmes, it is essential that they are carefully evaluated in “field trials”, which may be complex and expensive undertakings. Descriptions of the detailed procedures and methods used in trials that have been conducted in the past have generally not been published. As a consequence, those p...
Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of placebo controls wh...
In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda.
Ninety-six new TB patients hospitalised between 2003 and 2006 were...
Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.
A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety...
Background:
Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood.
Methods:
We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and me...
Background
Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized...
Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term...
Setting Reasons for variation in BCG protection against tuberculosis are not well understood. We therefore estimated the protection provided by BCG vaccination against tuberculosis and examined reasons for variation in different settings.
Methods We systematically searched English and non-English articles in 10 databases from inception to May 2009...
Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission.
To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculos...
Unlabelled:
To describe how, through a DSS in a rural area of The Gambia, it has been possible to measure substantial reductions in child mortality rates and how we investigated whether the decline paralleled the registered fall in malaria incidence in the country.
Methods:
Demographic surveillance data spanning 19.5 years (1 April 1989-30 Septe...
Clinical outcomes according to HIV and potential prognostic variables after completing the standard 8-mo retreatment regimen in 288 patients in Kampala, Uganda, 2003–2007.
(0.09 MB PDF)
Mortality by HIV status and potential explanatory factors.
(0.09 MB PDF)
AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.
An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optim...
Background
Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.Methods and finding...
Vaccines against human helminths are being developed but the choice of optimal parasitological endpoints and effect measures to assess their efficacy has received little attention. Assuming negative binomial distributions for the parasite counts, we rank the statistical power of three measures of efficacy: ratio of mean parasite intensity at the en...
Vaccines are designed primarily to protect vaccinated individuals against the target infection. In addition to this direct effect of vaccination, vaccination may increase the level of population (or herd) immunity by increasing the proportion of the population who are immune from infection. For infections that are transmitted from person-to-person,...
Accurate diagnostic tests have a key role in patient management and the control of most infectious diseases. Unfortunately, in many developing countries, clinical care is often critically compromised by the lack of regulatory controls on the quality of these tests. The information available on the performance of a diagnostic test can be biased or f...
The TDR Diagnostics Evaluation Expert Panel
CONSORT checklist.
(0.19 MB DOC)
Trial protocol details and amendments.
(6.45 MB PDF)
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
This was a 3-arm multic...
The Expanded Program on Immunization (EPI) has led to large reductions in morbidity and mortality among children in low-income countries. However, the basic EPI schedule may no longer be optimal because of changes in vaccines, programs, and epidemiologic circumstances. In addition, evidence has accumulated that some EPI vaccines may have nonspecifi...
The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice...
Routine vaccination programmes have led to substantial declines in the incidence of most of the target diseases. In these circumstances, vaccine effects beyond those on the target diseases may become evident. Several studies have suggested that certain vaccines may influence mortality in low income settings in ways that cannot be attributed to effe...
Drug resistant tuberculosis (TB) is a growing concern worldwide. Rapid detection of resistance expedites appropriate intervention to control the disease. Several technologies have recently been reported to detect rifampicin resistant Mycobacterium tuberculosis directly in sputum samples. These include phenotypic culture based methods, tests for gen...
Several molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic reson...
In this paper we give guidance for the design and conduct of vaccine trials against Plasmodium vivax malaria. The paper supplements earlier guidelines on the planning of vaccine trials against Plasmodium falciparum malaria [WHO. Guidelines for the evaluation of Plasmodium falciparum vaccines in populations exposed to natural infections. Geneva: Wor...
With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. Thi...
Routine vaccination programmes have led to substantial declines in the incidence of most of the target diseases. In these circumstances, vaccine effects beyond those on the target diseases may become evident. Several studies have suggested that certain vaccines may influence mortality in low income settings in ways that cannot be attributed to effe...
Despite decades of investigation in countries on three continents, an efficacious vaccine against Leishmania infections has not been developed. Although some indication of protection was observed in some of the controlled trials conducted with "first-generation" whole, inactivated Leishmania parasite vaccines, convincing evidence of protection was...
Vaccines have contributed enormously in reducing the impact of many infectious diseases, and the expanded use of new and existing vaccines provides unprecedented potential for further reducing the global burden of infectious diseases. Yet, as with the deployment of other technologies, their use may also sometimes be associated with undesirable effe...
Recent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluati...
Tables 1–4. Tables summarising methods and reporting for identified randomized controlled trials of preventive malaria interventions.
The WHO Initiative for Vaccine Research and Global Malaria Programme convened a joint scientific forum in June 2008 to discuss scientific, regulatory and public health perspectives on the measurement of efficacy in malaria vaccine field efficacy trials. Participants included clinical trialists, statisticians and epidemiologists from both developed...
Accurate diagnostic tests have a key role in patient management and the control of most infectious diseases. Unfortunately, in many developing countries, clinical care is often critically compromised by the lack of regulatory controls on the quality of these tests. The information available on the performance of a diagnostic test can be biased or f...
First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates whi...