Trials In Low-income Countries Research Articles

Different antibiotic treatments for group A streptococcal pharyngitis.

Different antibiotic treatments for group A streptococcal pharyngitis.

Different drug approaches to COVID-19 treatment worldwide: an update of new drugs and drugs repositioning to fight against the novel coronavirus.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine's effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

Different antibiotic treatments for group A streptococcal pharyngitis.

Different antibiotic treatments for group A streptococcal pharyngitis.

What motivates or demotivates intravenous drug users to participate in hypothetical HIV vaccine efficacy trial? A qualitative study from urban Tanzania

Background:HIV vaccine efficacy trials require the active participation of volunteers who are committed and adherent to the study protocol. However, information about the influence of Injecting Drug Users (IDUs) to participate in HIV vaccine efficacy trials in low-income countries is inadequate. The present study explored the factors that motivate or hinder IDUs from participating in HIV vaccine efficacy trials in Dar es Salaam, Tanzania.Methods:A qualitative descriptive study design was employed among IDUs at Muhimbili National Hospital (MNH). A purposeful sampling technique was used to recruit the participants. Three (3) focus group discussions (FGDs) and 10 In-Depth Interviews (IDIs) were used to collect the data. The data from participants were audio-recorded, transcribed, and analysed using the content analysis approach.Findings:The participants reported that altruism and the desire to reduce risks of HIV infection were the motivators to participate in hypothetical HIV vaccine trials. In addition, participants reported to consult close relatives towards motivation to participate in the vaccine trial. In contrast, the perceived fear of vaccine side effects, lack of information about HIV vaccine studies, and HIV-related stigma towards participants were described as barriers to participate in the HIV vaccine trials.Conclusion:Participation in a hypothetical HIV vaccine trial among IDUs is influenced by positive and negative factors. Actual recruitment plans could be made through a better explanation of HIV vaccine trials, the expected individual and collective benefits associated with the trials. Community involvement and sensitisation is likely to enhance participation in future HIV vaccine trials in Tanzania.

Recommendations for fluid management of adults with sepsis in sub-Saharan Africa: a systematic review of guidelines

BackgroundSepsis guidelines are widely used in high-income countries and intravenous fluids are an important supportive treatment modality. However, fluids have been harmful in intervention trials in low-income countries, most notably in sub-Saharan Africa. We assessed the relevance, quality and applicability of available guidelines for the fluid management of adult patients with sepsis in this region.MethodsWe identified sepsis guidelines by systematic review with broad search terms, duplicate screening and data extraction. We included peer-reviewed publications with explicit relevance to sepsis and fluid therapy. We excluded those designed exclusively for specific aetiologies of sepsis, for limited geographic locations, or for non-adult populations. We used the AGREE II tool to assess the quality of guideline development, performed a narrative synthesis and used theoretical case scenarios to assess practical applicability to everyday clinical practice in resource-constrained settings.ResultsPublished sepsis guidelines are heterogeneous in sepsis definition and in quality: 8/10 guidelines had significant deficits in applicability, particularly with reference to resource considerations in low-income settings. Indications for intravenous fluid were hypotension (8/10), clinical markers of hypoperfusion (6/10) and lactataemia (3/10). Crystalloids were overwhelmingly recommended (9/10). Suggested volumes varied; 5/10 explicitly recommended “fluid challenges” with reassessment, totalling between 1 L and 4 L during initial resuscitation. Fluid balance, including later de-escalation of therapy, was not specifically described in any. Norepinephrine was the preferred initial vasopressor (5/10), specifically targeted to MAP > 65 mmHg (3/10), with higher values suggested in pre-existing hypertension (1/10). Recommendations for guidelines were almost universally derived from evidence in high-income countries. None of the guidelines suggested any refinement for patients with malnutrition.ConclusionsWidely used international guidelines contain disparate recommendations on intravenous fluid use, lack specificity and are largely unattainable in low-income countries given available resources. A relative lack of high-quality evidence from sub-Saharan Africa increases reliance on recommendations which may not be relevant or implementable.

Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis.

The incidence of nontuberculous mycobacterial (NTM) infections is increasing worldwide, particularly NTM lymphadenitis and skin infections (Buruli ulcer). This review summarizes the evidence for the protective effectiveness of BCG vaccination against NTM disease. A systematic search using PRISMA guidelines was done for controlled studies investigating the protective effectiveness of BCG vaccination against NTM disease in immunocompetent individuals. This revealed 10 studies, including almost 12 million participants. Three cohort studies in industrialized countries suggest that the incidence of NTM lymphadenitis is greatly reduced among BCG-vaccinated children compared with BCG-unvaccinated children, with a risk ratio (RR) of 0.04 (95% confidence interval [CI], .01-.21). In two randomized trials in low-income countries, BCG protected against Buruli ulcer for the first 12 months following vaccination (RR, 0.50 [95% CI, .37-.69]). Four case-control studies had conflicting results. One cohort study found that individuals with Buruli ulcer are less likely to develop osteomyelitis if they have a BCG scar (RR, 0.36 [95% CI, .22-.58]). No studies have compared different BCG vaccine strains or the effect of revaccination in this setting. The protective effect of BCG vaccination against NTM should be taken into consideration when deciding on recommendations for discontinuation of universal BCG vaccination programs and in assessing new vaccines designed to replace BCG.

G248 Long term survival of children from a cluster randomised controlled trial of women’s participatory groups in makwanpur district, nepal

Background Women’s groups practicing a participatory action learning approach (WPGs) to addressing issues around pregnancy, childbirth and newborn and child health have been shown in a number of trials in low income countries and on their meta-analysis to significantly reduce maternal and neonatal mortality. 1 Their long term impact on survival has never been explored. Aims To assess the long term impact of exposure to WPGs on maternal and child mortality in participants of the first cRCT of WPGs in Makwanpur District, rural Nepal (2001–2003). 2 Methods Outcome data were collected by interview from the mother or the household head or from wider family members or neighbours where the family had moved. Analysis was carried out on an intention to treat basis using the a priori analysis plan in the original trial. 2 Sensitivity analyses were performed using individual and cluster level comparison of person-years. Results A total of 5824 mothers and 6078 children were alive 4 weeks postpartum (Figure 1). Reliable outcome data were available for 74.2% (4321) and 72.5% (4406) and probable outcomes for a further 24.8% (1452) and 26.8% (1630) of mothers and children respectively. On individual analysis, children born into the intervention clusters had 32% reduced risk of mortality after 4 weeks of age up to age of follow-up compared to those born into the control clusters (Table 1; Odds ratio (OR): 0.68, confidence interval (CI): 0.51, 0.92). Multilevel modelling adjusting for the effects of clustering and pairing of clusters showed a similar effect size, (OR: 0.69 CI: 0.49, 0.96; Table 1). Analyses using child mortality rates per person years are more conservative and the effect size smaller and non-statistically significant (however, this method does not take into account pairing of clusters, nor variation in size of clusters, Table 3) Fewer women in the intervention clusters died than control clusters, but the difference was not statistically significant. (Figure 1, Table 2). Conclusion Our findings suggest there are long term survival benefits for children of WPGs beyond the neonatal period. Long term follow-up of other trials of WPGs are warranted. References Prost A, Colbourn T, Seward N, et al . Women’s groups practising participatory learning and action to improve maternal and newborn health in low-resource settings: a systematic review and meta-analysis. Lancet 2013; 381 :1736–46 Manandhar DS, Osrin D, Shrestha BP, et al . Effect of a participatory intervention with women’s groups on birth outcomes in Nepal: cluster-randomised controlled trial. Lancet 2004; 364 :970–9

Nonconsensual clinical trials: a foreseeable risk of offshoring under global corporatism.

This paper explores the connection of offshoring and outsourcing to nonconsensual global pharmaceutical trials in low-income countries. After discussing reasons why the topic of nonconsensual offshored clinical trials may be overlooked in bioethics literature, I suggest that when pharmaceutical corporations offshore clinical trials today, nonconsensual experiments are often foreseeable and not simply the result of aberrant ethical conduct by a few individuals. Offshoring of clinical trials is structured so that experiments can be presented as health care in a unique form of outsourcing from the host country to pharmaceutical corporations. Bioethicists' assessments of the risks and potential benefits of offshore corporate pharmaceutical trials should therefore systematically include not only the hoped for benefits and the risks of the experimental drug but also the risk that subjects will not have consented, as well as the broader international consequences of nonconsensual experimentation.

Global women's health: current clinical trials in low- and middle-income countries.

Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. To provide an overview of active women's health trials in LMICs. The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international prioritisation of maternal health.

Pediatric clinical drug trials in low-income countries: key ethical issues.

Potential child participants in clinical research trials in low-income countries are often vulnerable because of poverty, high morbidity and mortality, inadequate education, and varied local cultural norms. However, vulnerability by itself must not be accepted as an obstacle blocking children from the health benefits that may accrue as an outcome of sound clinical research. As greater emphasis is placed on evidence-based treatment of children, it should be anticipated that there will be a growing call for agreement on principles to guide clinical investigations in low-income countries. There is now general acceptance of the view that children must be protected from non-evidence-based interventions and from substandard treatments. The questions remaining relate to how best to stimulate clinical research activity that will serve the needs of infants, children, and youth in developing countries and how best to assign priority to ethically sound research that will meet their clinical requirements. In low-income countries, 39 % of citizens are 13 years of age or younger, and consequently it is certain that clinical investigations of some new therapeutic products will be conducted there more frequently. This review offers some suggestions for approaches that will help to achieve more effective ethical consideration, including (1) improving the quality of research ethics boards; (2) fostering collaborative partnerships among important stakeholders; (3) making concerted efforts to build capacity; (4) improving the quality of the consent and waiver process; and (5) developing improved governance for harmonized ethics platforms. Continuing support by international organizations is required to sustain the establishment and maintenance of stronger research ethics boards to protect children enrolled in clinical trials. This review underscores the importance of developing a culture of solidarity and true partnership between developed and low-income country organizations, which will allow all those involved, and especially child patients, to benefit from the advancement of therapeutics.

Ethics, human rights and HIV vaccine trials in low-income settings

The massive growth in global health research in past decades has posed many challenges for its effective ethical oversight, not least of which is how best to provide effective protection...

Smallpox vaccination and all-cause infectious disease hospitalization: a Danish register-based cohort study

There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections. From the Copenhagen School Health Records Register, a cohort of 4048 individuals was sampled, of whom 3559 had information about receiving or not receiving smallpox vaccination. Infectious disease hospitalizations were identified in the Danish National Patient Register. During 87,228 person-years of follow-up, 1440 infectious disease hospitalizations occurred. Smallpox-vaccinated individuals had a reduced risk of all-cause infectious disease hospitalization compared with smallpox-unvaccinated individuals [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.72-0.98]. The reduced risk of hospitalizations was seen for most subgroups of infectious diseases. The effect may have been most pronounced after early smallpox vaccination (vaccination age <3.5 years: HR 0.81; 95% CI 0.69-0.95; vaccination age ≥ 3.5 years: HR 0.91 95% CI 0.76-1.10). Among the smallpox-vaccinated, the risk of infectious disease hospitalization increased 6% with each 1-year increase in vaccination age (HR 1.06; 95% CI 1.02-1.10). Smallpox vaccination is associated with a reduced risk of infectious disease hospitalization in a high-income setting.

Assessing the Effectiveness and Public Health Impact of Rotavirus Vaccines after Introduction in Immunization Programs

Two new vaccines against severe rotavirus gastroenteritis that have high efficacy in middle- and high-income countries have recently been licensed in many countries worldwide. Clinical trials in low-income countries in Africa and Asia are ongoing. Experience gained through studies of natural rotavirus infection and the clinical trials for the current and previous rotavirus vaccines indicate that, as countries begin to introduce these newly approved vaccines into routine childhood immunization programs, monitoring their performance in real world settings should be a high priority. Key epidemiological considerations in the postlicensure period include (1) how the vaccine will perform against severe rotavirus disease under routine public health use; (2) how routine vaccination will impact the epidemiology of disease with regard to the burden of severe disease and death, age distribution of cases, seasonality, and serotype distribution; (3) whether vaccination will have a sufficient impact on transmission to reduce disease burden in unvaccinated age groups; and (4) whether vaccine will confer protection through the first 3 years of life, when most severe disease and mortality associated with rotavirus occur. Monitoring of impact with focus on these public health considerations will allow parents, health care providers, and decision makers to appreciate the health benefits of vaccination in reducing the burden of severe rotavirus disease. It will also allow assessment of the effectiveness of rotavirus vaccines in programmatic use and the need for modifying vaccination schedules or vaccine formulations to enhance the performance of immunization. In this article, we review data for the protective efficacy of the 2 new rotavirus vaccines, with emphasis on issues particularly important for consideration as these vaccines are introduced in routine infant immunization programs.

DESIGN OF A SURVEILLANCE SYSTEM FOR PREGNANCY AND ITS OUTCOMES IN RURAL NEPAL

IntroductionCommunity trials in low-income countries require monitoring and evaluation systems.The requirements of a community surveillance system include coherent design, training,field supervision and reporting, as well as the need for a robust and flexible database.Materials and methodsThis paper describes a surveillance system for identification of pregnancy and itsoutcomes in a rural area of Nepal. Mother Infant Research Activities (MIRA), incollaboration with the Institute of Child Health, London, are presently conducting astudy on the impact of a community-based participatory intervention to improveessential newborn care (ENC) in rural Nepal. The study is a cluster randomisedcontrolled trial involving 12 pairs of Village Development Committees (VDCs) inMakwanpur District. The surveillance system covers approximately 28 000 householdsand 28 000 married women of reproductive age. It was designed to identify pregnancy,its outcome for mother and infant, and activities such as antenatal care and problem-related health care seeking behaviour.DiscussionThe paper describes the processes of mapping and enumeration, pregnancyidentification, conduct of interviews, quality control and data management.Key Words: data quality, database, rural Nepal.