Fever In Africa Research Articles

Long-awaited update on estimates of acute rheumatic fever in Africa

Despite being the only cardiovascular disease of global impact that has been proven to be completely preventable, rheumatic heart disease remains prevalent in low-income and middle-income countries,1 including those in Africa, where primary prevention programmes are not well established due to lack of available resources.2 An understanding of the epidemiology of rheumatic heart disease has been facilitated through the number of studies published over the past decade, including some on group A streptococcus, the preceding infection thought to initiate the cascade of events leading to permanent valve damage.

Community Engagement in the Prevention and Control of Lassa Fever in Africa: A Systematic Review

Community Engagement in the Prevention and Control of Lassa Fever in Africa: A Systematic Review

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

Epidemiology of Viral Hemorrhagic Fever in Africa

A variety of viral hemorrhagic fevers such as Ebola virus disease exist in Africa and impose a great threat in public health due to their high fatality. It is considered to be difficult to eradicate the etiological agents of viral hemorrhagic fever because they have non-human natural hosts. Therefore, the importance of public health measures remains high in addition to the urgent need for the development of medicines for treatment and prevention. Furthermore, public health measures directly lead to the accumulation of epidemiological knowledge about the diseases. As an infectious disease consultant for the World Health Organization, I have been involved with public health activities including the development of clinical guidelines, the establishment of laboratory diagnostic systems, the training for infection, prevention and control, the planning of budget for outbreak response, and the analysis of epidemiological data. On the last point, I reported the situation of Ebola virus disease outbreak in Liberia, 2014-2015 and Lassa fever outbreak in Nigeria, 2018-2019 describing the risk factors, morbidity, and mortality of the diseases.

Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia

IntroductionFever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment...

Embarcadero: Species distribution modelling with Bayesian additive regression trees in r

Abstract embarcadero is an r package of convenience tools for species distribution modelling (SDM) with Bayesian additive regression trees (BART), a powerful machine learning approach that has been rarely applied to ecological problems. Like other classification and regression tree methods, BART estimates the probability of a binary outcome based on a set of decision trees. Unlike other methods, BART iteratively generates sets of trees based on a set of priors about tree structure and nodes, and builds a posterior distribution of estimated classification probabilities. So far, BARTs have yet to be applied to SDM. embarcadero is a workflow wrapper for BART species distribution models, and includes functionality for easy spartial prediction, an automated variable selection procedure, several types of partial dependence visualization and other tools for ecological application. The embarcadero package is an open source and available on Github. To show how embarcadero can be used by ecologists, I illustrate a BART workflow for a virtual species distribution model. The supplement includes a more advanced vignette showing how BART can be used for mapping disease transmission risk, using the example of Crimean–Congo haemorrhagic fever in Africa.

Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro

In recent decades, chikungunya virus (CHIKV) has re-emerged, leading to outbreaks of chikungunya fever in Africa, Asia and Central and South America. The disease is characterized by a rapid onset febrile illness with (poly)arthralgia, myalgia, rashes, headaches and nausea. In 30 to 40% of the cases, CHIKV infection causes persistent (poly)arthralgia, lasting for months or even years after initial infection. Despite the drastic re-emergence and clinical impact there is no vaccine nor antiviral compound available to prevent or control CHIKV infection. Here, we evaluated the antiviral potential of tomatidine towards CHIKV infection. We demonstrate that tomatidine potently inhibits virus particle production of multiple CHIKV strains. Time-of -addition experiments in Huh7 cells revealed that tomatidine acts at a post-entry step of the virus replication cycle. Furthermore, a marked decrease in the number of CHIKV-infected cells was seen, suggesting that tomatidine predominantly acts early in infection yet after virus attachment and cell entry. Antiviral activity was still detected at 24 hours post-infection, indicating that tomatidine controls multiple rounds of CHIKV replication. Solasodine and sarsasapogenin, two structural derivatives of tomatidine, also showed strong albeit less potent antiviral activity towards CHIKV. In conclusion, this study identifies tomatidine as a novel compound to combat CHIKV infection in vitro.

Current trends in the epidemiology and management of enteric fever in Africa: A literature review

Enteric fever remains a tropical disease of public health significance in Africa, due to its high endemicity and transmission rates, more in sub-Saharan Africa with 7.2 million cases of typhoid fever annually and incidence rate of 762 per 100 000 person-years when compared with Northern Africa with a reported incidence rate of 557 per 100 000 person-years and lower. Recent studies show that almost all regions of sub-Saharan Africa are tending towards high incidence rates, especially Central and Western Africa. Though clinically indistinguishable from paratyphoid fever, typhoid fever causes more morbidity and mortality than paratyphoid fever, with a greater threat to children. Risk factors include consumption of contaminated water, patronizing food vendors and a history of contact with a case or a chronic carrier, amongst others. Environmental factors such as the rainy season, open sewers, contaminated water bodies and areas of low elevation have been implicated. Diagnosis in Africa is challenging due to resource constraints, as many centres still depend on clinical diagnosis and serodiagnosis using Widal test, in an era where more sensitive and specific tests exist. The polymerase chain reaction is one of the most sensitive diagnostic methods, while culture (particularly bone marrow) is considered to be one of the most specific. Quinolones (ciprofloxacin) and third-generation cephalosporins, amongst others, remain potent in the management of enteric fever, with resistance to quinolones gradually on the rise. Poor diagnostics, poor antibiotic stewardship and lack of drug (antibiotic) regulation are contributors to the problem of antibiotic resistance in Africa. Prevention of typhoid fever through vaccination, especially in children is still under investigation, with steady progress being documented. Overall, long term prevention strategies for typhoid fever should be based on improved sources of drinking water, good sanitation and hygiene, food safety and poverty alleviation.

Present and future climatic suitability for dengue fever in Africa

ABSTRACT The number of dengue fever incidence and its distribution has increased considerably in recent years in Africa. However, due to inadequate research at the continental level, there is a limited understanding regarding the current and future spatial distribution of the main vector, the mosquitoAedes aegypti, and the associated dengue risk due to climate change. To fill this gap we used reported dengue fever incidences, the presence of Ae. aegypti, and bioclimatic variables in a species distribution model to assess the current and future (2050 and 2070) climatically suitable areas. High temperatures and with high moisture levels are climatically suitable for the distribution of Ae. aegypti related to dengue fever. Under the current climate scenario indicated that 15.2% of the continent is highly suitable for dengue fever outbreaks. We predict that climatically suitable areas for Ae. aegypti related to dengue fever incidences in eastern, central and western part of Africa will increase in the future and will expand further towards higher elevations. Our projections provide evidence for the changing continental threat of vector-borne diseases and can guide public health policy decisions in Africa to better prepare for and respond to future changes in dengue fever risk.

Availability and administration of benzathine penicillin G for the prevention of rheumatic fever in Africa: report of the Working Group on Penicillin, Pan-African Society of Cardiology Task Force on Rheumatic Heart Disease

Availability and administration of benzathine penicillin G for the prevention of rheumatic fever in Africa: report of the Working Group on Penicillin, Pan-African Society of Cardiology Task Force on Rheumatic Heart Disease

The Severe Typhoid Fever in Africa Program Highlights the Need for Broad Deployment of Typhoid Conjugate Vaccines.

The Typhoid Surveillance in Africa Program (TSAP) and the Severe Typhoid Fever in Africa (SETA) program have refined our understanding of age and geographic distribution of typhoid fever and other invasive salmonelloses in Africa and will help inform future typhoid control strategies, namely, introduction of typhoid conjugate vaccines.

The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis.

BackgroundInvasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis.MethodsA prospective healthcare facility–based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites.ResultsResearch data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae.ConclusionsSETA supports public health policy on typhoid immunization strategy in Africa.

The Monitoring and Evaluation of a Multicountry Surveillance Study, the Severe Typhoid Fever in Africa Program.

BackgroundThere is limited information on the best practices for monitoring multicountry epidemiological studies. Here, we describe the monitoring and evaluation procedures created for the multicountry Severe Typhoid Fever in Africa (SETA) study.MethodsElements from the US Food and Drug Administration (FDA) and European Centre for Disease Prevention and Control (ECDC) recommendations on monitoring clinical trials and data quality, respectively were applied in the development of the SETA monitoring plan. The SETA core activities as well as the key data and activities required for the delivery of SETA outcomes were identified. With this information, a list of key monitorable indicators was developed using on-site and centralized monitoring methods, and a dedicated monitoring team was formed. The core activities were monitored on-site in each country at least twice per year and the SETA databases were monitored centrally as a collaborative effort between the International Vaccine Institute and study sites. Monthly reports were generated for key indicators and used to guide risk-based monitoring specific for each country.ResultsPreliminary results show that monitoring activities have increased compliance with protocol and standard operating procedures. A reduction in blood culture contamination following monitoring field visits in two of the SETA countries are preliminary results of the impact of monitoring activities.ConclusionsCurrent monitoring recommendations applicable to clinical trials and routine surveillance systems can be adapted for monitoring epidemiological studies. Continued monitoring efforts ensure that the procedures are harmonized across sites. Flexibility, ongoing feedback, and team participation yield sustainable solutions.

A Multicenter Cost-of-Illness and Long-term Socioeconomic Follow-up Study in the Severe Typhoid Fever in Africa Program: Study Protocol.

BackgroundThere are limited data on typhoid fever cost of illness (COI) and economic impact from Africa. Health economic data are essential for measuring the cost-effectiveness of vaccination or other disease control interventions. Here, we describe the protocol and methods for conducting the health economic studies under the Severe Typhoid Fever in Africa (SETA) program.MethodsThe SETA health economic studies will rely on the platform for SETA typhoid surveillance in 4 African countries—Burkina Faso, Ethiopia, Ghana, and Madagascar. A COI and long-term socioeconomic study (LT-SES) will be its components. The COI will be assessed among blood culture–positive typhoid fever cases, blood culture–negative clinically suspected cases (clinical cases), and typhoid fever cases with pathognomonic gastrointestinal perforations (special cases). Repeated surveys using pretested questionnaires will be used to measure out-of-pocket expenses, quality of life, and the long-term socioeconomic impact. The cost of resources consumed for diagnosis and treatment will be collected at health facilities.ResultsResults from these studies will be published in peer-reviewed journals and presented at scientific conferences to make the data available to the wider health economics and public health research communities.ConclusionsThe health economic data will be analyzed to estimate the average cost per case, the quality of life at different stages of illness, financial stress due to illness, and the burden on the family due to caregiving during illness. The data generated are expected to be used in economic analysis and policy making on typhoid control interventions in sub-Saharan Africa.

A Systematic Review of Typhoid Fever Occurrence in Africa.

BackgroundOur current understanding of the burden and distribution of typhoid fever in Africa relies on extrapolation of data from a small number of population-based incidence rate estimates. However, many other records on the occurrence of typhoid fever are available, and those records contain information that may enrich our understanding of the epidemiology of the disease as well as secular trends in reporting by country and over time.MethodsWe conducted a systematic review of typhoid fever occurrence in Africa, published in PubMed, Embase, and ProMED (Program for Monitoring Emerging Diseases).ResultsAt least one episode of culture-confirmed typhoid fever was reported in 42 of 57 African countries during 1900–2018. The number of reports on typhoid fever has increased over time in Africa and was highly heterogeneous between countries and over time. Outbreaks of typhoid fever were reported in 15 countries, with their frequency and size increasing over time.ConclusionsEfforts should be made to leverage existing typhoid data, for example, by incorporating them into models for estimating the burden and distribution of typhoid fever.

How Can the Typhoid Fever Surveillance in Africa and the Severe Typhoid Fever in Africa Programs Contribute to the Introduction of Typhoid Conjugate Vaccines?

BackgroundThe World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar.MethodsData collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied.ResultsThe Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture–based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease.ConclusionsFor Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

Molecular Survey of Rickettsia spp., Anaplasma spp., Ehrlichia spp., Bartonella spp., and Borrelia spp. in Fleas and Lice in Ethiopia.

Bacterial arthropod-borne pathogens can often cause fever in Africa, but rural laboratories in these settings are usually too basic to provide a precise picture of their epidemiological impact. Our aim was to determine the prevalence of bacterial pathogens in fleas and lice in a rural area of southeast Ethiopia. Between July and November 2013, we extracted DNA from 91 fleas (Ctenocephalides felis [n = 50; 54.9%], Pulex irritans [n = 37; 40.1%], and C. canis [n = 4; 4.4%] and 30 lice (Pediculus humanus capitis [n = 16; 53.3%] and Pediculus humanus humanus [n = 14; 46.7%]), using two quantitative PCR (qPCR) analyses to look for bacteria from the genera: Anaplasma, Bartonella, Borrelia, Coxiella, Ehrlichia, Francisella, and Rickettsia. Of the 91 fleas analyzed, pathogens were present in 79 (86.8%), including Rickettsia felis (n = 41; 45%), Anaplasma platys (n = 40; 44.0%), Rickettsia monacensis (n = 2; 2.2%), Ehrlichia muris-like agent (n = 1; 1.1%), and Bartonella clarridgeiae (n = 1; 1.1%). P. irritans was the flea species most frequently infected with A. platys (67.7%), followed by C. felis (30.7%) (p < 0.001). Of the 30 lice identified, pathogens were present in 7 (23.3%): Bartonella quintana (n = 4; 16.7%), E. muris (n = 2, 6.7%), and Borrelia recurrentis (n = 1, 3.3%). Thus, in this rural area of Africa, fleas and lice can transmit parasitic pathogens to humans, causing febrile symptoms.

Arthropod-Borne Bacteria Cause Nonmalarial Fever in Rural Ethiopia: A Cross-Sectional Study in 394 Patients.

Bacterial arthropod-borne pathogens are a common cause of fever in Africa, but their precise impact is unknown and usually underdiagnosed in the basic rural laboratories of low-resourced African countries. Our aim was to determine the prevalence of arthropod-borne bacterial diseases causing fever among malaria smear-negative patients in a rural hospital located in Ethiopia. The study population included patients aged 2 years or older; referred to Gambo Rural General Hospital (West Arsi, Ethiopia), between July and November 2013, for fever or report of fever in the previous 48 h; attending the outpatient department; and testing negative for malaria by Giemsa-stained thin blood smears. We extracted DNA from 394 whole blood samples, using reverse line blot assays of amplicons to look for bacteria from the genera: Anaplasma, Bartonella, Borrelia, Coxiella, Ehrlichia, Francisella, and Rickettsia. Thirteen patients showed presence of DNA for these pathogens: three each by Borrelia spp., the Francisella group (F. tularensis tularensis, F. tularensis holartica, and F. novicia), Rickettsia bellii, and Rickettsia Felis, and one by Bartonella rochalimae. Thus, in this rural area of Africa, febrile symptoms could be due to bacteria transmitted by arthropods. Further studies are needed to evaluate the pathogenic role of R. bellii.

A Global Agenda for Typhoid Control-A Perspective from the Bill & Melinda Gates Foundation.

Recognizing that enteric fever disproportionately affects the poorest and the most vulnerable communities that have limited access to improved sanitation, safe water sources, and optimal medical care, the Bill & Melinda Gates Foundation has funded efforts to augment global understanding of the disease since the foundation’s inception. At the turn of the century, early efforts focused on characterizing the burden of disease in Asia and evaluating use of the available Vi-polysaccharide vaccines through the Diseases of the Most Impoverished projects at the International Vaccine Institute (IVI). More recent efforts have centered on supporting development of typhoid conjugate vaccines and expanding disease surveillance efforts into Africa, as well as generating a greater understanding of the clinical severity and sequelae of enteric fever in Africa, Asia, and India. The Typhoid Vaccine Accelerator Consortium is playing a critical role in coordinating these and other global efforts for the control of typhoid fever. Here, we outline the scope of support and strategic view of the foundation and describe how, by working through strong partnerships, we can realize a radical reduction of the significance of enteric fever as a global public health problem in the next 10 to 15 years.

The HPAfrica protocol: Assessment of health behaviour and population-based socioeconomic, hygiene behavioural factors - a standardised repeated cross-sectional study in multiple cohorts in sub-Saharan Africa

IntroductionThe objective of the Health Population Africa (HPAfrica) study is to determine health behaviour and population-based factors, including socioeconomic, ethnographic, hygiene and sanitation factors, at sites of the Severe Typhoid...