Typhoid Fever and the Challenge of Nonmalaria Febrile Illness in Sub-Saharan Africa

Background: Typhoid fever is a major health burden in Sub-Saharan Africa. Conventional anti-typhoid drugs are becoming more and more unavailable to most patients in Africa due to the increased costs and emerging drug resistance. Therefore, there is a need for discovery of new antimicrobial agents to combat typhoid fever. Objective: This work aimed to investigate the bioactive components in Cyperus sphacelatus Rottb. (Cyperaceae) and test the antisalmonellal activity of the isolated compounds. Methods: Compound purification was done through column chromatography. Structure elucidation was accomplished based on the 1D and 2D NMR, IR and mass spectra. The biological assay was done using five bacterial strains, including Salmonella enterica subsp. enterica sérovars Typhi ATCC 6539 (STS), S. enterica subsp. enterica sérovars Typhi (ST), S. enteritidis (STE), S. enterica subsp. enterica sérovars Typhimurim (STM), and a resistant isolate of S. enterica subsp. enterica sérovars Typhi (ST566). Results: Three natural products were isolated from the methylene chloride extract of the rhizomes of C. sphacelatus, including a new furanoquinone, scabequinon-6(14)-ene (1) and two known compounds, cyperotundone (2) and vanillin (3). Compound 1 showed moderate antisalmonellal activity, with a minimal inhibitory concentration (MIC) of 32 µg/mL against STM and STS. The best inhibitory result was obtained with compound 2 on STM with a MIC of 8 µg/mL. Compound 2 also gave the best minimum bactericidal concentration (MBC) of 32 µg/mL on the STM strain. Conclusion: Discovery of the three antisalmonellal compounds from C. sphacelatus supports the addition of this plant to typhoid fever preparations.

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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

BMJ Open ◽

10.1136/bmjopen-2019-035632 ◽

2020 ◽

Vol 10 (7) ◽

pp. e035632 ◽

Cited By ~ 1

Author(s):

Heidi Hopkins ◽

Quique Bassat ◽

Clare IR Chandler ◽

John A Crump ◽

Nicholas A Feasey ◽

...

Keyword(s):

Social Science ◽

Blood Sample ◽

Venous Blood ◽

Febrile Illness ◽

Clinical Diagnostics ◽

Control Measures ◽

Sub Saharan Africa ◽

Venous Blood Sample ◽

Open Access Journals ◽

Sub Saharan

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 for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps.Methods and analysisFIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use.Ethics and disseminationEthics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739).

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

Clinical Infectious Diseases ◽

10.1093/cid/ciz715 ◽

2019 ◽

Vol 69 (Supplement_6) ◽

pp. S422-S434 ◽

Cited By ~ 3

Author(s):

Se Eun Park ◽

Trevor Toy ◽

Ligia Maria Cruz Espinoza ◽

Ursula Panzner ◽

Ondari D Mogeni ◽

...

Keyword(s):

Typhoid Fever ◽

Democratic Republic Of Congo ◽

Natural Infection ◽

Healthcare Facility ◽

Sub Saharan Africa ◽

Host Immune Responses ◽

Salmonella Infections ◽

Control And Prevention ◽

Sub Saharan ◽

Study Sites

Abstract Background Invasive 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. Methods A 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. Results Research 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. Conclusions SETA supports public health policy on typhoid immunization strategy in Africa.

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The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa

Nature Communications ◽

10.1038/s41467-018-07370-z ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 25

Author(s):

Se Eun Park ◽

Duy Thanh Pham ◽

Christine Boinett ◽

Vanessa K. Wong ◽

Gi Deok Pak ◽

...

Keyword(s):

Typhoid Fever ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Sub Saharan

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The epidemiology of febrile illness in sub-Saharan Africa: implications for diagnosis and management

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2018.02.011 ◽

2018 ◽

Vol 24 (8) ◽

pp. 808-814 ◽

Cited By ~ 28

Author(s):

M.J. Maze ◽

Q. Bassat ◽

N.A. Feasey ◽

I. Mandomando ◽

P. Musicha ◽

...

Keyword(s):

Febrile Illness ◽

Sub Saharan Africa ◽

Diagnosis And Management ◽

Sub Saharan

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Updated estimates of typhoid fever burden in sub-Saharan Africa

The Lancet Global Health ◽

10.1016/s2214-109x(17)30328-5 ◽

2017 ◽

Vol 5 (10) ◽

pp. e969 ◽

Cited By ~ 23

Author(s):

Jong-Hoon Kim ◽

Vittal Mogasale ◽

Justin Im ◽

Enusa Ramani ◽

Florian Marks

Keyword(s):

Typhoid Fever ◽

Sub Saharan Africa ◽

Sub Saharan

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Rickettsioses and Q Fever in Tanzania: Estimating the Burden of Pervasive and Neglected Causes of Severe Febrile Illness in Sub-Saharan Africa

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0963 ◽

2021 ◽

Author(s):

Paul W. Blair ◽

Mohammed Lamorde ◽

J. Stephen Dumler

Keyword(s):

Q Fever ◽

Febrile Illness ◽

Sub Saharan Africa ◽

Sub Saharan

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Typhoid fever in sub-Saharan Africa: Challenges of diagnosis and management of infections

The Journal of Infection in Developing Countries ◽

10.3855/jidc.159 ◽

2008 ◽

Vol 2 (06) ◽

Cited By ~ 10

Author(s):

Samuel Kariuki

Keyword(s):

Typhoid Fever ◽

Sub Saharan Africa ◽

Diagnosis And Management ◽

Sub Saharan

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Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan Children

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx110 ◽

2017 ◽

Vol 4 (3) ◽

Cited By ~ 14

Author(s):

Jesse Waggoner ◽

Julie Brichard ◽

Francis Mutuku ◽

Bryson Ndenga ◽

Claire Jane Heath ◽

...

Keyword(s):

Real Time ◽

Clinical Diagnosis ◽

Lake Victoria ◽

Febrile Illness ◽

Primary Diagnosis ◽

Sub Saharan Africa ◽

Lake Victoria Region ◽

The Indian Ocean ◽

Polymerase Chain ◽

Sub Saharan

Abstract Background In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed. Methods Sera from 385 febrile Kenyan children, who presented to 1 of 4 clinical sites, were tested using microscopy and real-time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV), malaria, and Leptospira. Results Malaria was the primary clinical diagnosis for 254 patients, and an arboviral infection (DENV or CHIKV) was the primary diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32 patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain reaction, microscopy demonstrated a percent positive agreement of 49.7%. The percentage of malaria cases detected by microscopy varied significantly between clinical sites. Arboviral infections were the clinical diagnosis for patients on the Indian Ocean coast (91 of 238, 38.2%) significantly more often than patients in the Lake Victoria region (2 of 145, 1.4%; P < .001). However, detection of CHIKV infections was significantly higher in the Lake Victoria region (19 of 145 [13.1%] vs 13 of 239 [5.4%]; P = .012). Conclusions The clinical diagnosis of patients with an acute febrile illness, even when aided by microscopy, remains inaccurate in malaria-endemic areas, contributing to inappropriate management decisions.

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