The phylogeography and incidence of multi-drug resistant typhoid fever 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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Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa145 ◽

2020 ◽

Vol 222 (4) ◽

pp. 661-669 ◽

Cited By ~ 2

Author(s):

Steve M Taylor ◽

Brandt Levitt ◽

Betsy Freedman ◽

Mwayiwawo Madanitsa ◽

Kyaw-Lay Thwai ◽

...

Keyword(s):

Birth Weight ◽

Preventive Therapy ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Wild Type ◽

Resistance Marker ◽

Chain Reaction ◽

Delivery Outcomes ◽

Polymerase Chain ◽

Sub Saharan

Abstract Background Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. Methods We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles. Results Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46–457; P = .017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, −40 to 272; P = .142) and lower birth weights in women with A581G-bearing parasites (MD, 192 g; 95% CI, −264 to 648; P = .385) (Pinteraction = .033). Similar associations were noted on gestational age (Pinteraction = .075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, −376 to 139; P = .361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, −20 to 1586; P = .054) (Pinteraction = .005). Conclusions The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP. ISRCTN Registry www.isrctn.com/ISRCTN69800930.

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Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa

Tropical Medicine & International Health ◽

10.1111/j.1365-3156.2010.02581.x ◽

2010 ◽

Vol 15 (9) ◽

pp. 1052-1066 ◽

Cited By ~ 39

Author(s):

Giovanni Battista Migliori ◽

Keertan Dheda ◽

Rosella Centis ◽

Peter Mwaba ◽

Matthew Bates ◽

...

Keyword(s):

Multidrug Resistant ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Global Perspectives ◽

Extensively Drug Resistant ◽

Sub Saharan

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Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype

Genome Research ◽

10.1101/gr.091017.109 ◽

2009 ◽

Vol 19 (12) ◽

pp. 2279-2287 ◽

Cited By ~ 328

Author(s):

R. A. Kingsley ◽

C. L. Msefula ◽

N. R. Thomson ◽

S. Kariuki ◽

K. E. Holt ◽

...

Keyword(s):

Salmonella Typhimurium ◽

Invasive Disease ◽

Sub Saharan Africa ◽

Multiple Drug ◽

Drug Resistant ◽

Distinct Genotype ◽

Multiple Drug Resistant ◽

Sub Saharan

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Genomic investigation of a suspected multi-drug resistant Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa

10.1101/2020.08.06.236117 ◽

2020 ◽

Author(s):

Jennifer Cornick ◽

Patrick Musicha ◽

Chikondi Peno ◽

Ezgi Saeger ◽

Pui-ying Iroh Toh ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Resistance Genes ◽

Sub Saharan Africa ◽

Whole Genome ◽

Drug Resistant ◽

Sub Saharan ◽

Neonatal Care Unit ◽

Suspected Outbreak

ABSTRACTA suspected outbreak of multi-drug resistant (MDR) Klebsiella pneumoniae in a Malawian neonatal unit was investigated using whole-genome sequencing. Strain-types, virulence and resistance genes of K. pneumoniae isolated from patients from the hospital over a four-year period were identified. A MDR ST340 clone was implicated as the likely outbreak cause.

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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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