scholarly journals A longitudinal observational study of aetiology and long-term outcomes of sepsis in Malawi revealing the key role of disseminated tuberculosis

Author(s):  
Joseph M Lewis ◽  
Madlitso Mphasa ◽  
Lucy Keyala ◽  
Rachel Banda ◽  
Emma L Smith ◽  
...  

Abstract Background Sepsis protocols in sub-Saharan Africa (sSA) are typically extrapolated from high-income settings, yet sepsis in sSA is likely caused by distinct pathogens and may require novel treatment strategies. Data to guide such strategies are lacking. We aimed to define causes and modifiable factors associated with sepsis outcome in Blantyre, Malawi to inform design of treatment strategies tailored to sSA. Methods We recruited 225 adults meeting a sepsis case-definition defined by fever and organ dysfunction, in an observational cohort study at a single tertiary centre. Aetiology was defined using culture, antigen detection, serology and PCR. Effect of treatments on 28-day outcomes were assessed by Bayesian logistic regression. Results 143/213 (67%) of participants were HIV-infected. We identified a diagnosis in 145/225 (64%) participants: most commonly tuberculosis (34%) followed by invasive bacterial (17%) and arboviral infections (13%) and malaria (9%) Tuberculosis was associated with HIV infection whereas malaria and arboviruses with the absence of HIV infection. Antituberculous chemotherapy was associated with survival (aOR 28-day death 0.17 [95% CrI 0.05-0.49] for receipt of antituberculous therapy). Of those with confirmed aetiology, 83% received the broad-spectrum antibacterial ceftriaxone but it would be expected to be active in only 24%. Conclusions Sepsis in Blantyre, Malawi, is caused by a range of pathogens; the majority are not susceptible to the broad-spectrum antibacterials that most patients receive. HIV status is a key determinant of aetiology. Novel antimicrobial strategies for sepsis tailored to sSA – including consideration of empiric antitubercular therapy in the HIV-infected - should be developed and trialed.

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A63.1-A63
Author(s):  
Mosepele Mosepele ◽  
Cecilia Kanyama ◽  
David Meya ◽  
Fiona Cresswell ◽  
Timothee Chammard ◽  
...  

BackgroundCentral nervous system infections, including meningitis, continue to cause significant morbidity in Africa. HIV has contributed to the epidemiology of CNS infections in this setting. Notable advances in the study of CNS infections by several groups have demonstrated the utility of new diagnostic strategies and impact of novel treatment strategies. However, efforts to coordinate meningitis research in Africa, and between Africa and the rest of the world remain very limited.MethodsIn a bid to promote a coordinated study of CNS infections across Africa, and in collaboration with other meningitis groups globally, the researchers of the AMBITION study (High Dose Ambisome on a Fluconazole Backbone for Cryptococcal Meningitis Induction Therapy in Sub-saharan Africa: A Randomised Controlled Non-inferiority Trial) are leveraging the EDCTP support for the AMBITION trial to set up an Africa Meningitis Trials Network.ResultsThe Africa Meningitis Trials Network (AMNET) was launched in Malawi in early 2018. Main achievements since the launch of the network, include an internal review of meningitis research across network sites and launch of the network website. The network also has two study protocols pending ethics review at all sites. These studies will provide much needed information on resources available for meningitis care, research and provide a baseline epidemiology of meningitis in Africa.ConclusionAMNET provides a rare opportunity for investigators interested in meningitis research to leverage the ongoing AMBITION trial to conduct Africa-wide preliminary research on meningitis. The network is recruiting additional members in Africa and globally to collaborate on meningitis research, and also apply for research funding to support meningitis work. Anyone interested in knowing more about the network should contact the AMNET communications officer, Ms Phum’lani Machao, [email protected]


2021 ◽  
Vol 18 (2) ◽  
pp. 87-97
Author(s):  
Hubaida Fuseini ◽  
Ben A. Gyan ◽  
George B. Kyei ◽  
Douglas C. Heimburger ◽  
John R. Koethe

2020 ◽  
Vol 30 (11) ◽  
pp. 1588-1594
Author(s):  
Ogochukwu J. Sokunbi ◽  
Ogadinma Mgbajah ◽  
Augustine Olugbemi ◽  
Bassey O. Udom ◽  
Ariyo Idowu ◽  
...  

AbstractThe COVID-19 pandemic is currently ravaging the globe and the African continent is not left out. While the direct effects of the pandemic in regard to morbidity and mortality appear to be more significant in the developed world, the indirect harmful effects on already insufficient healthcare infrastructure on the African continent would in the long term be more detrimental to the populace. Women and children form a significant vulnerable population in underserved areas such as the sub-Saharan region, and expectedly will experience the disadvantages of limited healthcare coverage which is a major fall out of the pandemic. Paediatric cardiac services that are already sparse in various sub-Saharan countries are not left out of this downsizing. Restrictions on international travel for patients out of the continent to seek medical care and for international experts into the continent for regular mission programmes leave few options for children with cardiac defects to get the much-needed care.There is a need for a region-adapted guideline to scale-up services to cater for more children with congenital heart disease (CHD) while providing a safe environment for healthcare workers, patients, and their caregivers. This article outlines measures adapted to maintain paediatric cardiac care in a sub-Saharan tertiary centre in Nigeria during the COVID-19 pandemic and will serve as a guide for other institutions in the region who will inadvertently need to provide these services as the demand increases.


Author(s):  
Matthew J. Cummings ◽  
Barnabas Bakamutumaho ◽  
Nicholas Owor ◽  
John Kayiwa ◽  
Joyce Namulondo ◽  
...  

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.


AIDS ◽  
2001 ◽  
Vol 15 ◽  
pp. S31-S40 ◽  
Author(s):  
B. Auvert ◽  
A. Buvé ◽  
E. Lagarde ◽  
M. Kahindo ◽  
J. Chege ◽  
...  

2013 ◽  
Vol 648 (1) ◽  
pp. 136-158 ◽  
Author(s):  
Monica A. Magadi

Of the estimated 10 million youths living with HIV worldwide, 63 percent live in sub-Saharan Africa. This article focuses on migration as a risk factor of HIV infection among the youths in sub-Saharan Africa. The study is based on multilevel modeling, applied to the youth sample of the Demographic and Health Surveys (DHS), conducted from 2003 to 2008 in nineteen countries. The analysis takes into account country-level and regional-level variations. The results suggest that across countries in sub-Saharan Africa, migrants have on average about 50 percent higher odds of HIV infection than nonmigrants. The higher risk among migrants is to a large extent explained by differences in demographic and socioeconomic factors. In particular, migrants are more likely to be older, to have been married, or to live in urban areas, all of which are associated with higher risks of HIV infection. The higher risk among youths who have been married is particularly pronounced among young female migrants.


2021 ◽  
Vol 12 ◽  
Author(s):  
Thilona Arumugam ◽  
Upasana Ramphal ◽  
Theolan Adimulam ◽  
Romona Chinniah ◽  
Veron Ramsuran

With approximately 38 million people living with HIV/AIDS globally, and a further 1.5 million new global infections per year, it is imperative that we advance our understanding of all factors contributing to HIV infection. While most studies have focused on the influence of host genetic factors on HIV pathogenesis, epigenetic factors are gaining attention. Epigenetics involves alterations in gene expression without altering the DNA sequence. DNA methylation is a critical epigenetic mechanism that influences both viral and host factors. This review has five focal points, which examines (i) fluctuations in the expression of methylation modifying factors upon HIV infection (ii) the effect of DNA methylation on HIV viral genes and (iii) host genome (iv) inferences from other infectious and non-communicable diseases, we provide a list of HIV-associated host genes that are regulated by methylation in other disease models (v) the potential of DNA methylation as an epi-therapeutic strategy and biomarker. DNA methylation has also been shown to serve as a robust therapeutic strategy and precision medicine biomarker against diseases such as cancer and autoimmune conditions. Despite new drugs being discovered for HIV, drug resistance is a problem in high disease burden settings such as Sub-Saharan Africa. Furthermore, genetic therapies that are under investigation are irreversible and may have off target effects. Alternative therapies that are nongenetic are essential. In this review, we discuss the potential role of DNA methylation as a novel therapeutic intervention against HIV.


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