High-Dose Fluconazole Consolidation Therapy for Cryptococcal Meningitis in Sub-Saharan Africa: Much to Gain, Little to Lose

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]

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Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa

Clinical Infectious Diseases ◽

10.1093/cid/ciz864 ◽

2019 ◽

Vol 71 (3) ◽

pp. 525-531 ◽

Cited By ~ 1

Author(s):

Caleb Skipper ◽

Mark R Schleiss ◽

Ananta S Bangdiwala ◽

Nelmary Hernandez-Alvarado ◽

Kabanda Taseera ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Opportunistic Infections ◽

Survival Rates ◽

Hazard Ratio ◽

Sub Saharan Africa ◽

Persons Living With Hiv ◽

Median Plasma ◽

Sub Saharan ◽

Immunodeficiency Syndrome ◽

Living With Hiv

Abstract Background Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. Methods We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Results Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259–2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9–70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07–4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49–7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Conclusions Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). Clinical Trials Registration NCT01075152.

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AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study

BMJ Open ◽

10.1136/bmjopen-2018-026288 ◽

2019 ◽

Vol 9 (4) ◽

pp. e026288 ◽

Cited By ~ 2

Author(s):

Ponego Lloyd Ponatshego ◽

David Stephen Lawrence ◽

Nabila Youssouf ◽

Sile F Molloy ◽

Melanie Alufandika ◽

...

Keyword(s):

Economic Evaluation ◽

Economic Analysis ◽

Cryptococcal Meningitis ◽

Liposomal Amphotericin ◽

Standard Treatment ◽

Sub Saharan Africa ◽

Phase Iii ◽

High Dose ◽

Historical Cohort ◽

Single High Dose

IntroductionCryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation.Methods and analysisCountry-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial.Ethics and disseminationThe AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings.Trial registrationISRCTN72509687; Pre-results.

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Efficacy of a cry1Ab Gene for Control of Maruca vitrata (Lepidoptera: Crambidae) in Cowpea (Fabales: Fabaceae)

Journal of Economic Entomology ◽

10.1093/jee/toz367 ◽

2020 ◽

Vol 113 (2) ◽

pp. 974-979

Author(s):

Prince C Addae ◽

Mohammad F Ishiyaku ◽

Jean-Batiste Tignegre ◽

Malick N Ba ◽

Joseph B Bationo ◽

...

Keyword(s):

Insect Pests ◽

Field Trials ◽

Genetically Engineered ◽

Maruca Vitrata ◽

Sub Saharan Africa ◽

High Dose ◽

Cry1ab Protein ◽

Cry1ab Gene ◽

Pod Borer ◽

Sub Saharan

Abstract Cowpea [Vigna unguiculata (L) Walp.] is an important staple legume in the diet of many households in sub-Saharan Africa. Its production, however, is negatively impacted by many insect pests including bean pod borer, Maruca vitrata F., which can cause 20–80% yield loss. Several genetically engineered cowpea events that contain a cry1Ab gene from Bacillus thuringiensis (Bt) for resistance against M. vitrata were evaluated in Nigeria, Burkina Faso, and Ghana (West Africa), where cowpea is commonly grown. As part of the regulatory safety package, these efficacy data were developed and evaluated by in-country scientists. The Bt-cowpea lines were planted in confined field trials under Insect-proof netting and artificially infested with up to 500 M. vitrata larvae per plant during bud formation and flowering periods. Bt-cowpea lines provided nearly complete pod and seed protection and in most cases resulted in significantly increased seed yield over non-Bt control lines. An integrated pest management strategy that includes use of Bt-cowpea augmented with minimal insecticide treatment for protection against other insects is recommended to control pod borer to enhance cowpea production. The insect resistance management plan is based on the high-dose refuge strategy where non-Bt-cowpea and natural refuges are expected to provide M. vitrata susceptible to Cry1Ab protein. In addition, there will be a limited release of this product until a two-toxin cowpea pyramid is released. Other than South African genetically engineered crops, Bt-cowpea is the first genetically engineered food crop developed by the public sector and approved for release in sub-Saharan Africa.

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