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Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate‐amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar

February 16, 2021 - 15:49 -- Open Access
Leyre Pernaute-Lau, Ulrika Morris, Mwinyi Msellem, Andreas Mårtensson, Anders Björkman and Jose Pedro Gil
Malaria Journal 2021 20:90, 15 February 2021

The anti-malarial drug, amodiaquine, a commonly used, long-acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles, CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of these CYP2C8 polymorphisms on the efficacy and tolerability of artesunate–amodiaquine (AS–AQ) treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.

NOT Open Access | Why Asymptomatic Plasmodium falciparum Infections Are Common in Low-Transmission Settings

September 1, 2020 - 10:09 -- NOT Open Access
Björkman A, Morris U
Trends Parasitol. 2020 Aug 25:S1471-4922(20)30191-4

Plasmodium falciparum infections in low-transmission settings are often asymptomatic with low parasite densities despite low herd immunity. Based on studies in Zanzibar, this may be due to parasitic (nonvirulence) rather than host (immunity) factors.

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar

August 4, 2020 - 15:31 -- Open Access
Msellem M, Morris U, Soe A, Abbas FB, Ali AW, Barnes R, Frumento P, Ali AS, Mårtensson A, Björkman A
Emerg Infect Dis. 2020 Aug;26(8):1767-1777

Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ).

Patterns of human exposure to malaria vectors in Zanzibar and implications for malaria elimination efforts

June 26, 2020 - 15:11 -- Open Access
April Monroe, Dickson Msaky, Fredros Okumu, et al.
Malaria Journal 2020 19:212, 22 June 2020

Zanzibar provides a good case study for malaria elimination. The islands have experienced a dramatic reduction in malaria burden since the introduction of effective vector control interventions and case management. Malaria prevalence has now been maintained below 1% for the past decade and the islands can feasibly aim for elimination.

Malaria infection prevalence and sensitivity of reactive case detection in zanzibar

June 15, 2020 - 15:43 -- Open Access
Stuck L, Fakih BS, Yukich J, et al.
Int J Infect Dis. 2020 Jun 10:S1201-9712(20)30452-5

Reactive case detection (RCD) is a commonly used strategy for malaria surveillance and response in elimination settings. Many approaches to RCD assume detectable infections are clustered within and around homes of passively detected cases (index households), which has been evaluated in a number of settings with disparate results.

Monitoring the durability of the long-lasting insecticidal nets Olyset® and PermaNet® 2.0 in similar use environments in Zanzibar

May 25, 2020 - 08:41 -- Open Access
Khamis Ameir Haji, Bakari Omar Khatib, Albert Kilian, et al.
Malaria Journal 2020 19:187, 24 May 2020

Malaria transmission in Zanzibar has dramatically reduced in recent years but vector control interventions such as long-lasting insecticidal nets (LLIN) must continue to reach malaria elimination. To achieve this, the Zanzibar Malaria Elimination Programme needs actionable evidence of the durability of the LLIN brands distributed. This study compared physical and insecticidal durability of two LLIN brands: Olyset® and PermaNet© 2.0 in two similar districts on the islands of Unguja and Pemba.

Molecular methods for tracking residual Plasmodium falciparum transmission in a close-to-elimination setting in Zanzibar

February 3, 2020 - 17:07 -- Open Access
Benjamin Grossenbacher, Aurel Holzschuh, Natalie E. Hofmann, Kali Abdullah Omar, Logan Stuck, Bakar Shariff Fakih, Abdullah Ali, Joshua Yukich, Manuel W. Hetzel and Ingrid Felger
Malaria Journal 2020 19:50, 29 January 2020

Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. A method comparison was undertaken to identify the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs.

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

February 3, 2020 - 17:01 -- Open Access
Andrew P. Morgan, Nicholas F. Brazeau, Jonathan J. Juliano, et al.
Malaria Journal 2020 19:47, 28 January 2020

Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.

Harvard's Jessica Cohen: 'Zanzibar gains could be erased in months'

April 10, 2013 - 20:50 -- Bart G.J. Knols

Harvard University organised a mini-symposium on malaria on 5 April titled 'Defeating malaria, from the genes to the globe'. It was the first in a series examining global public health problems like malaria. Noteworthy in that regard are the views that were expressed during this symposium regarding the malaria situation on Zanzibar. Assistant Professor Jessica Cohen, who reportedly advised the government of Zanzibar on how to move forward with its fight against malaria made some pretty remarkable statements.

Cohen's predictions showed that malaria on Zanzibar could be eliminated in just 5 years if everyone on the island (more than a million people) would sleep under bednets. Moreover, she noted that if 'only' 65% of the population would use nets, it would take 22 years. The bad news followed: If usage rates drop to 50% she predicted an increase in prevalence to 5% in just 3 months, up from the 2% prevalence now. Worse, if it dropped to just 35%, malaria would strike back and prevalence would rise to 18% in just 3 months.

She concluded that 'these gains can be erased in months'...

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