I WAS completely devastated to hear that legendary bass player, music producer, songwriter, sound engineer and Jazz Invitation frontman Kelly Rusike, aged 59, is gone.
He died from diabetic complications on Wednesday.
Kelly played the funkiest and most memorable killer bass riffs Zimbabwe has ever seen.
Where were you in 1980 when Zimbabwe attained independence from British rule?
Perhaps you were not yet born, but I must tell you about the exciting moments of the 1980s.
There was this pop band which came from Zambia with a big bang. They called themselves the Rusike Brothers. Kelly Rusike was one of them.
The Rusike Brothers were a family band made up of five brothers, just like the Jackson Five.
They were very popular in the 1980s and 1990s and were famous for their dazzling dancing styles and also for their weird sense of fashion as evidenced by their donning saggy and baggy gunshot jeans with holes in them.
Sometimes they went out of their way to tear the jeans in keeping with the fashion trends of the day.
They were one of the first Zimbabwean pop groups in the 1990s at most club nights as well as dance halls such as Arcadia Community Hall in Harare.
For two decades, the Rusikes dominated the changing face of post-independence popular music in Zimbabwe when everybody danced to the pulse of rhythm from the Rusikes.
The Rusike family band was formed in 1978 in Lusaka, Zambia.
With the influence of their father who was simply known as A, B, C (short for Abiathar Benjamin Chakuvinga), Tawanda (born on June 9, 1958), Abbie, Phillip, the twins Kelly and Colin (born on March 17, 1964) became southern Africa’s answer to the Jackson Five.
Most of their early music was influenced by the Jacksons and their dancing routines were modelled around top Black American pop acts of the 1970s. They even tried the famous moonwalk.
It is difficult to separate Kelly from the Rusike Brothers, although at a later stage he formed his own band known as Jazz Invitation (more about that later).
The Rusikes had moved from Zimbabwe to Zambia in 1965 during the liberation struggle. Kelly was only one-year-old at the time.
Their father was also a musician in a band called The Boogie Woogie Stars in the 1960s.
He was also a teacher and journalist in the then Rhodesia.
After finding it difficult to continue to write freely in an oppressive State, he chose to move his family to Zambia, a country which had just attained its independence from Britain.
Kelly and Colin, the twins in the family, were only close to two years old at the time of their move to Zambia.
Kelly, in particular, told me about the moments he and Colin started school at the Dominican Convent in Ndola, where he learned to speak Bemba just like any Zambian.
From the albums his father bought, they used to listen to music from Sonny Sondo, who sang in Bemba.
Kelly had mastered the language to the extent that on April 28, 2015, he sang two songs when he shared the stage with the former President of Zambia, the late Kenneth Kaunda, one titled Tiende Pamodzi , and another called Mupende Bwino to which they both received a standing ovation from the audience present.
In 1980 when Zimbabwe attained Independence and after performing in front of large audiences in Zambia, the family packed their bags and returned to the newly independent Zimbabwe, where they were an instant hit with Saturday Night, their debut single.
With an aggressive push from ABC, who was also their manager, they were given several advertising jobs.
These included voice-overs on the Post Office Savings Bank advertisement, Roller Meal videos, Merlins linen, newspaper and video advertisements.
The most popular jingle they ever did was Ngwerewere Sadza, which advertised Ngwerewere mealie-meal, Zimbabwe’s staple food.
Two singles were released between 1981 and 1985 and despite this seemingly lack of progress in the recording business, the Rusikes made a lot of business in top night clubs of Harare and Bulawayo. They also made a great impact at live shows.
In 1982, they were the supporting act for ASWAD, a reggae group from England, when it toured Zimbabwe. In 1988, their debut album Rhythm of My Heart was released.
This included their hit single, a version of Simon Garfunkel’s Cecilia which featured on Radio 3’s (now Power FM) HitPick for 12 weeks.
In 1990, the Rusikes became the main support act for Randy Crawford’s show in Harare.
Work on a second album began at the same time, but a few snags at the studio plus the untimely death of their father, ABC, forced the Rusikes to abandon the work on the album.
Instead, a re-mix version of Saturday Night was released.
In 1992, I was part of the team that went to the United Kingdom with the Rusikes.
Due to poor planning on the part of their Malawian promoter, Jeff Macadam, their trip did not make a big impact overseas.
The Rusikes became Zimbabwe’s top family group which stayed together for a long time as performers.
It was also the Rusikes who started off artistes such as the now-internationally acclaimed Rozalla Miller whose hit single, Everybody is Free to Feel Good wowed the world a few years ago.
In 1995, they recorded an album that included a Paul Simon classic and hit song entitled If You Really Need Me.
Now back to Kelly as I promised:
I negotiated the contract for the jingle Ngwerewere Sadza with management at the Grain Marketing Board.
The band went to shoot a video of the advertisement. The contract was supposed to last one year only, but because the video was so popular in Zimbabwe, they kept playing it beyond the agreed 12 months.
Kelly came to me and suggested that I go with him to stop the advertisement.
We negotiated with the management and they gave us a cheque of an extra $10 000 on condition that the band changed from the black and white video to a colour one, which they would continue to use for another two years.
I suggested that the cheque should be written in Kelly’s name. Kelly went to cash the cheque and did not share the money with his brothers. Tawanda and Abby were upset.
The dispute rose to the extent that Kelly decided to quit the Rusike Brothers band.
It was a difficult decision as he remained part of the family which had a long and rich history together as a band.
By 2000, Colin and Kelly, the twins, had both left the group. Kelly formed his own group, The Jazz Invitation, with female singer Prudence Katomeni-Mbofana, Bernie Bismarck on keyboards, Simba Dembedza on drums, Matthew Ngorima on guitar, Vee Mukarati on saxophone and also Patience Musa on vocals.
Besides being the band leader of Jazz Invitation, Kelly also owned Shed Studios, which recorded songs such as BP Yangu Yakwira (written by Filbert Marova and sung by Prudence Katomeni-Mbofana).
Kelly, like Michael Jackson who decided to split from his brothers after the Victory Tour in 1984, also decided to go solo when he formed Jazz Invitation, which started to play a different genre of music from the Rusikes.
The concept, Jazz Invitation, was originally conceived by drummer and musical entrepreneur from Mutare, Sam Mataure, who initially invited different musicians to play at Jazz festivals around the country.
The novel idea caught on like wildfire as it brought together musicians of varied styles and tastes.
The band’s line-up changed several times over the years with Kelly (bassist/vocals) remaining the only constant.
It started with Victor on the drums and eventually incorporated Mataure, Richie Lopes, Kudzie and Louis Mhlanga.
When the Frontline Kids split up, Kelly took Filbert Marova as Jazz Invitation’s keyboards player.
I asked Kelly whether he no longer belonged to the Rusike Brothers and why he found it necessary to form a band without his brothers.
Here is what he had to say:
“I will always be a part of the Rusike Brothers, because, and most importantly, we are family. I owe a lot of my musical journey to my brothers. Even though Jazz Invitation is my pride and passion, I still do play with them from time to time and will continue to do so when time allows. We might have our differences, but the important thing is that we are family”.
Indeed, in June 2014, a music promoter in Slovakia visited the social media platform, YouTube, and saw the Rusike Brothers doing their thing.
He likened them to the Jackson 5 and was amazed to know that such a group existed in Africa. He was impressed. He called Zimbabwe to find out how he could get in touch with the group.
In no time at all, he had invited the Rusikes to do a two-week tour in Slovakia, where the three brothers Tawanda, Philip and Abbie teamed up with their prodigal brother, Kelly of Jazz Invitation, Jose on drums, Kurt Rusike on vocals and Isheunopa Jera on keyboards to showcase to the rest of the Czech Republic and Slovakia what the promoter saw and liked.
Missing from the original team was Kelly’s twin brother, Colin, who went to the UK during the Rusikes tour of the UK and has not been heard of since. There is speculation that he might also be dead.
Kelly’s skill and passion is legendary. He will be sorely missed.
His passing leaves a big void in Zimbabwe’s music legacy. May his dear soul rest in eternal peace.
Jennifer Frances Namuli Kizza was feeling tired after work one evening in March 2021. And yet she still kept a scheduled first phone call with Donald Mayfield Brown, whom she had met through a dating app.
Ms. Kizza, 28, from Gainesville, Fla., had previously given up on finding a serious relationship. But now, as a medical student at Harvard, she wanted to make the time. “It was really challenging for me to find people where I felt like we both had the same goals for our relationship and for what romance looked like,” she said.
Mr. Brown, 31, who goes by Field, was living in Starkville, Miss., at the time, teaching in the English and African American studies department at Mississippi State University and finishing his dissertation research. He changed his location on the dating app Hinge to Boston with the hope of pursuing a relationship while finishing his doctoral degree at Harvard.
Ms. Kizza expected their first phone call to be brief, but it lasted for nearly an hour. The two bonded over a shared Southern upbringing, their families and similar poundcake recipes they were fond of. Mr. Brown’s came from his mother.
On their first virtual date in April, they watched an episode of “Waffles + Mochi,” a Netflix series about healthy food hosted by Michelle Obama.
“Growing up in the conservative Black Belt South, I didn’t want to watch a show with a lot of explicit stuff on my first date,” Mr. Brown said. “I didn’t want to lead that way with the person I wanted to be with.”
They eventually moved on to the Starz drama series “Power” over several more virtual dates.
Before matching on Hinge, the two had nearly crossed paths several years earlier.
Mr. Brown was attending Oxford University as a Rhodes scholar, working toward a master’s degree in history. He left by July 2016 to return to Harvard to start a Ph.D. program, three months before Ms. Kizza arrived at Oxford to pursue a master’s in global health science. That spring, she had graduated from Harvard with a bachelor’s degree in neurobiology and global health and health policy.
In September 2017, she became a Fulbright research fellow in Uganda alongside her father, who received his grant to teach and research the impact of soil pollution. Ms. Kizza, who began medical school at Harvard in 2018, will be doing her residency at Massachusetts General Hospital this summer.
Mr. Brown graduated from Mississippi State University in 2014with a bachelor’s in philosophy and English. He earned a doctoral degree in English literature at Harvard last year and is currently a post-doctorate fellow at Brown.
Their first in-person date, at a Thai restaurant, wasn’t until July 2021, when Mr. Brown returned to Boston. He recalled their laughter and cheerful banter from that first meeting. “I never really had a date like that,” he said, adding that he was so wrapped up in their conversation that he left his credit card at the restaurant.
Mr. Brown would find more reasons to see Ms. Kizza again. When she needed to get to work for her medical rotations at Brigham and Women’s Hospital, he would wake up at 5 a.m. to drive her so she wouldn’t have to ride her bike.
Ms. Kizza invited him to attend her cousin’s wedding in Orlando, Fla., in February 2022. It was the first time he met Ms. Kizza’s family. Her mother is from Malawi and her father from Uganda; they live in Gainesville. It was a big step, and she knew her family would take it as a sign that the relationship was serious.
In the summer of 2022, Ms. Kizza met Mr. Brown’s parents in Vicksburg, Miss. At the time, she was dealing with her father’s cancer diagnosis and felt even more appreciative of the warm welcome she received.
“It was just the hardest times for my family and for me,” she said. “It just felt like a miracle to just have this beautiful extension of people to support me.”
Mr. Brown proposed last August. He planned a surprise outing to distract Ms. Kizza as he awaited the arrival of a photographer, her friends and her cousin at the Public Garden in Boston. First, they stopped at the cafe L.A. Burdick Handmade Chocolates to pick up her favorite pastry, and then they strolled around the Newbury Street shopping district. When they arrived at the garden, Mr. Brown got down on one knee.
The couple celebrated their upcoming nuptials with a kwanjula, a Ugandan engagement ceremony, in November in Gainesville. During an evening of costume changes, dancing and gifts presented to Ms. Kizza’s family, Mr. Brown asked to marry her, again, in front of 150 guests.
They wed on April 29 at the Chapel of Memories on Mississippi State University’s campus, a nod to Mr. Brown’s Southern roots and time as an undergraduate. The wedding was officiated by Reginald L. Walker, a pastor at the Word of Faith Christian Center in Vicksburg. The couple asked that the 100 guests be vaccinated to attend.
In her vows, Ms. Kizza recalled their first phone call. “I knew that day, romantic or not, Field was going to be in my life for the rest of my life,” she said.
Treatment response of P. falciparum malaria is influenced by many factors. Such factors include drug quality, pharmacokinetic characteristics of individual drugs, parasite sensitivity, host genetics,1 drug–drug interactions and food–drug interactions. Inter-individual variability with respect to extent and rate of absorption, metabolism, distribution, plasma protein binding and elimination has been shown to influence the plasma concentration of drugs, hence affecting treatment outcomes in return.2 The inter-individual variability is common in Africa due to genetic diversity and heterogenicity.3 The complex patterns of population expansion, migration, contraction and admixture during evolutionary history explain the diversity observed in African populations.4 Sub-Saharan Africa (SSA) uniquely bears the highest global disease burden of infectious diseases, particularly malaria and HIV (90% and 69%, respectively). Unfortunately, only about 3% of patients with African or SSA genetic background take part in clinical trials globally.5 This implies that drugs employed in clinical practice lack information on safety and efficacy in African populations, thus the information employed in SSA relies mainly on post-marketing surveillance. Employing information from clinical trials which do not involve African populations creates uncertainty regarding the impact of genetic diversity during treatment. Thus, characterization of different ethnic groups in SSA is pivotal for implementation of pharmacogenomics or implementation of treatment based on the major drug metabolizer genotypes in the region.
The role of heritable genetic variations on treatment outcomes in malaria has gained much attention over recent years. However, such studies began in the 1950s with a remarkable finding on higher occurrence of hemolytic anaemia among black American soldiers than their white counterparts when primaquine was administered.6
The pattern of genetic variants affecting efficacy and safety of commonly used drugs in clinical practice has been of major interest in pharmacogenetic studies in SSA. Though not all populations have been studied, there has been progress as various genome initiatives, such as malariaGEN, African pharmacogenomic consortium (APC), H3Africa and African Genome variation Project have been established.7 Globally, significant advances have been achieved whereby individualized therapy is recommended for anticoagulants (warfarin-CYP2C9*2&*3), antiplatelet agents (clopidogrel- CYP2C19*2), antipsychotics (amitriptyline-CYP2D6&citalopram-CYP2C19)8 and anticancer treatments (tacrolimus-CYP3A5).9 With regard to P. falciparum malaria, CYP450 genotype-based treatment has not been introduced. However, G6PD deficiency testing prior to primaquine treatment for P. vivax malaria patients is now common practice in some South East Asian countries.10
Genetic variability in cytochrome P450 (CYP450) enzyme family has been shown to determine pharmacokinetic profiles of many drugs, including the antimalarials.11 The CYP3A4 gene, which is located on chromosome 7q21.3-q22.1 consisting of 13 exons,12 contributes to metabolism of about 50% of drugs used in clinical practice.13–15 In the liver microsomes, CYP3A4 mediates its reactions through the nicotinamide adenine dinucleotide phosphate-dependent electron pathway.12 The major contributor in drug metabolism in the CYP3A4 family is CYP3A4*1B (rs2740574),16 which is a result of A to G transition at nucleotide 392 in the promoter sequence of the gene.17 This single nucleotide polymorphism (SNP) results in poor metabolism of artemether and lumefantrine.11,18
CYP3A5 isoenzyme is regarded as the second contributor to drug metabolism after CYP3A4.19,20 CYP3A5*3 (rs776746) SNP occurs at highest abundance and plays a major role in drug metabolism within the CYP3A5 gene. This SNP is a result of the replacement of a nucleotide A by nucleotide G at locus 6986 within intron 3, producing an mRNA splice defect and consequently producing a premature stop codon.19,20 The CYP3A5*3 plays a significant role in the metabolism of artemether, lumefantrine, mefloquine, primaquine and chloroquine.4
The expression of both CYP3A4 and CYP3A5 is inducible by drugs. The increased enzyme activity is a result of increased expression via nuclear receptors pregnane X receptor (PXR), glucocorticoid receptor (GR), constitutive androstane receptor-β (CAR), vitamin D receptor (VDR) and hepatocyte nuclear factor-4 (HNF4α).21,22 These nuclear receptors increase transcription and expression of CYP3A4/5 after binding to DNA segments present in the CYP3A promoter (for CYP3A4) region, mainly PXR responsive element (prPXRE), xenobiotics responsive enhancer module (XREM) and constitutive liver enhancer module (CLEM4).
CYP2C8*2 SNP exists at higher frequencies among African than Asian and Caucasian populations. Unlike CYP2C8*2, the CYP2C8*3 SNP is common in Caucasians and Asians, but very rare in Africans.23 Both CYP2C8*2 and CYP2C8*3 are associated with a significant reduction in amodiaquine (AQ) in vitro metabolism. AQ adverse events are rare (1:2000) but very serious. These adverse drug reactions (ADRs) include neutropenia effects and severe liver failure. Studies associate these ADRs with a highly reactive and short-lived quinine-imine (QI) species which are products of AQ and DEAQ (metabolite of AQ) metabolism.24 CYP1A1 and CYP1B1 enzymes have been shown to play a great role in the formation of QI from in vitro biotransformation of AQ and DEAQ,25 since CYP1A1 and CYP1B1 are extra-hepatic localized, this could explain the occurrence of neutropenia effects observed with amodiaquine since the biotransformation of AQ and DEAQ to QI occurs in blood and not in the liver.24 There is a high possibility that CYP1A1 and CYP1B1 fast metabolizers are likely to suffer from AQ therapy side effects.24
CYP2A6 and CYP2B6 play a minor role in the biotransformation of artemisinin derivatives to form dihydroartemisinin, which is an active metabolite.26 The low activity of CYP2A6*1B and CYP2B6*6 is suggested to predict low plasma concentrations of dihydroartemisinin.26,27 The elimination of dihydroartemisinin depends on its conversion of inactive glucuronide conjugates, which is mediated by the highly polymorphic uridine diphosphate glucuronosyltransferase (UGT1A6 &UGT2B7) enzymes.28 A summary of the human genetic variants important for antimalarial drug metabolism is shown in Table 1.
Table 1 CYP450 Single Nucleotide Polymorphisms Involved in Antimalarial Drugs Metabolism
We have previously reported the frequencies of cytochrome P450 polymorphisms responsible for metabolism of antimalarial drugs in Africa.40 Other researchers have also extensively assessed these frequencies in the region.22,41,42 In general, the most frequently recorded SNPs are CYP2C8*2 (15–22%), CYP2B6*6 (30–50%), CYP3A4*1B (50–80%) and CYP3A5*3 (15–80%). However, the information on the influence of these polymorphisms on metabolism of antimalarial drugs used in clinical settings in SSA is scanty, thus evidence on the impact of these SNPs on pharmacokinetic profiles, efficacy and safety is not established. In this review, we explore and synthesize available evidence on the influence of cytochrome P450 polymorphisms on pharmacokinetic profiles and treatment outcomes of ACTs and other antimalarial drugs employed in SSA.
Methods
Literature Search
Literature search for published studies assessing the influence of CYP450 enzymes on PK profiles (plasma concentrations), efficacy and safety of antimalarial drugs in SSA was done through the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, EMBASE, SCOPUS, PubMed, Medline and LILACS online databases.
The search terms used were: ((“amodiaquine” and “CYP2C8*2”) AND (“efficacy”)) OR ((“amodiaquine” and “CYP2C8*2”) AND (“efficacy”) AND (“Africa”)) OR ((“amodiaquine” and “CYP2C8*2”) AND (“safety”) AND (“Africa”)) OR ((“amodiaquine” and “CYP2C8*2”) AND (“Pharmacokinetics”) AND (“Africa”)) OR ((“amodiaquine” and “CYP2C8*2”) AND (“Plasma concentration”) AND (“Africa”)). For lumefantrine, the search terms used were “CYP3A4*1B”) AND (“efficacy”)) OR ((“lumefantrine” and “CYP3A4*1B”) AND (“efficacy”) AND (“Africa”)) OR ((“lumefantrine” and “CYP3A4*1B”) AND (“safety”) AND (“Africa”)) OR ((“lumefantrine” and “CYP3A4*1B”) AND (“Pharmacokinetics”) AND (“Africa”)) OR ((“lumefantrine” and “CYP3A4*1B”) AND (“Plasma concentration”) AND (“Africa”)). The same approach was used for other drugs by replacing the name of the drug and the CYP450 SNP involved in metabolism of the drug. We used the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015 checklist43 to identify studies to be included in our review.
Inclusion Criteria
Publications assessing the impact of CYP450 polymorphisms on PK profiles, safety and efficacy of antimalarials used for treatment of uncomplicated P. falciparum malaria in SSA were included. These studies were not time bound.
Exclusion Criteria
We excluded, for numerous reasons, studies assessing the influence of CYP450 SNPs on other drugs apart from antimalarials, studies assessing the influence of CYP450 on interaction between antiretroviral drugs (ART) and antimalarials excepting those with data for controls who are not on ART, studies assessing the impact of Phase II metabolizing enzymes on safety, efficacy and pharmacokinetic profiles, studies assessing the influence of drug transporters on pharmacokinetic profiles and treatment outcomes and studies assessing the influence of CYP450 polymorphisms on antimalarial treatment outcomes and PK profiles in regions other than SSA. Meeting communications and findings published based on animal models were not regarded as sufficient evidence and thus were also excluded. Studies assessing the influence of CYP450s on primaquine among P. vivax patients and volunteers were also excluded.
Methodological and Data Quality Assessment
Methodological quality assessment was done using the national institute of health (NIH) study quality assessment tools for controlled intervention, observational cohort and cross-sectional studies.44 The score ranged from 0 to 14, with a score of one point each that was then converted to percentages. The score range of 0–60% was regarded as low quality, 61–80% good quality and 81–100% excellent quality. Any difference in opinion with regard to extracted data and methodological quality assessment was resolved by consensus between the two independent reviewers. All included studies were of good to excellent quality as per the NIH scale.
Data Extraction
Two independent reviewers participated in the data extraction and screening of the results of the literature search and selected studies as per the inclusion criteria. Differences in opinion between reviewers on inclusion of studies were resolved through discussion. The basic information extracted included the author names, country in which the study was carried out, study population, sample size, SNPs, study endpoints, influence on pharmacokinetic profiles, influence on efficacy and influence on safety. Data was entered into extraction sheets.
Results
Study Characteristics
Fifty-six articles were included for full-text review from the 298 records (after removal of duplications) which were identified through the electronic database. Thirteen studies were finally included in data extraction after meeting the inclusion criteria. Details of the study search are shown in Figure 1. These studies originated from eight different countries within SSA.
Figure 1 PRISMA flow diagram for article searches and screening.
Note: Adapted from Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group* T. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine.2009 Aug 18;151(4):264-9.43
Treatment Outcome
Pernaute-Lau et al45 carried out a study to assess the influence of CYP2C8*2 (805A>T) and CYP2C8*3 (416A>G) on treatment outcomes and tolerability among P. falciparum malaria patients treated with artesunate amodiaquine (ASAQ) in a Zanzibar population, Tanzania. This study reported presence of CYP2C8*3, which is rare in African populations but common among whites and Caucasians. The study end points were adverse events, ACPR, recrudescence and re-infection among malaria patients after 28- and 42-day follow up. There was no significant difference in recrudescence between subjects carrying CYP2C8*2 mutant alleles and wild type alleles. Carrying CYP2C8*2 or CYP2C8*3 did not predict for ACPR and re-infection among malaria patients. However, carrying CYP2C8*2 or CYP2C8*3 was associated with occurrence of non-serious adverse events compared to those with wild type alleles (Table 2).
Table 2 Influence of CYP450 SNPs on Plasma Concentration and Treatment Outcomes
Habtemikael et al53 carried out a cross-sectional study among malaria patients on artesunate amodiaquine in Eritrea. This study reported lack of association between CYP2C8*2 (805A>T) or CYP2C8*3 (416A>G) and extra pyramidal effects among Eritreans.
Mutagonda et al49 did a prospective cohort study in Tanzanian pregnant women to assess the influence of pharmacogenetics on day 7 plasma concentration and treatment outcomes. This study did not report association between CYP2B6*6 (516G>T), CYP3A5*3 (6986A>G) and day 28 ACPR. Unexpectedly, the study reported association between CYP3A4*1B (392A>G) with day 28 ACPR but not day 7 lumefantrine plasma concentration. This finding may have happened by chance since it is the day 7 plasma concentration of the drug which is suggested to determine treatment outcomes in malaria patients (Table 2).
Adjei et al50 assessed the influence of CYP450 polymorphisms on treatment outcomes and adverse events among Ghanaian children with uncomplicated malaria receiving ASAQ or AQ. No difference in efficacy and adverse events was observed between patients with CYP2C8*2 mutant allele and those with wild type allele (Table 2).
The assessment on the impact of CYP2C19*2 among Gambian adults with uncomplicated receiving chlorproguanil by Janha et al55 reported lack of significance in area under the curve (AUC) and maximum plasma concentration (Cmax) between those with loss of function allele and those without. Full pharmacokinetic sampling was done after three daily doses and plasma concentrations were used to determine AUC and Cmax (Table 2).
Another study in Burkina Faso, by Parikh et al,29 assessed the influence of CYP2C8 genotypes on efficacy and adverse events among malaria patients with uncomplicated malaria receiving ASAQ after 28 days of follow up. In this study, treatment outcomes in terms of ACPR, recrudescence and re-infection did not vary between patients with CYP2C8*2 (805A>T) and wild alleles (Table 2).
The influence of CYP2B6 genotypes on treatment outcomes among HIV-positive patients in the absence of antiretroviral therapy (ART) co-treatment (control group) was studied in Tanzania by Maganda et al.54 This group included only HIV-infected patients on artemether lumefantrine but who had not started taking ART, thus the drug–drug interactions between lumefantrine and efavirenz which could affect the plasma concentrations of either drug were not observed. The major finding was lack of association between CYP2B6*6 genotypes with incidence of recurrent parasitaemia (Table 2).
Mballa et al52 evaluated the influence of CYP2C8*2 variant allele on treatment outcomes among children with uncomplicated P. falciparum malaria in Cameroon. This study also reported lack of influence on treatment outcomes associated with CYP2C8 genotypes.
Lumefantrine and Amodiaquine Plasma Concentrations
Some et al51 did a cross-sectional survey on the influence of CYP2C8*2 (805A>T) SNPs on amodiaquine metabolism in Burkina Faso. There was no difference in day 7 DEAQ plasma concentrations between those with homozygous wild type allele and those with mutant allele. CYP2C8 genotypes did not contribute to differences in DEAQ concentration between subjects with mutant alleles and those with wild type alleles in Ghanaian children receiving ASAQ and AQ50 (Table 2).
Mutagonda et al49 also reported lack of association between CYP2B6*6 (516G>T) and day 7 lumefantrine concentration among pregnant women with uncomplicated P. falciparum malaria. Similar findings are reported for CYP3A4*1B (392A>G). However, patients with CYP3A5*3 (6986A>G) genotype had slightly higher day 7 lumefantrine concentration than their counterparts (CYP3A5*1/1*) but treatment outcomes were not affected (Table 2).
Adjei et al50 assessed the influence of CYP450 polymorphisms on pharmacokinetics among Ghanaian children with uncomplicated malaria receiving ASAQ or AQ. CYP2C8 genotypes did not contribute to the difference in the mean day 3 DEAQ concentrations between subjects with mutant and wild type allele.
Another study in Burkina Faso, by Parikh et al,29 evaluated the influence of CYP2C8 genotypes on efficacy and pharmacokinetic profiles of ASAQ among malaria patients with uncomplicated malaria. In this study, the intrinsic clearance of AQ for CYP2C8*2(805A>T) was six-fold lower than that of wild type allele (Table 2).
A population pharmacokinetics study was done in Tanzania by Hodel et al.11 The study population was 150 Tanzanian patients with uncomplicated malaria treated with ALU. Cambodian patients assessed for ASAQ were not discussed in this review. Neither CYP3A4*1B nor CYP3A5*3 affected lumefantrine plasma concentrations significantly. Similar findings were observed for artemether, whereby patients with CYP3A4*1B and CYP3A5*3 did not have different plasma concentration values compared to their counterparts (patients with wild alleles).
The influence of CYP2B6, CYP3A4 and CYP3A5 genotypes on day 7 lumefantrine plasma concentrations among HIV-positive patients in the absence of ART co-treatment (control group) was also studied in Tanzania, by Maganda et al.54 This group included only HIV-infected patients on artemether lumefantrine who had not started taking ART, thus the drug–drug interactions between lumefantrine and efavirenz, which could affect the plasma concentrations of either drug, were not observed. CYP2B6*6, CYP3A4*1B and CYP3A5*3 genotypes did not influence day 7 lumefantrine concentrations significantly among this group of malaria patients (Table 2).
There are studies which report association between drug levels and treatment outcomes but did not assess CYP 450 polymorphisms. Since CYP450 polymorphisms affect treatment outcomes through influencing plasma concentrations, it is worth considering these studies (Table 3). The above studies report lack of correlation between day 7 lumefantrine concentration cut-off values and treatment outcomes in SSA.
Table 3 Influence of Lumefantrine Plasma Concentration Below Cut-off Values on Treatment Outcome in SSA Populations
Discussion
The major focus in studying CYP450 polymorphisms has been attainment of personalized medicine among patients. However, most studies only describe frequencies of CYP 450 variant alleles in different populations without assessing the effect of these polymorphisms on pharmacokinetics, efficacy and safety within populations. This review highlights evidence on the influence of CYP450 enzyme polymorphisms on antimalarial drug plasma concentrations and treatment outcomes among P. falciparum malaria patients in SSA.
The major CYP450 enzyme SNPs suggested to influence plasma concentrations and treatment outcomes (CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2) donot affect antimalarial drug plasma concentrations significantly in SSA, as shown in Table 2. In general, there was no difference in PK profiles between uncomplicated P. falciparum malaria patients with the mentioned CYP450 mutant alleles and those with wild type alleles in the region (Table 2). A similar finding was observed with antimalarial drug efficacy. These SNPs did not predict for low or high efficacy among patients with uncomplicated P. falciparum malaria. Findings from our review also suggest that a difference in ADRs between uncomplicated P. falciparum malaria patients with the CYP3A5*3, CYP3A4*1B and CYP2B6*6 SNPs and those with wild type alleles does not exist, with the exception of the CYP2C8*2 variant allele whereby a difference in minor adverse effects was observed in two studies. No difference was observed in terms of serious ADRs between subjects with CYP2C8*2 and those with wild type allele.
Lack of the influence of CYP450 polymorphisms on plasma concentrations, efficacy and serious adverse events suggests that dose optimization may not be necessary among P. falciparum malaria patients with CYP450 allelic variants in the region. Hodel et al also had a similar opinion to ours about ten years ago after employing genetic-based population pharmacokinetic modelling.11 Then, there were few studies on frequencies of genetic variants affecting the metabolism of antimalarial drugs in SSA. There has been advancement in terms of evidence on the presence of genetic variants in the region since Hodel et al suggested such findings. Our review provides a broader picture on the influence of CYP450 polymorphisms in treatment outcomes of P. falciparum malaria patients in various countries in SSA.
The suggestion that CYP450 genotyping-based treatment (tailored therapy) for uncomplicated P. falciparum malaria patients may not be of substantial worth is further supported by the recent findings in some SSA populations whereby lumefantrine plasma levels below cut-off values (<175ng/µL, 200ng/µL and 280ng/µL), which are suggested to predict treatment outcomes, did not affect treatment outcomes in these populations (Table 3). Drug plasma levels depend on enzyme metabolism as one of the key determinants, which in turn determines treatment response. Therefore, genotyping for variant alleles and their correlation with plasma levels may not be of great importance in these populations due to lack of an association between drug plasma levels and treatment outcomes. We observed similar findings in our recent study on association between day 3 and 7 lumefantrine plasma concentrations and treatment outcomes among P. falciparum malaria patients in Tanzania.58 Although studies included in this review have shown a lack of association between day 3 and 7 lumefantrine plasma concentrations and treatment outcomes, the influence of metabolites such as desbutyl-lumefantrine (usually not measured) on treatment outcomes in SSA needs to be assessed.
The lack of predictive effect of CYP450 polymorphisms and day 7 lumefantrine concentration on treatment outcomes in SSA may be attributed to high parasite sensitivity existing in the SSA region despite a growing threat of spread of resistant parasite strains from GMS regions. The acquired immunity among malaria patients in SSA populations, where most areas are malaria endemic thus individuals are exposed to multiple infections, may also account for the insignificant effect of CYP450 polymorphisms and plasma concentrations below cut-off values on treatment outcomes in the region. Although, the observation that lumefantrine plasma concentrations below cut-off values do not affect treatment outcomes in the region is encouraging, the impact of sub-optimal concentrations exposure to parasites should be worrying as far as selection of resistant parasites is concerned.
Our review focuses on SSA where most malaria patients are immune. Therefore, reviews of other regions of the world (where patients are non-immune) on the influence of CYP450 polymorphisms on antimalarial drug plasma concentrations, safety and efficacy among patients with uncomplicated P. falciparum malaria are warranted.
Like any other study, our review is not devoid of limitations. First, we understand there could be other unpublished data which we could not assess during our online search. Second, the lack of a sufficient number of studies (only a few countries are represented) assessing the influence of CYP450 polymorphisms on pharmacokinetic parameters, efficacy and safety in SSA limits the power of our review and did not allow us to carry out a meta-analysis.
There could be other factors, such as polymorphism in Phase II SNP genes encoding N-Acetyl Transferase 2, drug transporters (such as ABCB1 [MDR1], ABCC2 [MRP2]) and drug targets, which may also influence antimalarial drug plasma concentrations, safety and cure rates among malaria patients, thus limiting the findings reported in this study. However, since we only considered CYP450s, these factors are regarded as constant and thus their influence may not vary. We understand polypharmacy is common in SSA, thus drug–drug interactions are common and could influence CYP450 expression and treatment outcomes among malaria patients. To minimize this, only studies which followed the WHO protocol for assessment of the efficacy of antimalarials were included and studies assessing drug–drug interactions among malaria patients were excluded. Despite these limitations, this review is unique because it is the first review to assess the influence of CYP450 polymorphisms on antimalarial drug plasma concentrations, safety and efficacy among P. falciparum malaria patients in SSA.
Conclusion
This review reports lack of influence of CYP3A5*3, CYP3A4*1B, CYP2C8*3 and CYP2B6*6 SNPs on plasma concentrations, efficacy and safety among P. falciparum malaria patients in the region. This suggests that CYP450 genotyping-based dose optimization (personalized medicine) may not be important in malaria patients with the variant alleles in SSA.
No grant was received. However, authors have been receiving salaries by their respective universities during the literature search and manuscript writing.
Disclosure
The authors declare that they have no competing interests in this work.
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Few know the names Michelle Saahene or Melissa DePino. But millions have heard the beginning of their story.
They were witnesses at a Philadelphia Starbucks five years ago when two Black businessmen asked to use the restroom and a white barista called police, who led the men away in handcuffs.
“They didn’t do anything!” Saahene shouted as another customer recorded the confrontation.
Saahene and DePino didn’t know each other. But in their shock and anger, the two women started talking, and after DePino got a copy of the video, she conferred with Saahene before tweeting it out.
A showcase for compelling storytelling from the Los Angeles Times.
It also launched lucrative new careers for both women, who teamed up to promote awareness about racism and started a nonprofit that provided sensitivity talks to corporations just as the diversity, equity and inclusion industry was about to take off.
What they could not anticipate was how their joint venture would go awry — or how they themselves would become a potent illustration of the racial animosity and misunderstanding they had set out to combat.
“This is what happens when white women insert themselves into what should be Black-led organizations,” Saahene, who is Black and 36, said recently. “White supremacy and emotional abuse get masked under kindness.”
“This is what it looks like to be canceled,” said DePino, who is whiteand 55. “I’m not really sure what I did wrong.”
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‘Racism on display’
Within days of the April 12, 2018, arrest, the video had been played 8 million times. In interviews with CNN and other outlets, DePino accused Starbucks of racism.
By April 14, the company’s CEO issued a public apology to the men, who were never charged with a crime. Two days later, the corporation vowed toclose every company-owned U.S. store for an afternoon of racial bias training. Now many coffee shops, including Starbucks, let anyone use their restrooms with no questions asked.
The controversy ushered in a new genre of viral videos on race — clips showing people of color having cops called on them for shopping, barbecuing, swimming and other everyday activities.
In the aftermath, DePino tracked down Saahene, hoping to process what happened, gain insight from a Black woman and make a friend.
The two met over drinks, planting the seeds of a passion project they named From Privilege to Progress. It had a stated aim of creating “a national movement to desegregate the public conversation about race.” In reality, it was a few social media accounts attempting to go viral, with the women unsure of whether they were making a dent.
Adjoa Michelle Saahene’s anti-racist activism began in 2018 when she witnessed the unnecessary arrest of two Black men at a Philadelphia Starbucks and shouted at police to try to stop it.
(Luis Sinco / Los Angeles Times)
“I witnessed something wrong and spoke up about it and shared it in my social network, which happens to be mostly white,” DePino said at the time in an interview with The Times. “That brought attention to this issue that really happens all the time.”
Saahene put it more succinctly: “If it was me posting that video, it would be my Black friends seeing it and it would not be news to them.”
They slowly gained followers, mostly white liberals, on Facebook, Instagram, Twitter and YouTube. They posted about Eric Garner, the Black man choked to death by police in Staten Island, N.Y., in 2014, whose last words — “I can’t breathe” — became a protest cry. They released guides on “racism interrupters,” phrases that witnesses to racist acts can use to interject. They launched a website that sold one-on-one anti-racism coaching and $20 T-shirts with the logo “#ShowUp.”
And they pitched corporations to pay them to share their stories.
DePino, a marketingprofessional and liberal mother of two, told audiences of becoming an activist after “seeing racism on display right in front of my eyes” and of educating herself by reading Ta-Nehisi Coates, James Baldwin and Frederick Douglass.
Melissa DePino, an anti-racist activist who co-founded From Privilege to Progress with Saahene, sits in her rental house’s living room in Lewes, Del., one of many places she has lived over the last year while traveling across the U.S.
(Kent Nishimura / Los Angeles Times)
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She talked about growing up in a white, mostly Catholic suburb between Trenton, N.J., and Philadelphia. She admitted to not having Black friends until after college. She told audiences she’d always thought of herself “as not racist — one of the good ones” — but it wasn’t until that day in Starbucks that “it just hit me” that racism “never happens to me.”
Saahene, who studied health policy in college, spoke of entering corporate healthcare and becoming dismayed at the idea of profiting from helping people — before realizing her purpose was to push white people tospeak out against injustice. The daughter of Ghanaian immigrants, she used lessons she’d learned from an online diversity, equity and inclusion certificate course to talk about race.
She spoke of being one of the few Black children in her small town outside Hershey, Pa., and of never feeling “Black enough.” Black Americansoften told her she was instead “African,” and she felt more at home with Ghanaian culture than with Black American culture. She recounted painful memories of racism, including when the mother of a white boyfriend called her the N-word after they broke up.
Both DePino and Saahene believed fate led them to Starbucks that day to inspire others to do right.
They started to get noticed, landing occasional corporate gigs or appearances on university campuses. They went on “Red Table Talk,” the online show hosted by the actor Jada Pinkett-Smith, appeared on MSNBC and spoke at the Women’s March in Philadelphia.
Their effort could have stayed relatively small at a time when so many people wanted to make a dime off viral fame, when activism increasingly was happening from keyboards instead of on the streets.
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Then came May 25, 2020.
American soul-searching
The world watched as a police officer pressed his knee into a Black man’s neck for 9½ minutes on a Minneapolis street corner. Protests raged in response to George Floyd’s murder. America began soul-searching.
On Slack and in boardrooms, institutions grappled with the inequality within. Companies hired diversity specialists, created equity departments and held seminars on race.
Diversity initiatives had been around since the 1960s, when Congress passed laws outlawing racial and gender discrimination. As immigration grew and more women entered the workforce, many companies and schools tried to at least appear to be more welcoming. In the 1990s and 2000s, historic settlements in discrimination lawsuits against major banks pushed CEOs to pay more attention to diversity.
But this latest boom was unprecedented. Corporations pledged tens of billions of dollars to further racial equality. In California and New York, governments launched DEI initiatives. Schools, nonprofits and businesses across the U.S. hosted diversity summits. Many outsourced training to people like Saahene and DePino.
From Privilege to Progress — the project the women called P2P — took off.
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The number of followers on their Instagram account shot up from around 20,000 to roughly half a million. By late 2020, the women had monthly, sometimes weekly, paid engagements at Google, Spectrum, Ikea, Yale, MIT, Tufts and the United Nations.
“White people are tired of hearing this story,” Saahene told audiences. “We’re tired of living it, too. If you want to see racism dismantled, you have to show up to the conversation.”
“The word ‘privilege’ is triggering for white people,” DePino chimed in, telling audiences that Saahene “doesn’t dislike you for your privilege, she just wants it too.”
The two had become close. Saahene house-sat for DePino and had the code to her marijuana safe. They met each other’s families. It was a friendship and a business commingled with a sense of purpose and profit.
They launched an Instagram Live series and snagged interviews with Hollywood actors including Ilana Glazer, Jameela Jamil and Sophia Bush. They hosted “Unscripted,” a weekly video program in which they answered questions on the do’s and don’ts of being anti-racist.
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The duo nearly doubled their jointspeakers rate to $10,000total per appearance. In 2021, each netted more than $100,000.
Saahene did much of the work remotely. She was living for months at a time in Accra, Ghana, reconnecting with family members and disconnecting from news on police violence, racism and divisive politics in the U.S. Still, she talked to corporate audiences about it all on Zoom.
She left her healthcare job and was working life-coaching gigs on top of P2P. When not in Ghana, she lived with a boyfriend in Dallas.
“White people are tired of hearing this story,” Saahene used to tell audiences in talks she gave for From Privilege to Progress. “We’re tired of living it, too. If you want to see racism dismantled, you have to show up to the conversation.”
(Dania Maxwell / Los Angeles Times)
DePino, who was dating after a divorce, grew close with a new boyfriend, an artist and professor who is Black; he teaches in Delaware and has long collected videos of early 20th century Black family life. She adopted a mini sheepadoodle and her college-aged sons left Philadelphia to settle in Los Angeles. Though she still had her day job in the marketing firm she co-founded, DePino thought the cash flow from P2P was becoming enough for her to be a full-time activist.
The two women dreamed of a national tour and documentary series — and it felt within reach.
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‘I was the draw: my skin, my story’
Then the demand for talk and training on race slowly started to subside.
Part of the reason was national fatigue. The coast-to-coast movement spurred by Floyd’s murder led to a backlash, a belief among a segment of America that the course correction on race had gone too far. Activists accused institutions of papering over inequality with one-off DEI events.
Another part was politics. President Trump, whose words and policies provoked a constant stream of outrage that united activists and corporations on the left, was out of office. Now President Biden was promising to right racist wrongs.
And part was practical. Research has suggested that one-shot seminars, speeches and sensitivity exercises do little to curb unconscious biases. One study published in the Harvard Business Review looked at more than 800 major U.S. companies and found no correlation between mandatory diversity training and improvement in representation of women and racial minorities in management.
DePino and her boyfriend, Billy Colbert, at their former rental house in Lewes, Del.
(Kent Nishimura / Los Angeles Times)
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Corporations began to pull back from their big promises.
In 2021, the Washington Post asked the 50 most valuable U.S. companies, which had promised a total of $49.5 billion to diversity programs since 2020, how much they actually spent. It received responses from 37 confirming less than 4% of that amount— $1.7 billion.
The workforce research group Revelio Labs crunched data on 17 million layoff notices since 2020 and found that by the fall of 2021, diversity-related jobs were being cut at double the rate of non-DEI jobs.
Saahene and DePino experienced the trends in a simpler way: They were getting less traction on social media, one of the primary ways clients found them.
“We were used to putting speaking dates on the calendar months ahead of time,” Saahene said. “Then it began to go dry.”
Saahene grew introspective. Living in Ghana for long stretches had made her feel empowered in her Black skin. She began to question her role as a Black woman who spoke to white audiences about racism.
“I started to realize that I was the draw: my skin, my story,” Saahene said.
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She began to think back to disagreements she’d had with DePino — differences that had seemed minor at the time but in a new light felt more troubling.
One such conflict involved Saahene’s growing discomfort about capitalizing on the corporate interest in social justice that followed Floyd’s murder.
“I was growing faster and thinking about this all at a deeper, more complex level,” Saahene said. “I told her the pain I was feeling about how we were making money off of this. Her responses were cold.”
DePino said she saw it differently: “She was setting boundaries. I respected them. I never told her to do anything more than what she wanted.”
Saahene, center, co-hosts a recent fundraiser in Los Angeles for Kusewera, a charity that works with children in Malawi.
(Luis Sinco / Los Angeles Times)
Then there was the question of how to divide the profits from their business. The two women had always split them evenly, but in 2019 Saahene had suggested that she deserved a greater share. It seemed clear that the venture would have gotten little traction without a Black woman on board, and in her view, speaking about racism required more “emotional labor” on her part. She said DePino disagreed, contending that she did more background work: nonprofit filings, managing money and posting to social media accounts.
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Saahene had quickly backed down. But now she wished she had not let it pass so easily.
“I was reading and learning about equity models in businesses,” she said.
DePino said that she remembers brief disagreements that she believed the pair had moved beyond, but that she did not recall talk of a new pay model.
“If she wanted an equity model for pay, I would have been open to discussing that,” DePino said. “She was also the president. I was vice president. So she could have instituted one on her own.”
“I didn’t know she felt so wronged,” said DePino.
In her view, their venture was more a calling than a full-fledged business. DePino was also consumed by other worries. A close aunt was slowly dying of cancer.
Often unable to sleep, DePino was rethinking her priorities, and Saahene no longer felt like somebody she could lean on. Casual emails and texts became curt, professional exchanges.
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It felt to DePino like they were becoming strangers again.
A friendship and business fray
As she befriended African activists, Saahene heard stories of Black women who felt the sting of racism while working with white women. One was a group called No White Saviors, led by a Ugandan and a white American, that challenged the tradition of white-led charities in Africa but crumbled amid a bitter fight among its founders.
Saahene saw parallels.
In late November 2021, shetexted DePino: “I’m exploiting my trauma. … Someone said this to me yesterday, ‘No one asks a sexual assault survivor to retell their story, so why are Black people expected to tell theirs?’”
“You have to do what feels right by you,” DePino replied. “I support you completely.”
They continued to talk, to try to sort out differences. Saahene texted, saying she felt unheard and pointing out past moments she now considered “microaggressions.”
One involved a suggestion by DePino that they visit a lynching memorial in Alabama together. “As if we haven’t had numerous conversations about how traumatizing it is for me to witness violence against Black bodies,” Saahene wrote.
She called DePino “manipulative” and cited “the challenges of working with white women in racial justice,” arguing that “Black people shouldn’t always have to be in therapist or coach mode.”
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DePino replied: “I thought our personal relationship was so much deeper… this text sounds like we are strangers.”
Saahene emailed to say she was done sharing stages. Since returning from Ghana, Saahene wrote, she was on a “transformation of healing and decolonizing.” She accused DePino of “defensiveness and other manifestations of whiteness.”
DePino was overwhelmed. She was two weeks from leaving her marketing job of 17 years and about to move out of her Philadelphia row house. She was often at the hospital, tending to her aunt in her final weeks, and she was hurt to not be asked more about her own life’s transitions. Itall felt sudden.
“I thought we were working things out. I thought we were best friends,” DePino said in an interview. “Instead, I learned that we were not friends anymore. … The organization had a mission and she no longer supported it.”
They plotted how to publicly end their story. There was so much to untangle: social media, a website, a bank account, corporate contacts and a network of activists that knew them as a pair.
DePino emailed Saahene in March 2022: “I always planned on making the organization independent of the two of us and dedicating my time to fully developing it.”
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Saahene replied that she wanted the project “dissolved.” She objected that DePino kept posting on P2P’s Instagram because it was “misleading the public” into believing the partnership was alive.
On April 22, 2022, Saahene took over the platform. In a written statement to nearly 500,000 followers, she said DePino was “not honest” and had no “commitment to ending colonialism.” She plugged her personal Instagram.
“A staple of anti-racism is ‘listen to Black women.’ In this org that is not happening,” Saahene wrote.
DePino deleted the posts and dashed off an email: “You cannot legally slander me… I will send a cease-and-desist ASAP.”
Saahene shot back: “My life experiences and statements are truth.”
For weeks, the two tussled over the Instagram account. One posted. The other deleted. By the end of September, the website and social media accounts were permanently wiped offline.
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Saahene and DePino stopped communicating, except through lawyers.
Separate work, separate lives
The former partners were moving on — and so was much of the country.
DEI roles were among the first to go last year when Meta, Lyft and Netflix laid off thousands of workers. At Princeton, the University of South Florida and other colleges, relatively new DEI staffers quit in frustration, claiming they received little support and were set up to fail. Just this week, Florida Gov. Ron DeSantis signed a bill into law that blocks all publicly funded diversity programs at state colleges.
“It’s like people just stopped caring, even though the problem — racism — never went away,” Saahene said. “How real was the commitment everyone in the country had made?”
Seeking a new beginning with a community of Black activists, actors and social media creators, Saahene moved to Los Angeles. On her website, she described herself as a “speaker, activist, model, and global inclusion strategist.” She also hopes to start an African luxury imports business.
In the last several months, she has spoken at the University of Pittsburgh at Greensburg about racism, healing and self-care, visited Malawi to join the board of a nonprofit for children and co-hosted a fundraiser for the group in Los Angeles.
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Her next big project is organizing a six-day retreat for “changemakers” at a Black-owned luxury hotel in Morocco. She expects most attendees will be Black.
“I spent so much time talking to white people about a white problem: racism,” Saahene said. “It’s draining. I want to make Black people my audience.”
Recently, she reclaimed her Ghanaian name, asking new friends to call her Adjoa, the Asante word for women born on a Monday.
DePino, for her part, is still grieving for her aunt and recovering from an onslaught of online abuse, nearly all from white former followers. They called her a racist, a “Karen,” a manipulator, a fake.
DePino assists Colbert, her boyfriend, on a project in which he is digitizing and cataloging home videos of Black family life from the Jim Crow era.
(Kent Nishimura / Los Angeles Times)
The experience forced her to reassess her place in the world as a white woman who still wants to fight inequality. She often pages through “The Autobiography of Malcolm X,” pondering the phrase “white devil.”
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She pores over old essays by white abolitionists. “Those are the revolutionary white people throughout history that did not drop that ball,” DePino said recently. “But people didn’t always like them, either.”
She is helping her boyfriend digitize and catalog his video archive of Jim Crow-era Black family life, hoping it can be part of a permanent museum exhibit or public digital collection.
DePino finds comfort in moving from place to place: to Delaware to see her boyfriend, to New Mexico to see family, to New Orleans to hear jazz, to Los Angeles to be with her kids.
Last month, she relaunched her blog, where she sometimes signs posts with the moniker “That White Lady.” She is also working on a book, which she has titled “Uncomfortable.” It starts with that moment five years ago at Starbucks, but she’s not sure how she will address the demise of P2P or her friendship with Saahene.
On Instagram, Saahene has 38,000 followers and DePino 21,000, but neither posts about racial injustice as frequently as they did when they worked together. They haven’t spoken in months.
“I’m over it,” Saahene said recently about their relationship. “I’ve moved on. It’s a new chapter. A new me.”
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“I don’t really know where she is or what she’s doing,” DePino said. “But I wish her the best.”
In 2021, the sports world was starting to fully re-open after the Covid pandemic shut everything down for most of 2020. Fans were starting to return to stadiums in bigger numbers, and the action on the field continued to increase. What most people didn’t know is that 2021 was set to be Éduoard Mendy’s year.
In his first year with Chelsea FC, Mendy had supplanted Kepa Arrizabalaga as the starting goalkeeper on a team that was attempting to compete for the Champions League title as well as the Premier League title. However, the calendar year of 2021 started out rocky, with Chelsea losing a few games and their coach Frank Lampard being fired. The next day, Thomas Tuchel was hired, and a switch turned on for Mendy and Chelsea, at least in Champions League.
Mendy also went on a tear, rattling off 6 clean sheets in a row as Chelsea tried to fight back up the standings in the Premier League and continued to advance in the Champions League. After shutting out Real Madrid in the 2nd leg of the Champions League semifinal, Chelsea advanced to the Champions League final against Premier League rivals Manchester City. There, Mendy did what he does best: with yet another clean sheet as Chelsea lifted its second Champions League trophy.
He didn’t stop there as the 2021-22 season began, continuing to dominate for Chelsea between the posts as the full-time starter and for Senegal as they prepared for the postponed Africa Cup of Nations. He had 29 clean sheets across all competitions for club and country in 2021. For his efforts in 2021, Éduoard Mendy was named The Best FIFA Men’s Goalkeeper at their ceremony on January 17, 2022. He became the first African goalkeeper to win the prestigious award.
One would forgive Mendy for celebrating his historic accomplishment. But, when he received word that he had won FIFA’s The Best award, he was in the middle of the Africa Cup of Nations with Senegal, a team that was a favorite to win the tournament. The next morning, he did what few would do: held another clean sheet as Senegal drew Malawi. A little over 2 weeks later, Mendy and Senegal competed in the Africa Cup of Nations final against Egypt. Mendy kept Senegal in it by holding Egypt scoreless through 120 minutes of action. With the match scoreless heading to penalties to decide it, Mendy stopped 2 of them to help Senegal clinch its 1st AFCON title. Mendy was named the tournament’s best goalkeeper for having 4 clean sheets during Senegal’s run to the title.
Did he stop there? Nope. He immediately flew to Abu Dhabi, where his Chelsea squad was competing in the FIFA Club World Cup. He arrived in time to see his team win the semifinal to advance to the final against Palmeiras. 3 days later, he was back in goal, helping Chelsea lift the Club World Cup trophy after a 2-1 extra time win.
Three weeks, 4 major trophies. Éduoard Mendy was on top of the world, and continues to be one of the world’s great goalkeepers. But, he’s the first from Africa to have a simple title:
The Best.
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For more Black History Month stories, check out our Black History Month hub. We will be bringing stories throughout the month to highlight some of the biggest moments in Black American and world soccer history.
