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1.
Lancet Gastroenterol Hepatol ; 9(4): 383-392, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38367632

ABSTRACT

The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical trials represented populations in this region by searching the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for interventional clinical trials published in English between database inception and May 29, 2023, using the search term "Hepatitis B". We identified 1804 unique clinical trials, of which 18 (1·0%) recorded involvement of the WHO African region. There is no evidence that the number of HBV clinical trials in this region has improved over time. The diversity of new interventions and industry sponsorship in the WHO African region were low, with trials of HBV comparing poorly with those of other endemic infectious diseases (eg, malaria, HIV, and SARS-CoV-2). HBV research and clinical trial investigations have neglected the WHO African region, leading to profound health inequities. HBV clinical trials are urgently needed to evaluate the efficacy of newly discovered therapeutics and to ensure that interventions can be equitably distributed and deployed as they become available.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/epidemiology , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B/prevention & control , World Health Organization
2.
Sci Transl Med ; 15(682): eabn5993, 2023 02 08.
Article in English | MEDLINE | ID: mdl-36753561

ABSTRACT

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.


Subject(s)
Malaria, Falciparum , Malaria , Child , Adult , Animals , Humans , Antigens, Protozoan , Cohort Studies , Merozoites , Antibodies, Protozoan , Plasmodium falciparum , Killer Cells, Natural
3.
Preprint in English | medRxiv | ID: ppmedrxiv-22281455

ABSTRACT

BackgroundAnalysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data from household infections should aid its detailed epidemiological understanding. Using viral genomic sequence data, we investigated household SARS-CoV-2 transmission and evolution in coastal Kenya households. MethodsWe conducted a case-ascertained cohort study between December 2020 and February 2022 whereby 573 members of 158 households were prospectively monitored for SARS-CoV-2 infection. Households were invited to participate if a member tested SARS-CoV-2 positive or was a contact of a confirmed case. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Positive samples with an RT-PCR cycle threshold of <33.0 were subjected to whole genome sequencing followed by phylogenetic analysis. Ancestral state reconstruction was used to determine if multiple viruses had entered households. ResultsOf 2,091 NP/OP swabs that were collected, 375 (17.9%) tested SARS-CoV-2 positive. Viral genome sequences (>80% coverage) were obtained from 208 (55%) positive samples obtained from 61 study households. These genomes fell within 11 Pango lineages and four variants of concern (Alpha, Beta, Delta and Omicron). We estimated 163 putative transmission events involving members of the sequenced households, 40 (25%) of which were intra-household transmission events while 123 (75%) were infections that likely occurred outside the households. Multiple virus introductions (up-to-5) were observed in 28 (47%) households with the 1-month follow-up period. ConclusionsWe show that a considerable proportion of SARS-CoV-2 infections in coastal Kenya occurred outside the household setting. Multiple virus introductions frequently occurred into households within the same infection wave in contrast to observations from high income settings, where single introduction appears to be the norm. Our findings suggests that control of SARS-CoV-2 transmission by household member isolation may be impractical in this setting.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-22281446

ABSTRACT

The emergence and establishment of SARS-CoV-2 variants of concern presented a major global public health crisis across the world. There were six waves of SARS-CoV-2 cases in Kenya that corresponded with the introduction and eventual dominance of the major SARS-COV-2 variants of concern, excepting the first 2 waves that were both wild-type virus. We estimate that more than 1000 SARS-CoV-2 introductions occurred in the two-year epidemic period (March 2020 - September 2022) and a total of 930 introductions were associated with variants of concern namely Beta (n=78), Alpha(n=108), Delta(n=239) and Omicron (n=505). A total of 29 introductions were associated with A.23.1 variant that circulated in high frequencies in Uganda and Rwanda. The actual number of introductions is likely to be higher than these conservative estimates due to limited genomic sequencing. Our data suggested that cryptic transmission was usually underway prior to the first real-time identification of a new variant, and that multiple introductions were responsible. Following emergence of each VOC and subsequent introduction, transmission patterns were associated with hotspots of transmission in Coast, Nairobi and Western Kenya and follows established land and air transport corridors. Understanding the introduction and dispersal of major circulating variants and identifying the sources of new introductions is important to inform public health control strategies within Kenya and the larger East-African region. Border control and case finding reactive to new variants is unlikely to be a successful control strategy.

5.
Viruses ; 14(6)2022 06 16.
Article in English | MEDLINE | ID: mdl-35746789

ABSTRACT

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge was observed. Here, we investigated the potential drivers of the surge by genomic analysis of 1056 SARS-CoV-2 positive samples collected in Seychelles between 14 March 2020 and 31 December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1042 of which fell within four variants of concern, i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (lineage predominantly observed in Europe) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using the ancestral state reconstruction approach, we estimated that at least 78 independent SARS-CoV-2 introduction events occurred in Seychelles during the study period. The majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genomics , Humans , SARS-CoV-2/genetics , Seychelles/epidemiology
6.
Elife ; 112022 06 14.
Article in English | MEDLINE | ID: mdl-35699426

ABSTRACT

Background: Detailed understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regional transmission networks within sub-Saharan Africa is key for guiding local public health interventions against the pandemic. Methods: Here, we analysed 1139 SARS-CoV-2 genomes from positive samples collected between March 2020 and February 2021 across six counties of Coastal Kenya (Mombasa, Kilifi, Taita Taveta, Kwale, Tana River, and Lamu) to infer virus introductions and local transmission patterns during the first two waves of infections. Virus importations were inferred using ancestral state reconstruction, and virus dispersal between counties was estimated using discrete phylogeographic analysis. Results: During Wave 1, 23 distinct Pango lineages were detected across the six counties, while during Wave 2, 29 lineages were detected; 9 of which occurred in both waves and 4 seemed to be Kenya specific (B.1.530, B.1.549, B.1.596.1, and N.8). Most of the sequenced infections belonged to lineage B.1 (n = 723, 63%), which predominated in both Wave 1 (73%, followed by lineages N.8 [6%] and B.1.1 [6%]) and Wave 2 (56%, followed by lineages B.1.549 [21%] and B.1.530 [5%]). Over the study period, we estimated 280 SARS-CoV-2 virus importations into Coastal Kenya. Mombasa City, a vital tourist and commercial centre for the region, was a major route for virus imports, most of which occurred during Wave 1, when many Coronavirus Disease 2019 (COVID-19) government restrictions were still in force. In Wave 2, inter-county transmission predominated, resulting in the emergence of local transmission chains and diversity. Conclusions: Our analysis supports moving COVID-19 control strategies in the region from a focus on international travel to strategies that will reduce local transmission. Funding: This work was funded by The Wellcome (grant numbers: 220985, 203077/Z/16/Z, 220977/Z/20/Z, and 222574/Z/21/Z) and the National Institute for Health and Care Research (NIHR), project references: 17/63/and 16/136/33 using UK Aid from the UK government to support global health research, The UK Foreign, Commonwealth and Development Office. The views expressed in this publication are those of the author(s) and not necessarily those of the funding agencies.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genomics , Humans , Kenya/epidemiology , Phylogeny , Retrospective Studies , SARS-CoV-2/genetics
7.
Houriiyah Tegally; James E. San; Matthew Cotten; Bryan Tegomoh; Gerald Mboowa; Darren P. Martin; Cheryl Baxter; Monika Moir; Arnold Lambisia; Amadou Diallo; Daniel G. Amoako; Moussa M. Diagne; Abay Sisay; Abdel-Rahman N. Zekri; Abdelhamid Barakat; Abdou Salam Gueye; Abdoul K. Sangare; Abdoul-Salam Ouedraogo; Abdourahmane SOW; Abdualmoniem O. Musa; Abdul K. Sesay; Adamou LAGARE; Adedotun-Sulaiman Kemi; Aden Elmi Abar; Adeniji A. Johnson; Adeola Fowotade; Adewumi M. Olubusuyi; Adeyemi O. Oluwapelumi; Adrienne A. Amuri; Agnes Juru; Ahmad Mabrouk Ramadan; Ahmed Kandeil; Ahmed Mostafa; Ahmed Rebai; Ahmed Sayed; Akano Kazeem; Aladje Balde; Alan Christoffels; Alexander J. Trotter; Allan Campbell; Alpha Kabinet KEITA; Amadou Kone; Amal Bouzid; Amal Souissi; Ambrose Agweyu; Ana V. Gutierrez; Andrew J. Page; Anges Yadouleton; Anika Vinze; Anise N. Happi; Anissa Chouikha; Arash Iranzadeh; Arisha Maharaj; Armel Landry Batchi-Bouyou; Arshad Ismail; Augustina Sylverken; Augustine Goba; Ayoade Femi; Ayotunde Elijah Sijuwola; Azeddine Ibrahimi; Baba Marycelin; Babatunde Lawal Salako; Bamidele S. Oderinde; Bankole Bolajoko; Beatrice Dhaala; Belinda L. Herring; Benjamin Tsofa; Bernard Mvula; Berthe-Marie Njanpop-Lafourcade; Blessing T. Marondera; Bouh Abdi KHAIREH; Bourema Kouriba; Bright Adu; Brigitte Pool; Bronwyn McInnis; Cara Brook; Carolyn Williamson; Catherine Anscombe; Catherine B. Pratt; Cathrine Scheepers; Chantal G. Akoua-Koffi; Charles N. Agoti; Cheikh Loucoubar; Chika Kingsley Onwuamah; Chikwe Ihekweazu; Christian Noel MALAKA; Christophe Peyrefitte; Chukwuma Ewean Omoruyi; Clotaire Donatien Rafai; Collins M. Morang'a; D. James Nokes; Daniel Bugembe Lule; Daniel J. Bridges; Daniel Mukadi-Bamuleka; Danny Park; David Baker; Deelan Doolabh; Deogratius Ssemwanga; Derek Tshiabuila; Diarra Bassirou; Dominic S.Y. Amuzu; Dominique Goedhals; Donald S. Grant; Donwilliams O. Omuoyo; Dorcas Maruapula; Dorcas Waruguru Wanjohi; Ebenezer Foster-Nyarko; Eddy K. Lusamaki; Edgar Simulundu; Edidah M. Ong'era; Edith N. Ngabana; Edward O. Abworo; Edward Otieno; Edwin Shumba; Edwine Barasa; EL BARA AHMED; Elmostafa EL FAHIME; Emmanuel Lokilo; Enatha Mukantwari; Erameh Cyril; Eromon Philomena; Essia Belarbi; Etienne Simon-Loriere; Etile A. Anoh; Fabian Leendertz; Fahn M. Taweh; Fares Wasfi; Fatma Abdelmoula; Faustinos T. Takawira; Fawzi Derrar; Fehintola V Ajogbasile; Florette Treurnicht; Folarin Onikepe; Francine Ntoumi; Francisca M. Muyembe; FRANCISCO NGIAMBUDULU; Frank Edgard ZONGO Ragomzingba; Fred Athanasius DRATIBI; Fred-Akintunwa Iyanu; Gabriel K. Mbunsu; Gaetan Thilliez; Gemma L. Kay; George O. Akpede; George E Uwem; Gert van Zyl; Gordon A. Awandare; Grit Schubert; Gugu P. Maphalala; Hafaliana C. Ranaivoson; Hajar Lemriss; Hannah E Omunakwe; Harris Onywera; Haruka Abe; HELA KARRAY; Hellen Nansumba; Henda Triki; Herve Alberic ADJE KADJO; Hesham Elgahzaly; Hlanai Gumbo; HOTA mathieu; Hugo Kavunga-Membo; Ibtihel Smeti; Idowu B. Olawoye; Ifedayo Adetifa; Ikponmwosa Odia; Ilhem Boutiba-Ben Boubaker; Isaac Ssewanyana; Isatta Wurie; Iyaloo S Konstantinus; Jacqueline Wemboo Afiwa Halatoko; James Ayei; Janaki Sonoo; Jean Bernard LEKANA-DOUKI; Jean-Claude C. Makangara; Jean-Jacques M. Tamfum; Jean-Michel Heraud; Jeffrey G. Shaffer; Jennifer Giandhari; Jennifer Musyoki; Jessica N. Uwanibe; Jinal N. Bhiman; Jiro Yasuda; Joana Morais; Joana Q. Mends; Jocelyn Kiconco; John Demby Sandi; John Huddleston; John Kofi Odoom; John M. Morobe; John O. Gyapong; John T. Kayiwa; Johnson C. Okolie; Joicymara Santos Xavier; Jones Gyamfi; Joseph Humphrey Kofi Bonney; Joseph Nyandwi; Josie Everatt; Jouali Farah; Joweria Nakaseegu; Joyce M. Ngoi; Joyce Namulondo; Judith U. Oguzie; Julia C. Andeko; Julius J. Lutwama; Justin O'Grady; Katherine J Siddle; Kathleen Victoir; Kayode T. Adeyemi; Kefentse A. Tumedi; Kevin Sanders Carvalho; Khadija Said Mohammed; Kunda G. Musonda; Kwabena O. Duedu; Lahcen Belyamani; Lamia Fki-Berrajah; Lavanya Singh; Leon Biscornet; Leonardo de Oliveira Martins; Lucious Chabuka; Luicer Olubayo; Lul Lojok Deng; Lynette Isabella Ochola-Oyier; Madisa Mine; Magalutcheemee Ramuth; Maha Mastouri; Mahmoud ElHefnawi; Maimouna Mbanne; Maitshwarelo I. Matsheka; Malebogo Kebabonye; Mamadou Diop; Mambu Momoh; Maria da Luz Lima Mendonca; Marietjie Venter; Marietou F Paye; Martin Faye; Martin M. Nyaga; Mathabo Mareka; Matoke-Muhia Damaris; Maureen W. Mburu; Maximillian Mpina; Claujens Chastel MFOUTOU MAPANGUY; Michael Owusu; Michael R. Wiley; Mirabeau Youtchou Tatfeng; Mitoha Ondo'o Ayekaba; Mohamed Abouelhoda; Mohamed Amine Beloufa; Mohamed G Seadawy; Mohamed K. Khalifa; Mohammed Koussai DELLAGI; Mooko Marethabile Matobo; Mouhamed Kane; Mouna Ouadghiri; Mounerou Salou; Mphaphi B. Mbulawa; Mudashiru Femi Saibu; Mulenga Mwenda; My V.T. Phan; Nabil Abid; Nadia Touil; Nadine Rujeni; Nalia Ismael; Ndeye Marieme Top; Ndongo Dia; Nedio Mabunda; Nei-yuan Hsiao; Nelson Borico Silochi; Ngonda Saasa; Nicholas Bbosa; Nickson Murunga; Nicksy Gumede; Nicole Wolter; Nikita Sitharam; Nnaemeka Ndodo; Nnennaya A. Ajayi; Noel Tordo; Nokuzola Mbhele; Norosoa H Razanajatovo; Nosamiefan Iguosadolo; Nwando Mba; Ojide C. Kingsley; Okogbenin Sylvanus; Okokhere Peter; Oladiji Femi; Olumade Testimony; Olusola Akinola Ogunsanya; Oluwatosin Fakayode; Onwe E. Ogah; Ousmane Faye; Pamela Smith-Lawrence; Pascale Ondoa; Patrice Combe; Patricia Nabisubi; Patrick Semanda; Paul E. Oluniyi; Paulo Arnaldo; Peter Kojo Quashie; Philip Bejon; Philippe Dussart; Phillip A. Bester; Placide K. Mbala; Pontiano Kaleebu; Priscilla Abechi; Rabeh El-Shesheny; Rageema Joseph; Ramy Karam Aziz; Rene Ghislain Essomba; Reuben Ayivor-Djanie; Richard Njouom; Richard O. Phillips; Richmond Gorman; Robert A. Kingsley; Rosemary Audu; Rosina A.A. Carr; Saad El Kabbaj; Saba Gargouri; Saber Masmoudi; Safietou Sankhe; Sahra Isse Mohamed; Salma MHALLA; Salome Hosch; Samar Kamal Kassim; Samar Metha; Sameh Trabelsi; Sanaa Lemriss; Sara Hassan Agwa; Sarah Wambui Mwangi; Seydou Doumbia; Sheila Makiala-Mandanda; Sherihane Aryeetey; Shymaa S. Ahmed; SIDI MOHAMED AHMED; Siham Elhamoumi; Sikhulile Moyo; Silvia Lutucuta; Simani Gaseitsiwe; Simbirie Jalloh; Soafy Andriamandimby; Sobajo Oguntope; Solene Grayo; Sonia Lekana-Douki; Sophie Prosolek; Soumeya Ouangraoua; Stephanie van Wyk; Stephen F. Schaffner; Stephen Kanyerezi; Steve AHUKA-MUNDEKE; Steven Rudder; Sureshnee Pillay; Susan Nabadda; Sylvie Behillil; Sylvie L. Budiaki; Sylvie van der Werf; Tapfumanei Mashe; Tarik Aanniz; Thabo Mohale; Thanh Le-Viet; Thirumalaisamy P. Velavan; Tobias Schindler; Tongai Maponga; Trevor Bedford; Ugochukwu J. Anyaneji; Ugwu Chinedu; Upasana Ramphal; Vincent Enouf; Vishvanath Nene; Vivianne Gorova; Wael H. Roshdy; Wasim Abdul Karim; William K. Ampofo; Wolfgang Preiser; Wonderful T. Choga; Yahaya ALI ALI AHMED; Yajna Ramphal; Yaw Bediako; Yeshnee Naidoo; Yvan Butera; Zaydah R. de Laurent; Ahmed E.O. Ouma; Anne von Gottberg; George Githinji; Matshidiso Moeti; Oyewale Tomori; Pardis C. Sabeti; Amadou A. Sall; Samuel O. Oyola; Yenew K. Tebeje; Sofonias K. Tessema; Tulio de Oliveira; Christian Happi; Richard Lessells; John Nkengasong; Eduan Wilkinson.
Preprint in English | medRxiv | ID: ppmedrxiv-22273906

ABSTRACT

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks. One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

8.
Preprint in English | medRxiv | ID: ppmedrxiv-22272503

ABSTRACT

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge of SARS-CoV-2 cases was observed on the islands. Here, we investigated the potential drivers of the surge by genomic analysis 1,056 SARS-CoV-2 positive samples collected in Seychelles between 14th March 2020 and 31st December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1,042 of which fell within four variants of concern i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (European origin) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using ancestral state reconstruction approach, we estimated at least 78 independent SARS-CoV-2 introduction events into Seychelles during the study period. Majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.

9.
Nat Commun ; 12(1): 4809, 2021 08 10.
Article in English | MEDLINE | ID: mdl-34376689

ABSTRACT

Genomic surveillance of SARS-CoV-2 is important for understanding both the evolution and the patterns of local and global transmission. Here, we generated 311 SARS-CoV-2 genomes from samples collected in coastal Kenya between 17th March and 31st July 2020. We estimated multiple independent SARS-CoV-2 introductions into the region were primarily of European origin, although introductions could have come through neighbouring countries. Lineage B.1 accounted for 74% of sequenced cases. Lineages A, B and B.4 were detected in screened individuals at the Kenya-Tanzania border or returning travellers. Though multiple lineages were introduced into coastal Kenya following the initial confirmed case, none showed extensive local expansion other than lineage B.1. International points of entry were important conduits of SARS-CoV-2 importations into coastal Kenya and early public health responses prevented established transmission of some lineages. Undetected introductions through points of entry including imports from elsewhere in the country gave rise to the local epidemic at the Kenyan coast.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genome, Viral , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/transmission , Child , Child, Preschool , Female , Genetic Variation , Humans , Infant , Kenya/epidemiology , Male , Middle Aged , Pandemics , Phylogeny , Public Health , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Sequence Analysis , Tanzania , Travel , Young Adult
10.
Preprint in English | medRxiv | ID: ppmedrxiv-21259583

ABSTRACT

BackgroundThe transmission networks of SARS-CoV-2 in sub-Saharan Africa remain poorly understood. MethodsWe undertook phylogenetic analysis of 747 SARS-CoV-2 positive samples collected across six counties in coastal Kenya during the first two waves (March 2020 - February 2021). Viral imports and exports from the region were inferred using ancestral state reconstruction (ASR) approach. ResultsThe genomes were classified into 35 Pango lineages, six of which accounted for 79% of the sequenced infections: B.1 (49%), B.1.535 (11%), B.1.530 (6%), B.1.549 (4%), B.1.333 (4%) and B.1.1 (4%). Four identified lineages were Kenya specific. In a contemporaneous global subsample, 990 lineages were documented, 261 for Africa and 97 for Eastern Africa. ASR analysis identified >300 virus location transition events during the period, these comprising: 69 viral imports into Coastal Kenya; 93 viral exports from coastal Kenya; and 191 inter-county import/export events. Most international viral imports (58%) and exports (92%) occurred through Mombasa City, a key touristic and commercial Coastal Kenya center; and many occurred prior to June 2020, when stringent local COVID-19 restriction measures were enforced. After this period, local virus transmission dominated, and distinct local phylogenies were seen. ConclusionsOur analysis supports moving control strategies from a focus on international travel to local transmission. FundingThis work was funded by Wellcome (grant#: 220985) and the National Institute for Health Research (NIHR), project references: 17/63/and 16/136/33 using UK aid from the UK Government to support global health research, The UK Foreign, Commonwealth and Development Office.

11.
Eduan Wilkinson; Marta Giovanetti; Houriiyah Tegally; James E San; Richard Lessels; Diego Cuadros; Darren P Martin; Abdel-Rahman N Zekri; Abdoul Sangare; Abdoul Salam Ouedraogo; Abdul K Sesay; Adnene Hammami; Adrienne A Amuri; Ahmad Sayed; Ahmed Rebai; Aida Elargoubi; Alpha K Keita; Amadou A Sall; Amadou Kone; Amal Souissi; Ana V Gutierrez; Andrew Page; Arnold Lambisia; Arash Iranzadeh; Augustina Sylverken; Azeddine Ibrahimi; Bourema Kouriba; Bronwyn Kleinhans; Beatrice Dhaala; Cara Brook; Carolyn Williamson; Catherine B Pratt; Chantal G Akoua-Koffi; Charles Agoti; Collins M Moranga; James D Nokes; Daniel J Bridges; Daniel L Bugembe; Deelan Doolabh; Deogratius Ssemwanga; Derek Tshabuila; Diarra Bassirou; Dominic S.Y. Amuzu; Dominique Goedhals; Dorcas Maruapula; Edith N Ngabana; Eddy Lusamaki; Edidah Moraa; Elmostafa El Fahime; Emerald Jacob; Emmanuel Lokilo; Enatha Mukantwari; Essia Belarbi; Etienne Simon-Loriere; Etile A Anoh; Fabian Leendertz; Faida Ajili; Fares Wasfi; Faustinos T Takawira; Fawzi Derrar; Feriel Bouzid; Francisca M Muyembe; Frank Tanser; Gabriel Mbunsu; Gaetan Thilliez; Gert van Zyl; Grit Schubert; George Githinji; Gordon A Awandare; Haruka Abe; Hela H Karray; Hellen Nansumba; Hesham A Elgahzaly; Hlanai Gumbo; Ibtihel Smeti; Ikhlass B Ayed; Imed Gaaloul; Ilhem B.B. Boubaker; Inbal Gazy; Isaac Ssewanyana; Jean B Lekana-Douk; Jean-Claude C Makangara; Jean-Jacques M Tamfum; Jean M Heraud; Jeffrey G Shaffer; Jennifer Giandhari; Jingjing Li; Jiro Yasuda; Joana Q Mends; Jocelyn Kiconco; Jonathan A Edwards; John Morobe; John N Nkengasong; John Gyapong; John T Kayiwa; Jones Gyamfi; Jouali Farah; Joyce M Ngoi; Joyce Namulondo; Julia C Andeko; Julius J Lutwama; Justin O Grady; Kefenstse A Tumedi; Khadija Said; Kim Hae-Young; Kwabena O Duedu; Lahcen Belyamani; Lavanya Singh; Leonardo de O. Martins; Madisa Mine; Mahmoud el Hefnawi; Mahjoub Aouni; Maha Mastouri; Maitshwarelo I Matsheka; Malebogo Kebabonye; Manel Turki; Martin Nyaga; Matoke Damaris; Matthew Cotten; Maureen W Mburu; Maximillian Mpina; Michael R Wiley; Mohamed A Ali; Mohamed K Khalifa; Mohamed G Seadawy; Mouna Ouadghiri; Mulenga Mwenda; Mushal Allam; My V.T. Phan; Nabil Abid; Nadia Touil; Najla Kharrat; Nalia Ismael; Nedio Mabunda; Nei-yuan Hsiao; Nelson Silochi; Ngonda Saasa; Nicola Mulder; Patrice Combe; Patrick Semanda; Paul E Oluniyi; Paulo Arnaldo; Peter K Quashie; Reuben Ayivor-Djanie; Philip A Bester; Philippe Dussart; Placide K Mbala; Pontiano Kaleebu; Richard Njouom; Richmond Gorman; Robert A Kingsley; Rosina A.A. Carr; Saba Gargouri; Saber Masmoudi; Samar Kassim; Sameh Trabelsi; Sami Kammoun; Sanaa Lemriss; Sara H Agwa; Sebastien Calvignac-Spencer; Seydou Doumbia; Sheila M Madinda; Sherihane Aryeetey; Shymaa S Ahmed; Sikhulile Moyo; Simani Gaseitsiwe; Edgar Simulundu; Sonia Lekana-Douki; Soumeya Ouangraoua; Steve A Mundeke; Sumir Panji; Sureshnee Pillay; Susan Engelbrecht; Susan Nabadda; Sylvie Behillil; Sylvie van der Werf; Tarik Aanniz; Tapfumanei Mashe; Thabo Mohale; Thanh Le-Viet; Tobias Schindler; Upasana Ramphal; Magalutcheemee Ramuth; Vagner Fonseca; Vincent Enouf; Wael H Roshdy; William Ampofo; Wolfgang Preiser; Wonderful T Choga; Yaw Bediako; Yenew K. Tebeje; Yeshnee Naidoo; Zaydah de Laurent; Sofonias K Tessema; Tulio de Oliveira.
Preprint in English | medRxiv | ID: ppmedrxiv-21257080

ABSTRACT

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

12.
Wellcome Open Res ; 6: 22, 2021.
Article in English | MEDLINE | ID: mdl-35310901

ABSTRACT

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort's limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual's risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.

13.
Wellcome Open Res ; 6: 99, 2021.
Article in English | MEDLINE | ID: mdl-38779569

ABSTRACT

Background: Nasopharyngeal samples contain higher quantities of bacterial and host nucleic acids relative to viruses; presenting challenges during virus metagenomics sequencing, which underpins agnostic sequencing protocols. We aimed to develop a viral enrichment protocol for unbiased whole-genome sequencing of respiratory syncytial virus (RSV) from nasopharyngeal samples using the Oxford Nanopore Technology (ONT) MinION platform. Methods: We assessed two protocols using RSV positive samples. Protocol 1 involved physical pre-treatment of samples by centrifugal processing before RNA extraction, while Protocol 2 entailed direct RNA extraction without prior enrichment. Concentrates from Protocol 1 and RNA extracts from Protocol 2 were each divided into two fractions; one was DNase treated while the other was not. RNA was then extracted from both concentrate fractions per sample and RNA from both protocols converted to cDNA, which was then amplified using the tagged Endoh primers through Sequence-Independent Single-Primer Amplification (SISPA) approach, a library prepared, and sequencing done. Statistical significance during analysis was tested using the Wilcoxon signed-rank test. Results: DNase-treated fractions from both protocols recorded significantly reduced host and bacterial contamination unlike the untreated fractions (in each protocol p<0.01). Additionally, DNase treatment after RNA extraction (Protocol 2) enhanced host and bacterial read reduction compared to when done before (Protocol 1). However, neither protocol yielded whole RSV genomes. Sequenced reads mapped to parts of the nucleoprotein (N gene) and polymerase complex (L gene) from Protocol 1 and 2, respectively. Conclusions: DNase treatment was most effective in reducing host and bacterial contamination, but its effectiveness improved if done after RNA extraction than before. We attribute the incomplete genome segments to amplification biases resulting from the use of short length random sequence (6 bases) in tagged Endoh primers. Increasing the length of the random nucleotides from six hexamers to nine or 12 in future studies may reduce the coverage biases.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-20206730

ABSTRACT

We generated 274 SARS-CoV-2 genomes from samples collected during the early phase of the Kenyan pandemic. Phylogenetic analysis identified 8 global lineages and at least 76 independent SARS-CoV-2 introductions into Kenyan coast. The dominant B.1 lineage (European origin) accounted for 82.1% of the cases. Lineages A, B and B.4 were detected from screened individuals at the Kenya-Tanzania border or returning travellers but did not lead to established transmission. Though multiple lineages were introduced in coastal Kenya within three months following the initial confirmed case, none showed extensive local expansion other than cases characterised by lineage B.1, which accounted for 45 of the 76 introductions. We conclude that the international points of entry were important conduits of SARS-CoV-2 importations. We speculate that early public health responses prevented many introductions leading to established transmission, but nevertheless a few undetected introductions were sufficient to give rise to an established epidemic.

15.
Wellcome Open Res ; 5: 162, 2020.
Article in English | MEDLINE | ID: mdl-35330938

ABSTRACT

Background: The global COVID-19 outbreak relies on a quantitative real-time polymerase chain reaction (qRT-PCR) for the detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2), to facilitate the roll-out of patient care and infection control measures. There are several qRT-PCR assays with little evidence on their comparability. We report alterations to the developers' recommendations to sustain the testing capability in our setting, where the supply of testing reagents is limited. Methods: Standards generated from a serially-diluted positive control and previously identified positive/negative samples were used to determine the optimal volumes of the qRT-PCR reagents and to evaluate the validity and performance of four assays: Charité Berlin and European Virus Archive - GLOBAL (EVAg) primer-probe sets, and DAAN and Beijing Genomics Institute (BGI) premixed commercial kits. A multiplex and singleplex RT-PCR kit was used with the two primer-probe sets and the recommended assay volumes of the two premixed kits were altered. Results: In comparison to the multiplex RT-PCR kit, the singleplex RT-PCR kit combined with the primer-probe sets yielded consistent cycle threshold (Ct) values across the different titrations tested. The DAAN premixed kit produced comparable Ct values across the titrations, while the BGI kit showed incomparable Ct values and inconsistent results between batches using the manufacturer's recommended volumes. Conclusion: We achieved a 2.5-fold and 4-fold increase in the number of tests/kit for the premixed kits and the primer-probe sets, respectively. The primer-probe set assays were reliable and consistent, and we preferred a combination of an EVAg and a Berlin target. Any inconclusive result was repeated by different individuals following the same protocol. DAAN was a consistent and reliable assay even at lower concentrations from the stated recommendations. BGI in contrast, required dilution to improve its performance and was hence an assay that was used in combination with EVAg or Berlin targets.

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