Abstract The East African Community (EAC) grapples with many challenges in tackling infectious disease threats and antimicrobial resistance (AMR), underscoring the importance of regional and robust ...pathogen genomics capacities. However, a significant disparity exists among EAC Partner States in harnessing bacterial pathogen sequencing and data analysis capabilities for effective AMR surveillance and outbreak response. This study assesses the current landscape and challenges associated with pathogen next-generation sequencing (NGS) within EAC, explicitly focusing on World Health Organization (WHO) AMR-priority pathogens. The assessment adopts a comprehensive approach, integrating a questionnaire-based survey amongst National Public Health Laboratories (NPHLs) with an analysis of publicly available metadata on bacterial pathogens isolated in the EAC countries. In addition to the heavy reliance on third-party organizations for bacterial NGS, the findings reveal a significant disparity among EAC member States in leveraging bacterial pathogen sequencing and data analysis. Approximately 97% ( n = 4,462) of publicly available high-quality bacterial genome assemblies of samples collected in the EAC were processed and analyzed by external organizations, mainly in Europe and North America. Tanzania led in-country sequencing efforts, followed by Kenya and Uganda. The other EAC countries had no publicly available samples or had all their samples sequenced and analyzed outside the region. Insufficient local NGS sequencing facilities, limited bioinformatics expertise, lack of adequate computing resources, and inadequate data-sharing mechanisms are among the most pressing challenges that hinder the EAC’s NPHLs from effectively leveraging pathogen genomics data. These insights emphasized the need to strengthen microbial pathogen sequencing and data analysis capabilities within the EAC to empower these laboratories to conduct pathogen sequencing and data analysis independently. Substantial investments in equipment, technology, and capacity-building initiatives are crucial for supporting regional preparedness against infectious disease outbreaks and mitigating the impact of AMR burden. In addition, collaborative efforts should be developed to narrow the gap, remedy regional imbalances, and harmonize NGS data standards. Supporting regional collaboration, strengthening in-country genomics capabilities, and investing in long-term training programs will ultimately improve pathogen data generation and foster a robust NGS-driven AMR surveillance and outbreak response in the EAC, thereby supporting global health initiatives.
The emergence of SARS-CoV-2 mutants might lead to European border closures, which impact on trade and result in serious economic losses. In April 2020, similar border closures were observed during ...the first SARS-CoV-2 wave in East Africa.
Since 2017 the East African Community EAC together with the Bernhard-Nocht-Institute for Tropical Medicine BNITM established a mobile laboratory network integrated into the National Public Health Laboratories of the six Partner States for molecular diagnosis of viral haemorrhagic fevers and SARS-CoV-2. Since May 2020, the National Public Health Laboratories of Kenya, Rwanda, Burundi, Uganda and South Sudan deployed these mobile laboratories to their respective borders, issuing a newly developed "Electronic EAC COVID-19 Digital Certificate" to SARS-CoV-2 PCR-negative truck drivers, thus assuring regional trade.
Considering the large financial damages of border closures, such a mobile laboratory network as demonstrated in East Africa is cost-effective, easy to implement and feasible. The East African Community mobile laboratory network could serve as a blueprint for Europe and other countries around the globe.
To determine the prevalence of Plasmodium falciparum multi-drug resistant gene-1 (Pfmdr-1) N86Y and D1246Y genotypes among febrile malaria outpatients attending Lira Regional Referral Hospital, ...Uganda.
Overall, 92.3% (n = 48/52) and 90% (n = 45/50) of the parasites detected carried the wild type alleles 1246D and N86, respectively. Only 7.7% (n = 4/52) and 10% (n = 5/50) of these P. falciparum isolates carried the Pfmdr-1 mutant alleles 1246Y and 86Y, respectively. Our results show high prevalence of wild type alleles N86 and D1246 in P. falciparum isolates from Lira Regional Referral Hospital, which could translate to a decreased sensitivity to artemether-lumefantrine. Continued monitoring of prevalence of single nucleotide polymorphisms is warranted to timely inform malaria treatment policies and guidelines.
Background East Africa is home to 170 million people and prone to frequent outbreaks of viral haemorrhagic fevers and various bacterial diseases. A major challenge is that epidemics mostly happen in ...remote areas, where infrastructure for Biosecurity Level (BSL) 3/4 laboratory capacity is not available. As samples have to be transported from the outbreak area to the National Public Health Laboratories (NPHL) in the capitals or even flown to international reference centres, diagnosis is significantly delayed and epidemics emerge. Main text The East African Community (EAC), an intergovernmental body of Burundi, Rwanda, Tanzania, Kenya, Uganda, and South Sudan, received 10 million euro funding from the German Development Bank (KfW) to establish BSL3/4 capacity in the region. Between 2017 and 2020, the EAC in collaboration with the Bernhard-Nocht-Institute for Tropical Medicine (Germany) and the Partner Countries' Ministries of Health and their respective NPHLs, established a regional network of nine mobile BSL3/4 laboratories. These rapidly deployable laboratories allowed the region to reduce sample turn-around-time (from days to an average of 8h) at the centre of the outbreak and rapidly respond to epidemics. In the present article, the approach for implementing such a regional project is outlined and five major aspects (including recommendations) are described: (i) the overall project coordination activities through the EAC Secretariat and the Partner States, (ii) procurement of equipment, (iii) the established laboratory setup and diagnostic panels, (iv) regional training activities and capacity building of various stakeholders and (v) completed and ongoing field missions. The latter includes an EAC/WHO field simulation exercise that was conducted on the border between Tanzania and Kenya in June 2019, the support in molecular diagnosis during the Tanzanian Dengue outbreak in 2019, the participation in the Ugandan National Ebola response activities in Kisoro district along the Uganda/DRC border in Oct/Nov 2019 and the deployments of the laboratories to assist in SARS-CoV-2 diagnostics throughout the region since early 2020. Conclusions The established EAC mobile laboratory network allows accurate and timely diagnosis of BSL3/4 pathogens in all East African countries, important for individual patient management and to effectively contain the spread of epidemic-prone diseases. Keywords: East African Community, Viral haemorrhagic fevers, Ebola virus disease, Dengue fever, Mobile laboratory, COVID-19, Outbreak response, BSL4, Capacity building
In response to the largest recorded monkeypox virus outbreak outside of endemic Central and Western Africa, the East African Community (EAC), in cooperation with the Bernhard-Nocht- Institute for ...Tropical Medicine (BNITM), coordinated an emergency monkeypox diagnostic training for the East African Region. As of June 2022, the Democratic Republic of Congo reported a steady increase of suspected monkeypox cases, increasing the risk of spill-over into the remaining six EAC Partner States. Within the existing EAC Mobile Laboratories project, laboratory experts of the National Public Health Laboratories of the remaining six EAC Partner States (Burundi, Rwanda, Tanzania, Kenya, Uganda and South Sudan) participated in the workshop and were trained in reception of suspect samples, DNA extraction and diagnosis using RT-PCR. The EAC region is now equipped with the tools to prepare and rapidly respond to any emerging monkeypox outbreak.
Within the first 14 days after outbreak confirmation, the East African Community Mobile laboratory network was actively involved in providing Sudan virus disease and differential diagnostics in the ...epicentre at Mubende Regional Referral Hospital (and neighbouring districts), as well as in coordination of mobile laboratory preparedness activities in five other East African countries. Introduction On 20 September 2022, the Ugandan Ministry of Health declared an Ebola Sudan virus disease (SVD) outbreak in the Mubende District of the country, with one confirmed SVD death and six probable deaths reported in the region since 1 September 2022.1 Since 2017, and with funding from the German Federal Ministry for Economic Cooperation and Development through the KfW Development Bank, the East African Community (EAC) together with the Bernhard-Nocht-Institute for Tropical Medicine established a network of nine mobile EAC laboratories embedded within the National Public Health Laboratories (NPHLs) of six EAC Partner States (Tanzania, Kenya, Burundi, Rwanda, South Sudan and Uganda).2 3 These field-deployable mobile laboratories have the capacity to diagnose risk group four pathogens, such as SVD. On the same day of the SVD outbreak announcement (20 September 2022) by the Ugandan government, the EAC Health Department initiated their regional pandemic preparedness and response activities, which consisted of a two-pronged approach: while the mobilisation of the EAC mobile laboratory network commenced, the regional procurement of diagnostic kits for SVD and differential diagnosis was immediately initiated (for a detailed timeline of events, see table 1).Table 1 Timeline of regional SVD outbreak response and preparedness activities in six East African countries Days following outbreak announcement 1 2 3 4 5 6 7 8 9 10 11 12 13 14 SVD outbreak declared by Uganda MoH EAC secretariat Emergency pandemic preparedness meetings Emergency procurement initiated Logistical support (kit delivery) Technical country support Press Release No of SVD kits ordered/expected 1×96 tests (arrival day 20) Uganda SVD outbreak response Request for support to EAC Lab deployment from Kampala to Mubende Start of testing No of SVD kits ordered/received 4×96 tests No. Diagnostic workflows, standard operating procedures and supply of diagnostics kits The EAC Mobile laboratories consist of negative pressure gloveboxes (Könnecke, Germany) (see figure 2) for sample inactivation and Bio-Rad CFX96 RT-PCR platforms for molecular SVD diagnosis (for further details on the laboratory setup, see Affara et al2).
Abstract
Objective
Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated ...whether microbial translocation drives immune activation in HIV-infected Ugandan children.
Methods
Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing.
Results
Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range IQR, 1.7–4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%–24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9–9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%–39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12–22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001).
Conclusion
Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting.
Clinical Trials Registration
ISRCTN69078957.
We found no evidence of an association between microbial translocation and immune activation in Ugandan human immunodeficiency virus (HIV)–infected children over time during receipt of antiretroviral therapy or in comparison to HIV-uninfected controls. In this setting, other factors may be driving immune activation in both infected and uninfected children.
Summary Background WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors ...(NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz. Methods In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2–4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957. Findings Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2–4 clinical or grade 3/4 laboratory adverse events (835 clinical 634 grade 2; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio HR 0·99 95% CI 0·75–1·29; abacavir vs stavudine: HR 0·88 0·67–1·15). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00). Interpretation All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. Funding European Developing Countries Clinical Trials Partnership.
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