the interplay of two wicked problems

Funding Information: This work was funded by VLIR-UOS, grant numbers TZ2019SIN263 and TZ2020JOI032A101. Publisher Copyright: ©Concern is justified observing the link between the AIDS and COVID-19 pandemics. COVID-19 outcomes are significantly worse in many people living with HIV (PLHIV), even when vaccinated, because of their impaired immune system. Moreover, CD4 T-cells are affected by both HIV and SARS-CoV-2.1-3 SARS-CoV-2 variants can evolve in immunosuppressed patients due to prolonged viral replication in the context of an inadequate immune response.4 Accelerated intrahost evolution of SARS-CoV-2 was reported in a South African HIV patient with antiretroviral therapy (ART) failure.5 6 With 25 million HIV patients in sub-Saharan Africa (SSA) of whom an estimated 8 million are not virologically suppressed, this potentially creates a reservoir for future variants. Such variants, arising in PLHIV anywhere in the world, can spread to other continents, as has been reported for variants of concern (VoCs) (Beta, Omicron) and variants of interest (B.1.6.20, B.1.640.2) that arose in Africa.7-9 Conversely, the COVID-19 pandemic impacts HIV treatment programmes, due to supply chain issues, overburdening of healthcare systems, limiting access to testing, treatment and prevention programmes and further increasing inequalities.10 Modelled COVID-19 disruptions of HIV programmes in SSA included decreased functionality of HIV prevention programmes, HIV testing and treatment, healthcare services such as viral load testing, adherence counselling, drug regimen switches and ART interruptions, which may lead to selection of drug-resistant HIV.11 A 6-month interruption affecting 50% of the population would lead to a median number of excess deaths of 296 000, during 1 year. Scientists advocate for the AIDS and COVID-19 pandemics in Africa to be addressed simultaneously, by increasing African access to COVID-19 vaccines, prioritising research on the interaction between HIV care and COVID-19, maintaining high-quality HIV services and integrating health services for both viruses.7 Both the COVID-19 and the AIDS pandemic, more specifically the issue of HIV drug resistance (HIVDR), have previously been described as wicked problems which are best studied as complex adaptive systems (CASs).12-15Wicked problems consist of diverse interconnected factors and require complexity-informed and locally adapted solutions rather than one solution that fits all. We recently designed a qualitative model of all known factors influencing HIVDR in SSA and analysed its complexity.13 Our detailed systems map featured three main feedback loops driving HIVDR, representing (1) the alternation between adherence and non-adherence, (2) the impact of an overburdened healthcare system and (3) the importance of sustaining global efforts of tackling HIVDR even when new antiretroviral drugs with high genetic barriers become available. These HIV-related feedback loops are interconnected with COVID-19 pandemic impact (in yellow, figure 1). The loop starts from PLHIV with an unsuppressed viral load, which weakens the immune system and may in turn slow down immune clearance of SARS-CoV-2, allowing prolonged replication and mutation of the virus in the context of an inadequate immune response. Prolonged viral clearance facilitates the selection of immune escape SARS-CoV-2 variants. Variants may emerge that have a selective advantage and therefore may spread through populations due to increased transmissibility (with possibly increased virulence), thereby creating an additional burden on the healthcare system, putting the overall healthcare system and the HIV care at risk. These stressors on the healthcare system lead to a higher risk of unsuppressed viral load in PLHIV, increasing the risk of HIVDR. Figure 1 shows the need to address both wicked problems simultaneously and to do so in a complexity-informed manner as they are inevitably linked and influence each other. Evidently, the exact interconnections between both pandemics need to be locally assessed. For instance, a study in South Africa showed that while lockdown severely impacted HIV testing and ART initiation, ART provision was largely maintained, indicating that the strength of the connection between the virological suppression-related loop and the pandemic, indicated in figure 1, are context-dependent.16publishersversionpublishe

Gender Differences in HIV Disease Progression and Treatment Outcomes among HIV Patients One Year after Starting Antiretroviral Treatment (ART) in Dar es Salaam, Tanzania.

We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences

Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease

Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology

A ten year review of the sickle cell program in Muhimbili National Hospital, Tanzania

Background: Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studies providing reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established the Muhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seen in the first 10 years at Muhimbili National Hospital (MNH). Methods: Individuals seen at MNH known or suspected to have SCD were enrolled at clinic and laboratory testing for SCD, haematological and biochemical analyses done. Ethnicity was self-reported. Clinical and laboratory features of SCD were documented. Comparison was made with non-SCD population as well as within 3 different age groups (< 5, 5-17 and ≥ 18 years) within the SCD population. Results: From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in age group 5-17 years. There was variation in the geographical distribution of SCD. Individuals with SCD compared to non-SCD, had significantly lower blood pressure and peripheral oxygen saturation (SpO2). SCD patients had higher prevalence of severe anemia, jaundice and desaturation (SpO2 < 95%) as well as higher levels of reticulocytes, white blood cells, platelets and fetal hemoglobin. The main causes of hospitalization for SCD within a 12-month period preceding enrolment were pain (adults), and fever and severe anemia (children). When clinical and laboratory features were compared in SCD within 3 age groups, there was a progressive decrease in the prevalence of splenic enlargement and an increase in prevalence of jaundice. Furthermore, there were significant differences with monotonic trends across age groups in SpO2, hematological and biochemical parameters. Conclusion: This report confirms that the wide spectrum of clinical expression of SCD observed elsewhere is also present in Tanzania, with non-uniform geographical distribution across the country. Age-specific analysis is consistent with different disease-patterns across the lifespan

A ten year review of the sickle cell program in Muhimbili National Hospital, Tanzania.

BACKGROUND: Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studies providing reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established the Muhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seen in the first 10 years at Muhimbili National Hospital (MNH). METHODS: Individuals seen at MNH known or suspected to have SCD were enrolled at clinic and laboratory testing for SCD, haematological and biochemical analyses done. Ethnicity was self-reported. Clinical and laboratory features of SCD were documented. Comparison was made with non-SCD population as well as within 3 different age groups (< 5, 5-17 and ≥ 18 years) within the SCD population. RESULTS: From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in age group 5-17 years. There was variation in the geographical distribution of SCD. Individuals with SCD compared to non-SCD, had significantly lower blood pressure and peripheral oxygen saturation (SpO2). SCD patients had higher prevalence of severe anemia, jaundice and desaturation (SpO2 < 95%) as well as higher levels of reticulocytes, white blood cells, platelets and fetal hemoglobin. The main causes of hospitalization for SCD within a 12-month period preceding enrolment were pain (adults), and fever and severe anemia (children). When clinical and laboratory features were compared in SCD within 3 age groups, there was a progressive decrease in the prevalence of splenic enlargement and an increase in prevalence of jaundice. Furthermore, there were significant differences with monotonic trends across age groups in SpO2, hematological and biochemical parameters. CONCLUSION: This report confirms that the wide spectrum of clinical expression of SCD observed elsewhere is also present in Tanzania, with non-uniform geographical distribution across the country. Age-specific analysis is consistent with different disease-patterns across the lifespan

Dataset for a cross-sectional study on the prevalence of urinary tract infections and antibiogram of uropathogens isolated from under-five children attending Bagamoyo district hospital in Tanzania - dataset

Urinary tract infection (UTI) is a common condition in children that recurs frequently. This study aimed to determine the prevalence of UTIs among under-five children attending Bagamoyo District hospital and its association with nutritional status. This data was from a cross-sectional study that enrolled 214 under-five children attending Bagamoyo district hospital in Tanzania. Midstream urine was collected in sterile conditions and bottles. Samples were transported to the laboratory at Muhimbili University of Health and Allied Sciences for analysis, isolation and bacteria identification. Bacteria were isolated using CLED agar, followed by identification using Gram staining, single iron agar test, sulfide-indole motility test, catalase and oxidase tests. A susceptibility test was done using the disc diffusion method. Anthropometric measurements were employed to assess malnutrition status and body mass index determined using each child's weight and height. Presented are underlining data (in Microsoft Excel format) containing the data from the questionnaire and laboratory analyses resulting from bacteria identification and antimicrobial susceptibility testing. The second file is the questionnaire with the questions that were used in to capture the demographic information. The data marked 'NA' implies that for these patients who were negative for urinary tract infection, the data was not available for the type of bacteria and other tests

Prevalence of urinary tract infections and antibiogram of uropathogens isolated from under-five children attending Bagamoyo district hospital in Tanzania - dataset

Urinary tract infection (UTI) is a common condition in children that recurs frequently. This study aimed to determine the prevalence of UTIs among under-five children attending Bagamoyo District hospital and its association with nutritional status. This data was from a cross-sectional study that enrolled 214 under-five children attending Bagamoyo district hospital in Tanzania. Midstream urine was collected in sterile conditions and bottles. Samples were transported to the laboratory at Muhimbili University of Health and Allied Sciences for analysis, isolation and bacteria identification. Bacteria were isolated using CLED agar, followed by identification using Gram staining, single iron agar test, sulfide-indole motility test, catalase and oxidase tests. A susceptibility test was done using the disc diffusion method. Anthropometric measurements were employed to assess malnutrition status and body mass index determined using each child's weight and height

Dataset and supplementary materials for baseline evaluation of bioinformatics capacity in Tanzania in 2018

Due to the insufficient human and infrastructure capacity to use novel genomics and bioinformatics technologies, Sub-Saharan Africa countries have not entirely ripped the benefits in health and other sectors. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. The survey collected demographic information like age group, experience, seniority level, gender, number of respondents per institution, number of publications, and willingness to join the community of practice. The survey also investigated the capacity of individuals and institutions about computing infrastructure, operating system use, statistical packages in use, the basic Microsoft packages experience, programming language experience, bioinformatics tools and resources usage, and type of analyses performed. Moreover, respondents were surveyed about the challenges they faced in implementing bioinformatics and their willingness to join the bioinformatics community of practice in Tanzania. This dataset contains survey response data, supplementary tables and the data instrument (Questionnaire) used in the survey. In addition, a data dictionary is attached containing the map of all the 113 variables used in this survey. The total number of questions in the questionnaire was 54, but for multiple-choice questions, the variables were replicated per the number of options

Infrastructure for bioinformatics applications in Tanzania: Lessons from the Sickle Cell Programme

Sickle cell disease (SCD) is a common genetic disorder in Africa. Some ongoing work in SCD research includes the analysis and comparisons of variation in phenotypic presentations and disease outcomes with the genotypic signatures. This has contributed to the observed growth of molecular and genetic data in SCD. However, while the “omics” data continues to pile, the capacity to interpret and turn the genetic findings into clinical practice is still underdeveloped, especially in the developing region. Building bioinformatics infrastructure and capacity in the region is key to bridging the gap. This paper seeks to illustrate how the Sickle Cell Programme (SCP) at the Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania, modeled the integration of infrastructure for bioinformatics and clinical research while running day-to-day clinical care for SCD in Tanzania