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Ann M Moormann,1,* Jodi L Skiles,2,* Juliana A Otieno,3 Geoffrey C Buckle,1 Terry A Vik2 1University of Massachusetts Medical School, Worcester, MA, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA; 3Jaramogi Oginga Odinga Teaching and Referral Hospital, Ministry of Medical Services, Kisumu, Kenya *These authors contributed equally to this work Abstract: Endemic Burkitt lymphoma (BL) was publically described in 1958 and remains the most prevalent pediatric cancer in equatorial Africa with an annual incidence between two and five cases per 100,000 children. Several risk factors have been identified, including early-age infection with Epstein–Barr virus, a geographic association with high Plasmodium falciparum malaria transmission, and poor nutrition. However, other modifiable factors play a role in the survival of these children. Treatment regimens for BL have evolved over a time period that spans nearly 50 years. This review will compare survival between different combination chemotherapeutic regimens and discuss other key determinants of outcomes among children diagnosed with BL in resource-limited settings. A discussion of obstacles to diagnosis will be presented, including low community awareness of pediatric cancer, limited access to health facilities, inaccurate or delayed diagnosis often beginning at lower level health rural facilities that are typically staffed by those with limited training in oncology, and insufficient pathology support to confirm diagnosis. Other challenges examined here include those related to treatment adherence, specifically the social and economic stressors that can lead to abandonment of care, and treatment-related toxicity, a challenge compounded not only by the scarcity of medications for supportive care, but also the paucity of clinically trained medical professionals available to manage integrated care for these children. Future directions for enhancing BL survival will be discussed including molecular approaches for rational drug discovery as well as the benefits of forming a unified, global BL research network. Keywords: pediatric cancer, treatment regimen, Africa, social and economic predictors, biomarkers

Clinical practice guidelines are widely used in oncology to guide clinical decision making and inform health policy and planning. In recent years, the National Comprehensive Cancer Network and the American Society of Clinical Oncology, as well as other international groups, have developed resource-stratified guidelines to guide clinicians and policymakers on cancer diagnosis and management in settings with various levels of resource constraints. Current methods for developing resource-stratified guidelines rely heavily on supporting evidence originating from high-income countries. In this commentary, the authors discuss limitations of the existing methods to develop resource-stratified guidelines and offer perspective on ways to strengthen the guidelines and their evidence base. Pulling from conceptual frameworks in the health policy domain, the authors outline a more inclusive approach to evidence synthesis that seeks to integrate the growing volume of cancer research emerging from low- and middle-income countries. The authors also introduce a revised evidence framework that provides transparency into the generalizability of evidence within the guidelines. These changes have the potential to enhance resource-stratified guidelines and bring us one step closer to the goal of evidence-based guidelines that are appropriate for diverse settings and unique patient populations across the world., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: To describe the global landscape of clinical research into interventions for gastroesophageal cancers (GECs), with examination of trial characteristics, geographic distribution of trial sites, and factors associated with trial termination., Methods: We queried ClinicalTrials.gov to identify all completed or terminated phase III interventional studies investigating GECs (esophageal squamous cell carcinoma [ESCC], esophageal adenocarcinoma [EAC], gastroesophageal junctional [GEJ], and gastric adenocarcinoma). Data on all reported trial characteristics were extracted. Pearson's chi-square and Fisher's exact tests were used to compare differences in completed and terminated trials. Multivariate logistic regression evaluated predictors of termination., Results: A total of 179 trials were identified; of these, 90% were therapeutic. Most included sites in Asia (61%) and Europe (32%); few included sites in Africa (4%). Thirty percent included sites in low- and middle-income countries (LMICs). Most (70%) focused on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% on ESCC alone. Sixteen percent (n = 29) of trials terminated prematurely. In multivariate analysis, study site number, location of recruitment sites, and patient population emerged as predictors of termination. Trials recruiting from US-based sites were more likely to terminate (odds ratio [OR], 7.22 [95% CI, 1.59 to 32.69]). Trials conducted exclusively in LMICs were less likely to terminate (OR, 0.04 [95% CI, 0.01 to 0.59] v conducted in high-income countries [HICs] alone). Studies on ESCC were more likely to terminate (OR, 17.74 [95% CI, 1.49 to 210.69])., Conclusion: Although 80% of GECs occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Overall, this study highlights (1) a missed opportunity to recruit patients from high-incidence regions globally; and (2) a pressing need for increasing funding, infrastructure, and support for GEC trials in LMICs.

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute-designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients., (© 2022 UICC.)

Purpose: Eastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study., Materials and Methods: From 2013 to 2015, ESCC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for sex and age (± 10 years). Questionnaires were used to assess sociodemographic characteristics and environmental, dietary, and lifestyle risk exposures. Multivariate logistic regression models were used to estimate age-specific odds ratios of ESCC for exposures among participants age 30-44 and ≥ 45 years., Results: A total of 471 cases and 471 controls were enrolled. Among cases, 100 (21%) were < 45 years. Multiple exposures were identified as risk factors for early-onset ESCC, several of which were unique to this age group, including infrequent teeth cleaning, secondhand tobacco smoke exposure, and pest infestation of grain and/or nuts. Lower socioeconomic status, family history of ESCC, tobacco smoking, home-brewed alcohol consumption, home storage of grain and/or nuts, and use of firewood for cooking were associated in the older but not the younger age group. Hot beverage intake was associated with increased ESCC risk in both age groups., Conclusion: Our results suggest that ESCC risk factors in Tanzania vary between age groups. With the data currently available, environmental and behavioral risk factors appear to play an important role in the high incidence of ESCC among young people., Competing Interests: Geoffrey C. BuckleResearch Funding: Celgene Cancer Carelinks Beatrice P. MushiResearch Funding: Cepheid (Inst), Celgene Cancer Carelinks/BMS (Inst) Li ZhangConsulting or Advisory Role: Raydiant OximetryTravel, Accommodations, Expenses: Dendreon Katherine Van LoonSpeakers' Bureau: Physicans' Education Resource, AmgenResearch Funding: Celgene Cancer Carelinks (Inst)No other potential conflicts of interest were reported.

Background: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined., Methods: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach., Discussion: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research., Trial Registration: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 ., (© 2022. The Author(s).)

Esophageal cancer (EC) is a leading cause of cancer morbidity and mortality in Africa. Despite the high burden of disease, optimal management strategies for EC in resource-constrained settings have yet to be established. This systematic review evaluates the literature on treatments for EC throughout Africa and compares the efficacy and safety of varying treatment strategies in this context (PROSPERO CRD42017071546). PubMed, Embase and African Index Medicus were searched for studies published on treatment strategies for EC in Africa from 1980 to 2020. Searches were supplemented by examining bibliographies of included studies and relevant conference proceedings. Methodological quality/risk of bias was assessed using the Cochrane Risk-of-Bias tool and the Newcastle-Ottawa Scale. Forty-six studies were included. Case series constituted the majority of studies: 13 were case series reporting on outcomes of esophagectomies, 17 on palliative luminal or surgical interventions, four on radiotherapy and three on concurrent chemoradiation. Nine randomized controlled trials were identified, of which four prospectively compared different treatment modalities (one investigating radiotherapy vs chemoradiation, three evaluating rigid plastic stents vs other treatments). This review summarizes the research on EC treatments in Africa published over the last four decades and outlines critical gaps in knowledge related to management in this context. Areas in need of further research include (a) evaluation of the safety and efficacy of neoadjuvant therapy in patients with locally advanced disease; (b) strategies to improve long-term survival in patients treated with definitive chemoradiation; and (c) the comparative effectiveness of modern palliative interventions, focusing on quality of life and survival as outcome measures., (© 2020 Union for International Cancer Control.)

Background: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC)., Methods: We conducted an incident case-control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran-Mantel-Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone., Results: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41-4.68], former smoking (OR 2.45; 95% CI, 1.46-4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01-2.77), daily spicy chilies (OR 1.62; 1.04-2.52), and daily salted foods (OR 2.02; 95% CI, 1.06-3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16-0.80), fruit (OR 0.47; 95% CI, 0.27-0.82), and smoked fish (OR 0.31; 95% CI, 0.15-0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16-11.73), Northern-Lake (OR 2.40; 95% CI, 1.46-3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56-6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone., Conclusions: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania., Impact: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa. See related commentary by McCormack et al., p. 248 ., (©2020 American Association for Cancer Research.)

Background: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development., Methods: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time., Findings: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries., Interpretation: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Survival rates for children diagnosed with Burkitt lymphoma (BL) in Africa are far below those achieved in developed countries. Late stage of presentation contributes to poor prognosis, therefore this study investigated factors leading to delays in BL diagnosis and treatment of children in Uganda and western Kenya., Methods: Guardians of children diagnosed with BL were interviewed at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JTRH) and Uganda Cancer Institute (UCI) from Jan-Dec 2010. Information on sociodemographics, knowledge, attitudes, illness perceptions, health-seeking behaviors and prior health encounters was collected using a standardized, pre-tested questionnaire., Results: Eighty-two guardians were interviewed (20 JTRH, 62 UCI). Median "total delay" (1st symptoms to BL diagnosis) was 12.1 weeks [interquartile range (IQR) 4.9-19.9] in Kenya and 12.9 weeks (IQR 4.3-25.7) in Uganda. In Kenya, median "guardian delay" (1st symptoms to 1st health encounter) and "health system delay" (1st health encounter to BL diagnosis) were 9.0 weeks (IQR 3.6-15.7) and 2.0 weeks (IQR 1.6-5.8), respectively. Data on guardian and health system delay in Uganda were only available for those with < 4 prior health encounters (n = 26). Of these, median guardian delay was 4.3 weeks (range 0.7-149.9), health system delay 2.6 weeks (range 0.1-16.0), and total delay 10.7 weeks (range 1.7-154.3). Guardians in Uganda reported more health encounters than those in Kenya (median 5, range 3-16 vs. median 3, range 2-6). Among Kenyan guardians, source of income was the only independent predictor of delay, whereas in Uganda, guardian delay was influenced by guardians' beliefs on the curability of cancer, health system delay, by guardians' perceptions of cancer as a contagious disease, and total delay, by the number of children in the household and guardians' role as caretaker. Qualitative findings suggest financial costs, transportation, and other household responsibilities were major barriers to care., Conclusions: Delays from symptom onset to BL treatment were considerable given the rapid growth rate of this cancer, with guardian delay constituting the majority of total delay in both settings. Future interventions should aim to reduce structural barriers to care and increase awareness of BL in particular and cancer in general within the community, as well as among health professionals.

Background: Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies., Methods: We conducted a systematic literature review of the PubMed and Scopus databases using pre-defined criteria to identify population-based studies with typhoid fever incidence data published between 1980 and 2009. We also abstracted data from annual reports of notifiable diseases in countries with advanced surveillance systems. Typhoid and paratyphoid fever input data were grouped into regions and regional incidence and mortality rates were estimated. Incidence data were extrapolated across regions for those lacking data. Age-specific incidence rates were derived for regions where age-specific data were available. Crude and adjusted estimates of the global typhoid fever burden were calculated., Results: Twenty-five studies were identified, all of which contained incidence data on typhoid fever and 12 on paratyphoid fever. Five advanced surveillance systems contributed data on typhoid fever; 2 on paratyphoid fever. Regional typhoid fever incidence rates ranged from <0.1/100 000 cases/y in Central and Eastern Europe and Central Asia to 724.6/100 000 cases/y in Sub-Saharan Africa. Regional paratyphoid incidence rates ranged from 0.8/100 000 cases/y in North Africa/Middle East to 77.4/100 000 cases/y in Sub-Saharan Africa and South Asia. The estimated total number of typhoid fever episodes in 2010 was 13.5 million (interquartile range 9.1-17.8 million). The adjusted estimate accounting for the low sensitivity of blood cultures for isolation of the bacteria was 26.9 million (interquartile range 18.3-35.7 million) episodes. These findings are comparable to the most recent analysis of global typhoid fever morbidity, which reported crude and adjusted estimates of 10.8 million and 21.7 million typhoid fever episodes globally in 2000., Conclusion: Typhoid fever remains a significant health burden, especially in low- and middle-income countries. Despite the availability of more recent data on both enteric fevers, additional research is needed in many regions, particularly Africa, Latin America and other developing countries.

Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy., Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives., Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months., Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

Purpose of Review: The purpose of this review is to highlight new findings published in 2010-2011 related to noninvasive fibrosis assessment in HIV/hepatitis C virus (HCV) co-infected patients. Overall, in 2010-2011, 15 studies were published, of which two were excluded because they were published in languages other than English., Recent Findings: Eleven studies focused on serum marker panels. Studies sought to validate established panels in HIV/HCV co-infected patients often by comparing multiple serum marker panels in the same population; establish new marker panels using combinations of markers used in previously validated panels; and develop new marker panels using novel methodology. Overall, all panels performed within similar ranges of diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AUROC) but the FibroMeter panel and its derivations achieved the highest performance. Four studies focused on transient elastography. Two studies confirmed its accuracy for identifying fibrosis and cirrhosis and two studies confirmed that misclassification rates are higher in the presence of elevated triglycerides and steatosis., Summary: Overall, performance of transient elastography appeared superior to the majority of serum marker panels for the detection of significant fibrosis and cirrhosis in HIV/HCV co-infected patients. Challenges of widespread application of transient elastography remain high misclassification in some subgroups, lack of standardized cut-points and lack of widespread availability. Panels that were newly developed in 2010-2011 specifically for HIV/HCV appeared to perform better than existing panels such as APRI and FIB-4; however, additional external validation will be needed to confirm their accuracy.

The major incursion of human immunodeficiency virus type I (HIV-1) infection into the South African heterosexual population has been by southerly migration of the heterosexual HIV-1 epidemic from central Africa. Much important information can be obtained from blood donor seroprevalence data and cohort studies of those individuals infected during the early stages of the epidemic in South Africa. By the end of April 1989, over half a million blood donors in Natal had been screened and the presence of antibody to HIV-1 confirmed in more than 200. The majority of these anti-HIV-1 positive donors are young and single (many of them still at school), although a substantial proportion already have children of their own and a recent history of sexually transmitted disease is common. The Natal Blood Transfusion Service experience indicates that the heterosexual HIV-1 epidemic in Natal is essentially no different from the earlier stages of heterosexual epidemics elsewhere in Africa. There is still time for effective programmes to have a major impact on progression of the epidemic in South Africa, particularly if these programmes are directed at the young population in educational institutions.

The increased absolute lymphocyte counts of Indians and Blacks in comparison with Whites, observed in a former study, were shown, in a study on blood donors, to occur in women rather than men of these two groups. Neutrophil counts showed no sex differences, but were significantly highest in Whites and lowest in Blacks. Indians of both sexes had significantly higher mean red cell counts, together with smaller red cells, than subjects in the other two groups. In no group was a significant correlation observed between body mass and haemoglobin level.

The copper sulfate hemoglobin screening method was separately evaluated for three local population groups which do not conform to accepted normal standards of hemoglobin and/or plasma specific gravity (SG). This was carried out by a computer which simulated the distribution of plasma specific gravity and hemoglobin levels in random samples of blood donors. Simulations of 1,000 were carried out for males and for females in each of the three main population groups in Natal (Caucasians, Negroes and Asians). These were compared with a simulation of hypothetical normal subjects whose hemoglobin and plasma SG conformed to accepted standards. Variations in accuracy, relating to differences in plasma specific gravity and in hemoglobin, were demonstrated. Acceptances of donors who should be rejected (Type II errors) were most common in Negroes, but did not occur in the normal group. Type II errors did not occur in males with hemoglobin levels below 12.5 gm/dl or in females under 11.5 gm/dl. Erroneous rejections of prospective donors who, in fact, satisfied the criterion of acceptance (Type I errors) occurred in all groups, but were fewest in the normal group.