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Objective: Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression.Design: A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models.Setting: A public-sector HIV clinic in Lusaka, Zambia.Subjects: One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl.Results: Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported.Conclusions: Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Nutritional status may influence quality of life and prognosis among pancreatic cancer patients, yet few studies describe measures of nutritional status during treatment. We evaluated the nutritional status of locally advanced pancreatic cancer (LAPC) patients undergoing chemoradiotherapy who received baseline nutritional assessment and counseling.Methods: Fourteen newly diagnosed LAPC patients enrolled in phase I/II trials of capecitabine with concomitant radiotherapy were assessed for baseline clinical nutrition measures (body mass index, albumin, weight loss, total energy, and protein intake). Participants completed the Anorexia/Cachexia Subscale (A/CS) questionnaire at baseline and during the 6 weeks of treatment. We evaluated associations between baseline characteristics and subsequent A/CS scores with linear regression and changes in A/CS were assessed with the paired t test.Results: We observed a statistically significant increase in mean A/CS between baseline [24.9, standard deviation (SD) = 9.7] and end of treatment (29.9, SD = 6.2). Controlling for baseline A/CS score, only weight loss greater than 5% of body weight over 1 month was associated with A/CS scores at 6 weeks (β = 10.558, standard error = 3.307, p value = 0.009) and mean A/CS scores during the last 3 weeks of treatment (β = 12.739, standard error = 2.251, p value = 0.001).Conclusions: After 6 weeks of chemoradiotherapy, LAPC patients reported a statistically significant improvement in appetite and weight concerns. Increases in AC/S scores were associated with higher baseline A/CS scores and weight loss of 5% or more during 1 month. Further research is needed to determine the impact of nutritional support during treatment, as improvements in this domain may impact LAPC patients' overall quality of life. [ABSTRACT FROM AUTHOR]

We investigated whether total plasma homocysteine (tHcy) is associated with risk for cervical intraepithelial neoplasia (CIN). tHcy was evaluated, along with numerous risk factors for CIN and biochemical indexes of nutrients, in a previously reported study population of 294 subjects with CIN and 170 female controls without CIN. tHcy was significantly higher in cases than in controls (9.1 vs. 8.3 mumol/l, p = 0.002). Human papillomavirus type 16 infection [odds ratio (OR) = 6.7], oral contraceptive use (OR = 6.0), parity (OR = 2.2), and cigarette smoking (OR = 1.9) were significantly associated with CIN after adjustment for each other and for age, number of sexual partners, and plasma tHcy, folate, iron, and zinc. Human papillomavirus type 16 positivity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.7) than when it was < or = 9.12 mumol/l (OR = 3.0). Cigarette use increased risk for CIN when tHcy was > 9.12 mumol/l (OR = 3.9), but not when tHcy was < or = 9.12 mumol/l (OR = 1.5). Parity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.0) than when tHcy was < or = 9.12 mumol/l (OR = 2.0). These results suggest that elevated plasma tHcy is a risk factor for cervical dysplasia and that it enhances the effects of other risk factors. It is unknown whether tHcy is serving as a marker of folate deficiency or is acting through other mechanisms. [ABSTRACT FROM AUTHOR]

The Intersociety Professional Nutrition Education Consortium (IPNEC) has made substantial progress in its first 2 y. With support from 9 participating nutrition societies and certification organizations and with funding from the National Institutes of Health and several nutrition industry partners, a sustained, functioning consortium has been established. The consortium's 2 principal aims are to establish educational standards for fellowship training of physician nutrition specialists (PNSs) and to create a unified mechanism for certifying physicians who are so trained. Its long-term goals are to increase the pool of PNSs to enable every US medical school to have at least one PNS on its faculty and to surmount obstacles that currently impede the incorporation of nutrition education into the curricula of medical schools and residency programs. The consortium formulated and refined a paradigm for PNSs, conducted a national role delineation survey to define the scope of the discipline of clinical nutrition, and developed a preliminary curriculum template for training PNSs that can be completed in a minimum of 6 mo. IPNEC and its sponsoring societies are strategically positioned to play an important long-term role in nutrition education for physicians. We intend to continue soliciting broad input, especially from directors of fellowship training programs in nutrition and closely related subspecialties; to develop the core content for fellowships in nutrition and related subspecialties; and to initiate a unified PNS certification examination. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Context: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.Objective: To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.Design: Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.Setting and Participants: Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers.Intervention: Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks.Main Outcome Measures: Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.Results: A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels.Conclusions: Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors. [ABSTRACT FROM AUTHOR]

A significant obstacle to nutrition literacy among physicians is a paucity of Physician Nutrition Specialists (PNSs) on medical school faculties who can effectively advocate for change in medical school and residency curricula and who can serve as role models for incorporating nutrition into patient care. To address these issues, the Intersociety Professional Nutrition Education Consortium developed a paradigm for PNSs that is designed attract more physicians into the field; promulgated educational standards for fellowship training of PNSs; and established a unified mechanism for certifying PNSs, the American Board of Physician Nutrition Specialists (ABPNS). This article details the consensus paradigm and specific training standards and outlines the features and history of the ABPNS. The ABPNS certificate is intended to be the premier comprehensive credential for physicians who wish to identify nutrition as an area of expertise. Certification is equally accessible to physicians with backgrounds in any of the specialties relevant to clinical nutrition. It is hoped that more physicians will identify nutrition as a specialty interest if training opportunities are available in a variety of settings and are merged with their other professional interests. ABPNS invites input and feedback from colleagues around the world. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We previously reported that higher circulating concentrations of folate are independently associated with a lower likelihood of becoming positive for high-risk human papillomaviruses (HR-HPVs) and of having a persistent HR-HPV infection and a greater likelihood of becoming HR-HPV negative (Cancer Res 2004;64:8788-93). In the present study conducted in the same study population, we tested whether circulating folate concentrations modify the risk of cervical intraepithelial neoplasia (CIN) > or =2 associated with specific types of HR-HPV. METHODS: Multiple logistic regression models were used to assess associations (odds ratio with 95% confidence intervals) across HR-HPV, folate, and rigorously reviewed cervical histology of each subject. RESULTS: HPV-16-positive women with low red blood cell folate were significantly more likely to be diagnosed with CIN > or =2 than were HPV-16-negative women with higher red blood cell folate (odds ratio 9, 95% confidence interval 3.3-24.8). CONCLUSION: To our knowledge, this is the first study reporting an independent association of folate with risk of having CIN > or =2 in a population tested extensively for HR-HPV and CIN that also adequately controlled for several other micronutrients and known risk factors for CIN. Our findings suggest that improving the folate status in HR-HPV-infected women may reduce the risk of CIN and thus the risk of cervical cancer. Folate supplementation should be tested as a means of reducing the risk of developing CIN > or =2 in women exposed to HR-HPV, especially HPV-16. [ABSTRACT FROM AUTHOR]

The University of Zambia (UNZA) Mentor Training Program is conducted annually to strengthen the mentorship capacity of postgraduate programs for the health professions. This intensive five-session course trains faculty members in the mentorship of students. Established by senior UNZA leaders and US-based collaborators, this program was designed to address gaps in mentorship identified at the institutional level. Faculty facilitators developed the course curriculum and used a train-the-trainer model to ensure program sustainability. Participants were faculty members who mentor PhD and Master of Medicine students. To assess the program's impact, mentors and their mentees completed questionnaires on the mentor's mentoring competencies at the end of the course and 1 year later. Competency scores were compared longitudinally to quantify potential changes in mentoring behaviors. Mentors and mentees alike noted mentor growth in all competency domains from postcourse to 1 year later, providing evidence of a trend toward improvement in mentorship and that the program may have sustainable and positive effects on mentoring behaviors over time. Salient areas of growth corresponded to emphasized topics and discussions, including addressing diversity, aligning expectations, assessing capacities, motivating mentees, and fostering independence. These findings suggest that mentors internalized this content and transferred it to behavior change. The behavior changes may reveal a larger change in the institutional environment around the mentoring of students. The UNZA Mentor Training Program appears to have sustained impact after a year and should bode well for future benefits to students, faculty, and the institution.

In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center's Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey (response rate, 52.4%). There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally (including demonstrating respectful and ethical behavior) and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs.

Strong cultures of mentorship and research remain underdeveloped at many African universities, threatening future knowledge generation essential for health and development on the continent. To address these challenges, a mentorship program was developed in 2018 at the University of Zambia with an aim to enhance the institutional culture of mentorship and to build institutional capacity through an innovative 'train the trainer' faculty development model. In this study, we documented perceptions of lived experiences related to mentorship culture by following trainers and trainees and their mentees over two years. We analyzed these perceptions to assess changes in institutional attributes regarding mentorship. We identified positive change in institutional culture towards mentorship, and this change appeared sustainable over time. However, a slight decrease in indicators for year two emphasizes the need for a continued culture of learning rather than assuming that one-off training will be sufficient to change culture., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Background: Impaired vascular compliance is common among persons with HIV (PWH) and a risk factor for cardiovascular disease (CVD), though many studies documenting this are from regions with a high prevalence of overweight and obesity. The prevalence and characteristics of impaired vascular compliance among PWH with low body mass index (BMI) is not well described, particularly in sub-Saharan Africa (SSA) where the majority of PWH live, a low BMI is more common, and the burden of CVD is rising., Aim: To assess non-invasive vascular compliance measurements, including augmentation index (AIX), pulse wave velocity (PWV) and pulse waveforms, in underweight, normal weight, and overweight PWH on long-term antiretroviral therapy (ART) in SSA., Methods: A cross-sectional study among PWH on ART at the University Teaching Hospital in Lusaka, Zambia. All participants had been on a regimen of efavirenz, emtricitabine, and tenofovir disoproxil fumarate for five or more years. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and the corresponding augmentation indexes (cfAIX and crAIX), were measured in all participants, in addition to aortic pressure waveforms, classified as type A, B, C and D according to reflected wave timings and amplitude. Multiple linear regression assessed relationships between demographic and clinical factors with vascular measurement endpoints., Results: Ninety one PWH on long-term ART were enrolled; 38 (42%) were underweight (BMI < 18.5 kg/m 2 ), 43 (47%) were normal weight (18.5-24.9 kg/m 2 ) and 10 (11%) were overweight (> 25 kg/m 2 ). Median age was 41, 40 and 40 years, among the three groups, respectively, and the proportion of women increased with BMI level. Overweight participants had a 39% higher cfAIX compared to normal-weight participants, while being underweight was associated with 27% lower cfAIX, after adjusting for age, sex and blood pressure (P = 0.02 and P = 0.01, respectively), but measurements of cfPWV, crPWV and crAIX did not differ., Conclusion: Underweight PWH in SSA had lower cfAIX measurements compared to normal weight individuals, indicating less arterial stiffness. However, similar cfPWV, crPWV and crAIX values among the underweight and overweight PWH suggest a low BMI may not confer substantial protection against impaired vascular compliance as a contributor to CVD risk among individuals on ART., (© 2023. The Author(s).)

Objective: The goal of this study was to evaluate the prevalence of orofacial clefts (OFCs) in Tennessee over the span of 2000-2017, and evaluate the effects of race/ethnicity, sex, maternal/paternal age and socioeconomic status on the prevalence., Methods: Records of all live births and demographics of newborns in Tennessee from 2000 to 2017 were requested from the Tennessee Department of Health to calculate the prevalence of OFCs. Data from United States Census was also obtained. Data provided were deidentified., Results: Tennessee showed a significant decrease in prevalence rates of cleft lip, with and without cleft palate (CL ± P), when comparing the time periods of 2000-2007 to 2008-2017. A significant positive correlation was found with CL ± P prevalence rates in regions with higher Caucasian populations and a negative correlation in regions with higher African American populations. The CP prevalence rates showed a negative correlation with increased median household income., Conclusion: To our knowledge, this is the first study to show a significant negative correlation with median household income and CP prevalence rates. Our study showing an increase in prevalence rates of OFCs with decreased socioeconomic status indicates that the areas of Tennessee with the lowest median household income averages would likely benefit from understanding other possible modifiable factors that are driving this correlation., (Copyright © 2022. Published by Elsevier B.V.)

Background: Hypertension is common in people living with HIV (PLWH) on antiretroviral therapy (ART). In the general population and in experimental animal models, the incidence of hypertension is greater in males than in females, especially during the premenopausal period. However, it is not known whether there are sex differences in hypertension associated with HIV and ART, and the factors contributing to incident hypertension among PLWH have not been well characterized. In this study, we aimed to determine the time course, sex differences and factors associated with incident hypertension in PLWH initiating ART., Methods and Results: We conducted a retrospective study in which we used programmatic data from the ART registry to identify sex differences in the determinants of incident hypertension among PLWH initiating the ART regimen from Livingstone University Teaching Hospital in Zambia and followed for 8 years. Males developed hypertension earlier, 2 years after initiating ART, compared to 6 years in females. In multivariable analysis, increasing age, baseline systolic blood pressure and baseline mean arterial pressure (MAP) were associated with increased risk for developing incident hypertension. Also, participants who switched to the integrase strand transfer inhibitor, dolutegravir (DTG) or the protease inhibitor, lopinavir boosted with ritonavir were 2 and 3 times more likely to develop hypertension when compared to those on non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, these relationships were abrogated by sex, as self-reported male sex was the major contributor in predicting incident hypertension. While none of the factors remained significantly associated with incident hypertension upon multivariate analysis among females, body mass index (BMI), and use of protease inhibitors remained strongly associated with hypertension among males., Conclusion: Our results indicate that the use of protease inhibitors and BMI are important predictors of incident hypertension among males. Thus, blood pressure and BMI should be closely monitored, particularly in males living with HIV on protease inhibitors. In addition, identifying specific factors that protect females from developing hypertension early is important but remains to be determined., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Masenga, Povia, Mutengo, Hamooya, Nzala, Heimburger, Munsaka, Elijovich, Patel and Kirabo.)

Background: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor effect of salt is viewed as a chronic effect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this effect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments., Methods: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2 g of sodium chloride; their BP was monitored for 120 minutes in intervals of 10 minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data., Results: Median age was 30 years (interquartile range, 22-46 years) and 52% were female patients. An increase of ≥10 mmHg in mean arterial pressure (MAP), considered a clinically significant IPROS, was present in 62% of participants. Systolic BP 30 minutes after the salt load was a significant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting., Conclusions: We confirm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30 minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30 minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral salt-loads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our findings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP., (© 2022. The Author(s).)

Background: Peripartum cardiomyopathy (PPCM) disproportionately affects women of African descent, however knowledge about this disease in African countries is limited., Objectives: To describe the phenotype of women with PPCM seen at a referral hospital in Zambia and examine outcomes at 6 months., Methods: A prospective observational study describing characteristics and 6-month outcomes was performed at the University Teaching Hospital Echocardiography Lab in Lusaka, Zambia., Results: We enrolled 45 participants with PPCM and 38 were seen at 6-month follow up; 3 (7 %) died and 4 (9 %) were lost to follow up. Mean age was 32.9 years (SD:7.0); mean BMI was 25.3 kg/m 2 (SD:4.1), mean parity was 3.4 (SD:2.2) children and twin pregnancies occurred in 4 (9 %). Median time from symptom onset to diagnosis was 60 days (IQR: 1-280). 20 (44 %) reported gestational hypertension and 10 (22 %) reported preeclampsia. Baseline median left ventricular ejection fraction (LVEF) was 36 % (IQR: 11-45), median left ventricular end-diastolic volume (LVEDV) was 150 mL (IQR: 58-229) and 79 % described New York Heart Association (NYHA) functional class IV symptoms. Median LVEF after 6 months was 49 % (IQR: 23-68; p  < 0.001) and median LVEDV was 121 mL (IQR: 66-200; p  < 0.001). At 6-month follow up 45 % had LVEF ≥ 50 %, 42 % had LVEDV ≤ 106 mL and 1 (3 %) had NYHA functional class IV symptoms., Conclusions: Hypertension was prevalent in this cohort. Overall mortality rate was low and clinically significant improvements in cardiac parameters were seen in over 40%. Further research is needed to identify and mitigate gaps in diagnosis and management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objectives: Stunting, the most common form of childhood undernutrition, is associated with environmental enteropathy (EE). Enteric infections are believed to play a role in the pathophysiology of EE and stunting though the exact mechanism remains undetermined. The FUT2 (secretor) and FUT3 (Lewis) genes have been shown to be associated with some symptomatic enteric infections in both children and adults. These genes are responsible for the presence of histo-blood group antigens (HBGAs) in various secretions and epithelial surfaces.We evaluated whether the secretor and Lewis status influences asymptomatic enteric infections and thus EE severity on duodenal biopsies of stunted children., Methods: In this case-control study, we used saliva samples to determine the secretor and Lewis status of stunted children (cases, n = 113) enrolled in a nutritional rehabilitation program and from their well-nourished counterparts (controls, n = 42). Where available, saliva was also collected from the mothers. Baseline stool samples were used to detect asymptomatic enteropathogen carriage. Duodenal biopsies were collected from a subgroup of stunted children (n = 77) who had an upper gastrointestinal endoscopy done as part of the evaluation process for their non-response to nutritional therapy., Results: The proportion of secretors was similar between the cases and the controls (82% vs 81%, P = 0.81). The stunted children had significantly higher rates of carrying multiple enteropathogens, but this was not associated with their secretor status nor that of their mothers. The secretor status was also not associated with mucosal morphometry of duodenal biopsies., Conclusion: This case-control analysis in Zambian children does not support the hypothesis that fucosylation status determines asymptomatic enteropathogen carriage in stunting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Little is known about specific bacterial characteristics of Helicobacter pylori ( H. pylori ) infection influencing gastric carcinogenesis in Zambia. The aim of this study was to evaluate the associations between pre-selected H. pylori antibodies with gastric cancer, premalignant lesions and active gastritis., Methods: This was cross-sectional study with multiple comparisons of patients with gastric cancer (GC), gastric premalignant (GP) lesions and active or chronic gastritis. A fluorescent bead-based antibody multiplex serology assay was used to quantify antibodies to thirteen immunogenic H. pylori antigens. Logistic regression models were used to examine the associations., Results: Included were 295 patients with: 59 GC, 27 GP lesions, 48 active and 161 chronic gastritis. Overall, 257/295 (87%) were H. pylori positive. H. pylori seropositivity was not associated with sex, age, body mass index, socio-economic status, HIV infection, alcohol consumption or cigarette smoking (p-values all above 0.05). When compared to the patients with chronic gastritis, the presence of catalase and cinnamyl alcohol dehydrogenase (Cad) antibodies was positively associated with GP lesions (OR 3.53; 95% CI 1.52-8.17 and OR 2.47; 95% CI 1.08-5.67 respectively). However, seropositivity to Cad antibodies was significantly lower in GC patients (OR 0.28; 95% CI 0.09-0.83). Compared to chronic, active gastritis was significantly associated with (p<0.05) H. pylori sero-positivity (OR 9.46; 95% CI 1.25-71.52) and specific antibodies including cytotoxin-associated gene A, vacuolating cytotoxin A, Helicobacter cysteine -rich protein C, hypothetical protein HP0305 and outer membrane protein HP1564., Conclusions: Among Zambian patients seen at a single center, antibodies to H. pylori (CagA, VacA, Omp, HcpC, HP0305 and HpaA) were associated with active gastritis., Competing Interests: Authors have no conflict of interest to declare, (© 2022 The College of Medicine and the Medical Association of Malawi.)

Background: Schistosoma mansoni is hyperendemic in many rural areas of Zambia where up to 77% of people are positive for infection via serologic evaluation. Zambia also has a high prevalence of HIV infection. Individually, S. mansoni and HIV infection impair gastrointestinal barrier integrity and induce inflammation, but the effects of coinfection are not well understood. We set out to test the hypothesis that HIV would exacerbate intestinal barrier failure in patients with S. mansoni infection., Methods: Adults attending medical outpatient clinics in Kaoma, Western Province, Zambia, were enrolled in a case-control study to determine the relative contributions of schistosomiasis and HIV to microbial translocation (measured as soluble CD14 [sCD14] and lipopolysaccharide binding protein [LBP]) and inflammation (measured as CRP)., Results: Among 152 adults evaluated, 74 (49%) were HIV-seropositive, 45 (29%) were shedding schistosome ova (Kato-Katz), 120 (81%) were seropositive for schistosome antibodies (i.e. prior or current infection, with or without egg shedding) and 16 (11%) were HIV/schistosome coinfected (defined by Kato-Katz). HIV infection was associated with higher circulating sCD14 concentrations (p=0.003 by Kruskal-Wallis test), but schistosomiasis was not. HIV infection was associated with greater exposure to schistosomes assessed serologically (OR=2.48, 95% CI 1.05 to 5.86; p=0.03), but reduced likelihood of egg shedding (OR 0.47, 95% CI 0.21 to 1.01; p=0.03)., Conclusions: There was no evidence for a compounding or synergistic effect of coinfection on microbial translocation that appeared to be correlated with HIV infection. Further studies are needed to understand how the increase in LBP secondary to HIV infection may decrease schistosome egg excretion in coinfected individuals., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Training the next generation of global health researchers is vital for sustainable research partnerships and global health equity. The Fogarty International Center (National Institutes of Health) supports postdoctoral fellows and professional/graduate students in long-term, hands-on mentored research in low- and middle-income countries (LMICs). We surveyed 627 alumni (58% from the United States, 42% from LMICs) from three sequential Fogarty-sponsored global health research training programs (response rate: N = 257, 41%). Publications in the Index Medicus were used to ascertain scholarly output. Most alumni (63%) reported remaining engaged in LMICs and/or worked in academic/research careers (70%). Since completing their Fogarty fellowship, 144 alumni (56%) had received 438 new grants as principal investigator (PI), co-/multi-PI, or site PI. The 257 responding alumni had 5,318 publications during and since their Fogarty fellowships; 2,083 (39%) listed the Fogarty trainee as the first or senior author. These global health training programs highlight the value of LMIC research experience in nurturing the global health research workforce.

Background: Cardiovascular disease (CVD) prevalence is rising among persons with HIV (PLWH) in sub-Saharan Africa. Oxidative stress and endothelial activation, resulting in reduced vascular compliance, are contributors to CVD risk. However, there is a paucity of vascular health data in this population., Objectives: To assess the relationships of oxidative stress and endothelial activation with vascular stiffness among PLWH., Method: Fifty-four PLWH on antiretroviral therapy > 5 years and 57 HIV-negative controls, all aged 18-45 years, were enrolled from the University Teaching Hospital, Lusaka, Zambia. Oxidative stress was measured by nitrotyrosine, a peroxynitrite biomarker, and endothelial activation by soluble intercellular adhesion molecule-1 (sICAM-1) plasma levels. Vascular compliance was measured using carotid-radial pulse wave velocity (crPWV) and arterial stiffness index (crASI)., Results: PLWH had higher sICAM-1 levels (median 345 ng/mL) compared to controls (275 ng/mL, p < 0.01), as well as higher nitrotyrosine levels (297 versus 182 nM; p = 0.02). Median crPWV was similar between the groups, but PLWH had higher crASI (2.4 versus 2.2 cm/ms; p < 0.05). After adjusting for age, fat mass, and blood pressure, the estimated effect of a one unit increase in nitrotyrosine on crPWV were twofold higher in the PLWH, but neither reached significance. In a model pooling all participants, there were significant differences in the relationship of nitrotyrosine with crPWV and crASI by HIV status., Conclusion: PLWH in sub-Saharan Africa had significantly greater oxidative stress and endothelial activation compared to HIV-negative individuals. These factors may contribute to increased arterial stiffness and higher CVD prevalence in this population., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)

Persons living with HIV (PLWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) risk suffering TDF-associated nephrotoxicity (TDFAN). TDFAN can result in short- and long-term morbidity, including permanent loss of kidney function, chronic kidney disease (CKD), and end-stage kidney disease (ESKD) requiring dialysis. Currently, there is no model to predict this risk or discern which patients to initiate TDF-based therapy. Consequently, some patients suffer TDFAN within the first few months of initiating therapy before switching to another suitable antiretroviral or a lower dose of TDF. In a prospective observational cohort study of adult Zambian PLWH, we modelled the risk for TDFAN before initiating therapy to identify individuals at high risk for experiencing AKI after initiating TDF-based therapy. We enrolled 205 HIV-positive, ART-naïve adults initiating TDF-based therapy followed for a median of 3.4 months for TDFAN at the Adult Infectious Disease Research Centre (AIDC) in Lusaka, Zambia. We defined TDFAN as meeting any of these acute kidney disease (AKD) criteria: 1) An episode of estimated glomerular filtration rate (eGFR)< 60ml/ min/1.73m2 within 3 months, 2) reduced eGFR by> 35% within 3 months or 3) increased serum creatinine by> 50% within 3 months. A total of 45 participants (22%) developed acute kidney disease (AKD) after TDF-based therapy. The development of AKD within the first 3 months of commencing TDF-based therapy was associated with an increase in baseline serum creatinine, age, baseline eGFR and female sex. We concluded that baseline characteristics and baseline renal function biomarkers predicted the risk for AKD within the first 3-months of TDF-based therapy., Competing Interests: NO authors have competing interests. EDS reports consulting for Akebia, Inc. 4/19, honorarium for an invited educational talk at the Annual Da Vita Physician Leadership Conference 2/19, royalties as an author for UpToDate, and serving on the editorial board for the Clinical Journal of the American Society of Nephrology. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: Cancer occurrence is increasing in Africa, although research has lagged. The objective of this review was to analyze cancer research outputs from Africa, with a particular focus on Zambia., Methods: We searched PubMed for published cancer-related articles from African countries. All articles reporting on cancer in Africa were considered. We conducted analyses to explore correlations between cancer research output and total population, gross domestic product, and new cancer cases recorded in 2020. For Zambia articles, we also analyzed cancer types and time trends., Results: A total of 48,487 cancer-related publications from Africa were identified, with nearly half coming from Egypt (13,372; 28%) and South Africa (9,393; 19%). Cancer research output correlated significantly with country population (Spearman's correlation coefficient 0.74; P < .001) and the number of new cancer cases recorded in 2020 (Spearman's correlation coefficient 0.77; P < .001). Standardized by population size, Western Sahara (0.576), Seychelles (0.244), Tunisia (0.239), South Africa (0.158), and Egypt (0.131) had the highest overall output per 1,000 population. A total of 244 publications were from Zambia; the most studied cancers were cervical (25%), Kaposi sarcoma (24%), and breast (10%). Although an increase in cancer research output from Zambia was noted, only 33% of publications were first or last authored by Zambians. The major limitation of this review is that the evaluation was based on a single electronic database, PubMed., Conclusion: Cancer research output from Africa is very low, with many of the publications concentrated in a few countries. There is an urgent need to invest in both human resources and infrastructure to increase cancer research output from African countries, particularly in less populous countries.

Abstract: Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia.We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression.Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9-29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04-1.11), female sex (OR 3.02; 95% CI 1.55-5.91), VF (OR 1.98; 95% CI 1.01-3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05-4.20), hip-circumference (OR 1.03; 95% CI 1.01-1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44-3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01-1.29), and fasting insulin (OR 1.02; 95% CI 1.01-1.04) were significantly associated with MetS.Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To identify risk factors for delirium among hospitalized patients in Zambia., Methods: We conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. We report associations of exposures including sociodemographic and clinical factors with delirium over the first three days of hospital admission, assessed using a modified Brief Confusion Assessment Method (bCAM)., Findings: 749 patients were included for analysis (mean age, 42.9 years; 64.8% men; 47.3% with HIV). In individual regression analyses of potential delirium risk factors adjusted for age, sex and education, factors significantly associated with delirium included being divorced/widowed (OR 1.64, 95% CI 1.09-2.47), lowest tercile income (OR 1.58, 95% CI 1.04-2.40), informal employment (OR 1.97, 95% CI 1.25-3.15), untreated HIV infection (OR 2.18, 95% CI 1.21-4.06), unknown HIV status (OR 2.90, 95% CI 1.47-6.16), history of stroke (OR 2.70, 95% CI 1.15-7.19), depression/anxiety (OR 1.52, 95% CI 1.08-2.14), alcohol overuse (OR 1.96, 95% CI 1.39-2.79), sedatives ordered on admission (OR 3.77, 95% CI 1.70-9.54), severity of illness (OR 2.00, 95% CI 1.82-2.22), neurological (OR 7.66, 95% CI 4.90-12.24) and pulmonary-system admission diagnoses (OR 1.91, 95% CI 1.29-2.85), and sepsis (OR 2.44, 95% CI 1.51-4.08). After combining significant risk factors into a multivariable regression analysis, severity of illness, history of stroke, and being divorced/widowed remained predictive of delirium (p<0.05)., Conclusion: Among hospitalized adults at a national referral hospital in Zambia, severity of illness, history of stroke, and being divorced/widowed were independently predictive of delirium. Extension of this work will inform future efforts to prevent, detect, and manage delirium in low- and middle-income countries., Competing Interests: Dr. Ely has received research grants and/or honoraria from Hospira, Orion, Pfizer and Abbott. Dr. Heimburger has received honoraria from Danone Institute North America. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose of Review: Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among persons with HIV (PWH) initiating antiretroviral therapy (ART) in the region. In this review, we discuss the intersection of HIV infection and undernutrition, health outcomes among undernourished PWH starting ART, and the demonstrated and potential benefits of therapeutic interventions such as micro/macronutrient supplementation and pharmacological agents., Recent Findings: A low body mass index (BMI), used as a general indicator of poor nutrition in most studies, is associated with impaired immune recovery and increased mortality in the early ART period. The increased risk of mortality is multifactorial, and contributors include undernutrition-related immune system dysfunction, increased susceptibility to opportunistic infections, and metabolic and cardiovascular dysregulation. Clinical trials of micro/macronutrient supplementary feeding, appetite stimulants (hormones and anabolic agents), and recombinant adipokines have shown a benefit for weight gain and metabolic health, but there are few data on mortality or immune recovery. A substantial proportion of PWH in SSA are undernourished, and undernutrition contributes to an increased risk of mortality and other adverse health outcomes. To date, there have been few prospective trials of nutritional supplementation and/or pharmacologic therapy among undernourished PWH in SSA, though findings from other settings suggest a potential benefit in this population.

Background: Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA)., Objective: To determine the association between immune activation and arterial stiffness in lean PLWH in SSA., Method: Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) >5 years and 26 HIV-negative adults, all with BMI < 25 kg/m 2 and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status., Results: Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively; p < 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV; p = 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV; p = 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%; p < 0.05) in comparison to their HIV controls., Conclusion: Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)

Background: With the introduction of effective antiretroviral therapy (ART), people living with HIV (PLWH) are surviving longer and are at risk for developing metabolic abnormalities that contribute to cardiovascular disease (CVD). In Sub-Saharan Africa (SSA), there is a paucity of epidemiological data on lipid profiles among young adults receiving ART. This study aimed to estimate the prevalence of low high-density lipoprotein cholesterol (HDL-c), a cardioprotective lipid class, and whether it differed by age among adults on ART in Livingstone, Zambia., Methods: From April to December 2019, we conducted a cross-sectional study of 597 PLWH [n = 58 aged 18-24 years (young adults); n = 539 aged ≥25 years (adults)] on ART for ≥6 months. Data collected included demographic and lifestyle information, anthropometrics, viral load (VL), CD4 count, blood pressure, lipid profiles and fasting/random blood glucose. Clinical measures were defined as: low HDL-c [<1.0 mmol/L for men, <1.3 for women], increased waist circumference (WC) [≥94 cm for men, ≥80 cm for women], high triglycerides (TG) [≥1.7 mmol/l], and virological failure (VF) [VL ≥1000 copies/μl]. We used logistic regression to examine the association between age and low HDL-c after adjusting for multiple variables., Results: Among the young adults, 60% (35/58) were women, median (25th, 75th percentile) age 21 years (18, 23), and median time on ART 116 months (60, 144). Among adults, 63% (342/539) were women, median age 46 years (40, 53) and median time on ART 108 months (60, 144). Young adults had a lower CD4 count compared to adults (median, 492 vs. 568 cells/μL, p = 0.010) and higher prevalence of VF (29% vs. 17%, p = 0.016). In young adults, prevalence of low HDL-c was significantly higher than in adults (63 vs. 38%, p<0.001). A high proportion of young adults (75%) and adults (58%) with low HDL-c were on dolutegravir (DTG)-based ART regimens. After adjusting for sex, duration on ART, WC, body mass index, ART regimen, VF, CD4 count, low density lipoprotein cholesterol, blood pressure and smoking, young adults were significantly more likely than adults to have low HDL-c (odds ratio 2.93; 95% confidence interval 1.46-5.86)., Conclusion: Low HDL-c is highly prevalent among young adult with HIV in SSA independent of other risk factors for metabolic derangements. Lipid abnormalities among young PLWH may contribute to the early development of cardiovascular diseases in this population. This highlights the need to consider low HDL-c in the quest to reduce CVD risk among young adults on ART in SSA., Competing Interests: The authors have declared that no competing interests exist.

Objective: To study the epidemiology and outcomes of delirium among hospitalized patients in Zambia., Methods: We conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. The primary exposure was delirium duration over the initial 3 days of hospitalization, assessed daily using the Brief Confusion Assessment Method. The primary outcome was 6-month mortality. Secondary outcomes included 6-month disability, evaluated using the World Health Organization Disability Assessment Schedule 2.0., Findings: 711 adults were included (median age, 39 years; 461 men; 459 medical, 252 surgical; 323 with HIV). Delirium prevalence was 48.5% (95% CI, 44.8%-52.3%). 6-month mortality was higher for delirious participants (44.6% [39.3%-50.1%]) versus non-delirious participants (20.0% [15.4%-25.2%]; P < .001). After adjusting for covariates, delirium duration independently predicted 6-month mortality and disability with a significant dose-response association between number of days with delirium and odds of worse clinical outcome. Compared to no delirium, presence of 1, 2 or 3 days of delirium resulted in odds ratios for 6-month mortality of 1.43 (95% CI, 0.73-2.80), 2.20 (1.07-4.51), and 3.92 (2.24-6.87), respectively (P < .001). Odds of 6-month disability were 1.20 (0.70-2.05), 1.73 (0.95-3.17), and 2.80 (1.78-4.43), respectively (P < .001)., Conclusion: Among hospitalized medical and surgical patients in Zambia, delirium prevalence was high and delirium duration independently predicted mortality and disability at 6 months. This work lays the foundation for prevention, detection, and management of delirium in low-income countries. Long-term follow up of outcomes of critical illness in resource-limited settings appears feasible using the WHO Disability Assessment Schedule., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Ely has received research grants and/or honoraria from Hospira, Orion, Pfizer and Abbott. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population., Methods: We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10-15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor., Results: The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001)., Conclusions: The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.

Background: Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while in underweight persons, oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo ). The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15-20 hours post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial dependent and independent vascular relaxation after pre-constriction of aortic rings with phenylephrine., Results: Nitrotyrosine levels in saline-treated rats were similar among the weight-groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, R max (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower R max in the underweight (106%) compared to the normal weight (112%). Overweight rats had a significant decrease in R max (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower R max accompanied an increase in peroxynitrite after acetylcholine challenge in all weight-groups., Conclusions: Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction., Competing Interests: Competing interests The authors declare that they have no competing interests.

Introduction: Hemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders., Methods: Blood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT)., Results: The mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM., Conclusions: HbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency., Competing Interests: All authors declare that they have no competing interests.

Purpose of Review: With the advent of highly active antiretroviral therapy (ART), the life span of persons with HIV (PWH) has been nearly normalized. With aging, prevalence of the metabolic syndrome (MetS), including hypertension, has increased in the HIV population and exceeds that in the general population in some studies. This is due to a combination of traditional risk factors in addition to the effects attributable to the virus and ART. We review recent findings on the mechanisms contributing to MetS and hypertension in PWH, particularly those specific to the viral infection and to ART., Recent Findings: Activation of the renin-angiotensin-aldosterone system (RAAS) and chronic immune activation contribute to the development of MetS and hypertension in PWH. HIV proteins and some ART agents alter adipocyte health contributing to dyslipidemias, weight gain, and insulin resistance. HIV infection also contributes to hypertension by direct effects on the RAAS that intertwine with inflammation by the RAAS also contributing to T cell activation. Recent data suggest that in addition to current ART, therapeutic targeting of the MetS and hypertension in PWH, by interfering with the RAAS, treating insulin resistance directly or by use of immunomodulators that dampen inflammation, may be critical for preventing or treating these risk factors and to improve overall cardiovascular complications in the HIV-infected aging population.

The human immunodeficiency virus (HIV) pandemic heavily affects sub-Saharan Africa. It is associated with persistently active Epstein-Barr virus (EBV) infection. To determine if this translates into increased frequency of EBV-associated gastric cancer (EBVaGC), we evaluated molecular profiles of gastric cancer (GC) in Zambia. Patients with GC or premalignant gastric lesions were enrolled in Lusaka, Zambia. We used patients without any of these lesions as a control group. Chromogenic in situ hybridization (CISH) on tumor tissue was used to identify EBVaGC. To identify the microsatellite unstable subtype, immunofluorescence staining for MutL homolog 1 (MLH1) was used. Exposure to EBV and HIV was assessed serologically. We enrolled 369 patients (median age 52 years [IQR 41-65]; 198 (54%) female). Of these, 72 (20%) had GC and 35 (9%) had gastric premalignant lesions (PL). CISH identified EBVaGC in 5/44 (11%) of those with adequate tissue, while MLH1 loss was identified in 29/45 (64%). Both GC and PL were associated with the highest titers of antibodies to Early antigen-diffuse (OR 2.5, 95% CI 1.0-6.1, P = .048 and OR 3.9, 95% CI 1.1-12.9, P = .03, respectively) at high concentrations. Human immunodeficiency virus infection was associated with a range of antibodies to EBV, but not with any cancer subtype. Despite the association of HIV with persistent EBV, the proportion of EBVaGC in Zambia is similar to populations with a low prevalence of HIV infection. The proportion of microsatellite unstable tumors may be higher than other populations., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania., Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes., Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT., Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma. More than 220 million people worldwide were estimated to have active schistosomiasis in 2017, 90% of whom live on the African continent, but only 102 million were reported to have received treatment. Africa is also disproportionately burdened by HIV, with an estimated 26 million people living with HIV in 2017. Given these overlapping epidemics, we conducted a systematic review to ascertain the contribution of schistosomes to HIV acquisition risk, the contribution of HIV to schistosome acquisition, the impact of HIV on schistosomiasis-related morbidity, the impact of schistosomes on HIV disease progression and immune response, the impact of HIV on the efficacy of praziquantel treatment, and the impact of HIV on egg shedding. We reviewed studies of people living in sub-Saharan Africa coinfected with HIV and Schistosoma spp. between January 1996 and July 2018. We found that 1) infection with Schistosoma haematobium increases the risk of HIV acquisition, 2) there is currently a lack of data on whether HIV infection increases the risk of Schistosoma acquisition, 3a) HIV coinfection was not an accelerating factor for adverse Schistosoma outcomes, 3b) schistosomiasis may be an important contributor to immune activation in HIV coinfected people, 4) praziquantel use in coinfected people may improve immune reconstitution on antiretroviral therapy for HIV, and 5) there is evidence that HIV infection reduces egg excretion in individuals infected with Schistosoma mansoni .

Purpose: We investigated the association between gastric cancer and environmental and dietary exposures. In addition, we explored probable mechanistic pathways for the influence of biomass smoke on gastric carcinogenesis., Patients and Methods: The study was conducted in Lusaka, Zambia. Questionnaires were used to collect data on risk factors, whereas enzyme-linked immunosorbent assays and high-performance liquid chromatography were used to measure biologic exposures. Study data were analyzed using contingency tables and logistic regression., Results: We enrolled 72 patients with gastric adenocarcinoma and 244 controls. Gastric cancer was positively associated with rural residence (odds ratio [OR], 2.9; 95% CI, 1.5 to 5.3), poverty (OR, 4.2; 95% CI, 1.9 to 9.1), and daily consumption of processed meat (OR, 6.4; 95% CI, 1.3 to 32) and negatively associated with consumption of green vegetables (OR, 0.2; 95% CI, 0.1 to 0.5). Gastric cancer was also associated with biomass smoke exposure (OR, 3.5; 95% CI, 1.9 to 6.2; P < .0001), an association that was stronger for intestinal-type cancers (OR, 3.6; 95% CI, 1.5 to 9.1; P = .003). Exposure to biomass smoke in controls was associated with higher urinary levels of 8-isoprostane ( P < .0001), 8-hydroxydeoxyguanosine ( P = .029), and 1-hydroxypyrene ( P = .041). Gastric cancer was not associated with biochemical measures of current exposure to aflatoxins or ochratoxins., Conclusion: In Zambia, exposure to biomass smoke, daily consumption of processed meat, and poverty are risk factors for gastric cancer, whereas daily consumption of green vegetables is protective against gastric cancer. Exposure to biomass smoke was associated with evidence of oxidative stress and DNA damage, suggesting mechanistic plausibility for the observed association, and the association was restricted to intestinal-type gastric cancer.