Changes in access to viral load testing, incidence rates of viral load suppression and rebound following the introduction of the 'universal test and treat' guidelines in Cameroon: A retrospective follow-up analysis.

Cameroon adopted and started implementing in 2016, the 'universal test and treat' (UTT) guidelines to fast-track progress towards the 95-95-95 ambitious targets to end the HIV epidemic. Achieving the third 95 (viral load suppression) is the most desirable target in HIV care. We aimed to evaluate the effectiveness of this novel approach on access to viral load testing (VLT), viral suppression (VLS), and viral load rebound (VLR). A retrospective cohort study was conducted at The Nkongsamba Regional Hospital to compare VLT outcomes between the pre-UTT (2002 to 2015) and the post-UTT (2016 to 2020) periods. We used a data extraction form to collect routine data on adult patients living with HIV. We measured uptake levels of the first and serial VLT and compared the incidence rates of VLS (VL<1000 copies/ml) and viral load rebound (VLR) before and after introducing the UTT approach using Kaplan Meier plots and log-rank tests. Cox regression was used to screen for factors independently associated with VLS and VLR events between the guideline periods. Access to initial VLT increased significantly from 6.11% to 25.56% at 6 months and from 12.00% to 73.75% at 12 months before and after introducing the UTT guidelines respectively. After a total observation time at risk of 17001.63 person-months, the UTT group achieved an incidence rate of 90.36 VLS per 1000 person-months, four-fold higher than the 21.71 VLS per 1000 person-months observed in the pre-UTT group (p<0.0001). After adjusting for confounding, the VLS rate was about 6-fold higher in the UTT group than in the pre-UTT group (adjusted Hazard Rate (aHR) = 5.81 (95% confidence interval (95%CI): 4.43-7.60). The incidence of VLR increased from 12.60 (95%CI: 9.50-16.72) to 19.11 (95%CI: 14.22-25.67) per 1000 person-months before and after the introduction of UTT guidelines respectively. After adjusting, VLR was more than twice as high in the UTT group than in the pre-UTT group (aHR = 2.32, 95%CI: 1.30-4.13). Increased access to initial VLT and higher rates of VLS have been observed but there are concerns that the suppressed viral load may not be durable since the introduction of the UTT policy in this setting.

The declining trend in HIV prevalence from population-based surveys in Cameroon between 2004 and 2018: myth or reality in the universal test and treat era?

BACKGROUND: HIV remains an epidemic of major public health importance in Cameroon but a decline in HIV prevalence has been observed according to population-based surveys conducted in 2004, 2011 and 2018. We sought to review current evidence for declining HIV prevalence despite increasing survival owing to 'universal test and treat' and to explore the reason for the decrease, particularly the role of behavioural change. METHODS: We conducted a secondary analysis using HIV prevalence, behavioural and social determinants data of the Demographic and Health Survey Program databases. Trend lines were fitted to data that were available for a minimum of three points in time during the 1991-2018 period. Regression coefficients associated p-values and 95% confidence intervals were obtained using Microsoft Excel software. RESULTS: Overall adult HIV prevalence decreased significantly from 5.4% (95%CI: 4.8-6.0) in 2004 to 4.3% (95%CI: 3.8-4.8) in 2011 and further down to 2.7% (95%CI: 2.3-3.1) in 2018 at a rate of about 1.4% every septennium (ß = -1.4, R² = 0.98, p = 0.03). Yet, the number of persons surviving with HIV increased from about 0.05 million in 1991 to 0.5 million in 2018 corresponding to an increase in access to antiretroviral therapy from less than 10% to universal coverage of 80% respectively. Concurrent reductions in risky sexual behaviours were observed: a delayed sexual debut by one year, decreased sexual violence by 7%, decreased polygamous unions by 16%, decreased multiple sexual partners by 15.3% and increased condom use by 26.3%. CONCLUSION: The observed decline in HIV prevalence is statistically valid and reflects the observed decline in risky sexual behaviour that need to be sustained by the National HIV programme. Though universal access to ART has increased the number of persons surviving with HIV, this has not led to an increased prevalence of HIV in a setting with a rising population.

The effect of the Universal Test and Treat policy uptake on CD4 count testing and incidence of opportunistic infections among people living with HIV infection in Cameroon: a retrospective analysis of routine data.

Background: Cameroon adopted and started implementing in 2016, the 'universal test and treat' (UTT) guidelines to fast-track progress towards the 95-95-95 ambitious targets to end the HIV epidemic. UTT has shown inconsistent results elsewhere and has not yet been assessed in Cameroon. We aimed to evaluate the effectiveness of this novel approach on the quality of care and health outcomes of people living with HIV (PLHIV). Methods: A retrospective cohort design was conducted at The Nkongsamba Regional Hospital, using routine clinical service delivery data to measure uptake levels of UTT and CD4 testing, and to compare the incidence of opportunistic infections (OI) between PLHIV initiated on ART based on the "Universal Test and Treat" strategy and those initiated on ART based on the standard deferred approach between 2002 and 2020. Kaplan Meier plots and log-rank tests were used to compare OI events between the pre-UTT and post-UTT eras. The Cox regression model was used to screen for factors independently associated with the risk of acquisition of OI. Results: The uptake of UTT ranged from 39.1% to 92.8% while baseline CD4 count testing reduced drastically from 89.4% to 0.4% between 2016 to 2020 respectively. The median delay in ART initiation declined significantly from 21 days (IQR: 9 - 113) in the pre-UTT era to the same day of diagnosis (IQR: 0 - 2) in the UTT era (p < 0.001). The incidence of all OI events reported was over five times higher during the UTT era than in the pre-UTT era [aHR = 5.55 (95% CI: 3.18 - 9.69), p < 0.001]. Conclusion: The UTT policy has been effectively rolled out and has contributed to improved access to rapid and immediate ART initiation, but a higher incidence of OIs was observed with a rollback of baseline CD4 testing. We advocate for a return to routine baseline CD4 measurement to identify PLHIV who should benefit from interventions to prevent OIs for optimal outcomes under the UTT approach.

The case series of functional adrenal tumors: Experience of two tertiary hospitals in Yaoundé, Cameroon.

INTRODUCTION: Adrenal tumors are often found incidentally during abdominal imaging. Functioning adrenal tumors are less frequent than these incidentalomas discovered unexpectedly. We report treatment outcomes (major complications) of 7 cases of symptomatic adrenal masses from 2009 to 2019. PRESENTATION OF THE CASES: Seven cases of functioning adrenal tumors: four adenomas presenting with Cushing's syndrome, two adrenal carcinomas, and one pheochromocytoma are described. The preoperative diagnoses were made through clinical manifestations, an increase in urinary free cortisol with normal ACTH, elevated metanephrine and enlarged masses on CT. The diagnoses were established on histopathology of adrenalectomy specimens. Adrenal insufficiency in two patients following surgery was corrected with corticoid replacement therapy. One patient died of hypovolemia the day of surgery and another from anaphylactic shock (allergy) late in the post-operative period. DISCUSSION: Pre, intra and post-operative complications from vascular instability often complicate surgery in functioning adrenal tumors. Adrenal adenomas manifest as Cushing's syndrome in 10-15 % of patients. They are the most common adrenal tumor although the diagnosis is most often coincidental to abdominal imaging. The incidence of adrenal adenoma increases with age, up to 7 % in the seventh decade. Laparoscopic adrenalectomy, which was not available in our hospitals then, is standard treatment for most tumors. It is alleged to have better outcomes in trained and tested hands. CONCLUSION: Surgery of functioning adrenal tumors demands close collaboration of multiple clinical disciplines to manage vascular instability and adrenal insufficiency, especially in resource strapped communities.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes.

AIM: Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. METHODS: In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. RESULTS: The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=-0.085, P=0.38). CONCLUSION: Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier.

Influence of migration on characteristics of type 2 diabetes in sub-Saharan Africans.

AIM: This study compared the clinical and biochemical characteristics and microvascular complications found in three groups of type 2 diabetes (T2D) patients: Africans living in Africa; African immigrants living in France; and Caucasians living in France. METHODS: Diagnosed T2D Africans living in Cameroon (n=100) were compared with 98 African migrants diagnosed with T2D after having moved to France, and a group of 199 T2D Caucasian patients living in France. All underwent clinical and biochemical evaluations, and all were assessed for microvascular complications. RESULTS: The median duration of stay of the migrants in France was 15years before being diagnosed with diabetes. Despite similar durations of diagnosis, they were 8.9years younger at the time of diagnosis than Africans living in Cameroon (P<0.001). Caucasians and African immigrants in France had lower HbA1c values than Africans in Cameroon (P<0.001); they were also more aggressively treated for hypertension and dyslipidaemia and, therefore, had significantly lower blood pressure levels and better lipid profiles. Diabetic nephropathy and retinopathy rates were higher in Cameroon than in the two other groups. After adjusting for age, diabetes duration, HbA1c, hypertension and other covariates, only the prevalence of diabetic nephropathy (OR: 5.61, 95% CI: 2.32-13.53; P<0.0001) was higher in Cameroon compared with those living in France. CONCLUSION: Our results suggest that Africans who emigrate to France may develop diabetes earlier than those staying in their home country. However, the latter may be a reflection of late diagnosis of diabetes. Also, the less adequate diabetes and hypertension control in the latter would explain their higher rates of nephropathy. Large-scale cohorts are now warranted to substantiate these observations.

Prevalence and determinants of electrocardiographic abnormalities in sub-Saharan African individuals with type 2 diabetes.

AIM: This study assessed the prevalence and determinants of electrocardiographic abnormalities in a group of type 2 diabetes patients recruited from two referral centres in Cameroon. METHODS: A total of 420 patients (49% men) receiving chronic diabetes care at the Douala General and Yaoundé Central hospitals were included. Electrocardiographic abnormalities were investigated, identified and related to potential determinants, with logistic regressions. RESULTS: The mean age and median duration of diagnosis were 56.7 years and four years, respectively. The main electrocardiographic aberrations (prevalence %) were: T-wave abnormalities (20.9%), Cornell product left ventricular hypertrophy (16.4%), arrhythmia (16.2%), ischaemic heart disease (13.6%), conduction defects (11.9%), QTc prolongation (10.2%) and ectopic beats (4.8%). Blood pressure variables were consistently associated with all electrocardiographic abnormalities. Diabetes-specific factors were associated with some abnormalities only. CONCLUSIONS: Electrocardiographic aberrations in this population were dominated by repolarisation, conduction defects and left ventricular hypertrophy, and were more related to blood pressure than diabetes-specific factors.

Impact of diabetes mellitus on clinical presentation and prognosis of pancreatic cancer.

INTRODUCTION: The aim of this study was to investigate possible effects of diabetes mellitus on clinical manifestations and prognosis of pancreatic cancer (PC). PATIENTS AND METHODS: We retrospectively reviewed the clinical files of 122 patients with PC, and divided them into two groups: those with diabetes (56 patients) and those without diabetes (66 patients). The two groups were then compared for demographic profiles, clinical manifestations of PC, features of the tumor and fatal outcomes. RESULTS: Mean age, sex distribution, body mass index at cancer diagnosis, prevalence of hypertension, dyslipidemia, weight loss, abdominal pain, lumbar pain, signs of dyspepsia, and size, and histological features of the tumor were similar between the two groups. The cancer was located in the head of the pancreas in 50% of those with diabetes, and 80% of those without diabetes (P=0.04). The median survival time was similar. CONCLUSIONS: Clinical features, tumor size and prognosis of PC are similar in people with and without diabetes. Having diabetes does not seem to contribute to earlier diagnosis of PC.

The polymorphism Arg585Gln in the gene of the sterol regulatory element binding protein-1 (SREBP-1) is not a determinant of ketosis prone type 2 diabetes (KPD) in Africans.

AIM: Ketosis prone type 2 diabetes (KPD) is an atypical form of diabetes described mainly in people of sub-Saharan African origin. Its pathogenesis is unknown, although we have previously described a high prevalence of glucose-6-phosphate-dehydrogenase (G6PD) deficiency in patients with KPD. However, 50% of these deficient patients lacked the G6PD gene mutation. The isoforms of the transcription factor sterol regulatory element binding protein 1 (SREBP-1) are known to stimulate G6PD gene expression, and some polymorphisms in the SREBP-1 gene (SREBF-1) have been described only in Africans. We investigated one of these, the Arg585Gln polymorphism, in a candidate gene approach for KPD. METHODS: We examined the presence of the Arg585Gln polymorphism in SREBF-1 in 217 consecutive unrelated Africans [73 patients with KPD, 80 with classical type 2 diabetes (T2D) and 64 nondiabetic subjects]. Patients underwent clinical and biochemical evaluations, and were assessed for G6PD activity and insulin secretion (glucagon test). RESULTS: There were no differences in frequency of the Arg585Gln polymorphism and the 585Gln allele among the three groups (allele frequency: KPD: 0.089, T2D: 0.031, nondiabetic group: 0.070; P=0.1). When the 585Gln allele frequency was compared separately between patients with KPD and those with T2D, it was significantly higher in the former (P=0.032). There was no difference between carriers and noncarriers of the 585Gln allele regarding G6PD activity and insulin secretion. CONCLUSION: The results of this exploratory study show that the polymorphism Arg585Gln in SREBF-1 is not associated with the KPD phenotype. Further studies in larger populations are needed to confirm our findings.

Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes.

Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was likely to be developed as a therapeutic agent for this disease.

The spectrum of coma among people with diabetes in Cameroon: an appraisal of the implications and challenges at the Yaounde Central Hospital.

The present study was undertaken to assess the prevalence and prognosis of comas, the most serious acute complications of diabetes, among people with diabetes in Cameroon. The medical records of diabetic patients admitted to the endocrinolgy service of the Yaounde Central Hospital between November 1999 and October 2002 were reviewed. For each patient, data were collected on past medical history, clinical parameters, results of laboratory investigations, treatment received, and outcome. Coma was found to account for 10.2% (52) of the 509 admissions of diabetic patients, and to be responsible for a diagnosis of diabetes in 11 patients. The underlying causes of the comas were hypoglycaemia (28.8%), ketoacidosis (25%), hyperosmolar syndrome (25%), stroke (5.8%), uraemic syndrome (5.8%) and meningitis (5.8%). Hypoglycaemia was treated with intravenous (10%) glucose. Careful rehydration and subcutaneous injections of low doses of regular insulin were used to manage the hyperglycaemic crises, and broad-spectrum antibiotics were used to treat the infections. Despite the treatments, 11 of the coma cases died in hospital, six (55%) of the deaths being ultimately attributed to infection. Diabetic comas are relatively frequent in Yaounde and sometimes the first indication that an individual is diabetic. Associated deaths are regularly the result of infection. The management of the comas, using techniques that are not particularly aggressive, generates outcomes similar to those reported elsewhere.

How to measure hepatic insulin resistance?

The liver plays a pivotal role in energy metabolism. Under the control of hormones, especially insulin, the liver stores or releases glucose as needed by the body's systems. It is also responsible for an important part of non-esterified fatty-acid and aminoacid metabolism. Assessing hepatic insulin resistance is almost always synonymous with measuring hepatic glucose production (HGP) and calculating indices of hepatic insulin resistance. The most frequently used method to this end is the isotope dilution technique using a tracer. Among tracers, stable isotope-labelled glucose molecules are particularly advantageous over radioactive isotope-labelled glucose and are, therefore, the tracers of choice. The tracer is infused either on its own after an overnight fast to evaluate fasting HGP, or with some among the usual insulin-sensitivity tests to assess HGP suppression by insulin and/or glucose. In a fasting state, HGP is easily calculated whereas, during insulin or glucose infusion, some formula are needed to correct for the non-steady-state condition. The hepatic insulin-resistance index is the product of HGP and the corresponding plasma insulin concentration. Although subject to error, the isotope dilution method nevertheless remains an irreplaceable tool for assessing hepatic insulin resistance in clinical research. From a practical point of view, some easily obtainable indices and clinical or biochemical parameters can serve as surrogates or markers of hepatic insulin resistance in clinical practice. Finally, drugs such as metformin or glitazones can improve hepatic insulin resistance, hence their use in hepatic insulin-resistant states such as type 2 diabetes and non-alcoholic fatty liver disease.

Diabetic foot ulcers in Cameroon: can microflora prevalence inform probabilistic antibiotic treatment?

OBJECTIVE: To determine the clinical features, regularly associated microorganisms and their susceptibility to antibiotics, and the clinical outcomes of foot ulcers in patients with diabetes at the Yaoundé Central Hospital, Cameroon. METHOD: A retrospective analysis of routinely collected hospital data, and data validation by survey of clinical notes was conducted from November 1999 to October 2002 for adult diabetic patients with foot ulcers. Clinical data were recorded for each patient, followed by a record of microbiological investigations where available. RESULTS: Of 503 patients with diabetes admitted during the study period, 54 (10.7%) had foot ulcers. Male subject represented 66.7% of this population. The mean age of the study population was 59.66 +/- 1.52 years. The foot ulcer led to the diagnosis of diabetes in six patients in whom the condition was previously unidentified. Of the 54 patients with foot ulcers, nine (16.7%) were selected for surgery and the remaining 45 were managed conservatively. Microbiological investigations were available for 21 patients. Proteus mirabilis was the most frequent microorganism yielded, and was regularly associated with Staphylococcus aureus. All the microorganisms isolated showed high sensitivity to second-generation quinolone antibiotics and were regularly sensitive to aminoglycoside antibiotics. Nine (16.7%) patients died and seven (13%) were discharged at their own request. CONCLUSION: The mortality rate among our diabetic patients with foot ulcers is high and the combination of second-generation quinolone and aminoglycoside antibiotics can be proposed as a probabilistic antibiotic approach to treating foot infection.