Aga Khan Hospital Dar es Salaam

OBJECTIVE: To describe the prevalence, detection, treatment and control of hypertension in an urban and rural area of Tanzania. DESIGN: Two linked cross-sectional population-based surveys. SETTING: A middle-income urban district of Dar es Salaam (Ilala) and a village in the relatively prosperous rural area of Kilimanjaro (Shari). PARTICIPANTS: Seven hundred and seventy adults (> 15 years) in Ilala and 928 adults in Shari were studied. RESULTS: Hypertension prevalence (blood pressure > or = 140 and/or 90 mmHg, or known hypertensives receiving anti-hypertensive treatment) was 30% (95% confidence interval, 25.1-34.9%) in men and 28.6% (24.3-32.9%) in women in Ilala, and 32.2% (27.7-36.7%) in men and 31.5% (27.8-35.2%) in women in Shari. Age-standardized hypertension (to the New World Population) prevalence was 37.3% (32.2-42.5%) among men and 39.1% (34.2-44.0%) in women in Ilala, and 26.3% (22.4-30.4%) in men and 27.4% (24A-30.4%) in women in Shari. In both areas, just under 20% of hypertensive subjects were aware of their diagnosis, approximately 10% reported receiving treatment and less than 1% were controlled (blood pressure < 140/90 mmHg). Hypertensive subjects were older, had greater body mass indices and waist: hip ratios, and had more risk factors for hypertension and its complications (smoking, heavy alcohol consumption, physical inactivity, obesity and diabetes) than non-hypertensives. CONCLUSIONS: There is a high prevalence of hypertension in rural and urban areas of Tanzania, with low levels of detection, treatment and control. This demonstrates the need for cost-effective strategies for primary prevention, detection and treatment of hypertension and the growing public health challenge of non-communicable diseases in Sub-Saharan Africa.

A daily intake of 5 portions of fruit and vegetables (FV) is recommended for protection against non-communicable diseases (NCDs). Inadequate FV intake is a global problem but resource-poor countries like Tanzania are most deprived and constitute settings where little is known for informing public health interventions. This study aimed to describe the prevalence of inadequate FV intake, frequency of FV intake, portions of FV intake and their associations with socio-demographic/lifestyle factors in South-Eastern Tanzania. Data on FV dietary indicators, socio-demographic factors, smoking, alcohol and healthcare use were collected from 7953 participants (≥15 years) of the population-based MZIMA open community cohort (2012-2013). Multivariable logistic regression was used to examine associations between FV intake outcomes and their socio-demographic/lifestyle determinants. Most (82%) of the participants did not meet the recommended daily FV intake While only a fraction consumed fruits daily (15.5%), almost half consumed vegetables daily (44.2%). However, the median (IQR) number of vegetable portions consumed was lower (2(1)/person/day) than that for fruits (2(2)/person/day) People with higher education were more likely to consume fruits daily. Independent correlates of inadequate FV intake included young age, being male, low education, low-income occupations, low alcohol, high tobacco and low healthcare use. Public health interventions should target the socio-economically deprived and culturally-rooted preferences while prioritizing promotion of vegetable for most immediate gain in overall FV intake.

A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin. Two or three premixed insulin injections per day may be used (A). The target glycated hemoglobin A1c (HbA1c) for all children with T1DM, including preschool children, is recommended to be < 7.5% (< 58 mmol/mol). The target is chosen aiming at minimizing hyperglycemia, severe hypoglycemia, hypoglycemic unawareness, and reducing the likelihood of development of long-term complications (B). For patients prone to glycemic variability, glycemic control is best evaluated by a combination of results with self-monitoring of blood glucose (SMBG) (B). Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy (B). In T2DM patients, with regards to achieving glycemic goals, insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol); and is essential for treatment in those with HbA1c ≥ 10% (≥ 86 mmol/mol), when diet, physical activity, and other antihyperglycemic agents have been optimally used (B). The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic drugs (OADs) (B). If the desired glucose targets are not met, rapid-acting or short-acting (bolus or prandial) insulin can be added at mealtime to control the expected postprandial raise in glucose. An insulin regimen should be adopted and individualized but should, to the extent possible, closely resemble a natural physiologic state and avoid, to the extent possible, wide fluctuating glucose levels (C). Blood glucose monitoring is an integral part of effective insulin therapy and should not be omitted in the patient's care plan. Fasting plasma glucose (FPG) values should be used to titrate basal insulin, whereas both FPG and postprandial glucose (PPG) values should be used to titrate mealtime insulin (B). Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C). Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia (D). Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia (B). The shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular (IM) injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them (A). Many patients in East Africa reuse syringes for various reasons, including financial. This is not recommended by the manufacturer and there is an association between needle reuse and lipohypertrophy. However, patients who reuse needles should not be subjected to alarming claims of excessive morbidity from this practice (A). Health care authorities and planners should be alerted to the risks associated with syringe or pen needles 6 mm or longer in children (A).

BACKGROUND: The management of childhood infections remains inadequate in resource-limited countries, resulting in high mortality and irrational use of antimicrobials. Current disease management tools, such as the Integrated Management of Childhood Illness (IMCI) algorithm, rely solely on clinical signs and have not made use of available point-of-care tests (POCTs) that can help to identify children with severe infections and children in need of antibiotic treatment. e-POCT is a novel electronic algorithm based on current evidence; it guides clinicians through the entire consultation and recommends treatment based on a few clinical signs and POCT results, some performed in all patients (malaria rapid diagnostic test, hemoglobin, oximeter) and others in selected subgroups only (C-reactive protein, procalcitonin, glucometer). The objective of this trial was to determine whether the clinical outcome of febrile children managed by the e-POCT tool was non-inferior to that of febrile children managed by a validated electronic algorithm derived from IMCI (ALMANACH), while reducing the proportion with antibiotic prescription. METHODS AND FINDINGS: We performed a randomized (at patient level, blocks of 4), controlled non-inferiority study among children aged 2-59 months presenting with acute febrile illness to 9 outpatient clinics in Dar es Salaam, Tanzania. In parallel, routine care was documented in 2 health centers. The primary outcome was the proportion of clinical failures (development of severe symptoms, clinical pneumonia on/after day 3, or persistent symptoms at day 7) by day 7 of follow-up. Non-inferiority would be declared if the proportion of clinical failures with e-POCT was no worse than the proportion of clinical failures with ALMANACH, within statistical variability, by a margin of 3%. The secondary outcomes included the proportion with antibiotics prescribed on day 0, primary referrals, and severe adverse events by day 30 (secondary hospitalizations and deaths). We enrolled 3,192 patients between December 2014 and February 2016 into the randomized study; 3,169 patients (e-POCT: 1,586; control [ALMANACH]: 1,583) completed the intervention and day 7 follow-up. Using e-POCT, in the per-protocol population, the absolute proportion of clinical failures was 2.3% (37/1,586), as compared with 4.1% (65/1,583) in the ALMANACH arm (risk difference of clinical failure -1.7, 95% CI -3.0, -0.5), meeting the prespecified criterion for non-inferiority. In a non-prespecified superiority analysis, we observed a 43% reduction in the relative risk of clinical failure when using e-POCT compared to ALMANACH (risk ratio [RR] 0.57, 95% CI 0.38, 0.85, p = 0.005). The proportion of severe adverse events was 0.6% in the e-POCT arm compared with 1.5% in the ALMANACH arm (RR 0.42, 95% CI 0.20, 0.87, p = 0.02). The proportion of antibiotic prescriptions was substantially lower, 11.5% compared to 29.7% (RR 0.39, 95% CI 0.33, 0.45, p < 0.001). Using e-POCT, the most common indication for antibiotic prescription was severe disease (57%, 103/182 prescriptions), while it was non-severe respiratory infections using the control algorithm (ALMANACH) (70%, 330/470 prescriptions). The proportion of clinical failures among the 544 children in the routine care cohort was 4.6% (25/544); 94.9% (516/544) of patients received antibiotics on day 0, and 1.1% (6/544) experienced severe adverse events. e-POCT achieved a 49% reduction in the relative risk of clinical failure compared to routine care (RR 0.51, 95% CI 0.31, 0.84, p = 0.007) and lowered antibiotic prescriptions to 11.5% from 94.9% (p < 0.001). Though this safety study was an important first step to evaluate e-POCT, its true utility should be evaluated through future implementation studies since adherence to the algorithm will be an important factor in making use of e-POCT's advantages in terms of clinical outcome and antibiotic prescription. CONCLUSIONS: e-POCT, an innovative electronic algorithm using host biomarker POCTs, including C-reactive protein and procalcitonin, has the potential to improve the clinical outcome of children with febrile illnesses while reducing antibiotic use through improved identification of children with severe infections, and better targeting of children in need of antibiotic prescription. TRIAL REGISTRATION: ClinicalTrials.gov NCT02225769.

We estimated the proportion of patients reaching a pediatric ophthalmology unit (Comprehensive Community Based Rehabilitation for Tanzania Disability Hospital, CCBRT) or an oncology unit (ORCI) in east Africa and investigated presentation, histology, and treatment outcomes of patients with retinoblastoma. A 5-year retrospective study identified 91 patients, representing approximately 18% of the nationwide total. Mean lag time was 10 months (standard deviation (SD) = 17) and mean follow-up was 8 months (SD = 11, range 0-40, n = 91). Thirty months disease-free survival probability was 0.23 (standard error = 0.07). Outcomes for retinoblastoma in Africa remain poor. The data presented here suggest strategies for improving the outcomes, including encouraging earlier presentation and establishment of multi-disciplinary treatment centers.

PURPOSE: In the 1960s in Tanzania, L. Jilek-Aall observed a seizure disorder characterized by head nodding (HN). Decades later, "nodding disease," reminiscent of what was seen in Tanzania, was reported from Sudan. To date this seizure disorder has not been classified and possible causes still remain obscure. METHODS: In a prospective study in southern Tanzania, we evaluated 62 patients with HN. Selected patients underwent blood (n = 51) and cerebrospinal fluid (CSF) (n = 48) analyses. Others were chosen for MRI (n = 12) and EEG (n = 10). RESULTS: Seizure type was classified as "head nodding only" and "head nodding plus," the latter being combined with other types of seizure (n =34). During HN, consciousness was impaired in 11 patients (17.7%) and supportive signs of epileptic seizures were described by 15 (24.2%) patients. Precipitating factors were confirmed by 11 (17.7%) patients. Fifty-six (90.3%) patients had at least one relative with epilepsy. EEG confirmed interictal epileptic activity in two patients and unspecific changes in four patients. MRI showed hippocampus pathologies (n = 5) and gliotic changes (n = 5). Skin polymerase chain reaction (PCR) positivity for Onchocerca volvulus was significantly associated with lesions on MRI. However, PCR of the CSF was negative in all cases. CONCLUSIONS: We present a comprehensive clinical description of the "HN syndrome," possibly a new epilepsy disorder in sub-Saharan Africa. MRI lesions and their association with positive skin PCR for O. volvulus despite negative PCR of the CSF is intriguing and deserves attention. Furthermore, the high prevalence of hippocampus sclerosis and familial clustering of epilepsy may point toward other potential pathogenetic mechanisms.

OBJECTIVE: We systematically reviewed publications on prevalence and risk factors for gestational diabetes mellitus (GDM) in the 47 countries of sub-Saharan Africa. METHODS: We conducted a systematic search in PUBMED and reviewed articles published until June 2014 and searched the references of retrieved articles. We explored sources of heterogeneity among prevalence proportions with metaregression analysis. RESULTS: Of 1069 articles retrieved 22 studies were included. Half were from West Africa, specifically Nigeria, five from South Africa and six from East and Central Africa. There were differences in screening methods and diagnosis criteria used, even between studies carried out in the same country and same time period. Metaregression analysis indicated high heterogeneity among the studies (I(2) = 100, P < 0.001), which could not be sufficiently explained by study setting, population, diagnostic criteria or time trend, although we observed a relatively higher prevalence in studies carried out after 2000 (5.1% vs. 3.2%), when women at risk were selected (6.5% vs. 3.8%) and when more current diagnostic criteria were used (5.1% vs. 4.2%). Associations with risk factors were reported in six studies. Significant risk factors reported in more than one study were overweight and/or obesity, family history for type 2 diabetes, previous stillbirth, previous macrosomic child and age >30 years. CONCLUSIONS: There are few studies on prevalence and risk factors for GDM in Sub-Saharan Africa and heterogeneity is high. Prevalence was up to about 14% when high-risk women were studied. Preventive actions should be taken to reduce the short- and long-term complications related to GDM in Sub-Saharan Africa.

To date, insulin therapy remains the cornerstone of diabetes management; but the art of injecting insulin is still poorly understood in many health facilities. To address this gap, the Forum for Injection Technique and Therapy Expert Recommendations (FITTER) published recommendations on injection technique after a workshop held in Rome, Italy in 2015. These recommendations are generally applicable to the majority of patients on insulin therapy, athough they do not explore alternative details that may be suitable for low- and middle-income countries. The East Africa Diabetes Study Group sought to address this gap, and furthermore to seek consensus on some of the contextual issues pertaining to insulin therapy within the East African region, specifically focusing on scarcity of resources and its adverse effect on the quality of care. A meeting of health care professionals, experts in diabetes management and patients using insulin, was convened in Kigali, Rwanda on 11 March 2018, and the following recommendations were made: (1) insulin should be transported safely, without undue shaking and exposure to high (> 32 °C) temperature environments. (2) Insulin should not be transported below 0 °C. (3) If insulin is to be stored at home for over 2 months, it should be stored at the recommended temperature of 2-8 °C. (4) Appropriate instructions should be given to patients while dispensing insulin. (5) Insulin in use should be kept at room temperature and should never be kept immersed under water. Immersing insulin under water after the vial has been pierced carries a high risk of contamination, leading to loss of potency and likelihood of causing injection abscesses. (6) The shortest available needles (4 mm for pen and 6 mm for insulin syringe) should be preferred for all patients. (7) In routine care, intramuscular injections should be avoided, especially with long-acting insulins, as it may result in severe hypoglycaemia. (8) The practice of slanting the needle excessively should be avoided as it results in sub-epidermal injection of insulin which leads to poor absorption and may cause "tattooing" of the skin and scarring. (9) In patients presenting in a wasted state, with "paper-like skin", injections should, if possible, be initiated with pen injection devices, so as to utilise the 4-mm needle without lifting a skin fold (pinching the skin); otherwise lifting of a skin fold is required, if longer needles are utilised. (10) Reuse of needles and syringes is not recommended. However, as the reuse of syringes and needles is practiced for various reasons, and by many patients, individuals should not be given alarming messages; and usage should be limited to discarding when injections become more painful; but at any rate not to exceed reusing a needle more than 5 times.

Asians from the Indian subcontinent have received greater attention in diabetes studies because of their migration in large numbers. The prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in migrant Indians is higher than that in the population residing in the Indian subcontinent and is also usually higher than in the other racial groups in the host country. However, before drawing any conclusions with reference to the high prevalence of NIDDM in the migrant Indians, careful comparisons are required with more up-to-date information available from the Indian subcontinent itself. Recent data from India indeed indicate that the prevalence rates have either been underestimated in the past or are rising. The problem is compounded by the different diagnostic criteria used for defining diabetes. Some of the possible factors which cause variations in the rates of NIDDM in this population are discussed.

OBJECTIVE: The purpose of this study was to assess glycemic control and complications of type 1 diabetes in children and adolescents in Tanzania. RESEARCH DESIGN AND METHODS: This demographic and clinical survey included 99 children aged between 5 and 18 years attending Muhimbili National Hospital Clinic for Diabetes. A structured questionnaire was used for evaluating socioeconomic data and for estimation of the prevalence of acute complications occurring over the last 6 months. The prevalences of retinopathy and diabetic nephropathy were determined by fundus ophthalmoscopy and by microalbuminuria, respectively. RESULTS: All of these children were treated with a conventional insulin regimen. The mean +/- SD duration of diabetes was 4.76 +/- 3.58 years. Only 1 child (1%) had good glycemic control (A1C <7.5%), 60 children (60.6%) had moderate glycemic control (A1C 7.5-10%), 14 children (14.1%) had poor glycemic control (A1C >10-12.5%), and 24 children (24.2%) had very poor glycemic control (A1C >12.5%). At onset of diabetes, 75% of children presented with diabetic ketoacidosis (DKA); 89 children (89.80%) had at least one episode of DKA, and 55 children (55.67%) had symptomatic hypoglycemic episodes. Microalbuminuria was present in 29 (29.3%) and retinopathy in 22 (22.68%) children. CONCLUSIONS: Although there are some methodological limitations, this survey highlights the difficulties of achieving good metabolic control and the high prevalence of acute and chronic complications in Tanzanian children with type 1 diabetes. These results clearly show that major efforts are needed to improve quality of care in children with type 1 diabetes in Tanzania.

OBJECTIVE: To assess the agreement of different diagnostic methods for the diagnosis and confirmation of the clinical suspicion of Plasmodium infection in children in Tanzania and Kenya. METHOD: Blood samples were collected by the finger prick method from 338 children. Blood samples were collected from 338 children with the clinical suspicion of uncomplicated malaria in health clinics in Tanzania and Kenya. The presence of Plasmodium parasites was assessed with microscopy, rapid diagnostic tests (RDTs) and the molecular assays, quantitative nucleic acid sequence based amplification (QT-NASBA) and polymerase chain reaction (PCR). The results were compared and analysed for agreement. RESULTS: There was a high degree of agreement (88.6-100%) between RDTs or molecular tests and microscopy. In rural Kenya, with a high incidence of malaria cases, the correlation coefficient ranged from 0.94 for RDTs to 0.76 for PCR. In urban Tanzania, where there was a low incidence of cases, R for RDTs was 1.0 but only 0.25 for PCR and 0.33 for NASBA. CONCLUSION: Malaria is overestimated if the diagnosis is based solely on clinical signs. Therefore, laboratory confirmation is essential. Microscopy is a reliable method in rural areas where malaria is prevalent, but RDTs offer a good alternative with the advantage that it is an easy and rapid method. Molecular tests are more sensitive but difficult to implement in rural areas. In areas with lower incidence, molecular tests detect a significantly higher number of Plasmodium infections than RDTs or microscopy. Although implementation of molecular tools can be difficult, the prospect of an easy and cheap detection system makes them promising tools for the near future.

INTRODUCTION: The decline of malaria and scale-up of rapid diagnostic tests calls for a revision of IMCI. A new algorithm (ALMANACH) running on mobile technology was developed based on the latest evidence. The objective was to ensure that ALMANACH was safe, while keeping a low rate of antibiotic prescription. METHODS: Consecutive children aged 2-59 months with acute illness were managed using ALMANACH (2 intervention facilities), or standard practice (2 control facilities) in Tanzania. Primary outcomes were proportion of children cured at day 7 and who received antibiotics on day 0. RESULTS: 130/842 (15∙4%) in ALMANACH and 241/623 (38∙7%) in control arm were diagnosed with an infection in need for antibiotic, while 3∙8% and 9∙6% had malaria. 815/838 (97∙3%;96∙1-98.4%) were cured at D7 using ALMANACH versus 573/623 (92∙0%;89∙8-94∙1%) using standard practice (p<0∙001). Of 23 children not cured at D7 using ALMANACH, 44% had skin problems, 30% pneumonia, 26% upper respiratory infection and 13% likely viral infection at D0. Secondary hospitalization occurred for one child using ALMANACH and one who eventually died using standard practice. At D0, antibiotics were prescribed to 15∙4% (12∙9-17∙9%) using ALMANACH versus 84∙3% (81∙4-87∙1%) using standard practice (p<0∙001). 2∙3% (1∙3-3.3) versus 3∙2% (1∙8-4∙6%) received an antibiotic secondarily. CONCLUSION: Management of children using ALMANACH improve clinical outcome and reduce antibiotic prescription by 80%. This was achieved through more accurate diagnoses and hence better identification of children in need of antibiotic treatment or not. The building on mobile technology allows easy access and rapid update of the decision chart. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201011000262218.

BACKGROUND: Low-income and middle-income countries are struggling to manage growing numbers of patients with chronic non-communicable diseases (NCDs), while services for patients with HIV infection are well established. There have been calls for integration of HIV and NCD services to increase efficiency and improve coverage of NCD care, although evidence of effectiveness remains unclear. In this review, we assess the extent to which National HIV and NCD policies in East Africa reflect the calls for HIV-NCD service integration. METHODS: Between April 2018 and December 2020, we searched for policies, strategies and guidelines associated with HIV and NCDs programmes in Burundi, Kenya, Rwanda, South Sudan, Tanzania and Uganda. Documents were searched manually for plans for integration of HIV and NCD services. Data were analysed qualitatively using document analysis. RESULTS: Thirty-one documents were screened, and 13 contained action plans for HIV and NCDs service integration. Integrated delivery of HIV and NCD care is recommended in high level health policies and treatment guidelines in four countries in the East African region; Kenya, Rwanda, Tanzania and Uganda, mostly relating to integrating NCD care into HIV programmes. The increasing burden of NCDs, as well as a move towards person-centred differentiated delivery of services for people living with HIV, is a factor in the recent adoption of integrated HIV and NCD service delivery plans. Both South Sudan and Burundi report a focus on building their healthcare infrastructure and improving coverage and quality of healthcare provision, with no reported plans for HIV and NCD care integration. CONCLUSION: Despite the limited evidence of effectiveness, some East African countries have already taken steps towards HIV and NCD service integration. Close monitoring and evaluation of the integrated HIV and NCD programmes is necessary to provide insight into the associated benefits and risks, and to inform future service developments.

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus–TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis ‘DOTS’ model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A1c (HbA1c) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases. Définir l’agenda de recherche pour réduire la charge de la maladie conjointe entre diabète sucré et tuberculose La croissance constante de l’épidémie de diabète sucré constitue une menace mondiale pour la lutte contre la tuberculose (TB). Des études antérieures ont identifié une association importante entre le diabète sucré et la TB. Toutefois, ces études ont des limitations: très peu ont été menées dans les pays à faibles revenus, aucune en Afrique, suscitant des inquiétudes sur la force de l’association entre diabète sucré et TB dans ces régions et de nombreuses questions cruciales restent sans réponse. Une réunion d’experts s’est tenue en novembre 2009 pour discuter des preuves existantes suffisantes pour formuler des recommandations fermes sur la prise en charge conjointe de ces deux maladies, des lacunes dans la recherche et élaborer un programme de recherche. Dix questions clés pour la recherche ont été identifiées dont 4 ont été sélectionnées comme étant hautement prioritaires: i) faut-il, quand et comment dépister la TB chez les patients avec un diabète sucré et vice versa, ii) l’impact de l’hyperglycémie du diabète sucré et non-diabétique sur les résultats du traitement de la TB et les décès, ainsi que l’élaboration de stratégies visant à améliorer les résultats, iii) l’instauration et l’évaluation du modèle “DOTS” pour la TB dans la prise en charge du diabète sucré et iv) le développement et l’évaluation de meilleurs tests de diagnostic et de contrôle, utilisables sur les lieux des soins, tels que la mesure de la glycémie et de l’hémoglobine glyquée A1c (HbA1c) pour les patients atteints de diabète sucré. L’instauration de ce programme de recherche sera bénéfique pour le contrôle des deux maladies. Definiendo la agenda de investigación para reducir la carga conjunta de la enfermedad por Diabetes mellitus y la Tuberculosis El aumento constante de la epidemia de la diabetes mellitas (DM) pone en peligro el control global de la tuberculosis (TB). Estudios anteriores han identificado una asociación importante entre la DM y la TB. Sin embargo, estos estudios tienen limitaciones: muy pocos fueron llevados a cabo en países en vías de desarrollo, ninguno en África, dando lugar a dudas acerca de la asociación entre la DM y la TB en estos lugares, y con muchas preguntas críticas estando aún sin respuesta. Se realizó una reunión de expertos en Noviembre del 2009 con el fin de discutir si había suficiente evidencia para hacer recomendaciones sobre el manejo conjunto de ambas enfermedades, sobre si enfocarse para resolver “huecos” en la investigación y desarrollar una nueva agenda de investigación. Se identificaron diez preguntas claves, de las cuales se seleccionaron 4 de alta prioridad: i) cuando y como tamizar a los pacientes de TB con DM y vice versa; ii) el impacto de la DM y la hipoglicemia no relacionada con DM sobre los resultados del tratamiento para y muertes por TB, y el desarrollo de estrategias para mejorar los resultados; iii) la implementación y evaluación del modelo de “DOTS” en TB para el manejo de la DM; y iv) el desarrollo y la evaluación de un mejor diagnóstico “point-of-care” y pruebas de monitorización, incluyendo medidas de glucosa en sangre y hemoglobina glicosilada A1c (HbA1c) para pacientes con DM. La implementación de esta agenda de investigación beneficiará el control de ambas enfermedades. The global burden of disease from diabetes mellitus and tuberculosis (TB) is immense. In 2010, there will be an estimated 285 million people living with diabetes mellitus with approximately 4 million deaths (International Diabetes Federation 2009). In 2007, there were an estimated 14.4 million people living with TB, 9.2 million new cases and 1.7 million deaths (WHO 2009). While it is widely known that 95% of patients with TB live in the low- and middle-income countries, 70% of patients with diabetes mellitus also live in these same countries, especially in South-east Asia and the Western Pacific. Among several risk factors for TB, which include HIV/AIDS, silicosis, malnutrition, alcoholism and smoking, diabetes mellitus has received recent recognition. A systematic review of the literature in 2008 identified 13 age-adjusted, quantitative, observational studies in North America, UK, Russia, Mexico, Korea, Taiwan and India, finding a relative risk of TB in patients with diabetes mellitus of 3.1 in cohort studies and odds ratios that ranged from 1.16 to 7.83 in case–control studies (Jeon & Murray 2008). These findings were similar to those reported in a previous systematic review (Stevenson et al. 2007a), were supported by data included in an epidemiological model indicating that, in India, diabetes mellitus might account for nearly 15% of pulmonary tuberculosis (PTB) cases (Stevenson et al. 2007b), and have been further endorsed by a review in 2009 that provided a synopsis of the evidence of the role of diabetes mellitus in influencing the clinical presentation and response to treatment for TB (Dooley & Chaisson 2009). The important association between diabetes mellitus and TB is not in doubt. However, the previous studies published between 1965 and 2009 have limitations. Many are health facility-based case–control studies using medical chart diagnoses of diabetes mellitus and may be subject to confounding. Most studies are from industrialized countries. The evidence base from low-income countries is weak, with none at all from Africa, raising uncertainty about the strength of the diabetes mellitus association in these settings. There are also many critical unanswered questions: Should patients with diabetes mellitus be screened for TB in diabetes mellitus clinics and vice versa, and how and when? What is the effect of diabetes mellitus on the presentation of TB and subsequent TB treatment outcomes? What is the natural history of multidrug-resistant TB (MDR-TB) in patients with diabetes mellitus, and what steps are needed for prevention and management? Should TB preventive therapy be considered in patients with diabetes mellitus? Would life-style changes be helpful in preventing both diseases? As a result of these uncertainties and questions, a systematic review of the literature was commissioned from the Harvard School of Public Health, USA, in May 2009. The review addressed key questions such as screening for TB and diabetes mellitus in routine clinics, TB chemoprophylaxis and the impact of diabetes mellitus on clinical and programmatic management of TB. The systematic review was completed by the end of August, and the findings presented and discussed at an expert meeting in November 2009 at the International Union Against Tuberculosis and Lung Disease, Paris, France. The main objectives of the meeting were to determine whether there was enough evidence to make policy recommendations about joint diagnosis and management of both diseases, address research gaps and develop a research agenda around these gaps. This article summarizes the research agenda that emerged at the meeting, which we believe if carried out will assist in reducing the joint burden of disease from diabetes mellitus and TB. The key research questions are shown in Table 1, divided into high, medium and low priority. We identified four high-priority research questions: whether and how to screen for TB in patients with diabetes mellitus and vice versa; the impact of diabetes mellitus or non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development and testing of strategies to improve outcomes; implementation and evaluation of the tuberculosis ‘DOTS’ model for diabetes mellitus management; and development and evaluation of better point-of-care (POC) diagnostic tests for patients with diabetes mellitus. Patients with diabetes mellitus, particularly those with sub-optimal control, should be screened for active TB in areas of high TB prevalence. Prospective observational cohort studies should be conducted in diabetes mellitus clinics with a focus on adults and stratified by quality of diabetes mellitus control. Key questions, similar to those being asked about intensified TB case finding in people living with HIV (Havlir et al. 2008; Kranzer et al. 2010), include: (i) what type of screening algorithm will be most effective, i.e. should all patients with diabetes mellitus be investigated by standard TB laboratory investigations or should these investigations be targeted to those with symptoms suggesting active TB or with poor control of diabetes mellitus as defined by symptoms or measurements of blood glucose or glycated haemoglobin A1c (HbA1c); (ii) how often should screening be conducted; and (iii) what are the most appropriate screening tools (sputum smear examination and chest radiography for pulmonary disease, ultrasound for extra-pulmonary abdominal lymphadenopathy) and how do these compare to the gold standard of sputum culture for Mycobacterium tuberculosis. In determining the most appropriate strategy, the impact of diabetes mellitus on clinical manifestations of TB should be considered. The value of formal clinic education in diabetes clinics with TB posters, leaflets or group talks about the links between diabetes mellitus and TB needs to be explored in terms of improving health care staff and patient awareness and for future guidelines and training materials. Urban and other settings known to have high TB and diabetes mellitus incidence would be the most appropriate places to conduct such studies, for example Dar es Salaam in Tanzania, Blantyre in Malawi, Chennai in India and Beijing in China all being possibilities. For patients with TB, previous studies suggest that it is more reliable to screen for diabetes mellitus later in the course of anti-TB treatment rather than at the start (Dooley & Chaisson 2009), because TB as a chronic infectious disease may elevate blood glucose levels because of cytokine stimulation resulting in false positive diabetes mellitus diagnoses if investigations are performed too early. However, delayed screening may be a missed opportunity for subsequently modifying treatment, and many TB programmes, especially in Africa, have decentralized services to peripheral facilities where it is difficult to get laboratory investigations performed (Edginton 1990; Drabo et al. 2006). Research is required to determine the optimal time and best methods for diagnosing diabetes mellitus in patients with TB, focusing on adults stratified by type of disease (smear-positive PTB, smear-negative PTB and extra-pulmonary TB). The most appropriate ways of screening should be explored [urine, random or fasting blood glucose and/or glycated haemoglobin A1c (HbA1c)]. Patients identified by the two screening strategies discussed earlier need to be entered into prospective studies assessing the impact of diabetes mellitus or non-diabetes mellitus hyperglycaemia on TB treatment outcomes, using standardized TB regimens and outcomes, in which other confounding factors (age, smoking status, alcohol, body mass index and HIV) are taken into account. The level of hyperglycaemia and quality of diabetes control, measured, for example by HbA1c, are important factors to consider. Primary treatment outcomes should include (i) liver function tests; (ii) pharmacokinetic levels of rifampicin and oral diabetes medications; (iii) TB treatment outcomes; (iv) recurrence of TB 1 year after completion of TB treatment as determined by sputum culture; and (v) culture and drug-sensitivity testing, at the start of treatment and at the time of failure or TB recurrence to assess linkages and associations with drug-resistant TB. Death is reported to be more frequent in patients with diabetes mellitus on anti-TB treatment (Dooley & Chaisson 2009), but research is required to address unanswered questions such as when death occurs in relation to start of anti-TB treatment, the aetiology, and whether better diabetes mellitus control or modified TB drug regimens, duration of anti-TB therapy and TB drug doses reduce case fatality. The concept of using components of the Tuberculosis ‘DOTS Model’ for managing diabetes mellitus has already been proposed (Harries et al. 2008), and diabetes clinics in urban areas in high-burden countries need to pilot and evaluate this approach through operational research, and particularly to assess whether quarterly cohort reporting of incident cases, cumulative outcomes, complications and survival analysis can lead to better management and care, more rational drug forecasting and uninterrupted drug supplies (Harries et al. 2009). In the same way that the rapid POC HIV test revolutionized counselling and HIV testing replacing cumbersome and slow HIV-ELISA methodology (De Cock & Odhiambo 2006), better POC tests need to be developed for diabetes mellitus management. These tests could include measurements of blood glucose and HbA1c, the latter helping to differentiate diabetes mellitus from stress-related hyperglycaemia, and they should be assessed for both diagnosis and monitoring of the disease. If such tests are to be used widely in resource-poor settings, they should be simple to use; rely on finger-prick blood sampling; be independent of instrumentation or electronics; be robust and able to withstand elevated ambient temperatures without cold-chain shipment or storage; have a long shelf-life; and be inexpensive (e.g. costing less than USD$2 per test). These would have the potential to be used in peripheral clinics and remote health centres in Africa and Asia and would improve access to diabetes mellitus diagnosis and care. Other research questions are listed in Table 1. Among these, we consider TB preventive therapy to have low priority. Two studies conducted before the 1970s indicated that active TB in patients with diabetes mellitus could be reduced through TB chemoprophylaxis (Pfaffenberg & Jahler 1958; Lesnichii & Karpina 1969). Both studies were flawed, and therefore, the true benefit of chemoprophylaxis remains unknown. The question can only be properly addressed through a randomized controlled trial (RCT). However, given the expense of conducting RCTs, the low uptake of isoniazid preventive therapy in people living with HIV despite proven efficacy from a number of well-conducted RCTs (World Health Organization 2009) and other issues such as feasibility of implementation, this research is not given high priority because we feel it is unlikely to be carried forward to policy and practice. Better diabetes mellitus control might be safer and more cost-effective in preventing TB and reducing other diabetes mellitus complications. The epidemic of non-communicable diseases, especially diabetes mellitus, is steadily growing. Diabetes mellitus in particular threatens TB control efforts and the achievement of the 2015 TB targets (WHO 2006). In the same way, HIV threatens TB control and has lead to the development of an HIV-TB research agenda (Smart 2009); the threat of diabetes mellitus requires a research agenda focussed on providing tools for national and international agencies charged with the control of both these diseases. Many critical questions regarding the association between diabetes mellitus and TB remain unanswered because of either poorly conducted studies or no studies at all. These major concerns led to the assembly of an expert group who systematically reviewed existing data and developed a research agenda providing a clear basis for future action.

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

With the growing prevalence of type 2 diabetes, particularly in emerging countries, its management in the context of available resources should be considered. International guidelines, while comprehensive and scientifically valid, may not be appropriate for regions such as Asia, Latin America or Africa, where epidemiology, patient phenotypes, cultural conditions and socioeconomic status are different from America and Europe. Although glycaemic control and reduction of micro- and macrovascular outcomes remain essential aspects of treatment, access and cost are major limiting factors; therefore, a pragmatic approach is required in restricted-resource settings. Newer agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in particular, are relatively expensive, with limited availability despite potentially being valuable for patients with insulin resistance and cardiovascular complications. This review makes a case for the role of more accessible second-line treatments with long-established efficacy and affordability, such as sulfonylureas, in the management of type 2 diabetes, particularly in developing or restricted-resource countries.

PURPOSE: To compare whether free spectacles or only a prescription for spectacles influences wearing rates among Tanzanian students with un/undercorrected refractive error (RE). DESIGN: Cluster randomised trial. SETTING: 37 secondary schools in Dar es Salaam, Tanzania. PARTICIPANTS: Distance visual acuity was measured in 6,904 year-1 students (90.2% response rate; median age 14 years; range 11-25 years) using a Snellen E-chart. 135 had RE requiring correction. INTERVENTIONS: Schools were randomly allocated to free spectacles (arm A) or prescription only (arm B). PRIMARY OUTCOME: Spectacle use at 3 months. RESULTS: The prevalence of un/undercorrected RE was 1.8% (95% CI: 1.5 to 2.2%). At 3 months, 27/58 (47%) students in arm A were wearing spectacles or had them at school compared with 13/50 (26%) in arm B (adjusted OR 2.4, 95% CI 1.0 to 6.7). Free spectacles and myopia were independently associated with spectacle use. CONCLUSIONS: The low prevalence of un/undercorrected RE and poor uptake of spectacles, even when provided free, raises doubts about the value of vision-screening programmes in Tanzanian secondary schools. Policy decisions on school vision screening in middle- and low-income countries should take account of the cost-effectiveness as well as competing demands for scarce resources.

There is an excessive burden of diabetes complications in low-resource settings. We conducted a systematic review to determine the nature and frequency of diabetes complications in newly diagnosed with type 2 diabetes. A systematic search was performed using Medline, CINAHL and Global Health online databases from inception to July 2020. Articles reporting prevalence of microvascular or macrovascular complications within six months of type 2 diabetes diagnosis and published in English or French from low- and middle-income countries (LMICs) were eligible for analysis. Data were extracted using a standardized data extraction tool. Descriptive statistics were used to describe the prevalence of micro and macrovascular complications in newly diagnosed type 2 diabetes. Assessment of heterogeneity was conducted using the inconsistency index (I2) and Cochran-Q chi2 statistical tests. Publication bias was assessed by the Funnel plot and Egger test. A total of 3 292 records underwent title or abstract screening and 95 articles underwent full text review. Thirty-three studies describing 13 283 participants (aged 20 years and older) met the inclusion criteria. The eligible studies were from Asia (n = 24), Africa (n = 4), Oceania (n = 2), South America (n = 2) and the Caribbean (n = 1). For microvascular complications, the median prevalence (interquartile range) of retinopathy, nephropathy and neuropathy were 12% (6%-15%), 15% (7%-35%) and 16% (10%25%) respectively. For macrovascular complications, the median prevalence (interquartile range) was 10% (7%-17%) for ischaemic heart disease, 6% (1%-20%) for peripheral arterial disease and 2% (1%-4%) for stroke. There was evidence of substantial heterogeneity between studies for all outcomes (I2 > 90%. We found a high prevalence of complications in newly diagnosed type 2 diabetes in LMICs. Findings suggest that many people live with diabetes and are only diagnosed when they present with complications in LMICs. Research is needed to guide timely and effective identification of people living with diabetes in these settings.

OBJECTIVE: To assess the impact of tick-borne relapsing fever (TBRF) on the outcome of pregnancy. DESIGN: Case control study of 137 pregnant women (cases) and 120 non-pregnant women (controls) with TBRF between 1985 and 1995. SETTING: A rural hospital in Tabora Region, Tanzania. RESULTS: Risk of birth during the attack of TBRF was 58.0%, with an extremely high perinatal mortality of 436 per 1000 births. The total loss of pregnancies including abortions was 475. per 1000. Case-fatality rate in pregnant women was 1.5%, compared to 1.7% in the non-pregnant women. A Jarisch-Herxheimer reaction was seen in 1.5% of the cases and in 1.7% of controls. Relapse rate was 3.6%, compared to 1.7% in non-pregnant women. Pregnant women with TBRF show higher densities of spirochetes than non-pregnant women (p < 0.001). The risk of delivery during the attack was positively correlated to increasing density of the spirochetemia (p < 0.001) and to gestational age (p < 0.001). Perinatal death was related to low birthweight (p < 0.001) and low gestational age (p < 0.001) and not to degree of spirochetemia. CONCLUSIONS: The extremely high perinatal mortality rate during an attack asks for prevention and early effective management of TBRF. This is a challenge where access to health services in rural areas of developing countries is hampered by many factors.

BackgroundIn sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania.MethodsIn INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688.FindingsBetween June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were –0·65% (95% CI –5·76 to 4·46; p=0·80) unadjusted and –0·60% (–5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were –0·37% (one-sided 95% CI –1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and –0·36% (–1·99 to 1·28; pnon-inferiority<0·0001 adjusted).InterpretationIn sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV.FundingEuropean Union Horizon 2020 and Global Alliance for Chronic Diseases.