Management of type 1 diabetes in low- and middle-income countries: Comparative health system assessments in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.

EADSG Guidelines: Insulin Storage and Optimisation of Injection Technique in Diabetes Management.

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.

Capacity and capability of Tanzania health facilities to diagnose and manage diabetes mellitus in pregnancy.

AIMS: Gestational Diabetes Mellitus (GDM) remains a neglected cause of maternal and foetal morbidity and mortality in developing countries exacerbated by limited screening and management strategies. This study aimed to understanding how the RCH health system works in Tanzania, so as to provide opportunity for improving GDM screening and management. METHODS: A questionnaire was administered to facility staff and physical performance observed in 30 randomly selected public RCH facilities. RESULTS: Deficiencies identified included limited understaffing, late booking at ANC, and limited screening for GDM due to lack of equipment and supplies. Most women (96%) attending ANCs and postnatal care (87%) were managed at respective facilities with only 12% and 22% respectively being referred to higher levels of care. Facility staff were less trained or received fewer refresher courses in diabetes (0-5%), hypertension (4-6%), and other NCDs (0-16%) compared to training in PMCTC (39%), management of postpartum bleeding (31%) and HIV/AIDs (31%). CONCLUSION: Diabetes during pregnancy is rarely sought in public health facilities and its management is suboptimal. Training and refresher courses of staff in diabetes and hypertension should be uplifted and health systems should be strengthened to improve capacity and capability of facilities for better quality of care.

Clinical and virological response to antiretroviral drugs among HIV patients on first-line treatment in Dar-es-Salaam, Tanzania.

INTRODUCTION: In Tanzania, the follow-up on antiretroviral therapy (ART) response is based on clinical outcomes. We investigated virological response and ARV resistance mutations in relation to clinical response in ARV-treated patients. METHODOLOGY: A cross-sectional study of a cohort of 150 patients taking first-line ART in Dar-es-Salaam was conducted. Data were collected using standardized questionnaires and patients' blood samples. HIV viral load testing and genotyping was performed on all viremic samples. Statistical analyses compared clinical responders and non-responders. RESULTS: The median time on ART was 20 months; 71 (47%) patients were ART clinical responders. Clinical non-responders were more likely to have started ART with advanced disease with significantly lower median percentage weight gain (6% versus 20%) with respect to pre-treatment levels. Sixty-one (86%) and 64 (81%) of clinical responders and non-responders, respectively, had undetectable viral loads. Genotyping was successful in 24 (96%) virologically failing patients, among whom 83% had resistance mutations; 67% had dual nucleoside reverse transcriptase inhibitor (NRTI)/non-NRTI (NNRTI) resistance mutations. Seventeen (71%) and 19 (79%) patients had NRTI and NNRTI resistance mutations, respectively, which were related to the ART in use, with no difference between clinical responders and non-responders. The most prevalent subtypes were A and C, found in 9 (38%) and 7 (29%) patients, respectively. CONCLUSIONS: The observed virological response was high and did not correlate with clinical response. The prevalence of ARV resistance mutations was high in viraemic patients and was related to the ARV prescribed. We recommend use of viral load monitoring during ART in Tanzania.

Non communicable diseases in Tanzania: a call for urgent action.

Globally there is evidence of the growing burden of Non Communicable diseases (NCDs) especially in developing countries including Tanzania. This paper summarises the review of published papers on the magnitude of Non Communicable Diseases in the country. Current opportunities for management and control of NCDs are also explored. In this review diseases such as diabetes and hypertension have been shown to have increased over the years. Prevalence of risk factors such as obesity, dyslipidemia and smoking has been shown to be high with clear gender and urban rural differences. Generally there is paucity of national representative data on the burden of risk factors and prevalence of non-communicable diseases. The main risk factors for NCDs namely smoking, alcohol intake, unhealthy diet and low physical activity are prevalent in both rural and urban communities. The socio-demographic and economic transition has a big role in the current rise of non-communicable diseases in Tanzania. There are initiatives to control the burden of non-communicable diseases in the country. However there is need to focus more on primary prevention at population level targeting interventions to reduce exposure to tobacco, reduce alcohol intake, reduce salt intake, promote healthy diets and physical activity. For the prevention and control of NCDs, there needs to be a continuum from primary to tertiary prevention and a scope of interventions from the community level up to the national level. Community-based interventions are needed targeting the risk factors for primary prevention. In addition, secondary prevention measures are needed targeting those at high risk to ensure that they are identified early through a high risk targeted screening for early identification and appropriate care. Effective policies are needed to support such interventions.

Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania.

BACKGROUND: Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. METHODS: A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. RESULTS: Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). CONCLUSION: Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.

Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra Plus study.

OBJECTIVE: The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with highly active antiretroviral therapy (HAART) during breastfeeding. METHODS: Mitra Plus was an open-label, nonrandomized, prospective cohort study. HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine (ZDV) + lamivudine (3TC) + nevirapine (NVP). NVP was later replaced by nelfinavir for mothers with CD4 cell counts >200 cells per microliter or with adverse reaction to NVP. HAART was initiated at 34 weeks of gestation. For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microliter, HAART was started earlier if possible. Treatment of the mothers was stopped at 6 months except for those mothers who needed HAART for their own health. The infants received ZDV + 3TC for 1 week after birth. Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months. Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A. RESULTS: There were 441 infants included in the analysis of HIV-1 transmission. The cumulative transmission of HIV-1 was 4.1 % [95% confidence interval (CI): 2.2 to 6.0] at 6 weeks, 5.0% (95% CI: 2.9 to 7.1) at 6 months, and 6.0% (95% CI: 3.7 to 8.3) at 18 months after delivery. The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0% and between 6 months and 18 months 1.1%. The cumulative HIV infection or death rate was 8.6% (95% CI: 6.0 to 11.2) at 6 months and 13.6% (95% CI: 10.3 to 16.9) at 18 months after delivery. Viral load at enrollment and duration of HAART before delivery were significantly associated with transmission but CD4 cell count at enrollment was not. The median time of breastfeeding was 24 weeks. The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery (adjusted relative hazard = 0.49, P < 0.001). The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trial arm A at 18 months (adjusted relative hazard = 0.61, P = 0.007). NVP-related mucocutaneous rash was demonstrated in 6.5% of 429 NVP-exposed women. The incidence of NVP-related grade 3 or 4 hepatotoxicity was low (0.5%). CONCLUSIONS: HAART given to HIV-infected mothers in late pregnancy and during breastfeeding resulted in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding. The extended maternal prophylaxis with HAART for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need HAART for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness.

Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study.

OBJECTIVE: To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period. DESIGN: An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra). METHODS: HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration. RESULTS: There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL. CONCLUSIONS: The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.

Patterns of sexually transmitted infections in adolescents and youth in Dar es Salaam, Tanzania.

BACKGROUND: Syndromic management of STIs has been advocated as simplified and cheap approach. Youth have been reported to be at increased risk of acquiring STIs which can facilitate HIV transmission. We have investigated the relationship between the syndromic management and specific aetiology diagnosis and its relationship with HIV infection and health seeking behaviour among youth attending a reproductive health clinic in Dar es Salaam, Tanzania. METHODS: Between September 1998 and February 1999 among 1895 adolescents and youth below 25 years seen in the clinic 199 (10.5%) were randomly selected and consented to participate in the study. A standard questionnaire was administered. Blood and vaginal or urethral specimens were taken and investigated for STI causative agents. RESULTS: Among a total of 199 studied adolescents and youth 22.6 % were teenagers, with fewer females 17.8% than males; 27.5% (p < 0.018). 20.8% of the females compared to 11.5% in males were HIV infected. Genital discharge was the most common complaint which was reported in 54.1% of male and 63.4 % of female patients. All males with gonorrhoea and four out of five with Chlamydia were given appropriate treatment with syndromic management, while 28% women with gonorrhoea or Chlamydia received appropriate treatment by syndromic management. All patients found with active syphilis by serology had not complained of genital ulcers and would not have been assigned to syndromic treatment for syphilis at the initial visit. CONCLUSION: The burden of STIs in this youth population is large indicating that youth are at increased risk of STIs and will certainly require youth friendly clinics. There is a need to refine the current syndromic management guidelines.

Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania.

The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.

The natural course of disease following HIV-1 infection in dar es salaam, Tanzania: a study among hotel workers relating clinical events to CD4 T-lymphocyte counts.

Current HIV management guidelines are based on natural history studies from the developed world. Data on the similarity of the natural course of HIV-1 infection conflict with studies in the developing world. A cohort of 1887 hotel workers with no access to antiretroviral therapy was followed between 1990 and 1998 in Dar es Salaam through annual clinical evaluations and CD4+ T-lymphocyte (CD4 cell) count determinations. 196 (10.4%) were HIV-1 sero-prevalents; 133 (7.9%) were HIV-1 sero-incidents; and 1558 (82.6%) remained HIV seronegative. Follow-up duration was 13,719 and 82,742 months for HIV-1 seropositives and HIV seronegatives respectively. Clinical events occurred at median CD4 cell counts similar to those previously reported from the developed world, but death occurred at higher counts. Off-duty last 6 months, chronic diarrhoea and a faster CD4 cell count decline were associated with faster disease progression and death. In Tanzania HIV natural history is similar to that from the developed world and similar management guidelines could be employed.

Rate of decline of absolute number and percentage of CD4 T lymphocytes among HIV-1-infected adults in Dar es Salaam, Tanzania.

OBJECTIVE: To determine the rate of decline of CD4 T lymphocytes among HIV-1-infected individuals. DESIGN AND SETTING: A prospective open cohort study of workers in three hotels in Dar es Salaam. METHODS: The workers were seen yearly during the study. CD4 T lymphocyte counts were determined using flow cytometry. The CD4 T-lymphocyte slopes were determined using a linear regression model. RESULTS: During the 9-year study period 682 subjects were selected for lymphocyte subset determinations. Of these, 94 HIV-1-seroprevalent (72%), 77 HIV-1-seroincident (67%) and 325 seronegative (75%) individuals had three or more CD4 T-cell determinations, and were used for calculations of CD4 cell slopes with a mean follow-up period of 71.4, 52.9 and 86.0 months, respectively. The median yearly decline of the CD4 T-lymphocyte counts and percentages among seroprevalent individuals was -21.5 cells/microl and -1.3%; among the seroincident individuals the median decline was -22.0 cells/microl and -1.5%. In seroincident individuals the mean duration to a CD4 T-lymphocyte level corresponding to a definition of AIDS was 13.3 years or 11.8 years for CD4 cell counts or percentages, respectively. HIV-1-seropositive subjects who died had significantly steeper CD4 cell slopes than those who survived. CONCLUSION: The rates of CD4 T-lymphocyte decline in HIV-1-infected individuals in our population are similar to those reported in Europe and north America.

The prevalence and pattern of skin diseases in relation to CD4 counts among HIV-infected police officers in Dar es Salaam.

Among HIV-infected individuals, skin diseases cause significant morbidity and are frequently the initial indication of immunosuppression. From an on-going cohort study to determine prevalence and incidence of HIV infection among police officers (POs) and their suitability for HIV vaccine trials, a sub-study was carried out to determine the prevalence and pattern of skin diseases among HIV-infected POs and relate this to their immunodeficiency status. Consenting HIV-infected POs and their age and sex-matched HIV-negative officers were assessed for presence and type of skin diseases at their workplaces. A questionnaire was used for data collection. Immunodeficiency was measured by plasma CD4+ lymphocytes using flow cytometry. Between November 1998 and 31 December 2000, 716 POs were assessed. Overall HIV-1 prevalence was 17.7% (127/716). One hundred and ninety-one POs (26.7%) had at least one skin diagnosis. HIV-infected POs had significantly higher (41.7%) prevalence of skin diseases than HIV-uninfected POs (26.4%), P = 0.002. Fungal infections were common in both HIV-infected and uninfected POs. Among the HIV infected, other common diseases were: herpes zoster (11.8%); pruritic papular eruption (PPE) (7.1%); seborrheic dermatitis (5.5%); and Kaposi's sarcoma (KS) (1.6%). KS and PPE were associated with severe immunodeficiency, with mean absolute (percentage) CD4+ counts of 75.5 cells/microL (4.0%) and 71.7 cells/microL (4.8%), respectively. The values for herpes zoster and seborrheic dermatitis were 271.1 cells/micronL (12.4%) and 206.3 cells/microL (11.3%), respectively. Skin diseases were common among HIV-infected POs. PPE and KS are markers of severe immunodeficiency due to HIV. PPE, herpes zoster and KS strongly suggest underlying HIV-related immunodeficiency and patients with these conditions should be counselled and tested for HIV.