Barriers to Accessing Internationally Controlled Essential Medicines in Uganda: A Qualitative Study.

CONTEXT: Access to internationally controlled essential medicines is a problem worldwide. More than five billion people cannot access opioids for pain and palliative care or do not have access to surgical care or anesthetics, 25 million people living with epilepsy do not have access to their medicines, and 120,000 women die annually owing to postpartum hemorrhage. In Uganda, access to controlled medicines is also problematic, but a lack of data on factors that influence access exists. OBJECTIVES: The objective of this study was to identify the social, cultural, and regulatory barriers that influence access to internationally controlled essential medicines in Uganda. METHODS: Semistructured interviews with 15 key stakeholders with knowledge on controlled medicines from relevant institutions in Uganda. Interviews were transcribed verbatim and analyzed using the Access to Medicines from a Health System Perspective framework. RESULTS: Barriers in accessing controlled medicines were experienced owing to lack of prioritization, difficulties in finding the balance between access and control, deficiencies in the workings of the estimate and distribution system, lack of knowledge, inadequate human resources, expenses related to use and access, and stigma. It was believed that some abuse of specific controlled medicines occurred. CONCLUSION: The findings of this research indicate that to improve access to internationally controlled essential medicines in Uganda, health system strengthening is needed on multiple fronts. Active engagement and concerted efforts are needed from all stakeholders to ensure access and prevent abuse.

A Cross-Sectional Examination of Physical Activity Levels and Their Socio-Demographic Determinants in Southern Tanzania.

Physical activity is essential for healthy aging. Evidence suggests that vigorous-intensity physical activity (VPA) may be more beneficial than moderate-intensity physical activity (MPA). We examined physical activity levels (MPA, VPA and total physical activity), and their socio-demographic determinants in 2311 participants (15⁻93 years; 68% women) of the MZIMA Open Community Cohort, who had complete relevant data. Physical activity levels were estimated in minutes per week across three domains—work, leisure and transport. We created three outcome variables: low MPA (<150 min per week of MPA), low VPA (<75 min per week of VPA) and insufficient physical activity (IPA: <150 min per week of total physical activity) and applied sample-weighted multivariable logistic regression to assess associations with potential socio-demographic determinants. Prevalence of IPA, low MPA and low VPA were 25%, 26% and 65% respectively. IPA and low MPA were correlated (Spearman R = 0.98; p < 0.001). Work, leisure and transport contributed 54%, 25% and 21% to total physical activity respectively. IPA and low VPA were significantly associated with female sex, lower education, non-manual occupation and frequent fruit consumption. We observed significant differences by sex (Pheterogeneity < 0.001), on the associations between education and IPA, and between age, occupation and low VPA. In conclusion, low levels of VPA, which were more pronounced in women, support the monitoring and promotion of VPA alongside overall physical activity. Leisure-related activities should also be promoted towards gains in vigorous-intensity and total physical activity in this setting.

Insufficient Fruit and Vegetable Intake in a Low- and Middle-Income Setting: A Population-Based Survey in Semi-Urban Tanzania.

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.

Provider initiated tuberculosis case finding in outpatient departments of health care facilities in Ghana: yield by screening strategy and target group.

BACKGROUND: Meticulous identification and investigation of patients presenting with tuberculosis (TB) suggestive symptoms rarely happen in crowded outpatient departments (OPDs). Making health providers in OPDs diligently follow screening procedures may help increase TB case detection. From July 2010 to December 2013, two symptom based TB screening approaches of varying cough duration were used to screen and test for TB among general outpatients, PLHIV, diabetics and contacts in Accra, Ghana. METHODS: This study was a retrospective analysis comparing the yield of TB cases using two different screening approaches, allocated to selected public health facilities. In the first approach, the conventional 2 weeks cough duration with or without other TB suggestive symptoms was the criterion to test for TB in attendants of 7 general OPDs. In the second approach the screening criteria cough of >24 hours, as well as a history of at least one of the following symptoms: fever, weight loss and drenching night sweats were used to screen and test for TB among attendants of 3 general OPDs, 7 HIV clinics and 2 diabetes clinics. Contact investigation was initiated for index TB patients. The facilities documented the number of patients verbally screened, with presumptive TB, tested using smear microscopy and those diagnosed with TB in order to calculate the yield and number needed to screen (NNS) to find one TB case. Case notification trends in Accra were compared to those of a control area. RESULTS: In the approach using >24-hour cough, significantly more presumptive TB cases were identified among outpatients (0.82% versus 0.63%), more were tested (90.1% versus 86.7%), but less smear positive patients were identified among those tested (8.0% versus 9.4%). Overall, all forms of TB cases identified per 100,000 screened were significantly higher in the >24-hour cough approach at OPD (92.7 for cough >24 hour versus 82.7 for cough >2 weeks ), and even higher in diabetics (364), among contacts (693) and PLHIV (995). NNS (95% Confidence Interval) varied from 100 (93-109) for PLHIV, 144 (112-202) for contacts, 275 (197-451) for diabetics and 1144 (1101-1190) for OPD attendants. About 80% of the TB cases were detected in general OPDs. Despite the intervention, notifications trends were similar in the intervention and control areas. CONCLUSION: The >24-hour cough approach yielded more TB cases though required TB testing for a larger number of patients. The yield of TB cases per 100,000 population screened was highest among PLHIV, contacts, and diabetics, but the majority of cases were detected in general OPDs. The intervention had no discernible impact on general case notification.

A pragmatic approach to measuring, monitoring and evaluating interventions for improved tuberculosis case detection.

The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings.

Serodiagnosis of tuberculous lymphadenitis using a combination of antigens.

BACKGROUND: The diagnosis of extra-pulmonary tuberculosis (EPTB) by conventional methods such as culture and microscopy has low sensitivity and requires an invasive procedure. A simple rapid serological test would be of great value. METHODS: Six antigens (ESAT-6, Ag85A, TB10.4, Rv3881c, lipoarabinomannan (LAM) and Ara6-BSA) were tested in an ELISA to detect antigen specific IgG and IgM antibodies in sera from 54 culture and histology-confirmed tuberculous lymphadenitis (TBLN) patients, among whom four were HIV seropositive, sera from 25 smear positive pulmonary tuberculosis (PTB) patients, 15 culture and histology-negative lymphadenitis (non-TBLN) patients (n=15) and 22 healthy controls (HCs). RESULTS: The sensitivities of the antigens for the detection of IgG in sera of TBLN patients ranged from 4 to 30 %. Specificities ranged from 91 to 100 % with sera from HCs. Sensitivities of the antigens for detection of IgM ranged from 0 to 15 % and specificities ranged from 91 to 100 %. LAM was the most potent antigen followed by ESAT-6 and Rv3881c for detection of IgG. However, the sensitivity for antigen specific IgG antibody detection was improved when LAM was combined with ESAT-6 and Rv3881c.The sensitivity was 54 % and the specificity 91 %. CONCLUSIONS: The study suggests that the combined use of LAM, ESAT-6 and Rv3881c for the detection of IgG in sera of TBLN patients could be a supplement to microscopy of fine- needle aspirate (FNA) to diagnose EPTB.

A relação entre soroprevalência de anticorpos contra o glicolipídeo fenólico-I entre crianças em idade escolar e endemicidade da hanseníase no Brasil / The relation between seroprevalence of antibodies against phenolic glycolipid-I among school children and leprosy endemicity in Brazil

Os programas de controle da hanseníase se beneficiariam de um método fácil para estimar prevalência e avaliar o impacto das ações de controle na prevalência da doença. A determinação da soroprevalência de anticorpos contra PGL-I através de estudos com crianças em idade escolar foi sugerida como indicador útil da taxa de prevalência da hanseníase a nível municipal.Para investigar se a soropositividade estaria associada aos coeficientes de detecção da hanseníase e se poderia ser usada como indicador da prevalência em outras áreas, 7.073 crianças em três estados endêmicos de hanseníase no Brasil foram testadas. Resultados mostram uma considerável variação da distribuição de soropositividade nas comunidades, independente do número de casos de hanseníase detectados. A soroprevalência foi significativamente menor nos colégios. Nenhuma diferença na distribuição da soropositividade determinada por ELISA ou dipstick foi observada. Nenhuma correlação entre o coeficiente de detecção da hanseníase e soropositividade pôde ser estabelecida.

Leprosy control programs would benefit expressively from an easy method to estimate disease prevalence and to assess the effect of leprosy control measures on disease prevalence. Determination of the seroprevalence of antibodies to PGL-I through school children surveys might be a useful indicator of leprosy prevalence at the district level. To investigate whether seropositivity rates could be related to leprosy detection rates and whether seropositivity could be used as a proximal indicator to predict the leprosy incidence in other areas, 7,073 school children in three different leprosy-endemic states in Brazil were tested. The results show a widely varying distribution of seropositivity in the communities independent of the number of leprosy cases detected. Seroprevalence was significantly lower at private schools. No differences in the patterns of seropositivity between ELISA and dipstick were observed. No correlation between leprosy detection rate and seropositivity rates could be established.

Comparison of PCR with the routine procedure for diagnosis of tuberculosis in a population with high prevalences of tuberculosis and human immunodeficiency virus.

Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) as employed in most low-income countries is cheap and easy to use, but its low sensitivity is a major drawback. The low specificity of chest X-rays, used for the diagnosis of smear-negative TB, risks high levels of overdiagnosis. Major advances in molecular techniques, which rapidly identify mycobacterial DNA in sputa, may overcome these obstacles. In this study, the AMPLICOR PCR system was used to diagnose pulmonary TB in a developing country with high prevalences of both TB and human immunodeficiency virus (HIV). The sensitivity and specificity of this technique were compared to those of the usual diagnostic techniques. Sputum specimens were collected from 1,396 TB suspects attending the Rhodes Chest Clinic, Nairobi, Kenya. The specimens were analyzed for the presence of Mycobacterium tuberculosis by PCR; culture on Löwenstein-Jensen medium was used as the "gold standard." All culture-positive samples were genotyped to identify the mycobacterial species. The sensitivity and specificity of PCR were 93 and 84%, respectively. HIV status did not affect the sensitivity of PCR. A total of 99.7% of the true smear-positive and 82.1% of the true smear-negative TB patients were correctly identified by PCR. PCR detected M. tuberculosis in 11.7% of the culture-negative suspects, 60% of which had one or two PCR-positive sputum specimens. Of the 490 positive cultures, 486 were identified as M. tuberculosis. The high sensitivity of Amplicor PCR merits usage in a clinical setting with high TB and HIV burdens. Thus, PCR can be considered as an alternative to ZN staining in combination with chest X-ray for diagnosis of TB; however, cost-effectiveness studies and operational studies are required to support an evidence-based decision of introducing PCR for TB control in high-burden environments.

Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05) on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease

Epidemiology of leprosy on five isolated islands in the Flores Sea, Indonesia.

We conducted a population-based survey on five small islands in South Sulawesi Province (Indonesia) to collect baseline data previous to a chemoprophylactic intervention study aiming at interrupting the transmission of Mycobacterium leprae. Here we describe the present leprosy epidemiology on these geographically isolated islands. Of the 4774 inhabitants living in the study area 4140 were screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new and 11 old patients), representing a new case detection rate (CDR) of 205/10 000 and a prevalence rate of 195/10 000. CDRs were similar for males and females. Male patients were more often classified as multibacillary (MB) than women. Of the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB) 2-5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy endemicity leprosy patients were extensively clustered, i.e. not equally distributed among the islands and within the islands among the houses.