Linkage to care for newly diagnosed human immunodeficiency virus (HIV) patients is important to ensure that patients have good access to care. However, there is little information about factors ...influencing linkage to care for HIV patients. We aimed to identify existing measures in place that promote linkage to care and to explore facilitators and barriers to linkage to care for clients diagnosed with HIV/acquired immune deficiency syndrome at a rural health center in Uganda. This descriptive qualitative study enrolled 33 purposively selected participants who included expert clients, linkage facilitators, heads of families with people living with HIV, and health workers. Data were collected using in-depth interviews that were audio-recorded, transcribed, and translated. The data were manually analyzed to generate themes. The following four themes were generated: 1) availability of services that include counseling, testing, treatment, follow-up, referral, outreach activities, and support systems. 2) Barriers to linkage to care were at the individual, health facility, and community levels. Individual-level barriers were socioeconomic status, high transport costs, fear of adverse drug effects, fear of broken relationships, and denial of positive results or treatment, while health facility barriers were reported to be long waiting time, negative staff attitude, and drug stock outs. Community barriers were mostly due to stigma experienced by HIV clients, resulting in discrimination by community members. 3) Facilitators to linkage to care were positive staff attitudes, access to information, fear of death, and support from others. 4) Suggestions for improving service delivery were shortening waiting time, integrating HIV services, increasing staff numbers, and intensifying outreaches. Our findings highlight the importance of stakeholder involvement in linkage to care. Access and linkage to care are positively and negatively influenced at the individual, community, and health facility levels. However, integration of HIV services and intensifying outreaches are key to improving linkage to care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy ...and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.
A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda ISRCTN32849447. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15-2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73-0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome.
Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.
Current Controlled Trials ISRCTN32849447.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aimed to investigate life-course factors associated with blood pressure (BP) among Ugandan adolescents. Between 9th April 2003 and 24th November 2005, 2507 pregnant women from Entebbe municipality ...and Katabi sub-county were enrolled into a deworming trial. The resulting 2345 live-born offspring were followed to age 10 or 11 years, when between 20th May 2014 to 16th June 2016, BP was measured following standard protocols. Factors associated with BP were assessed using multivariable linear regression. BP was measured in 1119 adolescents with a median age of 10.2 years. Mean systolic BP and diastolic BP was 105.9 mmHg (standard deviation (SD) 8.2) and 65.2 mmHg (SD 7.3), respectively. Maternal gestational body mass index (BMI), higher maternal education status and family history of hypertension were positively associated with adolescent BP. Childhood (age ≤5 years) malaria was associated with lower adolescent systolic BP. Factors measured at time of BP measurement positively associated with systolic BP were age, BMI, waist circumference and Trichuris trichiura (whipworm) infection; higher vegetable consumption was associated with lower systolic BP. Results for diastolic BP were similar, except higher fruit, rather than higher vegetable consumption was associated with lower diastolic BP and there was no association with waist circumference or Trichuris trichiura infection. In summary, life-course exposures were associated with adolescent BP in this tropical birth cohort. Malaria early in life could impact later BP. Interventions initiated early in life targeting individuals with family history of hypertension, aiming to reduce adiposity (in pregnancy and adolescence) and promoting fruit and vegetable consumption might contribute to reducing the risk of high BP and subsequent cardiovascular diseases.
IntroductionVaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering ...identification of strategies for optimising vaccine effectiveness. We hypothesise that urban–rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections.Methods and analysisThree related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day ‘0’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and ‘trans-kingdom’ mediators in parasite modulation of vaccine-specific responses.Ethics and disseminationEthics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numbersISRCTN60517191, ISRCTN62041885, ISRCTN10482904.
IntroductionThere is evidence that BCG immunisation may protect against unrelated infectious illnesses. This has led to the postulation that administering BCG before unrelated vaccines may enhance ...responses to these vaccines. This might also model effects of BCG on unrelated infections.Methods and analysisTo test this hypothesis, we have designed a randomised controlled trial of BCG versus no BCG immunisation to determine the effect of BCG on subsequent unrelated vaccines, among 300 adolescents (aged 13–17 years) from a Ugandan birth cohort. Our schedule will comprise three main immunisation days (week 0, week 4 and week 28): BCG (or no BCG) revaccination at week 0; yellow fever (YF-17D), oral typhoid (Ty21a) and human papillomavirus (HPV) prime at week 4; and HPV boost and tetanus/diphtheria (Td) boost at week 28. Primary outcomes are anti-YF-17D neutralising antibody titres, Salmonella typhi lipopolysaccharide-specific IgG concentration, IgG specific for L1-proteins of HPV-16/HPV-18 and tetanus and diphtheria toxoid-specific IgG concentration, all assessed at 4 weeks after immunisation with YF, Ty21a, HPV and Td, respectively. Secondary analyses will determine effects on correlates of protective immunity (where recognised correlates exist), on vaccine response waning and on whether there are differential effects on priming versus boosting immunisations. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of BCG revaccination on vaccine responses. Further analyses will assess which life course exposures influence vaccine responses in adolescence.Ethics and disseminationEthics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN10482904.
Background: The postpartum period is a critical time to address the unmet family planning needs and reduce the risk of too-soon pregnancies, maternal and child morbidity, and mortality. The study was ...conducted to determine the factors influencing the uptake of postpartum family planning among postpartum mothers 0 to 6 weeks postpartum Method: The study was a cross-sectional study that employed quantitative methods for data collection. 56 postpartum mothers present at the study area at the time of data collection were counseled and interviewed using a semi-structured questionnaire. Result: There is a significant association between age and uptake of PPFP where mothers at a younger age are more likely to use PPFP within 6 weeks after delivery x2(1) =6.222a; p<0.045, between religion and uptake of PPFP x2(1) =6.257a; p<0.044. Also, a significant association between attitude and uptake of PPFP where mothers who perceived PPFP to be both very good and good are more likely to use PPFP x2(1) =7.840a; p<0.020. In the same way, challenges such as inadequate counseling, long waiting time, inadequate staffing, and uncooperative health workers may affect the use of PPFP within 6 weeks after delivery x2(1) =10.114a; p<0.039. Conclusion: Commonly identified socio-demographic factors including age groups, religion, and attitude were significantly associated with the utilization of PPFP within 0-6 weeks. These socio-demographic factors are made worst by some health facility factors such as inadequate counseling of mothers, uncooperative health workers, and often few skilled service providers leading to over waiting by the clients. Recommendation: Strengthening the health facility's ability to adequately disseminate accurate information to mothers and the community at large concerning IPPFP. Healthcare providers should build the capacity of community health workers to promote effective community awareness about PPFP and its advantages to families and society at large.
Background
Genetic association studies of blood pressure (BP) have mostly been conducted in non‐African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic ...variants associated with BP among Ugandan adolescents.
Methods
Systolic and diastolic BP were measured among 10‐ and 11‐year olds. Whole‐genome genotype data were generated using Illumina omni 2.5M arrays and untyped variants were imputed. Genome‐wide association study (GWAS) was conducted using linear mixed model regression to account for population structure. Linear regression analysis was used to assess whether variants previously associated with BP (p < 5.0 × 10−8) in published BP GWASs were replicated in our study.
Results
Of the 14 million variants analyzed among 815 adolescents, none reached genome‐wide significance (p < 5.0×10−8) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10−7) for systolic BP and rs12991132 (p = 4.0 × 10−7) for diastolic BP. Thirty‐three (17 single nucleotide polymorphisms (SNPs) for systolic BP, 15 SNPs for diastolic BP and one SNP for both) of 330 variants previously identified as associated with BP were replicated in this study, but none remained significant after accounting for multiple testing.
Conclusion
Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings.
Using the Entebbe Mother and Baby Study, we aimed to identify genetic variants associated with blood pressure (BP) among Ugandan adolescents. We conducted Genome‐wide association study (GWAS) and replication analysis for variants associated with BP. Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings.
Trials done in infants with low birthweight in west Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against ...non-tuberculous infections. This study investigated whether BCG alters all-cause infectious disease morbidity in healthy infants in a different high-mortality setting, and explored whether the changes are mediated via trained innate immunity.
This was an investigator-blind, randomised, controlled trial done at one hospital in Entebbe, Uganda. Infants who were born unwell (ie, those who were not well enough to be discharged directly home from the labour ward because they required medical intervention), with major congenital malformations, to mothers with HIV, into families with known or suspected tuberculosis, or for whom cord blood samples could not be taken, were excluded from the study. Any other infant well enough to be discharged directly from the labour ward was eligible for inclusion, with no limitation on gestational age or birthweight. Participants were recruited at birth and randomly assigned (1:1) to receive standard dose BCG 1331 (BCG-Danish) on the day of birth or at age 6 weeks (computer-generated randomisation, block sizes of 24, stratified by sex). Investigators and clinicians were masked to group assignment; parents were not masked. Participants were clinically followed up to age 10 weeks and contributed blood samples to one of three immunological substudies. The primary clinical outcome was physician-diagnosed non-tuberculous infectious disease incidence. Primary immunological outcomes were histone trimethylation at the promoter region of TNF, IL6, and IL1B; ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation; and transferrin saturation and hepcidin levels. All outcomes were analysed in the modified intention-to-treat population of all randomly assigned participants except those whose for whom consent was withdrawn. This trial is registered with the International Standard Randomised Controlled Trial Number registry (#59683017).
Between Sept 25, 2014, and July 31, 2015, 560 participants were enrolled and randomly assigned to receive BCG at birth (n=280) or age 6 weeks (n=280). 12 participants assigned to receive BCG at birth and 11 participants assigned to receive BCG at age 6 weeks were withdrawn from the study by their parents shortly after randomisation and were not included in analyses. During the first 6 weeks of life before the infants in the delayed vaccination group received BCG vaccination, physician-diagnosed non-tuberculous infectious disease incidence was lower in infants in the BCG at birth group than in the delayed group (98 presentations in the BCG at birth group vs 129 in the delayed BCG group; hazard ratio HR 0·71 95% CI 0·53–0·95, p=0·023). After BCG in the delayed group (ie, during the age 6–10 weeks follow-up), there was no significant difference in non-tuberculous infectious disease incidence between the groups (88 presentations vs 76 presentations; HR 1·10 0·87–1·40, p=0·62). BCG at birth inhibited the increase in histone trimethylation at the TNF promoter in peripheral blood mononuclear cells occurring in the first 6 weeks of life. H3K4me3 geometric mean fold-increases were 3·1 times lower at the TNF promoter (p=0·018), 2·5 times lower at the IL6 promoter (p=0·20), and 3·1 times lower at the IL1B promoter (p=0·082) and H3K9me3 geometric mean fold-increases were 8·9 times lower at the TNF promoter (p=0·0046), 1·2 times lower at the IL6 promoter (p=0·75), and 4·6 times lower at the IL1B promoter (p=0·068), in BCG-vaccinated (BCG at birth group) versus BCG-naive (delayed BCG group) infants. No clear effect of BCG on ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation, or transferrin saturation and hepcidin concentration, was detected (geometric mean ratios between 0·68 and 1·68; p≥0·038 for all comparisons).
BCG vaccination protects against non-tuberculous infectious disease during the neonatal period, in addition to having tuberculosis-specific effects. Prioritisation of BCG on the first day of life in high-mortality settings might have significant public-health benefits through reductions in all-cause infectious morbidity and mortality.
Wellcome Trust.
For the Luganda and Swahili translations of the abstract see Supplementary Materials section.
BCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A–MVA85A ...compared with BCG revaccination among Ugandan adolescents.
After ChAdOx1 85A dose escalation and age de-escalation, we did a randomised open-label phase 2a trial among healthy adolescents aged 12–17 years, who were BCG vaccinated at birth, without evident tuberculosis exposure, in Entebbe, Uganda. Participants were randomly assigned (1:1) using a block size of 6, to ChAdOx1 85A followed by MVA85A (on day 56) or BCG (Moscow strain). Laboratory staff were masked to group assignment. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 28 and serious adverse events (SAEs) throughout the trial; and IFN-γ ELISpot response to antigen 85A (day 63 geometric mean and days 0–224 area under the curve; AUC).
Six adults (group 1, n=3; group 2, n=3) and six adolescents (group 3, n=3; group 4, n=3) were enrolled in the ChAdOx1 85A-only dose-escalation and age de-escalation studies (July to August, 2019). In the phase 2a trial, 60 adolescents were randomly assigned to ChAdOx1 85A–MVA85A (group 5, n=30) or BCG (group 6, n=30; December, 2019, to October, 2020). All 60 participants from groups 5 and 6 were included in the safety analysis, with 28 of 30 from group 5 (ChAdOx1 85A–MVA85A) and 29 of 30 from group 6 (BCG revaccination) analysed for immunogenicity outcomes. In the randomised trial, 60 AEs were reported among 23 (77%) of 30 participants following ChAdOx1 85A–MVA85A, 31 were systemic, with one severe event that occurred after the MVA85A boost that was rapidly self-limiting. All 30 participants in the BCG revaccination group reported at least one mild to moderate solicited AE; most were local reactions. There were no SAEs in either group. Ag85A-specific IFN-γ ELISpot responses peaked on day 63 in the ChAdOx1 85A–MVA85A group and were higher in the ChAdOx1 85A-MVA85A group compared with the BCG revaccination group (geometric mean ratio 30·59 95% CI 17·46–53·59, p<0·0001, day 63; AUC mean difference 57 091 95% CI 40 524–73 658, p<0·0001, days 0–224).
The ChAdOx1 85A–MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines.
UK Research and Innovations and Medical Research Council.
For the Swahili and Luganda translations of the abstract see Supplementary Materials section.
Abstract
Background
The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, ...community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity.
Methods
In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly.
Results
The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio RR 1.11, 95% confidence interval CI 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms.
Conclusions
Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions.
Clinical Trials Registration
ISRCTN47196031.
In a cluster-randomized trial of intensive versus standard anthelminthic treatment, intensive treatment reduced Schistosoma mansoni intensity and hookworm prevalence, but did not effect atopy, allergy-related diseases, or helminth-related pathology. Additional interventions are required to reduce transmission in schistosomiasis hot spots.
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