Isoniazid preventive therapy completion between July-September 2019: A comparison across HIV differentiated service delivery models in Uganda.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). To prevent TB among PLHIV, the Ugandan national guidelines recommend Isoniazid Preventive Therapy (IPT) across differentiated service delivery (DSD) models, an effective way of delivering ART. DSD models include Community Drug Distribution Point (CDDP), Community Client-led ART Delivery (CCLAD), Facility-Based Individual Management (FBIM), Facility-Based Group (FBG), and Fast Track Drug Refill (FTDR). Little is known about the impact of delivering IPT through DSD. METHODS: We reviewed medical records of PLHIV who initiated IPT between June-September 2019 at TASO Soroti (TS), Katakwi Hospital (KH) and Soroti Regional Referral Hospital (SRRH). We defined IPT completion as completing a course of isoniazid within 6-9 months. We utilized a modified Poisson regression to compare IPT completion across DSD models and determine factors associated with IPT completion in each DSD model. RESULTS: Data from 2968 PLHIV were reviewed (SRRH: 50.2%, TS: 25.8%, KH: 24.0%); females: 60.7%; first-line ART: 91.7%; and Integrase Strand Transfer Inhibitor (INSTI)-based regimen: 61.9%. At IPT initiation, the median age and duration on ART were 41.5 (interquartile range [IQR]; 32.3-50.2) and 6.0 (IQR: 3.7-8.6) years, respectively. IPT completion overall was 92.8% (95%CI: 91.8-93.7%); highest in CDDP (98.1%, 95%CI: 95.0-99.3%) and lowest in FBG (85.8%, 95%CI: 79.0-90.7%). Compared to FBIM, IPT completion was significantly higher in CDDP (adjusted rate ratio [aRR] = 1.15, 95%CI: 1.09-1.22) and CCLAD (aRR = 1.09, 95% CI 1.02-1.16). In facility-based models, IPT completion differed between sites (p<0.001). IPT completion increased with age for FBIM and CCLAD and was lower among female participants in the CCLAD (aRR = 0.82, 95%CI 0.67-0.97). CONCLUSION: IPT completion was high overall but highest in community-based models. Our findings provide evidence that supports integration of IPT within DSD models for ART delivery in Uganda and similar settings.

Bacterial isolates and antibiotic susceptibility among women with abnormal vaginal discharge attending the gynecology clinic at a tertiary hospital in southwestern Uganda: a cross-sectional study.

BACKGROUND: Abnormal vaginal discharge is a common complaint among women of reproductive age, affecting about one- third of all women. In resource-limited settings where access to laboratory services is limited, treatment is usually syndromic. This approach may result in ineffective treatment, with high recurrence rates and a potential of developing antibiotic resistance. This study aimed to determine the bacterial isolates and antibiotic susceptibility among women with an abnormal vaginal discharge attending the gynecology clinic at a tertiary hospital in Southwestern Uganda. METHODS: We conducted a hospital based cross-sectional study among 361 women aged 15-49 years, presenting with abnormal vaginal discharge at the gynecology clinic of Mbarara Regional Referral Hospital from December 2020 to June 2021. Demographic characteristics were collected using a structured questionnaire. We collected cervical and vaginal sterile swabs and subjected them to wet preparation and gram stain. The specimens were cultured for bacterial isolates. Susceptibility testing was performed on samples with bacterial isolates using the Kirby-Bauer disc diffusion method, on the commonly prescribed antibiotics in this setting. We summarized and described the bacterial isolates and antibiotic susceptibility patterns as frequencies and percentages. RESULTS: We enrolled 361 women with abnormal vaginal discharge. Bacteria were isolated in 29.6% (107/361) of the women, and the commonest isolates included; Staphylococcus aureus 48.6% (52/107), Klebsiella pneumoniae 29.9% (32/107) and Enterococcus faecalis 15% (16/107). Yeast cells were found in 17.7% (64/361) of the women with abnormal vaginal discharge. Cefuroxime (90.7%) and Ciprofloxacin (81.3%) had a high level of sensitivity while high levels of resistance were observed for Doxycycline (86.0%) and Azithromycin (67.0%). CONCLUSION: The common bacterial isolates were Staphylococcus aureus, Klebsiella pneumoniae and Enterococcus faecalis. The isolated bacteria were most sensitive to Cefuroxime and Ciprofloxacin but resistant to Doxycycline and Azithromycin. There is need for routine culture and susceptibility testing of women with abnormal vaginal discharge so as to guide treatment, minimize inappropriate antibiotic use and consequently reduce antibiotic resistance.

Repeatability of Pulse Oximetry Measurements in Children During Triage in 2 Ugandan Hospitals.

BACKGROUND: In low- and middle-income countries, health workers use pulse oximeters for intermittent spot measurements of oxygen saturation (SpO2). However, the accuracy and reliability of pulse oximeters for spot measurements have not been determined. We evaluated the repeatability of spot measurements and the ideal observation time to guide recommendations during spot check measurements. METHODS: Two 1-minute measurements were taken for the 3,903 subjects enrolled in the study conducted April 2020-January 2022 in Uganda, collecting 1 Hz SpO2 and signal quality index (SQI) data. The repeatability between the 2 measurements was assessed using an intraclass correlation coefficient (ICC), calculated using a median of all seconds of non-zero SpO2 values for each recording (any quality, Q1) and again with a quality filter only using seconds with SQI 90% or higher (good quality, Q2). The ICC was also recalculated for both conditions of Q1 and Q2 using the initial 5 seconds, then the initial 10 seconds, and continuing with 5-second increments up to the full 60 seconds. Lastly, the whole minute ICC was calculated with good quality (Q2), including only records where both measurements had a mean SQI of more than 70% (Q3). RESULTS: The repeatability ICC with condition Q1 was 0.591 (95% confidence interval [CI]=0.570, 0.611). Using only the first 5 seconds of each measurement reduced the repeatability to 0.200 (95% CI=0.169, 0.230). Filtering with Q2, the whole-minute ICC was 0.855 (95% CI=0.847, 0.864). The ICC did not improve beyond the first 35 seconds. For Q3, the repeatability rose to 0.908 (95% CI=0.901, 0.914). CONCLUSIONS: Training guidelines must emphasize the importance of signal quality and duration of measurement, targeting a minimum of 35 seconds of adequate-quality, stable data. In addition, the design of new devices should incorporate user prompts and force quality checks to encourage more accurate pulse oximetry measurements.

Best practices in the African Medicines Regulatory Harmonization initiative: Perspectives of regulators and medicines manufacturers.

In the African Medicines Regulatory Harmonization initiative, national regulatory authorities (NRAs) within each of Africa's regional economic communities coordinate their activities, rely on the work of one another and other trusted regulatory authorities, and apply other principles of smart regulation. The first regional medicines regulatory harmonization (MRH) initiative in Africa was launched in 2012, with the goal of accelerating access to quality, safe, effective medical products, and now five MRH initiatives are active on the continent. Thus, a wealth of knowledge regarding best practices and approaches to dealing with common challenges has accumulated. The goal of this qualitative study was to gather and share information on these best practices. To do this, we conducted interviews with key participants from four regional MRH initiatives-the East African Community (EAC), Southern African Development Community (SADC), Economic Community of West African States (ECOWAS), and Intergovernmental Authority on Development (IGAD)-as well as representatives from the pharmaceutical industry. Here we explore major themes that emerged from the interviews: 1. Transparency and reliability are critical; 2. Reliance is essential for smart regulation; 3. Multiple successful strategies for NRA capacity building have been identified; 4. Communication between heads of agencies is essential; 5. Cooperation at the regional level is not possible without leadership at the NRA level; 6. Sustainable funding remains challenging; and 7. Industry has important insights. We hope that the information on best practices shared in this article can benefit regional MRH initiatives inside and outside of Africa, ultimately helping them accelerate access to quality, safe, effective medical products.

Regulation of community advisory boards during conduct of clinical trials in Uganda: a qualitative study involving stakeholders.

BACKGROUND: Community advisory structures such as Community Advisory Boards (CABs) play an important role of helping researchers to better understand the community at each phase of the clinical trial. CABs can be a source of accurate information on the community, its perception of proposed research and may identify factors that make community members vulnerable to the problem under investigation. Although CABs help to build mutually beneficial relationships between the researcher(s) and the communities in which the clinical trial is being implemented, effective engagement would require ethical guidance and regulatory oversight. The study assessed the stakeholders' perspectives regarding the regulatory oversight of CABs in Uganda. METHODS: This was an exploratory study employing qualitative methods of data collection and analysis. Key informant interviews (KIIs) with the trial investigators, CAB chairpersons, community liaison officers, regulators and Research Ethics Committee (REC) chairpersons were conducted. A KII guide was designed and utilized during key informant interviews. The guide included questions on role of investigators and CAB members in clinical trials; challenges of community engagement; facilitation of CABs; regulatory oversight of CABs; work relationships between investigators and CABs; and opinions on how community trials should be conducted among others. All interviews were conducted in English. Qualitative data were transcribed verbatim. A code book was generated based on the transcripts and study objectives. Thematic analysis was used to analyze data and identify themes. Atlas ti was used to support data analysis. RESULTS: Of the 34 respondents, 35.3% were investigators, 32.3% CAB chairpersons, 23.5% research regulators/REC Chairs and 8.8% community liaison officers. The findings of the study revealed that CABs are appointed by the research institution/researcher, operate under the guidance of the researcher with limited independence. Additionally, the CABs provide voluntary service and lack guidelines or regulatory oversight. Four themes emerged. CONCLUSION: The operations and activities of CABs are not regulated by the national regulators or RECs. The regulatory oversight of CABs should be based on contextualized ethical guidelines. Need for additional training in research ethics, community engagement and sensitization on available ethics guidelines for research.

Effect of universal test and treat on retention and mortality among people living with HIV-infection in Uganda: An interrupted time series analysis.

BACKGROUND: Few studies have analysed the effect of HIV universal test and treat (UTT) on retention and mortality among people living with HIV (PLHIV) in routine care. We examined six-month retention and mortality at 11 health facilities (HFs) run by a large NGO, The AIDS Support Organisation (TASO), before and after UTT. METHODS: We used a quasi-experimental study using patient data extracted from 11 TASO HFs. Two periods, one before UTT (2015-2016) and the other during UTT (2017-2018) were compared. The primary outcome was six-month retention defined as the proportion of PLHIV who were alive and in care at six months from enrolment. The secondary outcome was six-month mortality defined as the proportion of PLHIV who died within six months from enrolment. We performed an interrupted time series analysis using graphical aids to study trends in six-month retention and mortality and a segmented regression to evaluate the effect of UTT. We used a generalized linear mixed model (GLMM) and generalized estimating equations (GEE) to account for facility-level clustering. RESULTS: Of the 20,171 PLHIV registered between 2015 and 2018 and included in the analysis, 12,757 (63.2%) were enrolled during the UTT period. 5256/7414 (70.9%) of the pre-UTT period compared to 12239/12757 (95.9%) of the UTT were initiated on ART treatment with 6 months from enrolment. The median time from enrolment to initiating ART was 14 (interquartile range (IQR): 0-31) days for the pre-UTT compared to 0 (IQR: 0-0) days for the UTT period. The median age at enrolment was 32.5 years for the pre-UTT and 35.0 years for the UTT period. Overall, the six-month retention just after scale-up of UTT, increased by 9.2 percentage points (p = 0.002) from the baseline value of 82.6% (95% CI: 77.6%-87.5%) but it eventually decreased at a rate 1.0 percentage point (p = 0.014) for cohorts recruited each month after UTT. The baseline six-month mortality was 3.3% (95% CI: 2.4%-4.2%) and this decreased by 1.6 percentage points (p = 0.003) immediately after UTT. The six-month mortality continued decreasing at a rate of 0.1 percentage points (p = 0.002) for cohorts enrolled each month after UTT. Retention differed between some health facilities with Rukungiri HF having the highest and Soroti the lowest retention. Retention was slightly higher among males and younger people. Mortality was highest among people aged 50 years and more. The effect of UTT on retention and mortality was similar across sex and age groups. CONCLUSION: Overall, UTT significantly led to an immediate increase in retention and decrease in mortality among PLHIV enrolled in HIV care from 11 HFs run by TASO in Uganda. However, retention (and mortality) significantly decreased for cohorts enrolled each month after UTT. Retention was highest in Rukungiri and lowest in Soroti HFs and slightly higher in males and younger people. Mortality was highest in older patients and lowest in adolescents. We recommend for innovative interventions to improve the overall retention particularly in facilities reporting low retention in order to achieve the UNAIDS 2030 target of 95-95-95.

Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system.

OBJECTIVE: To determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system. METHODS: Using data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index. RESULTS: A model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91. CONCLUSIONS: Reducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.

Capacity of community advisory boards for effective engagement in clinical research: a mixed methods study.

BACKGROUND: Community engagement is a key component in health research. One of the ways health researchers ensure community engagement is through Community Advisory Boards (CABs). The capacity of CABs to properly perform their role in clinical research has not been well described in many resource limited settings. In this study, we assessed the capacity of CABs for effective community engagement in Uganda. METHODS: We conducted a cross sectional study with mixed methods. We used structured questionnaires and key informant interviews (KII) to collect data from CAB members, trial investigators, and community liaison officers. For quantitative data, we used descriptive statistics while for qualitative data we used content analysis. RESULTS: Seventy three CAB members were interviewed using structured questionnaires; 58.9% males, median age 49 years (IQR 24-70), 71.2% had attained tertiary education, 42.5% never attended any research ethics training, only 26% had a training in human subject protection, 30.1% had training in health research, 50.7% never attended any training about the role of CABs, and 72.6% had no guidelines for their operation. On the qualitative aspect, 24 KIIs cited CAB members to have some skills and ability to understand and review study documents, offer guidance on community norms and expectations and give valuable feedback to the investigators. However, challenges like limited resources, lack of independence and guidelines, and knowledge gaps about research ethics were cited as hindrances of CABs capacity. CONCLUSION: Though CABs have some capacity to perform their role in the Ugandan setting, their functionality is limited by lack of resources to facilitate their work, lack of independence, lack of guidelines for their operations and limited knowledge regarding issues of research ethics and protection of the rights of trial participants.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Acceptability, perceived reliability and challenges associated with distributing HIV self-test kits to young MSM in Uganda: a qualitative study.

INTRODUCTION: HIV self-testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self-test (HIVST) to young men who have sex with men (MSM) in Uganda. METHODS: Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management. RESULTS: MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non-painful; and non-stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop-in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services. CONCLUSIONS: Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow-up, linkage to HIV care and prevention services are needed for effective results.

HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda.

OBJECTIVES: Recent publications suggest that fishing populations may be highly affected by the HIV epidemic. However, accurate data are scarce. The authors determined HIV and syphilis prevalence and associated risk factors in a fishing population of Lake Victoria in Uganda. METHODS: 10,188 volunteers aged ≥ 13 years from a census carried out in five fishing communities between February and August 2009 were invited to attend central study clinics established in each community. After informed consent, 2005 randomly selected volunteers responded to socio-demographic and risk assessment questions, provided blood for HIV testing and 1618 volunteers were also tested for syphilis. Risk factors were analysed using logistic regression. RESULTS: HIV and active syphilis (rapid plasma reagin titre ≥ 1:8) prevalences were 28.8% (95% CI 26.8 to 30.8) and 4.3% (95% CI 3.3 to 5.4), respectively, and high risk sexual behaviour was frequently reported. HIV prevalence was independently associated with female sex, increasing age, occupation (highest in fishermen), relationship to household head, self-reported genital sores and knowledge of an HIV infected partner. Alcohol consumption, syphilis and sexually transmitted infections (STIs) reported by health workers were associated with HIV in women, and genital discharge and inconsistent condom use in men. Syphilis prevalence was independently associated with age and alcohol consumption in women, and recent genital sores and sex under the influence of drugs in men. CONCLUSION: This fishing population characterised by a very high HIV prevalence, high syphilis prevalence and frequently reported sexual risk behaviours, urgently needs improved STI services and targeted behavioural interventions.