Can an integrated intervention package including peer support increase the proportion of health facility births? A cluster randomised controlled trial in Northern Uganda.

OBJECTIVE: To assess the effect of an integrated intervention package compared with routine government health services on the frequency of health facility births. SETTING: Three subcounties of Lira district in Northern Uganda. DESIGN: A cluster randomised controlled trial where a total of 30 clusters were randomised in a ratio of 1:1 to intervention or standard of care. PARTICIPANTS: Pregnant women at ≥28 weeks of gestation. INTERVENTIONS: Participants in the intervention arm received an integrated intervention package of peer support, mobile phone messaging and birthing kits during pregnancy while those in the control arm received routine government health services ('standard of care'). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of women giving birth at a health facility in the intervention arm compared with the control arm. Secondary outcomes were perinatal and neonatal deaths. RESULTS: In 2018-2019, 995 pregnant women were included in 15 intervention clusters and 882 in 15 control clusters. The primary outcome was ascertained for all except one participant who died before childbirth. In the intervention arm, 754/994 participants (76%) gave birth at a health facility compared with 500/882 (57%) in the control arm. Participants in the intervention arm were 35% more likely to give birth at a health facility compared with participants in the control arm, (risk ratio 1.35 (95% CI 1.20 to 1.51)) and (risk difference 0.20 (95% CI 0.13 to 0.27)). Adjusting for baseline differences generated similar results. There was no difference in secondary outcomes (perinatal or neonatal mortality or number of postnatal visits) between arms. CONCLUSION: The intervention was successful in increasing the proportion of facility-based births but did not reduce perinatal or neonatal mortality. TRIAL REGISTRATION NUMBER: NCT02605369.

Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats.

Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.

Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda.

BACKGROUND: Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance of Plasmodium species to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda. METHODS: An ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor. RESULTS: A total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species were Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica and Mangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed. CONCLUSION: This study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.

Are antibiotic prescription practices in Eastern Uganda concordant with the national standard treatment guidelines? A cross-sectional retrospective study.

OBJECTIVES: This study aimed to evaluate the antibiotic prescription patterns of health workers in Eastern Uganda and more specifically whether they are in accordance with the Ugandan standard treatment guidelines and other indicators of appropriate antimicrobial prescription. METHODS: Patient data were obtained from the health management information system of the outpatient department registers of Soroti and Mbale Regional Referral Hospitals from 2016-2018. RESULTS: The prevalence of non-adherence to treatment guidelines when prescribing antibiotics was 82.6% (95% CI 81.4-83.7%). Guidelines were more likely to be adhered to when prescribing antibiotics for individuals aged 13-19 years compared with their counterparts aged 0-12 years [adjusted odds ratio (aOR) = 0.55, 95% CI 0.40-0.74]. When prescribing antibiotics for males, health workers were twice as likely not to adhere to guidelines compared with when prescribing for females (aOR = 2.09, 95% CI 1.61-2.72). When prescribing cephalosporins and nitroimidazoles, health workers were likely not to adhere to guidelines compared with when prescribing penicillin (cephalosporins, aOR = 1.92, 95% CI 1.28-2.86; nitroimidazoles, aOR = 1.70, 95% CI 1.09-2.65). Health workers were most likely not to follow guidelines when prescribing antibiotics in combination (two antibiotics, aOR = 1.27, 95% CI 1.03-1.56). CONCLUSION: Non-adherence to treatment guidelines for an indicated diagnosis and inappropriate antibiotic prescription are significantly prevalent in Eastern Uganda. Health workers were more likely not to follow guidelines when prescribing for males, children up to 12 years of age and when prescribing cephalosporins, nitroimidazoles or double antibiotic combinations.

Incidence of home delivery among women living with HIV in Lira, Northern Uganda: a prospective cohort study.

BACKGROUND: Home delivery has been associated with mother-to-child transmission of HIV and remains high among HIV-infected women. Predictors for home delivery in the context of HIV have not been fully studied and understood in Northern Uganda. We therefore aimed to find out the incidence and risk factors for home delivery among women living with HIV in Lira, Northern Uganda. METHODS: This prospective cohort study was conducted between August 2018 and January 2020 in Lira district, Northern Uganda. A total of 505 HIV infected women receiving antenatal care at Lira regional referral hospital were enrolled consecutively and followed up at delivery. We used a structured questionnaire to obtain data on exposures which included: socio-demographic, reproductive-related and HIV-related characteristics. Data was analysed using Stata version 14.0 (StataCorp, College Station, Texas, U.S.A.). We estimated adjusted risk ratios using Poisson regression models to ascertain risk factors for the outcome of interest which was home delivery (which is delivering an infant outside a health facility setting under the supervision of a non-health worker). RESULTS: The incidence of home delivery among women living with HIV was 6.9% (95%CI: 4.9-9.5%). Single women were more likely to deliver at home (adjusted risk ratio = 4.27, 95%CI: 1.66-11). Women whose labour started in the night (night time onset of labour ARR = 0.39, 95%CI: 0.18-0.86) and those that were adherent to their ART (ARR = 0.33, 95%CI: 0.13-0.86) were less likely to deliver at home. CONCLUSION: Home delivery remains high among women living with HIV especially those that do not have a partner. We recommend intensified counselling on birth planning and preparedness in the context of HIV and PMTCT especially for women who are: separated, divorced, widowed or never married and those that are not adherent to their ART.

Incidence and determinants of perinatal mortality among women with obstructed labour in eastern Uganda: a prospective cohort study.

BACKGROUND: In Uganda, the incidence and determinants of perinatal death in obstructed labour are not well documented. We determined the incidence and determinants of perinatal mortality among women with obstructed labour in Eastern Uganda. METHODS: Between July 2018 and September 2019, 584 with obstructed labour were recruited and followed up to the 7th day postnatal. Information on maternal characteristics, obstetric factors and laboratory parameters was collected. Each patient received the standard perioperative care. We used a generalized linear model for the Poisson family, with a log link and robust variance estimation to determine the association between the exposure variables and perinatal death. RESULTS: Of the 623 women diagnosed with obstructed labour, 584 met the eligibility criteria. There were 24 fresh still births (FSB) and 32 early neonatal deaths (ENND) giving an FSB rate of 43.8 (95% CI 28.3-64.4) deaths per 1000 total births; early neonatal death rate of 58.4 (95% CI 40.3-81.4) deaths per 1000 and an overall perinatal mortality rate of 102.2 (95% CI 79.4-130.6) deaths in the first 7 days of life. A mother being referred in active labour adjusted risk ratio of 2.84 (95% CI: 1.35-5.96) and having high blood lactate levels at recruitment adjusted risk ratio 2.71 (95% CI: 1.26-4.24) were the determinants of perinatal deaths. CONCLUSIONS: The incidence of perinatal death was four times the regional and national average. Babies to women referred in active labour and those with high maternal blood lactate were more likely to die.

Experiences and views of healthcare professionals on the prescription of antibiotics in Eastern Uganda: A qualitative study.

OBJECTIVES: This study aimed to explore the experiences and views of healthcare professionals on antibiotic prescription in Eastern Uganda. METHODS: This was an exploratory qualitative study using semi-structured interviews. Participants included 16 healthcare professionals from Mbale and Soroti Regional Referral Hospitals. Additionally, two workshops were held (one in each hospital) with a total of 56 healthcare professionals to discuss the findings. Thematic analysis was used to analyse the data. RESULTS: Healthcare professionals' prescriptions are influenced by (i) healthcare workers' perceptions and practices, (ii) patients' perceptions and beliefs, and (iii) contextual factors. Healthcare workers' prescriptions depend on the presence of bacterial infection and the severity of the condition, the availability and cost of medication, previous experience with antibiotic prescribing, patient characteristics, and trial and error. They also have limited knowledge and share little information on the use of antibiotics with patients. Patient factors included demand for a particular antibiotic, inability to afford expensive drugs, and limited knowledge about antibiotic use and resistance. Contextual factors that contributed to antibiotic prescribing were an overburdened healthcare system, the influence of pharmaceutical companies and pharmacies, the use of (treatment) guidelines, and difficulties with laboratory services. CONCLUSION: This study showed that healthcare professionals are aware of the problem of antibiotic resistance but do not feel ownership of the problem. Instead, they rather blame the overburdened system, local drug shops, pharmacies, drug representatives and patients. There is a need for a multisectoral and holistic approach toward fighting antibiotic resistance.

Prevalence of antibiotic-resistant bacteria among patients in two tertiary hospitals in Eastern Uganda.

OBJECTIVE: The aim of this study was to determine the prevalence and antibiotic resistance patterns of bacterial isolates from inpatients and outpatients in Mbale and Soroti regional referral hospitals in Eastern Uganda. METHODS: A retrospective analysis of culture and antibiotic sensitivity test results from the microbiology laboratories of the two tertiary hospitals was conducted for a 3-year period (January 2016-December 2018). RESULTS: Microbiology records of 3092 patients were reviewed and analysed, with 1305 (42.1%) samples yielding clinical isolates. The most prevalent isolates were Escherichia coli (n = 442; 33.9%), Staphylococcus aureus (n = 376; 28.8%), Klebsiella pneumoniae (n = 237; 18.2%), and Streptococcus pneumoniae (n = 76; 5.8%). High rates of antimicrobial resistance were detected across both Gram-negative and Gram-positive bacteria. Escherichia coli and K. pneumoniae were resistant to several agents such as amoxicillin/clavulanate (83.5%; 64.6%), cefotaxime (74.2%; 52.7%), ciprofloxacin (92.1%; 27.8%), gentamicin (51.8%; 76%), imipenem (3.2%; 10.5%), tetracycline (98%; 74.5%), and trimethoprim-sulfamethoxazole (74.1%; 74.3%), respectively. Staphylococcus aureus and S. pneumoniae exhibited the following resistance profile: cefoxitin (44.4%; 40.9%), chloramphenicol (69.1%; 27.6%) clindamycin (21.5%; 24.4%), gentamicin (83.2%; 66.9%), penicillin (46.5%; -) tetracycline (85.6%; 97.6%), trimethoprim-sulfamethoxazole (88%; 91.3%), and vancomycin (41.2%; -). CONCLUSION: We observed high resistance rates to antibiotics among the majority of microorganisms that were isolated from the samples collected from patients in Eastern Uganda. Furthermore, measures should be undertaken locally to improve microbiology diagnostics and to prevent the spread of antibiotic-resistant strains as this impedes the optimal treatment of bacterial infections and narrows the choice of effective therapeutic options.

Effect of pre-operative bicarbonate infusion on maternal and perinatal outcomes among women with obstructed labour in Mbale hospital: A double blind randomized controlled trial.

INTRODUCTION: Oral bicarbonate solution is known to improve both maternal and perinatal outcomes among women with abnormal labour (dystocia). Its effectiveness and safety among women with obstructed labour is not known. OBJECTIVE: To determine the effect and safety of a single-dose preoperative infusion of sodium bicarbonate on maternal and fetal blood lactate and clinical outcomes among women with obstructed labour (OL) in Mbale hospital. METHODS: We conducted a double blind, randomised controlled trial from July 2018 to September 2019. The participants were women with OL at term (≥37 weeks gestation), carrying a singleton pregnancy with no other obstetric emergency, medical comorbidity or laboratory derangements. INTERVENTION: A total of 477 women with OL were randomized to receive 50ml of 8.4% sodium bicarbonate (238 women) or 50 mL of 0.9% sodium chloride (239 women). In both the intervention and controls arms, each participant was preoperatively given a single dose intravenous bolus. Every participant received 1.5 L of normal saline in one hour as part of standard preoperative care. OUTCOME MEASURES: Our primary outcome was the mean difference in maternal venous blood lactate at one hour between the two arms. The secondary outcomes were umbilical cord blood lactate levels at birth, neonatal sepsis and early neonatal death upto 7 days postnatal, as well as the side effects of sodium bicarbonate, primary postpartum hemorrhage, maternal sepsis and mortality at 14 days postpartum. RESULTS: The median maternal venous lactate was 6.4 (IQR 3.3-12.3) in the intervention and 7.5 (IQR 4.0-15.8) in the control group, with a statistically non-significant median difference of 1.2 mmol/L; p-value = 0.087. Vargha and Delaney effect size was 0.46 (95% CI 0.40-0.51) implying very little if any effect at all. CONCLUSION: The 4.2g of preoperative intravenous sodium bicarbonate was safe but made little or no difference on blood lactate levels. TRIAL REGISTRATION: PACTR201805003364421.

Prevalence and predictors for unintended pregnancy among HIV-infected pregnant women in Lira, Northern Uganda: a cross-sectional study.

Prevention of unintended pregnancies is a global strategy to eliminate mother-to-child transmission of HIV. Factors surrounding unintended pregnancy among women living with HIV are not well understood. We aimed to determine the prevalence and predictors for unintended pregnancy among these women in Northern Uganda. We conducted a cross-sectional survey among 518 women using a structured questionnaire. We asked questions on socio-demographic, reproductive-related and HIV-related characteristics. We conducted multivariable logistic regression and reported adjusted odds ratios. The prevalence of unintended pregnancy was 41.1%. The predictors for unintended pregnancy were: being single (not living with a partner or being in a marital union), having five or more children and taking antiretroviral drugs for long periods of time. HIV counselling services should target women living with HIV who are not in a marital union, those having a higher parity and those who have taken ART for longer periods.

Exclusive breastfeeding among HIV exposed infants from birth to 14 weeks of life in Lira, Northern Uganda: a prospective cohort study.

BACKGROUND: Breastfeeding is important for growth, development and survival of HIV exposed infants. Exclusive breastfeeding reduces the risk of morbidity, mortality and increases HIV free survival of infants. Evidence on risk factors for inappropriate breastfeeding in Northern Uganda is limited. OBJECTIVE: This study determined the risk factors for non-exclusivity of breastfeeding in the first 14 weeks of life. METHODS: This prospective cohort study was conducted among 466 mother-infant pairs between August 2018 and February 2020 in Lira district, Northern Uganda. HIV infected pregnant women were enrolled and followed up at delivery, 6- and 14- weeks postpartum. We used a structured questionnaire to obtain data on socio-demographic, reproductive-related, HIV-related characteristics and exclusive breastfeeding. Data were analysed using Stata version 14.0 (StataCorp, College Station, Texas, USA.). We estimated adjusted risk ratios using modified Poisson regression models. RESULTS: The proportion of HIV exposed infants that were exclusively breastfed reduced with increasing age. Risk factors for non-exclusive breastfeeding included infants being born to HIV infected women who: were in the highest socioeconomic strata (adjusted risk ratio = 1.5, 95%CI: 1.01- 2.1), whose delivery was supervised by a non-health worker (adjusted risk ratio = 1.6, 95%CI: 1.01- 2.7) and who had not adhered to their ART during pregnancy (adjusted risk ratio = 1.3, 95%CI: 1.01- 1.7). CONCLUSIONS: HIV infected women: with highest socioeconomic status, whose delivery was not supervised by a health worker and who did not adhere to ART were less likely to practice exclusive breastfeeding. We recommend ART adherence and infant feeding counselling to be emphasised among HIV infected women who are at risk of having a home delivery, those with poor ART adherence and those of higher socioeconomic status. We also recommend integration of these services into other settings like homes, community and work places instead of limiting them to hospital settings. ABBREVIATIONS: HIV: Human Immunodeficiency Virus; ART: Antiretroviral therapy; HEI: HIV exposed infant; PMTCT: Prevention of mother-to-child transmission of HIV; MTCT: Mother-to-child transmission of HIV; AFASS: Acceptable, Feasible, Affordable, Sustainable and Safe; LRRH: Lira regional referral hospital; CI: confidence interval; ARR: Adjusted risk ratio; SD: Standard deviation; PCA: Principal component analysis.

Barriers and enablers of adherence to infant nevirapine prophylaxis against HIV 1 transmission among 6-week-old HIV exposed infants: A prospective cohort study in Northern Uganda.

BACKGROUND: Sub-optimal adherence to infant prophylaxis has been associated with mother-to-child-transmission of HIV. However, the factors associated have not been well characterised in different settings. This study describes barriers and enablers of adherence to infant prophylaxis among 6-week-old HIV exposed infants in Lira district, Northern Uganda. METHODS: This prospective cohort study was conducted from 2018-2020 at the PMTCT clinic at Lira Regional Referral Hospital and included 472 mother-infant pairs. HIV-infected pregnant women were recruited, followed up at delivery and 6 weeks postpartum. We used a structured questionnaire to obtain data on socio-demographic, reproductive-related, HIV-related characteristics and adherence. Data were analysed using Stata to estimate adjusted risk ratios using Poisson regression models to ascertain barriers and enablers of adherence to infant nevirapine prophylaxis. RESULTS: Barriers to infant adherence are maternal characteristics including: younger age (≤20 years adjusted risk ratio (ARR) = 1.55; 95% CI: 1.1-2.2), missing a viral load test during pregnancy (ARR: 1.4; 95% CI: 1.1-1.7) and not receiving nevirapine syrup for the baby after childbirth (ARR = 6.2; 95% CI: 5.1-7.6). Enablers were: having attained ≥14 years of schooling (ARR = 0.7; 95% CI: 0.5-0.9), taking a nevirapine-based regimen (ARR = 0.6; 95% CI: 0.4-0.9), long-term ART (≥ 60 months ARR = 0.75; 95% CI: 0.6-0.9), accompanied by a husband to hospital during labour and childbirth (ARR = 0.5; 95% CI: 0.4-0.7) and labour starting at night (ARR = 0.7; 95% CI: 0.6-0.8). CONCLUSION AND RECOMMENDATIONS: Despite mothers receiving nevirapine syrup from the health workers for the infant, non-adherence rates still prevail at 14.8%. The health system needs to consider giving HIV infected pregnant women the nevirapine syrup before birth to avoid delays and non-adherence. There is need to pay particular attention to younger women and those who recently started ART.

Detectable HIV-RNA Viral Load Among HIV-Infected Pregnant Women on Treatment in Northern Uganda.

BACKGROUND / OBJECTIVES: Detectable HIV viral load among HIV-infected pregnant women remains a public health threat. We aimed to determine factors associated with detectable viral load among HIV-infected pregnant women in Lira, Northern Uganda. METHODS: We conducted a cross-sectional survey among 420 HIV-infected pregnant women attending Lira Regional Referral Hospital using a structured questionnaire and combined it with viral load tests from Uganda National Health Laboratories. We conducted multivariable logistic regression while adjusting for confounders to determine the factors associated with detectable viral load and we report adjusted odds ratios and proportion of women with viral load less than 50 copies/ml and above 1000 copies, respectively. RESULTS: The prevalence of detectable viral load (>50 copies/ml) was 30.7% (95%CI: 26.3% - 35.4%) and >1000 copies/ml was 8.1% (95% CI: 5.7% - 11.1%). Factors associated with detectable viral load were not belonging to the Lango ethnicity (adjusted odds ratio = 1.92, 95%CI: 1.05 - 3.90) and taking a second-line (protease inhibitor-based) regimen (adjusted odds ratio = 4.41, 95%CI: 1.13 - 17.22). CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: HIV-infected pregnant women likely to have detectable viral load included those taking a protease inhibitor-based regimen and those who were not natives of Lira. We recommend intensified clinical and psychosocial monitoring for medication compliance among HIV-infected pregnant women that are likely to have a detectable viral load to significantly lower the risk of vertical transmission of HIV in Lira specifically those taking a protease inhibitor-based regimen and those who are non-natives to the study setting. Much as the third 90% of the global UNAIDS 90-90-90 target has been achieved, the national implementation of PMTCT guidelines should be tailored to its contextual needs.

Three year survival among patients with aids-related Kaposi sarcoma treated with chemotherapy and combination antiretroviral therapy at Moi teaching and referral hospital, Kenya.

BACKGROUND: AIDS-related Kaposi sarcoma (AIDS-KS), a common malignancy in Kenya is associated with high morbidity and mortality. AIDS-KS is treated using bleomycin and vincristine (BV) plus or minus doxorubicin in most low resource settings, with response rates ranging from 24.8 to 87%. Survival in low resource settings has not been well documented. We report the three-year survival in a cohort of seventy patients referred to Moi Teaching and Referral Hospital (MTRH). METHODS: Study participants are part of a randomized phase IIA trial on the use of gemcitabine compared to bleomycin plus vincristine for the treatment of Kaposi sarcoma after combination antiretroviral therapy (cART) in Western Kenya. All patients were followed for three years in MTRH. Survival was determined by three monthly physical examination and analysed using Kaplan-Meier method, while possible determinants of survival such as baseline characteristics, type of chemotherapy, initial CD4 counts, age at enrolment, gender and early response to chemotherapy were analysed using univariate and multivariate Cox regression. RESULTS: Participants were aged between 19 and 70 years with 56% being male. The median CD4 count was 224 cells/µl, median duration of HIV diagnosis was 12.0 months and median duration of KS lesions after histology diagnosis before initiating chemotherapy was 4.8 weeks. At three years, 60 (85.7%) patients were alive. Six of those who died were under treatment with BV while four with gemcitabine. There was no difference in the probability of survival between the patients on either treatment arm (HR = 0.573 [95% C. I 0.143, 2.292; p = 0.4311]). Additionally, the hazard ratio (HR) for response after six weeks, age at enrolment and gender indicated that they were not significant determinants of survival. Patients with normal CD4 cell counts (> = 500/µl), had a HR of 0.401(0.05,3.23; p = 0.391), suggesting better survival. CONCLUSIONS: Patients with AIDS-KS treated with combined antiretroviral drugs had excellent three-year survival regardless of whether they were treated with BV or gemcitabine as first line therapy. An initial CD4 cell count of > = 500/µl appeared to improve survival while gender, age and early response to chemotherapy were not predictors of survival after three years. TRIAL REGISTRATION: Number PACTR201510001.

Randomized Phase IIA Trial of Gemcitabine Compared With Bleomycin Plus Vincristine for Treatment of Kaposi's Sarcoma in Patients on Combination Antiretroviral Therapy in Western Kenya.

PURPOSE: Kaposi's sarcoma (KS) is a spindle cell tumor resulting from growth dysregulation in the setting of infection with human herpes virus-8 (also called KS herpes virus). Advanced KS is characterized by poor responses to antiretroviral therapy and some of the chemotherapy readily accessible to patients in low-resource areas. Gemcitabine induced partial and complete regression of AIDS-associated KS (AIDS-KS) in 11 of 24 patients in a pilot study. The current study compares the antimetabolite gemcitabine with the standard care bleomycin and vincristine (BV) in the treatment of chemotherapy-naïve patients with AIDS-KS in a resource-limited setting. PATIENTS AND METHODS: Patients with persistent or progressive KS despite treatment with combined antiretroviral therapy were randomly assigned to receive gemcitabine 1,000 mg/m2 or bleomycin 15 IU/ m2 and vincristine 1.4 mg/m2 given twice weekly. The main end point was objective response by bidirectional measurement, adverse events, and quality of life after three cycles of chemotherapy. RESULTS: Of 70 participants enrolled, 36 received gemcitabine and 34 received BV. Complete response was achieved in 12 patients (33.3%) in the gemcitabine arm and six (17.6%) in the BV arm ( P = .175). The partial response rate was 52.8% (n = 19) in the gemcitabine arm and 58.8% (n = 20) in the BV arm. Both study arms reported similar neurologic and hematologic adverse events; there was statistically significant baseline to post-treatment improvement in health-related quality-of-life scores. CONCLUSION: The results of this randomized, phase IIA trial demonstrate gemcitabine activity in chemotherapy-naïve patients with AIDS-KS, on the basis of response rates, adverse events, and health-related quality-of-life scores.

Potential of Zanthoxylum leprieurii as a source of active compounds against drug resistant Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis (TB) is still a global health problem mainly due to development of resistance and co-infection with the Human immune Virus (HIV). Treatment of multi and extensively drug resistant TB requires use of second line drugs which are less efficacious, expensive and very toxic. This has necessitated a need to search for new treatment regimens especially from medicinal plants. Zanthoxylum leprieurii, a plant species from Rutaceae is used locally in the treatment of tuberculosis in Uganda. The aim of the study was to isolate, identify and characterize bio active compounds from Z. leprieurii stem bark with antimycobacterial activity. METHODS: Crude extracts, fractions and compounds from air dried stem bark of Z. leprieurii were tested against pan sensitive (H37rv), isoniazid resistant (TMC 301) and rifampicin resistant (TMC 331) strains of M. tuberculosis using micro plate alamar blue assay. Isolation of active compounds was done by using column chromatography and thin layer chromatography. They were analysed using nuclear magnetic resonance spectroscopy and mass spectroscopy. RESULTS: The methanol extract had minimum inhibitory concentrations (MIC) of 47.5, 75.3 and 125.0 µg/ml on the pan sensitive strain, rifampicin resistant and isozianid resistant strains of M. tuberculosis respectively. The chloroform extract had MIC values of 260 µg/ml agnaist the pan sensitive strain and 156 µg/ml on the rifampicin resistant strain. Of the sixteen fractions from the methanol extract, fraction Za4 (MIC = 6.3 µg/mL, 23.0 µg/mL, 11.7 µg/mL) and Za6 (MIC = 11.7 µg/mL 31.2 µg/ml, 31.2 µg/ml) were the most active. Three acridone alkaloids; hydroxy-1, 3-dimethoxy-10-methyl-9-acridone (1), 1-hydroxy-3-methoxy-10-methyl-9-acridone (2) and 3-hydroxy-1, 5, 6-trimethoxy-9-acridone (3) were isolated from Za4 and Za6. The MIC of compound 3 was found to be 5.1 µg/ml, 4.5 µg/ml and 3.9 µg/ml on H37rv, TMC 331 and TMC 301 while that of 1 was found to be 1.5 µg/ml, 8.3 µg/ml and 3.5 µg/ml respectively. CONCLUSION: The results of this study suggest that Z. leprieurii is active on resistant strains of M. tuberculosis and could be a potential source of new leads against resistant tuberculosis. It also verifies the local use of the plant in treatment of tuberculosis.

Oil-Fortified Maize Porridge Increases Absorption of Lumefantrine in Children with Uncomplicated Falciparum Malaria.

Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria. Absorption of lumefantrine (LUM) is fat dependent, and in children, intake is recommended with milk. We investigated whether oil-fortified maize porridge can be an alternative when milk is not available. In an open-label pharmacokinetic study, Ugandan children <5 years with uncomplicated Plasmodium falciparum malaria were randomized to receive standard six-dose AL treatment [one tablet (20 mgA/120 mg LUM) if <15 kg and two tablets if >15 kg] with milk (A) or maize porridge plus oil (B). Parametric two-sample t-test was used to compare relative oral LUM bioavailability. The primary end-point was LUM exposure till 8 hr after the first dose (AUC0-8 hr ). Secondary outcome included day 7 concentrations (d7LUM ), LUM exposure between days 7 and 28 (AUCd7-28 ) and day 28 PCR-adjusted parasitological response. Evaluable children (n = 33) included 16 in arm A and 17 in arm B. The AUC0-8 hr was comparable between A and B [geometric mean (95% CI): 6.01 (3.26-11.1) versus 6.26 (4.5-8.43) hr*µg/mL, p = 0.9]. Less interindividual variability in AUC0-8 hr was observed in B (p = 0.01), but d7LUM and AUCd7-28 were comparable. Children receiving two tablets had significantly higher exposure than those receiving one tablet [median d7LUM (505 versus 289 ng/mL, p = 0.02) and AUCd7-28 (108 versus 41 hr*µg/mL, p = 0.006)]. One parasitological failure (d28 recrudescence) was observed. Our findings suggest that oil-fortified maize porridge can be an alternative to milk in augmenting absorption of LUM. The lower LUM exposure observed in children dosed with one AL tablet needs further attention.

Medication Error Disclosure and Attitudes to Reporting by Healthcare Professionals in a Sub-Saharan African Setting: A Survey in Uganda.

BACKGROUND: Medication errors (MEs) are largely under-reported, which undermines quality improvement and medication risk management in healthcare. OBJECTIVES: To assess attitudes of Ugandan healthcare professionals (HCPs) towards ME reporting, and identify characteristics of HCPs who endorsed integration of ME and adverse drug reaction (ADR) reporting, valued patient involvement in ME reporting, disclosed having ever made potentially harmful MEs, or observed possibly harmful MEs committed by other HCPs. METHODS: Healthcare professionals self-completed a questionnaire on their attitudes towards the occurrence and reporting of MEs in purposively selected Ugandan health facilities (public/private) including the national referral and six regional referral hospitals representative of all regions. RESULTS: Response rate was 67 % (1345/2000). Most HCPs (91 %; 1174/1289) approved a national ME reporting system for Uganda and 58 % (734/1261) endorsed integration of ME and ADR reporting. Two-thirds (65 %; 819/1267) of HCPs valued patient involvement in ME reporting, one-fifth (18 %; 235/1310) disclosed that they had ever made potentially harmful MEs, while two-fifths (41 %; 542/1323) had ever identified possibly harmful MEs committed by other HCPs. Endorsing patient involvement in ME reporting was more likely by HCPs who valued root-cause analysis and reporting of both actual and potential MEs, or who conceded inadequate communication and lack of time. Self-disclosure of having ever committed potentially harmful MEs was more likely with the need for confidentiality, working in stressful conditions, and willingness to report ADRs. Identifying possibly harmful MEs committed by other HCPs was more likely by non-nurses and those who reported blame culture, stressful conditions, ever encountered a fatal ADR, or attachment to hospital-level health facility. CONCLUSION: A non-punitive healthcare environment and patient involvement may promote ME disclosure and reporting in Uganda and possibly other African countries.

Rare, serious, and comprehensively described suspected adverse drug reactions reported by surveyed healthcare professionals in Uganda.

BACKGROUND: Lack of adequate detail compromises analysis of reported suspected adverse drug reactions (ADRs). We investigated how comprehensively Ugandan healthcare professionals (HCPs) described their most recent previous-month suspected ADR, and determined the characteristics of HCPs who provided comprehensive ADR descriptions. We also identified rare, serious, and unanticipated suspected ADR descriptions with medication safety-alerting potential. METHODS: During 2012/13, this survey was conducted in purposively selected Ugandan health facilities (public/private) including the national referral and six regional referral hospitals representative of all regions. District hospitals, health centres II to IV, and private health facilities in the catchment areas of the regional referral hospitals were conveniently selected. Healthcare professionals involved in prescribing, transcribing, dispensing, and administration of medications were approached and invited to self-complete a questionnaire on ADR reporting. Two-thirds of issued questionnaires (1,345/2,000) were returned. RESULTS: Ninety per cent (241/268) of HCPs who suspected ADRs in the previous month provided information on five higher-level descriptors as follows: body site (206), drug class (203), route of administration (127), patient age (133), and ADR severity (128). Comprehensiveness (explicit provision of at least four higher-level descriptors) was achieved by at least two-fifths (46%, 124/268) of HCPs. Received descriptions were more likely to be comprehensive from HCPs in private health facilities, regions other than central, and those not involved in teaching medical students. Overall, 106 serious and 51 rare previous-month suspected ADRs were described. The commonest serious and rare ADR was Stevens-Johnson syndrome (SJS); mostly associated with oral nevirapine or cotrimoxazole, but haemoptysis after diclofenac analgesia and paralysis after quinine injection were also described. CONCLUSION: Surveyed Ugandan HCPs who had suspected at least one ADR in the previous month competently provided comprehensive ADR descriptions: more, indeed, than are received per annum nationally. Properly analyzed, and with local feed-back, voluntary ADR reports by HCPs could be an essential alerting tool for identifying rare and serious suspected ADRs in Uganda.

A consortium approach to competency-based undergraduate medical education in Uganda: process, opportunities and challenges.

BACKGROUND: Uganda, like the rest of Africa, is faced with serious health challenges including human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS), other infectious diseases and increasing non-communicable diseases, yet it has a significant shortage of health workers. Even the few health workers available may lack desired competencies required to address current and future health challenges. Reducing Uganda's disease burden and addressing health challenges requires Ugandan medical schools to produce health workers with the necessary competencies. This study describes the process which a consortium of Ugandan medical schools and the Medical Education Partnership for Equitable Services to all Ugandans (MESAU) undertook to define the required competencies of graduating doctors in Uganda and implement competency-based medical education (CBME). METHODS: A retrospective qualitative study was conducted in which document analysis was used to collect data employing pre-defined checklists, in a desktop or secondary review of various documents. These included reports of MESAU meetings and workshops, reports from individual institutions as well as medical undergraduate curricula of the different institutions. Thematic analysis was used to extract patterns from the collected data. RESULTS: MESAU initiated the process of developing competencies for medical graduates in 2011 using a participatory approach of all stakeholders. The process involved consultative deliberations to identify priority health needs of Uganda and develop competencies to address these needs. Nine competence domain areas were collaboratively identified and agreed upon, and competencies developed in these domains. DISCUSSION: Key successes from the process include institutional collaboration, faculty development in CBME and initiating the implementation of CBME. The consortium approach strengthened institutional collaboration that led to the development of common competencies desired of all medical graduates to address priority health challenges in Uganda. It is important that the MESAU consortium continues engaging all stakeholders in medical education to support the implementation and sustainability of CBME in Uganda.