Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study.

BACKGROUND: Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. METHODS: DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. FINDINGS: From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). INTERPRETATION: DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. FUNDING: European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases.

Silent Tears of Midwives: 'I Want Every Mother Who Gives Birth to Have Her Baby Alive'-A Narrative Inquiry of Midwives Experiences of Very Early Neonatal Death from Tanzania.

BACKGROUND: Midwives working in settings with limited clinical resources experience high rates of very early neonatal deaths. Midwives manage the impact of this grief and trauma almost daily, which may affect patient care and their own well-being. RESEARCH AIMS: To explore how midwives are impacted by and cope with high rates of very early neonatal deaths. To document midwives' insights and local solutions that may reduce very early neonatal deaths in limited resource settings. To document the stories of midwives in order to create awareness and garner support for midwives and their critical work in low resource settings. METHODS: Narrative inquiry utilizing semi structured interviews. Twenty-one midwives with at least six months experience who had experienced or witnessed very early neonatal death were interviewed. Data were audio recorded and transcribed, and reflexive thematic analysis of transcripts was conducted. RESULTS AND DISCUSSION: Three themes were identified: (1) deep sadness resulting from very early neonatal deaths leading to internal struggles; (2) use of spirituality, including prayer and occasional beliefs that unexplainable deaths were 'God's plan'; and (3) development of resilience by seeking solutions, educating themselves, taking accountability and guiding mothers. Participating midwives noted that inadequate staff and high caseloads with limited basic supplies hindered their clinical practice. Participants articulated that they concentrated on active solutions to save babies during labour, such as vigilant foetal rate heart monitoring and partogram. Further, reduction and prevention of very early neonatal death is a complex problem requiring multidisciplinary teams and woman-centred care approaches to address issues contributing to the health of mothers and their new-borns. CONCLUSIONS: Midwives' narratives highlighted ways of coping with grief and deep sadness, through prayer, and further education of both mothers and fellow colleagues to achieve better antenatal and intrapartum care and outcomes. This study gave midwives an opportunity for their voices to be heard and to generate solutions or insights that can be shared with colleagues in similar low-resource settings.

High burden of tuberculosis infection and disease among people receiving medication-assisted treatment for substance use disorder in Tanzania.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) disease and infection as well as incident TB disease among people who use drugs (PWUD) attending Medication Assisted Treatment (MAT) clinics in Dar-es-Salaam, Tanzania. METHODS: In this prospective cohort study, a total of 901 consenting participants were enrolled from November 2016 to February 2017 and a structured questionnaire administered to them through the open data kit application on android tablets. Twenty-two months later, we revisited the MAT clinics and reviewed 823 of the 901 enrolled participant's medical records in search for documentation on TB disease diagnosis and treatment. Medical records reviewed included those of participants whom at enrolment were asymptomatic, not on TB disease treatment, not on TB preventive therapy and those who had a documented tuberculin skin test (TST) result. RESULTS: Of the 823 medical records reviewed 22 months after enrolment, 42 had documentation of being diagnosed with TB disease and initiated on TB treatment. This is equivalent to a TB disease incidence rate of 2,925.2 patients per 100,000 person years with a total follow up time of 1,440 person-years. At enrolment the prevalence of TB disease and TB infection was 2.6% and 54% respectively and the HIV prevalence was 44% and 16% among females and males respectively. CONCLUSION: PWUD attending MAT clinics bear an extremely high burden of TB and HIV and are known to have driven TB epidemics in a number of countries. Our reported TB disease incidence is 12 times that of the general Tanzanian incidence of 237 per 100,000 further emphasizing that this group should be prioritized for TB screening, testing and treatment. Gender specific approaches should also be developed as female PWUDs are markedly more affected with HIV and TB disease than male PWUDs.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Prevalence of chronic kidney disease using estimated glomerular filtration rate among diabetes patients attending a tertiary clinic in Botswana.

OBJECTIVES: Diabetes mellitus (DM) is one of the most common contributors of chronic kidney disease (CKD). The epidemiology of CKD, a concern among patients with DM, has not been studied in Botswana. Consequently, the objective of this study was to estimate its prevalence among these patients in Botswana to provide future guidance to both government personnel and physicians. METHODS: Observational cross-sectional study in a leading clinic in Botswana. Demographic and clinical data were obtained from patients through interviews and from their notes using a standard questionnaire. The study was conducted from July to October 2015. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet for Renal Disease equation. CKD was defined as an eGFR < 60 ml/min/1.73 m2. Multivariable logistic regression analyses were performed to assess the associations between CKD and potential factors. RESULTS: The mean age and duration of DM among study participants were 54.67 years (range 21-92 years) and 5.0 years, respectively. Over half, i.e. 213/370 (57.6%) and 232/370 (62.7%), had an average blood pressure greater than 140/90 mmHg and poor glycemic control (HbA1c > 7%), respectively. 31/370 patients (8.4%) had CKD. However, only 18/370 (4.9%) had a diagnosis of CKD documented in their charts. Age, level of education, and duration of diabetes were independently associated with CKD. CONCLUSION: The prevalence of CKD by estimated eGFR was low compared to most previous studies. However, half of patients with CKD are not documented resulting in the potential for prescription errors and drug toxicity. A substantial number of our patients had uncontrolled hypertension and poor glycemic control. Older age, low level of education and longer duration of DM were associated with CKD. There is a need to carry out prospective studies to determine the association and role of glycemic and blood pressure control in CKD causation among patients with DM in Botswana.

Prevalence, risk factors and clinical correlates of COPD in a rural setting in Tanzania.

Chronic obstructive pulmonary disease (COPD) causes substantial burden of disease in developed countries, but there are limited data from Africa. We aimed to estimate the prevalence of COPD in Tanzania and identify the risk factors associated with it.This was a cross-sectional descriptive survey involving adults aged ≥35 years. We collected data on symptoms and risk factors using the Burden of Obstructive Lung Diseases questionnaire. Spirometry was performed and COPD diagnosed based on post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <70%. We also measured indoor and outdoor carbon monoxide (CO) levels.A total of 869 participants (49.1% females) completed the questionnaires. Of these, 57.1% completed post-bronchodilator spirometry. Of the 25.2% ever-smokers, only 5.4% were current smokers. COPD prevalence was estimated at 17.5% (21.7% in males and 12.9% in females). COPD was associated with a history of cough, phlegm production and wheezing. 51.7% of COPD patients reported cough and 85% had mild to moderate airway limitation. Females had a higher rate of exacerbation. Pulmonary tuberculosis (TB) was reported in 10% of patients. Only 1.7% of patients who were diagnosed as COPD had ever received any medication, with only one female COPD patient having received an inhaler. 99.5% of the population used biomass fuels for cooking. The majority of households had CO levels up to 20 ppm.The prevalence of COPD in Tanzania is high, with a peak at a relatively young age and a preponderance in males. A history of TB, cigarette smoking and male sex are important risk factors. Indoor air pollution coupled with use of biomass fuel for cooking and heating may be an important risk factor for developing COPD in rural Tanzania. However, these factors need to be studied further.

Asthma prevalence, knowledge, and perceptions among secondary school pupils in rural and urban coastal districts in Tanzania.

BACKGROUND: Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. METHODS: A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A ≥ 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. RESULTS: The mean age of participants was 16.8 (±1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. CONCLUSION: The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools.