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.

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.