High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.

BACKGROUND: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. CONCLUSIONS: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.

Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.

BACKGROUND: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa. METHODS: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. RESULTS: Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. CONCLUSIONS: Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU.

Loss to follow-up correction increased mortality estimates in HIV-positive people on antiretroviral therapy in Mozambique.

OBJECTIVES: People living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) may be lost to follow-up (LTFU), which hampers the assessment of outcomes. We estimated mortality for patients starting ART in a rural region in sub-Saharan Africa and examined risk factors for death, correcting for LTFU. STUDY DESIGN AND SETTING: We analyzed data from Ancuabe, Mozambique, where patients LTFU are traced by phone and home visits. We used cumulative incidence functions to estimate mortality and LTFU. To correct for LTFU, we revised outcomes based on tracing data using different inverse probability weights (maximum likelihood, Ridge regression, or Bayesian model averaging). We fitted competing risk models to identify risk factors for death and LTFU. RESULTS: The analyses included 4,492 patients; during 8,152 person-years of follow-up, 486 patients died, 2,375 were LTFU, 752 were traced, and 603 were found. At 4 years after starting ART, observed mortality was 11.9% (95% confidence interval [CI]: 10.9-13.0), but 23.5% (95% CI: 19.8-28.0), 21.6% (95% CI: 18.7-25.0), and 23.3% (95% CI: 19.7-27.6) after correction with maximum likelihood, Ridge regression, and Bayesian model averaging weights, respectively. The risk factors for death included male sex, lower CD4 cell counts, and more advanced clinical stage. CONCLUSION: In ART programs with substantial LTFU, mortality estimates need to take LTFU into account.

Correction to: Clinical and economic effects of an antimicrobial stewardship intervention in a surgical intensive care unit.

The original version of this article unfortunately contained a mistake.

Clinical and economic effects of an antimicrobial stewardship intervention in a surgical intensive care unit.

PURPOSE: To study the effects of an Antimicrobial Stewardship (AMS) programme designed as a once-weekly "Prospective Audit with Feedback and Intervention" in a surgical intensive care unit. METHODS: Retrospective, pre-/post-observational comparison of antimicrobial drug use, patient safety, and cost of care. RESULTS: During the 12-month AMS period the consumption of antimicrobials dropped by 18.3%. While the consumption of broad-spectrum antibiotics decreased by 17.4% the consumption of narrow spectrum penicillins increased by 89.9%, reaching 26.3% of the total antibiotic consumption. Treatment outcomes and rates of Clostridioides difficile infections before and during the programme were not significantly different. The reduction in antimicrobial costs of 46,393€ was offset by an expenditure of 8,047€, for both human resources and additional radiological procedures, resulting in a net saving of 38,346€. 92% of the antibiotic related savings were due to the reduced use of tigecycline and linezolid, and decreases in drug retail prices. CONCLUSIONS: AMS programmes can both reduce the consumption of antimicrobials and modify their spectrum in intensive care without negatively affecting treatment outcomes. The resulting cost savings are negligible. The incentive to implement such programmes cannot, therefore, be immediate institutional cost savings, but should be rather the long-term goal of reducing antibiotic resistance, and its consequences, in terms of long-term health care costs.

Triage conducted by lay-staff and emergency training reduces paediatric mortality in the emergency department of a rural hospital in Northern Mozambique.

INTRODUCTION: The majority of emergency paediatric death in African countries occur within the first 24 h of admission. A coloured triage system is widely implemented in high-income countries and the emergency triage and assessment treatment (ETAT) is recommended by the World Health Organization, but not put into practice in Mozambique. We implemented a three-colour triage system in a rural district hospital with lay-staff workers conducting the first triage. METHODS: A retrospective, before and after, mortality analysis was performed using routine patient files from the district hospital between 2014 and 2017. The triage system was implemented in August 2016. Inclusion criteria were children under 15 years of age that entered the emergency centre. Primary outcome was child mortality rate. Secondary outcomes included the percentage agreement between the clinical and non-clinical staff and the duration from triage to first treatment. We used a negative binomial model in STATA 15 to compare mortality rates, and Kappa statistics to estimate the agreement between clinical and non-clinical staff. RESULTS: 4176 admissions were included. The mortality rate ratio (MMR) was 45% lower after the start of the intervention (2016; MRR = 0.55; 0.38, 0.81; p = 0.002), compared to before. To estimate the agreement between non-clinical and clinical staff, 548 (of the 671) patient files were included. The agreement was estimated at 88.7% (Kappa = 0.644; p < 0.001). The median waiting time decreased with urgency of the triage: 2 h33 for 'green'/least serious (IQR 1 h58-3 h30), 21 min for yellow/serious (IQR 0 h10-0 h58) and nine minutes for 'red'/urgent (IQR 2-40 min). CONCLUSION: In a rural setting with nurse-led clinical care and non-clinician staff working at the triage reception, implementation of a three-coloured triage system was feasible. Triage and ETAT training was associated with a decrease of 45% of paediatric deaths. The impact on mortality, low cost, and ease of the implementation supports scaling this intervention in similar settings.

Acceptability and performance of a directly assisted oral HIV self-testing intervention in adolescents in rural Mozambique.

INTRODUCTION: Whereas progress in HIV testing and treatment has been made globally, the UNAIDS goal of "90 90 90" is still out of sight in rural northern Mozambique. New strategies that promote testing in hard to reach groups will aid Mozambique's response to the HIV epidemic. HIV self-testing (HIVST) is recommended by the WHO as an additional approach to augment the HIV testing services available to adolescents. This study evaluates acceptability and performance of a directly assisted oral HIVST intervention for adolescents in rural Mozambique. METHODS: Adolescents aged 16-20 years were included at schools and invited to attend the local hospital's youth friendly service for directly assisted oral HIVST. Baseline and post-test questionnaires were obtained. OraQuick Rapid HIV-1/2 Anti body test® was used. Results were read by the participant and by a nurse. Results were confirmed by finger prick HIV test (Determine® HIV 1/2 Alere and Unigold™ HIV Trinity Biotech) according to the Mozambican national standard. RESULTS: Between September and November 2016, 496 adolescents were included, of which 299 performed an oral HIV self-test. 70% were first time testers. The positivity rate was 1.7%. The inter-rater agreement between adolescent and nurse was 99.6% (kappa 0.93); there were no false negative or false positive results of the oral HIV self-test. Five tests were invalid. 7.1% found the test difficult to use. Over 80% preferred directly assisted HIVST compared to the standard finger prick testing. While 20% thought it would be good to do HIVST at home, 76% preferred to do HIVST at the health centre, for reasons including increased security, privacy, and the presence of a counsellor. CONCLUSIONS: Directly assisted oral HIVST is a feasible intervention for adolescents in rural Mozambique and showed encouraging results for first time HIV testers.

TST positivity in household contacts of tuberculosis patients: a case-contact study in Malawi.

BACKGROUND: Screening household contacts of active tuberculosis (TB) patients is recommended for TB control. Due to resource constraints this rarely occurs in lower income countries. Demographic and clinical features of index cases may influence the likelihood of onwards TB transmission. It has also been proposed that accumulation of intracellular lipid bodies within M. tuberculosis cells may also enhance bacterial transmissibility. This study explored whether clinical and bacteriological observations recorded at baseline in TB cases in Malawi could help identify those with the highest risk of onwards transmission, to prioritise contact tracing. METHODS: In this case-contact study, data on clinical presentation, sputum bacterial load and the percentage of lipid body positive acid-fast bacilli (%LB + AFB) on sputum smears were recorded in adults with sputum smear and culture positive pulmonary TB before initiation of therapy. The Tuberculin Skin Test (TST) was used to detect infection with M. tuberculosis amongst household contacts under the age of 15 years. TST positivity of the child contacts was related to characteristics of the index case. RESULTS: Thirty four index cases brought 56 contacts (median: 1, range: 1-4 contacts each). 37 (66%) of contacts had a positive TST. Cavities or a high percentage of lung affected on index patient CXRs were associated with TST positivity. Multivariate analysis of non-radiological factors showed that male sex, HIV-negative status and raised peripheral blood white blood count (WBC) in index patients were also independent risk factors of TST positivity. Lower %LB + AFB counts were associated with TST positivity on univariate analysis only. CONCLUSION: TST positivity is common amongst household contacts of sputum smear positive adult TB patients in Malawi. Contact tracing in this high risk population could be guided by prioritising index cases with CXR cavities and extensive radiological disease or, in the absence of CXRs, those who are HIV-negative with a raised WBC.

Increasing Partner Attendance in Antenatal Care and HIV Testing Services: Comparable Outcomes Using Written versus Verbal Invitations in an Urban Facility-Based Controlled Intervention Trial in Mbeya, Tanzania.

In many Sub-Saharan African settings male partner involvement in antenatal care (ANC) remains low, although great benefits for maternal and infant health outcomes have been long recognised, in particular regarding the prevention of HIV transmission. Yet there is paucity on evidence regarding the effectiveness of strategies to increase male partner involvement. This controlled intervention trial in Ruanda Health Centre in Mbeya, Tanzania, assessed the effectiveness of invitation letters for male involvement in ANC. Pregnant women approaching ANC without partners received official letters inviting the partner to attend ANC. A control group was instructed to verbally invite partners. Partner attendance was recorded at two subsequent ANC visits. Rates for male partner return, couple voluntary counselling and testing (CVCT), and influencing factors were analysed. From 199 ANC clients in total, 97 were assigned to the invitation letter group; 30 of these (30.9%) returned with their male partners for ANC. In the control group of 102 women, 28 (27.5%) returned with their partner. In both groups CVCT rates among jointly returning couples were 100%. Partner return/CVCT rate was not statistically different in intervention and control group (OR 1.2, p = 0.59). Former partner attendance at ANC during a previous pregnancy was the only factor found to be significantly linked with partner return (p = 0.03). Our study demonstrates that rather simple measures to increase male partner attendance in ANC and CVCT can be effective, with written and verbal invitations having comparable outcomes. In terms of practicability in Sub-Saharan African settings, we recommend systematic coaching of ANC clients on how to verbally invite male partners in the first instance, followed by written invitation letters for partners in case of their non-attendance. Further studies covering both urban and rural settings will be more informative for effective translation into policy.

Burden and spectrum of infectious disease in Germany 2009-2014: a multicentre study from Berlin's Municipal Hospitals.

PURPOSE: This study aimed at assessing the burden and spectrum of infectious diseases (ID) in a Metropolitan population in Germany. METHODS: A discharge database using ICD-10 codes enabled the identification of hospitalizations with infection-related diagnoses. All hospital admissions between 2009 and 2014 were analysed from 9 municipal hospitals serving approximately one-third of an urban population of 3.5 million people. RESULTS: We identified 114,168 admissions with a primary (first-listed) ID diagnosis and 220,483 admissions with any-listed ID diagnosis, accounting for 8.9 % [95 % confidence interval (CI) 8.9-9.0 %] and 17.2 % (95 % CI 17.1-17.3) of all 1,284,559 admissions, respectively. Annually, 439,837 bed-days (range 413,707-488,520) were occupied by patients with an ID diagnosis, utilizing 22.8 % of total bed capacity. The median length of stay for patients with primary ID diagnosis and secondary ID diagnosis was 6 days (IQR 3-11) and 10 days (IQR 5-19), respectively. The most common diagnosis across all age groups was "pneumonia" (22.8 and 16.2 % of ID admissions as primary and secondary diagnosis, respectively). In-hospital mortality was 6.8 % (95 % CI 6.6-6.9) and 8.9 % (95 % CI 8.7-9.1) for ID as primary and secondary diagnosis, respectively. CONCLUSION: Infectious diseases contribute significantly to the overall burden of disease in a health system caring for an urban German population. In view of the magnitude of ID's contribution, establishing more specialists in ID medicine and adjusting the reimbursements for managing infection-related admissions should be made a public health priority in Germany.

Neuroimaging of HIV-associated cryptococcal meningitis: comparison of magnetic resonance imaging findings in patients with and without immune reconstitution.

To determine the frequency, imaging characteristics, neuroanatomical distribution and dynamics of magnetic resonance imaging findings in HIV-associated cryptococcal meningitis in immunocompromised patients we compared patients without antiretroviral therapy with patients undergoing immune reconstitution. Neuroimaging and clinical data of 21 consecutive patients presenting to a German HIV centre in a 10-year period between 2005 and 2014 were reviewed. We identified eight patients with magnetic resonance imaging findings related to cryptococcal disease: five patients without antiretroviral therapy and three patients receiving effective antiretroviral therapy resulting in immune reconstitution. The pattern of magnetic resonance imaging manifestations was different in the two groups. In patients not on antiretroviral therapy, pseudocysts (n = 3) and lacunar ischaemic lesions (n = 2) were detected. Contrast-enhancing focal leptomeningeal and/or parenchymal lesions were found in all patients under immune reconstitution (n = 3). Magnetic resonance imaging lesions suggestive of leptomeningitis or meningoencephalitis were detected in all patients with a recurrence of cryptococcal meningitis under immune reconstitution, which differs from the classical magnetic resonance imaging findings in patients without antiretroviral therapy. In antiretroviral therapy-treated patients with past medical history of cryptococcal meningitis, detection of contrast-enhancing focal meningeal and/or parenchymal lesions should prompt further investigations for a recurrence of cryptococcal meningitis under immune reconstitution.

Official invitation letters to promote male partner attendance and couple voluntary HIV counselling and testing in antenatal care: an implementation study in Mbeya Region, Tanzania.

BACKGROUND: The benefits of male partner involvement in antenatal care (ANC) and prevention of mother-to-child transmission of HIV (PMTCT) for maternal and infant health outcomes have been well recognised. However, in many sub-Saharan African settings, male involvement in these services remains low. Previous research has suggested written invitation letters as a way to promote male partner involvement. METHODS: In this implementation study conducted at three study sites in southwest Tanzania, acceptability of written invitation letters for male partners was assessed. Pre-study CVCT rates of 2-19 % had been recorded at the study sites. Pregnant women approaching ANC without a male partner were given an official letter, inviting the partner to attend a joint ANC and couple voluntary counselling and testing (CVCT) session. Partner attendance was recorded at subsequent antenatal visits, and the invitation was repeated if the partner did not attend. Analysis of socio-demographic indices associated with male partner attendance at ANC was also performed. RESULTS: Out of 318 women who received an invitation letter for their partner, 53.5 % returned with their partners for a joint ANC session; of these, 81 % proceeded to CVCT. Self-reported HIV-positive status at baseline was negatively associated with partner return (p = 0.033). Male attendance varied significantly between the rural and urban study sites (p < 0.001) with rates as high as 76 % at the rural site compared to 31 % at the urban health centre. The majority of women assessed the joint ANC session as a favourable experience, however 7 (75 %) of women in HIV-positive discordant or concordant relationships reported problems during mutual disclosure. Beneficial outcomes reported one month after the session included improved client- provider relationship, improved intra-couple communication and enhanced sexual and reproductive health decision-making. CONCLUSION: Official invitation letters are a feasible intervention in a resource limited sub-Saharan African context, they are highly accepted by couple members, and are an effective way to encourage men to attend ANC and CVCT. Pre-intervention CVCT rates were improved in all sites. However, urban settings might require extra emphasis to reach high rates of partner attendance compared to smaller rural health centres.

Cryptococcosis in HIV-infected hospitalized patients in Germany: Evidence for routine antigen testing.

OBJECTIVES: To investigate the diagnostic value of routine cryptococcal antigen (CRAG) testing in HIV-infected patients in a low prevalence setting. METHODS: Retrospective single centre cohort study of a 10-year period (2005-2014). RESULTS: 5461 patients tested for CRAG were included. Cryptococcal antigenaemia was found in 1.6% and 1.1% of patients with CD4 counts of ≤100/µl and 101-200/µl, respectively. The positive predictive values for identifying clinically relevant cryptococcal disease was 96% and 100%, respectively. Half of the patients had a non-specific presentation and median time-to-diagnosis was high (5 days, range 1-44 days). The median time-to-diagnosis in direct admissions to our centre with routine CRAG testing was significantly shorter: 1 day (range: 1-17) vs. 7 days (range: 2-44), p = 0.003. Prevalence of cryptococcal antigenaemia was 2.8% in patients with pneumocystis pneumonia and median time-to-diagnosis of cryptococcosis was significantly longer in this subgroup (15 days; range: 1-44 vs. 3 days; range: 1-17; p = 0.008). CRAG titres ≥1:512 were associated with disseminated disease (OR 21.3, p = 0.0008, 95% CI 1.64-277), however, 10% of patients with disseminated cryptococcosis had CRAG titres <1:16. CONCLUSION: Our data support routine CRAG testing in hospitalized HIV-infected patients with CD4 counts ≤200/µl, and/or pneumocystis pneumonia.