Optimizing integrated imaging service delivery by tier in low-resource health systems.

Access to imaging diagnostics has been shown to result in accurate treatment, management, and optimal outcomes. Particularly in low-income and low-middle-income countries (LICs, LMICs), access is limited due to a lack of adequate resources. To achieve Sustainable Development Goal (SDG) 3, access to imaging services is critical at every tier of the health system. Optimizing imaging services in low-resource settings is best accomplished by prescriptive, integrated, and coordinated tiered service delivery that takes contextual factors into consideration. To our knowledge, this is the first recommendation for optimized, specific imaging care delivery by tier. A model for tier-based essential imaging services informs and guides policymakers as they set priorities and make budgetary decisions. In this paper, we recommend a framework for tiered imaging services essential to reduce the global burden of disease and attain universal health coverage (UHC). A lack of access to basic imaging services, even at the lowest tier of the health system, can no longer be justified by cost. Worldwide, affordable modalities of modern ultrasound and X-ray are becoming an accessible mainstay for the investigation of common conditions such as pregnancy, pneumonia, and fractures, and are safely performed and interpreted by qualified professionals. Finally, given the vast gap in access to imaging resources between LMICs and high-income countries (HICs), a scale-up of tiered imaging services in low-resource settings has the potential to reduce health disparities between, and within countries. As the access to appropriately integrated imaging services improves, UHC may be achieved.

WhatsApp Linking Lilongwe, Malawi to Los Angeles: Impacting Medical Education and Clinical Management.

Background: Subspecialty expertise is often lacking in clinical environments in low-resource settings. As a result, medically complicated patients can receive suboptimal care, local clinicians can feel inadequately supported, and global health engagements can be difficult for medical trainees accustomed to more expert supervision at their home institutions. Objective: We created WhatsApp Messenger discussion groups to connect subspecialists at the University of California, Los Angeles (UCLA) David Geffen School of Medicine with clinicians and rotating global health residents at Partners in Hope (PIH) Medical Center in Lilongwe, Malawi. Methods: Case submitters and subspecialist respondents were surveyed about their experience in the discussion groups. Findings: Over a three-year period, 95 cases were discussed in ten subspecialty groups, with dermatology and radiology/pulmonology receiving the most submissions. Participants were surveyed and reported excellent educational outcomes; large majorities of both case submitters (89%) and experts (71%) agreed or strongly agreed that the case discussions improved their medical education. The surveys also suggested positive impact on medical management decisions and patient outcomes. The major challenge to our intervention was low utilization of this resource by Malawian clinicians in comparison to medical residents. We hope to further address the barriers to participation and adapt the intervention to better support our Malawian colleagues. Conclusion: Because the discussion groups are free to create and require very little maintenance, this intervention can be easily replicated at other institutions looking to augment their global health educational engagements and support their clinical partners abroad.

Diagnostic Utility and Impact on Clinical Decision Making of Focused Assessment With Sonography for HIV-Associated Tuberculosis in Malawi: A Prospective Cohort Study.

BACKGROUND: The focused assessment with sonography for HIV-associated tuberculosis (TB) (FASH) ultrasound protocol has been increasingly used to help clinicians diagnose TB. We sought to quantify the diagnostic utility of FASH for TB among individuals with HIV in Malawi. METHODS: Between March 2016 and August 2017, 210 adults with HIV who had 2 or more signs and symptoms that were concerning for TB (fever, cough, night sweats, weight loss) were enrolled from a public HIV clinic in Lilongwe, Malawi. The treating clinicians conducted a history, physical exam, FASH protocol, and additional TB evaluation (laboratory diagnostics and chest radiography) on all participants. The clinician made a final treatment decision based on all available information. At the 6-month follow-up visit, we categorized participants based on clinical outcomes and diagnostic tests as having probable/confirmed TB or unlikely TB; association of FASH with probable/confirmed TB was calculated using Fisher's exact tests. The impact of FASH on empiric TB treatment was determined by asking the clinicians prospectively about whether they would start treatment at 2 time points in the baseline visit: (1) after the initial history and physical exam; and (2) after history, physical exam, and FASH protocol. RESULTS: A total of 181 participants underwent final analysis, of whom 56 were categorized as probable/confirmed TB and 125 were categorized as unlikely TB. The FASH protocol was positive in 71% (40/56) of participants with probable/confirmed TB compared to 24% (30/125) of participants with unlikely TB (odds ratio=7.9, 95% confidence interval=3.9,16.1; P<.001). Among those classified as confirmed/probable TB, FASH increased the likelihood of empiric TB treatment before obtaining any other diagnostic studies from 9% (5/56) to 46% (26/56) at the point-of-care. For those classified as unlikely TB, FASH increased the likelihood of empiric treatment from 2% to 4%. CONCLUSION: In the setting of HIV coinfection in Malawi, FASH can be a helpful tool that augments the clinician's ability to make a timely diagnosis of TB.

Ultrasound for Breast Cancer Detection Globally: A Systematic Review and Meta-Analysis.

PURPOSE: Mammography is not always available or feasible. The purpose of this systematic review and meta-analysis is to assess the diagnostic performance of ultrasound as a primary tool for early detection of breast cancer. MATERIALS AND METHODS: For this systematic review and meta-analysis, we comprehensively searched PubMed and SCOPUS to identify articles from January 2000 to December 2018 that included data on the performance of ultrasound for detection of breast cancer. Studies evaluating portable, handheld ultrasound as an independent detection modality for breast cancer were included. Quality assessment and bias analysis were performed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity analyses and meta-regression were used to explore heterogeneity. The study protocol has been registered with the international prospective register of systematic reviews (PROSPERO identifier: CRD42019127752). RESULTS: Of the 526 identified studies, 26 were eligible for inclusion. Ultrasound had an overall pooled sensitivity and specificity of 80.1% (95% CI, 72.2% to 86.3%) and 88.4% (95% CI, 79.8% to 93.6%), respectively. When only low- and middle-income country data were considered, ultrasound maintained a diagnostic sensitivity of 89.2% and specificity of 99.1%. Meta-analysis of the included studies revealed heterogeneity. The high sensitivity of ultrasound for the detection of breast cancer was not statistically significantly different in subgroup analyses on the basis of mean age, risk, symptoms, study design, bias level, and study setting. CONCLUSION: Given the increasing burden of breast cancer and infeasibility of mammography in certain settings, we believe these results support the potential use of ultrasound as an effective primary detection tool for breast cancer, which may be beneficial in low-resource settings where mammography is unavailable.

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil.

Importance: Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings. Objective: To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection. Design, Setting, and Participants: This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children's hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018. Exposures: Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay. Main Outcomes and Measures: Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury. Results: A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001). Conclusions and Relevance: Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.

M#1045: Training Course in Focused Assessment with Sonography for HIV/TB in HIV Prevalent Medical Centers in Malawi.

PURPOSE: Training medical providers of different backgrounds the "focused assessment with sonography for HIV-associated TB" (FASH) exam to expand the availability of ultrasound for TB diagnosis in resource poor settings in the central region of Malawi. METHODS AND MATERIALS: A survey was completed by the 19 eligible participants before and after a 4-day training course regarding the utility of the FASH exam. A six-question quiz was used to assess knowledge of the use of ultrasound in the FASH exam before and after the course. RESULTS: Participants' knowledge of the FASH technique significantly improved after the four-day course with a 32% increase in total quiz questions answered correctly (p<0.001).Ninety-five percent (n= 18) of participants answered that they would "likely" incorporate FASH in their clinical practice. Furthermore, 100% (n=19) of participants agreed that the FASH exam would improve their ability to diagnose TB and 95% (n=18) agreed that FASH would improve patient care in their clinic. CONCLUSIONS: After completing a 4-day training course, medical providers were more knowledgeable about the FASH exam and its findings, and felt more comfortable using ultrasound for the diagnosis of TB. Participants were also unanimous in opinion that the FASH ultrasound exam would improve their ability to diagnose TB.

Technical aspects of mediastinal ultrasound for pediatric pulmonary tuberculosis.

Diagnosing childhood pulmonary tuberculosis (TB) may be challenging due to difficulties in obtaining adequate sputum samples, paucibacillary disease and the low sensitivity of diagnostic tests. Chest radiography is an important diagnostic tool for pulmonary TB, but it involves radiation exposure, requires facilities that can house X-ray equipment and has poor inter-reader agreement. The cardinal radiologic finding of mediastinal lymphadenopathy may be detected using mediastinal ultrasound (US). We describe technical aspects of performing mediastinal US, which may assist diagnosis of paediatric pulmonary TB.

Effect of deletion or overexpression of the 19-kilodalton lipoprotein Rv3763 on the innate response to Mycobacterium tuberculosis.

The 19-kDa lipoprotein of Mycobacterium tuberculosis is an important target of the innate immune response. To investigate the immune biology of this antigen in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19-kDa-lipoprotein gene (Delta19) and complemented this strain by reintroduction of the 19-kDa-lipoprotein gene on a multicopy vector to produce Delta19::pSMT181. The Delta19 strain multiplied less well than Delta19::pSMT181 in human monocyte-derived macrophages (MDM) (P = 0.039). Surface expression of major histocompatibility complex class II molecules was reduced in phagocytes infected with M. tuberculosis; this effect was not seen in cells infected with Delta19. Delta19 induced lower interleukin 1beta (IL-1beta) secretion from monocytes and MDM. Overexpression of the 19-kDa protein increased IL-1beta, IL-12p40, and tumor necrosis factor alpha secretion irrespective of phagocyte maturity. These data support reports that the 19-kDa lipoprotein has pleiotropic effects on the interaction of M. tuberculosis with phagocytes. However, this analysis indicates that in the context of the whole bacillus, the 19-kDa lipoprotein is only one of a number of molecules that mediate the innate response to M. tuberculosis.