Robert Rolfe’s research while affiliated with Duke University and other places

Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii ( C. burnetii ) phase II antigens using immunofluorescent antibody (IFA) testing, and acute serum was tested for C. burnetii with PCR. Acute Q fever was defined as a fourfold or greater rise from the acute to convalescent sample in IFA reciprocal titer or PCR detection that was confirmed through repeat testing. Test characteristics were tabulated. Among 496 participants tested using both paired IFA and PCR testing, 463 (93.3%) tested negative on both IFA and PCR, five (1.0%) tested positive for Q fever on both IFA and PCR, and 28 (5.6%) tested positive for Q fever on IFA alone. The sensitivity of PCR testing using paired IFA testing as an index was 0.15 (5/33), and the specificity was 1 (463/463). C. burnetii PCR testing provides a clinically specific method that may aid in timely diagnosis in settings in which acute Q fever is a common cause of febrile illness. However, we found a low clinical sensitivity of PCR testing on serum when compared with paired IFA serology.

Background A periurban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016 to 2019 at hospitals serving the epizootic area. Methods From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at 2 hospitals in Moshi, Tanzania. Archived serum, plasma, or whole blood samples were retrospectively tested for RVFV by PCR. Human samples positive for RVFV were sequenced and compared to RVFV sequences obtained from cattle through a prospective livestock abortion study. Phylogenetic analysis was performed on complete RVFV genomes. Results Among 656 human participants, we detected RVFV RNA in 4 (0.6%), including 1 death with hepatic necrosis and other end-organ damage at autopsy. Humans infected with RVFV were enrolled from June through August 2018, and all resided in or near urban areas. Phylogenetic analysis of human and cattle RVFV sequences demonstrated that most clustered to lineage B, a lineage previously described in East Africa. A lineage E strain clustering with lineages in Angola was also identified in cattle. Conclusions We provide evidence that an apparently small RVFV outbreak among dairy cattle in northern Tanzania was associated with concurrent severe and fatal infections among humans. Our findings highlight the unidentified scale and diversity of interepizootic RVFV transmission, including near and within an urban area.

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007–April 2009. Among 788 participants, median age was 20 (interquartile range 2–38) years. We performed PCR amplification of V1–V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.

International travel can cause new illness or exacerbate existing conditions. Because primary care providers are frequent sources of health advice to travelers, they should be familiar with destination-specific disease risks, be knowledgeable about travel and routine vaccines, be prepared to prescribe chemoprophylaxis and self-treatment regimens, and be aware of travel medicine resources. Primary care providers should recognize travelers who would benefit from referral to a specialized travel clinic for evaluation. Those requiring yellow fever vaccination, immunocompromised hosts, pregnant persons, persons with multiple comorbid conditions, or travelers with complex itineraries may warrant specialty referral.

Abstract Background Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base. Main body High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children

Background To develop effective antimicrobial stewardship programs (ASPs) for low- and middle-income countries (LMICs), it is important to identify key targets for improving antimicrobial use. We sought to systematically describe the prevalence and patterns of antimicrobial use in three LMIC hospitals. Methods Consecutive patients admitted to the adult medical wards in three tertiary care hospitals in Tanzania, Kenya, and Sri Lanka were enrolled in 2018–2019. The medical record was reviewed for clinical information including type and duration of antimicrobials prescribed, indications for antimicrobial use, and microbiologic testing ordered. Results A total of 3,149 patients were enrolled during the study period: 1,103 from Tanzania, 750 from Kenya, and 1,296 from Sri Lanka. The majority of patients were male (1,783, 56.6% overall) with a median age of 55 years (IQR 38–68). Of enrolled patients, 1,573 (50.0%) received antimicrobials during their hospital stay: 35.4% in Tanzania, 56.5% in Kenya, and 58.6% in Sri Lanka. At each site, the most common indication for antimicrobial use was lower respiratory tract infection (LRTI; 40.2%). However, 61.0% received antimicrobials for LRTI in the absence of LRTI signs on chest radiography. Among patients receiving antimicrobials, tools to guide antimicrobial use were under-utilized: microbiologic cultures in 12.0% and microbiology consultation in 6.5%. Conclusion Antimicrobials were used in a substantial proportion of patients at tertiary care hospitals across three LMIC sites. Future ASP efforts should include improving LRTI diagnosis and treatment, developing antibiograms to direct empiric antimicrobial use, and increasing use of microbiologic tests.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. Methods: We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. Results: Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. Conclusions: The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.

Antibiotic resistance is an emerging global public health threat. One of the main drivers of this threat is the inappropriate use of antibiotics. In Sri Lanka, antibiotic consumption is increasing, but little is known locally about how patients perceive antibiotics. We conducted a qualitative study to gain a better understanding of the knowledge, perceptions, and attitudes of patients regarding antibiotics and antibiotic resistance. Semi-structured interviews involving 18 patients with lower respiratory tract infection (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka were conducted. Interviews were analyzed to identify themes regarding the patients’ knowledge of LRTI etiology and treatment, perceptions and attitudes toward LRTI treatment, including antibiotics, and patient–physician communication. Most patients mentioned multiple care visits and the use of multiple pharmaceuticals prior to admission. Patients sought a quick resolution to their ailments and frequently visited several private physicians to obtain a satisfying answer. Self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment, and bought over-the-counter antibiotics. Patients’ knowledge of disease etiology and antibiotics was poor. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, patient–provider communication was limited and mainly confined to prescription instructions. This qualitative study performed in Sri Lanka suggests that inappropriate use of antibiotics is a multifactorial problem. To improve antibiotic use, a multifactorial approach that includes educating the public, increasing awareness among physicians, and implementing systems-level changes to restrict access to antibiotics is urgently needed.