Miriam Haverkamp

Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana

Cryptococcus neoformans var. grubii (Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub‐Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MATa allele were observed in both clinical and environmental isolates; however, the mating‐type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MATa and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans.

Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population of C. neoformans from sub-Saharan Africa, commonly isolated from mopane trees, to determine how selective pressures in the environment coincidentally adapted C. neoformans for human virulence. Genome sequencing and phylogenetic analysis of 387 isolates, representing the global VNI and African VNB lineages, highlighted a deep, nonrecombining split in VNB (herein, VNBI and VNBII). VNBII was enriched for clinical samples relative to VNBI, while phenotypic profiling of 183 isolates demonstrated that VNBI isolates were significantly more resistant to oxidative stress and more heavily melanized than VNBII isolates. Lack of melanization in both lineages was associated with loss-of-function mutations in the BZP4 transcription factor. A genome-wide association study across all VNB isolates revealed sequence differences between clinical and environmental isolates in virulence factors and stress response genes. Inositol transporters and catabolism genes, which process sugars present in plants and the human nervous system, were identified as targets of selection in all three lineages. Further phylogenetic and population genomic analyses revealed extensive loss of genetic diversity in VNBI, suggestive of a history of population bottlenecks, along with unique evolutionary trajectories for mating type loci. These data highlight the complex evolutionary interplay between adaptation to natural environments and opportunistic infections, and that selection on specific pathways may predispose isolates to human virulence.

A root-cause analysis of maternal deaths in Botswana: towards developing a culture of patient safety and quality improvement

BackgroundIn 2007, 95% of women in Botswana delivered in health facilities with 73% attending at least 4 antenatal care visits. HIV-prevalence in pregnant women was 28.7%. The maternal mortality ratio in 2010 was 163 deaths per 100 000 live births versus the government target of 130 for that year, indicating that the Millennium Development Goal 5 was unlikely to be met. A root-cause analysis was carried out with the aim of determining the underlying causes of maternal deaths reported in 2010, to categorise contributory factors and to prioritise appropriate interventions based on the identified causes, to prevent further deaths.MethodsCase-notes for maternal deaths were reviewed by a panel of five clinicians, initially independently then discussed together to achieve consensus on assigning contributory factors, cause of death and whether each death was avoidable or not at presentation to hospital. Factors contributing to maternal deaths were categorised into organisational/management, personnel, technology/equipment/supplies, environment and barriers to accessing healthcare.ResultsFifty-six case notes were available for review from 82 deaths notified in 2010, with 0–4 contributory factors in 19 deaths, 5–9 in 27deaths and 9–14 in nine. The cause of death in one case was not ascertainable since the notes were incomplete. The high number of contributory factors demonstrates poor quality of care even where deaths were not avoidable: 14/23 (61%) of direct deaths were considered avoidable compared to 12/32 (38%) indirect deaths. Highest ranking categories were: failure to recognise seriousness of patients’ condition (71% of cases); lack of knowledge (67%); failure to follow recommended practice (53%); lack of or failure to implement policies, protocols and guidelines (44%); and poor organisational arrangements (35%). Half the deaths had some barrier to accessing health services.ConclusionsRoot-cause analysis demonstrates the interactions between patients, health professionals and health system in generating adverse outcomes for patients. The lessons provided indicate where training of undergraduate and postgraduate medical, midwifery and nursing students need to be intensified, with emphasis on evidence-based practice and adherence to protocols. Action plans and interventions aimed at changing the circumstances that led to maternal deaths can be implemented and re-evaluated.

Airborne Outreach: Building HIV Capacity and Strengthening Health-Care Systems in Rural Botswana

There is a paucity of research demonstrating how HIV-funded services in Africa have improved equity and access to non-HIV services for both HIV-infected and uninfected patients. In this short communication, we describe the impact of an airborne outreach program to provide HIV services to high-HIV burden health facilities in rural Botswana. The analysis demonstrates how this HIV-funded program enhanced access to essential subspecialist services at several rural health facilities across Botswana.

Building Health System Capacity through Medical Education: A Targeted Needs Assessment to Guide Development of a Structured Internal Medicine Curriculum for Medical Interns in Botswana

Background: Medical internship is the final year of training before independent practice for most doctors in Botswana. Internship training in Botswana faces challenges including variability in participants’ level of knowledge and skill related to their completion of medical school in a variety of settings (both foreign and domestic), lack of planned curricular content, and limited time for structured educational activities. Data on trainees’ opinions regarding the content and delivery of graduate medical education in settings like Botswana are limited, which makes it difficult to revise programs in a learner-centered way. Objective: To understand the perceptions and experiences of a group of medical interns in Botswana, in order to inform a large curriculum initiative. Methods: We conducted a targeted needs assessment using structured interviews at one district hospital. The interview script included demographic, quantitative, and free- response questions. Fourteen interns were asked their opinions about the content and format of structured educational activities, and provided feedback on the preferred characteristics of a new curriculum. Descriptive statistics were calculated. Findings: In the current curriculum, training workshops were the highest-scored teaching format, although most interns preferred lectures overall. Specialists were rated as the most useful teachers, and other interns and medical officers were rated as average. Interns felt they had adequate exposure to content such as HIV and tuberculosis, but inadequate exposure to areas including medical emergencies, non-communicable diseases, pain management, procedural skills, X-ray and EKG interpretation, disclosing medical information, and identifying career goals. For the new curriculum, interns preferred a structured case discussion format, and a focus on clinical reasoning and procedural skills. Conclusions: This needs assessment identified several foci for development, including a shift toward interactive sessions focused on skill development, the need to empower interns and medical officers to improve teaching skills, and the value of shifting curricular content to mirror the epidemiologic transition occurring in Botswana. Interns’ input is being used to initiate a large curriculum intervention that will be piloted and scaled nationally over the next several years. Our results underscore the value of seeking the opinion of trainees, both to aid educators in building programs that serve them and in empowering them to direct their education toward their needs and goals.

Correction to: Strengthening medical training programmes by focusing on professional transitions: a national bridging programme to prepare medical school graduates for their role as medical interns in Botswana

CorrectionForllowing publication of the original article [1], the first author reported that there was a typographical error in the name of one of his co-authors. The correct spelling is Alemayehu Bedada, not Alemayhu Bedada.