Adult surgical admissions at a Botswana tertiary teaching hospital - spectrum, comorbidity profile, and outcomes.

BACKGROUND: Documentation on the spectrum, comorbidities, profile, and outcomes of adult surgical admissions in Botswana is limited. This information may guide manpower distribution for proposed rotations in the new general surgery training programmes. METHODS: The medical records of adult surgical admissions for a period of one year (August 2017 - July 2018) were reviewed retrospectively. Demographics, types of admissions, dates of admission and discharge, and known comorbidities were captured and the outcomes were analysed. RESULTS: Of the 2610 admissions the mean age was 44.4 years and 60.8% were male. Gastrointestinal tract (GIT), neurosurgical, and cardiothoracic admissions constituted 60.7%. Emergency admissions constituted 50.1%. Comorbidities were found in 45.6% of the admissions, and HIV-prevalence was 697/1822 (38.3%) among known HIV-status patients. Elective admissions underwent more surgical procedures, 776/1303 (59.6%), p = 0.001 (COR 1.9, 95% CI:1.7-2.3). A total of 220/2610 complications (8.4%) were documented, including 42/1355 (3.1%) superficial surgical site infections and 159/2610 deaths (6.1%). Hypertension and diabetes mellitus were associated with higher mortality, p = 0.002 (COR 1.8,95% CI:1.2-2.6) and p = 0.031 (COR 1.9, 95% CI:1.1-3.4) respectively. HIV-positive patients had longer hospital stays than HIV-negative patients, p = 0.001 (COR 1.03, 95% CI:1.02-1.04). HIV-positive admissions with CD4 count < 200 had significantly higher composite complication and mortality rate than those with ≥ 200, p = 0.002 (COR 3.03, 95% CI:1.52-6.04) and p = 0.001 (COR 4.34, 95% CI:2.08-9.05) respectively. CONCLUSION: Contributions of emergency and elective admissions were even. A higher burden of diseases was found in gastroenterology. The higher mortalities associated with hypertension, diabetes, and CD4 count < 200 warrant further study.

Unveiling the pathogenic mechanisms of NPR2 missense variants: insights into the genotype-associated severity in acromesomelic dysplasia and short stature.

Introduction: Natriuretic peptide receptor 2 (NPR2 or NPR-B) plays a central role in growth development and bone morphogenesis and therefore loss-of-function variations in NPR2 gene have been reported to cause Acromesomelic Dysplasia, Maroteaux type 1 and short stature. While several hypotheses have been proposed to underlie the pathogenic mechanisms responsible for these conditions, the exact mechanisms, and functional characteristics of many of those variants and their correlations with the clinical manifestations have not been fully established. Methods: In this study, we examined eight NPR2 genetic missense variants (p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg318Gly, p.Arg388Gln, p.Arg495Cys, p.Arg557His, and p.Arg932Cys) Acromesomelic Dysplasia, Maroteaux type 1 and short stature located on diverse domains and broadly classified as variants of uncertain significance. The evaluated variants are either reported in patients with acromesomelic dysplasia in the homozygous state or short stature in the heterozygous state. Our investigation included the evaluation of their expression, subcellular trafficking and localization, N-glycosylation profiles, and cyclic guanosine monophosphate (cGMP) production activity. Results and Discussion: Our results indicate that variants p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg388Gln have defective cellular trafficking, being sequestered within the endoplasmic reticulum (ER), and consequently impaired cGMP production ability. Conversely, variants p.Arg318Gly, p.Arg495Cys, and p.Arg557His seem to display a non-statistically significant behavior that is slightly comparable to WT-NPR2. On the other hand, p.Arg932Cys which is located within the guanylyl cyclase active site displayed normal cellular trafficking profile albeit with defective cGMP. Collectively, our data highlights the genotype-phenotype relationship that might be responsible for the milder symptoms observed in short stature compared to acromesomelic dysplasia. This study enhances our understanding of the functional consequences of several NPR2 variants, shedding light on their mechanisms and roles in related genetic disorders which might also help in their pathogenicity re-classification.

Contribution of Xpert® MTB/RIF to tuberculosis case finding among pregnant women in Botswana.

SETTING: Seven health facilities with antenatal care (ANC) clinics in two districts near Gaborone, Botswana. OBJECTIVES: To determine 1) the prevalence of tuberculosis (TB) and HIV-TB co-infection in pregnancy, and 2) the sensitivities of symptomatic TB screening and Xpert testing against gold standard culture. DESIGN: This was a cross-sectional study. Pregnant women were randomly enrolled and screened using TB symptoms. HIV status was determined from ANC clinics' client records. Two sputum specimens were collected from all clients and each was tested using Xpert® and culture for Mycobacterium tuberculosis. RESULTS: Of 407 cases, eight had one or more TB symptoms, and all tested negative with Xpert® and culture. Another two (0.5%, 95%CI 0.08-1.96) asymptomatic clients tested positive with both tests. The adjusted TB prevalence was higher than that of the general population (0.6% vs. 0.24%; P < 0.001). The prevalence of TB among HIV-positive and HIV-negative clients was 1/69 (1.45%, 95%CI 0.29-2.61) and 1/336 (0.3%, 95%CI 0.23-0.83), respectively (Fisher's exact test P = 0.312). Xpert® demonstrated a 100% sensitivity and 100% specificity, while symptom screening had 0.0% sensitivity and 98% specificity. CONCLUSIONS: TB prevalence among pregnant women was high and TB symptom screening had limited ability to detect TB. An alternative TB screening algorithm for pregnant women is urgently needed irrespective of TB symptoms.

OBJECTIFS: Déterminer 1) la prévalence de la tuberculose (TB) et de la co-infection VIH-TB pendant la grossesse, et 2) la sensibilité du dépistage de la TB basé sur les symptômes et de l'Xpert® MTB/RIF par rapport à l'étalon or de la culture. SCHÉMA: Ceci est une étude transversale. Des femmes enceintes venant de sept centres de santé ont été enrôlées de façon aléatoire et dépistées en fonction des symptômes de TB. Deux échantillons de crachats ont été recueillis chez toutes les femmes et chacune a eu un test Xpert® et une culture. Le statut VIH a été déterminé grâce aux dossiers de consultation prénatale. RÉSULTATS: Sur 407 femmes enrôlées et analysées, huit (2,0% IC95% 0,62­3,32) avaient un ou plusieurs symptômes de TB et toutes ont été négatives pour l'Xpert® et la culture. Deux autres femmes (0,5% ; IC95% 0,08­1,96) asymptomatiques ont été positives pour les deux tests. La prévalence ajustée de TB est plus élevée que dans la population générale (0,6% contre 0,24% ; P < 0,001). La prévalence de TB parmi les femmes positives au VIH et non infectées a été respectivement de 1/69 (1,45% ; IC95% 0,29­2,61) et 1/336 (0,3% ; IC95% 0,23­0,83) (test exact de Fisher, P = 0,312). L'Xpert® a démontré une sensibilité de 100% et une spécificité de 100,0% alors que le dépistage sur les symptômes a eu une sensibilité de 0,0% mais une spécificité de 98%. CONCLUSION: La prévalence de la TB chez les femmes enceintes est élevée et le dépistage sur les symptômes a une capacité limitée de détection de la TB. Il y a un besoin urgent d'un algorithme alternatif de dépistage de la TB pour les femmes enceintes quels que soient leurs symptômes de TB.

Tuberculosis preventive treatment opportunities at antiretroviral therapy initiation and follow-up visits.

SETTING: Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%. OBJECTIVES: To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV. DESIGN: A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the Xpert® MTB/RIF Package Rollout Evaluation Study between 2012 and 2015. RESULTS: Of 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4 <200 cells/mm3 (aOR = 1.4, P = 0.030); anemia (aOR = 2.39, P < 0.001); cough (aOR = 11.21, P < 0.001); fever (aOR = 2.15, P = 0.001); and weight loss (aOR = 2.60, P = 0.002). CONCLUSION: Eligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana.

MARCO DE REFERENCIA: Veintidós consultorios que prestan atención y tratamiento relacionados con la infección por el virus de la inmunodeficiencia humana (VIH) en Botswana, donde la comorbilidad por tuberculosis (TB) e infección por el VIH puede alcanzar 49%. OBJETIVOS: Evaluar los criterios para recibir el tratamiento preventivo de la TB (TPT) durante las consultas de iniciación y seguimiento del tratamiento antirretrovírico (TAR) y describir la prevalencia de TB y los factores asociados en el momento del inicio y el rendimiento del diagnóstico de TB en cada cita de seguimiento del TAR. MÉTODO: Fue este un estudio prospectivo de los datos obtenidos sistemáticamente en las personas con infección por el VIH (PLHIV), inscritas en la atención para el estudio de evaluación del despliegue de la prueba Xpert® MTB/RIF del 2012 al 2015. RESULTADOS: De los 6041 PLHIV que iniciaron el TAR, 69% (4177/6041) cumplía los criterios para recibir el TPT al comienzo; 93% (5408/5815) en la primera consulta de seguimiento; 95% (5234/5514) en la segunda; 96% (4869/5079) en la tercera; y 97% (3925/4075) en la cuarta cita de seguimiento. La prevalencia inicial de TB fue 11% y durante el seguimiento fue 2%, 3%, 3% y 6%, respectivamente. Al comienzo del TAR, los factores de riesgo independientes de diagnóstico de TB fueron una cifra de linfocitos CD4 <200 células/mm3 (aOR 1,4; P = 0,030), la anemia (aOR 2,39; P < 0,001), la tos (aOR 11,21; P = <0,001), la fiebre (aOR 2,15; P = 0,001) y la pérdida de peso (aOR 2,60; P = 0,002). CONCLUSIÓN: Los pacientes cumplen las condiciones para recibir el TPT con mayor frecuencia en las consultas posteriores al comienzo del TAR, pero la mayoría de los casos de TB activa se detecta al iniciarlo. Las oportunidades desaprovechadas para detectar casos de TB dificultan aún más el control de esta enfermedad en las PLHIV en Botswana.