Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).

Pediatric tuberculosis outcomes and factors associated with unfavorable treatment outcomes in Botswana, 2008-2019: a retrospective analysis.

INTRODUCTION: Globally, the amount of research on the outcomes of pediatric tuberculosis (TB) is disproportionately less than that of adult TB. The diagnosis of paediatric TB is also problematic in developing countries. The aim of this study was to describe the outcomes of pediatric TB in Botswana and to identify the factors associated with unfavorable outcomes. METHODS: This was a retrospective analysis of pediatric TB outcomes in Botswana, over a 12-year period from January 2008 to December 2019. Treatment success (treatment completion or cured) was considered a favorable outcome, while death, loss to follow-up and treatment failure were considered unfavorable outcomes. Program data from drug-sensitive TB (DS-TB) cases under the age of 15 years were included. Sampling was exhaustive. Binary logistic regression was used to determine the factors associated with unfavorable outcomes during TB treatment. A p value of < 0.05 was considered a statistically significant association between the predictor variables and unfavorable outcomes. RESULTS: The data of 6,004 paediatric TB cases were extracted from the Botswana National TB Program (BNTP) electronic registry and analyzed. Of these data, 2,948 (49.4%) were of female patients. Of the extracted data, 1,366 (22.8%) were of HIV positive patients and 2,966 (49.4%) were of HIV negative patients. The rest of the data were of patients with unknown HIV status. Pulmonary TB accounted for 4,701 (78.3%) of the cases. Overall, 5,591 (93.1%) of the paediatric TB patient data showed treatment success, 179 (3.0%) were lost to follow-up, 203 (3.4%) records were of patients who died, and 31 (0.5%) were of patients who experienced treatment failure. The factors associated with unfavorable outcomes were positive HIV status (AOR 2.71, 95% CI: 2.09-3.52), unknown HIV status (AOR 2.07, 95% CI: 1.60-2.69) and retreatment category (AOR 1.92, 95% CI: 1.30-2.85). Compared with the 0-4 years age category, the 5-9 years (AOR 0.62, 95% CI: 0.47-0.82) and 10-14 years (AOR 0.76, 95% CI: 0.60-0.98) age categories were less likely to experience the unfavorable outcomes. CONCLUSION: This study shows a high treatment success rate among paediatric TB cases in Botswana. The government under the National TB Program should maintain and consolidate the gains from this program. Public health interventions should particularly target children with a positive or unknown HIV status, those under 5 years, and those who have been previously treated for TB.

Predictors of mass psychogenic illness in a junior secondary school in rural Botswana: A case control study.

Background: In March 2019, students at Lempu Secondary School in Kweneng District, Botswana displayed symptoms including headache, abnormal leg movements and difficulty walking. Within days, 133 students were admitted to Scottish Livingstone Hospital where mass psychogenic illness (MPI) was diagnosed. Aim: To identify predictors of this illness. Setting: Kweneng West District, Botswana. Methods: This was a case control study using interviewer-administered questionnaires. Cases were students who displayed MPI symptoms from the 2nd of March to the time of the interviews or who were admitted with MPI diagnosis. Analysis was restricted to female students. Logistic regression was used to generate odds ratios. A p value of < 0.05 was considered to demonstrate significant association between variables. Results: Interviews were conducted with 142 cases and 202 controls. The median age was 15 years. Most of the cases (95.8%) were boarding girls. Residence in school campus (AOR 13.2), history of evaluation by psychologist and/or social worker (AOR 2.6), history of traumatic events (AOR 1.8), contact with sick peers (AOR 2.3) and contact with spiritual healer (AOR 2.0) were independent predictors of MPI. Additionally, perception of adequate security in the dormitories (AOR 0.3) and perception of poor lighting (AOR 6.8) were significant predictors of MPI amongst boarding girls. Conclusion: The outbreak in Lempu Community Junior Secondary School (CJSS) was typical of mass psychogenic illness affecting mainly boarding girls and was associated with psychological and environmental risk factors. Changing the boarding environment and continuous psychological support are key to preventing future outbreaks. Interventions should also target the identified risk factors.

COVID-19 in Princess Marina Hospital, Botswana: An Outbreak Investigation.

The Princess Marina Hospital in Gaborone, Botswana, had an outbreak of COVID-19 from early August 2020. The aim of this paper was to describe the outbreak investigation. The investigation's specific objectives were to describe the COVID-19 cases in terms of person, place, and time (PPT) and to determine measures to prevent further transmission of the infection. The data reported herein were collected over a 3-month period from beginning of August to end of October 2020. The investigation included all COVID-19 cases i.e. both patients and healthcare workers. It followed the steps of an outbreak investigation. These included assembling an investigation team comprising both the hospital and DHMT staff. All the wards reported their confirmed cases to the infection control team who in turn prepared line lists and case reports. Epicurves were produced from date of positive result. A total of 193 cases were reported, of which 110 (57.0%) were patients and 83 (43.0%) were healthcare workers. The median age was 35 years. Females accounted for 154 (79.8%) participants. Most of the wards were affected. The wards with the highest numbers of cases were female medical ward (39), emergency department (24), gynecology ward (17), and pediatric medical ward (10). Control measures included restricting movement into the hospital as well as clinical screening at all entry points. Furthermore, all patients were tested before admission into the wards. Surveillance of COVID-19 cases was continued beyond the 3 months reported in this paper. COVID-19 can spread rapidly in hospital settings affecting both patients and healthcare workers. Outbreak investigations including describing cases in terms of person, place, and time are critical if the most effective and efficient control measures are to be implemented.

Knowledge, attitudes and preventive practices towards COVID-19 among workers at two points of entry in South-Eastern Botswana: A cross-sectional study.

INTRODUCTION: Adherence to control measures and provision of appropriate information at international borders and points of entry (POE) are key to limiting the importation of COVID-19. This study aimed to describe the knowledge, attitudes, and practices (KAPs) of POE staff towards COVID-19 in Botswana. METHODS: This was a cross-sectional study of the COVID-19 KAPs among workers at Tlokweng border and Sir Seretse Khama International Airport (SSKIA) using a self-administered questionnaire. The tool incorporated the participants' demographics and selected questions on COVID-19 KAPs. Analysis was descriptive. Categorical data were summarized with frequencies while numeric data were summarized with medians and interquartile ranges (IQR). The total knowledge and practice scores of each individual were computed by adding their individual scores for each question. The scores were then categorized according to Bloom's cutoffs of good (80-100%), moderate (60-79%) and poor (<60%). RESULTS: A total of 276 individuals participated in the study. Of these, 70 were from Tlokweng border and 206 were from SSKIA. The participants performed worst on questions on the frequency of severe disease and asymptomatic transmission of COVID-19. The attitudes were mainly positive. However, 54.6% of participants thought that the COVID-19 burden is exaggerated. For practice, the worst performance was on social distancing, sanitizing shared surfaces, and going to work while symptomatic. Overall, good and moderate knowledge was observed in 47.8% and 38.0% of participants, respectively. Similarly, good and moderate performance on practices was observed in 63.6% and 24.4% of participants respectively. CONCLUSION: The knowledge, attitudes, and practices were generally good at the 2 points of entry. More than 85% of respondents had moderate or good performance on knowledge and practice questions. However, the respondents performed poorly in some key questions. Targeted health information and promotion must address the identified gaps.

High-risk behaviors and factors for HIV and sexually transmitted infections among transgender people in Gaborone, Botswana: results from a national survey.

Introduction: key populations and transgender people in particular are at a high risk of HIV infection. However, very little is known about risk behaviors of transgender people in Botswana. The aim of this study was to determine the prevalence of high-risk behaviors for HIV and sexually transmitted infections (STIs) among transgender people in Botswana. Methods: data from the Botswana 2017 Biological and Behavioral Surveillance Survey of HIV/STIs among select key populations (BBSS-2) was used. The cross sectional survey documented behavioral risk factors for these infections. This paper only focused on the analysis of the transgender data. Descriptive analysis was done with IBM Statistical Software for the Social Sciences (SPSS) version 24. Results: there were 56 transgender people identified of which 12 (21.4%) were transgender women. The median age was 24 (interquartile range (IQR) 22-28). Among transgender women, 2 (16.7%) reported concurrent sexual partners and 9 (75%) reported condom use at last intercourse. However, only 7 (58.3%) reported consistent lubricant use. About 45% of the respondents did not know the HIV status of their last male partner. Only one of the transgender women reported intercourse with at least 1 female in the last month. About a third reported that they had STI symptoms in the past year. Alcohol use was reported in 50% of respondents while 83% had disclosed gender identity and had been accepted by their families. However, 25% reported discrimination by a healthcare worker. Conclusion: the high-risk behaviors were frequent among transgender women. This study underlines the need for sustained efforts to reach this key population.

Outcomes and predictors of tuberculosis mortality in Kweneng West District, Botswana: a retrospective cohort study.

Introduction: Botswana is among the countries with the highest tuberculosis (TB) notification rates in the world. However, there is paucity of data on the outcomes and predictors of TB mortality at district level in Botswana. This study was aimed at describing the TB outcomes and identifying the predictors of mortality in Kweneng West district, Botswana. Methods: this was a retrospective cohort study of TB outcomes in Kweneng West, from January 2008 to December 2016. All documented drug-sensitive TB (DS-TB) patients aged 16 years and above were included. The World Health Organization (WHO) definitions of treatment outcomes for DS-TB were used. Binary logistic regression was used to identify predictors of mortality. Results: there were 1475 TB notifications in the study period. The median age was 36 years and 41.5% were female. A total of 728 (49.4%) were HIV positive. Pulmonary TB (PTB) accounted for 87.3% of all cases. The overall treatment success rate (TSR) was 81.9% and the mortality rate was 9.4%. Compared to the 16-25 years age group, patients aged more than 65 years had the highest risk of mortality (AOR=9.63). Other significant predictors of mortality were male sex (AOR=1.63), no sputum microscopy (AOR=1.77), positive HIV (AOR=2.13) and unknown HIV status (AOR=4.47). Positive sputum microscopy (AOR=0.50) and extra-pulmonary TB (EPTB) (AOR=0.56) were associated with less mortality. Conclusion: while Botswana has relatively good TB treatment success rates, the mortality rates are high. Public health interventions should target the identified risk factors of mortality.

Prevalence and predictors of depression, anxiety and stress among frontline healthcare workers at COVID-19 isolation sites in Gaborone, Botswana.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been associated with mental health outcomes and healthcare workers (HCWs) are at the highest risk. The aim of this study was to determine the prevalence and predictors of depression, anxiety and stress, among frontline HCWs at COVID-19 isolation and treatment sites in Gaborone, Botswana. METHODS: This was a cross-sectional study using self-administered questionnaires at the six (6) isolation facilities. The 42-item Depression, Anxiety and Stress Scale (DASS-42) was used to assess for the outcomes. The proportions are presented with 95% confidence intervals (95% CI). Logistic regression analysis identified predictors of the outcomes. A p value of <0.05 was considered significant. RESULTS: A total of 447 participants with a median age of 30 years responded. Depression, anxiety and stress were detected in 94 (21.0% (95% CI 17.3-25.1%)), 126 (28.2% (CI 24.1-32.6%)) and 71 (15.9% (12.6-19.6%)) of the participants respectively. Depression was associated with smoking (AOR 2.39 (95% CI 1.23-4.67)), working at the largest COVID-19 isolation centre, Sir Ketumile Masire Teaching Hospital (SKMTH) (AOR 0.25 (95% CI 0.15-0.43)) and experience of stigma (AOR 1.68 (95% CI 1.01-2.81)). Tertiary education (AOR 1.82 (95% CI 1.07-3.07)), SKMTH (AOR 0.49 (95% CI 0.31-0.77)), household members with chronic lung or heart disease (AOR 2.05 (95% CI 1.20-3.50)) and losing relatives or friends to COVID-19 (AOR 1.72 (95% CI 1.10-2.70)) were predictors of anxiety. Finally, predictors of stress were smoking (AOR 3.20 (95% CI 1.42-7.39)), household members with chronic heart or lung disease (AOR 2.44 (95% CI 1.27-4.69)), losing relatives or friends to COVID-19 (AOR 1.90 (1.05-3.43)) and working at SKMTH (AOR 0.24 (0.12-0.49)). CONCLUSION: Depression, anxiety and stress are common among frontline HCWs working in the COVID-19 isolation sites in Gaborone. There is an urgent need to address the mental health outcomes associated with COVID-19 including addressing the risk factors identified in this study.

Human Herpesvirus-6 Detection in Cerebrospinal Fluid on the BioFire FilmArray Meningitis/Encephalitis Panel in a High Human Immunodeficiency Virus-Prevalence African Setting.

The prevalence and clinical relevance of human herpesvirus-6 (HHV-6) detection in cerebrospinal fluid (CSF) using multiplex polymerase chain reaction (PCR) testing in patients with suspected meningoencephalitis in high human immunodeficiency virus-prevalence African settings are not known. We describe the clinical and laboratory characteristics of 13 patients with HHV-6 CSF PCR positivity in Botswana.

University of Botswana Public Health Medicine Unit contributions to the national COVID-19 response.

COVID-19 was declared a Public Health Emergency of International Concern (PHEIC) in January 2020 and a pandemic in March 2020. Botswana reported its first case on 30th March 2020 and as of 31st January 2021 had 21,293 cases and 46 deaths. The University of Botswana Public Health Medicine Unit has made significant contributions to the national preparedness and response to COVID-19. The program alumni and Public Health Medicine residents have and continue to provide key technical support to the Ministry of Health and Wellness across the major pillars of COVID-19. This includes key roles in national and subnational coordination and planning, surveillance, case investigations and rapid response teams, points of entry, travel and transportation, infection prevention and control and case management. The unit is thus supporting the country in achieving the World Health Organization (WHO) primary objective of limiting human-to-human transmission, optimal care of the affected and maintaining essential services during the outbreak. The Public Health Medicine Unit has played a key role in capacity building including early rapid COVID-19 training of healthcare workers across the country. Furthermore faculty members and residents are involved in several COVID-19 research projects and collaborations.