Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored. METHODS: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1ß, IL-6, IL-10, and TGF-ß1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use. RESULTS: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1ß and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower. CONCLUSIONS: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.

Comparison of the Causes of Death Identified Using Automated Verbal Autopsy and Complete Autopsy among Brought-in-Dead Cases at a Tertiary Hospital in Sub-Sahara Africa.

BACKGROUND: Over one-third of deaths recorded at health facilities in Zambia are brought in dead (BID) and the causes of death (CODs) are not fully analyzed. The use of automated verbal autopsy (VA) has reportedly determined the CODs of more BID cases than the death notification form issued by the hospital. However, the validity of automated VA is yet to be fully investigated. OBJECTIVES: To compare the CODs identified by automated VA with those by complete autopsy to examine the validity of a VA tool. METHODS: The study site was the tertiary hospital in the capital city of Zambia. From September 2019 to January 2020, all BID cases aged 13 years and older brought to the hospital during the daytime on weekdays were enrolled in this study. External COD cases were excluded. The deceased's relatives were interviewed using the 2016 World Health Organization VA questionnaire. The data were analyzed using InterVA, an automated VA tool, to determine the CODs, which were compared with the results of complete autopsies. RESULTS: A total of 63 cases were included. The CODs of 50 BID cases were determined by both InterVA and complete autopsies. The positive predictive value of InterVA was 22%. InterVA determined the CODs correctly in 100% cases of maternal CODs, 27.5% cases of noncommunicable disease CODs, and 5.3% cases of communicable disease CODs. Using the three broader disease groups, 56.0% cases were classified in the same groups by both methods. CONCLUSION: While the positive predictive value was low, more than half of the cases were categorized into the same broader categories. However, there are several limitations in this study, including small sample size. More research is required to investigate the factors leading to discrepancies between the CODs determined by both methods to optimize the use of automated VA in Zambia.

A 10-year Review of TB Notifications and Mortality Trends Using a Joint Point Analysis in Zambia - a High TB burden country.

BACKGROUND: Zambia is one of the TB high-burden countries. It is important to track the progress being made towards enhancing case finding and reducing mortality. We reviewed routine TB notifications and mortality trends, over a decade from all facilities in Zambia. METHODS: A 10-year retrospective study of TB notifications and mortality trends was performed using a Joint Point Analysis version 4.9.0.0, NCI. We extracted the annual national TB program data for the period under review. RESULTS: There was a decline in annual point average for notification between 2010 and 2020 in both males and females, but the females notification rates had a higher rate of decline (AAPC = -6.7, 95%CI:-8.3 to -5.0), p<0.001) compared to the decline in males notification rate (AAPC = -4.1, 95%CI:-4.1 to -5.1, P<0.001). We found a significant growth rate in the proportion of TB patients that were bacteriologically confirmed (AAPC = 6.1, 95% CI: 3.6 to 8.7, p< 0.001), while the proportion of clinically diagnosed patients declined (AAPC= -0.1, 95%CI: -2.3 to 2.1, p<0.001). Notification of drug-resistant TB increased exponentially (AAPC=27.3, 95% CI: 13 to 41), p< 0.001) while mortality rate declined from 21.3 in 2011 to 12.7 in 2019 per 100,000 population (AAP=-5.6, 95%CI: -9.6 to -1.5, p=0.008). CONCLUSIONS: This study has illustrated the importance of reviewing and analyzing routinely collected TB data by national programs. The study revealed areas of improvement in terms of TB control and underscores the need for increased and sustained investment in case detection and diagnostics.

Tuberculosis, HIV/AIDS and Malaria Health Services in sub-Saharan Africa - A Situation Analysis of the Disruptions and Impact of the COVID-19 Pandemic.

BACKGROUND: The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries' health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. METHODS: In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. RESULTS: The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. CONCLUSIONS: Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa's economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.

Incidental Tuberculosis in sudden, unexpected, and violent deaths in the community Lusaka, Zambia - A descriptive forensic post-mortem examination study.

OBJECTIVES: Tuberculosis remains a global emergency. In Zambia only 55% of tuberculosis cases are diagnosed. We performed a study to determine incidental cases of tuberculosis seen at forensic autopsy of individuals who died suddenly and unexpectedly in the community in Lusaka, Zambia. METHODS: Whole-body autopsies were performed according to Standard Operating Procedures. Representative samples obtained from relevant organs were subjected to pathological examination. Information on circumstances surrounding the death was obtained. Data on patient demographics, gross and microscopic pathological findings, and cause(s) of death were analysed. RESULTS: Incidental tuberculosis was found in 52 cases (45 male, 7 female, age range 14-66) out of 4286 whole-body autopsies. 41/52 (80%) were aged 21-50 years. One was a 14-year old boy who died during a football match. 39/52 (75%) deaths were attributable specifically to tuberculosis only. Other deaths were due to acute alcohol intoxication(4), violence(7), ruptured ectopic pregnancy(1), bacterial meningitis (1). All the cases were from poor socio-economic backgrounds and lived in high-density areas of Lusaka. CONCLUSIONS: Incidental cases of active tuberculosis undiagnosed antemortem seen at forensic autopsy reflects major gaps in the national TB control programs. More investments into proactive screening, testing, treatment activities, and accurate data collection are required.

Cardiac cysticercosis and neurocysticercosis in sudden and unexpected community deaths in Lusaka, Zambia: a descriptive medico-legal post-mortem examination study.

BACKGROUND: Cysticercosis is a World Health Organization designated neglected human zoonosis worldwide. Data on cardiac cysticercosis and its contribution to sudden and unexpected community deaths are scarce and require study. METHODS: A study was performed of cysticercosis-related deaths and other incidental cases of cysticercosis seen at forensic post-mortem examination over a period of 12 months, in individuals who died suddenly and unexpectedly in the community in Lusaka, Zambia. Whole-body post-mortem examinations were performed according to standard operating procedures for post-mortem examinations. Representative samples were obtained from all body organs and subjected to histopathological examination. Information was obtained on circumstances surrounding the death. Data were collated on patient demographics, history, co-morbidities, pathological gross and microscopic findings, and forensic autopsy cause(s) of death. The available literature on cardiac cysticercosis was also reviewed. RESULTS: Nine cases of cysticercosis were identified. Eight of the nine cases had cardiac cysticercosis. There was no prior history of cysticercosis before death. All were male, aged between 28 and 56 years, and from high population density and low socioeconomic communities. There was no community case clustering identified. CONCLUSIONS: Cardiac cysticercosis and neurocysticercosis are important incidental findings in sudden and unexpected deaths in the community and can easily be missed antemortem. More investment in forensic autopsy services is required to define the undiagnosed burden of deaths due to treatable communicable diseases.

COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.

BACKGROUND: Data from Africa regarding sudden and unexpected COVID-19 community deaths and underlying pathological, demographic, and co-morbidity features require definition. METHODS: We performed a case series of COVID-19-related deaths seen at Forensic Post-Mortem examination of sudden and unexpected Community Deaths in Lusaka, Zambia, Africa. Whole-body Post-Mortem examinations were performed according to Standard Operating Procedures. Patient demographics, history, co-morbidities, pathological gross and microscopic findings, and cause(s) of death were recorded. Variables were grouped as frequencies and percentages. Comparison of data was made with autopsy findings of hospital COVID-19 deaths. FINDINGS: Of 21 COVID-19 decedents, 14/21 (66.7%) were male; 18/21, (85.7%) were below 55 years of age (mean age, 40 ± 12.3; range, 20-73). The median duration of symptoms was 1 day (range 0-2); 9/21 (42.9%) had co-morbidities, with hypertension and obesity being the most common. Main post-mortem findings were diffuse alveolar damage (DAD) (80.9%), saddle and shower emboli (38.1%, respectively), and pneumonia (14.3%). Pulmonary thromboembolism (76.2%), DAD (14.3%), and SARS-CoV-2 pneumonia (9.5%) were common causes of death. CONCLUSIONS: COVID-19 is an important cause of death to consider in forensic investigations of sudden and unexpected community deaths. Risk factors for the younger age of COVID-19 deaths and thromboembolism need to be identified.

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.

BACKGROUND: Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa. METHODS: We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages. FINDINGS: Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%). CONCLUSIONS: A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation.

The role of forensic pathology in the COVID-19 pandemic in Zambia.

Although forensic pathology is less visible on the front lines of public health, it plays a significant role in safeguarding public health by investigating and identifying unusual infectious disease deaths such as those caused by COVID-19. Given that forensic pathology is responsible for investigating deaths that are sudden, unexplained, or unattended by a physician, its participation in mortality and disease surveillance contributes data useful to clinicians and epidemiologists. The data provides demographic details, the extent of disease, and causes of death. Utilizing forensic pathology data provides a wealth of information that helps understand the Covid-19 disease and inform public health policy. This paper aims to describe the role of forensic pathology in the COVID-19 pandemic era in Zambia. With the confirmation of the first COVID-19 cases in Zambia, the forensic pathology service developed a screening tool for probable detection of COVID-19 infections in brought-in-dead cases undergoing forensic autopsies at the University Teaching Hospital. The screened cases were tested for COVID-19. Notably, most of the COVID-19 deaths recorded in Zambia are from the BID that were tested. During the COVID-19 pandemic, autopsies were conducted using forensic pathology principles to determine the cause of death and document the extent of disease, thus contributing to the body of knowledge in public health and infectious disease science COVID-19.In conclusion, the forensic pathology service has contributed to the management of patients infected with COVID-19. It has also been useful to public health through mortality and disease surveillance of broughtin- dead cases.

A case report: primary amoebic meningoencephalitis in a young Zambian adult.

BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a fulminant disease of the brain caused by Naegleria fowleri. Although the disease is rare, the case fatality rate is very high. In this report, we describe the first case of PAM in Zambia. CASE PRESENTATION: The patient presented with sudden onset of seizures and fever on admission. On physical examination he was febrile, comatose and with a stiff neck. Cerebral spinal fluid (CSF) collected on admission did not reveal any organism on microscopy or culture but showed elevated white cell count. A working diagnosis of severe septicemia with acute meningoencephalitis was then made and the patient was started on IV Cephtriaxone (2 g) twice daily. Despite receiving treatment, his condition deteriorated. A second CSF sample collected on day 3 was also negative for bacteria and other organisms. However, a repeat CSF sample collected on day 8 revealed numerous motile organisms that were identified as Naegleria on microscopy and confirmed to be N. fowleri on polymerase chain reaction. The patient died on day 8 of hospital admission after having received one dose of Amphotericin B (50 mg). Features consistent with PAM were detected on autopsy. CONCLUSION: The isolation of N. fowleri in this patient calls for increased awareness among clinical and laboratory staff on suspected PAM cases to promptly diagnose and effectively manage the disease.