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.

An assessment of excess mortality during the COVID-19 pandemic, a retrospective post-mortem surveillance in 12 districts - Zambia, 2020-2022.

BACKGROUND: The number of COVID-19 deaths reported in Zambia (N = 4069) is most likely an underestimate due to limited testing, incomplete death registration and inability to account for indirect deaths due to socioeconomic disruption during the pandemic. We sought to assess excess mortality during the COVID-19 pandemic in Zambia. METHODS: We conducted a retrospective analysis of monthly-death-counts (2017-2022) and individual-daily-deaths (2020-2022) of all reported health facility and community deaths at district referral health facility mortuaries in 12 districts in Zambia. We defined COVID-19 wave periods based on a sustained nationally reported SARS-CoV-2 test positivity of greater than 5%. Excess mortality was calculated as the difference between observed monthly death counts during the pandemic (2020-2022) and the median monthly death counts from the pre-pandemic period (2017-2019), which served as the expected number of deaths. This calculation was conducted using a Microsoft Excel-based tool. We compared median daily death counts, median age at death, and the proportion of deaths by place of death (health facility vs. community) by wave period using the Mann-Whitney-U test and chi-square test respectively in R. RESULTS: A total of 112,768 deaths were reported in the 12 districts between 2020 and 2022, of which 17,111 (15.2%) were excess. Wave periods had higher median daily death counts than non-wave periods (median [IQR], 107 [95-126] versus 96 [85-107], p < 0.001). The median age at death during wave periods was older than non-wave periods (44.0 [25.0-67.0] versus 41.0 [22.0-63.0] years, p < 0.001). Approximately half of all reported deaths occurred in the community, with an even greater proportion during wave periods (50.6% versus 53.1%, p < 0.001), respectively. CONCLUSION: There was excess mortality during the COVID-19 pandemic in Zambia, with more deaths occurring within the community during wave periods. This analysis suggests more COVID-19 deaths likely occurred in Zambia than suggested by officially reported numbers. Mortality surveillance can provide important information to monitor population health and inform public health programming during pandemics.

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.

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.

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.

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.

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.