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

Open AccessPublished:March 10, 2022DOI:https://doi.org/10.1016/j.ijid.2022.03.005

      Highlights

      • Forensic autopsies of community deaths show incidental, undiagnosed TB cases
      • Undiagnosed TB and related deaths reveal gaps in TB control programs
      • TB remains an important public health problem in Lusaka, Zambia
      • Low social-economic status and TB are intertwined in these cases

      ABSTRACT

      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.

      Keywords

      INTRODUCTION

      Community (sudden, unexpected, and violent) deaths have significant medicolegal importance (
      • Spitz W.U
      Medicolegal Investigation of Death: Guidelines for the Application of Pathology to Crime Investigation.
      ,

      Inquests Act, Vol:4 Chapter 36 of the Laws of Zambia https://www.parliament.gov.zm/node/736 . Accessed on February 1st, 2022.

      ). The coroner thus scrutinises these deaths with the aid of the Office of the State Forensic Pathologist (OSFP) to establish the cause and manner of death using forensic procedures (

      Inquests Act, Vol:4 Chapter 36 of the Laws of Zambia https://www.parliament.gov.zm/node/736 . Accessed on February 1st, 2022.

      ,

      The National Forensic Act, 2020, Act number:2. https://www.parliament.gov.zm/node/8571, Accessed on Feb 20th 2022.

      ). Forensic procedures, specifically the forensic autopsy, provides a unique opportunity to study a range of underlying communicable and non-communicable diseases not detected ante-mortem (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ;
      • Himwaze CM
      • Telendiy V
      • Maate F
      • Mupeta S
      • Chitalu C
      • Chanda D
      • et al.
      Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.
      ).
      Despite treatment being available, Tuberculosis (TB) remains a global emergency and is the second commonest infectious disease worldwide causing death (

      WHO. Global tuberculosis report 2021. October 14, 2021 https://www.who.int/publications/i/item/9789240037021, accessed 30th January, 2022.

      ). In 2018, the total burden of TB in Zambia was estimated to be 72 495, and of these, 40 176 (55%) were diagnosed with TB. Of the 36 431 (50%) started on treatment, only 32 700 (45%) completed treatment (
      • Lungu P
      • Kerkhoff AD
      • Kasapo CC
      • Mzyece J
      • Nyimbili S
      • Chimzizi R
      • et al.
      Tuberculosis care cascade in Zambia - identifying the gaps in order to improve outcomes: a population-based analysis.
      ). Forensic autopsy data may thus provide insight into the undiagnosed and sub-clinical burden of clinically undiagnosed TB in the community and who may be succumbing to the disease. Autopsies can also play a critical role in defining cryptic presentations of TB (
      • Rampatige R
      • Gilks CF.
      Autopsies and better data on causes of death in Africa.
      ). Undetected TB has significant implications as infected individuals may be a source of transmission in the community. However, the burden of undiagnosed TB in community deaths has not been estimated in Lusaka, Zambia.
      We performed a case series study of incidental TB cases seen at forensic autopsy of individuals who died suddenly, unexpectedly, and violently in the community in Lusaka, Zambia. We also reviewed literature on tuberculosis findings at autopsy.

      MATERIALS AND METHODS

      Ethics approval

      The coroner gave authority to conduct the forensic autopsies through an Order for Post-mortem Examination of community deaths. Forensic autopsies are mandated by law; thus, no consent or ethical permission is required to conduct the autopsy. Approval was obtained from the OSFP to access this anonymized data. The OSFP granted permission to access autopsy reports (autopsy findings and causes of death) and publish the data (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ).

      Study design

      We conducted retrospective case series analyses of whole-body forensic autopsies we had performed on community deaths in Lusaka, Zambia from January 2016 to December 2021 in which TB was an incidental finding or a cause of death. Information on the circumstances surrounding the death, symptoms, and past medical history was obtained from the next of kin by the Forensic Pathologist (FP) or Anatomic Pathologist (AP) as per procedure before the autopsy was conducted and the Coroners Order for Post-Mortem Examination.

      Autopsy procedures

      Autopsies were performed by either an FP or an AP. Personal Protective Equipment (PPE) was used, including a full gown, plastic apron, gloves (including cut-proof under gloves), face visor, boots, and N95 masks. Autopsies were performed in line with guidelines in the Practice Manual for Medicolegal Death Investigations at the OSFP in Zambia. In all cases, we followed universal precautions using PPE. A double pair of standard disposable surgical latex gloves in addition to cut-resistant gloves were also used (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ).

      Tissues sampled and histological examination

      Representative samples were obtained from the relevant organs as required, submitted in standard tissue cassettes, and fixed in 10% neutral buffered formalin for 72 hours. The samples were processed, embedded in paraffin, sectioned, mounted onto glass slides, and stained using hematoxylin and eosin (H&E) staining according to the Standard Operating Procedure Manual at the UTH histopathology Laboratory. All slides were examined together by the FP and AP (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ). Slides that revealed granulomatous inflammation were further subjected to Ziehl-Neelsen (ZN) staining techniques to confirm the presence of acid-fast bacilli.

      Diagnosis of Tuberculosis

      The diagnosis of Pulmonary TB (PTB) was based on autopsy findings of consolidation or cavitation in the apices of the lungs, caseating lesions, histology showing granulomatous inflammation, and confirmation of tubercle bacilli by using ZN stain. Diagnosis of Extra Pulmonary TB (EPTB) was based on caseating lesions, histology showing granulomatous inflammation, and confirmation of tubercle bacilli using ZN stain.

      Data collection and analyses

      Data on the decedent demographics, history, circumstances, autopsy findings, and opinion of the cause of death was entered in Excel and analysed using STATA version 14. The variables were grouped and presented as frequencies and percentages (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ).

      Cause(s) of Death Formulation

      The cause of death was formulated within the context of the circumstances surrounding the death, history of the case, post-mortem examination findings, and ancillary studies (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ).

      RESULTS

      Table 1 summarises the demographics and circumstances decedents. They all died suddenly, unexpectedly, and violently and were brought in dead (BID). There were fifty-two cases with active TB disease of 4286 whole-body autopsies performed. None of them had been detected or suspected ante-mortem. All decedents were from poor social-economic backgrounds and lived in high-density areas of Lusaka.
      Table 1Decedent's demographics, circumstances of death.
      FrequencyPercentCum.
      Age in Years
       11-2035.775.77
       21-301223.0828.85
       31-402038.4667.31
       41-50917.3184.62
       51-6047.6992.31
       61-7047.69100
      Sex
       Female713.513.5
       Male4586.5100
      Circumstances of Death
       Assaulted47.697.69
       Road Traffic Accident35.7713.46
       Sudden Unexpected Death at Home3771.1584.62
       Sudden Unexpected Death at Work35.7790.38
       Sudden Unexpected Death on Way to Hospital59.62100
      Forty-five were male, and seven were female, and the age ranged from 14-66 years. There was one paediatric TB death. The age ranges 31-40, 21-30, and 41-50 years were the most common at 20 (38.48%), 12 (23.08%), and 9 (17.31%), respectively. The age ranges 51-60 and 61-70 had 4 cases each at 7.69%, respectively. Three (5.77%) cases were in the age range 11-20.
      Thirty-seven (71.15%) cases died at home, while five (9.62%) died enroute to the hospital, with three (5.77%) cases died at the workplace. Seven cases were referred for a forensic autopsy for violent deaths, three (5.77%) for road traffic accidents, and four (7.69%) for assault. One paediatrics TB death involved a 14-year old boy who died suddenly while playing football.
      Table 2 summarises the autopsy findings. PTB was the most common finding in 36 (69.23%). “Mesenteric lymph node, splenic, and PTB” were present in 6 (11.5%) of cases. “Mesenteric lymph node hilar lymph node TB” was found in 2 (3.85%) cases. “Abdominal and pelvic TB,” “Cardiac and hepatic TB,” “Kaposi's’ sarcoma and PTB,” “Pulmonary, abdominal, and renal TB,” “PTB, aspergillosis, bacterial meningitis, neurocysticercosis,” “Pulmonary, renal, splenic and hepatic TB,” “Pulmonary, TB pericarditis, and Cardiac cysticercosis” and “TB pericarditis” were found at 1 case (1.92%), in each combination respectively. PTB was also found in cases with other sites of involvement in nine (9) cases (17.30%). Mesenteric lymph node involvement was found in 8 (15.35%) cases in cases with other TB sites. Hepatic TB was found in 2 (3.85%) of cases with other TB sites. TB infection of the heart was found in 2 (3.85%) cases.
      Table 2Organs affected by Tuberculosis at Autopsy.
      FrequencyPercentCum.
      Abdominal and pelvic TB11.921.92
      Cardiac and hepatic TB11.923.85
      Kaposi's sarcoma and Pulmonary TB11.925.77
      Mesenteric and Hilar lymph node TB23.859.62
      Mesenteric lymph node, Splenic and Pulmonary TB611.519.23
      Pulmonary TB3669.2388.46
      Pulmonary, Abdominal and Renal TB11.9290.38
      Pulmonary TB, Pulmonary aspergillosis, Bacterial Meningitis, Neurocysticercosis11.9292.31
      Pulmonary, Renal, Splenic and Hepatic TB11.9294.23
      Pulmonary and TB Pericarditis, Cardiac cysticercosis11.9298.08
      TB Pancarditis11.92100.00
      Table 3 summarises the Cause of Death (CoD) statements. PTB and disseminated TB were the commonest causes of death in 23 (44.23%) and 10 (19.23%) cases, respectively. Acute alcohol intoxication and EPTB were CoDs in 8 cases at 7.69% each. Road traffic accidents caused three (5.76%) deaths. Blunt impact trauma due to assault, manual strangulation, and pulmonary haemorrhage due to PTB were CoDs in 6 cases at 3.85%, respectively. Two cases had CoDs attributed to ruptured ectopic pregnancy and bacterial meningitis at 1.92%, each.
      Table 3Autopsy Cause(s) of Death.
      FrequencyPercentCum.
      Acute Alcohol Intoxication47.697.69
      Blunt Impact trauma to head due to Assault23.8511.54
      Blunt impact trauma to the head due to RTA35.7617.31
      Disseminated TB1019.2336.54
      Ruptured Ectopic pregnancy11.9238.46
      Extrapulmonary TB47.6946.15
      Manual Strangulation23.8550.00
      Bacterial Meningitis11.9251.92
      Pulmonary TB2344.2396.15
      Pulmonary haemorrhage due to Pulmonary TB23.85100.00

      Gross pathology and microscopic findings

      Figure 1 shows representative gross pathology and microscopic pathology images.
      Figure 1:
      Figure 1Secondary tuberculous-apical cavitation in lung.

      Gross pathology

      The image in Figure 1 A shows an apical cavity with whitish central caseation. The image in Figure 1 B shows hilar lymphadenopathy with a firm consistency and grey colour Figure 1. C depicts Miliary pulmonary and splenic disease, with individual lesions that are small, firm (2-mm) foci of white consolidation scattered through the lung and spleen parenchyma. The images in Figure 1 D depicts TB pericarditis with pericardial thickening caused by fibrin and collagen formation.

      Micrographs

      The micrograph in Figure 1 E shows a necrotic area that appears as a structureless collection of fragmented cells and amorphous granular debris within a distinctive inflammatory border in the lung parenchyma Figure 1. F shows a necrotic area that appears as a structureless collection of lysed cells and amorphous granular debris within a distinctive border within the kidney parenchyma.
      Figure 3:
      Figure 3Miliary tuberculous in Lung (Left) and Spleen (Right).
      Figure 5:
      Figure 5Caseating granuloma in lung (Micrograph at x 4 magnification).
      Figure 6:
      Figure 6Caseating granuloma in kidney (Micrograph at magnification x 10).

      DISCUSSION

      There are several notable findings from this series. First, the majority of TB deaths occurred at home or in community settings. Second, forensic autopsies of community deaths can reveal undetected TB. Third, forty-seven of the fifty-two cases showed pulmonary disease. Fourth, PTB was a definitive cause of death in thirty-six cases and a contributing cause in eleven others. Fifth, all fifty-two cases of decedents with TB seen at autopsy were not suspected of having TB prior to death and the diagnosis was only apparent on autopsy.
      Tuberculosis is the second most common cause of death from infectious diseases worldwide (

      WHO, Fact sheets 2021, Tuberculosis. https://www.who.int/news-room/fact-sheets/detail/tuberculosis, accessed 3rd February, 2022

      ). In sub-Saharan Africa, poor economic and social factors together with suboptimal performance of national TB programs due to lack of resources required to proactively screen, find and treat all cases of TB, continue to drive the TB epidemic (

      WHO, Fact sheets 2021, Tuberculosis. https://www.who.int/news-room/fact-sheets/detail/tuberculosis, accessed 3rd February, 2022

      ). In 2019, the incidence rate of TB was 333 per 100 000 per year in Zambia, with 15 400 TB-related deaths (
      • Lungu P
      • Kerkhoff AD
      • Kasapo CC
      • Mzyece J
      • Nyimbili S
      • Chimzizi R
      • et al.
      Tuberculosis care cascade in Zambia - identifying the gaps in order to improve outcomes: a population-based analysis.
      ).
      Several studies conducted worldwide have shown TB at forensic autopsies. A study from India showed a 5.1% rate of TB at forensic autopsies. An ante-mortem diagnosis was not made in 84.6% (
      • Punia RS
      • Mundi I
      • Mohan H
      • Chavli KH
      • Harish D.
      Tuberculosis prevalence at autopsy: a study from North India.
      ). Another study from Turkey reported a 1 % TB rate among forensic autopsies (
      • Ozsoy S
      • Demirel B
      • Albay A
      • Kisa O
      • Dinc AH
      • Safali M.
      Tuberculosis prevalence in forensic autopsies.
      ). A study in New Zealand identified TB as a cause of death in 0.2% of autopsies done (
      • Lum D
      • Koelmeyer T.
      Tuberculosis in Auckland autopsies, revisited.
      ). In Cape Town, South Africa, a study revealed a TB prevalence of 6.2% in persons with sudden unexpected death (
      • Osman M
      • Verster J
      • Dempers JJ
      • Du Preez K
      • von Delft A
      • Dunbar R
      • et al.
      Tuberculosis in persons with sudden unexpected death, in Cape Town, South Africa.
      ). The variation in the prevalence of TB cases identified at forensic autopsy may allude to regional differences in the prevalence of the infection.
      Undiagnosed tuberculosis identified at forensic autopsy is not uncommon since TB is a chronic disease and take several weeks or months to manifest clinically (
      • Rastogi P
      • Kanchan T
      • Menezes RG
      Sudden unexpected deaths due to tuberculosis: an autopsy based study.
      ). Previous autopsy studies from Zambia showed an undiagnosed case load of TB in adults and children inpatients (
      • Chintu C
      • Mudenda V
      • Lucas S
      • Nunn A
      • Lishimpi K
      • Maswahu D
      • et al.
      Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study.
      ;
      • Bates M
      • Mudenda V
      • Shibemba A
      • Kaluwaji J
      • Tembo J
      • Kabwe M
      • et al.
      Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study.
      ;
      • Bates M
      • Shibemba A
      • Mudenda V
      • Chimoga C
      • Tembo J
      • Kabwe M
      • et al.
      Burden of respiratory tract infections at post mortem in Zambian children.
      ,
      • Hussain SA
      • Madadin M
      • Menezes RG.
      Tuberculosis burden at post mortem.
      ).
      This case series shows decedents at autopsy without suspicion of having TB prior to death. Their demographics, circumstances of death, co-infections, and the extent of the disease have been highlighted. All the cases in the series were of poor social-economic status and lived in high-density areas of Lusaka. A high proportion of low socio-economic status individuals live in overcrowded households, which directly fosters TB transmission (

      WHO, Fact sheets 2021, Tuberculosis. https://www.who.int/news-room/fact-sheets/detail/tuberculosis, accessed 3rd February, 2022

      ). We postulate that groups from high-density and poor social-economic status areas, household contacts of those with infectious TB, and contacts known to be HIV positive must be targeted for screening given that Lusaka high-density areas are also known to have high HIV prevalence.
      Forty-one of fifty-two cases were in the age range 21-50 years, with the 31-40 range contributing most cases. This finding contrasts with a study in Germany which showed that most of the cases were within the age ranges of 30-59 and 80-99 (
      • Theegarten D
      • Kahl B
      • Ebsen M.
      Häufigkeit und Morphologie der Tuberkulose bei Obduktionen: Zunahme aktiver Formen [Frequency and morphology of tuberculosis in autopsies: increase of active forms].
      ) The difference is related to the differences in HIV prevalence and the social-economic status of the countries. The difference may also be attributed to differences in the age structure of the two populations (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ). However, our results are similar to a study in a forensic population by
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      in Lusaka, who found similar results and concluded that this age group was most at risk of premature death due to increased alcohol intake and outdoor activities in the forensic population (
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ). There were more males than females in our series. This is consistent with our previous autopsy studies (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ;
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ). It has been suggested that males are more predisposed to sudden, unexpected, and violent deaths due to complications of disease arising from poor health-seeking habits (
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ).
      Regarding the circumstances surrounding the death, many sudden and unexpected deaths occurred outside the hospital facility, either at home, at work, or on the way to the health facility in the series. These circumstances again emphasize the hypothesis that this predominantly male population dies suddenly and unexpectedly outside the health facility due to complications of disease arising from poor health-seeking habits (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ;
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ). An autopsy study in South Africa revealed a high proportion of pulmonary TB in people who died at home without an apparent cause of death. This was attributed to the high burden of HIV infection (
      • Omar T
      • Variava E
      • Moroe E
      • Billioux A
      • Chaisson RE
      • Lebina L
      • et al.
      Undiagnosed TB in adults dying at home from natural causes in a high TB burden setting: a post-mortem study.
      )
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ., found an HIV prevalence of 31% in the forensic population at autopsy in Lusaka (
      • Himazwe C
      • Mucheleng'anga L
      • Siyumbwa SN
      • Kaile T
      • Julius P
      Prevalence of Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C Viral Infections among Forensic Autopsy Cases at the University Teaching Hospital in Lusaka, Zambia.
      ). The forensic population is known to suffer from advanced disease due to the self-rationalisation of symptoms and a failure to seek medical attention (
      • Spitz W.U
      Medicolegal Investigation of Death: Guidelines for the Application of Pathology to Crime Investigation.
      ;
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ). The one paediatric TB death involved a 14-year-old boy who died suddenly during a football match. This is a telling example where TB kills "silently." At autopsy, a TB pancarditis was diagnosed. The screening of TB contacts for individuals who are both symptomatic and asymptomatic, often neglected, can be an essential benefit to the community of individual children. This child would have benefited from TB treatment if screening had been conducted (
      • Omar T
      • Variava E
      • Moroe E
      • Billioux A
      • Chaisson RE
      • Lebina L
      • et al.
      Undiagnosed TB in adults dying at home from natural causes in a high TB burden setting: a post-mortem study.
      ).
      Pulmonary TB (apical cavitation, consolidation, granulomatous inflammation), was our series' most common autopsy finding. These were confirmed on histology and confirmed by positive ZN staining. We observe that the spleen and mesenteric lymph nodes were the second and third most common sites of infection in this series. Three cases had coinfections, the first with aspergillosis, bacterial meningitis and neurocysticercosis. The second with Kaposi's sarcoma and HIV, while the third with TB pericarditis and cardiac cysticercosis.
      TB was the primary cause of death in thirty-nine of fifty-two incidental TB cases of TB seen at autopsy, with Pulmonary (23 cases) and disseminated (10 cases) being the commonest CoD, respectively. Four cases had pulmonary TB but died of acute alcohol intoxication. Seven cases were violent deaths but revealed TB on autopsy. Evidence of undiagnosed TB suggests that TB-related mortality is under-ascertained and under reported. There is therefore need for more research into active screening methods in the community as autopsies provide the most accurate data about cause of death despite being operationally difficult and expensive .We postulate that more TB cases could be found by searching more actively among specific population groups (
      • Omar T
      • Variava E
      • Moroe E
      • Billioux A
      • Chaisson RE
      • Lebina L
      • et al.
      Undiagnosed TB in adults dying at home from natural causes in a high TB burden setting: a post-mortem study.
      ).
      Diagnosis of incidental TB in community deaths reflects the burden of disease within the community and while public health efforts worldwide are being directed towards reducing the spread of TB, the forensic autopsy is a vital tool in detecting unknown TB cases in the community (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ). Forensic autopsy data are thus indispensable for disease intelligence and prevention and may be helpful and lead to timely medical intervention for the decedent's relatives who might have been exposed to TB. These data can help public health map disease surveillance systems, implement public awareness programs for prevention, and treat sources in households and the community (Rasika & Gilks, 2015;
      • Dye C
      • Harries AD
      • Maher D
      • et al.
      Tuberculosis.
      ).
      There have been previous calls to conduct forensic autopsy studies in community deaths to identify undiagnosed TB cases (Syed, et al., 2015). The actual data on the causes of deaths in the community (rural and urban) and in hospitals in most SSA countries remain unknown, and the quality of cause-specific mortality statistics remains poor. Thus, there is an urgent need to obtain more accurate cause-of-death data from SSA countries by reviving routine autopsies which declined in most SSA countries because of several reasons, such as lack of resources to maintain an effective pathology service, scarcity of trained pathologists, inadequate infrastructure, and difficulties in obtaining consent for autopsies due to cultural beliefs and religious sensitivities (
      • Chintu C
      • Mudenda V
      • Lucas S
      • Nunn A
      • Lishimpi K
      • Maswahu D
      • et al.
      Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study.
      ). This case series is one such activity related to that clarion call.
      Our data should be viewed under the limitations of the study. This case series is limited by the small number of cases because not all violent deaths such suicides and road traffic accidents undergo a whole body autopsy, possibly leading to missed incidental TB. Additionally culture and polymerase chain reaction testing was not done. ZN staining that was used to confirm the presence of tubercle bacilli in tissue at autopsy does not distinguish tuberculous from non-tuberculous mycobacterial infections. Future autopsy studies should include mycobacterial culture and molecular analyses for more accurate diagnosis of Mycobacterium tuberculosis (Mtb) in autopsy tissues.
      Our autopsy study serves as a pivotal starting point for conversations around future autopsy studies in the SSA focused on TB pathology, pathogenesis and co-infections. Undiagnosed TB cases and other co-morbidities such as HIV, malaria, COVID-19, hypertension, diabetes, and other diseases require further investigation. Our previous COVID-19 autopsy studies in Zambia have highlighted the need for sequencing data to align to autopsy studies (
      • Mucheleng'anga LA
      • Telendiy V
      • Hamukale A
      • Shibemba AL
      • Zumla A
      • Himwaze CM.
      COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.
      ;
      • Himwaze CM
      • Telendiy V
      • Maate F
      • Mupeta S
      • Chitalu C
      • Chanda D
      • et al.
      Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.
      ). Apart from more investments into TB programs, for more proactive screening, testing and treatment activities, accurate data collection, revamping autopsy studies worldwide would provide more insights into the actual mortality burden. Mtb can persist intracellularly in lung tissue without histological evidence of tuberculous lesions (Hernandez-Pando et al, 2000), and autopsy studies provide opportunities to study latent TB infection, early TB disease not manifest clinically and host-Mtb interactions.

      Transparency declaration

      This article is part of a supplement entitled Commemorating World Tuberculosis Day March 24th, 2022: “Invest to End TB. Save Lives” published with support from an unrestricted educational grant from QIAGEN Sciences Inc.

      Declaration of Competing Interest

      The authors declare no conflict of interest.

      Author contributions

      Luchenga Mucheleng'anga and Alimuddin Zumla ideated the study and contributed equally. Luchenga Adam Mucheleng'anga, Viktor Telendiy and Cordilia Maria Himwaze performed the forensic autopsy investigations. Amos Hamukale analysed the data. All authors contributed to intellectual discussions and manuscript writing.

      Acknowledgements

      We thank the mortuary staff for their assistance with performing the autopsies.
      Authors are co-Investigators of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET – https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme. AZ and FN acknowledge support from EDCTP CANTAM-3. Sir Zumla is a Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize Laureate, and is in receipt of a UK National Institues of health rEsearch Senior Invesigator Award.

      Funding

      The authors did not receive any funding for this series.

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