Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities ...and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings.
A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles.
The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs.
A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people ...may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6-15%), including four maternal deaths. One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission. Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease. This is the first report of the presence of C. gattii infection in Mozambique.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and ...HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively p < 0.001). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Programmed death-ligand 1 (PD-L1) is overexpressed in squamous cervical cancer (SCC) and can be used for targeted immunotherapy. The highest mortality rates of SCC are reported in ...sub-Saharan Africa, where Human immunodeficiency virus (HIV) prevalence is high. In Mozambique most SCC patients present at advanced stages. Thus, there is a need to introduce new treatment options. However, immunocompromised patients were frequently excluded in previous clinical trials. Our aim was to determine if PD-L1 expression in SCC is as prevalent among women living with HIV (WLWH) as among other patients. 575 SCC from Maputo Central Hospital were included. HIV status was available in 266 (46%) cases PD-L1 expression was scored through tumour proportion score (TPS) and combined positive score (CPS). PD-L1 was positive in 20.1% of the cases (n = 110), TPS (score ≥ 25%) and in 26.3% (n = 144), CPS (score ≥ 1). Stratifying according to the HIV status, WLWH were TPS positive in 16.7%, compared to 20.9%, p = 0.43, and concerning CPS 21.1% versus 28.7%, p = 0.19, respectively. PD-L1 status was not influenced by stage, Ki-67 or p16, CD8 expression influenced only CPS status. Our data indicates that the documented effect of PD-L1 therapy on SCC should be confirmed in randomized clinical trials in an HIV endemic milieu.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Mozambique, cervical cancer is the most frequent cancer in women. However, studies about cervical cancer treatment and prognosis are scarce. We describe the clinical characteristics, treatment and ...survival of patients with cervical cancer admitted to Maputo Central Hospital (MCH) in 2016 to 2018. Sociodemographic, clinical and cancer‐related data were retrieved from clinical records of patients admitted to the Oncology Service of the MCH with an incident cervical cancer in 2016 to 2018 (n = 407). The Pathology Service database was used to obtain information regarding pathological diagnosis. Survival data was obtained through the MCH Cancer Registry and clinical records. Odds ratios for the association between patients' characteristics and the diagnosis of advanced stage cancer were computed using logistic regression. Survival analyses were performed using the Kaplan‐Meier estimator. A total of 91.2% of the patients were diagnosed with advanced disease (stage IIB‐IV) and squamous cell carcinoma was the predominant histological subtype. Most of the patients underwent chemotherapy (93.1%) but <7% were submitted to surgery, radiotherapy or brachytherapy. Those living with HIV had 3.4‐fold higher odds of advanced disease. Overall survival was 72.7% (95% confidence interval CI: 67.9‐77.0) at 1‐year and 51.0% (95%CI: 45.3‐56.3) at 2‐years. Those with early stage (IA‐IIA) and asymptomatic at diagnosis had a significantly higher 2‐year overall survival. In Mozambique, cervical cancer is diagnosed mostly in advanced stages, resulting in poor prognosis. This highlights the importance of HPV vaccination and screening, to decrease the burden of cervical cancer in this context.
What's new?
Cervical cancer incidence is exceptionally high in Mozambique, where high prevalence of human immunodeficiency virus and human papillomavirus (HPV) infections and limited screening uptake contribute to disease burden. Information about clinical characteristics, treatment and survival of cervical cancer patients in Mozambique, however, remains sparse. Here, analysis of clinical characteristics and management of cervical cancer patients admitted to Maputo Central Hospital shows that most patients are diagnosed with advanced disease and experience poor prognosis. Survival was better for patients diagnosed at early stages. The findings highlight a need for improved uptake of prevention strategies, particularly cervical cancer screening and HPV testing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
6.
"Pomegranate" Spleen in Disseminated Tuberculosis García-Basteiro, Alberto L; Ismail, Mamudo R; Carrilho, Carla ...
American journal of respiratory and critical care medicine,
2015-Aug-01, 2015-08-01, 20150801, Volume:
192, Issue:
3
Journal Article
Peer reviewed
Open access
A 33-year-old HIV-infected female patient who had died at Maputo Central Hospital, Maputo, Mozambique, after less than 24 hours of hospitalization, underwent a full postmortem examination to ...ascertain the cause of death. Antemortem chest radiography showed hyperinflated lungs, with scattered bilateral lesions compatible with a diagnosis of miliary tuberculosis (TB), which was (after postmortem examination) determined to be the final cause of death. The spleen was firm at touch, with multiple yellowish nodules randomly distributed throughout the surface of the spleen capsule. Gross examination of the spleen sections showed that the nodules and plaques massively infiltrated the spleen parenchyma, which showed a characteristic pomegranate aspect (Figures 1A and 1B). The histological sections confirmed the presence of caseous granulomas (Figure 1C). The presence of Mycobacterium tuberculosis bacilli in the spleen samples was confirmed by a specific in-house real-time polymerase chain reaction (1) and by Xpert MTB/RIF assay. The main differential diagnosis of this rarely reported macroscopic finding would be splenic neoplasms, infarcts, abscesses, and granulomas of varying etiology; and, in endemic areas, melioidosis (2). Although scarce data exist in the literature, the frequency of the underlying disease causing this macroscopic finding varies significantly depending on the geographical area. Infectious diseases account for a significant proportion of these lesions in developing countries (3), whereas in Western countries the predominant causes are neoplasms, mainly malignant lymphomas or metastatic carcinomas (4). Knowledge of the macroscopic aspect of splenic TB, which at cross-section resembles the inside of a pomegranate, could guide pathologists to rule in disseminated TB diagnosis on the basis of gross pathology, especially in high-burden TB/HIV countries.
BackgroundGlobal malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate ...malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard.MethodsObservational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry).FindingsMalaria infection was considered the cause of death in 6/264 (2.3%) cases: 2/54 children (3.7%, both less than 5 years old) and 4/57 (7.0%) maternal deaths. The sensitivity and specificity of the VA, the clinical data and the MIA to identify malaria-specific deaths were 33.3% and 96.1%, 66.7% and 96.1%, and 100% and 100%, respectively. In addition, malaria was identified as a possible contributor in 14 additional patients who died of other diseases. These cases were also accurately identified by the MIA (sensitivity 82.4%, specificity 100%).InterpretationThe high sensitivity and specificity of the MIA in identifying malaria may help to improve current estimates of malaria-specific mortality in endemic areas.
Minimally invasive tissue sampling (MITS) is a simplified postmortem examination technique that has shown to be an adequate approach for cause of death investigation in low-resource settings. It ...requires relatively low level of infrastructures and can be performed by health professionals with no background in pathology. A training program has been developed for the Child Health and Mortality Prevention Surveillance (CHAMPS) network to guarantee standardization of specimen collection techniques, procedures, and laboratory methods.
The training program has included assessment of the site capacities and training on a standardized protocol of MITS sampling and histological processing. The project has also introduced a program of training for trainers for the personnel from Mozambique. To guarantee the adequacy of the procedure in each site, a trainer accompanied the local teams when the activities started. Training outcomes were assessed by evaluating the quality of the samples obtained and the quality of the slides produced locally.
Between June 2016 and October 2018, the laboratories of 7 sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) have been evaluated and upgraded. Training has been delivered to 63 staff members from all sites. More than 600 MITS procedures have been performed. The quantity of tissue obtained in the MITS by the local teams was sufficient or abundant in 73%, and 87% of the slides were considered as technically acceptable or excellent.
Satisfactory standardization of MITS and histology procedures has been achieved across all CHAMPS sites through organized capacity-building plans.
In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries ...remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting.
In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive and negative predictive values of the MIA diagnoses were calculated. A CoD was identified in all cases in the CDA and in 52/54 (96%) of the cases in the MIA, with infections and malignant tumors accounting for the majority of diagnoses. The MIA categorization of disease showed a substantial concordance with the CDA categorization (Kappa = 0.70, 95% CI 0.49-0.92), and sensitivity, specificity, and overall accuracy were high. The ICD-10 diagnoses were coincident in up to 75% (36/48) of the cases. The MIA allowed the identification of the specific pathogen deemed responsible for the death in two-thirds (21/32; 66%) of all deaths of infectious origin. Discrepancies between the MIA and the CDA in individual diagnoses could be minimized with the addition of some basic clinical information such as those ascertainable through a verbal autopsy or clinical record. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.
The MIA showed substantial concordance with CDA for CoD identification in this series of pediatric deaths in Mozambique. This minimally invasive approach, simpler and more readily acceptable than the more invasive CDA, could provide robust data for CoD surveillance, especially in resource-limited settings, which could be helpful for guiding child survival strategies in the future.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of ...Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3-99.7) and a specificity of 95.7% (95% CI: 78.1-99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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