73 research outputs found
Carriage prevalence of Salmonella enterica serotype Typhi in gallbladders of adult autopsy cases from Mozambique
INTRODUCTION: Typhoid fever is an important public health
problem in many low-income countries where asymptomatic carriers
play an important role in its dissemination. The bacterium
causing typhoid fever can live in the gallstones of asymptomatic
persons after the infection. These carriers are reservoirs of S.
Typhi, are highly contagious, and spread the disease through the
secretion of bacteria in feces and urine. The aim of this study
was to determine the carrier rate in an area of Mozambique.
METHODOLOGY: The presence of S. Typhi was analyzed in
gallbladder samples obtained from 99 adult corpses (in-hospital
deaths) from Mozambique by gold-standard culture and polymerase
chain reaction (PCR). RESULTS: Only one sample was positive with
the culture. However, nine additional samples were positive by
PCR and confirmed by DNA sequencing. Thus, the prevalence of S.
Typhi was 10.1% (10/99). CONCLUSIONS: We report a high
prevalence of S. Typhi in gallbladders among adult autopsy cases
from Mozambique
Pathological Methods Applied to the Investigation of Causes of Death in Developing Countries: Minimally Invasive Autopsy Approach
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 countrie
The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues
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
'Pomegranate' Spleen in Disseminated Tuberculosis
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
Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Maputo Central Hospital, Mozambique
Sensitive tools are
needed to accurately establish the diagnosis of tuberculosis
(TB) at death, especially in low-income countries. The objective
of this study was to evaluate the burden of TB in a series of
patients who died in a tertiary referral hospital in sub-Saharan
Africa using an in-house real time PCR (TB-PCR) and the Xpert
MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies
were performed in a series of 223 deaths (56.5% being
HIV-positive), including 54 children, 57 maternal deaths and 112
other adults occurring at the Maputo Central Hospital,
Mozambique. TB-PCR was performed in all lung, cerebrospinal
fluid and central nervous system samples in HIV-positive
patients. All samples positive for TB-PCR or showing
histological findings suggestive of TB were analysed with the
Xpert Ultra assay.TB was identified as the cause of death in 31
patients: 3/54 (6%) children, 5/57 (9%) maternal deaths and
23/112 (21%) other adults. The sensitivity of the main clinical
diagnosis to detect TB as the cause of death was 19.4% (95% CI:
7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to
autopsy findings. Concomitant TB (TB disease in a patient dying
of other causes) was found in 31 additional cases. Xpert Ultra
helped to identify 15 cases of concomitant TB. In 18 patients, "
- " DNA was identified by TB-PCR and Xpert Ultra in the absence
of histological TB lesions. Overall, 62 cases (27.8%) had TB
disease at death and 80 (35.9%) had TB findings.The use of
highly sensitive, easy to perform molecular tests in complete
diagnostic autopsies may contribute to identifying TB cases at
death that would have otherwise been missed. Routine use of
these tools in certain diagnostic algorithms for hospitalised
patients needs to be considered. Clinical diagnosis showed poor
sensitivity for the diagnosis of TB at death
Validity of a minimally invasive autopsy for cause of death determination in maternal deaths in Mozambique: An observational study
BACKGROUND: Despite global health efforts to reduce maternal
mortality, rates continue to be unacceptably high in large parts
of the world. Feasible, acceptable, and accurate postmortem
sampling methods could provide the necessary evidence to improve
the understanding of the real causes of maternal mortality,
guiding the design of interventions to reduce this burden.
METHODS AND FINDINGS: The validity of a minimally invasive
autopsy (MIA) method in determining the cause of death was
assessed in an observational study in 57 maternal deaths by
comparing the results of the MIA with those of the gold standard
(complete diagnostic autopsy [CDA], which includes any available
clinical information). Concordance between the MIA and the gold
standard diagnostic categories was assessed by the kappa
statistic, and the sensitivity, specificity, positive and
negative predictive values and their 95% confidence intervals
(95% CI) to identify the categories of diagnoses were estimated.
The main limitation of the study is that both the MIA and the
CDA include some degree of subjective interpretation in the
attribution of cause of death. A cause of death was identified
in the CDA in 98% (56/57) of cases, with indirect obstetric
conditions accounting for 32 (56%) deaths and direct obstetric
complications for 24 (42%) deaths. Nonobstetric infectious
diseases (22/32, 69%) and obstetric hemorrhage (13/24, 54%) were
the most common causes of death among indirect and direct
obstetric conditions, respectively. Thirty-six (63%) women were
HIV positive, and HIV-related conditions accounted for 16 (28%)
of all deaths. Cerebral malaria caused 4 (7%) deaths. The MIA
identified a cause of death in 86% of women. The overall
concordance of the MIA with the CDA was moderate (kappa = 0.48,
95% CI: 0.31-0.66). Both methods agreed in 68% of the diagnostic
categories and the agreement was higher for indirect (91%) than
for direct obstetric causes (38%). All HIV infections and
cerebral malaria cases were identified in the MIA. The main
limitation of the technique is its relatively low performance
for identifying obstetric causes of death in the absence of
clinical information. CONCLUSIONS: The MIA procedure could be a
valuable tool to determine the causes of maternal death,
especially for indirect obstetric conditions, most of which are
infectious diseases. The information provided by the MIA could
help to prioritize interventions to reduce maternal mortality
and to monitor progress towards achieving global health targets
High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden setting
Objectives: To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants. Methods: Genotypic analysis by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden. Results: Genotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue. Conclusions: Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed
Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: an observational study
Background Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs) the gold standard for cause of death determination are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed. Methods and findings In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction. Conclusions The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented
Contribution of the clinical information to the accuracy of the minimally invasive and the complete diagnostic autopsy
Although autopsy diagnosis includes routinely, a thorough
evaluation of all available pathological results and also of any
available clinical data, the contribution of this clinical
information to the diagnostic yield of the autopsy has not been
analyzed. We aimed to determine to which degree the use of
clinical data improves the diagnostic accuracy of the complete
diagnostic autopsy (CDA) and the minimally invasive autopsy
(MIA), a simplified pathological postmortem procedure designed
for low-income sites. 264 coupled MIA and CDA procedures (112
adults, 57 maternal deaths, 54 children and 41 neonates) were
performed at the Maputo hospital, Mozambique. We compared the
diagnoses obtained by the MIA blind to clinical data (MIAb), the
MIA adding the clinical information (MIAc), and the CDA blind to
clinical information (CDAb), with the results of the gold
standard, the CDA with clinical data, by comparing the ICD-10
codes and the main diagnostic classes obtained with each
evaluation strategy (MIAb, MIAc, CDAb, CDAc). The clinical data
increased diagnostic coincidence to the MIAb with the gold
standard in 30/264 (11%) cases and modified the CDAb diagnosis
in 20/264 (8%) cases. The increase in concordance between MIAb
and MIAc with the gold standard was significant in neonatal
deaths (kappa increasing from 0.404 to 0.618, P=.0271), adult
deaths (kappa increasing from 0.732 to 0.813, P=.0221) and
maternal deaths (kappa increasing from 0.485 to 0.836,
P<.0001). In conclusion, the use of clinical information
increases the precision of MIA and CDA and may strengthen the
performance of the MIA in resource-limited settings
Postmortem Interval and Diagnostic Performance of the Autopsy Methods
Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), an innovative approach to post-mortem sampling and cause of death investigation, are commonly performed within 24 hours after death because the quality of the tissues deteriorates over time. This short timeframe may hamper the feasibility of the procedure. In this study, we compared the diagnostic performance of the two postmortem procedures when carried out earlier and later than 24 hours after death, as well as the impact of increasing postmortem intervals (PMIs) on the results of the microbiological tests in a series of 282 coupled MIA/CDA procedures performed at the Maputo Central Hospital in Mozambique between 2013 and 2015. 214 procedures were conducted within 24 hours of death (early autopsies), and 68 after 24 hours of death (late autopsies). No significant differences were observed in the number of non-conclusive diagnoses (2/214 [1%] vs. 1/68 [1%] p = 0.5645 for the CDA; 27/214 [13%] vs. 5/68 [7%] p = 0.2332 for the MIA). However, increasing PMIs were associated with a raise in the number of bacteria identified (rate: 1.014 per hour [95%CI: 1.002-1.026]; p = 0.0228). This increase was mainly due to rising numbers of bacteria of the Enterobacteriaceae family and Pseudomonas genus strains. Thus, performing MIA or CDA more than 24 hours after death can still render reliable diagnostic results, not only for non-infectious conditions but also for many infectious diseases, although, the contribution of Enterobacteriaceae and Pseudomonas spp. as etiological agents of infections leading to death may be overestimated
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