32 research outputs found
Hypoxaemia in Mozambican children < 5 years of age admitted to hospital with clinical severe pneumonia: clinical features and performance of predictor models
OBJECTIVE: To determine the prevalence of hypoxaemia among
under-five children admitted to hospital with clinical severe
pneumonia, and to assess the performance to diagnose hypoxaemia
of models based on clinical signs. METHODS: We conducted a
hospital-based survey in a district hospital from Southern
Mozambique. RESULTS: A total of 825 children were recruited
after obtaining an informed consent. The prevalence of
hypoxaemia on admission was 27.9%, and 19.8% of these children
died (OR compared to non-hypoxaemic children 3.22, 95%CI 1.98 -
5.21, p<0.001). The model with larger area under the ROC
curve (AUC-ROC) to predict hypoxaemia included cyanosis or
thoracoabdominal breathing or respiratory rate >/= 70 breaths
per minute. None of the models performed well when tested in
different case scenarios of oxygen availability through
mathematical modelling, with over 50% of hypoxaemic children not
receiving oxygen even in favourable case scenarios. CONCLUSIONS:
Clinical signs alone or in combination are not suitable to
diagnose hypoxaemia. The use of pulse oximeters should be
strongly encouraged. This article is protected by copyright. All
rights reserved
High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children < 5 years of age admitted to hospital with clinical severe pneumonia
We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa, and
to investigate PCP-associated risk factors. During 2006-2007 we
used molecular methods to test children younger than 5 years old
admitted with severe pneumonia to a hospital in Southern
Mozambique for Pneumocystis infection. We recruited 834
children. PCP prevalence was 6.8% and HIV prevalence was 25.7%.
The in-hospital and delayed mortality were significantly higher
among children with PCP (20.8% vs. 10.2 %, p=0.021, and 11.5%
vs. 3.6%, p=0.044, respectively). Clinical features were mostly
overlapping between the two groups. Independent risk factors for
PCP were age less than a year (OR 6.34, 95%CI 1.86-21.65), HIV
infection (OR 2.99, 95%CI 1.16-7.70), grunting (OR 2.64, 95%CI
1.04-6.73), and digital clubbing (OR 10.75, 95%CI 1.21-95.56).
PCP is a common and life-threatening cause of severe pneumonia
in Mozambican children. Mother-to-child HIV transmission
prevention should be strengthened. Better diagnostic tools are
needed
Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates
Plasmodium falciparum proteins involved in erythrocyte invasion
are main targets of acquired immunity and important vaccine
candidates. We hypothesized that anti-parasite immunity acquired
upon exposure would limit invasion-related gene (IRG) expression
and affect the clinical impact of the infection. 11 IRG
transcript levels were measured in P. falciparum isolates by
RT-PCR, and IgG/IgM against invasion ligands by Luminex(R), in
50 Mozambican adults, 25 children with severe malaria (SM) and
25 with uncomplicated malaria (UM). IRG expression differences
among groups and associations between IRG expression and
clinical/immunologic parameters were assessed. IRG expression
diversity was higher in parasites infecting children than adults
(p = 0.022). eba140 and ptramp expression decreased with age (p
= 0.003 and 0.007, respectively) whereas p41 expression
increased (p = 0.022). pfrh5 reduction in expression was abrupt
early in life. Parasite density decreased with increasing pfrh5
expression (p < 0.001) and, only in children, parasite
density increased with p41 expression (p = 0.007), and decreased
with eba175 (p = 0.013). Antibody responses and IRG expression
were not associated. In conclusion, IRG expression is associated
with age and parasite density, but not with specific antibody
responses in the acute phase of infection. Our results confirm
the importance of multi-antigen vaccines development to avoid
parasite immune escape when tested in malaria-exposed
individuals
Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy.
BACKGROUND: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. METHODS: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. RESULTS: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). CONCLUSIONS: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others.)
Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
Cytoadhesion of Plasmodium falciparum infected erythrocytes to
gC1qR has been associated with severe malaria, but the parasite
ligand involved is currently unknown. To assess if binding to
gC1qR is mediated through the P. falciparum erythrocyte membrane
protein 1 (PfEMP1) family, we analyzed by static binding assays
and qPCR the cytoadhesion and var gene transcriptional profile
of 86 P. falciparum isolates from Mozambican children with
severe and uncomplicated malaria, as well as of a P. falciparum
3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript
levels of DC8 correlated positively with cytoadhesion to gC1qR
(rho = 0.287, P = 0.007), were higher in isolates from children
with severe anemia than with uncomplicated malaria, as well as
in isolates from Europeans presenting a first episode of malaria
(n = 21) than Mozambican adults (n = 25), and were associated
with an increased IgG recognition of infected erythrocytes by
flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c
(5.3-fold transcript levels relative to Seryl-tRNA-synthetase
gene) compared to the unselected line (0.001-fold). DBLbeta12
from PFD0020c bound to gC1qR in ELISA-based binding assays and
polyclonal antibodies against this domain were able to inhibit
binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum
isolates by 50%. Our results show that DC8-type PfEMP1s mediate
binding to gC1qR through conserved surface epitopes in DBLbeta12
domain which can be inhibited by strain-transcending functional
antibodies. This study supports a key role for gC1qR in
malaria-associated endovascular pathogenesis and suggests the
feasibility of designing interventions against severe malaria
targeting this specific interaction
Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy
Background Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known.
Methods We assessed the prevalence of Plasmodium falciparum
infection among 1819 Mozambican women who delivered infants
between 2003 and 2012. We used microscopic and histologic
examination and a quantitative polymerase-chain-reaction (qPCR)
assay, as well as flow-cytometric analysis of IgG antibody
responses against two parasite lines. Results Positive qPCR
tests for P. falciparum decreased from 33% in 2003 to 2% in 2010
and increased to 6% in 2012, with antimalarial IgG antibody
responses mirroring these trends. Parasite densities in
peripheral blood on qPCR assay were higher in 2010-2012
(geometric mean [+/-SD], 409+/-1569 genomes per microliter) than
in 2003-2005 (44+/-169 genomes per microliter, P=0.02), as were
parasite densities in placental blood on histologic assessment
(50+/-39% of infected erythrocytes vs. 4+/-6%, P<0.001). The
malaria-associated reduction in maternal hemoglobin levels was
larger in 2010-2012 (10.1+/-1.8 g per deciliter in infected
women vs. 10.9+/-1.7 g per deciliter in uninfected women; mean
difference, -0.82 g per deciliter; 95% confidence interval [CI],
-1.39 to -0.25) than in 2003-2005 (10.5+/-1.1 g per deciliter
vs. 10.6+/-1.5 g per deciliter; difference, -0.12 g per
deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth
weight (2863+/-440 g in women with past or chronic infections
vs. 3070+/-482 g in uninfected women in 2010-2012; mean
difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994+/-487 g
vs. 3117+/-455 g in 2003-2005; difference, -44.8 g; 95% CI,
-139.1 to 49.5). Conclusions Antimalarial antibodies were
reduced and the adverse consequences of P. falciparum infections
were increased in pregnant women after 5 years of a decline in
the prevalence of malaria. (Funded by Malaria Eradication
Scientific Alliance and others.)
Procalcitonin and C-Reactive Protein for Invasive Bacterial Pneumonia Diagnosis among Children in Mozambique, a Malaria-Endemic Area
Background: Pneumonia is the major cause of mortality and morbidity in children worldwide. Procalcitonin (PCT) and C-reactive protein (CRP) are used in developed countries to differentiate between viral and bacterial causes of pneumonia. Validity of these markers needs to be further explored in Africa. Methodology and Principal Findings: We assessed the utility of PCT and CRP to differentiate viral from invasive bacterial pneumonia in children <5 years hospitalized with clinical severe pneumonia (CSP) in rural Mozambique, a malaria-endemic area with high HIV prevalence. Prognostic capacity of these markers was also evaluated. Out of 835 children with CSP, 87 fulfilled definition of viral pneumonia and 89 of invasive bacterial pneumonia. In absence of malaria parasites, levels of PCT and CRP were lower in the viral group when compared to the invasive bacterial one (PCT: median = 0.21 versus 8.31 ng/ml, p<0.001; CRP: 18.3 vs. 185.35 mg/l, p<0.001). However, in presence of malaria parasites distribution between clinical groups overlapped (PCT: median = 23.1 vs. 21.75 ng/ml, p = 0.825; CRP: median = 96.8 vs. 217.4 mg/l, p = 0.052). None of the two markers could predict mortality. Conclusions: Presence of malaria parasites should be taken into consideration, either for clinical or epidemiological purposes, if using PCT or CRP to differentiate viral from invasive bacterial pneumonia in malaria-endemic areas
Glucose-6-Phosphate Dehydrogenase Deficiency, Chlorproguanil-Dapsone with Artesunate and Post-treatment Haemolysis in African children treated for uncomplicated Malaria
Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria
A 10 year study of the cause of death in children under 15 years in Manhiça, Mozambique
<p>Abstract</p> <p>Background</p> <p>Approximately 46 million of the estimated 60 million deaths that occur in the world each year take place in developing countries. Further, this mortality is highest in Sub-Saharan Africa, although causes of mortality in this region are not well documented. The objective of this study is to describe the most frequent causes of mortality in children under 15 years of age in the demographic surveillance area of the Manhiça Health Research Centre, between 1997 and 2006, using the verbal autopsy tool.</p> <p>Methods</p> <p>Verbal autopsy interviews for causes of death in children began in 1997. Each questionnaire was reviewed independently by three physicians with experience in tropical paediatrics, who assigned the cause of death according to the International Classification of Diseases (ICD-10). Each medical doctor attributed a minimum of one and a maximum of 2 causes. A final diagnosis is reached when at least two physicians agreed on the cause of death.</p> <p>Results</p> <p>From January 1997 to December 2006, 568499 person-year at risk (pyrs) and 10037 deaths were recorded in the Manhiça DSS. 3730 deaths with 246658 pyrs were recorded for children under 15 years of age. Verbal autopsy interviews were conducted on 3002 (80.4%) of these deaths. 73.6% of deaths were attributed to communicable diseases, non-communicable diseases accounted for 9.5% of the defined causes of death, and injuries for 3.9% of causes of deaths. Malaria was the single largest cause, accounting for 21.8% of cases. Pneumonia with 9.8% was the second leading cause of death, followed by HIV/AIDS (8.3%) and diarrhoeal diseases with 8%.</p> <p>Conclusion</p> <p>The results of this study stand out the big challenges that lie ahead in the fight against infectious diseases in the study area. The pattern of childhood mortality in Manhiça area is typical of developing countries where malaria, pneumonia and HIV/AIDS are important causes of death.</p
A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial
BackgroundArtemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.Methods and findingsBetween 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37-0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.ConclusionsThis large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.Trial registrationClinicalTrials.gov NCT00393679; Pan African Clinical Trials Registry PACTR200901000091175