64 research outputs found
Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack
With malaria elimination back on the international agenda,
programs face the challenge of targeting all Plasmodium
infections, not only symptomatic cases. As asymptomatic
individuals are unlikely to seek treatment, they are missed by
passive surveillance while remaining infectious to mosquitoes,
thus acting as silent reservoirs of transmission. To estimate
the risk of asymptomatic infections in various phases of malaria
elimination, we need a deeper understanding of the underlying
mechanisms favoring carriage over disease, which may involve
both pathogen and host factors. Here we review our current
knowledge on the determinants leading to Plasmodium falciparum
symptomless infections. Understanding the host-pathogen
interactions that are most likely to affect transitions between
malaria disease states could guide the development of tools to
tackle asymptomatic carriers in elimination settings
A prospective cohort study to assess the micro-epidemiology of Plasmodium falciparum clinical malaria in Ilha Josina Machel (Manhiça, Mozambique)
Background: After the decrease in clinical malaria incidence observed in Mozambique until 2009, a steady resurgence of cases per year has been reported nationally, reaching alarming levels in 2014. However, little is known about the clinical profile of the cases presented, or the possible epidemiological factors contributing to the resurgence of cases. Methods:
An analysis of surveillance data collected between July 2003 and June 2013 in the high malaria-transmission area of Ilha Josina Machel (Southern Mozambique) through a paediatric outpatient morbidity surveillance system was conducted to calculate hospital-based clinical malaria rates, slide-positivity rates, and minimum community-based incidence rates (MCBIRs) and incidence rate ratios per malaria season in children younger than 15 years of age. Clinical malaria was defined as a fever ≥37.5 °C or a reported fever in the previous 24 h with a positive blood smear. Yearly mean age, geometric mean parasitaemia (GMP) and mean packed cell volume (PCV) were also described for all clinical malaria cases and compared between seasons using DID analysis or ANOVA tests. Results: During the study period, the percentage of outpatient visits presenting with confirmed clinical malaria decreased from 51 % in the 2003–2004 season to 23 % in 2008–2009, followed by an increase back to 51 % in 2012–2013. The yearly mean age of cases significantly increased from 2.9 (95 % CI 2.8–3.0) in 2003–2004 to 5.7 (95 % CI 5.6–5.7) in 2012–2013, compared to non-malaria cases. An increase in mean PCV levels was also observed (p < 0.001), as well as in GMPs: from 5778 parasites/µL in 2002–2003 to 17,316 parasites/µL in 2012–2013 (p < 0.001) mainly driven by an increase in GMP in children older than 1 year of age. MCBIRs in infants decreased by 70 % (RR = 0.3, p < 0.001) between 2003–2004 and 2012–2013. Incidence diminished by a third among children 1- to 4-years between 2003 and 2007, although such drop was unsustained as observed in 2012–2013 (RR = 1.0, 95 % CI 0.9–1.0). Finally, the incidence among children 5–14 years was 3.8 (95 % CI 3.4–4.3) times higher in 2012–2013 compared to 2003–2004. Conclusion: Since 2003, Ilha Josina Machel observed a significant reduction of clinical malaria cases which was followed by an upsurge, following the national trend. A shift in the age distribution towards older children was observed, indicating that the changes in the transmission intensity patterns resulted in a slower acquisition of the naturally acquired immunity to malaria in children
Long-Lasting Immune Protection and Other Epidemiological Findings after Chikungunya Emergence in a Cambodian Rural Community, April 2012.
The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3-4 weeks after the outbreak, and determined the sensitivity and specificity of case definitions and factors associated with infection by CHIKV. Self-reported clinical presentation consisted mostly of fever, rash and arthralgia. The presence of all three clinical signs or symptoms was identified as the most sensitive (67%) and specific (84%) self-reported diagnostic clinical indicator compared to biological confirmation by MAC-ELISA or RT-PCR used as a reference. Having an indoor occupation was associated with lower odds of infection compared with people who remained at home (adjOR 0.32, 95%CI 0.12-0.82). In contrast with findings from outbreaks in other settings, persons aged above 40 years were less at risk of CHIKV infection, likely reflecting immune protection acquired when Chikungunya circulated in Cambodia before the Khmer Rouge regime in 1975. In view of the very particular history of Cambodia, our epidemiological data from Trapeang Roka are the first to support the persistence of CHIKV antibodies over a period of 40 years
Changing plasma cytokine, chemokine and growth factor profiles upon differing malaria transmission intensities
Background: Malaria epidemiological and immunological data suggest that parasite tolerance wanes in the absence
of continuous exposure to the parasite, potentially enhancing pathogenesis. The expansion of control interventions
and elimination campaigns raises the necessity to better understand the host factors leading to susceptibility or
tolerance that are afected by rapid changes in malaria transmission intensity (MTI). Mediators of cellular immune
responses are responsible for the symptoms and pathological alterations during disease and are expected to change
rapidly upon malaria exposure or cessation.
Methods: The plasma concentrations of 30 cytokine, chemokine and growth factors in individuals of all ages from
a malaria endemic area of southern Mozambique were compared between 2 years of diferent MTI: 2010 (lower,
n=234) and 2013 (higher, n=143). The efect of the year on the correlations between cytokines, chemokines and
growth factors and IgGs to Plasmodium falciparum (markers of exposure) was explored. The efects of age, sex, neighbourhood and parasitaemia on analyte levels and their interactions with year were also assessed.
Results: An inverse correlation of several cellular immune mediators with malarial antibodies in 2013, and a lack of
correlation or even a positive correlation in 2010 were observed. Most cytokines, chemokines and growth factors,
regardless of their immune function, had higher concentrations in 2010 compared with 2013 in P. falciparum-infected
and uninfected subjects. Age and neighbourhood showed an efect on analyte concentrations.
Conclusions: The results show a diferent regulation of the cellular immune response in 2010 vs 2013 which could
be related to a loss of immune-tolerance after a decline in MTI in 2010 and previous years, and a rapid re-establishment of tolerance as a consequence of more continuous exposure as MTI began increasing in 2012. Cellular immune
mediators warrant further investigation as possible surrogates of MTI-associated host susceptibility or tolerance
Molecular surveillance of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum isolates from Mozambique
BACKGROUND: Malaria programmes use Plasmodium falciparum
histidine-rich protein-2 (PfHRP2) based rapid diagnostic tests
(RDTs) for malaria diagnosis. The deletion of this target
antigen could potentially lead to misdiagnosis, delayed
treatment and continuation of active transmission. METHODS:
Plasmodium falciparum isolates (n = 1162) collected in Southern
Mozambique were assessed by RDTs, microscopy and/or 18SrRNA
qPCR. pfhrp2 and pfhrp3 deletions were investigated in isolates
from individuals who were negative by RDT but positive by
microscopy and/or qPCR (n = 69) using gene-specific PCRs, with
kelch13 PCR as the parasite DNA control. RESULTS: Lack of pfhrp2
PCR amplification was observed in one of the 69 isolates
subjected to molecular analysis [1.45% (95% CI 0.3-7.8%)].
CONCLUSIONS: The low prevalence of pfhrp2 deletions suggests
that RDTs will detect the vast majority of the P. falciparum
infections. Nevertheless, active surveillance for changing
deletion frequencies is required
Dynamics of Afebrile Plasmodium falciparum Infections in Mozambican Men
Background: Afebrile Plasmodium falciparum infections usually
remain undetected and untreated in the community and could
potentially contribute to sustaining local malaria transmission
in areas aiming for malaria elimination. Methods: Thirty-two men
with afebrile P. falciparum infections detected with rapid
diagnostic test (RDTs) were followed for 28 days. Kaplan-Meier
estimates were computed to estimate probability of parasite
positivity and of reducing parasitaemia by half of its initial
level by day 28. Trends of parasite densities quantified by
microscopy and qPCR were assessed using Poisson regression
models, and the microscopy to qPCR positivity ratio was
calculated at each time point. Three survival distributions
(Gompertz, Weibull, and gamma) were used to evaluate their
strength of fit to the data and to predict the median lifetime
of infection. Results: The cumulative probability of parasite
qPCR positivity by day 28 was 81% (95% CI 60.2-91.6). Geometric
mean parasitemia at recruitment was 516.1 parasites/muL and fell
to <100 parasites/muL by day 3, reaching 56.7 parasites/muL
on day 28 (p-value<0.001). The ratio of P. falciparum
positive samples by microscopy to qPCR decreased from 0.9 to
0.52 from recruitment to day 28. The best model fit to the data
was obtained assuming a Gompertz distribution. Conclusions:
Afebrile P.falciparum infections detectable by RDT in
semi-immune adults fall and stabilize at low-density levels
during the first four days since detection, suggesting a rapid
decline of potential transmissibility in this hidden parasite
reservoir
Heterogeneity of G6PD deficiency prevalence in Mozambique: a school-based cross-sectional survey in three different regions
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary enzymatic abnormality that affects more than 400 million people worldwide. Most deficient individuals do not manifest any symptoms; however, several precipitant agents—such as fava intake, infections, or several drugs—may trigger acute haemolytic anaemia. Countries should be informed of the prevalence of this enzymatic anomaly within their borders, in order to make safe and appropriate national decisions regarding the use of potentially unsafe drugs for G6PD deficient individuals. Methods: A school-based cross-sectional survey was conducted in three districts in Mozambique, namely Manhiça, located in the south; Mocuba in the centre; and Pemba in the northern tip of the country. G6PD deficiency was evaluated using the CareStart™ diagnostic test, and enzyme activity levels were measured through fluorescence spectrophotometry in deficient individuals. Chi squared and ANOVA tests were used to assess prevalence and mean enzyme activity differences, and logistic regression was used to identify risk factors associated to the deficiency. Results:
G6PD deficiency prevalence estimates were lowest in the northern city of Pemba (8.3%) and among Emakhuwas and Shimakondes, and higher in the centre and southern regions of the country (16.8 and 14.6%, respectively), particularly among Elomwes and Xichanganas. G6PD deficiency was significantly more prevalent among male students than females (OR = 1.4, 95% CI 1.0–1.8, p = 0.02), although enzyme activity levels were not different among deficient individuals from either gender group. Finally, median deficiency levels were found to be more severe among the deficient students from the north (0.7 U/gHg [0.2–0.7] p < 0.001) and south (0.7 U/gHg [0.5–2.5]), compared to those from the centre (1.4 U/gHg [0.6–2.1]). Conclusion: These findings suggest that Mozambique, as a historically high malaria-endemic country has considerable levels of G6PD deficiency, that vary significantly across the country. This should be considered when planning national strategies for the use of licensed drugs that may be associated to haemolysis among G6PD individuals, or prior to the performance of future trials using primaquine and other 8-aminoquinolines derivatives
In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies
Recent reports regarding the re-emergence of parasite
sensitivity to chloroquine call for a new consideration of this
drug as an interesting complementary tool in malaria elimination
efforts, given its good safety profile and long half-life. A
randomized (2:1), single-blind, placebo-controlled trial was
conducted in Manhica, Mozambique, to assess the in-vivo efficacy
of chloroquine to clear plasmodium falciparum (Pf) asymptomatic
infections. Primary study endpoint was the rate of adequate and
parasitological response (ACPR) to therapy on day 28
(PCR-corrected). Day 0 isolates were analyzed to assess the
presence of the PfCRT-76T CQ resistance marker. A total of 52
and 27 male adults were included in the CQ and Placebo group
respectively. PCR-corrected ACPR was significantly higher in the
CQ arm 89.4% (95%CI 80-98%) compared to the placebo (p <
0.001). CQ cleared 49/50 infections within the first 72 h while
placebo cleared 12/26 (LRT p < 0.001). The PfCRT-76T mutation
was present only in one out of 108 (0.9%) samples at baseline,
well below the 84% prevalence found in 1999 in the same area.
This study presents preliminary evidence of a return of
chloroquine sensitivity in Mozambican Pf isolates, and calls for
its further evaluation in community-based malaria elimination
efforts, in combination with other effective anti-malarials.
TRIAL REGISTRATION: www.clinicalTrials.gov NCT02698748
Demographic and health community-based surveys to inform a malaria elimination project in Magude district, southern Mozambique
--- - Label: OBJECTIVES NlmCategory: OBJECTIVE content: A
Demographic and Health Platform was established in Magude in
2015, prior to the deployment of a project aiming to evaluate
the feasibility of malaria elimination in southern Mozambique,
named the Magude project. This platform aimed to inform the
design, implementation and evaluation of the Magude project,
through the identification of households and population; and the
collection of demographic, health and malaria information. -
Label: SETTING NlmCategory: METHODS content: Magude is a rural
district of southern Mozambique which borders South Africa. It
has nine peripheral health facilities and one referral health
centre with an inpatient ward. - Label: INTERVENTION
NlmCategory: METHODS content: "A baseline census enumerated and
geolocated all the households, and their resident and
non-resident members, collecting demographic and socio-economic
information, and data on the coverage and usage of malaria
control tools. Inpatient and outpatient data during the
5\xE2\x80\x89years (2010 to 2014) before the survey were
obtained from the district health authorities. The demographic
platform was updated in 2016." - Label: RESULTS NlmCategory:
RESULTS content: "The baseline census conducted in 2015 reported
48\xE2\x80\x89448 (92.1%) residents and 4133 (7.9%)
non-residents, and 10\xE2\x80\x89965 households. Magude's
population is predominantly young, half of the population has no
formal education and the main economic activities are
agriculture and fishing. Houses are mainly built with
traditional non-durable materials and have poor sanitation
facilities. Between 2010 and 2014, malaria was the most common
cause of all-age inpatient discharges (representing 20% to 40%
of all discharges), followed by HIV (12% to 22%) and anaemia
(12% to 15%). In early 2015, all-age bed-net usage was between
21.8% and 27.1%\xE2\x80\x89and the reported coverage of indoor
residual spraying varied across the district between 30.7% and
79%." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: This
study revealed that Magude has limited socio-economic
conditions, poor access to healthcare services and low coverage
of malaria vector control interventions. Thus, Magude
represented an area where it is most pressing to demonstrate the
feasibility of malaria elimination. - Label: TRIAL REGISTRATION
NUMBER NlmCategory: BACKGROUND content: NCT02914145;
Pre-results
Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique.
BACKGROUND: An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. This study aimed to compare the diagnostic performance of the PfHRP2-based Abbott Malaria Ag P. falciparum ultrasensitive RDT (uRDT) to that of the conventional SD-Bioline Malaria Ag P. falciparum RDT (cRDT) when performed under field conditions. METHODS: Finger-prick blood samples were collected from adults and children in two cross-sectional surveys in May of 2017 in southern Mozambique. Using real-time quantitative PCR (RT-qPCR) as the reference method, the age-specific diagnostic performance indicators of the cRDT and uRDT were compared. The presence of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) antigens was evaluated in a subset from dried blood spots by a quantitative antigen assay. pfhrp2 and pfhrp3 gene deletions were assessed in samples positive by RT-qPCR and negative by both RDTs. RESULTS: Among the 4,396 participants with complete test results, the sensitivity of uRDTs (68.2; 95% CI 60.8 to 74.9) was marginally better than that of cRDTs (61.5; 95% CI 53.9 to 68.6) (p-value = 0.004), while the specificities were similar (uRDT: 99.0 [95% CI 98.6 to 99.2], cRDT: 99.2 [95% CI 98.9 to 99.4], p-value = 0.02). While the performance of both RDTs was lowest in ≥ 15-year-olds, driven by the higher prevalence of low parasite density infections in this group, the sensitivity of uRDTs was significantly higher in this age group (54.9, 95% CI 40.3 to 68.9) compared to the sensitivity of cRDTs (39.2, 95% CI 25.8 to 53.9) (p-value = 0.008). Both RDTs detected P. falciparum infections at similar geometric mean parasite densities (112.9  parasites/μL for uRDTs and 145.5 parasites/μL for cRDTs). The presence of HRP2 antigen was similar among false positive (FP) samples of both tests (80.5% among uRDT-FPs and 84.4% among cRDT-FPs). Only one false negative sample was detected with a partial pfhrp2 deletion. CONCLUSION: This study showed that the uRDTs developed by Abbott do not substantially outperform SD-Bioline Pf malaria RDTs in the community and are still not comparable to molecular methods to detect P. falciparum infections in this study setting
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