Malaria Species Positivity Rates Among Symptomatic Individuals Across Regions of Differing Transmission Intensities in Mainland Tanzania.
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ABSTRACT: Background
Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized.Methods
We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Mainland Tanzania and performed quantitative real-time PCR to determine presence and parasitemia of each malaria species.Results
P. falciparum was most prevalent, but P. malariae and P. ovale were found in all but 1 region, with high levels (>5%) of P. ovale in 7 regions. The highest P. malariae positivity rate was 4.5% in Mara and 8 regions had positivity rates ≥1%. We only detected 3 P. vivax infections, all in Kilimanjaro. While most nonfalciparum malaria-positive samples were coinfected with P. falciparum, 23.6% (n = 13 of 55) of P. malariae and 14.7% (n = 24 of 163) of P. ovale spp. were monoinfections.Conclusions
P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of nonfalciparum species.
SUBMITTER: Popkin-Hall ZR
PROVIDER: S-EPMC11011190 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
Publications
Malaria Species Positivity Rates Among Symptomatic Individuals Across Regions of Differing Transmission Intensities in Mainland Tanzania.
Popkin-Hall Zachary R ZR Seth Misago D MD Madebe Rashid A RA Budodo Rule R Bakari Catherine C Francis Filbert F Pereus Dativa D Giesbrecht David J DJ Mandara Celine I CI Mbwambo Daniel D Aaron Sijenunu S Lusasi Abdallah A Lazaro Samwel S Bailey Jeffrey A JA Juliano Jonathan J JJ Ishengoma Deus S DS
The Journal of infectious diseases 20240401 4
<h4>Background</h4>Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized.<h4>Methods</h4>We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Ma ...[more]
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Project description:BackgroundDespite implementation of effective interventions in the past two decades, malaria is still a major public health problem in Tanzania. This study assessed the prevalence and drivers of malaria infections among symptomatic and asymptomatic members of selected communities from five regions with varying endemicity in mainland Tanzania.MethodsA cross-sectional community survey was conducted in five districts, including one district/region in Kagera, Kigoma, Njombe, Ruvuma and Tanga from July to August 2023. Participants aged ≥ 6 months were recruited and tested using rapid diagnostic tests (RDTs). Demographic, anthropometric, clinical, parasitological, type of house, and socio-economic status (SES) data were captured using structured questionnaires. Associations between parasite prevalence and potential drivers were determined by logistic regression, and the results were presented as crude (cOR) and adjusted odds ratios (aOR), with 95% confidence intervals (CIs).ResultsAmong 10,228 individuals tested, 3515 (34.4%) had positive results by RDTs. The prevalence of malaria varied from 21.6% in Tanga to 44.4% in Kagera, and from 14.4% to 68.5% among the different villages (P < 0.001). The odds of malaria infections were higher in males (aOR = 1.32, 95% CI 1.19-1.48, P < 0.001), under-fives (aOR = 2.02, 95% CI 1.74-2.40, P < 0.001), schoolchildren [aged 5-9 years (aOR = 3.23, 95% CI 1.19-1.48, P < 0.001) and 10-14 years (aOR = 3.53, 95% CI 3.03-4.11, P < 0.001)], and non-bednet users (aOR = 1.49, 95% CI 1.29-1.72, P < 0.001). Individuals from households with low SES (aOR = 1.40, 95% CI 1.16-1.69, P < 0.001), or living in houses with open windows (aOR = 1.24, 95% CI 1.06-1.45, P < 0.001) and/or holes on the walls (aOR = 1.43, 95% CI 1.14-1.81, P < 0.001) also had higher odds.ConclusionsMalaria prevalence varied widely across regions and villages, and the odds of infections were higher in males, schoolchildren, non-bednet users, and individuals with low SES or living in houses with open windows and/or holes on the walls. The identified vulnerable groups and hotspots should be targeted with specific interventions to reduce the disease burden and support the ongoing malaria elimination efforts in Tanzania.
| S-EPMC11760675 | biostudies-literature
Project description: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 affected 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 different MTI: 2010 (lower, n = 234) and 2013 (higher, n = 143). The effect of the year on the correlations between cytokines, chemokines and growth factors and IgGs to Plasmodium falciparum (markers of exposure) was explored. The effects 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 effect on analyte concentrations. CONCLUSIONS:The results show a different 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.
| S-EPMC6896751 | biostudies-literature
Project description:Recent studies point to the need to incorporate non-falciparum species detection into malaria surveillance activities in sub-Saharan Africa, where 95% of malaria cases occur. Although Plasmodium falciparum infection is typically more severe, diagnosis, treatment, and control for P. malariae, P. ovale spp., and P. vivax may be more challenging. The prevalence of these species throughout sub-Saharan Africa is poorly defined. Tanzania has geographically heterogeneous transmission levels but an overall high malaria burden. In order to estimate the prevalence of malaria species in Mainland Tanzania, 1,428 samples were randomly selected from 6,005 asymptomatic isolates collected in cross-sectional community surveys across four regions and analyzed via qPCR to detect each Plasmodium species. P. falciparum was most prevalent, with P. malariae and P. ovale spp. detected at lower prevalence (<5%) in all four regions. P. vivax was not detected. Malaria elimination efforts in Tanzania will need to account for these non-falciparum species.
| S-EPMC10793544 | biostudies-literature
Project description:We sought to identify a subset of Plasmodium falciparum antibody targets that would inform monitoring efforts needed to eliminate malaria in high transmission settings. IgG antibodies to 28 recombinant Pf antigens were measured in residents of two communities in western Kenya examined in 2003 and 2013, when the respective prevalence of asymptomatic parasitemia among children was 81 and 15 percent by microscopy. Annual seroconversion rates based on a sero-catalytic model that dichotomised antibody values to negative versus positive showed that rates were higher in 2003 than 2013 for 1 pre-erythrocytic and 7 blood-stage antigens. Antibody acquisition models that considered antibody levels as continuous variables showed that age-related antibody levels to Circumsporozoite Protein and 10 merozoite proteins increased at different rates with age in 2003 versus 2013. Both models found that antibodies to 5 proteins of the Merozoite Surface Protein 1 complex were differentially acquired between the cohorts, and that changes in antibody levels to Apical Membrane Antigen 1 suggested a decrease in transmission that occurred ~10 years before 2013. Further studies evaluating antibodies to this subset of Pf antigens as biomarkers of malaria exposure and naturally acquired immunity are warranted in endemic settings where transmission has been reduced but persists.
| S-EPMC5715086 | biostudies-literature
Project description:BackgroundRecent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world's malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae, P. ovale spp. and P. vivax, the latter may be more challenging to diagnose, treat, control and ultimately eliminate. The prevalence of non-falciparum species throughout sub-Saharan Africa is poorly defined. Tanzania has geographical heterogeneity in transmission levels but an overall high malaria burden.MethodsTo estimate the prevalence of malaria species in Mainland Tanzania, we randomly selected 1428 samples from 6005 asymptomatic isolates collected in previous cross-sectional community surveys across four regions and analyzed these by quantitative PCR to detect and identify the Plasmodium species.ResultsPlasmodium falciparum was the most prevalent species in all samples, with P. malariae and P. ovale spp. detected at a lower prevalence (< 5%) in all four regions; P. vivax was not detected in any sample.ConclusionsThe results of this study indicate that malaria elimination efforts in Tanzania will need to account for and enhance surveillance of these non-falciparum species.
| S-EPMC10960463 | biostudies-literature
Project description:Tanzania is undergoing an epidemiological transition for malaria transmission with some areas of the country having <10% (hypoendemic) and other areas 10% - 50% malaria prevalence (mesoendemic). It is not known whether there is a difference in the quality of malaria case management based on endemicity in Tanzania mainland. We examined the influence of endemicity on the quality of malaria case management at health facilities. We conducted a cross-sectional analysis of 1713 health facilities in Tanzania mainland, using data collected by the National Malaria Control Program through an assessment tool to evaluate quality of malaria case management. The data was gathered from September 2017 to December 2018. Using standard quality factors, mean scores from facilities in the different endemicity regions were compared by a Student's t-test. Simple and multiple linear regression analyses were performed to determine the association between facility performance (score) and endemicity (mesoendemic vs. hypoendemic). Facilities in mesoendemic regions scored higher than those in hypoendemic regions on the overall quality of services [difference in mean scores ([Formula: see text]) = 2.52; (95% Confidence Interval (CI) 1.12, 3.91)], site readiness [[Formula: see text] = 2.97; (95% CI 1.30, 4.61)], availability of malaria reference materials [[Formula: see text] = 4.91; (95% CI 2.05, 7.76)], availability of Health Management Information System tools [[Formula: see text] = 5.86; (95% CI 3.80, 7.92)] and patient satisfaction [[Formula: see text] = 6.61; (95% CI 3.75, 9.48)]. Predictors associated with lower facility scores included; being located in a hypoendemic region [β: -2.49; (95% CI -3.83, -1.15)] and urban area [β: -3.84; (95% CI -5.60, -2.08)]. These findings highlight the differences in quality of malaria case management based on endemicity, but there is still a need to target improvement efforts in underperforming facilities, regardless of endemicity.
| S-EPMC10441786 | biostudies-literature
Project description:BackgroundTanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania.MethodsPlasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites.ResultsOverall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥ 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (RS = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic.ConclusionMicrosatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-α, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-α alone or with any of the other three markers could be adopted for use in TES in Tanzania.
| S-EPMC10943981 | biostudies-literature
Project description:BackgroundUnderstanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and price of anti-malarials and malaria diagnosis in 2016.MethodsA nationally-representative malaria outlet survey was conducted between 18th May and 2nd July, 2016. A census of public and private outlets with potential to distribute malaria testing and/or treatment was conducted among a representative sample of administrative units. An audit was completed for all anti-malarials, malaria rapid (RDT) diagnostic tests and microscopy.ResultsA total of 5867 outlets were included in the nationally representative survey, across both public and private sectors. In the public sector, availability of malaria testing was 92.3% and quality-assured (QA) ACT was 89.1% among all screened outlets. Sulfadoxine-pyrimethamine (SP) was stocked by 51.8% of the public sector and injectable artesunate was found in 71.4% of all screened public health facilities. Among anti-malarial private-sector stockists, availability of testing was 15.7, and 65.1% had QA ACT available. The public sector accounted for 83.4% of the total market share for malaria diagnostics. The private sector accounted for 63.9% of the total anti-malarial market, and anti-malarials were most commonly distributed through accredited drug dispensing outlets (ADDOs) (39.0%), duka la dawa baridi (DLDBs) (13.3%) and pharmacies (6.7%). QA ACT comprised 33.1% of the national market share (12.2% public sector and 20.9% private sector). SP accounted for 53.3% of the total market for anti-malarials across both private and public sectors (31.3 and 22.0% of the total market, respectively). The median price per adult equivalent treatment dose (AETD) of QA ACT in the private sector was $1.40, almost 1.5 times more expensive than the median price per AETD of SP ($1.05). In the private sector, 79.3% of providers perceived ACT to be the most effective treatment for uncomplicated malaria for adults and 88.4% perceived this for children.ConclusionsWhile public sector preparedness for appropriate malaria testing and case management is showing encouraging signs, QA ACT availability and market share in the private sector continues to be sub-optimal for most outlet types. Furthermore, it is concerning that SP continues to predominate in the anti-malarial market. The reasons for this remain unclear, but are likely to be in part related to price, availability and provider knowledge or preferences. Continued efforts to implement government policy around malaria diagnosis and case management should be encouraged.
| S-EPMC5437635 | biostudies-literature
Project description:BackgroundResistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria transmission.MethodsP. falciparum at delivery was assessed by microscopy, quantitative PCR (qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant women from Benin, Gabon, Kenya and Mozambique. Resistance was defined by the proportion of submicroscopic infections and the levels of anti-parasite antibodies quantified by Luminex, and tolerance by the relationship of pregnancy outcomes with parasite densities at delivery.ResultsP. falciparum prevalence by qPCR in peripheral and/or placental blood of HIV-uninfected Mozambican, Gabonese and Beninese women at delivery was 6% (21/340), 11% (28/257) and 41% (143/349), respectively. The proportion of peripheral submicroscopic infections was higher in Benin (83%) than in Mozambique (60%) and Gabon (55%; P = 0.033). Past or chronic placental P. falciparum infection was associated with an increased risk of preterm birth in Mozambican newborns (OR = 7.05, 95% CI 1.79 to 27.82). Microscopic infections were associated with reductions in haemoglobin levels at delivery among Mozambican women (-1.17 g/dL, 95% CI -2.09 to -0.24) as well as with larger drops in haemoglobin levels from recruitment to delivery in Mozambican (-1.66 g/dL, 95% CI -2.68 to -0.64) and Gabonese (-0.91 g/dL, 95% CI -1.79 to -0.02) women. Doubling qPCR-peripheral parasite densities in Mozambican women were associated with decreases in haemoglobin levels at delivery (-0.16 g/dL, 95% CI -0.29 to -0.02) and increases in the drop of haemoglobin levels (-0.29 g/dL, 95% CI -0.44 to -0.14). Beninese women had higher anti-parasite IgGs than Mozambican women (P < 0.001). No difference was found in the proportion of submicroscopic infections nor in the adverse impact of P. falciparum infections in HIV-infected women from Kenya (P. falciparum prevalence by qPCR: 9%, 32/351) and Mozambique (4%, 15/417).ConclusionsThe lowest levels of resistance and tolerance in pregnant women from areas of low malaria transmission were accompanied by the largest adverse impact of P. falciparum infections. Exposure-dependent mechanisms developed by pregnant women to resist the infection and minimise pathology can reduce malaria-related adverse outcomes. Distinguishing both types of defences is important to understand how reductions in transmission can affect malaria disease.Trial registrationClinicalTrials.gov NCT00811421 . Registered 18 December 2008.
| S-EPMC5513247 | biostudies-literature
Project description:BackgroundDiversification of artemisinin-based combination therapy (ACT) is suggested as one of the strategies that can be used to contain artemisinin resistance. Artesunate-amodiaquine (ASAQ) is one of the artemisinin-based combinations that can be used in the diversification strategy as an alternative first-line treatment for uncomplicated malaria in mainland Tanzania. There is however limited data on the efficacy of ASAQ in mainland Tanzania. This study assessed the efficacy of ASAQ for treatment of uncomplicated Plasmodium falciparum malaria in selected sentinel sites for therapeutic efficacy studies in mainland Tanzania.MethodsBetween December 2018 and March 2020, children aged between 6 months and 10 years, attending at Nagaga, Mkuzi, and Mlimba primary health facilities, and with suspected uncomplicated malaria infection were screened for eligibility to participate in the study. Malaria infection was screened using microscopy. Children with uncomplicated P. falciparum monoinfection and who fulfilled all other inclusion criteria, and had none of the exclusion criteria, according to the World Health Organization (WHO) guidelines, were treated with ASAQ. Follow-up visits were scheduled on days 0, 1, 2, 3, 7, 14, 21, and 28 or on any day of recurrent infection for clinical and laboratory assessment. Polymerase chain reaction (PCR)-corrected cure rate on day 28 was the primary outcome.ResultsA total of 264 children, 88 in each of the three study sites (Mlimba, Mkuzi and Nagaga health facilities) were enrolled and treated with ASAQ. The ASAQ PCR-corrected cure rate was 100% at all the three study sites. None of the participants had early treatment failure or late clinical failure. Furthermore, none of the participants had a serious adverse event.ConclusionASAQ was highly efficacious for the treatment of uncomplicated P. falciparum malaria in mainland Tanzania, therefore, it can be deployed as an alternative first-line treatment for uncomplicated malaria as part of diversification strategy to contain the spread of partial artemisinin resistance in the country.
| S-EPMC10979577 | biostudies-literature