Applied mathematical modelling to inform national malaria policies, strategies and operations in Tanzania

More than ever, it is crucial to make the best use of existing country data, and analytical tools for developing malaria control strategies as the heterogeneity in malaria risk within countries is increasing, and the available malaria control tools are expanding while large funding gaps exist. Global and local policymakers, as well as funders, increasingly recognize the value of mathematical modelling as a strategic tool to support decision making. This case study article describes the long-term use of modelling in close collaboration with the National Malaria Control Programme (NMCP) in Tanzania, the challenges encountered and lessons learned.; In Tanzania, a recent rebound in prevalence led to the revision of the national malaria strategic plan with interventions targeted to the malaria risk at the sub-regional level. As part of the revision, a mathematical malaria modelling framework for setting specific predictions was developed and used between 2016 and 2019 to (1) reproduce setting specific historical malaria trends, and (2) to simulate in silico the impact of future interventions. Throughout the project, multiple stakeholder workshops were attended and the use of mathematical modelling interactively discussed.; In Tanzania, the model application created an interdisciplinary and multisectoral dialogue platform between modellers, NMCP and partners and contributed to the revision of the national malaria strategic plan by simulating strategies suggested by the NMCP. The uptake of the modelling outputs and sustained interest by the NMCP were critically associated with following factors: (1) effective sensitization to the NMCP, (2) regular and intense communication, (3) invitation for the modellers to participate in the strategic plan process, and (4) model application tailored to the local context.; Empirical data analysis and its use for strategic thinking remain the cornerstone for evidence-based decision-making. Mathematical impact modelling can support the process both by unifying all stakeholders in one strategic process and by adding new key evidence required for optimized decision-making. However, without a long-standing partnership, it will be much more challenging to sensibilize programmes to the usefulness and sustained use of modelling and local resources within the programme or collaborating research institutions need to be mobilized

Mapping intra-urban malaria risk using high resolution satellite imagery:A case study of Dar es Salaam

Background: With more than half of Africa's population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection. However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements. The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs. In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014. Methods: High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam. Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam. Results: Results indicate that the risk of malaria infection varied across the city. The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs. The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors. Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas. Conclusions: The predictive maps produced can serve as valuable resources for municipal councils aiming to shrink the extents of malaria across cities, target resources for vector control or intensify mosquito and disease surveillance. The semi-automated modelling process developed can be replicated in other urban areas to identify factors that influence heterogeneity in malaria risk patterns and detect vulnerable zones. There is a definite need to expand research into the unique epidemiology of malaria transmission in urban areas for focal elimination and sustained control agendas.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Are interferon-gamma release assays reliable to detect tuberculosis infection in patients with rheumatoid arthritis treated with Janus kinase inhibitors

Screening for latent tuberculosis infection is recommended in patients with rheumatoid arthritis (RA) starting Janus kinase inhibitors (Jaki). Interferon (IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. Jaki tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with these drugs. Objectives: To compare the performance of QuantiFERON-TB Gold Plus (QFT-P) and QFT Gold In-tube (QFT-GIT) in RA patients treated with Jaki. Methods: RA patients underwent QFT-P and QFT-GIT at baseline (T0), and after 3 (T3) and 12 months (T12) of treatment with Jaki. The agreement between the two tests was calculated. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. The variability of QTF-P results was longitudinally assessed. Results: Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled. A perfect agreement was found between QFT-P and QFT-GIT at all times (κ = 1). At T0, no agreement was recorded between IGRAs and TST (κ = -0.08) and between TST and chest radiography (κ = -0.07), a low agreement was found between QFT-P and chest radiography (κ = 0.17). A variation of 33.3% in the results of QFT-P was recorded at T3 vs T0, of 29.4% at T12 vs T0, and of 11.8% at T12 vs T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-P decreased after 3 months followed by an increase after 12 months (not significant). No change in the median number of circulating lymphocytes was documented. Glucocorticoids intake was associated with a higher probability of negative or indeterminate IGRA results at T0 (p<0.0001). Conclusion: A response to IGRAs is detectable during treatment with Jaki. However, fluctuations in the results of IGRAs have been observed in the absence of correlation with clinical outcomes, thus challenging their interpretation

Sub-national stratification of malaria risk in mainland Tanzania: a simplified assembly of survey and routine data

Recent malaria control efforts in mainland Tanzania have led to progressive changes in the prevalence of malaria infection in children, from 18.1% (2008) to 7.3% (2017). As the landscape of malaria transmission changes, a sub-national stratification becomes crucial for optimized cost-effective implementation of interventions. This paper describes the processes, data and outputs of the approach used to produce a simplified, pragmatic malaria risk stratification of 184 councils in mainland Tanzania.; Assemblies of annual parasite incidence and fever test positivity rate for the period 2016-2017 as well as confirmed malaria incidence and malaria positivity in pregnant women for the period 2015-2017 were obtained from routine district health information software. In addition, parasite prevalence in school children (PfPR; 5to16; ) were obtained from the two latest biennial council representative school malaria parasitaemia surveys, 2014-2015 and 2017. The PfPR; 5to16; served as a guide to set appropriate cut-offs for the other indicators. For each indicator, the maximum value from the past 3 years was used to allocate councils to one of four risk groups: very low (< 1%PfPR; 5to16; ), low (1- < 5%PfPR; 5to16; ), moderate (5- < 30%PfPR; 5to16; ) and high (≥ 30%PfPR; 5to16; ). Scores were assigned to each risk group per indicator per council and the total score was used to determine the overall risk strata of all councils.; Out of 184 councils, 28 were in the very low stratum (12% of the population), 34 in the low stratum (28% of population), 49 in the moderate stratum (23% of population) and 73 in the high stratum (37% of population). Geographically, most of the councils in the low and very low strata were situated in the central corridor running from the north-east to south-west parts of the country, whilst the areas in the moderate to high strata were situated in the north-west and south-east regions.; A stratification approach based on multiple routine and survey malaria information was developed. This pragmatic approach can be rapidly reproduced without the use of sophisticated statistical methods, hence, lies within the scope of national malaria programmes across Africa

Mass Screening and Treatment on the Basis of Results of a Plasmodium falciparum-Specific Rapid Diagnostic Test Did Not Reduce Malaria Incidence in Zanzibar

Background. Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission. Methods. Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission. Results. Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas. Conclusions. Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phas

Pregnant women and infants as sentinel populations to monitor prevalence of malaria: results of pilot study in Lake Zone of Tanzania

As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination.; Pregnant women attending first ANC and infants nine to 12 months old presenting for measles vaccination at a non-probability sample of 54 HFs in Tanzania's Lake Zone (Mara, Mwanza and Kagera Regions) were screened for malaria infection using a malaria rapid diagnostic test (RDT) from December 2012 to November 2013, regardless of symptoms. Participants who tested positive were treated for malaria per national guidelines. Data were collected monthly.; Overall 89.9 and 78.1 % of expected monthly reports on malaria infection prevalence were received for pregnant women and infants, respectively. Among 51,467 pregnant women and 35,155 infants attending routine preventive HF visits, 41.2 and 37.3 % were tested with RDT, respectively. Malaria infection prevalence was 12.8 % [95 % confidence interval (CI) 11.3-14.3] among pregnant women and 11.0 % (95 % CI 9.5-12.5) among infants, and varied by month. There was good correlation of the prevalence of malaria among pregnant women and infants at the HF level (Spearman rho = 0.6; p &lt; 0.001). This approach is estimated to cost $1.28 for every person tested, with the RDT accounting for 72 % of the cost.; Malaria infection was common and well correlated among pregnant women and infants attending routine health services. Routine screening of these readily accessible populations may offer a practical strategy for continuously tracking malaria trends, particularly seasonal variation. Positivity rates among afebrile individuals presenting for routine care offer an advantage as they are unaffected by the prevalence of other causes of febrile illness, which could influence positivity rates among febrile patients presenting to outpatient clinics. The data presented here suggest that in addition to contributing to clinical management, ongoing screening of pregnant women could be used for routine surveillance and detection of hotspots

The potential of pregnant women as a sentinel population for malaria surveillance

With increasing spatial heterogeneity of malaria transmission and a shift of the disease burden towards older children and adults, pregnant women attending antenatal care (ANC) have been proposed as a pragmatic sentinel population for malaria surveillance. However, the representativeness of routine ANC malaria test-positivity and its relationship with prevalence in other population subgroups are yet to be investigated.; Monthly ANC malaria test-positivity data from all Tanzanian health facilities for January 2014 to May 2016 was compared to prevalence data from the School Malaria Parasitaemia Survey 2015, the Malaria Indicator Survey (MIS) 2015/16, the Malaria Atlas Project 2015, and a Bayesian model fitted to MIS data. Linear regression was used to describe the difference between malaria test-positivity in pregnant women and respective comparison groups as a function of ANC test-positivity and potential covariates.; The relationship between ANC test-positivity and survey prevalence in children follows spatially and biologically meaningful patterns. However, the uncertainty of the relationship was substantial, particularly in areas with high or perennial transmission. In comparison, modelled data estimated higher prevalence in children at low transmission intensities and lower prevalence at higher transmission intensities.; Pregnant women attending ANC are a pragmatic sentinel population to assess heterogeneity and trends in malaria prevalence in Tanzania. Yet, since ANC malaria test-positivity cannot be used to directly predict the prevalence in other population subgroups, complementary community-level measurements remain highly relevant

Impact of Artemisinin-Based Combination Therapy and Insecticide-Treated Nets on Malaria Burden in Zanzibar

Zanzibar has implemented artemisinin-based combination therapy for uncomplicated malaria, plus long-lasting insecticidal nets. Achuyt Bhattarai and colleagues found malaria morbidity and mortality decreased dramatically within two years

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19

Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999-2008

Background: In Zanzibar, the Ministry of Health and partners accelerated malaria control from September 2003 onwards. The impact of the scale-up of insecticide-treated nets (ITN), indoor-residual spraying (IRS) and artemisinin-combination therapy (ACT) combined on malaria burden was assessed at six out of seven in-patient health facilities. Methods. Numbers of outpatient and inpatient cases and deaths were compared between 2008 and the pre-intervention period 1999-2003. Reductions were estimated by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period. Results: In 2008, for all age groups combined, malaria deaths had fallen by an estimated 90% (95% confidence interval 55-98%)(p < 0.025), malaria in-patient cases by 78% (48-90%), and parasitologically- confirmed malaria out-patient cases by 99.5% (92-99.9%). Anaemia in-patient cases decreased by 87% (57-96%); anaemia deaths and out-patient cases declined without reaching statistical significance due to small numbers. Reductions were similar for children under-five and older ages. Among under-fives, the proportion of all-cause deaths due to malaria fell from 46% in 1999-2003 to 12% in 2008 (p < 0.01) and that for anaemia from 26% to 4% (p < 0.01). Cases and deaths due to other causes fluctuated or increased over 1999-2008, without consistent difference in the trend before and after 2003. Conclusions: Scaling-up effective malaria interventions reduced malaria-related burden at health facilities by over 75% within 5 years. In high-malaria settings, intensified malaria control can substantially contribute to reaching the Millennium Development Goal 4 target of reducing under-five mortality by two-thirds between 1990 and 2015