| 1. |
- Morris, Ulrika, et al.
(författare)
-
A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission.
- 2018
-
Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mass drug administration (MDA) has the potential to interrupt malaria transmission and has been suggested as a tool for malaria elimination in low-endemic settings. This study aimed to determine the effectiveness and safety of two rounds of MDA in Zanzibar, a pre-elimination setting.METHODS: A cluster randomised controlled trial was conducted in 16 areas considered as malaria hotspots, with an annual parasite index of > 0.8%. The areas were randomised to eight intervention and eight control clusters. The intervention included two rounds of MDA with dihydroartemisinin-piperaquine and single low-dose primaquine 4 weeks apart in May-June 2016. Primary and secondary outcomes were cumulative confirmed malaria case incidences 6 months post-MDA and parasite prevalences determined by PCR 3 months post-MDA. Additional outcomes included intervention coverage, treatment adherence, occurrence of adverse events, and cumulative incidences 3, 12, and 16 months post-MDA.RESULTS: Intervention coverage was 91.0% (9959/10944) and 87.7% (9355/10666) in the first and second rounds, respectively; self-reported adherence was 82.0% (881/1136) and 93.7% (985/1196). Adverse events were reported in 11.6% (147/1268) and 3.2% (37/1143) of post-MDA survey respondents after both rounds respectively. No serious adverse event was reported. No difference in cumulative malaria case incidence was observed between the control and intervention arms 6 months post-MDA (4.2 and 3.9 per 1000 population; p = 0.94). Neither was there a difference in PCR-determined parasite prevalences 3 months post-MDA (1.4% and 1.7%; OR = 1.0, p = 0.94), although having received at least the first MDA was associated with reduced odds of malaria infection (aOR = 0.35; p = 0.02). Among confirmed malaria cases at health facilities, 26.0% and 26.3% reported recent travel outside Zanzibar in the intervention and control shehias (aOR ≥ 85; p ≤ 0.001).CONCLUSIONS: MDA was implemented with high coverage, adherence, and tolerability. Despite this, no significant impact on transmission was observed. The findings suggest that two rounds of MDA in a single year may not be sufficient for a sustained impact on transmission in a pre-elimination setting, especially when the MDA impact is restricted by imported malaria. Importantly, this study adds to the limited evidence for the use of MDA in low transmission settings in sub-Saharan Africa.TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721186 (registration date: March 29, 2016).
|
|
| 2. |
- Morris, Ulrika, et al.
(författare)
-
Field deployment of loop-mediated isothermal amplification for centralized mass-screening of asymptomatic malaria in Zanzibar : a pre-elimination setting
- 2015
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Molecular tools for detection of low-density asymptomatic Plasmodium infections are needed in malaria elimination efforts. This study reports results from the hitherto largest implementation of loop-mediated isothermal amplification (LAMP) for centralized mass screening of asymptomatic malaria in Zanzibar.METHODS: Healthy individuals present and willing to participate in randomly selected households in 60 villages throughout Zanzibar were screened for malaria by rapid diagnostic tests (RDT). In 50 % of the study households, participants were asked to provide 60 μL of finger-prick blood for additional LAMP screening. LAMP was conducted in two centralized laboratories in Zanzibar, by trained technicians with limited or no previous experience of molecular methods. The LAMP assay was performed with Loopamp(TM) MALARIA Pan/Pf Detection Kit (Eiken Chemical Company, Japan). Samples positive for Plasmodium genus (Pan)-LAMP were re-tested using Plasmodium falciparum-specific LAMP kits.RESULTS: Paired RDT and LAMP samples were available from 3983 individuals. The prevalence of asymptomatic malaria was 0.5 % (CI 95 % 0.1-0.8) and 1.6 % (CI 95 % 1.1-2.2) by RDT and Pan-LAMP, respectively. LAMP detected 3.4 (CI 95 % 2.2-5.2) times more Plasmodium positive samples than RDT. DNA contamination was experienced, but solved by repetitive decontamination of all equipment and reagents.CONCLUSIONS: LAMP is a simple and sensitive molecular tool, and has potential in active surveillance and mass-screening programmes for detection of low-density asymptomatic malaria in pre-elimination settings. However, in order to deploy LAMP more effectively in field settings, protocols may need to be adapted for processing larger numbers of samples. A higher throughput, affordable closed system would be ideal to avoid contamination.
|
|
| 3. |
- Andersson, Maria Eva, et al.
(författare)
-
Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar.
- 2017
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure.Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens.Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children.Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
|
|
| 4. |
- Aydin-Schmidt, Berit, et al.
(författare)
-
Field Evaluation of a High Throughput Loop Mediated Isothermal Amplification Test for the Detection of Asymptomatic Plasmodium Infections in Zanzibar
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background New field applicable diagnostic tools are needed for highly sensitive detection of residual malaria infections in pre-elimination settings. Field performance of a high throughput DNA extraction system for loop mediated isothermal amplification (HTP-LAMP) was therefore evaluated for detecting malaria parasites among asymptomatic individuals in Zanzibar. Methods HTP-LAMP performance was evaluated against real-time PCR on 3008 paired blood samples collected on filter papers in a community-based survey in 2015. Results The PCR and HTP-LAMP determined malaria prevalences were 1.6% (95% CI 1.3-2.4) and 0.7% (95% CI 0.4-1.1), respectively. The sensitivity of HTP-LAMP compared to PCR was 40.8% (CI95% 27.0-55.8) and the specificity was 99.9% (CI95% 99.8-100). For the PCR positive samples, there was no statistically significant difference between the geometric mean parasite densities among the HTP-LAMP positive (2.5 p/mu L, range 0.2-770) and HTP-LAMP negative (1.4 p/mu L, range 0.1-7) samples (p = 0.088). Two lab technicians analysed up to 282 samples per day and the HTP-LAMP method was experienced as user friendly. Conclusions Although field applicable, this high throughput format of LAMP as used here was not sensitive enough to be recommended for detection of asymptomatic low-density infections in areas like Zanzibar, approaching malaria elimination.
|
|
| 5. |
- Aydin-Schmidt, Berit, et al.
(författare)
-
Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e103905-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Loop mediated isothermal amplification (LAMP) provides an opportunity for improved, field-friendly detection of malaria infections in endemic areas. However data on the diagnostic accuracy of LAMP for active case detection, particularly low-density parasitaemias, are lacking. We therefore evaluated the performance of a new LAMP kit compared with PCR using DNA from filter paper blood spots.METHODS AND FINDINGS:Samples from 865 fever patients and 465 asymptomatic individuals collected in Zanzibar were analysed for Pan (all species) and Pf (P. falciparum) DNA with the Loopamp MALARIA Pan/Pf kit. Samples were amplified at 65°C for 40 minutes in a real-time turbidimeter and results were compared with nested PCR. Samples with discordant results between LAMP and nested PCR were analysed with real-time PCR. The real-time PCR corrected nested PCR result was defined as gold standard. Among the 117 (13.5%) PCR detected P. falciparum infections from fever patients (mean parasite density 7491/µL, range 6-782,400) 115, 115 and 111 were positive by Pan-LAMP, Pf-LAMP and nested PCR, respectively. The sensitivities were 98.3% (95%CI 94-99.8) for both Pan and Pf-LAMP. Among the 54 (11.6%) PCR positive samples from asymptomatic individuals (mean parasite density 10/µL, range 0-4972) Pf-LAMP had a sensitivity of 92.7% (95%CI 80.1-98.5) for detection of the 41 P. falciparum infections. Pan-LAMP had sensitivities of 97% (95%CI 84.2-99.9) and 76.9% (95%CI 46.2-95) for detection of P. falciparum and P. malariae, respectively. The specificities for both Pan and Pf-LAMP were 100% (95%CI 99.1-100) in both study groups.CONCLUSION:Both components of the Loopamp MALARIA Pan/Pf detection kit revealed high diagnostic accuracy for parasite detection among fever patients and importantly also among asymptomatic individuals of low parasite densities from minute blood volumes preserved on filter paper. These data support LAMPs potential role for improved detection of low-density malaria infections in pre-elimination settings.
|
|
| 6. |
- Baltzell, Kimberly, et al.
(författare)
-
Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers' practices in Zanzibar.
- 2013
-
Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers' practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients. METHODS: Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children. RESULTS: The following themes were identified: 1) health workers use caregivers' history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers' resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making. CONCLUSIONS: This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.
|
|
| 7. |
- Beer, Netta, et al.
(författare)
-
High effective coverage of vector control interventions in children after achieving low malaria transmission in Zanzibar, Tanzania.
- 2013
-
Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Background: Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. Methods: A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Results: Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage. Conclusions: While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions.
|
|
| 8. |
- Björkman, Anders, et al.
(författare)
-
Spatial Distribution of Falciparum Malaria Infections in Zanzibar : Implications for Focal Drug Administration Strategies Targeting Asymptomatic Parasite Carriers
- 2017
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 64:9, s. 1236-1243
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting.Methods: P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities.Results: Among 5278 persons screened, 13 (0.2%) were positive by RDT and 123 (2.3%) by PCR. PCR-positive individuals were scattered over the study area, but logistic regression analysis suggested a propensity of these infections to cluster around RDT-positive individuals. The odds ratios for being PCR positive was 7.4 (95% confidence interval, 2.8-19.9) for those living in the household of an RDT-positive individual and 1.64 (1.0-2.8; P = .06) for those living within <300 m, compared with >1000 m. Treating everyone within households of RDT-positive individuals (1% population) would target 13% of those who are PCR positive. Treating all living within a radius of <300 or <1000 m (14% or 58% population) would target 30% or 66% of infections, respectively. Among 4431 serologically screened individuals, 26% were seropositive. Treating everyone within seropositive households (63% population) would target 77% of PCR-positive individuals.Conclusions: Presumptive malaria treatment seemed justified within RDT-positive households and potentially worth considering within, for example, a radius of <300 m. Serology was not discriminative enough in identifying ongoing infections for improving focal interventions in this setting but may rather be useful to detect larger transmission foci.
|
|
| 9. |
- Connelly, Sean, V, et al.
(författare)
-
Strong isolation by distance and evidence of population microstructure reflect ongoing Plasmodium falciparum transmission in Zanzibar
- 2024
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission. Methods: To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018. Results: Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Conclusions: Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
|
|
| 10. |
- Cook, Jackie, et al.
(författare)
-
Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar
- 2015
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14, s. 43-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics. This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting. Methods: Screening took place in three known hotspot areas prior to the short rains in November. Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses. LAMP results were compared to RDT and to PCR using McNemar's test. Results: Approximately 1,000 people were screened. RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections. However, PCR identified three infections that LAMP did not detect and vice versa. LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening. Conclusions: Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT. LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment.
|
|
| 11. |
- Cook, Jackie, et al.
(författare)
-
Mass Screening and Treatment on the Basis of Results of a Plasmodium falciparum-Specific Rapid Diagnostic Test Did Not Reduce Malaria Incidence in Zanzibar
- 2015
-
Ingår i: The Internet Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1528-8366 .- 0022-1899 .- 1537-6613. ; 211:9, s. 1476-1483
-
Tidskriftsartikel (refereegranskat)abstract
- 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 phase.
|
|
| 12. |
- Elfving, Kristina, et al.
(författare)
-
Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar : Aetiologies, Antibiotic Treatment and Outcome
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia.CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.
|
|
| 13. |
- Elfving, Kristina, et al.
(författare)
-
Pathogen Clearance and New Respiratory Tract Infections Among Febrile Children in Zanzibar Investigated With Multitargeting Real-Time Polymerase Chain Reaction on Paired Nasopharyngeal Swab Samples
- 2018
-
Ingår i: The Pediatric Infectious Disease Journal. - 0891-3668 .- 1532-0987. ; 37:7, s. 643-648
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children.METHODS: Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion.RESULTS: At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up.CONCLUSION: The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.
|
|
| 14. |
- Elfving, Kristina, et al.
(författare)
-
Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar : an observational study
- 2022
-
Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Methods: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ( "IMCI pneumonia ") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia ". Results: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. Conclusion: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia.
|
|
| 15. |
- Elfving, Kristina, et al.
(författare)
-
Real-time PCR threshold cycle (Ct) cut-offs help to identify agents causing acute childhood diarrhea in Zanzibar.
- 2014
-
Ingår i: Journal of clinical microbiology. - 1098-660X. ; 52:3, s. 916-923
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular assays might improve identification of causes of acute diarrheal disease, but may lead to more frequent detection of asymptomatic infections. In the present study real-time PCR targeting 14 pathogens was applied on rectal swabs from 330 children aged 2-59 months in Zanzibar, 165 with acute diarrhea and 165 asymptomatic controls. At least one pathogen was detected in 94% of patients and 84% of controls, with higher rates in patients for norovirus genogroup II (20% vs. 2.4%, p<0.0001), rotavirus (10% vs. 1.8%, p=0.003) and Cryptosporidium (30% vs. 11%, p<0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)-estA (33% vs. 24%), ETEC-eltB (44% vs. 46%), Shigella (35% vs. 33%), and Campylobacter (35% vs. 33%), but for these agents Ct (threshold cycle) values were lower (pathogen loads were higher) in sick children than in controls. In multivariate analysis, Ct values for norovirus genogroup II, rotavirus, Cryptosporidium, ETEC-estA and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents, and provides Ct values that may be critical for interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that assessment of pathogen load may improve identification of agents causing gastroenteritis in children.
|
|
| 16. |
- Friberg Hietala, Sofia, 1973, et al.
(författare)
-
Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria
- 2007
-
Ingår i: JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 12, s. 222-222
-
Tidskriftsartikel (refereegranskat)abstract
- The study aimed to characterize the population pharmacokinetics of amodiaquine (AQ) and its major metabolite N-desethylamodiaquine (N-DEAQ), and to assess the correlation between exposure to N-DEAQ and treatment outcome. Blood samples from children in two studies in Zanzibar and one in Papua New Guinea were included in the pharmacokinetic analysis (n = 86). The children had been treated with AQ in combination with artesunate or sulphadoxine-pyrimethamine. The population pharmacokinetics of AQ and N-DEAQ were modeled using the non-linear mixed effects approach as implemented in NONMEM. Bayesian post-hoc estimates of individual pharmacokinetic parameters were used to generate individual profiles of N-DEAQ exposure. The correlation between N-DEAQ exposure and effect was studied in 212 patients and modeled with logistic regression in NONMEM. The pharmacokinetics of AQ and N-DEAQ were best described by two parallel two-compartment models with a central and a peripheral compartment for each compound. The systemic exposure to AQ was low in comparison to N-DEAQ. The t (1/2lambda) of N-DEAQ ranged from 3 days to 12 days. There was a statistically significant, yet weak, association between N-DEAQ concentration on day 7 and treatment outcome. The age-based dosing schedule currently recommended in Zanzibar appeared to result in inadequate exposure to N-DEAQ in many patients.
|
|
| 17. |
- Morgan, Andrew P., et al.
(författare)
-
Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago
- 2020
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tanzania's Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria's persistence, but this paradigm has not been studied using modern genetic tools.Methods: Whole-genome sequencing (WGS) was used to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. Ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations were assessed by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.Results: Significant decreases in the effective population sizes were inferred in both populations that coincide with a period of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared long segments of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, two of isolates between the mainland and Zanzibar were identified that are related at the expected level of half-siblings, consistent with recent importation.Conclusions: These findings suggest that importation plays an important role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.
|
|
| 18. |
- Morris, Ulrika, et al.
(författare)
-
Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability.
- 2013
-
Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations.
|
|
| 19. |
- Msellem, Mwinyi I
(författare)
-
Efficacy of artemisinin based combination therapy and effectiveness of rapid diagnostic test for management of patients with plasmodium falciparum malaria in Zanzibar
- 2009
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Due to rapid spread of antimalarial drug resistance to Plasmodium falciparum malaria many African countries have recently changed their first-line treatment policy to artemisinin-based combination therapy (ACT). Zanzibar was one of the first regions in Africa to implement ACT free of charge to all age groups through public health facilities in 2003. The introduction of ACT, a highly efficacious but also considerably more expensive treatment than previously used mono-therapies, puts a heavy extra burden on malaria control programmes in Africa. This highlights the need of improved diagnostics to ensure targeting of ACT to patients with parasitologically confirmed malaria infection, particularly in settings beyond the reach of high quality microscopy service. Rapid diagnostic tests (RDT) for malaria represent such a potential candidate, considering they are simple to use and do not require highly trained staff, advanced laboratory facilities or electricity. The aim of this thesis was to study the efficacy of ACT in children with uncomplicated P. falciparum malaria and the effectiveness of RDT for management of fever patients in rural health facilities in Zanzibar. The studies included in the thesis are a part of the scientific evaluation of the ongoing integrated, wide scale, high coverage malaria control interventions in Zanzibar. Methods: Study I was a comparative clinical trial assessing the efficacy of artesunate+amodiaquine (ASAQ) and artemether-lumefantrine (AL) in children with microscopically confirmed uncomplicated P. falciparum malaria. Some 408 patients were enrolled in this study, which was conducted between November 2002 and February 2003 in Kivunge and Micheweni Cottage Hospitals, i.e. prior to the of deployment of the drugs as first- and second line treatment for uncomplicated malaria in Zanzibar. Follow-up was extended to 42 days. Primary end-point was polymerase chain reaction (PCR) adjusted cure rates by day 42 in the respective treatment arms. Study II was a cross-over validation study assessing the influence of RDT aided diagnosis on ACT prescription compared to clinical diagnosis (CD) only in patients with fever within the last 48 hours attending 4 primary health care facilities in Zanzibar. Some 1887 patients were enrolled between February and August 2005. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Results: Study I. PCR adjusted cure rates by day 42 were 188/206 (91%) for ASAQ and 185/197 (94%) for AL, [Odds ratio (OR) 1.48 95% CI 0.69-3.15; p=0.314]. However, AL provided a stronger protection against reinfections during follow-up. Study II. RDT was associated with lower prescription rate of ACT than CD alone, 361/1005 (36%) compared with 752/882 (85%) [OR 0.04 (95%CI 0.03-0.05) p<0.001]. In contrast, prescription of antibiotics was higher after RDT than CD alone, i.e. 372/1005 (37%) and 235/882 (27%) [OR 1.8 (95%CI 1.5-2.2) p<0.001]. Conclusion: Both ASAQ and AL were highly efficacious, which justify their introduction as new malaria treatment policy in Zanzibar. RDTs resulted in improved adequate treatment and may therefore represent an important tool for management of patients with fever in peripheral health care settings in Zanzibar.
|
|
| 20. |
- Msellem, Mwinyi, et al.
(författare)
-
Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar
- 2020
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 26:8, s. 1767-1777
-
Tidskriftsartikel (refereegranskat)abstract
- Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ). We studied its efficacy in Zanzibar after 14 years as first-line treatment directly by an in vivo, single-armed trial and indirectly by prevalences of different genotypes in the P. falciparum chloroquine-resistance transporter, multidrug-resistance 1, and Kelch 13 propeller domain genes. In vivo efficacy was higher during 2017 (100%; 95% CI 97.4%-100%) than during 2002-2005 (94.7%; 95% CI 91.9%-96.7%) (p = 0.003). Molecular findings showed no artemisinin resistance-associated genotypes and major increases in genotypes associated with high sensitivity/efficacy for amodiaquine than before ASAQ was introduced. Thus, the efficacy of ASAQ is maintained and appears to be increased after long-term use in contrast to what is observed for other ACTs used in Africa.
|
|
| 21. |
- Pernaute-Lau, Leyre, et al.
(författare)
-
Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar
- 2021
-
Ingår i: Malaria Journal. - : BioMed Central (BMC). - 1475-2875. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The anti-malarial drug, amodiaquine, a commonly used, long-acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles, CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of these CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine (AS-AQ) treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.METHODS: Dried blood spots on filter paper were collected from 618 children enrolled in two randomized clinical trials comparing AS-AQ and artemether-lumefantrine in 2002-2005 in Zanzibar. Study participant were under five years of age with uncomplicated falciparum malaria. Human CYP2C8*2 and CYP2C8*3 genotype frequencies were determined by PCR-restriction fragment length polymorphism. Statistical associations between CYP2C8*2 and/or CYP2C8*3 allele carriers and treatment outcome or occurrence of adverse events were assessed by Fisher's exact test.RESULTS: The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5 % (95 % CI 15.4-19.7) and 2.7 % (95 % CI 1.8-3.7), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with re-infections (44.1 %; 95 % CI 33.8-54.8) or those with recrudescent infections (48.3 %; 95 % CI 29.4-67.5), compared to those with an adequate clinical and parasitological response (36.7 %; 95 % CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either CYP2C8*2 or CYP2C8*3 alleles were significantly associated with an increased occurrence of non-serious adverse events, when compared with CYP2C8 *1/*1 wild type homozygotes (44.9 %; 95 % CI 36.1-54.0 vs. 28.1 %; 95 % CI 21.9-35.0, respectively; P = 0.003).CONCLUSIONS: CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to AS-AQ may be reduced in subjects carrying the CYP2C8*2 and CYP2C8*3 alleles. The importance of this non-negligible association with regard to amodiaquine-based malaria chemotherapy warrants further investigation.
|
|
