153 results on '"Don P, Mathanga"'
Search Results
2. Barriers to accessing malaria treatment amongst school-age children in rural Malawi
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Patani Mhango, Monica Patricia Malata, Effie Chipeta, Alick Sixpence, Terrie E. Taylor, Mark L. Wilson, Lauren M. Cohee, Charles Mangani, and Don P. Mathanga
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School-age children ,Case management ,Health care access ,Universal health care ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Over the last two decades, many countries have moved from malaria control toward malaria elimination. However, some sub-Saharan African countries, like Malawi, have recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. This study aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi. Methods A qualitative study was conducted between September and October 2020, where data were gathered in rural Malawi using free-listing interviews, key-informant interviews, semi-structured interviews and focus group discussions. Purposively sampled participants included SAC, parents of SAC, health workers and key stakeholders at community and district levels. Interviews were digitally recorded and transcribed verbatim. Data were organized using NVivo 12 software and analysed using the thematic method. Results The study recruited 252 participants, with 156 being SAC, equally divided between boys and girls. Health system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility. Conclusions This study shows most of the barriers to accessing malaria treatment among SAC are similar to those experienced by other population groups. Furthermore, COVID-19 adversely affected SAC’s access to treatment. Interventions that support SAC access to prompt diagnosis and treatment are urgently needed to improve the effective control of malaria.
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- 2023
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3. Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi
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Christopher C. Stanley, James Chirombo, Harrison Msuku, Vincent S. Phiri, Noel Patson, Lawrence N. Kazembe, Jobiba Chinkhumba, Atupele Kapito-Tembo, and Don P. Mathanga
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Malawi ,Malaria ,Fever ,Prompt treatment-seeking ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission. Methods As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics. Results From 4563 households included in the survey, 4856 children aged 5–48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7–43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6–34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11–3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27–6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21–0.92]. Conclusion The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.
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- 2023
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4. Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood
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Liana R. Andronescu, Andrea G. Buchwald, Ankur Sharma, Andy Bauleni, Patricia Mawindo, Yuanyuan Liang, Julie R. Gutman, Don P. Mathanga, Jobiba Chinkhumba, and Miriam K. Laufer
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Malaria ,Infants ,Incidence ,Hemoglobin ,Infant development ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. Methods Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. Results Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06–1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02–2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38–1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48–2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). Conclusions Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations.
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- 2023
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5. Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022 [version 2; peer review: 1 approved, 3 approved with reservations]
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Tapiwa Ntwere, Atupele Kapito-Tembo, Halima Twabi, Esloyn Musa, Don P. Mathanga, Nyanyiwe Masingi-Mbeye, Lumbani Munthali, Maclear Masambuka, Abdoulaye Bangoura, Melody Sakala, Michael Give Chipeta, Dianne J Terlouw, Chimwemwe Ligomba, Austin Gumbo, James Chirombo, Donnie Mategula, Judy Gichuki, Michael Kayange, Benard Banda, Jacob Kawonga, Patrick Ken Kalonde, Alinafe Kalanga, Gracious Hamuza, Colins Kwizombe, Jacob Kafulafula, Vincent Samuel, Colins Mitambo, Dina Kamowa, and Akuzike Banda
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Model-based geostatistics ,malaria ,Malawi ,Plasmodium falciparum ,eng ,Medicine ,Science - Abstract
Background Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2–10 years (PfPR 2–10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood method. District-level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modelled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale-up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data.
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- 2024
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6. Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection: implications for human-to-mosquito Plasmodium falciparum transmission
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Rex B. Mbewe, John B. Keven, Charles Mangani, Mark L. Wilson, Themba Mzilahowa, Don P. Mathanga, Clarissa Valim, Miriam K. Laufer, Edward D. Walker, and Lauren M. Cohee
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Malaria parasite transmission ,Microsatellites ,Vector-borne disease prevention ,Age-specific risk ,Human reservoirs of infection ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. Methods In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. Results Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31–75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6–15 years old). Conclusions The results support the hypothesis that humans aged 6–15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.
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- 2023
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7. Competing risks modeling of length of hospital stay enhances risk-stratification of patient care: application to under-five children hospitalized in Malawi
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Christopher C. Stanley, Madalitso Zulu, Harrison Msuku, Vincent S. Phiri, Lawrence N. Kazembe, Jobiba Chinkhumba, Tisungane Mvalo, and Don P. Mathanga
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competing risks ,Kaplan-Meier curve ,Cox proportional hazards ,modeling ,hospital stay ,Malawi ,Infectious and parasitic diseases ,RC109-216 - Abstract
IntroductionLength of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment. This study applied competing risk methods to investigate factors important for risk-stratifying patients based on LOS in order to enhance patient care.MethodsThis study analyzed data from ongoing safety surveillance of the malaria vaccine implementation program in Malawi's four district hospitals of Balaka, Machinga, Mchinji, and Ntchisi. Children aged 1–59 months who were hospitalized (spending at least one night in hospital) with a medical illness were consecutively enrolled between 1 November 2019 and 31 July 2021. Sub-distribution-hazard (SDH) ratios for the cumulative incidence of discharge were estimated using the Fine-Gray competing risk model.ResultsAmong the 15,463 children hospitalized, 8,607 (55.7%) were male and 6,856 (44.3%) were female. The median age was 22 months [interquartile range (IQR): 12–33 months]. The cumulative incidence of discharge was 40% lower among HIV-positive children compared to HIV-negative (sub-distribution-hazard ratio [SDHR]: 0.60; [95% CI: 0.46–0.76]; P
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- 2023
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8. Impact of school-based malaria intervention on primary school teachers’ time in Malawi: evidence from a time and motion study
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Jobiba Chinkhumba, Victor Kadzinje, Gomezgani Jenda, Michael Kayange, and Don P. Mathanga
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School-based health ,Time and motion study ,Learner Treatment Kit ,Malaria ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background School-based health (SBH) programmes that are contingent on primary school teachers are options to increase access to malaria treatment among learners. However, perceptions that provision of healthcare by teachers may be detrimental to teaching activities can undermine efforts to scale up school-based malaria control. The objective of this study was to assess the impact of school-based malaria diagnosis and treatment using the Learner Treatment Kit (LTK) on teachers’ time. Methods A time and motion study was conducted in 10 primary schools in rural Malawi. Teachers who had been trained to diagnose and treat uncomplicated malaria were continuously observed in real time during school sessions and the time they spent on all activities were recorded by independent observers before and after LTK implementation. A structured form, programmed digitally, was used for data collection. Paired sample t-tests were used to assess pre-post differences in average hours teachers spent on the following key activities: direct teaching; indirect teaching; administration; LTK and non-teaching tasks. Multivariable repeated measures mixed regression models were used to ascertain impact of LTK on average durations teachers spent on the key activities. Results Seventy-four teachers, trained to use LTK, were observed. Their mean age and years of teaching experience were 34.7 and 8.7, respectively. Overall, 739.8 h of teacher observations took place. The average time teachers spent in school before relative to after LTK was 5.8 vs. 4.8 h, p = 0.01. The cumulative percentage of time teachers spent on core teaching activities (teaching and administration) was approximately 76% and did not change substantially before and after LTK. Some 24.3% of teachers’ time is spent on non-teaching activities. On average, teachers spent 2.9% of their time providing LTK services daily. Per day, each teacher spent less time on administrative (0.74 vs. 1.07 h, p = 0.02) and non-teaching activities (0.96 vs. 1.41 h, p = 0.01) during LTK compared with the period before LTK. Conclusion School-based health (SBH) programmes are not detrimental to teaching activities. Teachers manage their time to ensure additional time required for SBH services is not at the expense of teaching duties. Programming and policy implications of tasking teachers with SBH does not have substantial opportunity costs. Teachers should continue delivering SBH programmes to promote learners’ health.
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- 2022
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9. A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Malawi
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Beth L. Rubenstein, Jobiba Chinkhumba, Ethel Chilima, Collins Kwizombe, Ashley Malpass, Shelby Cash, Katherine Wright, Peter Troell, Humphrey Nsona, Fannie Kachale, Doreen Ali, Evans Kaunda, Sosten Lankhulani, Michael Kayange, Don P. Mathanga, John Munthali, and Julie R. Gutman
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Malaria ,Pregnancy ,Community Health Workers ,Malawi ,Intermittent preventive treatment ,Sulfadoxine-pyrimethamine ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. Methods A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3 + and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n = 370, December 2017) and endline (n = 687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. Results Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0–5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0–9 doses). Despite overall increases, the change in IPTp3 + coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4 + coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). Conclusions In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers’ delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. Trial registration: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217 .
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- 2022
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10. An urban-to-rural continuum of malaria risk: new analytic approaches characterize patterns in Malawi
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Peter S. Larson, Joseph N. S. Eisenberg, Veronica J. Berrocal, Don P. Mathanga, and Mark L. Wilson
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Urbanicity ,Environmental risk ,Malaria prevention ,Remote sensing ,Spatial analysis ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The urban–rural designation has been an important risk factor in infectious disease epidemiology. Many studies rely on a politically determined dichotomization of rural versus urban spaces, which fails to capture the complex mosaic of infrastructural, social and environmental factors driving risk. Such evaluation is especially important for Plasmodium transmission and malaria disease. To improve targeting of anti-malarial interventions, a continuous composite measure of urbanicity using spatially-referenced data was developed to evaluate household-level malaria risk from a house-to-house survey of children in Malawi. Methods Children from 7564 households from eight districts throughout Malawi were tested for presence of Plasmodium parasites through finger-prick blood sampling and slide microscopy. A survey questionnaire was administered and latitude and longitude coordinates were recorded for each household. Distances from households to features associated with high and low levels of development (health facilities, roads, rivers, lakes) and population density were used to produce a principal component analysis (PCA)-based composite measure for all centroid locations of a fine geo-spatial grid covering Malawi. Regression methods were used to test associations of the urbanicity measure against Plasmodium infection status and to predict parasitaemia risk for all locations in Malawi. Results Infection probability declined with increasing urbanicity. The new urbanicity metric was more predictive than either a governmentally defined rural/urban dichotomous variable or a population density variable. One reason for this was that 23% of cells within politically defined rural areas exhibited lower risk, more like those normally associated with “urban” locations. Conclusions In addition to increasing predictive power, the new continuous urbanicity metric provided a clearer mechanistic understanding than the dichotomous urban/rural designations. Such designations often ignore urban-like, low-risk pockets within traditionally rural areas, as were found in Malawi, along with rural-like, potentially high-risk environments within urban areas. This method of characterizing urbanicity can be applied to other infectious disease processes in rapidly urbanizing contexts.
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- 2021
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11. Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014–2018
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Sarah E. Schmedes, Dhruviben Patel, Simran Dhal, Julia Kelley, Samaly S. Svigel, Pedro Rafael Dimbu, Adicatou-Laï Adeothy, Gauthier Mesia Kahunu, Papy Mandoko Nkoli, Abdoul Habib Beavogui, Simon Kariuki, Don P. Mathanga, Ousmane Koita, Deus Ishengoma, Ally Mohamad, Moonga Hawela, Leah F. Moriarty, Aaron M. Samuels, Julie Gutman, Mateusz M. Plucinski, Venkatachalam Udhayakumar, Zhiyong Zhou, Naomi W. Lucchi, Meera Venkatesan, Eric S. Halsey, and Eldin Talundzic
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Pfk13 mutations ,Plasmodium falciparum ,kelch 13 ,artemisinin resistance ,molecular surveillance ,Africa ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014–2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations.
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- 2021
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12. School-based screening and treatment may reduce P. falciparum transmission
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Lauren M. Cohee, Clarissa Valim, Jenna E. Coalson, Andrew Nyambalo, Moses Chilombe, Andrew Ngwira, Andy Bauleni, Karl B. Seydel, Mark L. Wilson, Terrie E. Taylor, Don P. Mathanga, and Miriam K. Laufer
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Medicine ,Science - Abstract
Abstract In areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact screening-and-treatment of asymptomatic Malawian schoolchildren (n = 364 in the rainy season and 341 in the dry season) had on gametocyte—the parasite stage responsible for human-to-mosquito transmission—carriage. We used concomitant household-based surveys to predict the potential reduction in transmission in the surrounding community. Among 253 students with P. falciparum infections at screening, 179 (71%) had infections containing gametocytes detected by Pfs25 qRT-PCR. 84% of gametocyte-containing infections were detected by malaria rapid diagnostic test. While the gametocyte prevalence remained constant in untreated children, treatment with artemether-lumefantrine reduced the gametocyte prevalence (p
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- 2021
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13. The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens
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Andreea Waltmann, Elizabeth T. Rogawski McQuade, Jobiba Chinkhumba, Darwin J. Operario, Enala Mzembe, Megumi Itoh, Michael Kayange, Sydney M. Puerto-Meredith, Don P. Mathanga, Jonathan J. Juliano, Ian Carroll, Luther A. Bartelt, Julie R. Gutman, and Steven R. Meshnick
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Pregnancy ,Gestational weight gain ,Birthweight ,IPTp ,Gut pathogens ,Sulfadoxine-pyrimethamine ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Poor pregnancy and birth outcomes are common in sub-Saharan Africa and have complex aetiologies. Sulfadoxine-pyrimethamine (SP), given for intermittent preventive therapy of malaria in pregnancy (IPTp), is one of few existing interventions that improves outcomes of both mother and baby despite widespread SP-resistant malaria. Compelling evidence exists that malaria-independent pathways contribute to this protective effect, but the exact sources of non anti-malarial protection remained unknown. We hypothesized that the beneficial effect of SP on birthweight is mediated by SP activity on maternal factors, including increased gestational weight gain and antibiotic activity on pathogens in the maternal gut. Methods: Expectant mothers from a larger randomized control trial comparing the efficacy of IPTp-SP to IPTp with dihydroartemisinin-piperaquine (DP) were also enrolled in this sub-study study at their first antenatal care visit before commencement of IPTp (n = 105). Participants were followed monthly until delivery. Weights and mid-to-upper-arm circumferences (MUAC) were recorded. Monthly stool samples were collected and screened for five Escherichia coli pathotypes, Shigella spp., Vibrio cholerae, Salmonella, Campylobacter coli/jejuni, and three protozoa (Giardia spp., Entameba histolytica, and Cryptosporidium spp.) using previously validated molecular assays. Findings: IPTp-SP vs. IPTP-DP was associated with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). GWG was found to be a mediator of the birthweight and IPTp-SP relationship, as the birthweight of SP infants, but not DP infants, varied according to maternal GWG. The burden of maternal enteric infections was high. The three most commonly observed pathogens were enteroaggregative E. coli (EAEC), atypical enteropathogenic E.coli/enterohaemorrhagic E. coli (aEPEC/EHEC), and typical enteropathogenic E.coli (tEPEC). We found that SP reduced the prevalence of EAEC in a dose-dependent manner. After 3 or more doses, SP-recipients were 90% less likely to be infected with EAEC compared to DP-recipients (ORadj = 0.07, CI95 = 0.12, 0.39, p = 0.002). Compared to DP, this coincided with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). The beneficial effect of SP on maternal GWG, MUAC and BMI, was lower if SP mothers had detectable EAEC, aEPEC/EHEC, tEPEC, and LT-ETEC at baseline. Maternal EAEC and tEPEC at baseline associated with lower birthweight for babies of both SP mothers and DP mothers. When comparing IPTp regimens, the positive effect of SP on birthweight compared to DP was only observed for infants of women who did not test positive for EAEC at baseline (adjusted mean birthweight difference SP vs. DP = 156.0 g, CI95 = -18.0 g, 336.9 g, p = 0.087), though confidence intervals crossed the null. Interpretation: Our findings indicate that in pregnant Malawian women, IPTp-SP vs. IPTp-DP is consistently associated with higher MUAC, BMI, and GWG following the WHO-recommended regimen of at least 3 doses, but carriage of maternal gut pathogens before initiation of IPTp lessens this effect. Because GWG was a mediator of the association between birthweight and SP, we show that SP's previously proven positive effect on birthweight is by promoting maternal weight gain. Overall, our results present one plausible pathway SP exerts malaria-independent protection against poor birth outcomes in the context of its waning antimalarial activity and warrants further investigation. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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- 2022
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14. Crowdsourcing to identify social innovation initiatives in health in low- and middle-income countries
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Lindi van Niekerk, Arturo Ongkeko, Rachel Alice Hounsell, Barwani Khaura Msiska, Don Pascal Mathanga, Josselyn Mothe, Noel Juban, Phyllis Awor, and Dina Balabanova
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Social innovation ,Health ,Crowdsourcing ,Grassroots initiatives ,Participatory research ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Crowdsourcing is a distributed problem-solving and production mechanism that leverages the collective intelligence of non-expert individuals and networked communities for specific goals. Social innovation (SI) initiatives aim to address health challenges in a sustainable manner, with a potential to strengthen health systems. They are developed by actors from different backgrounds and disciplines. This paper describes the application of crowdsourcing as a research method to explore SI initiatives in health. Methods The study explored crowdsourcing as a method to identify SI initiatives implemented in Africa, Asia and Latin America. While crowdsourcing has been used in high-income country settings, there is limited knowledge on its use, benefits and challenges in low- and middle-income country (LMIC) settings. From 2014 to 2018, six crowdsourcing contests were conducted at global, regional and national levels. Results A total of 305 eligible projects were identified; of these 38 SI initiatives in health were identified. We describe the process used to perform a crowdsourcing contest for SI, the outcome of the contests, and the challenges and opportunities when using this mechanism in LMICs. Conclusions We demonstrate that crowdsourcing is a participatory method, that is able to identify bottom-up or grassroots SI initiatives developed by non-traditional actors.
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- 2020
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15. Universities as catalysts of social innovation in health systems in low-and middle-income countries: a multi-country case study
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Lindi van Niekerk, Don Pascal Mathanga, Noel Juban, Diana Maria Castro-Arroyave, and Dina Balabanova
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Social innovation ,University ,Healthcare delivery ,Health system ,Low-and middle-income countries ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Social innovation (SI) in health holds potential to contribute to health systems strengthening and universal health coverage (UHC). The role of universities in SI has been well described in the context of high-income countries. An evidence gap exits on SI in healthcare delivery in the context of low- and middle-income countries (LMICs) as well as on the engagement of universities from these contexts. There is thus a need to build capacity for research and engagement in SI in healthcare delivery within these universities. The aim of this study was to examine the adoption and implementation of network of university hubs focused on SI in healthcare delivery within five countries across Africa, Asia and Latin America. The objectives were to describe the model, components and implementation process of the hubs; identify the enablers and barriers experienced and draw implications that could be relevant to other LMIC universities interested in SI. Methods A case study design was adopted to study the implementation process of a network of university hubs. Data from documentation, team discussions and post-implementation surveys were collected from 2013 to 2018 and analysed with aid of a modified policy analysis framework. Results/discussion SI university-based hubs serve as cross-disciplinary and cross-sectoral platforms, established to catalyse SI within the local health system through four core activities: research, community-building, storytelling and institutional embedding, and adhering to values of inclusion, assets, co-creation and hope. Hubs were implemented as informal structures, managed by a small core team, in existing department. Enablers of hub implementation and functioning were the availability of strong in-country social networks, legitimacy attained from being part of a global network on SI in health and receiving a capacity building package in the initial stages. Barriers encountered were internal institutional resistance, administrative challenges associated with university bureaucracy and annual funding cycles. Conclusions This case study shows the opportunity that reside within LMIC universities to act as eco-system enablers of SI in healthcare delivery in order to fill the evidence gap on SI and enhance cross-sectoral participation in support of achieving UHC.
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- 2020
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16. Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi
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Jimmy Vareta, Andrea G. Buchwald, Angelica Barrall, Lauren M. Cohee, Jenny A. Walldorf, Jenna E. Coalson, Karl Seydel, Alick Sixpence, Don P. Mathanga, Terrie E. Taylor, and Miriam K. Laufer
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Malaria ,Submicroscopic infection ,Plasmodium falciparum ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. This study evaluated whether participants with submicroscopic P. falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi. Methods A total of 16,650 children and adults were enrolled in the course of six cross-sectional surveys during the dry season (October–November) and after the rainy season (April–May) between 2012 and 2014 in three districts in southern Malawi. Demographic and socioeconomic data were collected in conjunction with data on clinical histories, use of malaria preventive measures, and anti-malarial medication taken within 2 weeks of the survey. Axillary temperatures were measured, and blood samples were collected for P. falciparum detection by microscopy and PCR. Participants without malaria parasites detected on microscopy but with a positive PCR for P. falciparum were defined as having submicroscopic infection. Fever was defined as having any one of: reported fever in the past 2 weeks, reported fever in the past 48 h, or a temperature of ≥ 37.5 °C measured at the time of interview. Results Submicroscopic P. falciparum infections and fever were both detected in 9% of the study population. In the final analysis adjusted for clustering within household and enumeration area, having submicroscopic P. falciparum infection was associated with reduced odds of fever in the dry season (odds ratio = 0.52; 95% CI 0.33–0.82); the association in the rainy season did not achieve statistical significance (odds ratio = 1.20; 95% CI 0.91–1.59). The association between submicroscopic infection and fever was consistent across all age groups. When the definition of fever was limited to temperature of ≥ 37.5 °C measured at the time of interview, the association was not statistically significant in either the rainy or dry season. Conclusions In this series of cross-sectional studies in southern Malawi, submicroscopic P. falciparum infection was not associated with increased risk of fever. Submicroscopic detection of the malaria parasite is important in efforts to decrease transmission but is not essential for the clinical recognition of malaria disease.
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- 2020
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17. Levels of knowledge regarding malaria causes, symptoms, and prevention measures among Malawian women of reproductive age
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Alick Sixpence, Owen Nkoka, Gowokani C. Chirwa, Edith B. Milanzi, Charles Mangani, Don P. Mathanga, and Peter A. M. Ntenda
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Malaria ,Malaria-related knowledge ,Multinomial logistic ,Knowledge scores ,Malawi ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malawi is a malaria-endemic country and approximately 6 million cases are reported annually. Improving knowledge of malaria causes and symptoms, and the overall perception towards malaria and its preventive measures is vital for malaria control. The current study investigated the levels of knowledge of the causes, symptoms and prevention of malaria among Malawian women. Methods Data from the 2017 wave of the Malawi Malaria Indicator Survey (MMIS) were analysed. In total, 3422 women of reproductive age (15–49 years) were sampled and analysed. The levels of women’s knowledge about: (1) causes of malaria; (2) symptoms of malaria; and, (3) preventive measures were assessed. The tertiles of the composite score were used as the cut-offs to categorize the levels of knowledge as ‘low’, ‘medium’ and ‘high’. Multinomial logistic regression models were constructed to assess the independent factors while taking into account the complex survey design. Results Approximately 50% of all respondents had high levels of knowledge of causes, symptoms and preventive measures. The high level of knowledge was 45% for rural women and 55% for urban dwellers. After adjusting for the a wide range of factors, women of age group 15–19 years adjusted odds ratio ((aOR): 2.58; 95% Confidence Interval (CI) 1.69–3.92), women with no formal education (aOR: 3.73; 95% CI 2.20–6.33), women whose household had no television (aOR: 1.50; 95% CI 1.02–2.22), women who had not seen/heard malaria message (aOR: 1.53; 95% CI 1.20–1.95), women of Yao tribe (aOR: 1.95; 95% CI 1.10–3.46), and women from rural areas had low levels of knowledge about the causes of malaria, symptoms of malaria and preventive measures. Additionally, the results also showed that women aged 15–19 years (beta [β] = − 0.73, standard error [SE] = 0.12); P
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- 2020
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18. Malaria knowledge and experiences with community health workers among recently pregnant women in Malawi
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Ashley Malpass, Jobiba Chinkhumba, Elizabeth Davlantes, John Munthali, Katherine Wright, Kathryn Ramsey, Peter Troell, Michael Kayange, Fannie Kachale, Don P. Mathanga, Dziko Chatata, and Julie R. Gutman
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Malaria ,Pregnancy ,Community Health Workers ,Malawi ,Intermittent preventive treatment ,Sulfadoxine-pyrimethamine ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The World Health Organization recommends three or more doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to mitigate the negative effects of malaria in pregnancy (MIP). Many pregnant women in Malawi are not receiving the recommended number of doses. Community delivery of IPTp (cIPTp) is being piloted as a new approach to increase coverage. This survey assessed recently pregnant women’s knowledge of MIP and their experiences with community health workers (CHWs) prior to implementing cIPTp. Methods Data were collected via a household survey in Ntcheu and Nkhata Bay Districts, Malawi, from women aged 16–49 years who had a pregnancy resulting in a live birth in the previous 12 months. Survey questions were primarily open response and utilized review of the woman’s health passport whenever possible. Analyses accounted for selection weighting and clustering at the health facility level and explored heterogeneity between districts. Results A total of 370 women were interviewed. Women in both districts found their community health workers (CHWs) to be helpful (77.9%), but only 35.7% spoke with a CHW about antenatal care and 25.8% received assistance for malaria during their most recent pregnancy. A greater proportion of women in Nkhata Bay than Ntcheu reported receiving assistance with malaria from a CHW (42.7% vs 21.9%, p = 0.01); women in Nkhata Bay were more likely to cite IPTp-SP as a way to prevent MIP (41.0% vs 24.8%, p = 0.02) and were more likely to cite mosquito bites as the only way to spread malaria (70.6% vs 62.0% p = 0.03). Women in Nkhata Bay were more likely to receive 3 + doses of IPTp-SP (IPTp3) (59.2% vs 41.8%, p = 0.0002). Adequate knowledge was associated with increased odds of receiving IPTp3, although not statistically significantly so (adjusted odds ratio = 1.50, 95% confidence interval 0.97–2.32, p-value 0.066). Conclusions Women reported positive experiences with CHWs, but there was not a focus on MIP. Women in Nkhata Bay were more likely to be assisted by a CHW, had better knowledge, and were more likely to receive IPTp3+ . Increasing CHW focus on the dangers of MIP and implementing cIPTp has the potential to increase IPTp coverage.
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- 2020
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19. Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials
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Noel Patson, Mavuto Mukaka, Kennedy N. Otwombe, Lawrence Kazembe, Don P. Mathanga, Victor Mwapasa, Alinune N. Kabaghe, Marinus J. C. Eijkemans, Miriam K. Laufer, and Tobias Chirwa
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Pregnancy ,Malaria ,Safety ,Prevention ,Clinical trials ,Statistical methods ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. Methods The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher’s exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann–Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.
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- 2020
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20. The effectiveness of older insecticide-treated bed nets (ITNs) to prevent malaria infection in an area of moderate pyrethroid resistance: results from a cohort study in Malawi
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Monica P. Shah, Laura C. Steinhardt, Dyson Mwandama, Themba Mzilahowa, John E. Gimnig, Andy Bauleni, Jacklyn Wong, Ryan Wiegand, Don P. Mathanga, and Kim A. Lindblade
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Malaria ,Insecticide-treated bed nets ,Prevention ,Vector control ,Insecticide resistance ,Holes ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background A previous cohort study in Malawi showed that users of new insecticide-treated bed nets (ITNs) were significantly protected against malaria compared to non-users, despite moderate levels of pyrethroid resistance among the primary mosquito vectors. The present study investigated whether ITNs that were 1–2 years old continued to protect users in the same area with moderate pyrethroid resistance. Methods One year following a baseline cross-sectional malaria parasitaemia prevalence survey and universal distribution of deltamethrin ITNs (May 2012), a fixed cohort of 1223 children aged 6–59 months was enrolled (April 2013). Children were tested for parasitaemia at monthly scheduled visits and at unscheduled sick visits from May to December 2013 using rapid diagnostic tests. ITN use the prior night and the condition of ITNs (based on presence of holes) was assessed by caregiver self-report. The incidence rate ratio (RR) comparing malaria infection among users and non-users of ITNs was modelled using generalized estimating equations adjusting for potential confounders and accounting for repeated measures on each child. The protective efficacy (PE) of ITN use was calculated as 1 − RR. Results In this cohort, self-reported ITN use remained consistently high (> 95%) over the study period. Although users of ITNs were slightly more protected compared to non-users of ITNs, the difference in incidence of infection was not statistically significant (RR 0.83, 95% confidence interval [CI] 0.54–1.27). Among ITN users, malaria incidence was significantly lower in users of ITNs with no holes (of any size) compared to users of ITNs with ≥ 1 hole (RR 0.82, 95% CI 0.69–0.98). Conclusions There was no significant PE of using 1–2 year-old ITNs on the incidence of malaria in children in an area of moderate pyrethroid resistance, but among ITN users, the authors found increased protection by ITNs with no holes compared to ITNs with holes. Given the moderate levels of pyrethroid resistance in the primary malaria vector and recent evidence of added benefits of ITNs with synergists or non-pyrethroid insecticides, next-generation ITNs may be a useful strategy to address pyrethroid resistance and should be further explored in Malawi.
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- 2020
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21. Community-based amoxicillin treatment for fast breathing pneumonia in young infants 7–59 days old: a cluster randomised trial in rural Bangladesh, Ethiopia, India and Malawi
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Humphreys Nsona, Tadesse Awoke Ayele, Sunita Taneja, Nita Bhandari, Abebaw Gebeyehu, Kassahun Alemu, Don P Mathanga, Lulu M Muhe, Samira Aboubaker, Gashaw Andargie, Zemene Tigabu, Salim Sadruddin, Gunjan Aggarwal, Yasir B Nisar, Suresh Dalpath, Jasmine Kaur, Yasir Bin Nisar, Golam Mothabbir, Shohel Rana, ASM Nawshad Ahmed, Alemayehu Teklu, Ashenafi Tazebew, Sudarshan Mundra, Amarnath Mehrotra, Amneet P. Kumar, Gomezgani Jenda, Peter Moschovis, and Shamim Ahmad Qazi
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction Young infants 7–59 days old with fast breathing pneumonia presented to a primary level health facility receive a 7-day course of amoxicillin as per the WHO guideline. However, community-level health workers (CLHW) are not allowed to treat these infants. This trial evaluated the community level treatment of non-hypoxaemic young infants with fast breathing pneumonia by CLHWs.Methods This cluster-randomised, open-label, non-inferiority trial was conducted in rural areas of Bangladesh, Ethiopia, India and Malawi. We randomly allocated clusters (first-level health facility) 1:1, stratified by the population size, to an intervention group (enhanced community case management) or control group (standard community case management). Infants aged 7–59 days with a respiratory rate of ≥60 breaths/min and oxygen saturation (SpO2) ≥90% were enrolled. In the intervention clusters, these infants were treated with a 7-day course of oral amoxicillin (according to WHO weight bands) and were regularly followed up by CLHWs. In the control clusters, CLHWs continued the standard management (assess and refer after pre-referral antibiotic dose) and followed up according to the national programme guideline. The primary outcome of treatment failure was assessed in both groups by independent outcome assessors on days 6 and 14 after enrolment. Secondary outcomes (accuracy and impact of pulse oximetry) were also assessed.Results Between September 2016 and December 2018, we enrolled 2334 infants (1168 in intervention and 1166 in control clusters) from 208 clusters (104 intervention and 104 control). Of 2334, 22 infants with fast breathing were excluded from analysis, leaving 2312 (1155 in intervention clusters and 1157 in control clusters) for intention-to-treat analysis. The proportion of treatment failure was 5.4% (63/1155) in intervention and 6.3% (73/1157) in the control clusters, including two deaths (0.2%) in each group. The adjusted risk difference for treatment failure between the two groups was −1.0% (95% CI −3.0% to 1.1%). The secondary outcome showed that CLHWs in the intervention clusters performed all recommended steps of pulse oximetry assessment in 94% (1050/1115) of enrolled patients.Conclusions The 7-day amoxicillin treatment for 7–59 days old non-hypoxaemic infants with fast breathing pneumonia by CLHWs was non-inferior to the currently recommended referral strategy.Trial registration numbers CTRI/2017/02/007761 and ACTRN12617000857303.
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- 2021
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22. Poverty and food security: drivers of insecticide-treated mosquito net misuse in Malawi
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Sara Berthe, Steven A. Harvey, Matthew Lynch, Hannah Koenker, Vincent Jumbe, Blessings Kaunda-Khangamwa, and Don P. Mathanga
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ITN ,Misuse ,Fishing ,Lake Malawi ,Malawi ,Food security ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Over the past decade, food insecurity, connected to erratic rains and reduced agricultural outputs, has plagued Malawi. Many households are turning to fishing to seek additional sources of income and food. There is anecdotal evidence that insecticide-treated net (ITN) recipients in Malawi are using their nets for purposes other than sleeping, such as for fishing, protecting crops, and displaying merchandise, among others. The objective of this qualitative study was to explore the factors leading residents of waterside communities in Malawi to use ITNs for fishing. Methods This study used qualitative and observational methods. Five waterside communities were identified, two each in the North, Central and Southern regions, representing a mix of lakeside and riverside settings. Fifteen focus group discussions were conducted with a total of 146 participants, including men, women, and community leaders. Results Respondents stated that they knew that ITNs should be slept under to protect from malaria. Respondents discussed financial hardships their communities were facing due to droughts, poverty, food scarcity, unemployment, and devaluation of the Malawian currency, the kwacha. Many described selling household goods, including clothes and cooking pots, to generate short-term income for their family. Though no respondents admitted to selling an ITN themselves, the practice was commonly known. Participants said that food shortages were forcing them to make difficult choices. Fishing with ITNs was reported to be common in the study sites, as a response to food insecurity, and was widely understood to be harmful over the longer term. Respondents felt that it was everyone’s responsibility to cut down on this practice, but that efforts to confiscate or burn nets and boats of those caught fishing with ITNs were counter-productive since boats, especially, were a required resource for a productive livelihood. Respondents feared that if the health workers, government officials and donors continued to see ITNs being misused for fishing, the distribution of free ITNs would end, which would worsen malaria in their communities. Conclusions Faced with economic hardships and food security crises, participants reported being forced to look for alternative incomes to feed their families. This sometimes included selling or repurposing their belongings, including ITNs, for income. This issue is complex and will require a community-led multisectoral response to preserve health, fisheries, and livelihoods.
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- 2019
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23. Net age, but not integrity, may be associated with decreased protection against Plasmodium falciparum infection in southern Malawi
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Liana R. Andronescu, Andrea G. Buchwald, Jenna E. Coalson, Lauren Cohee, Andy Bauleni, Jenny A. Walldorf, Chifundo Kandangwe, Themba Mzilahowa, Terrie E. Taylor, Don P. Mathanga, and Miriam K. Laufer
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ITN ,Malawi ,Efficacy ,Malaria control ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Distribution campaigns for insecticide-treated nets (ITN) have increased the use of ITNs in Malawi, but malaria prevalence remains high even among those using the nets. Previous studies have addressed ITN ownership, insecticide resistance, and frequency of ITN use as possible contributing factors to the high prevalence of malaria infection despite high ITN coverage, but have rarely considered whether the condition of the ITN, or how many people use it, impacts efficacy. This study assessed how ITN integrity, ITN age, and the number of persons sharing a net might mitigate or reduce protective efficacy among self-identified ITN users in Malawi. Methods From 2012 to 2014, six cross-sectional surveys were conducted in both the rainy and dry seasons in southern Malawi. Data were collected on ITN use, integrity (number and size of holes), and age. Blood samples for detecting Plasmodium falciparum infection were obtained from reported ITN users over 6 months of age. Generalized linear mixed models were used to account for clustering at the household and community level. The final model controlled for gender, household eaves, and community-level infection prevalence during the rainy season. Results There were 9646 ITN users with blood samples across six surveys, 15% of whom tested positive for P. falciparum infection. Among children under 5 years old, there was a 50% increased odds of P. falciparum infection among those sleeping under an ITN older than two years, compared to those using an ITN less than 2 years old (OR = 1.50; 95% CI 1.07–2.08). ITN integrity and number of individuals sharing an ITN were not associated with P. falciparum infection. Conclusions Older ITNs were associated with higher rates of P. falciparum in young children, which may indicate that insecticide concentrations play a larger role in infection prevention than the physical barrier of an ITN. ITN use was self-reported and the integrity measures lacked the precision of newer methods, suggesting a need for objective measures of ITN use and more precise assessment of ITN integrity.
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- 2019
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24. Systematic review of analytical methods applied to longitudinal studies of malaria
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Christopher C. Stanley, Lawrence N. Kazembe, Mavuto Mukaka, Kennedy N. Otwombe, Andrea G. Buchwald, Michael G. Hudgens, Don P. Mathanga, Miriam K. Laufer, and Tobias F. Chirwa
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Plasmodium falciparum ,Longitudinal studies ,Longitudinal analysis ,Cohort studies ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Modelling risk of malaria in longitudinal studies is common, because individuals are at risk for repeated infections over time. Malaria infections result in acquired immunity to clinical malaria disease. Prospective cohorts are an ideal design to relate the historical exposure to infection and development of clinical malaria over time, and analysis methods should consider the longitudinal nature of the data. Models must take into account the acquisition of immunity to disease that increases with each infection and the heterogeneous exposure to bites from infected Anopheles mosquitoes. Methods that fail to capture these important factors in malaria risk will not accurately model risk of malaria infection or disease. Methods Statistical methods applied to prospective cohort studies of clinical malaria or Plasmodium falciparum infection and disease were reviewed to assess trends in usage of the appropriate statistical methods. The study was designed to test the hypothesis that studies often fail to use appropriate statistical methods but that this would improve with the recent increase in accessibility to and expertise in longitudinal data analysis. Results Of 197 articles reviewed, the most commonly reported methods included contingency tables which comprised Pearson Chi-square, Fisher exact and McNemar’s tests (n = 102, 51.8%), Student’s t-tests (n = 82, 41.6%), followed by Cox models (n = 62, 31.5%) and Kaplan–Meier estimators (n = 59, 30.0%). The longitudinal analysis methods generalized estimating equations and mixed-effects models were reported in 41 (20.8%) and 24 (12.2%) articles, respectively, and increased in use over time. A positive trend in choice of more appropriate analytical methods was identified over time. Conclusions Despite similar study designs across the reports, the statistical methods varied substantially and often represented overly simplistic models of risk. The results underscore the need for more effort to be channelled towards adopting standardized longitudinal methods to analyse prospective cohort studies of malaria infection and disease.
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- 2019
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25. Comparison of msp genotyping and a 24 SNP molecular assay for differentiating Plasmodium falciparum recrudescence from reinfection
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Joseph Fulakeza, Sarah McNitt, Jimmy Vareta, Alex Saidi, Godfrey Mvula, Terrie Taylor, Don P. Mathanga, Dylan S. Small, Jacek Skarbinski, Julie R. Gutman, and Karl Seydel
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Malaria ,Plasmodium falciparum ,msp genotyping ,24 SNP genotyping ,Reinfection ,Recrudescence ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based on a panel of 24 single nucleotide polymorphism (SNP) markers. Methods Performance parameters of these two genotyping methods were compared using data from two recently completed drug efficacy trials. Blood samples from two anti-malarial therapeutic trials were analysed by both msp genotyping and the 24 SNP assay. Additionally, to conserve time and resources, the statistical program R was used to select the most informative SNPs for a set of unrelated Malawian samples to develop a truncated SNP-based assay for the region surrounding Blantyre, Malawi. The ability of this truncated assay to distinguish reinfection from recrudescence when compared to the full 24 SNP assay was then analysed using data from the therapeutic trials. Results A total of 360 samples were analysed; 66 for concordance of msp and SNP barcoding methodologies, and 294 for assessing the most informative of the 24 SNP markers. SNP genotyping performed comparably to msp genotyping, with only one case of disagreement among the 50 interpretable results, where the SNP assay identified the sample as reinfection and the msp typing as recrudescence. Furthermore, SNP typing was more robust; only 6% of samples were uninterpretable by SNP typing, compared to 19.7% when msp genotyping was used. For discriminating reinfection from recrudescence, a truncated 6 SNP assay was found to perform at 95.1% the accuracy of the full 24 SNP bar code. Conclusions The use of SNP analysis has similar sensitivity to the standard msp genotyping in determining recrudescence from reinfection. Although more expensive, SNP typing is faster and less work intensive. Limiting the assay to those SNPs most informative in the geographical region of interest may further decrease the workload and the cost, making this technique a feasible and affordable alternative in drug efficacy trials.
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- 2019
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26. Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies possible targets of allele-specific immunity to clinical malaria.
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Zalak Shah, Myo T Naung, Kara A Moser, Matthew Adams, Andrea G Buchwald, Ankit Dwivedi, Amed Ouattara, Karl B Seydel, Don P Mathanga, Alyssa E Barry, David Serre, Miriam K Laufer, Joana C Silva, and Shannon Takala-Harrison
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Genetics ,QH426-470 - Abstract
Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates.
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- 2021
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27. Impact of school-based malaria case management on school attendance, health and education outcomes: a cluster randomised trial in southern Malawi
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Katherine E Halliday, Stefan S Witek-McManus, Austin Mtali, Andrew Bauleni, Saidi Ndau, Emmanuel Phondiwa, Doreen Ali, Virginia Kachigunda, John H Sande, Mpumulo Jawati, Allison Verney, Tiyese Chimuna, David Melody, Helen Moestue, Natalie Roschnik, Simon J Brooker, and Don P Mathanga
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Abstract
IntroductionEvidence indicates children who suffer from ill-health are less likely to attend or complete schooling. Malaria is an important cause of morbidity and mortality in school-age children. However, they are less likely to receive malaria treatment at health facilities and evidence for how to improve schoolchildren’s access to care is limited. This study aimed to evaluate the impact of a programme of school-based malaria case management on schoolchildren’s attendance, health and education.MethodsA cluster randomised controlled trial was conducted in 58 primary schools in Zomba District, Malawi, 2011–2015. The intervention, implemented in 29 randomly selected schools, provided malaria rapid diagnostic tests and artemisinin-based combination therapy to diagnose and treat uncomplicated malaria as part of basic first aid kits known as ‘Learner Treatment Kits’ (LTK). The primary outcome was school attendance, assessed through teacher-recorded daily attendance registers and independent periodic attendance spot checks. Secondary outcomes included prevalence of Plasmodium spp infection, anaemia, educational performance, self-reported child well-being and health-seeking behaviour. A total of 9571 children from standards 1–7 were randomly selected for assessment of school attendance, with subsamples assessed for the secondary outcomes.ResultsBetween November 2013 and March 2015, 97 trained teachers in 29 schools provided 32 685 unique consultations. Female schoolchildren were significantly more likely than male to seek a consultation (unadjusted OR=1.78 (95% CI 1.58 to 2.00). No significant intervention effect was observed on the proportion of child-days recorded as absent in teacher registers (n=9017 OR=0.90 (95% CI 0.77 to 1.05), p=0.173) or of children absent during random school visits—spot checks (n=5791 OR=1.09 (95% CI 0.87 to 1.36), p=0.474). There was no significant impact on child-reported well-being, prevalence of Plasmodium spp, anaemia or education scores.ConclusionDespite high community demand, the LTK programme did not reduce schoolchildren’s absenteeism or improve health or education outcomes in this study setting.Trial registration numberClinicalTrials.gov NCT02213211.
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- 2020
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28. Household-level and surrounding peri-domestic environmental characteristics associated with malaria vectors Anopheles arabiensis and Anopheles funestus along an urban–rural continuum in Blantyre, Malawi
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Nicole F. Dear, Chifundo Kadangwe, Themba Mzilahowa, Andy Bauleni, Don P. Mathanga, Chifundo Duster, Edward D. Walker, and Mark L. Wilson
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Urban–rural ,Urban malaria ,Small-scale agriculture ,Vector ecology ,Anopheles ,Malawi ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria is increasing in some recently urbanized areas that historically were considered lower risk. Understanding what drives urban transmission is hampered by inconsistencies in how “urban” contexts are defined. A dichotomized “urban–rural” approach, based on political boundaries may misclassify environments or fail to capture local drivers of risk. Small-scale agriculture in urban or peri-urban settings has been shown to be a major risk determinant. Methods Household-level Anopheles abundance patterns in and around Malawi’s commercial capital of Blantyre (~ 1.9 M pop.) were analysed. Clusters (N = 64) of five houses each located at 2.5 km intervals along eight transects radiating out from Blantyre city centre were sampled during rainy and dry seasons of 2015 and 2016. Mosquito densities were measured inside houses using aspirators to sample resting mosquitoes, and un-baited CDC light traps to sample host seeking mosquitoes. Results Of 38,895 mosquitoes captured, 91% were female and 87% were Culex spp. Anopheles females (N = 5058) were primarily captured in light traps (97%). Anopheles abundance was greater during rainy seasons. Anopheles funestus was more abundant than Anopheles arabiensis, but both were found on all transects, and had similar associations with environmental risk factors. Anopheles funestus and An. arabiensis females significantly increased with distance from the urban centre, but this trend was not consistent across all transects. Presence of small-scale agriculture was predictive of greater Anopheles spp. abundance, even after controlling for urbanicity, number of nets per person, number of under-5-year olds, years of education, and season. Conclusions This study revealed how small-scale agriculture along a rural-to-urban transition was associated with An. arabiensis and An. funestus indoor abundances, and that indoor Anopheles density can be high within Blantyre city limits, particularly where agriculture is present. Typical rural areas with lower house density and greater distance from urban centres reflected landscapes more suitable for Anopheles reproduction and house invasion. However, similar characteristics and elevated Anopheles abundances were also found around some houses within the city limits. Thus, dichotomous designations of “urban” or “rural” can obscure important heterogeneity in the landscape of Plasmodium transmission, suggesting the need for more nuanced assessment of urban malaria risk and prevention efforts.
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- 2018
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29. Malawi ICEMR Malaria Research: Interactions and Results Influencing Health Policies and Practices
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Charles, Mangani, Themba, Mzilahowa, Lauren, Cohee, Michael, Kayange, Peter, Ntenda, Alick, Sixpence, Austin, Gumbo, Sosten, Lankhulani, Jessy, Goupeyou-Youmsi, Edward, Walker, Miriam, Laufer, Clarissa, Valim, Karl, Seydel, Mark L, Wilson, Terrie, Taylor, and Don P, Mathanga
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Adult ,Malawi ,Mosquito Control ,Piperonyl Butoxide ,Health Policy ,Malaria ,Insecticide Resistance ,Infectious Diseases ,Virology ,Animals ,Humans ,Parasitology ,Insecticide-Treated Bednets ,Child - Abstract
Malaria remains a threat to public health in Malawi. It is well acknowledged that malaria research and robust evidence can have an impact on malaria policy and practice, resulting in positive population health gains. We report policy-relevant research contributions that the Malawi International Center of Excellence for Malaria Research (ICEMR) in partnership with local and international collaborators has made. Findings from our ICEMR studies have shown that long-lasting insecticide-treated bed nets (LLINs) impregnated with piperonyl butoxide reduced mosquito blood feeding more compared with conventional LLINs. On the other hand, we showed that few LLINs are maintained up to the end of their 3-year life span, and that older nets are less effective. These results support the policy change decisions by the Malawi National Malaria Control Program to switch from conventional LLINs to piperonyl butoxide LLINs, and to conduct mass LLIN distribution campaigns every 2 years. Our studies on epidemiological patterns of malaria infection showed that school-age children have higher malaria infection rates and lower use of control measures compared with younger children and adults. These findings added to the evidence base that influenced the National Malaria Control Program to endorse school-based malaria interventions as part of its national policy. Research supported by the Malawi ICEMR is contributing to in-country policy decisions and to the implementation of evidence-based interventions. Through our long-term studies we intend to continue providing practical and policy-relevant evidence necessary, ultimately, to eliminate malaria infection in Malawi.
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- 2022
30. The effect of holes in long-lasting insecticidal nets on malaria in Malawi: results from a case–control study
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Anna A. Minta, Keren Z. Landman, Dyson A. Mwandama, Monica P. Shah, Jodi L. Vanden Eng, James F. Sutcliffe, Joseph Chisaka, Kim A. Lindblade, Don P. Mathanga, and Laura C. Steinhardt
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Malaria ,Physical integrity ,Holes ,Bed nets ,Long-lasting insecticidal nets ,Malawi ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Long-lasting insecticidal nets (LLINs) are a cornerstone of malaria prevention. Holes develop in LLINs over time and compromise their physical integrity, but how holes affect malaria transmission risk is not well known. Methods After a nationwide mass LLIN distribution in July 2012, a study was conducted to assess the relationship between LLIN damage and malaria. From March to September 2013, febrile children ages 6–59 months who consistently slept under LLINs (every night for 2 weeks before illness onset) were enrolled in a case–control study at Machinga District Hospital outpatient department. Cases were positive for Plasmodium falciparum asexual parasites by microscopy while controls were negative. Digital photographs of participants’ LLINs were analysed using an image-processing programme to measure holes. Total hole area was classified by quartiles and according to the World Health Organization’s proportionate hole index (pHI) cut-offs [ 790 cm2 (too torn)]. Number of holes by location and size, and total hole area, were compared between case and control LLINs using non-parametric analyses and logistic regression. Results Of 248 LLINs analysed, 97 (39%) were from cases. Overall, 86% of LLINs had at least one hole. The median number of holes of any size was 9 [interquartile range (IQR) 3, 22], and most holes were located in the lower halves of the nets [median 7 (IQR 2, 16)]. There were no differences in number or location of holes between LLINs used by cases and controls. The median total hole area was 10 cm2 (IQR 2, 125) for control LLINs and 8 cm2 (IQR 2, 47) for case LLINs (p = 0.10). Based on pHI, 109 (72%) control LLINs and 83 (86%) case LLINs were in “good” condition. Multivariable modeling showed no association between total hole area and malaria, controlling for child age, caregiver education, and iron versus thatched roof houses. Conclusions LLIN holes were not associated with increased odds of malaria in this study. However, most of the LLINs were in relatively good condition 1 year after distribution. Future studies should examine associations between LLIN holes and malaria risk with more damaged nets.
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- 2017
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31. Assessing bed net damage: comparisons of three measurement methods for estimating the size, shape, and distribution of holes on bed nets
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Jodi L. Vanden Eng, Don P. Mathanga, Keren Landman, Dyson Mwandama, Anna A. Minta, Monica Shah, James Sutcliffe, Joseph Chisaka, Kim A. Lindblade, and Laura Steinhardt
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Bed net ,Physical durability ,Hole index ,Malaria ,Vector control ,Image analysis ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Measuring the physical condition of long-lasting insecticidal nets (LLINs) under field conditions is of great importance for malaria control programmes to guide decisions on how frequently to replace LLINs. Current guidelines by the World Health Organization Pesticide Evaluation Scheme (WHOPES) propose a proportionate hole index (pHI) for assessing LLIN condition by counting the number of holes the size of a thumb, fist, head, and larger than a head. However, this method does not account for irregular hole shapes or exact hole sizes which could result in inaccurate decisions about when to replace LLINs. Methods LLINs were collected during a 2013 health facility-based malaria case control study in Machinga District, Malawi. To evaluate the accuracy of the pHI, the physical condition of 277 LLINs was estimated by the WHOPES method and then compared with two more thorough measurement methods: image analysis of digital photographs of each LLIN side; and for 10 nets, ruler measurements of the length, width, and location of each hole. Total hole counts and areas per net were estimated by each method, and detailed results of hole shapes and composite pictures of hole locations were generated using image analysis. Results The WHOPES method and image analysis resulted in similar estimates of total hole counts, each with a median of 10 (inter-quartile range (IQR) 4–24 and 4–23, respectively; p = 0.004); however, estimated hole areas were significantly larger using the WHOPES method (median 162 cm2, IQR 28–793) than image analysis (median 13 cm2, IQR 3–101; p
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- 2017
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32. Household costs among patients hospitalized with malaria: evidence from a national survey in Malawi, 2012
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Ian Hennessee, Jobiba Chinkhumba, Melissa Briggs-Hagen, Andy Bauleni, Monica P. Shah, Alfred Chalira, Dubulao Moyo, Wilfred Dodoli, Misheck Luhanga, John Sande, Doreen Ali, Julie Gutman, Kim A. Lindblade, Joseph Njau, and Don P. Mathanga
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Malaria ,Household costs ,Malawi ,Inpatient malaria ,Economic burden ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background With 71% of Malawians living on
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- 2017
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33. School-based diagnosis and treatment of malaria by teachers using rapid diagnostic tests and artemisinin-based combination therapy: experiences and perceptions of users and implementers of the Learner Treatment Kit, southern Malawi
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Treza Mphwatiwa, Stefan Witek-McManus, Austin Mtali, George Okello, Paul Nguluwe, Hard Chatsika, Natalie Roschnik, Katherine E. Halliday, Simon J. Brooker, and Don P. Mathanga
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Training teachers to diagnose uncomplicated malaria using malaria rapid diagnostic tests and treat with artemisinin-based combination therapy has the potential to improve the access of primary school children (6–14 years) to prompt and efficient treatment for malaria, but little is known about the acceptability of such an intervention. This qualitative study explored experiences and perceptions of users and implementers of a programme of school-based malaria case management via a first-aid kit—the Learner Treatment Kit (LTK)—implemented as part of a cluster-randomized controlled trial in Zomba district, Malawi. Methods From 29 primary schools where teachers were trained to test and treat school children for malaria using the LTK, six schools were purposively selected on the basis of relative intervention usage (low, medium or high); school size and geographical location. In total eight focus group discussions were held with school children, parents and guardians, and teachers; and 20 in-depth interviews were conducted with key stakeholders at the school, district and national levels. Interviews were recorded, transcribed, and analysed using a thematic analysis approach. Results The LTK was widely perceived by respondents to be a worthwhile intervention, with the opinion that trained teachers were trusted providers of malaria testing and treatment to school children. Benefits of the programme included a perception of improved access to malaria treatment for school children; decreased school absenteeism; and that the programme supported broader national health and education policies. Potential barriers to successful implementation expressed included increased teacher workloads, a feeling of inadequate supervision from health workers, lack of incentives and concerns for the sustainability of the programme regarding the supply of drugs and commodities. Conclusion Training teachers to test for and treat uncomplicated malaria in schools was well received by both users and implementers alike, and was perceived by the majority of stakeholders to be a valuable programme. Factors raised as critical to the success of such a programme included ensuring an effective supervisory system, a reliable supply chain, and the training of greater numbers of teachers per school to manage high consultation numbers, especially during the peak malaria transmission season.
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- 2017
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34. Seasonal variation of malaria cases in children aged less than 5 years old following weather change in Zomba district, Malawi
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Precious L. Hajison, Bonex W. Mwakikunga, Don P. Mathanga, and Shingairai A. Feresu
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Seasonal variation ,Malaria ,Outpatient children ,Weather change ,Malawi ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria is seasonal and this may influence the number of children being treated as outpatients in hospitals. The objective of this study was to investigate the degree of seasonality in malaria in lakeshore and highland areas of Zomba district Malawi, and influence of climatic factors on incidence of malaria. Methods Secondary data on malaria surveillance numbers and dates of treatment of children
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- 2017
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35. School-Based Malaria Screening and Treatment Reduces Plasmodium falciparum Infection and Anemia Prevalence in Two Transmission Settings in Malawi
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Lauren M Cohee, Ingrid Peterson, Andrea G Buchwald, Jenna E Coalson, Clarissa Valim, Moses Chilombe, Andrew Ngwira, Andy Bauleni, Sarah Schaffer-DeRoo, Karl B Seydel, Mark L Wilson, Terrie E Taylor, Don P Mathanga, and Miriam K Laufer
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Malawi ,Schools ,Artemether, Lumefantrine Drug Combination ,Plasmodium falciparum ,Anemia ,Malaria ,Antimalarials ,Infectious Diseases ,Prevalence ,Major Article ,Humans ,Immunology and Allergy ,Artemether ,Prospective Studies ,Malaria, Falciparum ,Child - Abstract
Background In areas highly endemic for malaria, Plasmodium falciparum infection prevalence peaks in school-age children, adversely affecting health and education. School-based intermittent preventive treatment reduces this burden but concerns about cost and widespread use of antimalarial drugs limit enthusiasm for this approach. School-based screening and treatment is an attractive alternative. In a prospective cohort study, we evaluated the impact of school-based screening and treatment on the prevalence of P. falciparum infection and anemia in 2 transmission settings. Methods We screened 704 students in 4 Malawian primary schools for P. falciparum infection using rapid diagnostic tests (RDTs), and treated students who tested positive with artemether-lumefantrine. We determined P. falciparum infection by microscopy and quantitative polymerase chain reaction (qPCR), and hemoglobin concentrations over 6 weeks in all students. Results Prevalence of infection by RDT screening was 37% (9%–64% among schools). An additional 9% of students had infections detected by qPCR. Following the intervention, significant reductions in infections were detected by microscopy (adjusted relative reduction [aRR], 48.8%; P Conclusions School-based screening and treatment reduced P. falciparum infection and anemia. This approach could be enhanced by repeating screening, using more-sensitive screening tests, and providing longer-acting drugs. Clinical Trials Registration NCT04858087.
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- 2022
36. Estimating risk factors of urban malaria in Blantyre, Malawi: A spatial regression analysis
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Lawrence N. Kazembe and Don P. Mathanga
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Urban malaria ,Travel history ,Spatial regression ,Geo-additive models ,Blantyre ,Malawi ,Arctic medicine. Tropical medicine ,RC955-962 ,Biology (General) ,QH301-705.5 - Abstract
Objective: To estimate risk factors of urban malaria in Blantyre, Malawi, with the goal of understanding the epidemiology and ecology of the disease, and informing malaria elimination policies for African urban cities that have markedly low prevalence of malaria. Methods: We used a case-control study design, with cases being children under the age of five years diagnosed with malaria, and matched controls obtained at hospital and communities. The data were obtained from Ndirande health facility catchment area. We then fitted a multivariate spatial logistic model of malaria risk. Covariate and risk factors in the model included child-specific, household and environmental risk factor (nearness to garden, standing water, river and swamps). The spatial component was assumed to follow a Gaussian process and model fitted using Bayesian inference. Results: Our findings showed that children who visited rural areas were 6 times more likely to have malaria than those who did not [odds ratio (OR) = 6.66, 95% confidence interval (CI): 4.79–9.61]. The risk of malaria increased with age of the child (OR = 1.01, 95% CI: 1.003–1.020), but reduced with high socio-economic status compared to lower status (OR = 0.39, 95% CI: 0.25–0.54 for the highest level and OR = 0.67, 95% CI: 0.47–0.94 for the medium level). Although nearness to a garden, river and standing water showed increased risk, these effects were not significant. Furthermore, significant spatial clusters of risk emerged, which does suggest other factors do explain malaria risk variability apart from those established above. Conclusions: As malaria in urban areas is highly fuelled by rural-urban migration, emphasis should be to optimize information, education and communication prevention strategies, particularly targeting children from lower socio-economic position.
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- 2016
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37. Capacity Development through the US President’s Malaria Initiative–Supported Antimalarial Resistance Monitoring in Africa Network
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Eric S. Halsey, Meera Venkatesan, Mateusz M. Plucinski, Eldin Talundzic, Naomi W. Lucchi, Zhiyong Zhou, Celine I. Mandara, Hawela Moonga, Busiku Hamainza, Abdoul Habib Beavogui, Simon Kariuki, Aaron M. Samuels, Laura C. Steinhardt, Don P. Mathanga, Julie Gutman, Yves Eric Denon, Aline Uwimana, Ashenafi Assefa, Jimee Hwang, Ya Ping Shi, Pedro Rafael Dimbu, Ousmane Koita, Deus S. Ishengoma, Daouda Ndiaye, and Venkatachalam Udhayakumar
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malaria ,antimalarial drugs ,Africa ,capacity building ,artemisinins ,antimicrobial resistance ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Antimalarial drug resistance is an evolving global health security threat to malaria control. Early detection of Plasmodium falciparum resistance through therapeutic efficacy studies and associated genetic analyses may facilitate timely implementation of intervention strategies. The US President’s Malaria Initiative–supported Antimalarial Resistance Monitoring in Africa Network has assisted numerous laboratories in partner countries in acquiring the knowledge and capability to independently monitor for molecular markers of antimalarial drug resistance.
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- 2017
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38. Joint modelling of multivariate longitudinal clinical laboratory safety outcomes, concomitant medication and clinical adverse events: application to artemisinin-based treatment during pregnancy clinical trial
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Miriam K. Laufer, Gertrude Chapotera, Tobias Chirwa, Don P. Mathanga, Umberto D'Alessandro, Victor Mwapasa, Mavuto Mukaka, Lawrence N. Kazembe, and Noel Patson
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medicine.medical_specialty ,Medicine (General) ,Epidemiology ,Concomitant medication ,Health Informatics ,Randomised controlled trials ,Poisson distribution ,Rate ratio ,Antimalarials ,symbols.namesake ,R5-920 ,Pregnancy ,Joint model ,Internal medicine ,medicine ,Humans ,Poisson regression ,Malaria, Falciparum ,Adverse effect ,Drug safety ,business.industry ,Research ,Incidence (epidemiology) ,Artemether, Lumefantrine Drug Combination ,Random effects model ,Artemisinins ,Clinical trial ,Concomitant ,Adverse events ,symbols ,Female ,Artemether ,Laboratories ,business - Abstract
Background In drug trials, clinical adverse events (AEs), concomitant medication and laboratory safety outcomes are repeatedly collected to support drug safety evidence. Despite the potential correlation of these outcomes, they are typically analysed separately, potentially leading to misinformation and inefficient estimates due to partial assessment of safety data. Using joint modelling, we investigated whether clinical AEs vary by treatment and how laboratory outcomes (alanine amino-transferase, total bilirubin) and concomitant medication are associated with clinical AEs over time following artemisinin-based antimalarial therapy. Methods We used data from a trial of artemisinin-based treatments for malaria during pregnancy that randomized 870 women to receive artemether–lumefantrine (AL), amodiaquine–artesunate (ASAQ) and dihydroartemisinin–piperaquine (DHAPQ). We fitted a joint model containing four sub-models from four outcomes: longitudinal sub-model for alanine aminotransferase, longitudinal sub-model for total bilirubin, Poisson sub-model for concomitant medication and Poisson sub-model for clinical AEs. Since the clinical AEs was our primary outcome, the longitudinal sub-models and concomitant medication sub-model were linked to the clinical AEs sub-model via current value and random effects association structures respectively. We fitted a conventional Poisson model for clinical AEs to assess if the effect of treatment on clinical AEs (i.e. incidence rate ratio (IRR)) estimates differed between the conventional Poisson and the joint models, where AL was reference treatment. Results Out of the 870 women, 564 (65%) experienced at least one AE. Using joint model, AEs were associated with the concomitant medication (log IRR 1.7487; 95% CI: 1.5471, 1.9503; p p = 0.906) and alanine aminotransferase (log IRR: 0.1153; 95% CI: − 0.0889, 0.3194; p = 0.269). The Poisson model underestimated the effects of treatment on AE incidence such that log IRR for ASAQ was 0.2118 (95% CI: 0.0082, 0.4154; p = 0.041) for joint model compared to 0.1838 (95% CI: 0.0574, 0.3102; p = 0.004) for Poisson model. Conclusion We demonstrated that although the AEs did not vary across the treatments, the joint model yielded efficient AE incidence estimates compared to the Poisson model. The joint model showed a positive relationship between the AEs and concomitant medication but not with laboratory outcomes. Trial registration ClinicalTrials.gov: NCT00852423
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- 2021
39. The Effect of Intermittent Preventive Treatment of Malaria During Pregnancy and Placental Malaria on Infant Risk of Malaria
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Liana R. Andronescu, Julie Gutman, Ankur Markand Sharma, Ingrid Peterson, Jobiba Chinkhumba, Miriam K. Laufer, Martin Kachingwe, Don P. Mathanga, Witness Kachepa, and Yuanyuan Liang
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Adult ,Malawi ,medicine.medical_specialty ,Season of birth ,Placenta ,030231 tropical medicine ,Population ,Parasitemia ,Piperazines ,Major Articles and Brief Reports ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,Dihydroartemisinin/piperaquine ,Pregnancy ,Sulfadoxine ,parasitic diseases ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,education ,education.field_of_study ,business.industry ,Obstetrics ,Incidence (epidemiology) ,Infant ,medicine.disease ,Artemisinins ,Sulfadoxine/pyrimethamine ,Malaria ,Drug Combinations ,Regimen ,Pyrimethamine ,Treatment Outcome ,Infectious Diseases ,Pregnancy Complications, Parasitic ,Quinolines ,Female ,business ,medicine.drug - Abstract
Background Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) provides greater protection from placental malaria than sulfadoxine-pyrimethamine (SP). Some studies suggest placental malaria alters risk of malaria infection in infants, but few have quantified the effect of IPTp on infant susceptibility to malaria. Methods Infants born to women enrolled in a randomized clinical trial comparing IPTp-SP and IPTp-DP in Malawi were followed from birth to 24 months to assess effect of IPTp and placental malaria on time to first malaria episode and Plasmodium falciparum incidence. Results In total, 192 infants born to mothers randomized to IPTp-SP and 195 randomized to IPTp-DP were enrolled. Infants in IPTp exposure groups did not differ significantly regarding incidence of clinical malaria (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], .58–1.86) or incidence of infection (IRR, 1.18; 95% CI, .92–1.55). Placental malaria exposure was not associated with incidence of clinical malaria (IRR, 1.03; 95% CI, .66–1.59) or infection (IRR, 1.15; 95% CI, .88–1.50). Infant sex, season of birth, and maternal gravidity did not confound results. Conclusions We did not find evidence that IPTp regimen or placental malaria exposure influenced risk of malaria during infancy in this population. Clinical Trials Registration. NCT03009526
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- 2021
40. Population Attributable Fraction of Anemia Associated with Plasmodium falciparum Infection in Children in Southern Malawi
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Jenna E. Coalson, Doris P. Yimgang, Atupele Kapito-Tembo, Miriam K. Laufer, Don P. Mathanga, Lauren M. Cohee, Andrea G. Buchwald, Andy Bauleni, Jenny A. Walldorf, and Terrie E. Taylor
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Male ,Wet season ,Malawi ,medicine.medical_specialty ,Adolescent ,Anemia ,030231 tropical medicine ,Population ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Virology ,Internal medicine ,parasitic diseases ,Dry season ,Prevalence ,medicine ,Humans ,Malaria, Falciparum ,Child ,education ,education.field_of_study ,business.industry ,Age Factors ,Articles ,medicine.disease ,Cross-Sectional Studies ,Infectious Diseases ,Falciparum infection ,Attributable risk ,Etiology ,Female ,Parasitology ,Seasons ,business ,Malaria - Abstract
Anemia is a leading cause of morbidity in sub-Saharan Africa. The etiologies of anemia are multifactorial, and it is unclear what proportion of anemia is attributable to malaria in children of different ages in Malawi. We evaluated the population attributable fraction (PAF) of anemia due to malaria using multiple cross-sectional surveys in southern Malawi. We found a high prevalence of anemia, with the greatest proportion attributable to malaria among school-age children (5–15 years) in the rainy season (PAF = 18.8% [95% CI: 16.3, 21.0], compared with PAF = 5.2% [95% CI: 4.0, 6.2] among young children pooled across season [< 5 years] and PAF = 9.7% [95% CI: 6.5, 12.4] among school-age children in the dry season). Malaria control interventions will likely lead to decreases in anemia, especially among school-age children.
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- 2021
41. Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi
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Doreen Ali, Terrie E. Taylor, Clarissa Valim, Osward M. Nyirenda, Paul Pensulo, Atupele Kapito-Tembo, Andrew Bauleni, Miriam K. Laufer, and Don P. Mathanga
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Male ,Malawi ,medicine.medical_specialty ,Adolescent ,Endemic Diseases ,Fever ,030231 tropical medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Ambulatory care ,Musculoskeletal Pain ,Sepsis ,Virology ,Trimethoprim, Sulfamethoxazole Drug Combination ,Health care ,Ambulatory Care ,Prevalence ,Humans ,Medicine ,Outpatient clinic ,Disease management (health) ,Medical prescription ,Medical diagnosis ,Young adult ,Child ,Respiratory Tract Infections ,business.industry ,Soft Tissue Infections ,Amoxicillin ,Disease Management ,Articles ,medicine.disease ,Anti-Bacterial Agents ,Gastroenteritis ,Malaria ,Infectious Diseases ,Child, Preschool ,Emergency medicine ,Female ,Parasitology ,business - Abstract
Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim–sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.
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- 2020
42. Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials
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Don P. Mathanga, Alinune N. Kabaghe, Tobias Chirwa, Victor Mwapasa, Lawrence N. Kazembe, Mavuto Mukaka, Noel Patson, Marinus J.C. Eijkemans, Kennedy Otwombe, and Miriam K. Laufer
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Adult ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Statistical methods ,lcsh:RC955-962 ,030231 tropical medicine ,Chemoprevention ,law.invention ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antimalarials ,0302 clinical medicine ,Clinical trials ,Randomized controlled trial ,law ,Pregnancy ,Chi-square test ,Medicine ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Pregnancy Complications, Infectious ,Adverse effect ,Randomized Controlled Trials as Topic ,Descriptive statistics ,business.industry ,Research ,Prevention ,Missing data ,medicine.disease ,3. Good health ,Malaria ,Clinical trial ,Exact test ,Infectious Diseases ,13. Climate action ,Data Interpretation, Statistical ,Emergency medicine ,Parasitology ,Female ,Safety ,business - Abstract
Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. Methods The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher’s exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann–Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.
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- 2020
43. Lack of Decline in Childhood Malaria, Malawi, 2001–2010
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Arantxa Roca-Feltrer, Collins J. Kwizombe, Miguel A. Sanjoaquin, Sanie S.S. Sesay, Brian Faragher, Jim Harrison, Karen Geukers, Storn Kabuluzi, Don P. Mathanga, Elizabeth Molyneux, Maganizo Chagomera, Terrie Taylor, Malcolm Molyneux, and Robert S. Heyderman
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malaria ,parasites ,trends ,hospital ,urban ,children ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum–positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts.
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- 2012
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44. Understanding the Intransigence of Malaria in Malawi
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Lauren M. Cohee, Jessy Goupeyou-Youmsi, Karl B. Seydel, Charles Mangani, Peter Ntenda, Alick Sixpence, Rex B. Mbewe, Alfred Matengeni, Shannon Takala-Harrison, Edward D. Walker, Mark L. Wilson, Themba Mzilahowa, Miriam K. Laufer, Clarissa Valim, Terrie E. Taylor, and Don P. Mathanga
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Insecticides ,Malawi ,Mosquito Control ,Piperonyl Butoxide ,Mosquito Vectors ,Malaria ,Insecticide Resistance ,Infectious Diseases ,Virology ,Child, Preschool ,Animals ,Humans ,Parasitology ,Insecticide-Treated Bednets ,Child - Abstract
Despite the scale-up of interventions against malaria over the past decade, this disease remains a leading threat to health in Malawi. To evaluate the epidemiology of both Plasmodium falciparum infection and malaria disease, the Malawi International Center of Excellence for Malaria Research (ICEMR) has developed and implemented diverse and robust surveillance and research projects. Descriptive studies in ICEMR Phase 1 increased our understanding of the declining effectiveness of long-lasting insecticidal nets (LLINs), the role of school-age children in malaria parasite transmission, and the complexity of host–parasite interactions leading to disease. These findings informed the design of ICEMR Phase 2 to test hypotheses about LLIN use and effectiveness, vector resistance to insecticides, demographic targets of malaria control, patterns and causes of asymptomatic to life-threatening disease, and the impacts of RTS,S vaccination plus piperonyl butoxide-treated LLINs on infection and disease in young children. These investigations are helping us to understand mosquito-to-human and human-to-mosquito transmission in the context of Malawi's intransigent malaria problem.
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- 2021
45. An urban-to-rural continuum of malaria risk: new analytic approaches characterize patterns in Malawi
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Veronica J. Berrocal, Don P. Mathanga, Peter S Larson, Joseph N. S. Eisenberg, and Mark L. Wilson
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Male ,Rural Population ,Malawi ,Urban Population ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 ,law.invention ,Risk Factors ,law ,Arctic medicine. Tropical medicine ,80 and over ,Prevalence ,2.2 Factors relating to the physical environment ,Urbanicity ,Aetiology ,Child ,Aged, 80 and over ,Middle Aged ,Remote sensing ,Infectious Diseases ,Geography ,Transmission (mechanics) ,Medical Microbiology ,Child, Preschool ,Public Health and Health Services ,Female ,Metric (unit) ,Infection ,Adult ,medicine.medical_specialty ,Adolescent ,Malaria prevention ,Microbiology ,Young Adult ,Rare Diseases ,Tropical Medicine ,Environmental health ,parasitic diseases ,medicine ,Humans ,Risk factor ,Preschool ,Aged ,Research ,Public health ,Spatial analysis ,Infant ,medicine.disease ,Environmental risk ,Malaria ,Vector-Borne Diseases ,Good Health and Well Being ,Predictive power ,Parasitology ,Rural area ,Blood sampling - Abstract
Background The urban–rural designation has been an important risk factor in infectious disease epidemiology. Many studies rely on a politically determined dichotomization of rural versus urban spaces, which fails to capture the complex mosaic of infrastructural, social and environmental factors driving risk. Such evaluation is especially important for Plasmodium transmission and malaria disease. To improve targeting of anti-malarial interventions, a continuous composite measure of urbanicity using spatially-referenced data was developed to evaluate household-level malaria risk from a house-to-house survey of children in Malawi. Methods Children from 7564 households from eight districts throughout Malawi were tested for presence of Plasmodium parasites through finger-prick blood sampling and slide microscopy. A survey questionnaire was administered and latitude and longitude coordinates were recorded for each household. Distances from households to features associated with high and low levels of development (health facilities, roads, rivers, lakes) and population density were used to produce a principal component analysis (PCA)-based composite measure for all centroid locations of a fine geo-spatial grid covering Malawi. Regression methods were used to test associations of the urbanicity measure against Plasmodium infection status and to predict parasitaemia risk for all locations in Malawi. Results Infection probability declined with increasing urbanicity. The new urbanicity metric was more predictive than either a governmentally defined rural/urban dichotomous variable or a population density variable. One reason for this was that 23% of cells within politically defined rural areas exhibited lower risk, more like those normally associated with “urban” locations. Conclusions In addition to increasing predictive power, the new continuous urbanicity metric provided a clearer mechanistic understanding than the dichotomous urban/rural designations. Such designations often ignore urban-like, low-risk pockets within traditionally rural areas, as were found in Malawi, along with rural-like, potentially high-risk environments within urban areas. This method of characterizing urbanicity can be applied to other infectious disease processes in rapidly urbanizing contexts.
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- 2021
46. A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Malawi
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Beth Rubenstein, Jobiba Chinkhumba, Ethel Chilima, Collins Kwizombe, Ashley Malpass, Shelby Cash, Katherine Wright, Peter Troell, Humphrey Nsona, Fannie Kachale, Doreen Ali, Evans Kaunda, Sosten Lankhulani, Michael Kayange, Don P Mathanga, John Munthali, and Julie Gutman
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Malawi ,Infant, Newborn ,Prenatal Care ,Malaria ,Antimalarials ,Drug Combinations ,Infectious Diseases ,Pyrimethamine ,Pregnancy ,Pregnancy Complications, Parasitic ,parasitic diseases ,Sulfadoxine ,Humans ,Parasitology ,Female - Abstract
Background Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. Methods A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3 + and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n = 370, December 2017) and endline (n = 687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. Results Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0–5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0–9 doses). Despite overall increases, the change in IPTp3 + coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4 + coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). Conclusions In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers’ delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. Trial registration: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217.
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- 2021
47. The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens
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Andreea Waltmann, Elizabeth T. Rogawski McQuade, Jobiba Chinkhumba, Darwin J. Operario, Enala Mzembe, Megumi Itoh, Michael Kayange, Sydney M. Puerto-Meredith, Don P. Mathanga, Jonathan J. Juliano, Ian Carroll, Luther A. Bartelt, Julie R. Gutman, and Steven R. Meshnick
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Cryptosporidiosis ,Cryptosporidium ,Infant ,General Medicine ,General Biochemistry, Genetics and Molecular Biology ,Gestational Weight Gain ,Malaria ,Antimalarials ,Drug Combinations ,Pyrimethamine ,Pregnancy ,Pregnancy Complications, Parasitic ,Sulfadoxine ,Escherichia coli ,Birth Weight ,Humans ,Female - Abstract
Poor pregnancy and birth outcomes are common in sub-Saharan Africa and have complex aetiologies. Sulfadoxine-pyrimethamine (SP), given for intermittent preventive therapy of malaria in pregnancy (IPTp), is one of few existing interventions that improves outcomes of both mother and baby despite widespread SP-resistant malaria. Compelling evidence exists that malaria-independent pathways contribute to this protective effect, but the exact sources of non anti-malarial protection remained unknown. We hypothesized that the beneficial effect of SP on birthweight is mediated by SP activity on maternal factors, including increased gestational weight gain and antibiotic activity on pathogens in the maternal gut.Expectant mothers from a larger randomized control trial comparing the efficacy of IPTp-SP to IPTp with dihydroartemisinin-piperaquine (DP) were also enrolled in this sub-study study at their first antenatal care visit before commencement of IPTp (n = 105). Participants were followed monthly until delivery. Weights and mid-to-upper-arm circumferences (MUAC) were recorded. Monthly stool samples were collected and screened for five Escherichia coli pathotypes, Shigella spp., Vibrio cholerae, Salmonella, Campylobacter coli/jejuni, and three protozoa (Giardia spp., Entameba histolytica, and Cryptosporidium spp.) using previously validated molecular assays.IPTp-SP vs. IPTP-DP was associated with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). GWG was found to be a mediator of the birthweight and IPTp-SP relationship, as the birthweight of SP infants, but not DP infants, varied according to maternal GWG. The burden of maternal enteric infections was high. The three most commonly observed pathogens were enteroaggregative E. coli (EAEC), atypical enteropathogenic E.coli/enterohaemorrhagic E. coli (aEPEC/EHEC), and typical enteropathogenic E.coli (tEPEC). We found that SP reduced the prevalence of EAEC in a dose-dependent manner. After 3 or more doses, SP-recipients were 90% less likely to be infected with EAEC compared to DP-recipients (OROur findings indicate that in pregnant Malawian women, IPTp-SP vs. IPTp-DP is consistently associated with higher MUAC, BMI, and GWG following the WHO-recommended regimen of at least 3 doses, but carriage of maternal gut pathogens before initiation of IPTp lessens this effect. Because GWG was a mediator of the association between birthweight and SP, we show that SP's previously proven positive effect on birthweight is by promoting maternal weight gain. Overall, our results present one plausible pathway SP exerts malaria-independent protection against poor birth outcomes in the context of its waning antimalarial activity and warrants further investigation.A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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- 2021
48. Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014-2018
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Ally Mohamad, Simran Dhal, Pedro Rafael Dimbu, Aaron M. Samuels, Gauthier Mesia Kahunu, Eric S. Halsey, Eldin Talundzic, Meera Venkatesan, Naomi W. Lucchi, Leah F. Moriarty, Don P. Mathanga, Zhiyong Zhou, Ousmane Koita, Abdoul Habib Beavogui, Venkatachalam Udhayakumar, Adicatou-Laï Adeothy, Mateusz M. Plucinski, Samaly S. Svigel, Sarah E. Schmedes, Julie Gutman, Moonga Hawela, Simon Kariuki, Julia Kelley, Dhruviben Patel, Deus S. Ishengoma, and Papy Mandoko Nkoli
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Microbiology (medical) ,Nonsynonymous substitution ,Pfk13 mutations ,Epidemiology ,030231 tropical medicine ,Plasmodium falciparum ,Drug Resistance ,Protozoan Proteins ,malaria ,Drug resistance ,Infectious and parasitic diseases ,RC109-216 ,artemisinin resistance ,parasites ,medicine.disease_cause ,03 medical and health sciences ,symbols.namesake ,Antimalarials ,0302 clinical medicine ,Antibiotic resistance ,parasitic diseases ,medicine ,Humans ,030212 general & internal medicine ,antimicrobial resistance ,Malaria, Falciparum ,Sanger sequencing ,Mutation ,biology ,Research ,kelch 13 ,Plasmodium falciparum kelch13 Mutations, 9 Countries in Africa, 2014–2018 ,molecular surveillance ,biology.organism_classification ,medicine.disease ,Virology ,Kenya ,Infectious Diseases ,Africa ,symbols ,Medicine ,Synonymous substitution ,Malaria - Abstract
The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations.
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- 2021
49. Impact of Multiplicity of Plasmodium falciparum Infection on Clinical Disease in Malawi
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Miriam K. Laufer, Dominique Earland, Andrea G. Buchwald, Milius Damson, Terrie E. Taylor, Alick Sixpence, Mabvuto Chimenya, Karl B. Seydel, and Don P. Mathanga
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biology ,business.industry ,viruses ,030231 tropical medicine ,Repeated measures design ,Plasmodium falciparum ,Disease ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,Multiplicity of infection ,Virology ,Immunology ,Genotype ,medicine ,Parasitology ,medicine.symptom ,Risk factor ,business ,Malaria - Abstract
Multiplicity of infection (MOI), the number of unique Plasmodium falciparum parasite genotypes found in one infected individual, may contribute to the development of clinical malaria disease. However, the independent contribution of MOI and parasite density to clinical disease has not been well characterized. We conducted a two-year longitudinal cohort study of adults and children in a high-transmission setting in Malawi to test the hypothesis that increased MOI was independently associated with clinical disease, after accounting for parasite density. Of 1,062 episodes of infection, 477 (44.9%) were associated with symptoms. After controlling for repeated measures within an individual, key demographic factors, and parasite density, there was no association between MOI and clinical disease (OR = 1.02, 95% CI: 0.70-1.51). Although the limited ability to discern MOI in low-density asymptomatic infections may have impacted our results, we conclude that MOI is not an independent risk factor for clinical disease.
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- 2019
50. The Effect of Text Message Reminders to Health Workers on Quality of Care for Malaria, Pneumonia, and Diarrhea in Malawi: A Cluster-Randomized, Controlled Trial
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Andy Bauleni, Ruth J. Namuyinga, Alexander K. Rowe, Humphreys Nsona, Monica P. Shah, Miwako Kobayashi, Don P. Mathanga, Austin Gumbo, Dyson Mwandama, Dubulao Moyo, Peter Troell, Dejan Zurovac, and Laura C. Steinhardt
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Adult ,Diarrhea ,Male ,Malawi ,medicine.medical_specialty ,Adolescent ,Health Personnel ,030231 tropical medicine ,Psychological intervention ,Disease cluster ,Ambulatory Care Facilities ,law.invention ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Virology ,Internal medicine ,medicine ,Cluster Analysis ,Humans ,Medical prescription ,Child ,Aged ,Quality of Health Care ,Text Messaging ,business.industry ,Pneumonia ,Articles ,Middle Aged ,medicine.disease ,Telemedicine ,Confidence interval ,Anti-Bacterial Agents ,Intention to Treat Analysis ,Malaria ,Infectious Diseases ,Practice Guidelines as Topic ,Female ,Parasitology ,Guideline Adherence ,medicine.symptom ,business - Abstract
The use of mobile technologies in medicine, or mHealth, holds promise to improve health worker (HW) performance, but evidence is mixed. We conducted a cluster-randomized controlled trial to evaluate the effect of text message reminders to HWs in outpatient health facilities (HFs) on quality of care for malaria, pneumonia, and diarrhea in Malawi. After a baseline HF survey (2,360 patients) in January 2015, 105 HFs were randomized to three arms: 1) text messages to HWs on malaria case management; 2) text messages to HWs on malaria, pneumonia, and diarrhea case management (latter two for children < 5 years); and 3) control arm (no messages). Messages were sent beginning April 2015 twice daily for 6 months, followed by an endline HF survey (2,536 patients) in November 2015. An intention-to-treat analysis with difference-in-differences binomial regression modeling was performed. The proportion of patients with uncomplicated malaria managed correctly increased from 42.8% to 59.6% in the control arm, from 43.7% to 55.8% in arm 1 (effect size −4.7%-points, 95% confidence interval (CI): −18.2, 8.9, P = 0.50) and from 30.2% to 50.9% in arm 2 (effect size 3.9%-points, 95% CI: −14.1, 22.0, P = 0.67). Prescription of first-line antibiotics to children < 5 years with clinically defined pneumonia increased in all arms, but decreased in arm 2 (effect size −4.1%-points, 95% CI: −42.0, 33.8, P = 0.83). Prescription of oral rehydration solution to children with diarrhea declined slightly in all arms. We found no significant improvements in malaria, pneumonia, or diarrhea treatment after HW reminders, illustrating the importance of rigorously testing new interventions before adoption.
- Published
- 2019
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