Publications by authors named "Jane Achan"

96 Publications

Mass drug administration of ivermectin and dihydroartemisinin-piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia.

Lancet Infect Dis 2022 04 15;22(4):519-528. Epub 2021 Dec 15.

Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia.

Background: Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin-piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions.

Methods: This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7-46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin-piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300-400 μg/kg per day for 3 consecutive days] and dihydroartemisinin-piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin-piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313.

Findings: Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin-piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention.

Interpretation: The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin-piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed.

Funding: Joint Global Health Trials Scheme.

Translation: For the French translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00557-0DOI Listing
April 2022

Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda.

Lancet Microbe 2022 Jan 25;3(1):e62-e71. Epub 2021 Oct 25.

Global Technical Team, Malaria Consortium, London, UK.

Background: The potential effects of SARS-CoV-2 and co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and co-infection in a high-burden malaria setting.

Methods: This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous exposure was determined with serological responses to a panel of antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0-20 years, 21-40 years, 41-60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with infection versus those without infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to versus those with high previous exposure to . The effect of previous exposure to on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities.

Findings: Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28-47). Overall prevalence of infection was 12% (95% CI 9·4-14·6; 70 of 597 participants), with highest prevalence in the age groups of 0-20 years (22%, 8·7-44·8; five of 23 patients) and older than 60 years (20%, 10·2-34·1; nine of 46 patients). Confusion (four [6%] of 70 patients eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients five [1%] of 527 patients; p=0·014] were more frequent among patients with infection than those without. Patients with low versus those with high previous exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high exposure (six [18%] of 33 patients one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0-75·5; p=0·049).

Interpretation: Although patients with COVID-19 with co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections.

Funding: Malaria Consortium (USA).
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http://dx.doi.org/10.1016/S2666-5247(21)00240-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545833PMC
January 2022

Costs and barriers faced by households seeking malaria treatment in the Upper River Region, The Gambia.

Malar J 2021 Sep 16;20(1):368. Epub 2021 Sep 16.

MRC The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.

Background: Malaria transmission in The Gambia decreased substantially over the last 20 years thanks to the scale-up of control interventions. However, malaria prevalence is still relatively high in eastern Gambia and represents both a health and a financial burden for households. This study aims to quantify the out-of-pocket costs and productivity losses of seeking malaria treatment at household level.

Methods: A household survey was carried out through in-person interviews. Respondents were asked about malaria prevention methods, their treatment-seeking behaviour, and any costs incurred for transport, services, food, and/or overnight stays. A bottom-up costing approach was used to calculate the unit cost of treatment and a tobit regression approach to investigate cost drivers.

Results: The survey included 864 respondents, mainly subsistence farmers. Most respondents (87%) considered malaria to be a problem affecting their ability to perform their regular duties. Respondents preferred going to a health facility for treatment. The primary reason for not going was related to costs; 70% of respondents incurred costs for seeking health care, with a median of £3.62 (IQR: £1.73 to £6.10). The primary driver of cost was living in one of the villages that are off the main road and/or far from health facilities. 66% reported productivity loss of 5 working days on average during a malaria episode of them or their child.

Conclusions: Although malaria prevalence is decreasing and treatment is provided free of charge, households seeking treatment are confronted with out-of-pocket expenditures and lost working days; particularly in remote villages.
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http://dx.doi.org/10.1186/s12936-021-03898-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447575PMC
September 2021

An assessment of the knowledge, practices and resources during the delivery of malaria health care services among private health care practitioners: a cross section study in the Mid-Western Region of Uganda.

BMC Health Serv Res 2021 Aug 10;21(1):788. Epub 2021 Aug 10.

Uganda Paediatric Association, Kampala, Uganda.

Background: Approximately 50 % of the population in Uganda seeks health care from private facilities but there is limited data on the quality of care for malaria in these facilities. This study aimed to document the knowledge, practices and resources during the delivery of malaria care services, among private health practitioners in the Mid-Western region of Uganda, an area of moderate malaria transmission.

Methods: This was a cross sectional study in which purposive sampling was used to select fifteen private-for-profit facilities from each district. An interviewer-administered questionnaire that contained both quantitative and open-ended questions was used. Information was collected on availability of treatment aides, knowledge on malaria, malaria case management, laboratory practices, malaria drugs stock and data management. We determined the proportion of health workers that adequately provided malaria case management according to national standards.

Results: Of the 135 health facilities staff interviewed, 61.48 % (52.91-69.40) had access to malaria treatment protocols while 48.89 % (40.19-57.63) received malaria training. The majority of facilities, 98.52 % (94.75-99.82) had malaria diagnostic services and the most commonly available anti-malarial drug was artemether-lumefantrine, 85.19 % (78-91), followed by Quinine, 74.81 % (67-82) and intravenous artesunate, 72.59 % (64-80). Only 14.07 % (8.69-21.10) responded adequately to the acceptable cascade of malaria case management practice. Specifically, 33.33 % (25.46-41.96) responded correctly to management of a patient with a fever, 40.00 % (31.67-48.79) responded correctly to the first line treatment for uncomplicated malaria, whereas 85.19 % (78.05-90.71) responded correctly to severe malaria treatment. Only 28.83 % submitted monthly reports, where malaria data was recorded, to the national database.

Conclusions: This study revealed sub-optimal malaria case management knowledge and practices at private health facilities with approximately 14 % of health care workers demonstrating correct malaria case management cascade practices. To strengthen the quality of malaria case management, it is recommended that the NMCD distributes current guidelines and tools, coupled with training; continuous mentorship and supportive supervision; provision of adequate stock of essential anti-malarials and RDTs; reinforcing communication and behavior change; and increasing support for data management at private health facilities.
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http://dx.doi.org/10.1186/s12913-021-06849-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356442PMC
August 2021

Infectivity of patent Plasmodium falciparum gametocyte carriers to mosquitoes: establishing capacity to investigate the infectious reservoir of malaria in a low-transmission setting in The Gambia.

Trans R Soc Trop Med Hyg 2021 12;115(12):1462-1467

Department of Infection Biology, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK.

Background: Understanding the human malaria infectious reservoir is important for elimination initiatives. Here, we implemented mosquito membrane feeding experiments to prepare for larger studies to quantify the transmission potential and relative contribution of the human infectious reservoir.

Methods: Patients with clinical malaria attending four health facilities with at least 16 Plasmodium falciparum gametocytes per μL were recruited during the 2018 transmission season. Infectiousness to mosquitoes was assessed by direct membrane feeding assay (DMFA). We compared our results with a Bayesian predictive model to investigate the relationship between infectiousness and gametocyte density and explore the impact of fever on gametocyte infectivity.

Results: A total of 3177 suspected malaria cases were screened; 43.3% (1376) had microscopically patent P. falciparum parasites and 3.6% (114) of them had gametocytes. Out of 68 DMFAs, 38 (55.9%) resulted in at least one infected mosquito, with a total of 15.4% (1178/7667) of mosquitoes infected with 1-475 oocysts per gut. The relationship between mosquito infection prevalence and gametocytaemia was similar to other African settings and negatively associated with fever (OR: 0.188, 95% CI 0.0603 to 0.585, p=0.0039).

Conclusions: Among symptomatic malaria patients, fever is strongly associated with transmission failure. Future studies can use DMFA to better understand the human malaria reservoir in settings of low endemicity in The Gambia and inform malaria elimination initiatives.
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http://dx.doi.org/10.1093/trstmh/trab087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643495PMC
December 2021

Reactive, self-administered malaria treatment against asymptomatic malaria infection: results of a cluster randomized controlled trial in The Gambia.

Malar J 2021 Jun 7;20(1):253. Epub 2021 Jun 7.

Medical Research Council Unit The Gambia At the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.

Background: Selectively targeting and treating malaria-infected individuals may further decrease parasite carriage in low-burden settings. Using a trans-disciplinary approach, a reactive treatment strategy to reduce Plasmodium falciparum prevalence in participating communities was co-developed and tested.

Methods: This is a 2-arm, open-label, cluster-randomized trial involving villages in Central Gambia during the 2017 and 2018 malaria transmission season. Villages were randomized in a 1:1 ratio using a minimizing algorithm. In the intervention arm, trained village health workers delivered a full course of pre-packed dihydroartemisinin-piperaquine to all residents of compounds where clinical cases were reported while in the control arm, compound residents were screened for infection at the time of the index case reporting. All index cases were treated following national guidelines. The primary endpoint was malaria prevalence, determined by molecular methods, at the end of the intervention period.

Results: The trial was carried out in 50 villages: 34 in 2017 and 16 additional villages in 2018. At the end of the 2018 transmission season, malaria prevalence was 0.8% (16/1924, range 0-4%) and 1.1% (20/1814, range 0-17%) in the intervention and control arms, respectively. The odds of malaria infection were 29% lower in the intervention than in the control arm after adjustment for age (OR 0.71, 95% CI 0.27-1.84, p = 0.48). Adherence to treatment was high, with 98% (964/979) of those treated completing the 3-day treatment. Over the course of the study, only 37 villages, 20 in the intervention and 17 in the control arm, reported at least one clinical case. The distribution of clinical cases by month in both transmission seasons was similar and the odds of new clinical malaria cases during the trial period did not vary between arms (OR 1.04, 95% CI 0.57-1.91, p = 0.893). All adverse events were classified as mild to moderate and resolved completely.

Conclusion: The systematic and timely administration of an anti-malarial treatment to residents of compounds with confirmed malaria cases did not significantly decrease malaria prevalence and incidence in communities where malaria prevalence was already low. Treatment coverage and adherence was very high. Results were strongly influenced by the lower-than-expected malaria prevalence, and by no clinical cases in villages with asymptomatic malaria-infected individuals.

Trial Registration: This study is registered with ClinicalTrials.gov, NCT02878200. Registered 25 August 2016. https://clinicaltrials.gov/ct2/show/NCT02878200 .
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http://dx.doi.org/10.1186/s12936-021-03761-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186162PMC
June 2021

The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis.

PLoS One 2021 24;16(5):e0251101. Epub 2021 May 24.

Malaria Consortium, London, United Kingdom.

Introduction: Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks.

Methods: We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity.

Results: From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)/Pl(+) and EBOV(+)/Pl(-) cases (62.8%, 95% CI 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway.

Conclusion: The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251101PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143409PMC
October 2021

Efficacy, Safety and Tolerability of Pyronaridine-artesunate in Asymptomatic Malaria-infected Individuals: a Randomized Controlled Trial.

Clin Infect Dis 2022 01;74(2):180-188

Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia.

Background: Pyronaridine-artesunate (PA) is a registered artemisinin-based combination therapy, potentially useful for mass drug administration campaigns. However, further data are needed to evaluate its efficacy, safety and tolerability as full or incomplete treatment in asymptomatic Plasmodium falciparum-infected individuals.

Methods: This phase II, multi-center, open label, randomized clinical trial was conducted in The Gambia and Zambia. Participants with microscopically confirmed asymptomatic P. falciparum infection were randomly assigned (1:1:1) to receive a 3-day, 2-day, or 1-day treatment regimen of PA (180:60 mg), dosed according to bodyweight. The primary efficacy outcome was polymerase chain reaction (PCR)-adjusted adequate parasitological response (APR) at day 28 in the per-protocol population.

Results: A total of 303 participants were randomized. Day 28 PCR-adjusted APR was 100% for both the 3-day (98/98) and 2-day regimens (96/96), and 96.8% (89/94) for the 1-day regimen. Efficacy was maintained at 100% until day 63 for the 3-day and 2-day regimens but declined to 94.4% (84/89) with the 1-day regimen. Adverse event frequency was similar between the 3-day (51.5% [52/101]), 2-day (52.5% [52/99]), and 1-day (54.4% [56/103]) regimens; the majority of adverse events were of grade 1 or 2 severity (85% [136/160]). Asymptomatic, transient increases (>3 times the upper limit of normal) in alanine aminotransferase/aspartate aminotransferase were observed for 6/301 (2.0%) participants.

Conclusions: PA had high efficacy and good tolerability in asymptomatic P. falciparum-infected individuals, with similar efficacy for the full 3-day and incomplete 2-day regimens. Although good adherence to the 3-day regimen should be encouraged, these results support the further investigation of PA for mass drug administration campaigns.

Clinical Trials Registration: NCT03814616.
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http://dx.doi.org/10.1093/cid/ciab425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800175PMC
January 2022

From informed consent to adherence: factors influencing involvement in mass drug administration with ivermectin for malaria elimination in The Gambia.

Malar J 2021 Apr 26;20(1):198. Epub 2021 Apr 26.

Unit of Socio-Ecological Health Research, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium.

Background: The World Health Organization (WHO) recommends consideration of mass drug administration (MDA) for malaria control in low-endemic settings approaching elimination. However, MDA remains a controversial strategy, as multiple individual, social, and operational factors have shown to affect its acceptability at local levels. This is further complicated by inconsistent definitions of key indicators derived from individual and community involvement-coverage, adherence, and compliance-that cast doubts about the actual and potential epidemiological impact of MDA on disease control and elimination. This study aimed to identify limitations and enabling factors impacting involvement at different stages of a large cluster-randomized trial assessing the effect of combining dihydroartemisinin-piperaquine (DP) and ivermectin (IVM) in malaria transmission in The Gambia.

Methods: This social science study used a mixed-methods approach. Qualitative data were collected in intervention and control villages through ethnographic methods, including in-depth interviews (IDIs), focus group discussions (FGDs), and participant observation conducted with trial participants and decliners, community leaders, and field staff. A cross-sectional survey was conducted in the intervention villages after the first year of MDA. Both strands of the study explored malaria knowledge and opinions, social dynamics influencing decision-making, as well as perceived risks, burdens, and benefits associated with this MDA.

Results: 157 IDIs and 11 FGDs were conducted, and 864 respondents were included in the survey. Barriers and enabling factors to involvement were differentially influential at the various stages of the MDA. Issues of social influence, concerns regarding secondary effects of the medication, costs associated with malaria, and acceptability of the implementing organization, among other factors, differently affected the decision-making processes throughout the trial. Rather than a linear trajectory, involvement in this MDA trial was subjected to multiple revaluations from enrolment and consent to medicine intake and adherence to treatment.

Conclusions: This study went beyond the individual factors often associated with coverage and adherence, and found that nuanced social dynamics greatly influence the decision-making process at all phases of the trial. These issues need to be consider for MDA implementation strategies and inform discussions about more accurate ways of reporting on critical effectiveness indicators.
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http://dx.doi.org/10.1186/s12936-021-03732-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073909PMC
April 2021

Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children.

Malar J 2021 Mar 26;20(1):169. Epub 2021 Mar 26.

Disease Control and Elimination Theme, Medical Research Council Unit The Gambia At London, School of Hygiene and Tropical Medicine, P.O Box 273, Banjul, The Gambia.

Background: Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children.

Methods: The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24-59 months old who were eligible to receive SMC (SMC group) and children 5-8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression.

Results: During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14-2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20-4.95; p = 1.0).

Conclusion: In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.
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http://dx.doi.org/10.1186/s12936-021-03706-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995796PMC
March 2021

Complexities in Defining the Unit of Intervention for Reactive Community-Based Malaria Treatment in the Gambia.

Front Public Health 2021 26;9:601152. Epub 2021 Feb 26.

Medical Anthropology Unit, Institute of Tropical Medicine, Antwerp, Belgium.

With significant declines in malaria, infections are increasingly clustered in households, or groups of households where malaria transmission is higher than in surrounding household/villages. To decrease transmission in such cases, reactive interventions target household members of clinical malaria cases, with the intervention unit (e.g., the "household/s") derived from an epidemiological and operational perspective. A lack of unanimity regarding the spatial range of the intervention unit calls for greater importance to be placed on social context in conceptualizing the appropriate unit. A novel malaria elimination strategy based on reactive treatment was recently evaluated by a cluster randomized trial in a low transmission setting in The Gambia. Transdisciplinary research was used to assess and improve the effectiveness of the intervention which consisted, among others, of reflecting on whether the household was the most adequate unit of analysis. The intervention was piloted on the smallest treatment unit possible and was further adapted following a better understanding of the social and epidemiological context. Intervention units defined according to (i) shared sleeping spaces and (ii) household membership, showed substantial limitations as it was not possible to define them clearly and they were extremely variable within the study setting. Incorporating local definitions and community preference in the trial design led to the appropriate intervention unit-the compound-defined as an enclosed space containing one or several households belonging to the same extended patrilineal family. Our study demonstrates the appropriateness of using transdisciplinary research for investigating alternative intervention units that are better tailored to reactive treatment approaches.
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http://dx.doi.org/10.3389/fpubh.2021.601152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952428PMC
May 2021

Understanding adherence to reactive treatment of asymptomatic malaria infections in The Gambia.

Sci Rep 2021 01 18;11(1):1746. Epub 2021 Jan 18.

Medical Anthropology Unit, Institute of Tropical Medicine, Antwerp, Belgium.

The impact of different types of reactive case detection and/or treatment strategies for malaria elimination depends on high coverage and participants' adherence. However, strategies to optimise adherence are limited, particularly for people with asymptomatic or no infections. As part of a cluster-randomized trial to evaluate the effect of reactive treatment in The Gambia, all residents in the compound of a diagnosed clinical malaria patient received dihydro-artemisinin-piperaquine (DP). Using a mixed method approach, we assessed which factors contribute to adherence among the contacts of malaria cases that showed no symptoms. Adherence was defined as the proportion of compound members that (1) returned all medicine bags empty and (2) self-reported (3-day) treatment completion. Among the 273 individuals from 14 compounds who received DP, 227 (83.1%) were available for and willing to participate in the survey; 85.3% (233/273) returned empty medicine bags and 91.6% (208/227) self-reported treatment completion. Although clinical malaria was not considered a major health problem, reported adherence was high. The drivers of adherence were the strong sense of responsibility towards protecting the individual, compound and the village. Adherence can be optimised through a transdisciplinary implementation research process of engaging communities to bridge the gap between research goals and social realities.
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http://dx.doi.org/10.1038/s41598-021-81468-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813830PMC
January 2021

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial.

JMIR Res Protoc 2020 Nov 19;9(11):e20904. Epub 2020 Nov 19.

Medical Research Council Unit Gambia, London School of Hygiene and Tropical Medicine, Banjul, Gambia.

Background: With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission.

Objective: The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions.

Methods: The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans.

Results: The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked.

Conclusions: This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission.

Trial Registration: ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313.

International Registered Report Identifier (irrid): DERR1-10.2196/20904.
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http://dx.doi.org/10.2196/20904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714640PMC
November 2020

Adoption of evidence-based global policies at the national level: intermittent preventive treatment for malaria in pregnancy and first trimester treatment in Kenya, Malawi, Mali and The Gambia.

Health Policy Plan 2021 Feb;35(10):1364-1375

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

In 2012, the World Health Organization (WHO) updated its policy on intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP). A global recommendation to revise the WHO policy on the treatment of malaria in the first trimester is under review. We conducted a retrospective study of the national policy adoption process for revised IPTp-SP dosing in four sub-Saharan African countries. Alongside this retrospective study, we conducted a prospective policy adoption study of treatment of first trimester malaria with artemisinin combination therapies (ACTs). A document review informed development and interpretation of stakeholder interviews. An analytical framework was used to analyse data exploring stakeholder perceptions of the policies from 47 in-depth interviews with a purposively selected range of national level stakeholders. National policy adoption processes were categorized into four stages: (1) identify policy need; (2) review the evidence; (3) consult stakeholders and (4) endorse and draft policy. Actors at each stage were identified with the roles of evidence generation; technical advice; consultative and statutory endorsement. Adoption of the revised IPTp-SP policy was perceived to be based on strong evidence, support from WHO, consensus from stakeholders; and followed these stages. Poor tolerability of quinine was highlighted as a strong reason for a potential change in treatment policy. However, the evidence on safety of ACTs in the first trimester was considered weak. For some, trust in WHO was such that the anticipated announcement on the change in policy would allay these fears. For others, local evidence would first need to be generated to support a change in treatment policy. A national policy change from quinine to ACTs for the treatment of first trimester malaria will be less straightforward than experienced with increasing the IPTp dosing regimen despite following the same policy processes. Strong leadership will be needed for consultation and consensus building at national level.
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http://dx.doi.org/10.1093/heapol/czaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886437PMC
February 2021

The Impact of Control Interventions on Malaria Burden in Young Children in a Historically High-Transmission District of Uganda: A Pooled Analysis of Cohort Studies from 2007 to 2018.

Am J Trop Med Hyg 2020 08 14;103(2):785-792. Epub 2020 May 14.

7Department of Medicine, University of California San Francisco, San Francisco, California.

There is limited evidence on whether malaria elimination is feasible in high-transmission areas of Africa. Between 2007 and 2018, we measured the impact of malaria control interventions in young children enrolled in three clinical trials and two observational studies in Tororo, Uganda, a historically high-transmission area. Data were pooled from children aged 0.5-2 years. Interventions included individually assigned chemoprevention and repeated rounds of indoor residual spraying (IRS) of insecticide. All children received long-lasting insecticidal nets (LLINs) and treatment for symptomatic malaria with artemisinin-based combination therapy. Malaria incidence was measured using passive surveillance and parasite prevalence by microscopy and molecular methods at regular intervals. Poisson's generalized linear mixed-effects models were used to estimate the impact of various control interventions. In total, 939 children were followed over 1,221.7 person years. In the absence of chemoprevention and IRS (reference group), malaria incidence was 4.94 episodes per person year and parasite prevalence 47.3%. Compared with the reference group, implementation of IRS was associated with a 97.6% decrease (95% CI: 93.3-99.1%, = 0.001) in the incidence of malaria and a 96.0% decrease (95% CI: 91.3-98.2%, < 0.001) in parasite prevalence (both measured after the fifth and sixth rounds of IRS). The addition of chemoprevention with monthly dihydroartemisinin-piperaquine to IRS was associated with a 99.5% decrease (95% CI: 98.6-99.9%, < 0.001) in the incidence of malaria. In a historically high-malaria burden area of Uganda, a combination of LLINs, effective case management, IRS, and chemoprevention was associated with almost complete elimination of malaria in young children.
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http://dx.doi.org/10.4269/ajtmh.20-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410449PMC
August 2020

Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.

Lancet Infect Dis 2020 08 8;20(8):953-963. Epub 2020 Apr 8.

Department of Population Health and Disease Prevention and Department of Epidemiology, University of California, Irvine, CA, USA.

Background: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.

Methods: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia.

Findings: The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity.

Interpretation: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission.

Funding: Wellcome Trust.
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http://dx.doi.org/10.1016/S1473-3099(20)30059-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391005PMC
August 2020

The prevalence of scabies, pyoderma and other communicable dermatoses in the Bijagos Archipelago, Guinea-Bissau.

PLoS Negl Trop Dis 2019 11 18;13(11):e0007820. Epub 2019 Nov 18.

Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Introduction: Skin diseases represent a significant public health problem in most low and middle income settings. Nevertheless, there is a relative paucity of high-quality epidemiological data on the prevalence of these conditions.

Materials/methods: We conducted two cross-sectional population-based skin-surveys of children (6 months to 9 years old) in the Bijagós Archipelago of Guinea-Bissau during the dry season (February-March 2018) and the wet season (June-July 2018). Following a period of training, a nurse performed a standardised examination for communicable dermatoses for each participant. We calculated the prevalence of each skin condition and investigated demographic associations.

Results: 1062 children were enrolled in the dry season survey of whom 318 (29.9%) had at least one skin diseases. The most common diagnosis was tinea capitis (154/1062, 14.5% - 95% CI 12.5-16.8%) followed by tinea corporis (84/1062, 7.9% - 95% CI 6.4-9.7%), pyoderma (82/1062, 7.7% - 95% CI 6.2-9.5%) and scabies (56/1062. 5.2% - 95%CI 4.0-6.8%). 320 children were enrolled in the wet season survey of whom 121 (37.8%) had at least one skin problem. Tinea capitis remained the most common diagnosis (79/320, 24.7% - 95% CI 20.1-29.9%), followed by pyoderma (38/320, 11.9% - 95% CI 8.6-16.1%), tinea corporis (23/320, 7.2% - 95% 4.7-10.7%) and scabies (6/320, 1.9% - 95% CI 0.8-4.2%).

Conclusions: Our study, which utilised robust population-based cluster random sampling methodology, demonstrates the substantial disease burden caused by common communicable dermatoses in this setting. Given these findings, there is a need to consider common dermatoses as part of Universal Health Coverage to deliver 'skin-health for all'.
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http://dx.doi.org/10.1371/journal.pntd.0007820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886863PMC
November 2019

Perceptions, attitudes and practices towards scabies in communities on the Bijagós Islands, Guinea-Bissau.

Trans R Soc Trop Med Hyg 2020 01;114(1):49-56

Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Background: Scabies is highly endemic among impoverished populations and has been recently included in the WHO's list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and healthcare-seeking behaviours towards scabies in the Bijagós Archipelago of Guinea-Bissau.

Methods: Data were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis.

Results: There was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance.

Conclusions: There is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers' training and skin NTD integrated control programmes should address the challenges highlighted in this study.
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http://dx.doi.org/10.1093/trstmh/trz102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974396PMC
January 2020

Long-distance transmission patterns modelled from SNP barcodes of Plasmodium falciparum infections in The Gambia.

Sci Rep 2019 09 18;9(1):13515. Epub 2019 Sep 18.

Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.

Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distance likelihood model to determine transmission paths from a 54 SNP barcode of 355 isolates. Samples were collected monthly during the 2013 malaria season from six pairs of villages spanning 300 km from western to eastern Gambia. There was spatial and temporal hierarchy in pairwise genetic relatedness, with the most similar barcodes from isolates within the same households and village. Constrained by travel data, the model detected 60 directional transmission events, with 27% paths linking persons from different regions. We identified 13 infected individuals (4.2% of those genotyped) responsible for 2 to 8 subsequent infections within their communities. These super-infectors were mostly from high transmission villages. When considering paths between isolates from the most distant regions (west vs east) and travel history, there were 3 transmission paths from eastern to western Gambia, all at the peak (October) of the malaria transmission season. No paths with known travel originated from the extreme west to east. Although more than half of all paths were within-village, parasite flow from east to west may contribute to maintain transmission in western Gambia, where malaria transmission is already low. Therefore, interrupting malaria transmission in western Gambia would require targeting eastern Gambia, where malaria prevalence is substantially higher, with intensified malaria interventions.
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http://dx.doi.org/10.1038/s41598-019-49991-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751170PMC
September 2019

Field performance of the malaria highly sensitive rapid diagnostic test in a setting of varying malaria transmission.

Malar J 2019 Aug 27;18(1):288. Epub 2019 Aug 27.

Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, P.O. Box 273, Banjul, The Gambia.

Background: The Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated.

Methods: A cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA).

Results: Malaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9-16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2-42.71) and 88.5% (2922/3301; 95% CI 87.4-89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3-58.5%) in high prevalence villages (20-50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT.

Conclusion: The HS-RDT's field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.
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http://dx.doi.org/10.1186/s12936-019-2929-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712604PMC
August 2019

Serologic Markers of Previous Malaria Exposure and Functional Antibodies Inhibiting Parasite Growth Are Associated With Parasite Kinetics Following a Plasmodium falciparum Controlled Human Infection.

Clin Infect Dis 2020 06;70(12):2544-2552

Disease Control and Elimination Theme, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.

Background: We assessed the impact of exposure to Plasmodium falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in 2 cohorts with different levels of previous malarial exposure.

Methods: Nine adult males with high (sero-high) and 10 with low (sero-low) previous exposure received 3200 P. falciparum sporozoites (PfSPZ) of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction. Endpoints were time to parasitemia, adverse events, and immune responses.

Results: Ten of 10 (100%) volunteers in the sero-low and 7 of 9 (77.8%) in the sero-high group developed parasitemia detected by TBS in the first 28 days (P = .125). The median time to parasitemia was significantly shorter in the sero-low group than the sero-high group (9 days [interquartile range {IQR} 7.5-11.0] vs 11.0 days [IQR 7.5-18.0], respectively; log-rank test, P = .005). Antibody recognition of sporozoites was significantly higher in the sero-high (median, 17.93 [IQR 12.95-24] arbitrary units [AU]) than the sero-low volunteers (median, 10.54 [IQR, 8.36-12.12] AU) (P = .006). Growth inhibitory activity was significantly higher in the sero-high (median, 21.8% [IQR, 8.15%-29.65%]) than in the sero-low group (median, 8.3% [IQR, 5.6%-10.23%]) (P = .025).

Conclusions: CHMI was safe and well tolerated in this population. Individuals with serological evidence of higher malaria exposure were able to better control infection and had higher parasite growth inhibitory activity.

Clinical Trials Registration: NCT03496454.
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http://dx.doi.org/10.1093/cid/ciz740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286377PMC
June 2020

Improving the quality of neonatal data capture and clinical care at a tertiary-care hospital in Uganda through enhanced surveillance, training and mentorship.

Paediatr Int Child Health 2020 05 10;40(2):92-104. Epub 2019 Jul 10.

Uganda Paediatric Association, Kampala, Uganda.

: Accurate documentation of neonatal morbidity and mortality is limited in many countries in sub-Saharan Africa. This project aimed to establish a surveillance system for neonatal conditions as an approach to improving the quality of neonatal care.: A systematic data capture and surveillance system was established at Jinja Regional Referral Hospital, Uganda using a standardised neonatal medical record form which collected detailed individual patient level data. Additionally, training and mentorship were conducted and basic equipment was provided.: A total of 4178 neonates were hospitalised from July 2014 to December 2016. Median (IQR) age on admission was one day (1-3) and 48.0% (1851/3859) were male. Median (IQR) duration of hospitalisation was 17 days (IQR 10-40) and the longest duration of hospitalisation was 47 days (IQR 41-58). The majority were referrals from government health facilities (54.4%, 2012/3699), though 30.6% (1123/3669) presented as self-referrals. Septicaemia (44.9%, 1962/4371), prematurity (21.0%, 917/4371) and birth asphyxia (19.1%, 833/4371) were the most common diagnoses. The overall mortality was 13.8% (577/4178) and the commonest causes of death included septicaemia (26.9%, 155/577), prematurity (24.3%, 140/577), birth asphyxia (21.0%, 121/577), hypothermia (9.9%, 57/577) and respiratory distress (8.0%, 46/577). The majority of deaths (51.5%, 297/577) occurred within the first 24 h of hospitalisation although a significant proportion of deaths also occurred after 7 days of hospitalisation (24.1%, 139/577). A modest decrease in mortality and improvement in clinical outcome were observed.: Improvement in neonatal data capture and quality of care was observed following establishment of an enhanced surveillance system, training and mentorship.: aOR: adjusted odds ratio; CHRP: Centre for Health research and Programmes; HC: health centre; HMIS: Health Management Information System; JRRH: Jinja Regional Referral Hospital; NMRF: neonatal medical record form; PMTCT: prevention of mother-to-child transmission of HIV; UPA: Uganda Paediatric Association.
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http://dx.doi.org/10.1080/20469047.2019.1638131DOI Listing
May 2020

Reduced mosquito survival in metal-roof houses may contribute to a decline in malaria transmission in sub-Saharan Africa.

Sci Rep 2019 05 23;9(1):7770. Epub 2019 May 23.

London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.

In The Gambia, metal-roof houses were hotter during the day than thatched-roof houses. After 24 h, the mortality of Anopheles gambiae, the principal African malaria vector, was 38% higher in metal-roof houses than thatched ones. During the day, mosquitoes in metal-roof houses moved from the hot roof to cooler places near the floor, where the temperature was still high, reaching 35 °C. In laboratory studies, at 35 °C few mosquitoes survived 10 days, the minimum period required for malaria parasite development. Analysis of epidemiological data showed there was less malaria and lower vector survival rates in Gambian villages with a higher proportion of metal roofs. Our findings are consistent with the hypothesis that the indoor climate of metal-roof houses, with higher temperatures and lower humidity, reduces survivorship of indoor-resting mosquitoes and may have contributed to the observed reduction in malaria burden in parts of sub-Saharan Africa.
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http://dx.doi.org/10.1038/s41598-019-43816-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533302PMC
May 2019

Congenital Malaria in Newborns Presented at Tororo General Hospital in Uganda: A Cross-Sectional Study.

Am J Trop Med Hyg 2019 05;100(5):1158-1163

Department of Pediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda.

Despite recent large-scale investments, malaria remains a major public health concern. Few studies have examined congenital malaria, defined as the presence of malaria parasitemia within the first 7 days of life, in endemic areas. This study aimed to determine the prevalence, to describe the clinical presentation, and to examine factors associated with congenital malaria in newborns aged up to 7 days attending Tororo General Hospital in Uganda. A total of 261 mother/baby pairs were recruited in this cross-sectional study. Giemsa-stained thick blood smears for malaria parasites and rapid malaria diagnostic tests were performed on capillary blood samples from all newborns and mothers, as well as on placental and cord samples from newborns delivered in the hospital. The prevalence of congenital malaria in the newborns was 16/261 (6.1%). No single clinical feature was associated with congenital malaria. However, there were associations between congenital malaria and maternal parasitemia ( < 0.001), gravidity of one ( = 0.03), maternal age < 19 years ( = 0.01), cord blood parasitemia ( = 0.01), and placental malaria ( = 0.02). In conclusion, congenital malaria is not rare in Uganda and there are no obvious clinical features associated with it in the newborn. Based on these findings, we recommend strengthening malaria prevention during pregnancy to reduce the occurrence of congenital malaria in newborns.
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http://dx.doi.org/10.4269/ajtmh.17-0341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493922PMC
May 2019

Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study.

Clin Infect Dis 2019 07;69(2):278-286

Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul.

Background: Mass drug administration (MDA) may further reduce malaria transmission in low-transmission areas. The impact of MDA on the dynamics of malaria transmission was determined in a prospective cohort study.

Methods: Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented were implemented in 2014 and 2015 in six village pairs before the malaria transmission season. Blood samples were collected from residents between July and December for microscopy and nested PCR. Incidence and prevalence of infection, clinical disease, and risk of malaria reinfection post-MDA were determined.

Results: Coverage of three DP doses was 68.2% (2014) and 65.6% (2015), compliance was greater than 80%. Incidence of infection was significantly lower in 2014 (incidence rate [IR] = 0.2 per person year [PPY]) than in 2013 (IR = 1.1 PPY; P < .01); monthly infection prevalence declined in the first three months post-MDA. Clinical malaria incidence was lower in 2014 (IR = 0.1 PPY) and 2015 (IR = 0.2 PPY) than in 2013 (IR = 0.4 PPY; P < .01), but remained higher in eastern Gambia. Individuals infected before MDA had a 2-fold higher odds of reinfection post-MDA (adjusted odds ratio = 2.5, 95% confidence interval 1.5-4.3; P < .01).

Conclusions: MDA reduced malaria infection and clinical disease during the first months. The reduction was maintained in low-transmission areas, but not in eastern Gambia. Annual MDA could be followed by focal MDA targeting individuals infected during the dry season. Repeated MDA rounds, some during the dry season over larger geographical areas, may result in a more marked and sustained decrease of malaria transmission.
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http://dx.doi.org/10.1093/cid/ciy870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603267PMC
July 2019

Do hotspots fuel malaria transmission: a village-scale spatio-temporal analysis of a 2-year cohort study in The Gambia.

BMC Med 2018 09 14;16(1):160. Epub 2018 Sep 14.

Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.

Background: Despite the biological plausibility of hotspots fueling malaria transmission, the evidence to support this concept has been mixed. If transmission spreads from high burden to low burden households in a consistent manner, then this could have important implications for control and elimination program development.

Methods: Data from a longitudinal cohort in The Gambia was analyzed. All consenting individuals residing in 12 villages across the country were sampled monthly from June (dry season) to December 2013 (wet season), in April 2014 (mid dry season), and monthly from June to December 2014. A study nurse stationed within each village recorded passively detected malaria episodes between visits. Plasmodium falciparum infections were determined by polymerase chain reaction and analyzed using a geostatistical model.

Results: Household-level observed monthly incidence ranged from 0 to 0.50 infection per person (interquartile range = 0.02-0.10) across the sampling months, and high burden households exist across all study villages. There was limited evidence of a spatio-temporal pattern at the monthly timescale irrespective of transmission intensity. Within-household transmission was the most plausible hypothesis examined to explain the observed heterogeneity in infections.

Conclusions: Within-village malaria transmission patterns are concentrated in a small proportion of high burden households, but patterns are stochastic regardless of endemicity. Our findings support the notion of transmission occurring at the household and village scales but not the use of a targeted approach to interrupt spreading of infections from high to low burden areas within villages in this setting.
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http://dx.doi.org/10.1186/s12916-018-1141-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137946PMC
September 2018

African women working in global health: closing the gender gap in Africa?

Lancet Glob Health 2018 04 7;6(4):e369. Epub 2018 Mar 7.

Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Serrekunda, The Gambia.

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http://dx.doi.org/10.1016/S2214-109X(18)30063-9DOI Listing
April 2018

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BMC Med 2018 01 18;16(1):11. Epub 2018 Jan 18.

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Background: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.

Methods: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses.

Results: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively.

Conclusions: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.
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http://dx.doi.org/10.1186/s12916-017-0990-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774032PMC
January 2018

Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial.

BMC Infect Dis 2017 12 28;17(1):794. Epub 2017 Dec 28.

Infectious Diseases Institute, Kampala, Uganda.

Background: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence.

Methods: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda.

Results: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms.

Conclusion: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed.

Trial Registration: The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).
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http://dx.doi.org/10.1186/s12879-017-2924-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745850PMC
December 2017
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