Publications by authors named "Jane Bruce"

58 Publications

Assessment of syndromic management of curable sexually transmitted and reproductive tract infections among pregnant women: an observational cross-sectional study.

BMC Pregnancy Childbirth 2021 Jan 30;21(1):98. Epub 2021 Jan 30.

Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: This study estimated the prevalence of curable sexually transmitted and reproductive tract infections (STIs/RTIs) among pregnant women attending antenatal care (ANC) in rural Zambia, evaluated the effectiveness of syndromic management of STIs/RTIs versus reference-standard laboratory diagnoses, and identified determinants of curable STIs/RTIs during pregnancy.

Methods: A total of 1086 pregnant women were enrolled at ANC booking, socio-demographic information and biological samples were collected, and the provision of syndromic management based care was documented. The Piot-Fransen model was used to evaluate the effectiveness of syndromic management versus etiological testing, and univariate and multivariate logistic regression analyses were used to identify determinants of STIs/RTIs.

Results: Participants had a mean age of 25.6 years and a mean gestational age of 22.0 weeks. Of 1084 women, 700 had at least one STI/RTI (64.6%; 95% confidence interval [CI], 61.7, 67.4). Only 10.2% of infected women received any treatment for a curable STI/RTI (excluding syphilis). Treatment was given to 0 of 56 women with chlamydia (prevalence 5.2%; 95% CI, 4.0, 6.6), 14.7% of participants with gonorrhoea (prevalence 3.1%; 95% CI, 2.2, 4.4), 7.8% of trichomoniasis positives (prevalence 24.8%; 95% CI, 22.3, 27.5) and 7.5% of women with bacterial vaginosis (prevalence 48.7%; 95% CI, 45.2, 51.2). An estimated 7.1% (95% CI, 5.6, 8.7) of participants had syphilis and received treatment. Women < 20 years old were more likely (adjusted odds ratio [aOR] = 5.01; 95% CI: 1.23, 19.44) to have gonorrhoea compared to women ≥30. The odds of trichomoniasis infection were highest among primigravidae (aOR = 2.40; 95% CI: 1.69, 3.40), decreasing with each subsequent pregnancy. Women 20 to 29 years old were more likely to be diagnosed with bacterial vaginosis compared to women ≥30 (aOR = 1.58; 95% CI: 1.19, 2.10). Women aged 20 to 29 and ≥ 30 years had higher odds of infection with syphilis, aOR = 3.96; 95% CI: 1.40, 11.20 and aOR = 3.29; 95% CI: 1.11, 9.74 respectively, compared to women under 20.

Conclusions: Curable STIs/RTIs were common and the majority of cases were undetected and untreated. Alternative approaches are urgently needed in the ANC setting in rural Zambia.
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http://dx.doi.org/10.1186/s12884-021-03573-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847014PMC
January 2021

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

Malar J 2021 Jan 22;20(1):61. Epub 2021 Jan 22.

Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population.

Methods: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population.

Results: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively.

Conclusion: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.
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http://dx.doi.org/10.1186/s12936-021-03596-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821718PMC
January 2021

Intermittent screening and treatment with dihydroartemisinin-piperaquine for the prevention of malaria in pregnancy: implementation feasibility in a routine healthcare system setting in western Kenya.

Malar J 2020 Nov 25;19(1):433. Epub 2020 Nov 25.

Disease Control Department, London School of Tropical Medicine and Hygiene, London, UK.

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for preventing malaria in pregnancy in areas of moderate-to-high transmission in sub-Saharan Africa. However, due to increasing parasite resistance to SP, research on alternative strategies is a priority. The study assessed the implementation feasibility of intermittent screening and treatment (ISTp) in the second and third trimester at antenatal care (ANC) with malaria rapid diagnostic tests (RDTs) and treatment of positive cases with dihydroartemisinin-piperaquine (DP) compared to IPTp-SP in western Kenya.

Methods: A 10-month implementation study was conducted in 12 government health facilities in four sub-counties. Six health facilities were assigned to either ISTp-DP or IPTp-SP. Evaluation comprised of facility audits, ANC observations, and exit interviews. Intermediate and cumulative effectiveness analyses were performed on all processes involved in delivery of ISTp-DP including RDT proficiency and IPTp-SP ± directly observed therapy (DOT, standard of care). Logistic regression was used to identify predictors of receiving each intervention.

Results: A total of 388 and 389 women were recruited in the ISTp-DP and IPTp-SP arms, respectively. For ISTp-DP, 90% (289/320) of eligible women received an RDT. Of 11% (32/289) who tested positive, 71% received the correct dose of DP and 31% the first dose by DOT, and only 6% were counselled on subsequent doses. Women making a sick visit and being tested in a facility with a resident microscopist were more likely to receive ISTp-DP (AOR 1.78, 95% CI 1.31, 2.41; and AOR 3.75, 95% CI 1.31, 2.40, respectively). For IPTp-SP, only 57% received a dose of SP by DOT. Payment for a laboratory test was independently associated with receipt of SP by DOT (AOR 6.43, 95% CI 2.07, 19.98).

Conclusions: The findings indicate that the systems effectiveness of ANC clinics to deliver ISTp-DP under routine conditions was poor in comparison to IPTp-SP. Several challenges to integration of ISTp with ANC were identified that may need to be considered by countries that have introduced screening at first ANC visit and, potentially, for future adoption of ISTp with more sensitive RDTs. Understanding the effectiveness of ISTp-DP will require additional research on pregnant women's adherence to ACT.
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http://dx.doi.org/10.1186/s12936-020-03505-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690090PMC
November 2020

Epidemiology of malaria among pregnant women during their first antenatal clinic visit in the middle belt of Ghana: a cross sectional study.

Malar J 2020 Oct 23;19(1):381. Epub 2020 Oct 23.

Kintampo Health Research Centre, Ghana Health Service, PO Box 200, Kintampo, Ghana.

Background: Malaria during pregnancy may result in unfavourable outcomes in both mothers and their foetuses. This study sought to document the current burden and factors associated with malaria and anaemia among pregnant women attending their first antenatal clinic visit in an area of Ghana with perennial malaria transmission.

Methods: A total of 1655 pregnant women aged 18 years and above with a gestational age of 13-22 weeks, who attended an antenatal care (ANC) clinic for the first time, were consented and enrolled into the study. A structured questionnaire was used to collect socio-demographic and obstetric data and information on use of malaria preventive measures. Venous blood (2 mL) was collected before sulfadoxine-pyrimethamine administration. Malaria parasitaemia and haemoglobin concentration were determined using microscopy and an automated haematology analyser, respectively. Data analysis was carried out using Stata 14.

Results: Mean age (SD) and gestational age (SD) of women at enrolment were 27.4 (6.2) years and 16.7 (4.3) weeks, respectively. Overall malaria parasite prevalence was 20.4% (95% CI 18.5-22.4%). Geometric mean parasite density was 442 parasites/µL (95% CI 380-515). Among women with parasitaemia, the proportion of very low (1-199 parasites/µL), low (200-999 parasites/µL), medium (1000-9999 parasites/µL) and high (≥ 10,000 parasites/µL) parasite density were 31.1, 47.0, 18.9, and 3.0%, respectively. Age ≥ 25 years (OR 0.57, 95% CI 0.41-0.79), multigravid (OR 0.50, 95% CI 0.33-0.74), educated to high school level or above (OR 0.53, 95% CI 0.33-0.83) and in household with higher socio-economic status (OR 0.34, 95% CI 0.21-0.54) were associated with a lower risk of malaria parasitaemia. The prevalence of anaemia (< 11.0 g/dL) was 56.0%, and the mean haemoglobin concentration in women with or without parasitaemia was 9.9 g/dL or 10.9 g/dL, respectively.

Conclusion: One out of five pregnant women attending their first ANC clinic visit in an area of perennial malaria transmission in the middle belt of Ghana had Plasmodium falciparum infection. Majority of the infections were below 1000 parasites/µL and with associated anaemia. There is a need to strengthen existing malaria prevention strategies to prevent unfavourable maternal and fetal birth outcomes in this population.
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http://dx.doi.org/10.1186/s12936-020-03457-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585211PMC
October 2020

Effectiveness of an intervention for Aedes aegypti control scaled-up under an inter-sectoral approach in a Colombian city hyper-endemic for dengue virus.

PLoS One 2020 1;15(4):e0230486. Epub 2020 Apr 1.

Eje de Salud Poblacional, Fundación Santa Fe de Bogotá, Bogotá, Colombia.

Aedes aegypti transmitted arboviral diseases are of significant importance in Colombia, particularly since the 2014/2015 introduction of chikungunya and Zika in the Americas and the increasing spread of dengue. In response, the Colombian government initiated the scaling-up of a community-based intervention under inter and multi-sector partnerships in two out of four sectors in Girardot, one of the most hyper-endemic dengue cities in the country. Using a quasi-experimental research design a scaled-up community-led Aedes control intervention was assessed for its capacity to reduce dengue from January 2010 to August 2017 in Girardot, Colombia. Reported dengue cases, and associated factors were analysed from available data sets from the Colombian disease surveillance systems. We estimated the reduction in dengue cases before and after the intervention using, Propensity Score Matching and an Autoregressive Moving Average model for robustness. In addition, the differences in dengue incidence among scaling-up phases (pre-implementation vs sustainability) and between treatment groups (intervention and control areas) were modelled. Evidence was found in favour of the intervention, although to maximise impact the scaling-up of the intervention should continue until it covers the remaining sectors. It is expected that a greater impact of the intervention can be documented in the next outbreak of dengue in Girardot.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112230PMC
July 2020

Evaluation of Implementation of Intermittent Screening and Treatment for Control of Malaria in Pregnancy in Jharkhand, India.

Am J Trop Med Hyg 2020 06;102(6):1343-1350

National Institute for Malaria Research, Delhi, India.

This study evaluated intermittent screening and treatment during pregnancy (ISTp) for malaria using rapid diagnostic tests (RDTs) at antenatal care (ANC) compared with passive case detection within the routine health system. The mixed-method evaluation included two cross-sectional household surveys (pre- and post-implementation of ISTp), in-depth interviews with health workers, and focus group discussions (FGDs) with pregnant women. Differences in proportions between surveys for a number of outcomes were tested; 553 and 534 current and recently pregnant women were surveyed (pre- and post-implementation, respectively). In-depth interviews were conducted with 29 health providers, and 13 FGDs were held with pregnant women. The proportion of pregnant women who received an RDT for malaria at ANC at least once during their pregnancy increased from pre- to post-implementation (19.2%; 95% CI: 14.9, 24.3 versus 42.5%; 95% CI: 36.6, 48.7; < 0.0001), and the proportion of women who had more than one RDT also increased (16.5%; 95% CI: 13.1, 20.5 versus 27.7%; 95% CI: 23.0, 33.0; = 0.0008). Post-implementation, however, only 8% of women who had completed their pregnancy received an RDT on three visits to ANC. Health workers were positive about ISTp mainly because of their perception that many pregnant women with malaria were asymptomatic. Health workers perceived pregnant women to have reservations about ISTp because of their dislike of frequent blood withdrawal, but pregnant women themselves were more positive. Intermittent screening and treatment during pregnancy was not sufficiently adopted by health workers to ensure the increased detection of malaria infections achievable with this strategy in this setting.
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http://dx.doi.org/10.4269/ajtmh.19-0514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253127PMC
June 2020

Effectiveness of intermittent screening and treatment for the control of malaria in pregnancy: a cluster randomised trial in India.

BMJ Glob Health 2019 29;4(4):e001399. Epub 2019 Jul 29.

Department of Disease Control, London School of Hygiene & Tropical Medicine Faculty of Infectious and Tropical Diseases, London, UK.

Background: The control of malaria in pregnancy (MiP) in India relies on testing women who present with symptoms or signs suggestive of malaria. We hypothesised that intermittent screening and treatment for malaria at each antenatal care visit (ISTp) would improve on this approach and reduce the adverse effects of MiP.

Methods: A cluster randomised controlled trial comparing ISTp versus passive case detection (PCD) was conducted in Jharkhand state. Pregnant women of all parities with a gestational age of 18-28 weeks were enrolled. Women in the ISTp group were screened with a rapid diagnostic test (RDT) for malaria at each antenatal clinic visit and those in the PCD group were screened only if they had symptoms or signs suggestive of malaria. All RDT positive women were treated with artesunate/sulfadoxine-pyrimethamine. The primary endpoint was placental malaria, determined by placental histology, and the key secondary endpoints were birth weight, gestational age, vital status of the newborn baby and maternal anaemia.

Results: Between April 2012 and September 2015, 6868 women were enrolled; 3300 in 46 ISTp clusters and 3568 in 41 PCD clusters. In the ISTp arm, 4.9% of women were tested malaria positive and 0.6% in the PCD arm. There was no difference in the prevalence of placental malaria in the ISTp (87/1454, 6.0%) and PCD (65/1560, 4.2%) groups (6.0% vs 4.2%; OR 1.34, 95% CI 0.78 to 2.29, p=0.29) or in any of the secondary endpoints.

Conclusion: ISTp detected more infections than PCD, but monthly ISTp with the current generation of RDT is unlikely to reduce placental malaria or impact on pregnancy outcomes. ISTp trials with more sensitive point-of-care diagnostic tests are needed.
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http://dx.doi.org/10.1136/bmjgh-2019-001399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666812PMC
July 2019

Evaluation of the implementation of single screening and treatment for the control of malaria in pregnancy in Eastern Indonesia: a systems effectiveness analysis.

Malar J 2018 Aug 24;17(1):310. Epub 2018 Aug 24.

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.

Background: Indonesia introduced single screening and treatment (SST) of pregnant women for the control of malaria in pregnancy in 2012. Under this policy pregnant women are screened for malaria at their first antenatal clinic (ANC) visit and on subsequent visits are tested for malaria only if symptomatic. The implementation of this policy in two districts of Indonesia was evaluated. Cross sectional survey structured observations of the ANC visit and exit interviews with pregnant women were conducted to assess health provider compliance with SST guidelines. Systems effectiveness analysis was performed on components of the strategy. Multiple logistic regression was used to test for predictors of women being screened at their first ANC visit.

Results: A total of 865 and 895 ANC visits in Mimika and West Sumba across seven and ten health facilities (plus managed health posts) respectively, were included in the study. Adherence to malaria screening at first ANC visit among pregnant women was 51.4% (95% CI 11.9, 89.2) in health facilities in Mimika (94.8% in health centres) and 24.8% (95% CI 10.3, 48.9) in West Sumba (60.0% in health centres). Reported fever was low amongst women presenting for their second and above ANC visit (2.8% in Mimika and 3.5% in West Sumba) with 89.5% and 46.2% of these women tested for malaria in Mimka and West Sumba, respectively. Cumulative systems effectiveness for SST on first visit to ANC was 7.6% for Mimika and 0.1% for West Sumba; and for second or above visits to ANC was 0.7% in Mimika and 0% in West Sumba. Being screened on a 1st visit to ANC was associated with level of health facility in both sites.

Conclusion: Cumulative systems effectiveness of the SST strategy was poor in both sites. Both elements of the SST strategy, screening on first visit and passive case detection on second and above visits, was driven by the difference in implementation of malaria testing in health centres and health posts, and by low malaria transmission levels and reported fever.
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http://dx.doi.org/10.1186/s12936-018-2448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108152PMC
August 2018

Efficacy of two artemisinin-based combinations for the treatment of malaria in pregnancy in India: a randomized controlled trial.

Malar J 2018 Jul 4;17(1):246. Epub 2018 Jul 4.

National Institute of Malaria Research, New Delhi, India.

Background: In India, the recommended first-line treatment for malaria in the second and third trimester of pregnancy is artesunate + sulfadoxine-pyrimethamine (AS+SP). However, data on safety and efficacy of artemisinin-based combination therapy (ACT) in pregnancy is limited. This study assessed the safety and efficacy of AS+SP and artesunate + mefloquine (AS+MQ) for treatment of Plasmodium falciparum in pregnancy in India.

Methods: This open-label, randomized clinical trial was conducted from October 2010 to December 2013 at three sites in India (Ranchi and Jamshedpur in Jharkhand state, and Rourkela in Odisha state). Pregnant women in the second or third trimester who had P. falciparum mono-infection of any parasite density with or without fever were randomized to receive AS+SP or AS+MQ. Blood slides and filter paper samples for Polymerase Chain Reaction (PCR) were collected on days 0, 1, 2, 3, 14, 21, 28, 42 and 63 post treatment. Women were followed up at delivery and at day 42 postpartum.

Findings: Two hundred and forty-eight women of 7064 pregnant women (3.5%) who were screened at monthly antenatal clinics had a P. falciparum mono-infection and were randomized to receive AS+SP (125) or AS+MQ (123) and all of these women were included in the intention to treat (ITT) analysis. The primary endpoint of an adequate clinical and parasite response (ACPR) on day 63 was not available for 9 women who were counted as treatment failure in the ITT analysis. In the ITT population, the ACPR was 121/125 (96.8%; 95% Confidence interval (CI) 92.0-99.1%) in the AS+SP group and 117/123 (95.1%; 95% CI 89.7-98.2) in the AS+MQ group. Among the 239 women (121 from the AS+SP arm and 118 from the AS+MQ arm) who completed the day 63 follow up (per protocol analysis) the ACPR was 100% in the AS+SP group and 99.2% (117/118) in the AS+MQ group. There were five serious adverse events (SAE) among pregnant women (4 in the AS+SP group and 1 in the AS+MQ group) and 13 fetal/neonatal SAEs (7 in the AS+SP group and 6 in the AS+MQ) but none of them were related to the study drugs. A higher proportion of women in the AS+MQ arm reported vomiting within 7 days post-treatment than did women in the AS+SP arm (6.9 vs. 1.6%; p = 0.001).

Conclusion: Both AS+SP and AS+MQ are safe and effective for treatment of uncomplicated falciparum malaria in pregnancy in India. Trial registration CTRI This study is registered with Clinical Trial Registry India (CTRI), number CTRI/2009/091/001055. Date of Registration 11 January 2010, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=1185&EncHid=&userName=anvikar.
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http://dx.doi.org/10.1186/s12936-018-2393-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030775PMC
July 2018

Effectiveness of two community-based strategies on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia in Ghana.

BMC Public Health 2017 Dec 12;17(1):948. Epub 2017 Dec 12.

Disease Control Department, London School of Hygiene and Tropical Medicine, London, UK.

Background: Ghana has developed two community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia, and to improve household and family practices: integrated Community Case Management (iCCM) and Community-based Health Planning and Services (CHPS). The objective of the study was to assess the effectiveness of iCCM and CHPS on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia.

Methods: A household survey was conducted two and eight years after implementation of iCCM in the Volta and Northern Regions of Ghana respectively, and more than ten years of CHPS implementation in both regions. The study population included 1356 carers of children under- five years of age who had fever, diarrhoea and/or cough in the two weeks prior to the interview. Disease knowledge was assessed based on the knowledge of causes and identification of signs of severe disease and its association with the sources of health education messages received. Health behaviour was assessed based on reported prompt care seeking behaviour, adherence to treatment regime, utilization of mosquito nets and having improved sanitation facilities, and its association with the sources of health education messages received.

Results: Health education messages from community-based agents (CBAs) in the Northern Region were associated with the identification of at least two signs of severe malaria (adjusted Odds Ratio (OR) 1.8, 95%CI 1.0, 3.3, p = 0.04), two practices that can cause diarrhoea (adjusted OR 4.7, 95%CI 1.4, 15.5, p = 0.02) 0and two signs of severe pneumonia (adjusted OR 7.7, 95%CI2.2, 26.5, p = 0.01)-the later also associated with prompt care seeking behaviour (p = 0.04). In the Volta Region, receiving messages on diarrhoea from CHPS was associated with the identification of at least two signs of severe diarrhoea (adjusted OR 3.6, 95%CI 1.4, 9.0), p = 0.02). iCCM was associated with prompt care seeking behaviour in the Volta Region and CHPS with prompt care seeking behaviour in the Northern Region (p < 0.5).

Conclusions: Both iCCM and CHPS were associated with disease knowledge and health behaviour, but this was more pronounced for iCCM and in the Northern Region. HBC should continue to be considered as the strategy through which community-IMCI is implemented.
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http://dx.doi.org/10.1186/s12889-017-4964-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727982PMC
December 2017

Cost-effectiveness analysis of the national implementation of integrated community case management and community-based health planning and services in Ghana for the treatment of malaria, diarrhoea and pneumonia.

Malar J 2017 07 5;16(1):277. Epub 2017 Jul 5.

Disease Control Department, London School of Hygiene and Tropical Medicine, London, UK.

Background: Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia: the integrated community case management (iCCM) and the community-based health planning and services (CHPS). The aim of the study was to assess the cost-effectiveness of these strategies under programme conditions.

Methods: A cost-effectiveness analysis was conducted. Appropriate diagnosis and treatment given was the effectiveness measure used. Appropriate diagnosis and treatment data was obtained from a household survey conducted 2 and 8 years after implementation of iCCM in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under-5 years who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. Costs data was obtained mainly from the National Malaria Control Programme (NMCP), the Ministry of Health, CHPS compounds and from a household survey.

Results: Appropriate diagnosis and treatment of malaria, diarrhoea and suspected pneumonia was more cost-effective under the iCCM than under CHPS in the Volta Region, even after adjusting for different discount rates, facility costs and iCCM and CHPS utilization, but not when iCCM appropriate treatment was reduced by 50%. Due to low numbers of carers visiting a CBA in the Northern Region it was not possible to conduct a cost-effectiveness analysis in this region. However, the cost analysis showed that iCCM in the Northern Region had higher cost per malaria, diarrhoea and suspected pneumonia case diagnosed and treated when compared to the Volta Region and to the CHPS strategy in the Northern Region.

Conclusions: Integrated community case management was more cost-effective than CHPS for the treatment of malaria, diarrhoea and suspected pneumonia when utilized by carers of children under-5 years in the Volta Region. A revision of the iCCM strategy in the Northern Region is needed to improve its cost-effectiveness. Long-term financing strategies should be explored including potential inclusion in the National Health Insurance Scheme (NHIS) benefit package. An acceptability study of including iCCM in the NHIS should be conducted.
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http://dx.doi.org/10.1186/s12936-017-1906-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498878PMC
July 2017

Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.

Int J Parasitol Drugs Drug Resist 2016 12 29;6(3):220-229. Epub 2016 Sep 29.

Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.
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http://dx.doi.org/10.1016/j.ijpddr.2016.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094156PMC
December 2016

Malarial Infection and Curable Sexually Transmitted and Reproductive Tract Infections Among Pregnant Women in a Rural District of Zambia.

Am J Trop Med Hyg 2016 Nov 26;95(5):1069-1076. Epub 2016 Sep 26.

Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Malarial infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes. Reducing the burden of these infections in pregnancy requires interventions that can be easily integrated into the antenatal care (ANC) package. However, efforts to integrate the control of malarial infection and curable STIs/RTIs in pregnancy have been hampered by a lack of evidence related to their coinfection. Thus, we investigated the prevalence of coinfection among pregnant women of rural Zambia. A prospective cohort study was conducted in Nchelenge District, Zambia, involving 1,086 first ANC attendees. We screened participants for peripheral malarial infection and curable STIs/RTIs (syphilis, Chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis), and collected relevant sociodemographic data at booking. Factors associated with malarial and STI/RTI coinfection were explored using univariate and multivariate regression models. Among participants with complete results (N = 1,071), 38.7% (95% confidence interval [CI] = 35.7-41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI = 16.5-21.2) were infected with malaria parasites only; 26.0% (95% CI = 23.5-28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI = 14.1-18.6) had no infection. Human immunodeficiency virus (HIV)-infected women had a higher risk of being coinfected than HIV-uninfected women (odds ratio [OR] = 3.59 [95% CI = 1.73-7.48], P < 0.001). The prevalence of malarial and STI/RTI coinfection was high in this population. An integrated approach to control malarial infection and STIs/RTIs is needed to reduce this dual burden in pregnancy.
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http://dx.doi.org/10.4269/ajtmh.16-0370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094219PMC
November 2016

Cost-Effectiveness Analysis of Test-Based versus Presumptive Treatment of Uncomplicated Malaria in Children under Five Years in an Area of High Transmission in Central Ghana.

PLoS One 2016 3;11(10):e0164055. Epub 2016 Oct 3.

Department for Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: The presumptive approach of confirming malaria in health facilities leads to over-diagnosis of malaria, over use of anti-malaria drugs and the risk of drug resistance development. WHO recommends parasitological confirmation before treatment with artemisinin-based combination therapy (ACT) in all suspected malaria patients. The use of malaria rapid diagnostic tests (mRDTs) would make it possible for prescribers to diagnose malaria at point-of-care and better target the use of antimalarials. Therefore, a cost-effectiveness analysis was performed on the introduction of mRDTs for management of malaria in under-five children in a high transmission area in Ghana where presumptive diagnosis was the norm in public health centres.

Methods: A cluster-randomised controlled trial where thirty-two health centres were randomised into test-based diagnosis of malaria using mRDTs (intervention) or clinical judgement (control) was used to measure the effect of mRDTs on appropriate treatment: 'a child with a positive reference diagnosis prescribed a course of ACT or a child with a negative reference diagnosis not given an ACT'. Cost data was collected from five purposively selected health centres and used to estimate the health sector costs of performing an mRDT and treat children for malaria and other common febrile illnesses. Costs of training healthcare personnel and supervision in the study period were also collected. A sample of caregivers to children participating in the trial was interviewed about household cost incurred on transport, drugs, fees, and special food during a period of one week after the health centre visit as well as days unable to work. A decision model approach was used to calculate the incremental cost-effectiveness ratios (ICERs). Univariate and multivariate sensitivity analyses were applied to assess the robustness of ICERs.

Results: The availability of mRDTs for malaria diagnosis resulted in fewer ACT treatments compared to the clinical judgement approach (73% versus 81%) and more children appropriately treated (70% versus 57%). The introduction of mRDT-based diagnosis would cost the Ministry of Health US$18.6 per extra appropriately treated child under five compared to clinical judgement while the ICER from a societal perspective was lower at US$11.0 per appropriately treated child. ICERs were sensitive to a decrease in adherence to negative mRDTs, malaria positivity rate and specificity of the mRDT.

Conclusion: The introduction of mRDTs is likely to be considered cost-effective in this high transmission setting as this intervention increased the number of appropriately treated children at low cost.

Trial Registration: ClinicalTrials.gov NCT00832754.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164055PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047443PMC
June 2017

A faecal exposure assessment of farm workers in Accra, Ghana: a cross sectional study.

BMC Public Health 2016 07 16;16:587. Epub 2016 Jul 16.

Department of Disease Control, Faculty of Infectious and Tropical Diseases, Environmental Health Group, London School of Hygiene and Tropical Medicine, Keppel street, London, WC1E 7HT, UK.

Background: Wastewater use in urban agriculture is common as a result of rapid urbanisation, and increasing competition for good quality water. In order to minimize risks to farmers and consumers of wastewater irrigated produce the World Health Organization (WHO) has developed guidelines for the safe use of wastewater in agriculture. These guidelines are based on a Quantitative Microbial Risk Assessment (QMRA) model, though the reliability of this model has been questioned due to a lack of primary data. This study aimed to assess the ability of the WHO guidelines to protect farmers' health, by identifying and quantifying key exposures associated with the transmission of faecal pathogens in wastewater irrigated agriculture.

Methods: Eighty farmers were observed and interviewed during the dry and wet seasons, and water and soil samples were analysed for the presence of E. coli. STATA 12 was used for descriptive analyses of farmers' exposure and risk practices, and also to determine risk factors for soil and irrigation water contamination, while the WHO QMRA model and @Risk 6 were used to model farmers' infection risk to pathogens.

Results: The results showed that although irrigation water was highly contaminated (5.6 Log E. coli/100 ml), exposure to farm soil (2.3 Log E. coli/g) was found to be the key risk pathway due to soil-to-mouth events. During the observations 93 % of farmers worked barefoot, 86 % experienced hand-to-soil contact, while 53 % experienced 'soil'-to-mouth events, while no 'water' to mouth contacts were observed. On average, farmers were found to have 10 hand-to-mouth events per day. From the indicator based QMRA model the estimated norovirus infection risk to farmers was found to be higher than guidelines set by the WHO.

Conclusions: This study found exposure to soil as the critical pathway of pathogen risk in wastewater farmers, and that this risk exceeded recommended health targets. The study recommends the incorporation of hand-to-mouth events, the use of actual pathogen concentrations, and the use of direct exposure frequencies in order to improve the reliability of risk estimates from QMRA models.
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http://dx.doi.org/10.1186/s12889-016-3266-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947311PMC
July 2016

Results of clubfoot treatment after manipulation and casting using the Ponseti method: experience in Harare, Zimbabwe.

Trop Med Int Health 2016 Oct 26;21(10):1311-1318. Epub 2016 Jul 26.

International Centre for Evidence in Disability, London School of Hygiene and Tropical Medicine, London, UK.

Objectives: The objective of this study was to evaluate the outcomes of the Ponseti manipulation and casting method for clubfoot in a tertiary hospital in Zimbabwe and explore predictors of these outcomes.

Methods: A cohort study included children with idiopathic clubfoot managed from 2011 to 2013 at Parirenyatwa Hospital. Demographic data, clinical features and treatment outcomes were extracted from clinic records. The primary outcome measure was the final Pirani score (clubfoot severity measure) after manipulation and casting. Secondary outcomes included change in Pirani score (pre-treatment to end of casting), number of casts for correction, proportion receiving tenotomy and proportion lost to follow up.

Results: A total of 218 children (337 feet) were eligible for inclusion. The median age at treatment was 8 months; 173 children (268 feet) completed casting treatment within the study period. The mean length of time for corrective treatment was 10.2 weeks (9.5-10.9 weeks). Of the 45 children who did not complete treatment, 28 were under treatment and 17 were lost to follow up. A Pirani score of 1 or less was achieved in 85% of feet. Mean Pirani score at presentation was 3.80 (SD 1.15) and post-treatment 0.80 (SD 0.56, P-value <0.0001). Severity of deformity and being male were associated with a higher (worse) final Pirani score. Severity and age over two were associated with an increase in the number of casts required to correct deformity.

Conclusion: This case series demonstrates that the majority (80%+) of children with clubfoot can achieve a good outcome with the Ponseti manipulation and casting method.
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http://dx.doi.org/10.1111/tmi.12750DOI Listing
October 2016

Integrated community case management and community-based health planning and services: a cross sectional study on the effectiveness of the national implementation for the treatment of malaria, diarrhoea and pneumonia.

Malar J 2016 07 2;15(1):340. Epub 2016 Jul 2.

Dodowa Health Research Center, Ghana Health Service, Dodowa, Ghana.

Background: Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and pneumonia: the Home-based Care (HBC) and the Community-based Health Planning and Services (CHPS). The objective was to assess the effectiveness of HBC and CHPS on utilization, appropriate treatment given and users' satisfaction for the treatment of malaria, diarrhoea and pneumonia.

Methods: A household survey was conducted 2 and 8 years after implementation of HBC in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under-five who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. HBC and CHPS utilization were assessed based on treatment-seeking behaviour when the child was sick. Appropriate treatment was based on adherence to national guidelines and satisfaction was based on the perceptions of the carers after the treatment-seeking visit.

Results: HBC utilization was 17.3 and 1.0 % in the Volta and Northern Regions respectively, while CHPS utilization in the same regions was 11.8 and 31.3 %, with large variation among districts. Regarding appropriate treatment of uncomplicated malaria, 36.7 % (n = 17) and 19.4 % (n = 1) of malaria cases were treated with ACT under the HBC in the Volta and Northern Regions respectively, and 14.7 % (n = 7) and 7.4 % (n = 26) under the CHPS in the Volta and Northern Regions. Regarding diarrhoea, 7.6 % (n = 4) of the children diagnosed with diarrhoea received oral rehydration salts (ORS) or were referred under the HBC in the Volta Region and 22.1 % (n = 6) and 5.6 % (n = 8) under the CHPS in the Volta and Northern Regions. Regarding suspected pneumonia, CHPS in the Northern Region gave the most appropriate treatment with 33.0 % (n = 4) of suspected cases receiving amoxicillin. Users of CHPS in the Volta Region were the most satisfied (97.7 % were satisfied or very satisfied) when compared with those of the HBC and of the Northern Region.

Conclusions: HBC showed greater utilization by children under-five years of age in the Volta Region while CHPS was more utilized in the Northern Region. Utilization of HBC contributed to prompt treatment of fever in the Volta Region. Appropriate treatment for the three diseases was low in the HBC and CHPS, in both regions. Users were generally satisfied with the CHPS and HBC services.
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http://dx.doi.org/10.1186/s12936-016-1380-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930600PMC
July 2016

Effectiveness of the delivery of interventions to prevent malaria in pregnancy in Kenya.

Malar J 2016 Apr 18;15:221. Epub 2016 Apr 18.

Disease Control Department, London School of Hygiene and Tropical Medicine, London, UK.

Background: Coverage with malaria in pregnancy interventions remains unacceptably low. Implementation research is needed to identify and quantify the bottlenecks for the delivery and use of these life-saving interventions through antenatal clinics (ANC).

Methods: A cross-sectional study was carried out in ANC across nine health facilities in western Kenya. Data were collected for an individual ANC visit through structured observations and exit interviews with the same ANC clients. The cumulative and intermediate systems effectiveness for the delivery of intermittent preventive treatment (IPTp) and insecticide-treated nets (ITNs) to eligible pregnant women on this one specific visit to ANC were estimated.

Results: Overall the ANC systems effectiveness for delivering malaria in pregnancy interventions was suboptimal. Only 40 and 53 % of eligible women received IPTp by directly observed therapy as per policy in hospitals and health centres/dispensaries respectively. The overall systems effectiveness for the receipt of IPTp disregarding directly observed therapy was 62 and 72 % for hospitals and lower level health facilities, respectively. The overall systems effectiveness for ITNs for first ANC visit was 63 and 67 % for hospitals and lower level facilities, respectively.

Conclusion: This study found that delivery of IPTp and ITNs through ANC was ineffective and more so for higher-level facilities. This illustrates missed opportunities and provider level bottlenecks to the scale up and use of interventions to control malaria in pregnancy delivered through ANC. The high level of clustering within health facilities suggest that future studies should assess the feasibility of implementing interventions to improve systems effectiveness tailored to the health facility level.
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http://dx.doi.org/10.1186/s12936-016-1261-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835845PMC
April 2016

Effect of Test-Based versus Presumptive Treatment of Malaria in Under-Five Children in Rural Ghana--A Cluster-Randomised Trial.

PLoS One 2016 7;11(4):e0152960. Epub 2016 Apr 7.

Department of Disease Control, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.

Background: Malaria-endemic countries in sub-Saharan Africa are shifting from the presumptive approach that is based on clinical judgement (CJ) to the test-based approach that is based on confirmation through test with rapid diagnostic tests (RDT). It has been suggested that the loss of the prophylactic effect of presumptive-administered ACT in children who do not have malaria will result in increase in their risk of malaria and anaemia.

Methods And Findings: We undertook a cluster-randomized controlled trial to compare the effects of the presumptive approach using clinical judgment (CJ-arm) and the test-based approach using RDTs (RDT-arm in a high-transmission setting in Ghana. A total of 3046 eligible children (1527 in the RDT arm and 1519 in the CJ- arm) living around 32 health centres were enrolled. Nearly half were female (48.7%) and 47.8% were below the age of 12 months as at enrolment. Over 24-months, the incidence of all episodes of malaria following the first febrile illness was 0.64 (95% CI 0.49-0.82) and 0.76 (0.63-0.93) per child per year in the RDT and CJ arms respectively (adjusted rate ratio 1.13 (0.82-1.55). After the first episode of febrile illness, the incidence of severe anaemia was the same in both arms (0.11 per child per year) and that of moderate anaemia was 0.16 (0.13-0.21) vs. 0.17 (0.14-0.21) per child year respectively. The incidence of severe febrile illness was 0.15 (0.09, 0.24) in the RDT arm compared to 0.17 (0.11, 0.28) per child per year respectively. The proportion of fever cases receiving ACT was lower in the RDT arm (72% vs 81%; p = 0.02).

Conclusion: The test-based approach to the management of malaria did not increase the incidence of malaria or anaemia among under-five children in this setting.

Trial Registration: ClinicalTrials.gov NCT00832754.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152960PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824463PMC
August 2016

Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda.

Am J Trop Med Hyg 2016 06 28;94(6):1251-1258. Epub 2016 Mar 28.

Serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. Plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. Clusters of P. falciparum parasite prevalence and high antibody responses to MSP-119 were detected and compared. Results show that P. falciparum prevalence and seroprevalence generally decreased with increasing altitude. However, transmission was heterogeneous with hotspots of prevalence and/or seroprevalence detected in both highland and highland fringe altitudes, including a serological hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an additional tool to identify hotspots of malaria transmission that might be difficult to detect using traditional cross-sectional parasite surveys or through vector studies. Our study findings identify ways in which malaria prevention and control can be more effectively targeted in highland or low transmission areas via serological measures. These tools will become increasingly important for countries with an elimination agenda and/or where malaria transmission is becoming patchy and focal, but receptivity to malaria transmission remains high.
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http://dx.doi.org/10.4269/ajtmh.15-0653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889741PMC
June 2016

Risk Perceptions of Wastewater Use for Urban Agriculture in Accra, Ghana.

PLoS One 2016 15;11(3):e0150603. Epub 2016 Mar 15.

Faculty of Infectious and Tropical Diseases, Environmental Health Group, London School of Hygiene and Tropical Medicine, Keppel street, WC1E 7HT, London, United Kingdom.

Poor food hygiene is a significant risk to public health globally, but especially in low and middle-income countries where access to sanitation, and general hygiene remain poor. Food hygiene becomes even more pertinent when untreated, or poorly treated wastewater is used in agriculture. In such circumstances the WHO recommends the adoption of a multiple-barrier approach that prescribes health protective measures at different entry points along the food chain. This study sought to assess the knowledge and awareness of wastewater use for crop production, its related health risks, and adoption of health protective measures by farmers, market salespersons and consumers using questionnaires and focus group discussions. In the period from September 2012 to August 2013, 490 respondents were interviewed during two cropping seasons. The study found that awareness of the source of irrigation water was low among consumers and street food vendors, though higher among market vendors. In contrast, health risk awareness was generally high among salespersons and consumers, but low among farmers. The study found that consumers did not prioritize health indicators when buying produce from vendors but were motivated to buy produce, or prepared food based on taste, friendship, cost, convenience and freshness of produce. Similarly, farmers' awareness of health risk did not influence their adoption of safer farm practices. The study recommends the promotion of interventions that would result in more direct benefits to both producers and vendors, together with hygiene education and enforcement of food safety byelaws in order to influence behaviour change, and increase the uptake of the multiple-barrier approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150603PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792467PMC
July 2016

A Farm to Fork Risk Assessment for the Use of Wastewater in Agriculture in Accra, Ghana.

PLoS One 2015 10;10(11):e0142346. Epub 2015 Nov 10.

Environmental Health Group, Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel street, WC1E 7HT, London, United Kingdom.

The need to minimise consumer risk, especially for food that can be consumed uncooked, is a continuing public health concern, particularly in places where safe sanitation and hygienic practices are absent. The use of wastewater in agriculture has been associated with disease risks, though its relative significance in disease transmission remains unclear. This study aimed at identifying key risk factors for produce contamination at different entry points of the food chain. Over 500 produce and ready-to-eat salad samples were collected from fields, markets, and kitchens during the dry and wet seasons in Accra, Ghana, and over 300 soil and irrigation water samples were collected. All samples were analysed for E. coli, human adenovirus and norovirus using standard microbiological procedures, and real time RT-PCR. Finally, critical exposures associated with microbial quality of produce were assessed through observations and interviews. The study found that over 80% of produce samples were contaminated with E. coli, with median concentrations ranging from 0.64 to 3.84 Log E. coli/g produce. Prepared salad from street food vendors was found to be the most contaminated (4.23 Log E. coli/g), and that consumption of salad exceeded acceptable health limits. Key risk factors identified for produce contamination were irrigation water and soil at the farm level. Storage duration and temperature of produce had a significant influence on the quality of produce sold at markets, while observations revealed that the washed water used to rinse produce before sale was dirty. The source of produce and operating with a hygiene permit were found to influence salad microbial quality at kitchens. This study argues for a need to manage produce risk factors at all domains along the food chain, though it would be more effective to prioritise at markets and kitchens due to cost, ease of implementation and public health significance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142346PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640866PMC
June 2016

The effect of single or repeated home visits on the hanging and use of insecticide-treated mosquito nets following a mass distribution campaign--a cluster randomized, controlled trial.

PLoS One 2015 16;10(3):e0119078. Epub 2015 Mar 16.

Johns Hopkins Bloomberg School of Public Health Center for Communication Programs, Baltimore, MD, United States of America.

Background: Study objective was to evaluate the effectiveness of commonly used post-campaign hang-up visits on the hanging and use of campaign nets.

Methods: A cluster-randomized trial was carried out in Uganda following an ITN distribution campaign. Five clusters (parishes, consisting of ∼11 villages each) were randomly selected for each of the three study arms with between 7,534 and 9,401 households per arm. Arm 1 received one hang-up visit, while Arm 2 received two visits by volunteers four and seven months after the campaign. Visits consisted of assistance hanging the net and education on net use. The control arm was only exposed to messages during the campaign itself. Three cross-sectional surveys with a two-stage cluster sampling design, representative of the study populations, were carried out to capture the two key outcome variables of net hanging and ITN use. Sample size was calculated to detect at least a 15 percentage-points change in net use, and was 1811 at endline. The analysis used an intention-to-treat approach.

Findings: Both hanging and use of ITN increased during follow-up in a similar way in all three study arms. The proportion of the population using an ITN the previous night was 64.0% (95% CI 60.8, 67.2), for one additional visit, 68.2% (63.8, 72.2) for two visits and 64.0% (59.4, 68.5) for the control. The proportion of households with all campaign nets hanging increased from 55.7% to 72.5% at endline (p<0.0005 for trend), with no difference between study arms. Financial cost per household visited was estimated as USD 2.33 for the first visit and USD 2.24 for the second.

Conclusions: Behavior change communication provided during the campaign or through other channels was sufficient to induce high levels of net hanging and use and additional "hang-up" activities were not cost-effective.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361725PMC
February 2016

Association between recent internal travel and malaria in Ugandan highland and highland fringe areas.

Trop Med Int Health 2015 Jun 17;20(6):773-80. Epub 2015 Mar 17.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Objective: To examine the association between travel (recency of travel, transmission intensity at destination compared to origin and duration of travel) and confirmed malaria in Uganda.

Methods: Health facility-based case-control study in highland (~2200 m), and highland fringe (~1500 m) areas with adjustment for other covariates.

Results: In the highland site, patients who had travelled to areas of higher transmission intensity than their home (origin) areas recently were nearly seven times more likely to have confirmed malaria than those who had not (OR 6.9; P = 0.01, 95% CI: 1.4-33.1). In the highland fringe site, there was also a statistically significant association between travel and malaria (OR 2.1; P = 0.04, 95% CI: 1.1-3.9).

Conclusions: For highland areas, or areas of low malaria transmission, health authorities need to consider internal migrants when designing malaria control programs. Control interventions should include information campaigns reminding residents in these areas of the risk of malaria infection through travel and to provide additional mosquito nets for migrants to use during travel. Health authorities may wish to improve diagnosis in health facilities in highland areas by adding travel history to malaria case definitions. Where routine monitoring data are used to evaluate the impact of interventions on the malaria burden in highland areas, health authorities and donors need ensure that only cases from the local area and not 'imported cases' are counted.
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http://dx.doi.org/10.1111/tmi.12480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006858PMC
June 2015

Risk factors associated with recurrent diarrheal illnesses among children in Kabul, Afghanistan: a prospective cohort study.

PLoS One 2015 13;10(2):e0116342. Epub 2015 Feb 13.

Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Introduction: Childhood diarrheal illnesses are a major public health problem. In low-income settings data on disease burden and factors associated with diarrheal illnesses are poorly defined, precluding effective prevention programs. This study explores factors associated with recurrent diarrheal illnesses among children in Kabul, Afghanistan.

Methods: A cohort of 1-11 month old infants was followed for 18 months from 2007-2009. Data on diarrheal episodes were gathered through active and passive surveillance. Information on child health, socioeconomics, water and sanitation, and hygiene behaviors was collected. Factors associated with recurrent diarrheal illnesses were analyzed using random effects recurrent events regression models.

Results: 3,045 children were enrolled and 2,511 (82%) completed 18-month follow-up. There were 14,998 episodes of diarrheal disease over 4,200 child-years (3.51 episodes/child-year, 95%CI 3.40-3.62). Risk of diarrheal illness during the winter season was 63% lower than the summer season (HR = 0.37, 95%CI 0.35-0.39, P<0.001). Soap for hand washing was available in 72% of households and 11.9% had toilets with septic/canalization. Half of all mothers reported using soap for hand washing. In multivariate analysis diarrheal illness was lower among children born to mothers with post-primary education (aHR = 0.79, 95%CI 0.69-0.91, p = 0.001), from households where maternal hand washing with soap was reported (aHR = 0.83, 95%CI 0.74-0.92, p<0.001) and with improved sanitation facilities (aHR = 0.76, 95%CI 0.63-0.93, p = 0.006). Malnourished children from impoverished households had significantly increased risks for recurrent disease [(aHR = 1.15, 95%CI 1.03-1.29, p = 0.016) and (aHR = 1.20, 95%CI 1.05-1.37, p = 0.006) respectively].

Conclusions: Maternal hand washing and improved sanitation facilities were protective, and represent important prevention points among public health endeavors. The discrepancy between soap availability and utilization suggests barriers to access and knowledge, and programs simultaneously addressing these aspects would likely be beneficial. Enhanced maternal education and economic status were protective in this population and these findings support multi-sector interventions to combat illness.

Trial Registration: www.ClinicalTrials.gov NCT00548379 https://www.clinicaltrials.gov/ct2/show/NCT00548379.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332656PMC
January 2016

Management of febrile children under five years in hospitals and health centres of rural Ghana.

Malar J 2014 Jul 9;13:261. Epub 2014 Jul 9.

Disease Control Department, London School of Hygiene and Tropical Medicine, London, UK.

Background: The case management of febrile children in hospitals' and health centres' pre-roll out of the new WHO policy on parasitological diagnosis was assessed. The delivery of artemisinin combination therapy (ACT) at these two levels of the health system was compared.

Methods: Structured observations and exit interviews of 1,222 febrile children attending five hospitals and 861 attending ten health centres were conducted in six districts of the Brong Ahafo Region of Ghana. Effectiveness of delivery of case management of malaria was assessed. Proportions of children receiving ACT, anti-malarial monotherapy and antibiotics were described. Predictors of: a febrile child being given an ACT, a febrile child being given an antibiotic and of carers knowing how to correctly administer the ACT were assessed using logistic regression models stratified by hospitals and health centres.

Results: The system's effectiveness of delivering an ACT to febrile children diagnosed with malaria (parasitologically or clinically) was 31.4 and 42.4% in hospitals and health centres, respectively. The most ineffective process was that of ensuring that carers knew how to correctly administer the ACT. Overall 278 children who were not given an ACT were treated with anti-malarial monotherapy other than quinine. The majority of these children, 232/278 were given amodiaquine, 139 of these were children attending hospitals and 93 attending health centres. The cadre of health staff conducting consultation was a common predictor of the outcomes of interest. Presenting symptoms and examinations conducted were predictive of being given an ACT in hospitals and antibiotic in hospitals and health centres but not of being given an ACT in health centres. Treatment-seeking factors were predictive of being given an ACT if it was more than seven days since the fever began and an antibiotic in hospitals but not in health centres.

Conclusion: Interventions to improve adherence to negative parasitological tests are needed, together with guidance on dispensing of antibiotics, but improving the education of carers on how to administer ACT will lead to the greatest immediate increase in the effectiveness of case management. Guidance is needed on implementation of the new test-based treatment for malaria policy in health facilities.
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http://dx.doi.org/10.1186/1475-2875-13-261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114131PMC
July 2014

Effectiveness of antenatal clinics to deliver intermittent preventive treatment and insecticide treated nets for the control of malaria in pregnancy in Mali: a household survey.

PLoS One 2014 20;9(3):e92102. Epub 2014 Mar 20.

Disease Control Department, London School of Tropical Medicine and Hygiene, London, United Kingdom.

Background: WHO recommends intermittent-preventive-treatment (IPTp) with sulphadoxine-pyrimethamine (SP) and insecticide-treated-nets (ITNs) to prevent malaria in pregnancy in sub-Saharan Africa, however uptake remains unacceptably low. We evaluated the effectiveness of antenatal clinics (ANC) to deliver two doses of IPTp and ITNs to pregnant women in Segou district, Mali.

Methods: We used household data to assess the systems effectiveness of ANC to deliver IPTp and ITNs to pregnant women and used logistic regression to identify predictors of ANC attendance, receipt of IPTp and ITN use during pregnancy, and the impact on community effectiveness.

Results: Of 81% of recently pregnant women who made at least one ANC visit, 59% of these attended during the eligible gestational age for IPTp. Of these, 82% reported receiving one dose of SP and 91% attended ANC again, of whom 66% received a second dose, resulting in a cumulative effectiveness for 2-dose IPTp of 29%, most of whom used an ITN (90%). Cumulative effectiveness of 2-dose SP by directly observed therapy (DOT) was very low (6%). ITN use was 92%, and ANC was the main source (81%). Reported and ANC-card data showed some doses of SP are given to women in their first trimester. Women were less likely to receive two doses by DOT if they were married (OR 0.10; CI 0.03, 0.40), or lived <5 km from the health facility (OR 0.34; CI 0.14, 0.83). A high household person-LLIN ratio predicted low ITN use in pregnant women (OR 0.16; CI 0.04, 0.55).

Conclusion: Our findings suggest poor adherence by health workers to provision of IPTp by eligible gestational age and DOT, contributing to low effectiveness of this strategy in this setting. ITN delivery and use among women was substantially higher. Efforts to improve health worker adherence to IPTp guidelines are needed to improve service delivery of IPTp.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092102PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961285PMC
December 2014

Vitamin D₃supplementation and childhood diarrhea: a randomized controlled trial.

Pediatrics 2013 Oct 9;132(4):e832-40. Epub 2013 Sep 9.

MSc, SUNY Downstate Medical Center, Department of Emergency Medicine, 450 Clarkson Ave, Brooklyn, NY 11203.

Objective: To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan.

Methods: This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥ 3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models.

Results: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per child-year (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons.

Conclusions: Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases.
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http://dx.doi.org/10.1542/peds.2012-3986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866796PMC
October 2013

Prevention of malaria in pregnancy with intermittent preventive treatment and insecticide treated nets in Mali: a quantitative health systems effectiveness analysis.

PLoS One 2013 28;8(6):e67520. Epub 2013 Jun 28.

Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Introduction: The objectives of the study were to evaluate the health system effectiveness of ANC for the delivery of a dose of IPTp and an ITN to women attending ANC during eligible gestation, and to identify the predictors of systems effectiveness.

Methods: A cross sectional study was undertaken in 10 health facilities including structured non-participant observations of the ANC process for 780 pregnant women followed by exit interviews. The proportion of pregnant women receiving a dose of IPTp-SP and an ITN was assessed. Predictors of each ineffective intermediate process were identified using multivariable logistic regression.

Results: Overall, 0% and 24.5% of pregnant women of eligible gestation on the first visit to ANC received a dose of IPTp-SP by DOT at the district and community levels respectively. Ineffective intermediate processes were 'given IPTp-SP at the ANC' 63.9% and 74.0% (95% CI 62.0, 83.3), and 'given IPTp-SP by DOT' 0% and 34.3% (95% CI 10.5, 69.8), at district and community levels, respectively. Delivery of ITNs was effective where they were in stock; however stock-outs were a problem. Predictors of receiving IPTp-SP at the district level were 4 to 6 months gestation, not reporting symptoms of malaria at ANC visit and the amount of money spent during the visit. At the community level, the predictors were 4 to 6 months gestation, maternal education below primary level, routine ANC visit (not for an illness), palpation of the abdomen, and expenditure of money in ANC.

Conclusion: In Segou District, the delivery of IPTp-SP was ineffective; whilst ITN delivery was effective if ITNs were in stock. Predictors of receiving IPTp-SP at the district and community levels included gestational age, the amount of expenditure during the ANC visit and no illness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067520PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695962PMC
April 2014

Effectiveness of antenatal clinics to deliver intermittent preventive treatment and insecticide treated nets for the control of malaria in pregnancy in Kenya.

PLoS One 2013 14;8(6):e64913. Epub 2013 Jun 14.

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Background: Malaria in pregnancy can have devastating consequences for mother and baby. Coverage with the WHO prevention strategy for sub-Saharan Africa of intermittent-preventive-treatment (IPTp) with two doses of sulphadoxine-pyrimethamine (SP) and insecticide-treated-nets (ITNs) in pregnancy is low. We analysed household survey data to evaluate the effectiveness of antenatal clinics (ANC) to deliver IPTp and ITNs to pregnant women in Nyando district, Kenya.

Methods: We assessed the systems effectiveness of ANC to deliver IPTp and ITNs to pregnant women and the impact on low birthweight (LBW). Logistic regression was used to identify predictors of receipt of IPTp and ITN use during pregnancy.

Results: Among 89% of recently pregnant women who attended ANC at least once between 4-9 months gestation, 59% reported receiving one dose of SP and 90% attended ANC again, of whom 57% received a second dose, resulting in a cumulative effectiveness for IPTp of 27%, most of whom used an ITN (96%). Overall ITN use was 89%, and ANC the main source (76%). Women were less likely to receive IPTp if they had low malaria knowledge (0.26, 95% CI 0.08-0.83), had a child who had died (OR 0.36, 95% CI 0.14-0.95), or if they first attended ANC late (OR 0.20, 95% CI 0.06-0.67). Women who experienced side effects to SP (OR 0.18, CI 0.03-0.90) or had low malaria knowledge (OR 0.78, 95% CI 0.11-5.43) were less likely to receive IPTp by directly observed therapy. Ineffective delivery of IPTp reduced its potential impact by 231 LBW cases averted (95% CI 64-359) per 10,000 pregnant women.

Conclusion: IPTp presents greater challenges to deliver through ANC than ITNs in this setting. The reduction in public health impact on LBW resulting from ineffective delivery of IPTp is estimated to be substantial. Urgent efforts are required to improve service delivery of this important intervention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064913PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683044PMC
January 2014
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