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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial.

BACKGROUND: Vitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D(3) (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population. METHODS: We did a randomised placebo-controlled trial to compare oral 100,000 IU (2·5 mg) vitamin D(3) with placebo given to children aged 1-11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379. FINDINGS: 1524 children were assigned to receive vitamin D(3) and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129-0·164) and the placebo group (0.137, 0·121-0·155); the incidence rate ratio was 1·06 (95% CI 0·89-1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group--a toxic level. INTERPRETATIONS: Quarterly bolus doses of oral vitamin D(3) supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting. FUNDING: Wellcome Trust and British Council.

Who attends antenatal care and expanded programme on immunization services in Chad, Mali and Niger? The implications for insecticide-treated net delivery.

BACKGROUND: Malaria remains one of the largest public health problems facing the developing world. Insecticide-treated nets (ITNs) are an effective intervention against malaria. ITN delivery through routine health services, such as antenatal care (ANC) and childhood vaccination (EPI), is a promising channel of delivery to reach individuals with the highest risk (pregnant women and children under five years old). Decisions on whether to deliver ITNs through both channels depends upon the reach of each of these systems, whether these are independent and the effectiveness and cost effectiveness of each. Predictors of women attending ANC and EPI separately have been studied, but the predictors of those who attend neither service have not been identified. METHODS: Data from Chad, Mali and Niger demographic and health surveys (DHS) were analyzed to determine risk factors for attending neither service. A conceptual framework for preventative health care-seeking behaviour was created to illustrate the hierarchical relationships between the potential risk factors. The independence of attending both ANC and EPI was investigated. A multivariate model of predictors for non-attendance was developed using logistic regression. RESULTS: ANC and EPI attendance were found to be strongly associated in all three countries. However, 47% of mothers in Chad, 12% in Mali and 36% in Niger did not attend either ANC or EPI. Region, mother's education and partner's education were predictors of non-attendance in all three countries. Wealth index, ethnicity, and occupation were associated with non-attendance in Mali and Niger. Other predictors included religion, healthcare autonomy, household size and number of children under five. CONCLUSIONS: Attendance of ANC and EPI are not independent and therefore the majority of pregnant women in these countries will have the opportunity to receive ITNs through both services. Although attendance at ANC and EPI are not independent, delivery through both systems may still add incrementally to delivery through one alone. Therefore, there is potential to increase the proportion of women and children receiving ITNs by delivering through both of these channels. However, modelling is required to determine the level of attendance and incremental potential at which it's cost effective to deliver through both services.

Taking stock: provider prescribing practices in the presence and absence of ACT stock.

BACKGROUND: Globally, the monitoring of prompt and effective treatment for malaria with artemisinin combination therapy (ACT) is conducted largely through household surveys. This measure; however, provides no information on case management processes at the health facility level. The aim of this review was to assess evidence from health facility surveys on malaria prescribing practices using ACT, in the presence and absence of ACT stock, at time and place where treatment was sought. METHODS: A systematic search of published literature was conducted. Findings were collated and data extracted on proportion of patients prescribed ACT and alternative anti-malarials in the presence and absence of ACT stock. RESULTS: Of the 14 studies identified in which ACT prescription for uncomplicated malaria in the public sector was evaluated, just six, from three countries (Kenya, Uganda and Zambia), reported this in the context of ACT stock. Comparing facilities with ACT stock to facilities without stock (i) ACT prescribing was significantly higher in all six studies, increasing by a range of 21.3% in children < 5 yrs weighing ≥ 5 kg (p < 0.001; Kenya 2006) to 51.7% in children ≥ 10 kg (p < 0.001; Zambia 2006); (ii) SP prescribing decreased significantly in five studies, by a range of 14.4% (p < 0.001; Kenya 2006), to 46.3% (p < 0.001; Zambia 2006); (iii) Where quinine was a reported alternative, prescriptions decreased in five of the six studies by 0.1% (p = 1.0, Kenya 2010) to 10.2% (p < 0.001; Zambia 2006). At facilities with no ACT stock on the survey day, the proportion of febrile patients prescribed ACT was < 10% in five of the nine target groups included in the six studies, with the proportion prescribed ACT ranging from 0 to 28.4% (Uganda 2007). CONCLUSIONS: Prescriber practices vary based on ACT availability. Although ACT prescriptions increased and alternative anti-malarials prescriptions decreased in the presence of ACT stock, ACT was prescribed in the absence, and alternative anti-malarials were prescribed in the presence of, ACT. Presence of stock alone does not ensure that treatment guidelines are followed. More health facility surveys, together with qualitative research, are needed to understand the role of ACT stock-outs on provider prescribing behaviours and preferences.

Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial.

OBJECTIVES: To determine whether (i) supplementation of oral 100,000 iu of vitamin D(3) (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes. METHODS: Double-blind individually randomised placebo-controlled trial in an inner-city hospital in Kabul, of 453 children aged 1-36 months, diagnosed with non-severe or severe pneumonia at the outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or wheeze, were excluded. Children were given vitamin D(3) or placebo drops additional to routine pneumonia treatment. RESULTS: Two hundred and twenty-four children received vitamin D(3;) and 229 received placebo. There was no significant difference in the mean number of days to recovery between the vitamin D(3) (4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention (92/204; 45%) than the placebo group [122/211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitamin D(3) group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53-0.95; P = 0.02). CONCLUSION: A single high-dose oral vitamin D(3) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.

Health worker performance in the management of paediatric fevers following in-service training and exposure to job aids in Kenya.

BACKGROUND: Improving the way artemether-lumefantrine (AL) is provided to patients attending clinics is critical to maximize the benefit of this new medicine. In 2007, a new initiative was launched in one part of Kenya to improve malaria case-management through enhanced in-service training and provision of job aids. METHODS: An evaluation of the intervention using pre- and post-intervention cross sectional health facility surveys was conducted in Bondo district. The surveys included: audit of government health facilities, health worker structured interviews and exit interviews with caretakers of sick children below five years of age. The outcome indicators were the proportions of febrile children who had AL prescribed, AL dispensed, and four different dispensing and counseling tasks performed. RESULTS: At baseline 33 government health facilities, 48 health workers and 386 febrile child consultations were evaluated. At follow-up the same health facilities were surveyed and 36 health workers and 390 febrile child consultations evaluated. The findings show: 1) no health facility or health worker was exposed to all components of the intervention; 2) the proportion of health workers who received the enhanced in-service training was 67%; 3) the proportion of febrile children with uncomplicated malaria treated with the first-line anti-malarial drug, artemether-lumefantrine (AL), at health facilities where AL was in stock increased from 76.9% (95%CI: 69.4, 83.1) to 87.6% (95% CI: 82.5, 91.5); 4) there were modest but non-significant improvements in dispensing and counseling practices; and 5) when the analyses were restricted to health workers who received the enhanced in-service training and/or had received new guidelines and job aids, no significant improvements in reported case-management tasks were observed compared to baseline. CONCLUSION: In-service training and provision of job aids alone may not be adequate to improve the prescribing, dispensing and counseling tasks necessary to change malaria case-management practices and the inclusion of supervision and post-training follow-up should be considered in future clinical practice change initiatives.

From fever to anti-malarial: the treatment-seeking process in rural Senegal.

BACKGROUND: Currently less than 15% of children under five with fever receive recommended artemisinin-combination therapy (ACT), far short of the Roll Back Malaria target of 80%. To understand why coverage remains low, it is necessary to examine the treatment pathway from a child getting fever to receiving appropriate treatment and to identify critical blockages. This paper presents the application of such a diagnostic approach to the coverage of prompt and effective treatment of children with fever in rural Senegal. METHODS: A two-stage cluster sample household survey was conducted in August 2008 in Tambacounda, Senegal, to investigate treatment behaviour for children under five with fever in the previous two weeks. The treatment pathway was divided in to five key steps; the proportion of all febrile children reaching each step was calculated. Results were stratified by sector of provider (public, community, and retail). Logistic regression was used to determine predictors of treatment seeking. RESULTS: Overall 61.6% (188) of caretakers sought any advice or treatment and 40.3% (123) sought any treatment promptly within 48 hours. Over 70% of children taken to any provider with fever did not receive an anti-malarial. The proportion of febrile children receiving ACT within 48 hours was 6.2% (19) from any source; inclusion of correct dose and duration reduced this to 1.3%. The proportion of febrile children receiving ACT within 48 hours (not including dose & duration) was 3.0% (9) from a public provider, 3.0% (9) from a community source and 0.3% (1) from the retail sector. Inclusion of confirmed diagnosis within the public sector treatment pathway as per national policy increases the proportion of children receiving appropriate treatment with ACT in this sector from 9.4% (9/96) to an estimated 20.0% (9/45). CONCLUSIONS: Process analysis of the treatment pathway for febrile children must be stratified by sector of treatment-seeking. In Tambacounda, Senegal, interventions are needed to increase prompt care-seeking for fever, improve uptake of rapid diagnostic tests at the public and community levels and increase correct treatment of parasite-positive patients with ACT. Limited impact will be achieved if interventions to improve prompt and effective treatment target only one step in the treatment pathway in any sector.