Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.

Gaps in treatment of epileptic seizures in a Zambian rural area.

BACKGROUND: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area. METHODS: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap. RESULTS: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine. CONCLUSION: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap.

A qualitative assessment of the health systems factors influencing the prevention of malaria in pregnancy using intermittent preventive treatment and insecticide-treated nets in Ghana.

BACKGROUND: Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana. METHODS: This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcribed and imported into NVivo for analysis. Using the World Health Organization (WHO) Health Systems Framework as the theoretical basis, thematic analysis was conducted under broad themes of the building blocks. Findings are presented in narrative quotes, with a mindmap used to summarize the various health system factors and their interrelated relationship influencing the delivery of IPTp-SP and ITN. RESULTS: Health system factors identified included health staff untrained on malaria delivery directives due to an ineffective trainer of trainer (ToT) system. Additionally, health worker confusion on when to commence SP (at quickening or ≥ 16 weeks) was found to result in delayed start of SP. Stock-outs in facilities due to procurement delays at the national level resulted in missed opportunities to deliver SP to eligible pregnant women at the ANC. Similarly, ITN stock outs led to eligible pregnant women not receiving one at ANC clinics. CONCLUSION: Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC.

Motivators and demotivators to accessing malaria in pregnancy interventions in sub-Saharan Africa: a meta-ethnographic review.

BACKGROUND: Despite the introduction of efficacious interventions for malaria control, sub-Saharan Africa continues to bear the highest burden of malaria and its associated effects on vulnerable populations, such as pregnant women and children. This meta-ethnographic review contributes to literature on malaria in pregnancy interventions in sub-Saharan Africa by offering insights into the multiple factors that motivate or demotivate women from accessing MiP interventions. METHODS: A meta-ethnographic approach was used for the synthesis. Original qualitative research articles published from 2010 to November 2021 in English in sub-Saharan Africa were searched for. Articles focusing on WHO's recommended interventions such as intermittent preventive treatment with sulfadoxine-pyrimethamine, long-lasting insecticidal nets and testing and treatment of Malaria in Pregnancy (MiP) were included. Selected articles were uploaded into Nvivo 11 for thematic coding and synthesis. RESULTS: Twenty-seven original qualitative research articles were included in the analysis. Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women's knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather condition and nearness to a health facility. Factors that demotivated women from using MiP services were: (1) stock-outs, ANC charges and health providers failure to provide women with ample education on the need for MiP care; (2) perception of not being at risk and the culture of self-medication; (3) fear of being bewitched if pregnancy was noticed early, women's lack of decision-making power and dependence on traditional remedies and (4) warm weather, long distances to health facilities and the style of construction of houses making it difficult to hang LLINs. CONCLUSIONS: Health system gaps need to be strengthened in order to ensure that MiP interventions become accessible to women. Additionally, health managers need to involve communities in planning, designing and implementing malaria interventions for pregnant women. It is important that the health system engage extensively with communities to facilitate pregnant women and communities understanding of MiP interventions and the need to support pregnant women to access them.

Assessing health system factors affecting access and delivery of IPTp-SP and ITN to pregnant women attending ANC clinics in Ghana.

INTRODUCTION: Malaria interventions including use of Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment (IPTp-SP) and distribution of Insecticide Treated Nets (ITNs) have been implemented through ante-natal clinic (ANC) services in Ghana. Yet, the high ANC attendance is not commensurate with the uptake of these interventions, with missed opportunities to deliver the interventions. This study sought to assess the health system factors affecting access and delivery of IPTp-SP and ITN as defined by the Ghana Malaria Policy Guideline to eligible pregnant women attending ANC clinic sessions. METHODS: A quantitative cross-sectional study was conducted in the Volta Region of Ghana, with data collected across three levels of health care delivery facilities, including hospitals, health centres and Community-Based Health Planning Service (CHPS) compounds. Data collection included structured observation checklists to document the communication and interaction between the ANC health staff and pregnant women. Additionally, structured questionnaires were used to elicit information on cadre, trainings attended, knowledge and delivery practices of health workers on IPTp-SP and ITN. Stata 16 was used for data analysis, and a defined delivery algorithm was used to compute appropriate and inappropriate delivery practices, using the Ghana policy directive as a guide. Predictors of appropriate delivery were determined using logistic regression analysis. RESULTS: Approximately 97% of the 680 ANC observations had complete information for analysis. Of these, 78% (511/657) were eligible for IPTp-SP after excluding women who have less than 16 weeks of gestation, G6PD deficient, malaria positive and have taken 5 doses of IPTp-SP prior to day of observation. Appropriate delivery of IPTp-SP was 76% (390/511). Despite the availability of SP, 15% (75/511) of all eligible women were not offered the medication and 37% (44/119) of inappropriate delivery was recorded during periods of stock out. ITNs were appropriately delivered to 59% (139) out of 237 eligible women. Thirty-two percent (77/237) of eligible women, mostly continuing ANC clients, were not given ITN despite stock availability. CONCLUSIONS: IPTp-SP was appropriately delivered to most of the eligible pregnant women compared to ITN. While stock out of both intervention could account for inappropriate delivery, despite stock availability, IPTp-SP and ITN were not delivered to some eligible women.

Managing intermittent preventive treatment of malaria in pregnancy challenges: an ethnographic study of two Ghanaian administrative regions.

BACKGROUND: Malaria in pregnancy (MiP) is an important public health problem across sub-Saharan Africa. The package of measures for its control in Ghana in the last 20 years include regular use of long-lasting insecticide-treated bed nets (LLINs), directly-observed administration (DOT) of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and prompt and effective case management of MiP. Unfortunately, Ghana like other sub-Saharan African countries did not achieve the reset Abuja targets of 100% of pregnant women having access to IPTp and 100% using LLINs by 2015. METHODS: This ethnographic study explored how healthcare managers dealt with existing MiP policy implementation challenges and the consequences on IPTp-SP uptake and access to maternal healthcare. The study collected date using non-participant observations, conversations, in-depth interviews and case studies in eight health facilities and 12 communities for 12 months in two Administrative regions in Ghana. RESULTS: Healthcare managers addressed frequent stock-outs of malaria programme drugs and supplies from the National Malaria Control Programme and delayed reimbursement from the NHIS, by instituting co-payment, rationing and prescribing drugs for women to buy from private pharmacies. This ensured that facilities had funds to pay creditors, purchase drugs and supplies for health service delivery. However, it affected their ability to enforce DOT and to monitor adherence to treatment. Women who could afford maternal healthcare and MiP services and those who had previously benefitted from such services were happy to access uninterrupted services. Women who could not maternal healthcare services resorted to visiting other sources of health care, delaying ANC and skipping scheduled ANC visits. Consequently, some clients did not receive the recommended 5 + doses of SP, others did not obtain LLINs early and some did not obtain treatment for MiP. Healthcare providers felt frustrated whenever they could not provide comprehensive care to women who could not afford comprehensive maternal and MiP care. CONCLUSION: For Ghana to achieve her goal of controlling MiP, the Ministry of Health and other supporting institutions need to ensure prompt reimbursement of funds, regular supply of programme drugs and medical supplies to public, faith-based and private health facilities.

Health system, socio-cultural, economic, environmental and individual factors influencing bed net use in the prevention of malaria in pregnancy in two Ghanaian regions.

BACKGROUND: Improving maternal health remains a priority to the Ghanaian government. Consequently, it has implemented the World Health Organization recommendation of distributing free long-lasting insecticidal nets (LLINs) to pregnant women-one of the effective strategies to combating malaria in pregnancy. However, the burden of negative outcomes of malaria in pregnancy such as low birth weight and miscarriages is still high. This may be related to the health system, socio-cultural and economic dynamics that influence LLIN use, but their role is not well understood. This ethnographic study sought to understand health system, socio-cultural, economic and environmental dynamics in utilization of LLINs among pregnant women in two Ghanaian regions. METHODS: An ethnographic study design was used. In-depth interviews and conversations were conducted among health workers, pregnant women and opinion leaders. Observations were conducted in 12 communities and eight health facilities. Ethical clearance was obtained from the University of Health and Allied Sciences' Research Ethics Committee. Nvivo 11 was used to support data coding. Data were triangulated and analysed using a thematic approach. RESULTS: Findings suggest health system, socio-cultural, economic, environmental and individual factors influenced LLIN use. Health facility readiness in stocking LLINs influenced ownership and use. Receiving appropriate information from health providers and encouragement from public officials improved LLIN use. Women with a history of LLIN use prior to becoming pregnant and women who had young children remained consistent users. Experiencing irritating effects of LLINs and preference for traditional methods to wade off mosquitoes, reduced LLIN use. Pregnant women whose household and family members used LLINs were influenced positively to use them. Gender power relations between husbands and wives influenced women's use of LLINs. The type of housing and weather conditions contributed to inconsistent use. Staying out late for business purposes and to converse, exposed pregnant women to mosquito bites. CONCLUSION: Giving out LLINs at facility level should be accompanied with comprehensive information, which is relevant to the socio-cultural context that women live in. Mass distribution should factor in individual and public information to promote community acceptance and proper use of ITNs. Facilities should be encouraged to constantly maintain LLINs stock in order to ensure that ANC registrants receive LLINs for use.

Stepwise approach for the control and eventual elimination of Taenia solium as a public health problem.

BACKGROUND: Taenia solium taeniosis/cysticercosis is a public health and agricultural problem, especially in low-income countries, and has been ranked the top foodborne parasitic hazard globally. In 2012, the World Health Organization published a roadmap that called for a validated strategy for T. solium control and elimination by 2015. This goal has not been met, and validated evidence of effective control or elimination in endemic countries is still incomplete. Measuring and evaluating success of control programmes remains difficult, as locally acceptable targets have not been defined as part of the 2012 roadmap nor from other sources, and the performance of tools to measure effect are limited. DISCUSSION: We believe that an international agreement supported by the tripartite World Health Organization, Food and Agriculture Organization of the United Nations, and World Organisation for Animal Health is needed to facilitate endemic countries in publicising SMART (Specific, Measurable, Achievable/attainable, Relevant, Time-bound) country-level control target goals. These goals should be achievable through locally acceptable adoption of options from within a standardised 'intervention tool-kit', and progress towards these goals should be monitored using standardised and consistent diagnostics. Several intervention tools are available which can contribute to control of T. solium, but the combination of these - the most effective control algorithm - still needs to be identified. In order to mount control efforts and ensure political commitment, stakeholder engagement and funding, we argue that a stepwise approach, as developed for Rabies control, is necessary if control efforts are to be successful and sustainable. CONCLUSIONS: The stepwise approach can provide the framework for the development of realistic control goals of endemic areas, the implementation of intervention algorithms, and the standardised monitoring of the evaluation of the progress towards obtaining the control target goals and eventually elimination.

Assessment of the societal cost of Taenia solium in Angónia district, Mozambique.

BACKGROUND: The zoonotic parasite Taenia solium is endemic in Angónia district, Tete province, Mozambique, though the burden of the disease complex is unknown. METHODS: As part of two cross-sectional studies on human and porcine cysticercosis in the area, unique epidemiological and cost data were collected in Angónia district, Mozambique in 2007. These data provided the basis for the assessment of the societal cost of T. solium in the district, which estimates the impact of the disease on human and pig populations and includes both health and economic approaches in the analysis. RESULTS: Approximately 0.7% (95% Uncertainty Interval (UI), 0.4-0.9) and 0.4% (95% UI, 0.2-0.6) of the total population in the district was estimated to suffer from neurocysticercosis (NCC)-associated epilepsy and headache. The estimated average number of disability-adjusted life years (DALYs) due to NCC-associated epilepsy and headache was 6 (95% UI, 4-8) per thousand persons per year. The total annual costs due to T. solium cysticercosis were estimated at 90,000 USD (95% UI, 39,483-201,463) of which 72% (95% UI, 45-91) were costs linked to human cysticercosis and 28% (95% UI, 9.5-55) to pig production losses. The annual economic burden per NCC-associated epilepsy case in the district amounted to 33 USD (95% UI, 10-76). CONCLUSIONS: In this highly endemic area of Mozambique a large number of individuals suffer from symptoms associated with NCC. Healthy years of life are lost and people are left living with disabilities. Infected pork poses a serious risk to the community and affects the economy of smallholder farmers. Cost for treatment and hospitalization of patients with NCC-associated epilepsy, and lack of productivity and inability of suffering patients to work, further hinder socioeconomic development. Feasible solutions framed within a country specific algorithm and stepwise approaches are needed to control the parasite in the country.

Caregivers' compliance with referral advice: evidence from two studies introducing mRDTs into community case management of malaria in Uganda.

BACKGROUND: Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. METHODS: Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010-July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers' referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. RESULTS: CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings < 10% of caregivers complied with referral advice. In the moderate-to-high transmission setting compliance was higher if children were tested with mRDT compared to children who were not tested with mRDT. In both settings, nearly all children treated with pre-referral rectal artesunate failed to comply with referral and compliance was independently associated with factors such as health centre distance and day of referral by a CHW. In the moderate-to-high transmission setting, time of presentation, severity of referral were also associated with compliance, whilst in the low-transmission setting, compliance was low if an ACT was prescribed. CONCLUSIONS: This analysis suggests there are several barriers to comply with CHWs referral advice by caregivers. This is concerning for children who received rectal artesunate. As CHW programmes continue scale-up, barriers to referral compliance need to be addressed to ensure a continuum of care from the community to the health centre. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov. Identifier NCT01048801 , 13th January 2010.

Dihydroartemisinin-piperaquine versus artesunate-amodiaquine for treatment of malaria infection in pregnancy in Ghana: an open-label, randomised, non-inferiority trial.

OBJECTIVE: To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy. METHODS: A total of 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomised to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-week post-partum to ascertain the health status of the babies. Parasitological efficacy (PE) by days 28 and 42 were co-primary outcomes. Analysis was per-protocol (PP) and modified intention-to-treat (ITT). Non-inferiority was declared if the two-sided 95% confidence interval for PE at the endpoints excluded 5% lower efficacy for DHA-PPQ. Secondary outcomes were assessed for superiority. RESULTS: In PP analysis, PE was 91.6% for DHA-PPQ and 89.3% for ASAQ by day 28 and 89.0% and 86.5%, respectively, by day 42. DHA-PPQ was non-inferior to ASAQ with respect to uncorrected PE [adjusted difference by day 28 (DHA-PPQ-ASAQ); 3.5% (95%CI: -1.5, 8.5); and day 42: 3.9% (95%CI: -2.7, 10.4)]. ITT analysis gave similar results. PCR to distinguish recrudescence and reinfection was unsuccessful. DHA-PPQ recipients had fewer adverse events of vomiting, dizziness, and general weakness compared to ASAQ. Both drugs were well-tolerated, and there was no excess of adverse birth outcomes. CONCLUSION: DHA-PPQ was non-inferior to ASAQ for treatment of malaria infection during pregnancy. No safety concerns were identified. Our findings contribute to growing evidence that DHA-PPQ is useful for control of malaria in pregnancy.

Referral of children seeking care at private health facilities in Uganda.

BACKGROUND: In Uganda, referral of sick children seeking care at public health facilities is poor and widely reported. However, studies focusing on the private health sector are scanty. The main objective of this study was to assess referral practices for sick children seeking care at private health facilities in order to explore ways of improving treatment and referral of sick children in this sector. METHODS: A survey was conducted from August to October 2014 in Mukono district, central Uganda. Data was collected using a structured questionnaire supplemented by Focus Group Discussions and Key Informant interviews with private providers and community members. RESULTS: A total of 241 private health facilities were surveyed; 170 (70.5%) were registered drug shops, 59 (24.5%) private clinics and 12 (5.0%) pharmacies. Overall, 104/241 (43.2%) of the private health facilities reported that they had referred sick children to higher levels of care in the two weeks prior to the survey. The main constraints to follow referral advice as perceived by caretakers were: not appreciating the importance of referral, gender-related decision-making and negotiations at household level, poor quality of care at referral facilities, inadequate finances at household level; while the perception that referral leads to loss of prestige and profit was a major constraint to private providers. CONCLUSION: In conclusion, the results show that referral of sick children at private health facilities faces many challenges at provider, caretaker, household and community levels. Thus, interventions to address constraints to referral of sick children are urgently needed.

Comparison of the capacity between public and private health facilities to manage under-five children with febrile illnesses in Uganda.

BACKGROUND: Public health facilities are usually the first to receive interventions compared to private facilities, yet majority of health seeking care is first done with the latter. This study compared the capacity to manage acute febrile illnesses in children below 5 years in private vs public health facilities in order to design interventions to improve quality of care. METHODS: A survey was conducted within 57 geographical areas (parishes), from August to October 2014 in Mukono district, central Uganda. The survey comprised both facility and health worker assessment. Data were collected on drug stocks, availability of treatment guidelines, diagnostic equipment, and knowledge in management of malaria, pneumonia and diarrhoea, using a structured questionnaire. RESULTS: A total of 53 public and 241 private health facilities participated in the study. While similar proportions of private and public health facilities stocked Coartem, the first-line anti-malarial drug, (98 vs 95%, p = 0.22), significantly more private than public health facilities stocked quinine (85 vs 53%, p < 0.01). Stocks of obsolete anti-malarial drugs, such as chloroquine, were reported in few public and private facilities (3.7 vs 12.5%, p = 0.06). Stocks of antibiotics-amoxycillin and gentamycin were similar in both sectors (≥90% for amoxicillin; ≥50 for gentamycin). Training in malaria was reported by 65% of public health facilities vs 56% in the private sector, p = 0.25), while, only 21% in the public facility and 12% in the private facilities, p = 0.11, reported receiving training in pneumonia. Only 55% of public facilities had microscopes. Malaria treatment guidelines were significantly lacking in the private sector, p = 0.01. Knowledge about first-line management of uncomplicated malaria, pneumonia and diarrhoea was significantly better in the public facilities compared to the private ones, though still sub-optimal. CONCLUSION: Deficiencies of equipment, supplies and training exist even in public health facilities. In order to significantly improve the capacity to handle acute febrile illness among children under five, training in proper case management, availability of supplies and diagnostics need to be addressed in both sectors.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. METHODS: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. RESULTS: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. CONCLUSIONS: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. TRIAL REGISTRATION: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Are we ready for Taenia solium cysticercosis elimination in sub-Saharan Africa?

The World Health Organization announced in November 2014 at the fourth international meeting on 'the control of neglected zoonotic diseases - from advocacy to action', that intervention tools for eliminating Taenia solium taeniosis/cysticercosis (TSTC) are in place. The aim of this work was to elucidate theoretical outcomes of various control options suggested for TSTC elimination in sub-Saharan Africa (SSA) over a 4-year period. Our current knowledge regarding T. solium epidemiology and control primarily builds on studies from Latin America. A simple transmission model - built on data from Latin America - has been used to predict the effect of various interventions such as mass treatment of humans, vaccination and treatment of pigs, and health education of communities, potentially leading to change in bad practices and reducing transmission risks. Based on simulations of the transmission model, even a 4-year integrated One Health approach fails to eliminate TSTC from a small community and in all simulations, the prevalence of human taeniosis and porcine cysticercosis start to rise as soon as the programmes end. Our current knowledge regarding transmission and burden of TSTC in SSA is scarce and while claiming to be tool ready, the selection of diagnostic and surveillance tools, as well as the algorithms and stepwise approaches for control and elimination of TSTC remain major challenges.

POTENTIAL CONTRIBUTION OF ADULT POPULATIONS TO THE MAINTENANCE OF SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTH INFECTIONS IN THE SIAVONGA AND MAZABUKA DISTRICTS OF ZAMBIA.

A majority of Zambian children live in impoverished communities that lack safe water and proper sanitation, exposing them to urogenital and intestinal helminths. Efforts to mitigate this plight have been implemented through mass drug administration aimed at deworming school-age and under-five children against schistosomiasis and soil-transmitted helminths. However, the disease status of adults living in the same communities as the treated children remains unknown. The aim of this study was to describe the potential contribution of infected adult populations to the transmission of these infections in southern Zambia. A cross-sectional study was conducted in April and May 2013 as part of baseline survey for a larger study in Mazabuka and Siavonga Districts. Stool and urine samples of 2829 adults from five catchment areas were collected and processed using Kato-Katz and urine filtration methods, respectively. Adults from Siavonga had a 13.9% combined prevalence of Schistosoma haematobium and S. mansoni, and 12.1% combined prevalence of Ascaris lumbricoides and hookworm. There was no S. mansoni in Mazabuka, and only a 5.3% prevalence of S. haematobium and 7.4% combined prevalence of A. lumbricoides and hookworm. Additionally, no Trichuris trichiura infections were observed in the two districts. Despite most of these infections being categorized as light intensity, heavy infection intensities were also found for all four parasite species. If this infected adult population is left untreated, the possibility of it acting as a reservoir of infections and ultimately transmitting the infections to treated children remains. Therefore, there is need to consider alternative treatment strategies that incorporate adults, thereby reducing the risk of contaminating the environment and perpetuating transmission to children.

The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections.

BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. METHODS: Primigravidae and secundigravidae who participated in the ISTp arm of a noninferiority trial in 4 West African countries were screened with an HRP2/pLDH RDT on enrollment and, in Ghana, at subsequent antenatal clinic (ANC) visits. Blood samples were examined subsequently by microscopy and by a polymerase chain reaction (PCR) assay. RESULTS: The sensitivity of the RDT to detect peripheral blood infections confirmed by microscopy and/or PCR at enrollment ranged from 91% (95% confidence interval [CI], 88%, 94%) in Burkina Faso to 59% (95% CI, 48%, 70% in The Gambia. In Ghana, RDT sensitivity was 89% (95% CI, 85%, 92%), 83% (95% CI, 76%, 90%) and 77% (95% CI, 67%, 86%) at enrollment, second and third ANC visits respectively but only 49% (95% CI, 31%, 66%) at delivery. Screening at enrollment detected 56% of all infections detected throughout pregnancy. Seventy-five RDT negative PCR or microscopy positive infections were detected in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. CONCLUSIONS: The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative malaria infections were not associated with adverse birth outcomes but missed infections were uncommon.

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/µl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.