Development of a theory and evidence-based program to promote community treatment of fevers in children under five in a rural district in Southern Ghana: An intervention mapping approach.

BACKGROUND: This paper describes the development and implementation of a program to promote prompt and appropriate care seeking for fever in children under the age of five. Designed as a multicomponent program, the intervention comprises elements to influence the behavior of caregivers of children, Community Health Workers, professional health care providers and the wider community. METHODS: Following the six fundamental steps of the Intervention Mapping protocol, we involved relevant stakeholders from the commencement of planning to program end. The IM protocol also recommends various behavior change methods to guide intervention development. RESULTS: The intervention components implemented were successful in achieving program goals. For example, the intervention resulted in the primary outcome of reductions in all-cause mortality of 30% and 44%, among children treated with an antimalarial and those treated with the antimalarial plus an antibiotic respectively. Most Community Health Workers were retained on the program, with an attrition rate of 21.2% over a period of 30 months and the Community Health Workers rate of adherence to performance guidelines was high at 94.6%. CONCLUSION: We were able to systematically develop a theory- and evidence-based health promotion program based on the Intervention Mapping protocol. This article contributes to the response to recent calls for a more detailed description of the development of interventions and trials. The intervention mapping approach can serve as a guide for others interested in developing community- based health interventions in similar settings.

Community perceptions and practices of treatment seeking for childhood pneumonia: a mixed methods study in a rural district, Ghana.

BACKGROUND: The World Health Organization recommends community case management of malaria and pneumonia for reduction of under-five mortality in developing countries. Caregivers' perception and understanding of the illness influences the care a sick child receives. Studies in Ghana and elsewhere have routinely shown adequate recognition of malaria by caregivers. Similarly, evidence from Asia and some African countries have shown adequate knowledge on pneumonia. However, in Ghana, little has been documented about community awareness, knowledge, perceptions and management of childhood pneumonia particularly in the Dangme West district. Therefore this formative study was conducted to determine community perceptions of pneumonia for the purpose of informing the design and implementation of context specific health communication strategies to promote early and appropriate care seeking behaviour for childhood pneumonia. METHODS: A mixed method approach was adopted. Data were obtained from structured interviews (N = 501) and eight focus group discussions made up of 56 caregivers of under-fives and eight community Key Informants. Descriptive and inference statistics were used for the quantitative data and grounded theory to guide the analysis of the qualitative data. RESULTS: Two-thirds of the respondents had never heard the name pneumonia. Most respondents did not know about the signs and symptoms of pneumonia. For the few who have heard about pneumonia, causes were largely attributed to coming into contact with cold temperature in various forms. Management practices mostly were self-treatment with home remedies and allopathic care. CONCLUSION: The low awareness and inadequate recognition of pneumonia implies that affected children may not receive prompt and appropriate treatment as their caregivers may misdiagnose the illness. Adequate measures need to be taken to create the needed awareness to improve care seeking behaviour.

Is home management of fevers a cost-effective way of reducing under-five mortality in Africa? The case of a rural Ghanaian District.

OBJECTIVE: To assess the cost-effectiveness of two strategies of home management of under-five fevers in Ghana - treatment using antimalarials only (artesunate-amodiaquine - AAQ) and combined treatment using antimalarials and antibiotics (artesunate-amodiaquine plus amoxicillin - AAQ + AMX). METHODS: We assessed the costs and cost-effectiveness of AAQ and AAQ + AMX compared with a control receiving standard care. Data were collected as part of a cluster randomised controlled trial with a step-wedged design. Approximately, 12,000 children aged 2-59 months in Dangme West District in southern Ghana were covered. Community health workers delivered the interventions. Costs were analysed from societal perspective, using anaemia cases averted, under-five deaths averted and disability-adjusted life years (DALYs) averted as effectiveness measures. RESULTS: Total economic costs for the interventions were US$ 204,394.72 (AAQ) and US$ 260,931.49 (AAQ + AMX). Recurrent costs constituted 89% and 90% of the total direct costs of AAQ and AAQ + AMX, respectively. Deaths averted were 79.1 (AAQ) and 79.9 (AAQ + AMX), with DALYs averted being 2264.79 (AAQ) and 2284.57 (AAQ + AMX). The results show that cost per anaemia case averted were US$ 150.18 (AAQ) and US$ 227.49 (AAQ + AMX) and cost per death averted was US$ 2585.58 for AAQ and US$ 3272.20 for AAQ + AMX. Cost per DALY averted were US$ 90.25 (AAQ) and US$ 114.21 (AAQ + AMX). CONCLUSION: Both AAQ and AAQ + AMX approaches were cost-effective, each averting one DALY at less than the standard US$ 150 threshold recommended by the World Health Organisation. However, AAQ was more cost-effective. Home management of under-five fevers in rural settings is cost-effective in reducing under-five mortality.

ALOX5 variants associated with susceptibility to human pulmonary tuberculosis.

The 5-lipoxygenase (ALOX5)-derived lipid mediators leukotrienes and lipoxins have regulatory functions in inflammation by modulating activities of immune cells and cytokine production. Recently, it was shown in ALOX5-/- mice that host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase (5-LO). ALOX5 polymorphisms were genotyped in 1916 sputum-positive patients with pulmonary tuberculosis (TB) from Ghana and in 2269 exposed, apparently healthy controls. Polymorphisms of a variable number of tandem repeats (VNTR) of the ALOX5 promoter and of the exonic non-synonymous variant g.760G>A were analysed by fragment length determination and fluorescence resonance energy transfer, respectively, and DNA sequencing. Mycobacterial lineages of >1400 isolates were differentiated biochemically and genetically. Carriers of one variant (n repeats not equal 5) and one wild-type VNTR allele (n = 5) or of the exonic allele g.760A had a higher risk of TB [P(corrected) = 0.026, odds ratio (OR) 1.19 (95% CI 1.04-1.37) and P(corrected) = 0.026, OR 1.21 (95% CI 1.04-1.41), respectively]. The association of the exonic variant was stronger in infections caused by the mycobacterial lineage M. africanum West-African 2 [P(corrected) = 0.024, OR 1.70; (95% CI 1.2-2.6)]. Determination of haplotypes revealed the strongest associaton with TB for the 'non-5/760A' haplotype compared with the 'non-5/760G' haplotype (P = 0.003, OR 1.50). Our observation of an association of ALOX5 variants with susceptibility to TB contributes evidence of the importance of 5-LO products to the regulation of immune responses to M. tuberculosis.

Treatment choices for fevers in children under-five years in a rural Ghanaian district.

BACKGROUND: Health care demand studies help to examine the behaviour of individuals and households during illnesses. Few of existing health care demand studies examine the choice of treatment services for childhood illnesses. Besides, in their analyses, many of the existing studies compare alternative treatment options to a single option, usually self-medication. This study aims at examining the factors that influence the choices that caregivers of children under-five years make regarding treatment of fevers due to malaria and pneumonia in a rural setting. The study also examines how the choice of alternative treatment options compare with each other. METHODS: The study uses data from a 2006 household socio-economic survey and health and demographic surveillance covering caregivers of 529 children under-five years of age in the Dangme West District and applies a multinomial probit technique to model the choice of treatment services for fevers in under-fives in rural Ghana. Four health care options are considered: self-medication, over-the-counter providers, public providers and private providers. RESULTS: The findings indicate that longer travel, waiting and treatment times encourage people to use self-medication and over-the-counter providers compared to public and private providers. Caregivers with health insurance coverage also use care from public providers compared to over-the-counter or private providers. Caregivers with higher incomes use public and private providers over self-medication while higher treatment charges and longer times at public facilities encourage caregivers to resort to private providers. Besides, caregivers of female under-fives use self-care while caregivers of male under-fives use public providers instead of self-care, implying gender disparity in the choice of treatment. CONCLUSIONS: The results of this study imply that efforts at curbing under-five mortality due to malaria and pneumonia need to take into account care-seeking behaviour of caregivers of under-fives as well as implementation of strategies.

Evaluating a novel neonatal-care assessment tool among trained delivery attendants in a resource-limited setting.

OBJECTIVE: To validate a novel objective structured clinical examination (OSCE) tool for assessing neonatal care skills among delivery attendants trained as part of the Essential Care for Every Baby (ECEB) program and to assess ECEB training effectiveness. METHODS: Between August 1 and September 30, 2015, a cross-sectional study enrolled ECEB-trained healthcare providers who attended deliveries from the Brong Ahafo and Eastern regions of Ghana. Participants completed a previously developed 21-item OSCE tool that assessed neonatal-care competency. Participant performance was scored independently by regional trainers and national master trainers. The inter-rater scoring reliability was assessed using the Cohen kappa coefficient and performance was compared across participant characteristics. RESULTS: The study enrolled 57 trained delivery attendants from 12 district hospitals. Inter-rater agreement was perfect (kappa 1.00) or almost perfect (kappa 0.81-0.99) for nine OSCE items, substantial (kappa 0.61-0.80) or moderate (kappa 0.41-0.60) for 11 items, and fair (kappa 0.21-0.40) for one item. Differences in OSCE-item performance were recorded based on participants' regions, facility type, age, and education level (P<0.05). CONCLUSIONS: In a resource-limited setting, the OSCE tool demonstrated substantial reliability and ECEB-trained healthcare practitioners exhibited satisfactory performance. The OSCE tool could be useful in similar settings and could have potential for up-scaled use in assessing neonatal-management skills.

Factors related to retention of community health workers in a trial on community-based management of fever in children under 5 years in the Dangme West District of Ghana.

BACKGROUND: In resource-constrained settings of developing countries, promotion of community-based health interventions through community health workers (CHWs) is an important strategy to improve child health. However, there are concerns about the sustainability of such programmes owing to the high rate of CHW attrition. This study examined factors influencing retention of volunteer CHWs in a cluster randomised trial on community management of under-5 fever in a rural Ghanaian district. METHODS: Data were obtained from structured interviews (n=520) and focus group discussions (n=5) with CHWs. Factors influencing CHWs' decisions to remain or leave the programme were analysed using a probit model, and focus group discussion results were used to elucidate the findings. RESULTS: The attrition rate among CHWs was 21.2%. Attrition was comparatively higher in younger age groups (25.9% in 15-25 years group, 18.2% in 26-45 years group and 16.5% in ≥46 years group). Approval of a CHW by the community (p<0.001) and the CHW's immediate family (p<0.05) were significant in influencing the probability of remaining in the programme. Motivation for retention was related to the desire to serve their communities as well as humanitarian and religious reasons. CONCLUSION: The relatively moderate rate of attrition could be attributed to the high level of community involvement in the selection process as well as other aspects of the intervention leading to high community approval and support. Attention for these aspects could help improve CHW retention in community-based health interventions in Ghana, and the lessons could be applied to countries within similar settings.

Impact of treating young children with antimalarials with or without antibiotics on morbidity: a cluster-randomized controlled trial in Ghana.

BACKGROUND: Community health workers in Dangme-West district, Ghana, treated children aged 2-59 months with fever with either artesunate-amodiaquine (AAQ) or AAQ plus amoxicillin (AAQ + AMX) within a cluster-randomized controlled trial (registration no. TDR/UNDP Trial registration A: 20189). The intervention was introduced in a stepped-wedge manner. The aim of the study was reduction of mortality. This paper reports on the reduction of morbidity, notably anaemia, severe anaemia and severe illness. Clusters of 100 children were randomized in to AAQ, AAQ + AMX and pre-intervention arms. Six months later the pre-intervention clusters were randomized in to the AAQ and AAQ + AMX arms. METHODS: Data were collected in eight cross-sectional surveys. Using stratified sampling, 10 clusters were randomly selected per survey. Blood samples were taken to assess haemoglobin. Caregivers were interviewed about diseases (signs and symptoms) among their children in the preceding 14 days. Multivariate logistic regression analysis was used to determine the impact on anaemia, severe anaemia and severe illness. RESULTS: Compared with the pre-intervention clusters, anaemia was reduced in the AAQ (OR = 0.20, 95% CI 0.12-0.33) and AAQ + AMX (OR = 0.23, 95% CI 0.15-0.36) clusters, severe anaemia was reduced in the AAQ (OR = 0.20, 95% CI 0.09-0.45) and AAQ + AMX (OR = 0.12, 95% CI 0.04-0.31) clusters and severe illness was reduced in the AAQ (OR = 0.46, 95% CI 0.26-0.80) and AAQ + AMX (OR = 0.38, 95% CI 0.22-0.63) clusters. No significant differences were found in outcome variables between the AAQ and AAQ + AMX clusters. CONCLUSIONS: Treating fever with antimalarials significantly reduced the prevalence of anaemia, severe anaemia and severe illness. We found no significant reduction in outcomes when the AAQ and AAQ+AMX clusters were compared.

Assessment of the adherence of community health workers to dosing and referral guidelines for the management of fever in children under 5 years: a study in Dangme West District, Ghana.

BACKGROUND: Community health workers (CHW) manage simple childhood illnesses in many developing countries. Information on CHWs' referral practices is limited. As part of a large cluster-randomised trial, this study assessed CHWs' adherence to dosing and referral guidelines. METHODS: Records of consultations of children aged 2-59 months with fever managed by CHWs were analysed. Appropriate use of drugs was defined as provision of the correct drug pack(s) for the child's age group. Symptoms requiring referral were categorised into danger signs, respiratory distress and symptoms indicating other illnesses. Multivariate logistic regression examined symptoms most likely to be noted as requiring referral and those associated with provision of a written referral. RESULTS: Most children (11 659/12 330; 94.6%) received the appropriate drug. Only 161 of 1758 (9.2%) children who, according to the guidelines required referral were provided with a written referral. Not drinking/breastfeeding, persistent vomiting, unconsciousness/lethargy, difficultly breathing, fast breathing, bloody stool, sunken eyes and pallor were symptoms significantly associated with being identified by CHWs as needing referral or receiving a written referral. CONCLUSIONS: CHWs' adherence to dosing guidelines was high. Adherence to referral guidelines was inadequate. More effort needs to be put into strengthening referral practices of CHWs within comparable community programmes.

Impact of community management of fever (using antimalarials with or without antibiotics) on childhood mortality: a cluster-randomized controlled trial in Ghana.

Malaria and pneumonia are leading causes of childhood mortality. Home Management of fever as Malaria (HMM) enables presumptive treatment with antimalarial drugs but excludes pneumonia. We aimed to evaluate the impact of adding an antibiotic, amoxicillin (AMX) to an antimalarial, artesunate amodiaquine (AAQ + AMX) for treating fever among children 2-59 months of age within the HMM strategy on all-cause mortality. In a stepped-wedge cluster-randomized, open trial, children 2-59 months of age with fever treated with AAQ or AAQ + AMX within HMM were compared with standard care. Mortality reduced significantly by 30% (rate ratio [RR] = 0.70, 95% confidence interval [CI] = 0.53-0.92, P = 0.011) in AAQ clusters and by 44% (RR = 0.56, 95% CI = 0.41-0.76, P = 0.011) in AAQ + AMX clusters compared with control clusters. The 21% mortality reduction between AAQ and AAQ + AMX (RR = 0.79, 95% CI = 0.56-1.12, P = 0.195) was however not statistically significant. Community fever management with antimalarials significantly reduces under-five mortality. Given the lower mortality trend, adding an antibiotic is more beneficial.

Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.

We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.

IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB.

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions -2849 , -1082 , -819 , and -592 and reconstructed the haplotypes. The IL10 low-producer haplotype -2849A/-1082A/-819C/-592C, compared to the high-producer haplotype -2849G/-1082G/-819C/-592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3-3.6) and PPD-positive controls (OR 2.09, CI 1.2-3.5). Lower IL-10 plasma levels in homozygous -2849A/-1082A/-819C/-592C carriers, compared to homozygous -2849G/-1082G/-819C/-592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.

Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis.

The current strategy for the interruption of transmission of lymphatic filariasis in areas where the disease is co-endemic with onchocerciasis is repeated annual mass treatment of endemic communities with ivermectin and albendazole. These drugs are not recommended for use in pregnancy. Pregnant women are excluded on the basis of their last menses. This exclusion criterion based on recall carries some inherent errors, leading sometimes to inadvertent exposure of foetuses to these drugs. This study set out to document the extent of inadvertent exposure of pregnant women to albendazole and ivermectin and assess the relative risk of congenital malformations because of inadvertent treatment with these drugs in early pregnancy. The study was conducted in the Ahanta West District of Ghana. Local pregnancy revelation norms were studied, followed by a household survey of women aged 15-45 years to assess drug administration coverage. All infants born within 42 weeks of the mass drug treatment were examined to document any congenital malformations. Mothers who had lost any such infants responded to a verbal autopsy to ascertain the probable cause of death. Health facilities and local Traditional Birth Attendants were also visited to review maternity records. Of 2985 women of childbearing age (15-49 years) who were interviewed, 343 were pregnant during the mass drug administration. The sensitivity of the last menstrual period in detecting pregnancy and thus being excluded from treatment was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been inadvertently treated. This represents 1.7% of women in fertile age group (15-49 years). Of the six children found with some congenital malformations in these communities, one had been exposed to the drugs in-utero. The relative risk for congenital malformation after exposure was 1.05 (P=1.0). Two of nine reported spontaneous abortions had been exposed to the drugs (P=0.62). We conclude that the local mode of excluding pregnancy in the current programme, while not perfect, is sufficiently effective and reliable for such a public health intervention; and importantly, that there is no evidence of a higher risk of congenital malformation or abortions in those who are inadvertently exposed.