Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Early results of integrated malaria control and implications for the management of fever in under-five children at a peripheral health facility: a case study of Chongwe rural health centre in Zambia

<p>Abstract</p> <p>Background</p> <p>Zambia has taken lead in implementing integrated malaria control so as to attain the National Health Strategic Plan goal of "reducing malaria incidence by 75% and under-five mortality due to malaria by 20% by the year 2010". The strategic interventions include the use of long-lasting insecticide-treated nets and indoor residual spraying, the use of artemisinin-based combination therapies (ACT) for the treatment of uncomplicated malaria, improving diagnostic capacity (both microscopy and rapid diagnostic tests), use of intermittent presumptive treatment for pregnant women, research, monitoring and evaluation, and behaviour change communication. Financial barriers to access have been removed by providing free malaria prevention and treatment services.</p> <p>Methods</p> <p>Data involving all under-five children reporting at the health facility in the first quarter of 2008 was evaluated prospectively. Malaria morbidity, causes of non-malaria fever, prescription patterns treatment patterns and referral cases were evaluated</p> <p>Results</p> <p>Malaria infection was found only in 0.7% (10/1378), 1.8% (251378) received anti-malarial treatment, no severe malaria cases and deaths occurred among the under-five children with fever during the three months of the study in the high malaria transmission season. 42.5% (586/1378) of the cases were acute respiratory infections (non-pneumonia), while 5.7% (79/1378) were pneumonia. Amoxicillin was the most prescribed antibiotic followed by septrin.</p> <p>Conclusion</p> <p>Malaria related OPD visits have reduced at Chongwe rural health facility. The reduction in health facility malaria cases has led to an increase in diagnoses of respiratory infections. These findings have implications for the management of non-malaria fevers in children under the age of five years.</p

The costs of introducing artemisinin-based combination therapy: evidence from district-wide implementation in rural Tanzania

BACKGROUND\ud \ud The development of antimalarial drug resistance has led to increasing calls for the introduction of artemisinin-based combination therapy (ACT). However, little evidence is available on the full costs associated with changing national malaria treatment policy. This paper presents findings on the actual drug and non-drug costs associated with deploying ACT in one district in Tanzania, and uses these data to estimate the nationwide costs of implementation in a setting where identification of malaria cases is primarily dependant on clinical diagnosis.\ud \ud METHODS\ud \ud Detailed data were collected over a three year period on the financial costs of providing ACT in Rufiji District as part of a large scale effectiveness evaluation, including costs of drugs, distribution, training, treatment guidelines and other information, education and communication (IEC) materials and publicity. The district-level costs were scaled up to estimate the costs of nationwide implementation, using four scenarios to extrapolate variable costs.\ud \ud RESULTS\ud \ud The total district costs of implementing ACT over the three year period were slightly over one million USD, with drug purchases accounting for 72.8% of this total. The composite (best) estimate of nationwide costs for the first three years of ACT implementation was 48.3 million USD (1.29 USD per capita), which varied between 21 and 67.1 million USD in the sensitivity analysis (2003 USD). In all estimates drug costs constituted the majority of total costs. However, non-drug costs such as IEC materials, drug distribution, communication, and health worker training were also substantial, accounting for 31.4% of overall ACT implementation costs in the best estimate scenario. Annual implementation costs are equivalent to 9.5% of Tanzania's recurrent health sector budget, and 28.7% of annual expenditure on medical supplies, implying a 6-fold increase in the national budget for malaria treatment.\ud \ud CONCLUSION\ud \ud The costs of implementing ACT are substantial. Although drug purchases constituted a majority of total costs, non-drug costs were also considerable. It is clear that substantial external resources will be required to facilitate and sustain effective ACT delivery across Tanzania and other malaria-endemic countries

Exploring Gender Dimensions of Treatment Programmes for Neglected Tropical Diseases in Uganda

Background Gender remains a recognized but relatively unexamined aspect of the potential challenges for treatment programmes for Neglected Tropical Diseases (NTDs). We sought to explore the role of gender in access to treatment in the Uganda National Neglected Tropical Disease Control Programme. Methodology/Principal Findings Quantitative and qualitative data was collected in eight villages in Buyende and Kamuli districts, Eastern Uganda. Quantitative data on the number of persons treated by age and gender was identified from treatment registers in each village. Qualitative data was collected through semi-structured interviews with sub-county supervisors, participant observation and from focus group discussions with community leaders, community medicine distributors (CMDs), men, women who were pregnant or breastfeeding at the time of mass-treatment, and adolescent males and females. Findings include the following: (i) treatment registers are often incomplete making it difficult to obtain accurate estimates of the number of persons treated; (ii) males face more barriers to accessing treatment than women due to occupational roles which keep them away from households or villages for long periods, and males may be more distrustful of treatment; (iii) CMDs may be unaware of which medicines are safe for pregnant and breastfeeding women, resulting in women missing beneficial treatments. Conclusions/Significance Findings highlight the need to improve community-level training in drug distribution which should include gender-specific issues and guidelines for treating pregnant and breastfeeding women. Accurate age and sex disaggregated measures of the number of community members who swallow the medicines are also needed to ensure proper monitoring and evaluation of treatment programmes

Persons treated in the NTD programme¹.

1<p>Total persons treated according to NTD Control Programme treatment registers and Village Household Register Books (using available data sources). Of the eight villages in which the study was conducted, only the above three villages had a treatment register that appeared complete enough to use for analysis.</p>*<p>Persons eligible for treatment include persons ages five and older who are not seriously ill (for praziquantel), persons ages five and older who are not seriously ill, pregnant or breastfeeding (for ivermectin and zithromax), or persons ages 1 and older who are not seriously ill, including pregnant women in their second or third trimester (for albendazole).</p>†<p>Treatment registers are kept by the CMDs in each community and are used to register participants who are eligible to participate in the NTD programme.</p>††<p>VHRB is Village Household Register Book which is kept by the Chairman of the Local Council (the Village Level government structure) in each village, and registers the number of persons living in each village (including births, deaths, new migrants, etc.) including age and gender.</p

Framework for gendered differences in access and adherence to NTD treatment programmes.

<p>Framework for gendered differences in access and adherence to NTD treatment programmes.</p

Total number of focus groups and study participants, Buyende and Kamuli districts, Uganda 2011.

1<p><i>Includes members of the Local Council 1 and Religious Leaders.</i></p

Intestinal schistosomiasis in Uganda at high altitude (>1400 m):malacological and epidemiological surveys on Mount Elgon and in Fort Portal crater lakes reveal extra preventive chemotherapy needs

BACKGROUND: Intestinal schistosomiasis is of public health importance in Uganda but communities living above 1400 m are not targeted for control as natural transmission is thought unlikely. To assess altitudinal boundaries and at-risk populations, conjoint malacological and epidemiological surveys were undertaken on Mount Elgon (1139 m-3937 m), in Fort Portal crater lakes and in the Rwenzori Mountains (1123 m-4050 m). METHODS: Seventy freshwater habitats [Mount Elgon (37), Fort Portal crater lakes (23), Rwenzori Mountains (8) and Lake Albert (2)] were inspected for Biomphalaria species. Water temperature, pH and conductivity were recorded. A parasitological examination of 756 schoolchildren [Mount Elgon (300), Fort Portal crater lakes (456)] by faecal microscopy of duplicate Kato-Katz smears from two consecutive stool samples was bolstered by antigen (urine-CCA dipstick) and antibody (SEA-ELISA) diagnostic assays. RESULTS: Biomphalaria spp. was found up to 1951 m on Mount Elgon and 1567 m in the Fort Portal crater lakes. Although no snail from Mount Elgon shed cercariae, molecular analysis judged 7.1% of snails sampled at altitudes above 1400 m as having DNA of Schistosoma mansoni; in Fort Portal crater lakes three snails shed schistosome cercariae. Prevalence of intestinal schistosomiasis as measured in schoolchildren by Kato-Katz (Mount Elgon = 5.3% v. Fort Portal crater lakes = 10.7%), CCA urine-dipsticks (18.3% v. 34.4%) and SEA-ELISA (42.3% v. 63.7%) showed negative associations with increasing altitude with some evidence of infection up to 2000 m. CONCLUSIONS: Contrary to expectations, these surveys clearly show that natural transmission of intestinal schistosomiasis occurs above 1400 m, possibly extending up to 2000 m. Using spatial epidemiological predictions, this now places some extra six million people at-risk, denoting an expansion of preventive chemotherapy needs in Uganda

Bar chart showing the proportion of children tested in each country with specified test results.

<p>For example, ‘pos/pos’ denotes the proportion of children in each country testing positive for both tests, and ‘pos/tr’ denotes the proportion of children in each country testing positive by Kato-Katz and trace by CCA. Note that the bar showing the proportion of children negative on both tests (75% in Côte d’Ivoire and 76% in Uganda) has been removed from the graph to enable easier comparison of non-negative results.</p