Costs and effects of two public sector delivery channels for long-lasting insecticidal nets in Uganda.

BACKGROUND: In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda. METHODS: Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used. RESULTS: After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani. CONCLUSIONS: Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged

Low prevalence of Plasmodium falciparum antigenaemia among asymptomatic HAART-treated adults in an urban cohort in Uganda

<p>Abstract</p> <p>Background</p> <p>Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).</p> <p>Methods</p> <p>Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect <it>Plasmodium falciparum </it>antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.</p> <p>Results</p> <p>Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic <it>P. falciparum </it>antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.</p> <p>Conclusions</p> <p>In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. <it>falciparum </it>antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.</p

Case Management of Severe Malaria - A Forgotten Practice: Experiences from Health Facilities in Uganda

INTRODUCTION: Severe malaria is a life-threatening medical emergency and requires prompt and effective treatment to prevent death. There is paucity of published information on current practices of severe malaria case management in sub-Saharan Africa; we evaluated the management practices for severe malaria in Ugandan health facilities METHODS AND FINDINGS: We did a cross sectional survey, using multi-stage sampling methods, of health facilities in 11 districts in the eastern and mid-western parts of Uganda. The study instruments were adapted from the WHO hospital care assessment tools. Between June and August 2009, 105 health facilities were surveyed and 181 health workers and 868 patients/caretakers interviewed. None of the inpatient facilities had all seven components of a basic care package for the management of severe malaria consistently available during the 3 months prior to the survey. Referral practices were appropriate for <10% (18/196) of the patients. Prompt care at any health facility was reported by 29% (247/868) of patients. Severe malaria was correctly diagnosed in 27% of patients (233).Though the quinine dose and regimen was correct in the majority (611/868, 70.4%) of patients, it was administered in the correct volumes of 5% dextrose in only 18% (147/815). Most patients (80.1%) had several doses of quinine administered in one single 500 ml bottle of 5% dextrose. Medications were purchased by 385 (44%) patients and medical supplies by 478 patients (70.6%). CONCLUSIONS: Management of severe malaria in Ugandan health facilities was sub-optimal. These findings highlight the challenges of correctly managing severe malaria in resource limited settings. Priority areas for improvement include triage and emergency care, referral practises, quality of diagnosis and treatment, availability of medicines and supplies, training and support supervision

Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial

Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children

HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.

BACKGROUND: Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings. CONCLUSIONS/SIGNIFICANCE: The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined

Prototype Positive Control Wells for Malaria Rapid Diagnostic Tests: Prospective Evaluation of Implementation Among Health Workers in Lao People's Democratic Republic and Uganda.

Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but lack of quality control at point of care restricts trust in test results. Prototype positive control wells (PCW) containing recombinant malaria antigens have been developed to identify poor-quality RDT lots. This study assessed community and facility health workers' (HW) ability to use PCWs to detect degraded RDTs, the impact of PCW availability on RDT use and prescribing, and preferred strategies for implementation in Lao People's Democratic Republic (Laos) and Uganda. A total of 557 HWs participated in Laos (267) and Uganda (290). After training, most (88% to ≥ 99%) participants correctly performed the six key individual PCW steps; performance was generally maintained during the 6-month study period. Nearly all (97%) reported a correct action based on PCW use at routine work sites. In Uganda, where data for 127,775 individual patients were available, PCW introduction in health facilities was followed by a decrease in antimalarial prescribing for RDT-negative patients ≥ 5 years of age (4.7-1.9%); among community-based HWs, the decrease was 12.2% (P < 0.05) for all patients. Qualitative data revealed PCWs as a way to confirm RDT quality and restore confidence in RDT results. HWs in malaria-endemic areas are able to use prototype PCWs for quality control of malaria RDTs. PCW availability can improve HWs' confidence in RDT results, and benefit malaria diagnostic programs. Lessons learned from this study may be valuable for introduction of other point-of-care diagnostic and quality-control tools. Future work should evaluate longer term impacts of PCWs on patient management

Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

<p>Abstract</p> <p>Background</p> <p>Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.</p> <p>Methods</p> <p>HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental <it>Plasmodium falciparum </it>malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.</p> <p>Results</p> <p>Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral <it>P. falciparum </it>malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental <it>P. falciparum </it>infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's <it>X </it>²> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's <it>X </it>²< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.</p> <p>Conclusion</p> <p>Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.</p

Use of RDTs to improve malaria diagnosis and fever case management at primary health care facilities in Uganda

<p>Abstract</p> <p>Background</p> <p>Early and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda.</p> <p>Methods</p> <p>All health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre - post' and 'intervention - control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices.</p> <p>Results</p> <p>A total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value = 0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value <0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection.</p> <p>Conclusion</p> <p>Use of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria.</p

Prototype positive control wells for malaria rapid diagnostic tests: Prospective evaluation of implementation among health workers in Lao People's Democratic Republic and Uganda

Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but lack of quality control at point of care restricts trust in test results. Prototype positive control wells (PCW) containing recombinant malaria antigens have been developed to identify poor-quality RDT lots. This study assessed community and facility health workers' (HW) ability to use PCWs to detect degraded RDTs, the impact of PCW availability on RDT use and prescribing, and preferred strategies for implementation in Lao People's Democratic Republic (Laos) and Uganda. A total of 557 HWs participated in Laos (267) and Uganda (290). After training, most (88% to ≥ 99%) participants correctly performed the six key individual PCW steps; performance was generally maintained during the 6-month study period. Nearly all (97%) reported a correct action based on PCW use at routine work sites. In Uganda, where data for 127,775 individual patients were available, PCW introduction in health facilities was followed by a decrease in antimalarial prescribing for RDT-negative patients ≥ 5 years of age (4.7–1.9%); among community-based HWs, the decrease was 12.2% (P < 0.05) for all patients. Qualitative data revealed PCWs as a way to confirm RDT quality and restore confidence in RDT results. HWs in malaria-endemic areas are able to use prototype PCWs for quality control of malaria RDTs. PCW availability can improve HWs' confidence in RDT results, and benefit malaria diagnostic programs. Lessons learned from this study may be valuable for introduction of other point-of-care diagnostic and quality-control tools. Future work should evaluate longer term impacts of PCWs on patient management

Operational accuracy and comparative persistent antigenicity of HRP2 rapid diagnostic tests for Plasmodium falciparum malaria in a hyperendemic region of Uganda

BACKGROUND: Parasite-based diagnosis of malaria by microscopy requires laboratory skills that are generally unavailable at peripheral health facilities. Rapid diagnostic tests (RDTs) require less expertise, but accuracy under operational conditions has not been fully evaluated in Uganda. There are also concerns about RDTs that use the antigen histidine-rich protein 2 (HRP2) to detect Plasmodium falciparum, because this antigen can persist after effective treatment, giving false positive test results in the absence of infection. An assessment of the accuracy of Malaria Pf immuno-chromatographic test (ICT) and description of persistent antigenicity of HRP2 RDTs was undertaken in a hyperendemic area of Uganda. METHODS: Using a cross-sectional design, a total of 357 febrile patients of all ages were tested using ICT, and compared to microscopy as the gold standard reference. Two independent RDT readings were used to assess accuracy and inter-observer reliability. With a longitudinal design to describe persistent antigenicity of ICT and Paracheck, 224 children aged 6-59 months were followed up at 7-day intervals until the HRP2 antigens where undetectable by the RDTs. RESULTS: Of the 357 patients tested during the cross-sectional component, 40% (139) had positive blood smears for asexual forms of P. falciparum. ICT had an overall sensitivity of 98%, a specificity of 72%, a negative predictive value (NPV) of 98% and a positive predictive value (PPV) of 69%. ICT showed a high inter-observer reliability under operational conditions, with 95% of readings having assigned the same results (kappa statistics 0.921, p 50,000/microl, the mean duration of persistent antigenicity was 37 days compared to 26 days for parasitaemia less than 1,000/microl (log rank 21.9, p < 0.001). CONCLUSION: ICT is an accurate and appropriate test for operational use as a diagnostic tool where microscopy is unavailable. However, persistent antigenicity reduces the accuracy of this and other HRP2-based RDTs. The low specificity continues to be of concern, especially in children below five years of age. These pose limitations that need consideration, such as their use for diagnosis of patients returning with symptoms within two to four weeks of treatment. Good clinical skills are essential to interpret test results