Helen Counihan

Malaria Misdiagnosis in Uganda – Implications for Policy Change

BackgroundIn Uganda, like in many other countries traditionally viewed as harbouring very high malaria transmission, the norm has been to recommend that febrile episodes are diagnosed as malaria. In this study, the policy implications of such recommendations are revisited.MethodsA cross-sectional survey was undertaken at outpatient departments of all health facilities in four Ugandan districts. The routine diagnostic practices were assessed for all patients during exit interviews and a research slide was obtained for later reading. Primary outcome measures were the accuracy of national recommendations and routine malaria diagnosis in comparison with the study definition of malaria (any parasitaemia on expert slide examination in patient with fever) stratified by age and intensity of malaria transmission. Secondary outcome measures were the use, interpretation and accuracy of routine malaria microscopy.Results1,763 consultations undertaken by 233 health workers at 188 facilities were evaluated. The prevalence of malaria was 24.2% and ranged between 13.9% in patients ≥5 years in medium-to-high transmission areas to 50.5% for children <5 years in very high transmission areas. Overall, the sensitivity and negative predictive value (NPV) of routine malaria diagnosis were high (89.7% and 91.6% respectively) while the specificity and positive predictive value (PPV) were low (35.6% and 30.8% respectively). However, malaria was under-diagnosed in 39.9% of children less than five years of age in the very high transmission area. At 48 facilities with functional microscopy, the use of malaria slide examination was low (34.5%) without significant differences between age groups, or between patients for whom microscopy is recommended or not. 96.2% of patients with a routine positive slide result were treated for malaria but also 47.6% with a negative result.ConclusionCurrent recommendations and associated clinical practices result in massive laria over-diagnosis across all age groups and transmission areas in Uganda. Yet, under-diagnosis is also common in children <5 years. The potential benefits of malaria microscopy are not realized. To address malaria misdiagnosis, Ugandas policy shift from presumptive to parasitological diagnosis should encompass introduction of malaria rapid diagnostic tests and substantial strengthening of malaria microscopy.

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

BackgroundParasite-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.MethodsUsing 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.ResultsOf 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 < 0.001).In children followed up after successful antimalaria treatment, the mean duration of persistent antigenicity was 32 days, and this duration varied significantly depending on pre-treatment parasitaemia. In patients with parasite density >50,000/μl, the mean duration of persistent antigenicity was 37 days compared to 26 days for parasitaemia less than 1,000/μl (log rank 21.9, p < 0.001).ConclusionICT 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.

Community Health Workers Use Malaria Rapid Diagnostic Tests (RDTs) Safely and Accurately: Results of a Longitudinal Study in Zambia

Malaria rapid diagnostic tests (RDTs) could radically improve febrile illness management in remote and low-resource populations. However, reliance upon community health workers (CHWs) remains controversial because of concerns about blood safety and appropriate use of artemisinin combination therapy. This study assessed CHW ability to use RDTs safely and accurately up to 12 months post-training. We trained 65 Zambian CHWs, and then provided RDTs, job-aids, and other necessary supplies for village use. Observers assessed CHW performance at 3, 6, and 12 months post-training. Critical steps performed correctly increased from 87.5% at 3 months to 100% subsequently. However, a few CHWs incorrectly read faint positive or invalid results as negative. Although most indicators improved or remained stable over time, interpretation of faint positives fell to 76.7% correct at 12 months. We conclude that appropriately trained and supervised CHWs can use RDTs safely and accurately in community practice for up to 12 months post-training.

Community acceptability of use of rapid diagnostic tests for malaria by community health workers in Uganda

BackgroundMany malarious countries plan to introduce artemisinin combination therapy (ACT) at community level using community health workers (CHWs) for treatment of uncomplicated malaria. Use of ACT with reliance on presumptive diagnosis may lead to excessive use, increased costs and rise of drug resistance. Use of rapid diagnostic tests (RDTs) could address these challenges but only if the communities will accept their use by CHWs. This study assessed community acceptability of the use of RDTs by Ugandan CHWs, locally referred to as community medicine distributors (CMDs).MethodsThe study was conducted in Iganga district using 10 focus group discussions (FGDs) with CMDs and caregivers of children under five years, and 10 key informant interviews (KIIs) with health workers and community leaders. Pre-designed FGD and KII guides were used to collect data. Manifest content analysis was used to explore issues of trust and confidence in CMDs, stigma associated with drawing blood from children, community willingness for CMDs to use RDTs, and challenges anticipated to be faced by the CMDs.ResultsCMDs are trusted by their communities because of their commitment to voluntary service, access, and the perceived effectiveness of anti-malarial drugs they provide. Some community members expressed fear that the blood collected could be used for HIV testing, the procedure could infect children with HIV, and the blood samples could be used for witchcraft. Education level of CMDs is important in their acceptability by the community, who welcome the use of RDTs given that the CMDs are trained and supported. Anticipated challenges for CMDs included transport for patient follow-up and picking supplies, adults demanding to be tested, and caregivers insisting their children be treated instead of being referred.ConclusionUse of RDTs by CMDs is likely to be acceptable by community members given that CMDs are properly trained, and receive regular technical supervision and logistical support. A well-designed behaviour change communication strategy is needed to address the anticipated programmatic challenges as well as community fears and stigma about drawing blood. Level of formal education may have to be a criterion for CMD selection into programmes deploying RDTs.

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

BackgroundMalaria 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.MethodsHRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum 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.ResultsAmong 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 P. falciparum 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 P. falciparum 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 (McNemars X2> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemars X2< 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.ConclusionUse 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.

The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial.

Objective  To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria‐related morbidity in children <5 years of age who already had access to home‐based management of malaria (HMM) for presumptive treatment of fevers.

Multi-country analysis of routine data from integrated community case management (iCCM) programs in sub-Saharan Africa.

Aim To identify better performing iCCM programs in sub–Saharan Africa (SSA) and identify factors associated with better performance using routine data. Methods We examined 15 evaluations or studies of integrated community case management (iCCM) programs in SSA conducted between 2008 and 2013 and with information about the program; routine data on treatments, supervision, and stockouts; and, where available, data from community health worker (CHW) surveys on supervision and stockouts. Analyses included descriptive statistics, Fisher exact test for differences in median treatment rates, the Kruskal-Wallis test for differences in the distribution of treatment rates, and Spearman’s correlation by program factors. Results The median percent of annual expected cases treated was 27% (1–74%) for total iCCM, 37% (1–80%) for malaria, 155% (7–552%) for pneumonia, and 27% (1–74%) for diarrhoea. Seven programs had above median total iCCM treatments rates. Four programs had above median treatment rates, above median treatments per active CHW per month, and above median percent of expected cases treated. Larger populations under–five targeted were negatively associated with treatment rates for fever, malaria, diarrhea, and total iCCM. The ratio of CHWs per population was positively associated with diarrhoea treatment rates. Use of rapid diagnostic tests (RDTs) was negatively associated with treatment rates for pneumonia. Treatment rates and percent of annual expected cases treated were equivalent between programs with volunteer CHWs and programs with salaried CHWs. Conclusions There is large variation in iCCM program performance in SSA. Four programs appear to be higher performing in terms of treatment rates, treatments per CHW per month, and percent of expected cases treated. Treatment rates for diarrhoea are lower than expected across most programmes. CHWs in many programmes are overtreating pneumonia. Programs targeting larger populations under–five tend to have lower treatment rates. The reasons for lower pneumonia treatment rates where CHWs use RDTs need to be explored. Programs with volunteer CHWs and those with salaried CHWs can achieve similar treatment rates and percent of annual expected cases treated but to do so volunteer programs must manage more CHWs per population and salaried CHWs must provide more treatments per CHW per month.

Introduction of Newborn Care within Integrated Community Case Management in Uganda

Ugandas Ministry of Health, together with partners, has introduced integrated community case management (iCCM) for children under 5 years. We assessed how the iCCM program addresses newborn care in three midwestern districts through document reviews, structured interviews, and focus group discussions with village health team (VHT) members trained in iCCM, caregivers, and other stakeholders. Almost all VHT members reported that they refer sick newborns to facilities and could identify at least three newborn danger signs. However, they did not identify the most important clinical indicators of severe illness. The extent of compliance with newborn referral and quality of care for newborns at facilities is not clear. Overall iCCM is perceived as beneficial, but caregivers, VHTs, and health workers want to do more for sick babies at facilities and in communities. Additional research is needed to assess the ability of VHTs to identify newborn danger signs, referral compliance, and quality of newborn treatment at facilities.

Finding parasites and finding challenges: improved diagnostic access and trends in reported malaria and anti-malarial drug use in Livingstone district, Zambia

BackgroundUnderstanding the impact of malaria rapid diagnostic test (RDT) use on management of acute febrile disease at a community level, and on the consumption of anti-malarial medicines, is critical to the planning and success of scale-up to universal parasite-based diagnosis by health systems in malaria-endemic countries.MethodsA retrospective study of district-wide community-level RDT introduction was conducted in Livingstone District, Zambia, to assess the impact of this programmed on malaria reporting, incidence of mortality and on district anti-malarial consumption.ResultsReported malaria declined from 12,186 cases in the quarter prior to RDT introduction in 2007 to an average of 12.25 confirmed and 294 unconfirmed malaria cases per quarter over the year to September 2009. Reported malaria-like fever also declined, with only 4,381 RDTs being consumed per quarter over the same year. Reported malaria mortality declined to zero in the year to September 2009, and all-cause mortality declined. Consumption of artemisinin-based combination therapy (ACT) dropped dramatically, but remained above reported malaria, declining from 12,550 courses dispensed by the district office in the quarter prior to RDT implementation to an average of 822 per quarter over the last year. Quinine consumption in health centres also declined, with the district office ceasing to supply due to low usage, but requests for sulphadoxine-pyrimethamine (SP) rose to well above previous levels, suggesting substitution of ACT with this drug in RDT-negative cases.ConclusionsRDT introduction led to a large decline in reported malaria cases and in ACT consumption in Livingstone district. Reported malaria mortality declined to zero, indicating safety of the new diagnostic regime, although adherence and/or use of RDTs was still incomplete. However, a deficiency is apparent in management of non-malarial fever, with inappropriate use of a low-cost single dose drug, SP, replacing ACT. While large gains have been achieved, the full potential of RDTs will only be realized when strategies can be put in place to better manage RDT-negative cases.

Integrated community case management of malaria, pneumonia and diarrhoea across three African countries: A qualitative study exploring lessons learnt and implications for further scale up.

Numerous studies highlight the effectiveness of an integrated approach for the management of malaria, pneumonia and diarrhoea at the community level. There has however been little study on lessons learnt from implementation in practice and stakeholder experiences which could inform future programmatic planning and evaluation frameworks. A participatory, qualitative evaluation was conducted in the three varied settings of South Sudan, Uganda and Zambia, which have seen the scale up of integrated community case management (iCCM) over the last five years. All key in–country stakeholders were consulted on study design, with a particular focus on scope and methodology. Data collection methods included stakeholder consultations (key informant interviews, focus group discussions), and a review of project and Ministry of Health documentation. Data analysis followed the Framework Approach. Results suggest that iCCM implementation generally followed national pre–agreed guidelines. Overarching key programmatic recommendations included: collaboration with implementing partners in planning stages to positively impact on community acceptance and ownership; adoption of participatory training methods adapted to low literacy populations; development of alternative support supervision methods such as peer support groups; full integration of community level data into the health management information system and emphasizing data analysis, use and feedback at all levels; strengthened supply chains through improved quantification and procurement of commodities in conjunction with the national distribution network; community engagement to establish a support system for community health workers to increase their motivation; enhanced sensitisation and behaviour change communication to raise awareness and usage of appropriate health services; and advocacy at the national level for funding and logistical support for the continuation and integration of iCCM. This qualitative study is a valuable contribution in understanding the ‘hows’ of iCCM implementation with key insights for improved feasibility and acceptability. Main findings show how community support to iCCM and community health workers is necessary for sustained health benefits coupled with a focus on strengthening and ‘enabling’ the public health system. The participatory study design and methodologies used enabled the scope of the research enquiry to effectively capture various stakeholder perspectives.