Adoption of rapid diagnostic tests for the diagnosis of malaria, a preliminary analysis of the global fund program data, 2005 to 2010

Introduction

The World Health Organization Guidelines for the Treatment of Malaria, in 2006 and 2010, recommend parasitological confirmation of malaria before commencing treatment. Although microscopy has been the mainstay of malaria diagnostics, the magnitude of diagnostic scale up required to follow the Guidelines suggests that rapid diagnostic tests (RDTs) will be a large component. This study analyzes the adoption of rapid diagnostic testing in malaria programs supported by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund), the leading international funder of malaria control globally.

Methods and Findings

We analyzed, for the period 2005 to 2010, Global Fund programmatic data for 81 countries on the quantity of RDTs planned; actual quantities of RDTs and artemisinin-based combination treatments (ACTs) procured in 2009 and 2010; RDT-related activities including RDTs distributed, RDTs used, total diagnostic tests including RDTs and microscopy performed, health facilities equipped with RDTs; personnel trained to perform rapid diagnostic malaria test; and grant budgets allocated to malaria diagnosis. In 2010, diagnosis accounted for 5.2% of malaria grant budget. From 2005 to 2010, the procurement plans include148 million RDTs through 96 malaria grants in 81 countries. Around 115 million parasitological tests, including RDTs, had reportedly been performed from 2005 to 2010. Over this period, 123,132 health facilities were equipped with RDTs and 137,140 health personnel had been trained to perform RDT examinations. In 2009 and 2010, 41 million RDTs and 136 million ACTs were purchased. The ratio of procured RDTs to ACTs was 0.26 in 2009 and 0.34 in 2010.

Conclusions/significance

Global Fund financing has enabled 81 malaria-endemic countries to adopt WHO guidelines by investing in RDTs for malaria diagnosis, thereby helping improve case management of acute febrile illness in children. However, roll-out of parasitological diagnosis lags behind the roll-out of ACT-based treatment, and will require prioritization of investments.     

Continued Decline of Malaria in The Gambia with Implications for Elimination

Background

A substantial decline in malaria was reported to have occurred over several years until 2007 in the western part of The Gambia, encouraging consideration of future elimination in this previously highly endemic region. Scale up of interventions has since increased with support from the Global Fund and other donors.

Methodology/Principal Findings

We continued to examine laboratory records at four health facilities previously studied and investigated six additional facilities for a 7 year period, adding data from 243,707 slide examinations, to determine trends throughout the country until the end of 2009. We actively detected infections in a community cohort of 800 children living in rural villages throughout the 2008 malaria season, and assayed serological changes in another rural population between 2006 and 2009. Proportions of malaria positive slides declined significantly at all of the 10 health facilities between 2003 (annual mean across all sites, 38.7%) and 2009 (annual mean, 7.9%). Statistical modelling of trends confirmed significant seasonality and decline over time at each facility. Slide positivity was lowest in 2009 at all sites, except two where lowest levels were observed in 2006. Mapping households of cases presenting at the latter sites in 2007–2009 indicated that these were not restricted to a few residual foci. Only 2.8% (22/800) of a rural cohort of children had a malaria episode in the 2008 season, and there was substantial serological decline between 2006 and 2009 in a separate rural area.

Conclusions

Malaria has continued to decline in The Gambia, as indicated by a downward trend in slide positivity at health facilities, and unprecedented low incidence and seroprevalence in community surveys. We recommend intensification of control interventions for several years to further reduce incidence, prior to considering an elimination programme.     

PfHRP2-PfHRP3 diversity among Kenyan isolates and comparative evaluation of PfHRP2/pLDH malaria RDT with microscopy and nested PCR methodologies

Rapid diagnostic tests (RDT) are valuable tools that support prudent and timely use of antimalarial drugs, particularly if reliable microscopy is not available. However, the performance and reliability of these tests vary between and within geographical regions. The present study evaluated the performance of routine malaria RDT in Kenyan febrile patients in Busia County, Kenya. A cross sectional study design was employed to recruit febrile patients attending health facilities between August and November 2016. A total of 192 febrile patients who were slide positive and negative were evaluated for their infection status by nested PCR and RDTs (PfHRP2/pLDH). In addition, P. falciparum diversity of the histidine-rich proteins 2 and 3, that influences the RDT test results were determined. All individuals were P. falciparum positive. Among the investigated 192 febrile patients, 76 (40%) were positive by microscopy, 101 (53%) by RDTs and 80 (42%) were PCR positive. The performance of the CareStart? HRP2/pLDH (pf) RDTs was better than microscopy (Sensitivity 94%; Specificity 75%) and Nucleic acid testing (sensitivity 95%, specificity 77%) with high negative predictive values, indicating the suitability of the RDT in routine practice. Specific pfhrp2/pfhrp3 deletions shown to associate with RDT false negativity was not observed. However, high genetic diversity among pfhrp2 gene was observed. Eleven new PfHRP2 and nine PfHRP3 repeats were observed. False positivity by microscopy and under reporting of infections may thus be a barrier in malaria control and elimination programs. The HRP2/pLDH(Pf) based RDT yet demonstrate to be an effective tool for malaria surveillance program.     

Trends in malaria cases, hospital admissions and deaths following scale-up of anti-malarial interventions, 2000-2010, Rwanda

ABSTRACT: BACKGROUND: To control malaria, the Rwandan government and its partners distributed insecticide-treated nets (ITN) and made artemisinin-based combination therapy (ACT) widely available from 2005 onwards. The impact of these interventions on malaria cases, admissions and deaths was assessed using data from district hospitals and household surveys. METHODS: District records of ITN and ACT distribution were reviewed. Malaria and non-malaria indictors in 30 district hospitals were ascertained from surveillance records. Trends in cases, admissions and deaths for 2000 to 2010 were assessed by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period, 2000-2005. Changes were estimated by comparing trends in post-intervention (2006-2010) with that of pre-intervention (2000-2005) period. All-cause deaths in children under-five in household surveys of 2005 and 2010 were also reviewed to corroborate with the trends of deaths observed in hospitals. RESULTS: The proportion of the population potentially protected by ITN increased from nearly zero in 2005 to 38% in 2006, and 76% in 2010; no major health facility stock-outs of ACT were recorded following their introduction in 2006. In district hospitals, after falling during 2006- 2008, confirmed malaria cases increased in 2009 coinciding with decreased potential ITN coverage and declined again in 2010 following an ITN distribution campaign. For all age groups, from the pre-intervention period, microscopically confirmed cases declined by 72%, (95% Confidence Interval [CI], 12-91%) in 2010, slide positivity rate declined 58%, (CI, 47%-68%), malaria inpatient cases declined 76% (CI, 49%-88%); and malaria deaths declined 47% (CI, 47%-81%). In children below five years of age, malaria inpatients decreased 82% (CI, 61%-92%) and malaria hospital deaths decreased 77% (CI, 40%-91%). Concurrently, outpatient cases, admissions and deaths due to non-malaria diseases in all age groups either increased or remained unchanged. Rainfall and temperature remained favourable for malaria transmission. The annual all-cause mortality in children under-five in household surveys declined from 152 per 1,000 live births during 2001-2005, to 76 per 1,000 live births in 2006-2010 (55% decline). The five-year cumulative number of all-cause deaths in hospital declined 28% (8,051 to 5,801) during the same period. CONCLUSIONS: A greater than 50% decline in confirmed malaria cases, admissions and deaths at district hospitals in Rwanda since 2005 followed a marked increase in ITN coverage and use of ACT. The decline occurred among both children under-five and in children five years and above, while hospital utilization increased and suitable conditions for malaria transmission persisted. Declines in malaria indicators were more striking than in the older age groups. The resurgence in cases associated with decreased ITN coverage in 2009 highlights the need for sustained high levels of anti-malarial interventions in Rwanda and other malaria endemic countries.     

Access to artemisinin combination therapy for malaria in remote areas of Cambodia

Background

Within the context of increasing antimalarial costs and or decreasing malaria transmission, the importance of limiting antimalarial treatment to only those confirmed as having malaria parasites becomes paramount. This motivates for this assessment of the cost-effectiveness of routine use of rapid diagnostic tests (RDTs) as an integral part of deploying artemisinin-based combination therapies (ACTs).

Methods

The costs and cost-effectiveness of using RDTs to limit the use of ACTs to those who actually have Plasmodium falciparum parasitaemia in two districts in southern Mozambique were assessed. To evaluate the potential impact of introducing definitive diagnosis using RDTs (costing $0.95), five scenarios were considered, assuming that the use of definitive diagnosis would find that between 25% and 75% of the clinically diagnosed malaria patients are confirmed to be parasitaemic. The base analysis compared two ACTs, artesunate plus sulfadoxine/pyrimethamine (AS+SP) costing $1.77 per adult treatment and artemether-lumefantrine (AL) costing $2.40 per adult treatment, as well as the option of restricting RDT use to only those older than six years. Sensitivity analyses considered lower cost ACTs and RDTs and different population age distributions.

Results

Compared to treating patients on the basis of clinical diagnosis, the use of RDTs in all clinically diagnosed malaria cases results in cost savings only when 29% and 52% or less of all suspected malaria cases test positive for malaria and are treated with AS+SP and AL, respectively. These cut-off points increase to 41.5% (for AS+SP) and to 74% (for AL) when the use of RDTs is restricted to only those older than six years of age. When 25% of clinically diagnosed patients are RDT positive and treated using AL, there are cost savings per malaria positive patient treated of up to $2.12. When more than 29% of clinically diagnosed cases are malaria test positive, the incremental cost per malaria positive patient treated is less than US$ 1. When relatively less expensive ACTs are introduced (e.g. current WHO preferential price for AL of $1.44 per adult treatment), the RDT price to the healthcare provider should be $0.65 or lower for RDTs to be cost saving in populations with between 30 and 52% of clinically diagnosed malaria cases being malaria test positive.

Conclusion

While the use of RDTs in all suspected cases has been shown to be cost-saving when parasite prevalence among clinically diagnosed malaria cases is low to moderate, findings show that targeting RDTs at the group older than six years and treating children less than six years on the basis of clinical diagnosis is even more cost-saving. In semi-immune populations, young children carry the highest risk of severe malaria and many healthcare providers would find it harder to deny antimalarials to those who test negative in this age group.     

Low quality of routine microscopy for malaria at different levels of the health system in Dar es Salaam

Background

Laboratory capacity to confirm malaria cases in Tanzania is low and presumptive treatment of malaria is being practiced widely. In malaria endemic areas WHO now recommends systematic laboratory testing when suspecting malaria. Currently, the use of Rapid Diagnostic Tests (RDTs) is recommended for the diagnosis of malaria in lower level peripheral facilities, but not in health centres and hospitals. In this study, the following parameters were evaluated: (1) the quality of routine microscopy, and (2) the effects of RDT implementation on the positivity rate of malaria test results at three levels of the health system in Dar es Salaam, Tanzania.

Methods

During a baseline cross-sectional survey, routine blood slides were randomly picked from 12 urban public health facilities in Dar es Salaam, Tanzania. Sensitivity and specificity of routine slides were assessed against expert microscopy. In March 2007, following training of health workers, RDTs were introduced in nine public health facilities (three hospitals, three health centres and three dispensaries) in a near-to-programmatic way, while three control health facilities continued using microscopy. The monthly malaria positivity rates (PR) recorded in health statistics registers were collected before (routine microscopy) and after (routine RDTs) the intervention in all facilities.

Results

At baseline, 53% of blood slides were reported as positive by the routine laboratories, whereas only 2% were positive by expert microscopy. Sensitivity of routine microscopy was 71.4% and specificity was 47.3%. Positive and negative predictive values were 2.8% and 98.7%, respectively. Median parasitaemia was only three parasites per 200 white blood cells (WBC) by routine microscopy compared to 1226 parasites per 200 WBC by expert microscopy. Before RDT implementation, the mean test positivity rates using routine microscopy were 43% in hospitals, 62% in health centres and 58% in dispensaries. After RDT implementation, mean positivity rates using routine RDTs were 6%, 7% and 8%, respectively. The sensitivity and specificity of RDTs using expert microscopy as reference were 97.0% and 96.8%. The positivity rate of routine microscopy remained the same in the three control facilities: 71% before versus 72% after. Two cross-sectional health facility surveys confirmed that the parasite rate in febrile patients was low in Dar es Salaam during both the rainy season (13.6%) and the dry season (3.3%).

Conclusions

The quality of routine microscopy was poor in all health facilities, regardless of their level. Over-diagnosis was massive, with many false positive results reported as very low parasitaemia (1 to 5 parasites per 200 WBC). RDTs should replace microscopy as first-line diagnostic tool for malaria in all settings, especially in hospitals where the potential for saving lives is greatest.

     

Clinical diagnosis of malaria on the Thai-Myanmar border.

BACKGROUND: To evaluate the prevailing practice of presumptively diagnosing malaria in all cases of febrile illness in a clinic serving a refugee population on the Thai-Myanmar border METHODS: A retrospective review of 3,506 patient charts from December 1993 through June 1994 at the MaeSot medical clinic to compare clinical signs of malaria to blood smear findings. Patients presenting without fever were assumed not to have malaria; the remaining 2,111 patients presenting with fever had blood smears examined for malaria infection. RESULTS: Fever alone sufferedfrom poorpositive predictive value (54.7 percent) and specificity (59.3 percent). When fever was combined with hepatosplenomegaly and anemia, the positive predictive value and specificity improved (84.5 percent and 98.5 percent, respectively). However, this combination also resulted in an unacceptably poor sensitivity (16.5 percent) and false negative error rate (835/1,000). CONCLUSIONS. In this nonimmune refugee population, severe complications of falciparum malaria occur quickly and commonly; aggressive chemotherapy is necessary to reduce morbidity and mortality. Until laboratory facilities are made available, all cases offever should continue to be treated presumptively as malaria.     

A cost-effectiveness analysis of provider and community interventions to improve the treatment of uncomplicated malaria in Nigeria: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: There is mounting evidence of poor adherence by health service personnel to clinical guidelines for malaria following a symptomatic diagnosis. In response to this, the World Health Organization (WHO) recommends that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or Rapid Diagnostic Test (RDT). The Government of Nigeria plans to introduce RDTs in public health facilities over the coming year. In this context, we will evaluate the effectiveness and cost-effectiveness of two interventions designed to support the roll-out of RDTs and improve the rational use of ACTs. It is feared that without supporting interventions, non-adherence will remain a serious impediment to implementing malaria treatment guidelines. Methods/design A three-arm stratified cluster randomized trial is used to compare the effectiveness and costeffectiveness of: (1) provider malaria training intervention versus expected standard practice in malaria diagnosis and treatment; (2) provider malaria training intervention plus schoolbased intervention versus expected standard practice; and (3) the combined provider plus school-based intervention versus provider intervention alone. RDTs will be introduced in all arms of the trial. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit primary health centers, pharmacies, and patent medicine dealers. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider and community knowledge. Costs will be estimated from both a societal and provider perspective using standard economic evaluation methodologies. Trial registration Clinicaltrials.gov NCT01350752.     

Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study

Objective To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission.Design Prospective observational study of children and adults over the course a year.Setting 10 hospitals in north east Tanzania.Participants 17 313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease.Main outcome measure Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system.Results Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged ≥ 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children.Conclusions In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.     

Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study

In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects.     

The Impact of Artemisinin Combination Therapy and Long-Lasting Insecticidal Nets on Forest Malaria Incidence in Tribal Villages of India, 2006–2011

Introduction

New tools for malaria control, artemisinin combination therapy (ACT) and long-lasting insecticidal nets (LLINs) were recently introduced across India. We estimated the impact of universal coverage of ACT and ACT plus LLINs in a setting of hyperendemic, forest malaria transmission.

Methods

We reviewed data collected through active and passive case detection in a vaccine trial cohort of 2,204 tribal people residing in Sundargarh district, Odisha between 2006 and 2011. We compared measures of transmission at the village and individual level in 2006–2009 versus 2010–2011 after ACT (in all villages) and LLINs (in three villages) were implemented.

Results

During 2006–2009 malaria incidence per village ranged from 156–512 per 1000 persons per year and slide prevalence ranged from 28–53%. Routine indoor residual spray did not prevent seasonal peaks of malaria. Post-intervention impact in 2010–2011 was dramatic with ranges of 14–71 per 1000 persons per year and 6–16% respectively. When adjusted for village, ACT alone decreased the incidence of malaria by 83% (IRR 0.17, 95%CI: 0.10, 0.27) and areas using ACT and LLINs decreased the incidence of malaria by 86% (IRR 0.14, 95%CI: 0.05, 0.38). After intervention, the age of malaria cases, their parasite density, and proportion with fever at the time of screening increased.

Conclusions

ACT, and LLINs along with ACT, effectively reduced malaria incidence in a closely monitored population living in a forest ecotype. It is unclear whether LLINs were impactful when prompt and quality antimalarial treatment was available. In spite of universal coverage, substantial malaria burden remained.     

External Quality Assessment of Reading and Interpretation of Malaria Rapid Diagnostic Tests among 1849 End-Users in the Democratic Republic of the Congo through Short Message Service (SMS)

Background

Although malaria rapid diagnostic tests (RDT) are simple to perform, they remain subject to errors, mainly related to the post-analytical phase. We organized the first large scale SMS based external quality assessment (EQA) on correct reading and interpretation of photographs of a three-band malaria RDT among laboratory health workers in the Democratic Republic of the Congo (DR Congo).

Methods and Findings

High resolution EQA photographs of 10 RDT results together with a questionnaire were distributed to health facilities in 9 out of 11 provinces in DR Congo. Each laboratory health worker answered the EQA by Short Message Service (SMS). Filled-in questionnaires from each health facility were sent back to Kinshasa. A total of 1849 laboratory health workers in 1014 health facilities participated. Most frequent errors in RDT reading were i) failure to recognize invalid (13.2–32.5% ) or negative test results (9.8–12.8%), (ii) overlooking faint test lines (4.1–31.2%) and (iii) incorrect identification of the malaria species (12.1–17.4%). No uniform strategy for diagnosis of malaria at the health facility was present. Stock outs of RDTs occurred frequently. Half of the health facilities had not received an RDT training. Only two thirds used the RDT recommended by the National Malaria Control Program. Performance of RDT reading was positively associated with training and the technical level of health facility. Facilities with RDT positivity rates >50% and located in Eastern DR Congo performed worse.

Conclusions

Our study confirmed that errors in reading and interpretation of malaria RDTs are widespread and highlighted the problem of stock outs of RDTs. Adequate training of end-users in the application of malaria RDTs associated with regular EQAs is recommended.     

Rapid Antigen Detection Tests for Malaria Diagnosis in Severely Ill Papua New Guinean Children: A Comparative Study Using Bayesian Latent Class Models

Background

Although rapid diagnostic tests (RDTs) have practical advantages over light microscopy (LM) and good sensitivity in severe falciparum malaria in Africa, their utility where severe non-falciparum malaria occurs is unknown. LM, RDTs and polymerase chain reaction (PCR)-based methods have limitations, and thus conventional comparative malaria diagnostic studies employ imperfect gold standards. We assessed whether, using Bayesian latent class models (LCMs) which do not require a reference method, RDTs could safely direct initial anti-infective therapy in severe ill children from an area of hyperendemic transmission of both Plasmodium falciparum and P. vivax.

Methods and Findings

We studied 797 Papua New Guinean children hospitalized with well-characterized severe illness for whom LM, RDT and nested PCR (nPCR) results were available. For any severe malaria, the estimated prevalence was 47.5% with RDTs exhibiting similar sensitivity and negative predictive value (NPV) to nPCR (≥96.0%). LM was the least sensitive test (87.4%) and had the lowest NPV (89.7%), but had the highest specificity (99.1%) and positive predictive value (98.9%). For severe falciparum malaria (prevalence 42.9%), the findings were similar. For non-falciparum severe malaria (prevalence 6.9%), no test had the WHO-recommended sensitivity and specificity of >95% and >90%, respectively. RDTs were the least sensitive (69.6%) and had the lowest NPV (96.7%).

Conclusions

RDTs appear a valuable point-of-care test that is at least equivalent to LM in diagnosing severe falciparum malaria in this epidemiologic situation. None of the tests had the required sensitivity/specificity for severe non-falciparum malaria but the number of false-negative RDTs in this group was small.     

Behavioral and environmental determinants of reproductive success in traditional Moroccan Berber groups

The reproductive histories of women aged 45–70 years from a homogeneous Berber population of South Morocco were sampled from three contrasting environments: a small town (n = 75), villages in the lowlands (n = 217), and villages in the highlands (n = 128). The main reproductive variables oppose the relatively better conditions of fertile life in the lowlands to the more hostile ones in the highlands. Path analysis confirms this difference through reproductive behaviors and suggests the existence of mechanisms for controlling family size in town and in the rural lowlands, but not in the highlands. The estimates of survival function show significant differences among the three groups, the conditions for survival in the highlands being clearly less favorable. Rank tests of the association of survival data with several covariates indicate the association of survival data with vaccinations and with conditions of delivery. In spite of the lower rate of offspring survival, the highlander group would demonstrate a higher overall number of children reaching reproductive maturity, thanks to an extended reproductive span. © 1996 Wiley-Liss, Inc.     

Feasibility of Distributing Rapid Diagnostic Tests for Malaria in the Retail Sector: Evidence from an Implementation Study in Uganda

Background

Despite the benefits of malaria diagnosis, most presumed malaria episodes are never tested. A primary reason is the absence of diagnostic tests in retail establishments, where many patients seek care. Malaria rapid diagnostic tests (RDTs) in drug shops hold promise for guiding appropriate treatment. However, retail providers generally lack awareness of RDTs and training to administer them. Further, unsubsidized RDTs may be unaffordable to patients and unattractive to retailers. This paper reports results from an intervention study testing the feasibility of RDT distribution in Ugandan drug shops.

Methods and Findings

92 drug shops in 58 villages were offered subsidized RDTs for sale after completing training. Data on RDT purchases, storage, administration and disposal were collected, and samples were sent for quality testing. Household surveys were conducted to capture treatment outcomes. Estimated daily RDT sales varied substantially across shops, from zero to 8.46 RDTs per days. Overall compliance with storage, treatment and disposal guidelines was excellent. All RDTs (100%) collected from shops passed quality testing. The median price charged for RDTs was 1000USH ($0.40), corresponding to a 100% markup, and the same price as blood slides in local health clinics. RDTs affected treatment decisions. RDT-positive patients were 23 percentage points more likely to buy Artemisinin Combination Therapies (ACTs) (p = .005) and 33.1 percentage points more likely to buy other antimalarials (p<.001) than RDT-negative patients, and were 5.6 percentage points more likely to buy ACTs (p = .05) and 31.4 percentage points more likely to buy other antimalarials (p<.001) than those not tested at all.

Conclusions

Despite some heterogeneity, shops demonstrated a desire to stock RDTs and use them to guide treatment recommendations. Most shops stored, administered and disposed of RDTs properly and charged mark-ups similar to those charged on common medicines. Results from this study suggest that distributing RDTs through the retail sector is feasible and can reduce inappropriate treatment for suspected malaria.     

Low Parasitemia in Submicroscopic Infections Significantly Impacts Malaria Diagnostic Sensitivity in the Highlands of Western Kenya

Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5–14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections.     

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons.     

A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation

Background

Angola's malaria case-management policy recommends treatment with artemether-lumefantrine (AL). In 2006, AL implementation began in Huambo Province, which involved training health workers (HWs), supervision, delivering AL to health facilities, and improving malaria testing with microscopy and rapid diagnostic tests (RDTs). Implementation was complicated by a policy that was sometimes ambiguous.

Methods

Fourteen months after implementation began, a cross-sectional survey was conducted in 33 outpatient facilities in Huambo Province to assess their readiness to manage malaria and the quality of malaria case-management for patients of all ages. Consultations were observed, patients were interviewed and re-examined, and HWs were interviewed.

Results

Ninety-three HWs and 177 consultations were evaluated, although many sampled consultations were missed. All facilities had AL in-stock and at least one HW trained to use AL and RDTs. However, anti-malarial stock-outs in the previous three months were common, clinical supervision was infrequent, and HWs had important knowledge gaps. Except for fever history, clinical assessments were often incomplete. Although testing was recommended for all patients with suspected malaria, only 30.7% of such patients were tested. Correct testing was significantly associated with caseloads < 25 patients/day (odds ratio: 18.4; p < 0.0001) and elevated patient temperature (odds ratio: 2.5 per 1°C increase; p = 0.007). Testing was more common among AL-trained HWs, but the association was borderline significant (p = 0.072). When the malaria test was negative, HWs often diagnosed patients with malaria (57.8%) and prescribed anti-malarials (60.0%). Sixty-six percent of malaria-related diagnoses were correct, 20.1% were minor errors, and 13.9% were major (potentially life-threatening) errors. Only 49.0% of malaria treatments were correct, 5.4% were minor errors, and 45.6% were major errors. HWs almost always dosed AL correctly and gave accurate dosing instructions to patients; however, other aspects of counseling needed improvement.

Conclusion

By late-2007, substantial progress had been made to implement the malaria case-management policy in a setting with weak infrastructure. However, policy ambiguities, under-use of malaria testing, and distrust of negative test results led to many incorrect malaria diagnoses and treatments. In 2009, Angola published a policy that clarified many issues. As problems identified in this survey are not unique to Angola, better strategies for improving HW performance are urgently needed.