WHAT'S NEW THIS THURSDAY: FIVE ON MALARIA RDTs AND ON MALARIA

Wednesday, 29th of August 2012

• FIVE ON MALARIA RDTs AND ON MALARIA
  
• SAVINGS FROM USE OF MALARIA RDTs

Am J Trop Med Hyg. 2012 Jul 30. [Epub ahead of print]

Reductions in Artemisinin-Based Combination Therapy Consumption after the Nationwide Scale up of Routine Malaria Rapid Diagnostic Testing in Zambia

Yukich JO, Bennett A, Albertini A, Incardona S, Moonga H, Chisha Z, Hamainza B, Miller JM, Keating J, Eisele TP, Bell D.

Source

Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; Ministry of Health, National Malaria Control Centre, Lusaka, Zambia; Akros Research, Lusaka, Zambia; PATH Malaria Control and Evaluation Partnership in Africa (MACEPA), National Malaria Control Centre, Lusaka, Zambia.

Abstract below; full text is at http://www.ajtmh.org/content/early/2012/07/26/ajtmh.2012.12-0127.long

The National Malaria Control Center of Zambia introduced rapid diagnostic tests (RDTs) to detect Plasmodium falciparum as a pilot in some districts in 2005 and 2006; scale up at a national level was achieved in 2009. Data on RDT use, drug consumption, and diagnostic results were collected in three Zambian health districts to determine the impact RDTs had on malaria case management over the period 2004-2009. Reductions were seen in malaria diagnosis and antimalarial drug prescription (66.1 treatments per facility-month (95% confidence interval [CI] = 44.7-87.4) versus 26.6 treatments per facility-month (95% CI = 11.8-41.4)) pre- and post-RDT introduction. Results varied between districts, with significant reductions in low transmission areas but none in high areas. Rapid diagnostic tests may contribute to rationalization of treatment of febrile illness and reduce antimalarial drug consumption in Africa; however, their impact may be greater in lower transmission areas. National scale data will be necessary to confirm these findings.

Malar J. 2012 Jul 2;11(1):221. [Epub ahead of print]

·       USE OF MALARIA RDTs IN RURAL TANZANIA

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.

Masanja IM, Selemani M, Amuri B, Kajungu D, Khatib R, Kachur SP, Skarbinski J.

Abstract below; full text is at  http://www.malariajournal.com/content/pdf/1475-2875-11-221.pdf

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.

• COCHRANE REVIEW: RAPID DIAGNOSTIC TESTS FOR DIAGNOSING UNCOMPLICATED P. FALCIPARUM MALARIA IN ENDEMIC COUNTRIES

Cochrane Database Syst Rev. 2011 Jul 6;(7):CD008122.

Abba K, Deeks JJ, Olliaro P, Naing CM, Jackson SM, Takwoingi Y, Donegan S, Garner P.

Source

International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, Merseyside, UK, L3 5QA.

Abstract

BACKGROUND:

Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries.

OBJECTIVES:

To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand.

SEARCH STRATEGY:

We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010.

SELECTION CRITERIA:

Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas.

DATA COLLECTION AND ANALYSIS:

For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate.

MAIN RESULTS:

We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively. Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively. For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%). Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively. For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.

AUTHORS' CONCLUSIONS:

The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures. 

Comment in

• Assessing rapid diagnostic tests for malaria. [Cochrane Database Syst Rev. 2011]

• MALARIA TRENDS, RWANDA

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

Corine Karema, Maru W Aregawi, Alphonse Rukundo, Alain Kabayiza, Monique Mulindahabi, Ibrahima S Fall, Khoti Gausi, Ryan O Williams, Michael Lynch, Richard Cibulskis, Ngabo Fidele, Jean-Pierre Nyemazi, Daniel Ngamije, Irenee Umulisa, Robert Newman and Agnes Binagwaho

Malaria Journal 2012, 11:236 doi:10.1186/1475-2875-11-236, Published: 23 July 2012

Abstract below; full text, with figures, is at

http://www.malariajournal.com/content/pdf/1475-2875-11-236.pdf

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.

• INDOOR RESIDUAL SPRAYING FOR PREVENTION OF MALARIA

The Lancet Infectious Diseases, Volume 12, Issue 8, Pages 581 - 582, August 2012

Published Online: 07 June 2012

Indoor residual spraying for prevention of malaria

Original Text

Raphael N'Guessan a b, Mark Rowland a

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the two primary vector control interventions for malaria prevention. Use of LLINs in malaria endemic sub-Saharan Africa has, with support from the Global Fund and other international agencies, become much more common in the past decade. LLINs are deemed a simpler intervention to implement than IRS, whereas IRS has the potential to reduce transmission more rapidly, if campaigns are implemented rigorously and with high levels of household coverage.

IRS has some advantages over LLINs for outbreak control but is usually perceived as a time-limited intervention and its application is difficult to continue indefinitely because of high cost implicated. Nevertheless, in 2010 alone, the President's Malaria Initiative attempted to protect more than 27 million residents of 15 African countries, including Benin, by means of IRS with DDT or pyrethroid insecticides.1 In countries where pyrethroid resistance is already prevalent, such as Benin, the government has embarked on a strategy of campaigns promoting high LLIN coverage plus IRS with an insecticide of choice, bendiocarb, a carbamate with activity of 2—6 months.2

In The Lancet Infectious Diseases, Vincent Corbel and colleagues3 present a cluster randomised trial of LLIN and IRS in 28 villages in southern Benin, from 2007 to 2010, the first of several studies ongoing in Africa. This unique randomised trial is soundly done, despite some limitations.

The primary aim of the study3 was to examine whether the IRS every 8 months, as practised by a President's Malaria Initiative programme, provided additional benefit over existing LLINs. The outcome variables were clinical malaria, mosquito population densities, and selection of vector resistance to pyrethroids and carbamates. The surprising conclusion was that in an endemic malaria setting with perennial transmission and high frequency of pyrethroid resistance, IRS with a short-lived carbamate insecticide once a year provides no additional benefit to LLINs in the reduction of malaria incidence or prevalence: the reasons are not fully clear. The investigators found no indication of carbamate resistance having been selected. Perhaps, spraying annually was just not sufficient given the short-lived residual activity of bendiocarb.2 Whether IRS did enhance LLIN efficacy during the active period of bendiocarb still needs to be studied.

Corbel and colleagues3 also trialled a new vector control intervention of durable wall lining treated with a bendiocarb (carbamate-treated plastic sheeting), which can last longer than spray residue.4 This hope was confirmed by means of mosquito bioassay. The wall liners were retreated rather frequently but, more importantly, the coverage of durable lining on interior surfaces was far from complete. We fear that some mosquito surviving the exposure to LLINs could have encountered untreated refugia, leading to ineffectiveness of the combination and spurious conclusion about the strategy as a whole. This possibility was recognised by the authors as a major limitation.

The investigators did a secondary analysis to identify whether pyrethoid resistance negatively affected LLIN efficacy. Results showed that the capacity of LLINs to provide protection was affected in an environment in which resistance was prevalent. However, this finding is far from conclusive because no suitable control group was available. The coverage of LLIN was quite similar across the study groups and the frequency of pyrethroid resistance (kdr) rose to similarly high rates—ie, to 86% (95% CI 80—92) in the group with LLIN coverage targeted to pregnant women and children younger than 6 years and to 91% (84—98) in the group with universal coverage of LLINs.

Corbel and colleague's study should not discourage initiatives to deploy IRS for malaria transmission control in endemic countries. The study draws attention to the need to improve the timing and duration of spray cycles in endemic settings. Elsewhere, for example in Bioko, Equatorial Guinea, application of bendiocarb has been used to good effect to control pyrethroid-resistant Anopheles gambiae.5 Further trials are needed in other settings to reach stronger conclusions. The findings do indicate that the policy of adding IRS with short-lived insecticide to LLINs without the resources to repeat the spray cycles will provide only short-term gains.

We hope that the study will help encourage the development of alternative long-lasting formulations of active ingredients for IRS to combine with LLINs within homes for more cost effective control of malaria and management of resistance in sub-Saharan Africa.

The threat posed by pyrethroid resistance must be assessed and tackled vigorously.6, 7 Because of its easy detection, kdr is always monitored as proxy of the resistance issue, whereas more complex packages of resistance are common.8—10 Efficient methods now exist to diagnose associate members of the cytochrome P450 genes involved in pyrethroid detoxification in anophelines.11 Direct assessments of their combined expression on phenotypic resistance are needed.

We declare that we have no conflicts of interest.

1 The President's Malaria Initiative. Fifth annual report to Congress. Washington DC: USAID, 2011. http://www.pmi.gov/resources/reports/index.html. (accessed May 27, 2012)

2 WHO. Guidelines for testing mosquito adulticides intended for indoor residual spraying (IRS) and insecticide treated nets (ITNs). WHO/CDS/NTD/WHOPES/GCDDP/2006.3.

3 Corbel V, Akogbeto M, Damien GB, et al. Combination of malaria vector control interventions in pyrethroid resistance area in Benin: a cluster randomised controlled trial. Lancet Infect Dis; published online June 7, 2012. DOI:10.1016/S1473-3099(12)70081-6.

4 Djènontin A, Chandre F, Dabiré KR, et al. Indoor use of plastic sheeting impregnated with carbamate combined with long-lasting insecticidal mosquito nets for the control of pyrethroid-resistant malaria vectors. Am J Trop Med Hyg 2010; 83: 266-270. CrossRef | PubMed

5 Sharp BL, Ridl FC, Govender D, Kuklinski J, Kleinschmidt I. Malaria vector control by indoor residual insecticide spraying on the tropical island of Bioko, Equatorial Guinea. Malar J 2007; 6: 52. CrossRef | PubMed

6 Trape JF, Tall A, Diagne N, Ndiath O, et al. Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study. Lancet Infect Dis 2011; 11: 925-932. Summary | Full Text | PDF(276KB) | PubMed

7 Rehman AM, Coleman M, Schwabe C, et al. How much does malaria vector control quality matter: the epidemiological impact of holed nets and inadequate indoor residual spraying. PLoS One 2011; 6: e19205. CrossRef | PubMed

8 Corbel V, N'Guessan R, Brengues C, et al. Multiple insecticide resistance mechanisms in Anopheles gambiae and Culex quinquefasciatus from Benin, West Africa. Acta Trop 2007; 101: 207-216. CrossRef | PubMed

9 N'Guessan R, Corbel V, Akogbeto M, Rowland M. Reduced efficacy of insecticide-treated nets and indoor residual spraying for malaria control in pyrethroid resistance area, Benin. Emerg Infect Dis 2007; 13: 199-206. PubMed

10 Koffi AA, Ahoua Alou LP, Adja MA, Kone M, Chandre F, N'Guessan R. Update on resistance status of Anopheles gambiae s.s. to conventional insecticides at a previous WHOPES field site, “Yaokoffikro”, 6 years after the political crisis in Cote d'Ivoire. Parasit Vectors 2012; 5: 68. PubMed

11 Müller P, Donnelly MJ, Ranson H. Transcription profiling of a recently colonised pyrethroid resistant Anopheles gambiae strain from Ghana. BMC Genomic 2007; 8: 36. PubMed

a London School of Hygiene and Tropical Medicine, Keppel Street, London, UK

b Centre de Recherche Entomologique de Cotonou, Cotonou, Benin