Multiple causes of an unexpected malaria outbreak in a high-transmission area in Madagascar.

BACKGROUND: The malaria burden in Madagascar dropped down last decade, largely due to scale-up of control measures. Nevertheless, a significant rise of malaria cases occurred in 2011-2012 in two regions of the rainy South-Eastern Madagascar, where malaria is considered as mesoendemic and the population is supposed to be protected by its acquired immunity against Plasmodium. A multidisciplinary investigation was conducted in order to identify the causes of the outbreak. METHODS: In March 2012, a cross-sectional study was conducted in 20 randomly selected clusters, involving the rapid diagnostic testing of all ≥6 month-old members of households and a questionnaire about socio-demographic data and exposure to malaria control interventions. Changes in environmental conditions were evaluated by qualitative interview of local authorities, climatic conditions were evaluated by remote-sensing, and stock outs of malaria supplies in health facilities were evaluated by quantitative means. Two long-lasting insecticidal nets (LLINs) were sampled in each cluster in order to evaluate their condition and the remanence of their insecticidal activity. The entomological investigation also encompassed the collection Anopheles vectors in two sites, and the measure of their sensitivity to deltamethrin. RESULTS: The cross-sectional survey included 1615 members of 440 households. The mean Plasmodium infection rate was 25.6 % and the mean bed net use on the day before survey was 71.1 %. The prevalence of Plasmodium infections was higher in 6-14 year-old children (odds ratio (OR) 7.73 [95 % CI 3.58-16.68]), in rural areas (OR 6.25 [4.46-8.76]), in poorest socio-economic tercile (OR 1.54 [1.13-2.08]), and it was lower in individuals sleeping regularly under the bed net (OR 0.51 [0.32-0.82]). Stock outs of anti-malarial drugs in the last 6 months have been reported in two third of health facilities. Rainfalls were increased as compared with the three previous rainy seasons. Vectors collected were sensitive to pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity, CONCLUSIONS: Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011-2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission.

The Affordable Medicines Facility-malaria--a success in peril.

The Affordable Medicines Facility-malaria (AMFm) has put into place a bold financing plan for artemisinin-combination therapy in a pilot phase in seven countries covering half the population at risk of malaria in Africa. A report of the AMFm independent evaluation, conducted by ICF International and the London School of Hygiene and Tropical Medicine, describes the success of the programme in the pilot sites: Ghana, Kenya, Madagascar, Niger, Nigeria, Tanzania (mainland and Zanzibar) and Uganda, comparing availability and affordability of high-quality artemisinin-combination therapies before and after AMFm launched. Proof of concept was achieved: AMFm increased availability and kept prices low, meeting its initial, ambitious benchmarks in most settings. Despite this overwhelming success, opposition to the programme and dwindling resources for malaria control conspire to cripple or kill AMFm.

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. METHODS: Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. RESULTS: 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. CONCLUSIONS: These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries.

BACKGROUND: Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm). METHODS: Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment. RESULTS: Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%). The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89). Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia). However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar). Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%). Awareness is higher in Zambia (49%) and Uganda (33%). CONCLUSIONS: Levels of effective fever treatment are low and inequitable in many contexts. The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector. Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment.

Nonradioactive heteroduplex tracking assay for the detection of minority-variant chloroquine-resistant Plasmodium falciparum in Madagascar.

BACKGROUND: Strains of Plasmodium falciparum genetically resistant to chloroquine (CQ) due to the presence of pfcrt 76T appear to have been recently introduced to the island of Madagascar. The prevalence of such resistant genotypes is reported to be low (< 3%) when evaluated by conventional PCR. However, these methods are insensitive to low levels of mutant parasites present in patients with polyclonal infections. Thus, the current estimates may be an under representation of the prevalence of the CQ-resistant P. falciparum isolates on the island. Previously, minority variant chloroquine resistant parasites were described in Malawian patients using an isotopic heteroduplex tracking assay (HTA), which can detect pfcrt 76T-bearing P. falciparum minority variants in individual patients that were undetectable by conventional PCR. However, as this assay required a radiolabeled probe, it could not be used in many resource-limited settings. METHODS: This study describes a digoxigenin (DIG)-labeled chemiluminescent heteroduplex tracking assay (DIG-HTA) to detect pfcrt 76T-bearing minority variant P. falciparum. This assay was compared to restriction fragment length polymorphism (RFLP) analysis and to the isotopic HTA for detection of genetically CQ-resistant parasites in clinical samples. RESULTS: Thirty one clinical P. falciparum isolates (15 primary isolates and 16 recurrent isolates) from 17 Malagasy children treated with CQ for uncomplicated malaria were genotyped for the pfcrt K76T mutation. Two (11.7%) of 17 patients harboured genetically CQ-resistant P. falciparum strains after therapy as detected by HTA. RFLP analysis failed to detect any pfcrt K76T-bearing isolates. CONCLUSION: These findings indicate that genetically CQ-resistant P. falciparum are more common than previously thought in Madagascar even though the fitness of the minority variant pfcrt 76T parasites remains unclear. In addition, HTAs for malaria drug resistance alleles are promising tools for the surveillance of anti-malarial resistance. The use of a non-radioactive label allows for the use of HTAs in malaria endemic countries.

Free mass distribution of long lasting insecticidal nets lead to high levels of LLIN access and use in Madagascar, 2010: A cross-sectional observational study.

BACKGROUND: Madagascar conducted the first two phases of a national free mass distribution campaign of long-lasting insecticidal nets (LLINs) during a political crisis in 2009 aiming to achieve coverage of two LLINs per household as part of the National Malaria Control Strategy. The campaign targeted households in 19 out of 91 total health districts. METHODS: A community-based cross-sectional household survey using a three-stage cluster sample design was conducted four months post campaign to assess LLIN ownership, access and use. Multivariable logistic regression analysis was used to identify factors associated with household LLIN access and individual LLIN use. RESULTS: A total of 2211 households were surveyed representing 8867 people. At least one LLIN was present in 93.5% (95% confidence interval [CI], 91.6-95.5%) of households and 74.8% (95% CI, 71.0-78.6%) owned at least two LLINs. Access measured as the proportion of the population that could potentially be covered by household-owned LLINs was 77.2% (77.2% (95% CI, 72.9-81.3%) and LLIN use by all individuals was 84.2% (95% CI, 81.2-87.2%). LLIN use was associated with knowledge of insecticide treated net use to prevent malaria (OR = 3.58, 95% CI, 1.85-6.94), household ownership of more LLINs (OR 2.82, 95% CI 1.85-4.3), presence of children under five (OR = 2.05, 95% CI, 1.67-2.51), having traveled to the distribution point and receiving information about hanging a bednet (OR = 1.56, 95% CI, 1.41-1.74), and having received a post-campaign visit by a community mobilizer (OR = 1.75, 95% CI, 1.26-2.43). Lower LLIN use was associated with increasing household size (OR = 0.81 95% CI 0.77-0.85) and number of sleeping spaces (OR = 0.55, 95% CI, 0.44-0.68). CONCLUSIONS: A large scale free mass LLIN distribution campaign was feasible and effective at achieving high LLIN access and use in Madagascar. Campaign process indicators highlighted potential areas for strengthening implementation to optimize access and equity.