Jodi Vanden Eng

Contribution of Integrated Campaign Distribution of Long-Lasting Insecticidal Nets to Coverage of Target Groups and Total Populations in Malaria-Endemic Areas in Madagascar

In October 2007, Madagascar conducted a nationwide integrated campaign to deliver measles vaccination, mebendazole, and vitamin A to children six months to five years of age. In 59 of the 111 districts, long-lasting insecticidal nets (LLINs) were delivered to children less than five years of age in combination with the other interventions. A community-based, cross-sectional survey assessed LLIN ownership and use six months post-campaign during the rainy season. LLIN ownership was analyzed by wealth quintile to assess equity. In the 59 districts, 76.8% of households possessed at least one LLIN from any source and 56.4% of households possessed a campaign net. Equity of campaign net ownership was evident. Post-campaign, the LLIN use target of > or = 80% by children less than five years of age and a high level of LLIN use (69%) by pregnant women were attained. Targeted LLIN distribution further contributed to total population coverage (60%) through use of campaign nets by all age groups.

Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya.

BackgroundResistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited.MethodsTemporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed.ResultsThe prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7 % in the first study (1996–2000) to 88 % in the third study (2008–2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4 % in 1998 to 44.4 % three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996–2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002–2008 and 2008–2009 studies. In addition, in the 2008–2009 study, 5.3 % of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples.ConclusionsThere was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug-resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP.

Impact of mass distribution of free long-lasting insecticidal nets on childhood malaria morbidity: The Togo National Integrated Child Health Campaign

BackgroundAn evaluation of the short-term impact on childhood malaria morbidity of mass distribution of free long-lasting insecticidal nets (LLINs) to households with children aged 9-59 months as part of the Togo National Integrated Child Health Campaign.MethodsThe prevalence of anaemia and malaria in children aged zero to 59 months was measured during two cross-sectional household cluster-sample surveys conducted during the peak malaria transmission, three months before (Sept 2004, n = 2521) and nine months after the campaign (Sept 2005, n = 2813) in three districts representative of Togos three epidemiological malaria transmission regions: southern tropical coastal plains (Yoto), central fertile highlands (Ogou) and northern semi-arid savannah (Tone).ResultsIn households with children <5 years of age, insecticide-treated net (ITN) ownership increased from <1% to >65% in all 3 districts. Reported ITN use by children during the previous night was 35.9%, 43.8% and 80.6% in Yoto, Ogou and Tone, respectively. Rainfall patterns were comparable in both years. The overall prevalence of moderate to severe anaemia (Hb < 8.0 g/dL) was reduced by 28% (prevalence ratio [PR] 0.72, 95% CI 0.62-0.84) and mean haemoglobin was increased by 0.35 g/dL (95% CI 0.25-0.45).The effect was predominantly seen in children aged 18-59 months and in the two southern districts: PR (95% CI) for moderate to severe anaemia and clinical malaria: Yoto 0.62 (0.44-0.88) and 0.49 (0.35-0.75); Ogou 0.54 (0.37-0.79) and 0.85 (0.57-1.27), respectively. Similar reductions occurred in children <18 months in Ogou, but not in Yoto. No effect was seen in the semi-arid northern district despite a high malaria burden and ITN coverage.ConclusionsA marked reduction in childhood malaria associated morbidity was observed in the year following mass distribution of free LLINs in two of the three districts in Togo. Sub-national level impact evaluations will contribute to a better understanding of the impact of expanding national malaria control efforts.

Comparison of anaemia and parasitaemia as indicators of malaria control in household and EPI-health facility surveys in Malawi

BackgroundThe World Health Organization has recommended that anaemia be used as an additional indicator to monitor malaria burden at the community level as malaria interventions are nationally scaled up. To date, there are no published evaluations of this recommendation.MethodsTo evaluate this recommendation, a comparison of anaemia and parasitaemia among 6-30 month old children was made during two repeated cross-sectional household (HH) and health facility (HF) surveys in six districts across Malawi at baseline (2005) and in a follow-up survey (2008) after a scale up of malaria control interventions.ResultsHH net ownership did not increase between the years (50.5% vs. 49.8%), but insecticide treated net (ITN) ownership increased modestly from 41.5% (95% CI: 37.2%-45.8%) in 2005 to 45.3% (95% CI: 42.6%-48.0%) in 2008. ITN use by children 6-30 months old, who were living in HH with at least one net, increased from 73.6% (95% CI:68.2%-79.1%) to 80.0% (95% CI:75.9%-84.1%) over the three-year period. This modest increase in ITN use was associated with a decrease in moderate to severe anaemia (Hb <8 g/dl) from 18.4% (95% CI:14.9%-21.8%) in 2005 to 15.4% (13.2%-17.7%) in 2008, while parasitaemia, measured as positive-slide microscopy, decreased from 18.9% (95% CI:14.7%-23.2%) to 16.9% (95% CI:13.8%-20.0%), a relative reduction of 16% and 11%, respectively. In HF surveys, anaemia prevalence decreased from 18.3% (95% CI: 14.9%-21.7%) to 15.4% (95% CI: 12.7%-18.2%), while parasitaemia decreased from 30.6% (95% CI: 25.7%-35.5%) to 13.2% (95% CI: 10.6%-15.8%), a relative reduction of 15% and 57%, respectively.ConclusionIncreasing access to effective malaria prevention was associated with a reduced burden of malaria in young Malawian children. Anaemia measured at the HF level at time of routine vaccination may be a good surrogate indicator for its measurement at the HH level in evaluating national malaria control programmes.

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

BackgroundMalarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined.MethodsFifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya.ResultsAn increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21).ConclusionsThis study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients.

Physical Durability of Two Types of Long-Lasting Insecticidal Nets (LLINs) Three Years After a Mass LLIN Distribution Campaign in Mozambique, 2008–2011

We conducted a prospective evaluation to measure the physical durability of two brands of long-lasting insecticidal nets (LLINs) distributed during a campaign in 2008 in Nampula Province, Mozambique. Households with LLINs tagged during the campaign (6,000) were geo-located (34%) and a random sample was selected for each of 3 years of follow-up. The LLINs were evaluated in the field and a laboratory for presence of holes and a proportional hole index (pHI) was calculated following the World Health Organization guidelines. We performed 567 interviews (79.0%) and found 75.3% (72.1-78.4%) of households retained at least one LLIN after 3 years; the most common cause of attrition was damage beyond repair (51.0%). Hole damage was evident after 1 year, and increased by year. Olyset had a significantly greater mean number of holes and pHI compared with PermaNet 2.0 brand (all P values ≤ 0.001). Additional information about LLIN durability is recommended to improve malaria control efforts.

Effect of transmission reduction by insecticide-treated bednets (ITNs) on antimalarial drug resistance in western Kenya.

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance.

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.