Analysing and Recommending Options for Maintaining Universal Coverage with Long-Lasting Insecticidal Nets: The Case of Tanzania in 2011.

Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of$449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered. The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency

Design, implementation and evaluation of a national campaign to distribute nine million free LLINs to children under five years of age in Tanzania.

BACKGROUND\ud \ud After a national voucher scheme in 2004 provided pregnant women and infants with highly subsidized insecticide-treated nets (ITNs), use among children under five years (U5s) in mainland Tanzania increased from 16% in 2004 to 26.2% in 2007. In 2008, the Ministry of Health and Social Welfare planned a catch-up campaign to rapidly and equitably deliver a free long-lasting insecticidal net (LLIN) to every child under five years in Tanzania.\ud \ud METHODS\ud \ud The ITN Cell, a unit within the National Malaria Control Programme (NMCP), coordinated the campaign on behalf of the Ministry of Health and Social Welfare. Government contractors trained and facilitated local government officials to supervise village-level volunteers on a registration of all U5s and the distribution and issuing of LLINs. The registration results formed the basis for the LLIN order and delivery to village level. Caregivers brought their registration coupons to village issuing posts during a three-day period where they received LLINs for their U5s. Household surveys in five districts assessed ITN ownership and use immediately after the campaign.\ud \ud RESULTS\ud \ud Nine donors contributed to the national campaign that purchased and distributed 9.0 million LLINs at an average cost of $7.07 per LLIN, including all campaign-associated activities. The campaign covered all eight zones of mainland Tanzania, the first region being covered separately during an integrated measles immunization/malaria LLIN distribution in August 2008, and was implemented one zone at a time from March 2009 until May 2010. ITN ownership at household level increased from Tanzania's 2008 national average of 45.7% to 63.4%, with significant regional variations. ITN use among U5s increased from 28.8% to 64.1%, a 2.2-fold increase, with increases ranging from 22.1-38.3% percentage points in different regions.\ud \ud CONCLUSION\ud \ud A national-level LLIN distribution strategy that fully engaged local government authorities helped avoid additional burden on the healthcare system. Distribution costs per net were comparable to other public health interventions. Particularly among rural residents, ITN ownership and use increased significantly for the intended beneficiaries. The upcoming universal LLIN distribution and further behaviour change communication will further improve ITN ownership and use in 2010-2011

African Malaria Control Programs Deliver ITNs and Achieve What the Clinical Trials Predicted

Thomas Eisele and Richard Steketee discuss new research in PLoS Medicine by Stephen Lim and colleagues that examined the association of insecticide-treated nets with the reduction of P. falciparum prevalence in children under 5 and all-cause post-neonatal mortality

Does the drug sensitivity of malaria parasites depend on their virulence?

<p>Abstract</p> <p>Background</p> <p>Chemotherapy can prompt the evolution of classical drug resistance, but selection can also favour other parasite traits that confer a survival advantage in the presence of drugs. The experiments reported here test the hypothesis that sub-optimal drug treatment of malaria parasites might generate survival and transmission advantages for virulent parasites.</p> <p>Methods</p> <p>Two <it>Plasmodium chabaudi </it>lines, one derived from the other by serial passage, were used to establish avirulent and virulent infections in mice. After five days, infections were treated with various doses of pyrimethamine administered over 1 or 4 days. Virulence measures (weight and anaemia), parasite and gametocyte dynamics were followed until day 21.</p> <p>Results</p> <p>All treatment regimes reduced parasite and gametocyte densities, but infections with the virulent line always produced more parasites and more gametocytes than infections with the avirulent line. Consistent with our hypothesis, drug treatment was disproportionately effective against the less virulent parasites. Treatment did not affect the relative transmission advantage of the virulent line. Neither of the lines contained known mutations conferring classical drug resistance.</p> <p>Conclusion</p> <p>Drug-sensitivity of malaria parasites can be virulence-dependent, with virulent parasites more likely to survive sub-optimal treatment. If this proves to be general for a variety of drugs and parasite species, selection imposed by sub-optimal drug treatment could result in the evolution of more aggressive malaria parasites.</p

Can universal insecticide-treated net campaigns achieve equity in coverage and use? the case of northern Nigeria

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated nets (ITNs) are effective tools for malaria prevention and can significantly reduce severe disease and mortality due to malaria, especially among children under five in endemic areas. However, ITN coverage and use remain low and inequitable among different socio-economic groups in sub-Saharan Africa, particularly in Nigeria. Several strategies have been proposed to increase coverage and use and reduce inequity in Nigeria, including free distribution campaigns recently conducted by the Nigerian federal government. Using data from the first post-campaign survey, the authors investigated the effect of the mass free distribution campaigns in achieving equity in household ownership and use of ITNs.</p> <p>Methods</p> <p>A post-campaign survey was undertaken in November 2009 in northern Nigeria to assess the effect of the campaigns in addressing equity across different socio-economic groups. The survey included 987 households randomly selected from 60 clusters in Kano state. Using logistic regression and the Lorenz concentration curve and index, the authors assessed equity in ITN coverage and use.</p> <p>Results</p> <p>ITN ownership coverage increased from 10% before the campaigns to 70%-a more than fivefold increase. The campaigns reduced the ownership coverage gap by 75%, effectively reaching parity among wealth quintiles (Concentration index 0.02, 95% CI (-0.02 ; 0.05) versus 0.21 95%CI (0.08 ; 0.34) before the campaigns). ITN use (individuals reporting having slept under an ITN the night before the survey visit) among individuals from households owning at least one ITN, was 53.1% with no statistically significant difference between the lowest, second, third and fourth wealth quintiles and the highest wealth quintile (lowest: odds ratio (OR) 0.87, 95% confidence interval (CI) (0.67 ; 1.13); second: OR 0.85, 95% CI (0.66 ; 1.24); third: OR 1.10 95% CI (0.86 ; 1.4) and fourth OR 0.91 95% CI (0.72 ; 1.15).</p> <p>Conclusion</p> <p>The campaign had a significant impact by increasing ITN coverage and reducing inequity in ownership and use. Free ITN distribution campaigns should be sustained to increase equitable coverage. These campaigns should be supplemented with other ITN distribution strategies to cover newborns and replace aging nets.</p

Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso

BACKGROUND: A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age. METHODS: During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol, was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria. RESULTS: PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits. CONCLUSION: While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use

Claims about the Misuse of Insecticide-Treated Mosquito Nets: Are These Evidence-Based?

Thomas Eisele and colleagues dispute reports in the media and elsewhere that insecticide-treated nets are not widely used, or are misused, and say that such misconceptions are not evidence-based and are damaging to malaria control efforts

Predation efficiency of Anopheles gambiae larvae by aquatic predators in western Kenya highlands

Abstract Background The current status of insecticide resistance in mosquitoes and the effects of insecticides on non-target insect species have raised the need for alternative control methods for malaria vectors. Predation has been suggested as one of the important regulation mechanisms for malaria vectors in long-lasting aquatic habitats, but the predation efficiency of the potential predators is largely unknown in the highlands of western Kenya. In the current study, we examined the predation efficiency of five predators on Anopheles gambiae s.s larvae in 24 hour and semi- field evaluations. Methods Predators were collected from natural habitats and starved for 12 hours prior to starting experiments. Preliminary experiments were conducted to ascertain the larval stage most predated by each predator species. When each larval instar was subjected to predation, third instar larvae were predated at the highest rate. Third instar larvae of An. gambiae were introduced into artificial habitats with and without refugia at various larval densities. The numbers of surviving larvae were counted after 24 hours in 24. In semi-field experiments, the larvae were counted daily until they were all either consumed or had developed to the pupal stage. Polymerase chain reaction was used to confirm the presence of An. gambiae DNA in predator guts. Results Experiments found that habitat type (P &lt; 0.0001) and predator species (P &lt; 0.0001) had a significant impact on the predation rate in the 24 hour evaluations. In semi-field experiments, predator species (P &lt; 0.0001) and habitat type (P &lt; 0.0001) were significant factors in both the daily survival and the overall developmental time of larvae. Pupation rates took significantly longer in habitats with refugia. An. gambiae DNA was found in at least three out of ten midguts for all predator species. Gambusia affins was the most efficient, being three times more efficient than tadpoles. Conclusion These experiments provide insight into the efficiency of specific natural predators against mosquito larvae. These naturally occurring predators may be useful in biocontrol strategies for aquatic stage An. gambiae mosquitoes. Further investigations should be done in complex natural habitats for these predators

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

Abstract Background: Malarial 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. Methods: Fifty-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. Results: An 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). Conclusions: This 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

Clinical trials to estimate the efficacy of preventive interventions against malaria in paediatric populations: a methodological review

BACKGROUND: Recent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluations between trials. METHODS: To prepare for a WHO consultation on design issues in malaria vaccine trials, controlled trials of preventive interventions against malaria in children in endemic countries were identified in which clinical malaria, or death, had been one of the main end-points. Trials were included that evaluated the impact of vaccines, insecticide-treated bed nets (ITN), intermittent presumptive or preventive therapy in infants (IPTi) or, in one instance, vitamin A supplementation. Methods that had been used in these trials were summarized and compared in order to identify issues that were directly relevant to the design of malaria vaccine trials. RESULTS: 29 controlled trials of preventive malaria interventions were identified, of which eight were vaccine trials. Vaccine trials that were designed to detect an effect on clinical malaria all reported the incidence rate of first episodes of clinical malaria as their primary endpoint. Only one trial of a preventive intervention (of ITN) was identified that was designed to detect an effect on severe malaria. A group of larger trials were designed to detect an effect of impregnated bed nets or curtains on all-cause mortality as the primary end-point. Key methodological and reporting differences between trials are noted in the text. Two issues have been identified that are of some concern. Firstly, the choice of primary endpoint is not stated in the reports of a number of the trials and, secondly, the relationship between pre-specified analysis plans and trial reports is rarely made clear. CONCLUSION: This article reports an investigation into the ways in which trial design and reporting could be improved and standardized to enable comparative evaluation of the relative merits of malaria control measures, and specifically with respect to the design of malaria vaccine trials. The need for standardization of clinical trial design, conduct, analysis and reporting has been also affirmed as a priority area by the Malaria Vaccine Technology Roadmap