Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear. METHODS: Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels. RESULTS: There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss. CONCLUSIONS: There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household.

Prevalence of malaria among patients attending public health facilities in Maputo City, Mozambique.

We conducted a health facility-based survey to estimate the prevalence of malaria among febrile patients at health facilities (HFs) in Maputo City. Patients answered a questionnaire on malaria risk factors and underwent malaria testing. A malaria case was defined as a positive result for malaria by microscopy in a patient with fever or history of fever in the previous 24 hours. Among 706 patients with complete information, 111 (15.7%) cases were identified: 105 were positive for Plasmodium falciparum only, two for Plasmodium ovale only, and four for both P. falciparum and P. ovale. Fever documented at study enrollment, age ≥ 5 years, rural HF, and travel outside Maputo City were statistically significantly associated with malaria by multivariate analysis. We found a high prevalence of laboratory-confirmed malaria among febrile patients in Maputo City. Further studies are needed to relate these findings with mosquito density to better support malaria prevention and control.

What drives community adherence to indoor residual spraying (IRS) against malaria in Manhiça district, rural Mozambique: a qualitative study.

BACKGROUND: Malaria control remains a challenge in sub-Saharan Africa. In 2006, the World Health Organization (WHO) reinforced the recommendation of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) to reduce malaria transmission. The National Malaria Control Programme has been reporting high coverage rates of IRS in Mozambique. It is important to establish to what extent these rates are a reflection of community acceptability, and to explore the factors associated with adherence, in order to recommend suitable approaches for interventions of this nature. OBJECTIVE: To understand the implementation process, reception and acceptability of the IRS program in Manhiça district, Southern Mozambique. METHODS: Qualitative data was collected through in-depth interviews, participant observation of IRS activities, informal interviews, and focus group discussions. Study participants comprised householders, community leaders, health care providers, sprayers, and community members. Qualitative data analysis was based on grounded theory. Secondary data from the Manhiça Demographic Surveillance System was used to complement the qualitative data. RESULTS: IRS was well received in most neighbourhoods. The overall coverage rates varied between 29% and 41% throughout the study period. The factors related to adherence to IRS were: immediate impact on insects in general, trust and obedience in the health authority, community leaders' influence, and acquaintance with the sprayers. Fighting malaria was not an important motivation for IRS adherence. There was a perception of limited efficacy of IRS against mosquitoes, but this did not affect adherence. Non-adherence to the intervention was mainly due to the unavailability of key householders, disagreement with the procedures, and the perception that spraying increased the burden of insects. Most respondents strongly favoured bed nets over IRS. CONCLUSION: The study suggests that the contribution of IRS to malaria and mosquito control is not entirely perceived by the beneficiaries, and that other as cost effective interventions such as insecticide-treated nets are favoured over IRS. Adherence to IRS was found to be influenced by socio-political factors. There is a need to redefine the community sensitization approaches in order to make IRS a genuinely participative, acceptable, and sustainable programme.

Prozone in malaria rapid diagnostics tests: how many cases are missed?

BACKGROUND: Prozone means false-negative or false-low results in antigen-antibody reactions, due to an excess of either antigen or antibody. The present study prospectively assessed its frequency for malaria rapid diagnostic tests (RDTs) and Plasmodium falciparum samples in an endemic field setting. METHODS: From January to April 2010, blood samples with P. falciparum high parasitaemia (≥ 4% red blood cells infected) were obtained from patients presenting at the Provincial Hospital of Tete (Mozambique). Samples were tested undiluted and 10-fold diluted in saline with a panel of RDTs and results were scored for line intensity (no line visible, faint, weak, medium and strong). Prozone was defined as a sample which showed no visible test line or a faint or weak test line when tested undiluted, and a visible test line of higher intensity when tested 10-fold diluted, as observed by two blinded observers and upon duplicate testing. RESULTS: A total of 873/7,543 (11.6%) samples showed P. falciparum, 92 (10.5%) had high parasitaemia and 76 were available for prozone testing. None of the two Pf-pLDH RDTs, but all six HRP-2 RDTs showed prozone, at frequencies between 6.7% and 38.2%. Negative and faint HRP-2 lines accounted for four (3.8%) and 15 (14.4%) of the 104 prozone results in two RDT brands. For the most affected brand, the proportions of prozone with no visible or faint HRP-2 lines were 10.9% (CI: 5.34-19.08), 1.2% (CI: 0.55-2.10) and 0.1% (CI: 0.06-0.24) among samples with high parasitaemia, all positive samples and all submitted samples respectively. Prozone occurred mainly, but not exclusively, among young children. CONCLUSION: Prozone occurs at different frequency and intensity in HRP-2 RDTs and may decrease diagnostic accuracy in the most affected RDTs.

Impact of malaria at the end of pregnancy on infant mortality and morbidity.

BACKGROUND: There is some consensus that malaria in pregnancy may negatively affect infant's mortality and malaria morbidity, but there is less evidence concerning the factors involved. METHODS: A total of 1030 Mozambican pregnant women were enrolled in a randomized, placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine, and their infants were followed up throughout infancy. Overall mortality and malaria morbidity rates were recorded. The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed. RESULTS: There were 58 infant deaths among 997 live-born infants. The risk of dying during infancy was increased among infants born to women with acute placental infection (odds ratio [OR], 5.08 [95% confidence interval (CI), 1.77-14.53)], parasitemia in cord blood (OR, 19.31 [95% CI, 4.44-84.02]), low birth weight (OR, 2.82 [95% CI, 1.27-6.28]) or prematurity (OR, 3.19 [95% CI, 1.14-8.95]). Infants born to women who had clinical malaria during pregnancy (OR, 1.96 [95% CI, 1.13-3.41]) or acute placental infection (OR, 4.63 [95% CI, 2.10-10.24]) had an increased risk of clinical malaria during infancy. CONCLUSIONS: Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy. Effective clinical management and prevention of malaria in pregnancy may improve infant's health and survival.

Malaria prevention with IPTp during pregnancy reduces neonatal mortality.

BACKGROUND: In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association. METHODS: In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP. FINDINGS: There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024]. CONCLUSIONS: Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health. TRIAL REGISTRATION: ClinicalTrials.gov NCT00209781.

An assessment of Lot Quality Assurance Sampling to evaluate malaria outcome indicators: extending malaria indicator surveys.

BACKGROUND: Large investments and increased global prioritization of malaria prevention and treatment have resulted in greater emphasis on programme monitoring and evaluation (M&E) in many countries. Many countries currently use large multistage cluster sample surveys to monitor malaria outcome indicators on a regional and national level. However, these surveys often mask local-level variability important to programme management. Lot Quality Assurance Sampling (LQAS) has played a valuable role for local-level programme M&E. If incorporated into these larger surveys, it would provide a comprehensive M&E plan at little, if any, extra cost. METHODS: The Mozambique Ministry of Health conducted a Malaria Indicator Survey (MIS) in June and July 2007. We applied LQAS classification rules to the 345 sampled enumeration areas to demonstrate identifying high- and low-performing areas with respect to two malaria program indicators-'household possession of any bednet' and 'household possession of any insecticide-treated bednet (ITN)'. RESULTS: As shown by the MIS, no province in Mozambique achieved the 70% coverage target for household possession of bednets or ITNs. By applying LQAS classification rules to the data, we identify 266 of the 345 enumeration areas as having bednet coverage severely below the 70% target. An additional 73 were identified with low ITN coverage. CONCLUSIONS: This article demonstrates the feasibility of integrating LQAS into multistage cluster sampling surveys and using these results to support a comprehensive national, regional and local programme M&E system. Furthermore, in the recommendations we outlined how to integrate the Large Country-LQAS design into macro-surveys while still obtaining results available through current sampling practices.

Combining indoor residual spraying and insecticide-treated net interventions.

Does scaling up of malaria control by combining indoor residual spraying (IRS) and long-lasting insecticidal nets (LLIN) enhance protection to populations? Results from a literature search and from recent household surveys in Bioko, Equatorial Guinea, and Zambezia, Mozambique are presented. Five out of eight previous studies reported a reduced risk of infection in those protected by both interventions compared with one intervention alone. Surveys in Bioko and Zambezia showed strong evidence of a protective effect of IRS combined with nets relative to IRS alone (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59-0.86 for Bioko, and OR = 0.63, 95% CI = 0.50-0.79, for Zambezia). The effect of both interventions combined, compared with those who had neither, was OR = 0.46, (95% CI = 0.76-0.81) in Bioko and 0.34 (95% CI = 0.21-0.56) in Zambezia. Although the effects of confounding cannot be excluded, these results provide encouragement that the additional resources for combining IRS and LLIN are justified.

A country-wide malaria survey in Mozambique. II. Malaria attributable proportion of fever and establishment of malaria case definition in children across different epidemiological settings.

BACKGROUND: Protection against clinical malaria episodes is acquired slowly after frequent exposure to malaria parasites. This is reflected by a decrease with increasing age in both parasite density and incidence of clinical episodes. In many settings of stable malaria transmission, the presence of asymptomatic malaria parasite carriers is common and the definition of clinical malaria remains uncertain. METHODS: Between February 2002 and April 2003, a country-wide malaria survey was conducted in 24 districts of Mozambique, aiming to characterize the malaria transmission intensities and to estimate the proportion of fever cases attributable to malaria infections in order to establish the malaria case definition. A total of 8,816 children less than ten years of age were selected for the study. Axillary temperature was measured in all participating subjects and finger prick blood collections were taken to prepare thick and thin films for identification of parasite species and determination of parasite density. The proportion of fever cases attributable to malaria infection was estimated using a logistic regression of the fever on a monotonic function of the parasite density and, using bootstrap facilities, bootstrapped estimated confidence intervals, as well as the sensitivity and specificity for different parasite density cut-offs were produced. RESULTS: Overall, the prevalence of Plasmodium falciparum was 52.4% (4,616/8,816). The prevalence of fever (axillary temperature >or= 37.5 degrees C) was 9.4% (766/8,816). Fever episodes peaked among children below 12 months of life [15.1% (206/1,517)]. The lowest fever prevalence of 5.9% (67/1,224) was recorded amongst children between five and seven years of age. Among 4,098 parasitized children, 498/4,098 (13.02%) had fever. The prevalence of malaria infections associated with fever peaked among children in the less than twelve months age group and thereafter decreased rapidly with increasing age (p < 0.001). High parasite densities were significantly associated with fever (p < 0.04). The proportion of fever attributed to malaria was 37.8% (95% CI 32.9% - 42.7%). An age-specific pattern was observed with significant variations across different regions in the country. In general, among children less than 12 months of life, the proportion of fever attributed to malaria infection was 43.5% (95% CI 25.8% - 61.2%), in children aged between 12 and 59 months of age was 39.6% (95% CI 30.3% - 48.9%), and among children aged between 5 and 10 years old was 21.5% (95% CI 11.6% - 31.4%). CONCLUSION: This study confirms that malaria remains a major cause of febrile illness during childhood. It also defines the relation between parasite density and fever and how this varies with age and region. This may help guide case definition for clinical trials of preventive tools, as well as provide definitions that may improve the precision of measurement of the burden of disease.

A country-wide malaria survey in Mozambique. I. Plasmodium falciparum infection in children in different epidemiological settings.

BACKGROUND: Across tropical Africa the bulk of malaria-related morbidity and mortality is particularly high during childhood. Classical malariometric surveys have relied on assessing malaria infection prevalence. The last comprehensive evaluation of the malaria situation in Mozambique was carried out during the 1950s. This study aims to characterize the malaria transmission intensities and to estimate the disease burden that may help guide control programme. METHODS: Between February 2002 and April 2003, a house-to-house survey, was carried out in 24 districts randomly selected. A total of 8,816 children aged below 10 years old were enrolled. Finger prick and blood collection were performed to prepare thick and thin films for malaria parasite species identification, density and haemoglobin concentration. Axillary temperature was also measured. Prevalence of infection, parasite density and anaemia were estimated for age groups category in each region/stratum. Comparisons between proportions were made using Chi-square test or Fisher exact. Relationship between age groups, region/stratum and parasite prevalence, density was determined using linear regression. All survey mean estimations were adjusted for sampling weights, clustering and stratification. RESULTS: Malaria parasite prevalence was 58.9% (5.190/8.816), the majority of blood smears 52.4% (4,616/8,816) were due to Plasmodium falciparum and geometric mean parasite density was 1,211 parasites/microl (95% CI, 1,141-1.286). Gametocytes prevalence, only for P. falciparum was 5.6% (518/8,816). The burden was highest in the northern regions and in the coastal stratum. Parasite infection and geometric mean parasite density peaked during the second year of life and thereafter decreased with increasing age. Mean haemoglobin concentrations was 9.9 g/dl (95% CI 9.5-10.2). Anaemia prevalence was 69.8% (6.257/8.816) and among anaemic children 11.5% (743/6.257) were severely anaemic. Anaemia rose dramatically during the first year of life to peak among children in the 12-23 months age group. Highest levels of anaemia were recorded in both northern and central-northern regions 77.9% and 79.4% respectively. CONCLUSION: This survey confirms that malaria especially that caused by P. falciparum, remains endemic throughout the country. The burden of malaria disease and anaemia-related malaria during childhood constitute a major public health problem and warrant integrated and collaborative interventions towards its control.

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic.

BACKGROUND: Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use. METHODS: 1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight. FINDINGS: Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was more than 90% in both groups. CONCLUSIONS: Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00209781.

Clinical malaria in African pregnant women.

BACKGROUND: There is a widespread notion, based on limited information, that in areas of stable malaria transmission most pregnant women with Plasmodium falciparum infection are asymptomatic. This study aim to characterize the clinical presentation of malaria in African pregnant women and to evaluate the adequacy of case management based on clinical complaints. METHODS: A hospital-based descriptive study between August 2003 and November 2005 was conducted at the maternity clinic of a rural hospital in Mozambique. All women attending the maternity clinic were invited to participate. A total of 2,330 women made 3,437 eligible visits, 3129 were analysed, the remainder were excluded because diagnostic results were unavailable or they were repeat visits. Women gave a standardized clinical history and had a medical exam. Malaria parasitaemia and haematocrit in capillary blood was determined for all women with signs or symptoms compatible with malaria including: presence and history of fever, arthromyalgias, headache, history of convulsions and pallor. Outcome measure was association of malaria symptoms or signs with positive blood slide for malaria parasitaemia. RESULTS: In 77.4% of visits pregnant women had symptoms suggestive of malaria; 23% (708/3129) were in the first trimester. Malaria parasitaemia was confirmed in 26.9% (842/3129) of visits. Headache, arthromyalgias and history of fever were the most common symptoms (86.5%, 74.8% and 65.4%) presented, but their positive predictive values for malaria parasitaemia were low [28% (27-30), 29% (28-31), and 33% (31-35), respectively]. CONCLUSION: Symptoms suggestive of malaria were very frequent among pregnant women attending a rural maternity clinic in an area of stable malaria transmission. However, less than a third of them were parasitaemic. In the absence of microscopy or rapid diagnostic tests, a large proportion of women, including those in the first trimester of gestation, would be unnecessarily receiving antimalarial drugs, often those with unknown safety profiles for pregnancy. Accessibility to malaria diagnostic tools needs to be improved for pregnant women and drugs with a safety profile in all gestational ages are urgently needed.

Intermittent preventive treatment for malaria control administered at the time of routine vaccinations in Mozambican infants: a randomized, placebo-controlled trial.

BACKGROUND: There is an urgent need to deploy and develop new control tools that will reduce the intolerable burden of malaria. Intermittent preventive treatment in infants (IPTi) has the potential to become an effective tool for malaria control. METHODS: We performed a randomized, double-blind, placebo-controlled trial of sulfadoxine-pyrimethamine (SP) treatment in 1503 Mozambican children. Doses of SP or placebo were given at 3, 4, and 9 months of age. The intervention was administered alongside routine vaccinations delivered through the Expanded Program on Immunization (EPI). Hematological and biochemical tests were done when infants were 5 months old. Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys when infants were 12 and 24 months old. RESULTS: IPTi was well tolerated, and no adverse events associated with SP were documented. During the first year of life, intermittent SP treatment reduced the incidence of clinical malaria by 22.2% (95% confidence interval [CI], 3.7%-37.0%; P=.020) and the rate of hospital admissions by 19% (95% CI, 4.0%-31.0%; P=.014). Although the incidence of severe anemia (packed cell volume of <25%) did not differ significantly between the 2 groups (protective effect, 12.7% [95% CI, -17.3% to 35.1%]; P=.36), there was a significant reduction in hospital admissions for anemia during the month after dosing for both the first and second dose. The serological responses to EPI vaccines were not modified by the intervention. CONCLUSIONS: IPTi with SP has been shown to moderately reduce the incidence of clinical malaria in Mozambican infants without evidence of rebound after stopping the intervention or of interactions with EPI vaccines. Its recommendation as a malaria control strategy in Mozambique needs to be balanced against the scarcity of affordable control tools and the burden of malaria in children.