Iron supplementation in anemic Zanzibari toddlers is associated with greater loss in erythrocyte iron isotope enrichment.

BACKGROUND: Heavy parasitic loads increase the risk of iron (Fe) deficiency anemia, which remains prevalent globally. Where parasites are common, understanding the influence of parasitic infections on Fe incorporation and erythropoiesis in toddlers is especially important. OBJECTIVES: The aim of this study was to identify the impacts of malarial and helminth infections on red blood cell (RBC) Fe incorporation and subsequent changes in RBC Fe isotope enrichment for 84 days postdosing in toddlers at high risk for parasitic infections. METHODS: Fe incorporation was measured in a group of Zanzibari toddlers (n = 71; 16-25 months) using a stable Fe isotopic method. At study entry, an oral stable Fe isotope was administered. Blood was collected 14 (D14) and 84 (D84) days postdosing for the assessment of Fe status indicators and RBC isotopic enrichment. Blood and stool samples were collected and screened for malaria and helminth parasites. Factors associated with changes in RBC Fe isotope enrichment were identified using regression models. RESULTS: Toddlers who had larger weight-for-age z-scores, lower total body Fe, and helminth infections (n = 26) exhibited higher RBC Fe incorporation. RBC Fe isotope enrichment decreased from D14 to D84 by -2.75 percentage points (P < 0.0001; n = 66). Greater loss in RBC Fe isotope enrichment from D14 to D84 was observed in those who received Fe supplementation, those with either helminths or both malarial and helminth infections, and in those with greater RBC Fe incorporation on D14. CONCLUSIONS: Toddlers who received Fe supplementation exhibited significantly greater losses of RBC Fe isotope enrichment over time. We speculate this greater loss of RBC Fe enrichment is indicative of increased erythropoiesis due to the provision of Fe among anemic or helminth-infected toddlers.

Artemisinin combination therapy mass drug administration in a setting of low malaria endemicity: programmatic coverage and adherence during an observational study in Zanzibar.

BACKGROUND: Mass drug administration (MDA) appears to be effective in reducing the risk of malaria parasitaemia. This study reports on programmatic coverage and compliance of MDA using artemisinin-based combination therapy (ACT) in four shehias (smallest administration unit) that had been identified as hotspots through Zanzibar's malaria case notification surveillance system. METHODS: Mass drug administration was done in four shehias selected on the basis of: being an established malaria hot spot; having had mass screening and treatment (MSaT) 2-6 weeks previously; and exceeding the epidemic alert threshold of 5 cases within a week even after MSaT. Communities were sensitized and MDA was conducted using a house-to-house approach. All household members, except pregnant women and children aged less than 2 months, were provided with ACT medicine. Two weeks after the MDA campaign, a survey was undertaken to investigate completion of ACT doses. RESULTS: A total of 8816 [97.1% of eligible; 95% confidence interval (CI) 96.8-97.5] people received ACT. During post MDA surveys, 2009 people were interviewed: 90.2% reported having completed MDA doses; 1.9% started treatment but did not complete dosage; 4.7% did not take treatment; 2.0% were absent during MDA and 1.2% were ineligible (i.e. infants <2 months and pregnant women). Main reasons for failure to complete treatment were experience of side-effects and forgetting to take subsequent doses. Failure to take treatment was mainly due to fear of side-effects, reluctance due to lack of malaria symptoms and caregivers forgetting to give medication to children. CONCLUSION: Mass drug administration for malaria was well accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates. Further work to investigate the potential of MDA in accelerating Zanzibar's efforts towards malaria elimination should be pursued.

Indoor residual spraying with micro-encapsulated pirimiphos-methyl (Actellic® 300CS) against malaria vectors in the Lake Victoria basin, Tanzania.

BACKGROUND: The indoor residual spraying programme for malaria vectors control was implemented in four districts of the Lake Victoria basin of Tanzania namely Ukerewe, Sengerema, Rorya andSerengeti. Entomological monitoring activities were implemented in one sentinel village in each district to evaluate the efficacy of pirimiphos-methyl 300 CS sprayed on different wall surfaces and its impact against malaria vectors post-IRS intervention. METHODS: The residual decay rate of p-methyl 300 CS applied at a target dosage of 1g a.i./m2 on thesprayed wall surfaces was monitored for a period of 43 weeks post-IRSusing the WHO cone wall bioassay method. The bioassays were performed by exposing 2-5 days old unfed susceptible female Anopheles gambiae s.s. (Kisumu strain) to sprayed wall surfaces for a period of 30 minutes. In each sentinel village, mosquito collection was carried out by trained community mosquito collectors. Monthly mosquito collections were carried out from 6.00pm to 6.00am using CDC light traps and clay pot methods for indoors host seekingand outdoors resting mosquitoes respectively. Six traps (2 CDC light traps and 4 clay pots) were set per sentinel village per night for28 consecutive days in a moon. PCR and ELISA were used for mosquito species identification and sporozoite detection, respectively. RESULTS: Based on the WHOPES recommendation, insecticides should have a minimum efficacy of ≥ 80% mosquito mortality at 24 hours post exposure on the sprayed wall surfaces to be considered effective. In this study, p-methyl 300 CS was demonstrated to have a long residual efficacy of 21-43 weeks post-IRS on mud, cement, painted and wood wall surfaces. Numberof anopheline mosquitoes decreased post-IRS interventions in all sentinel villages. The highest numbers ofanopheline mosquitoes were collected in November-December, 38-43 weeks post-IRS. A total of 270 female anopheline mosquitoes were analyzed by PCR; out of which 236 (87.4%) were An. gambiae s.l. and 34 (12.6%) were An. funestus group. Of the 236 An. gambiae s.l.identified 12.6% (n = 34) were An. gambiae s.s. and 68.6% (n = 162) were An. arabiensis. Ofthe 34 An. funestus group indentified 91.2% (n = 31) were An. parensis and 8.8% (n = 3) were An. rivulorum. The overall Plasmodium falciparum sporozoite rate was 0.7% (n = 2,098). CONCLUSIONS: Pirimiphos-methyl 300 CS was found to be effective for IRS in the Lake Victoria basin,Tanzania. P-methyl 300 CShas a long residual efficacy on sprayed wall surfaces and therefore it is effective in controlling principal malaria vectors of An. gambiae s.l and An. funestus which rest on wall surfaces after and before feeding.

Pregnant women and infants as sentinel populations to monitor prevalence of malaria: results of pilot study in Lake Zone of Tanzania.

BACKGROUND: As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination. METHODS: Pregnant women attending first ANC and infants nine to 12 months old presenting for measles vaccination at a non-probability sample of 54 HFs in Tanzania's Lake Zone (Mara, Mwanza and Kagera Regions) were screened for malaria infection using a malaria rapid diagnostic test (RDT) from December 2012 to November 2013, regardless of symptoms. Participants who tested positive were treated for malaria per national guidelines. Data were collected monthly. RESULTS: Overall 89.9 and 78.1 % of expected monthly reports on malaria infection prevalence were received for pregnant women and infants, respectively. Among 51,467 pregnant women and 35,155 infants attending routine preventive HF visits, 41.2 and 37.3 % were tested with RDT, respectively. Malaria infection prevalence was 12.8 % [95 % confidence interval (CI) 11.3-14.3] among pregnant women and 11.0 % (95 % CI 9.5-12.5) among infants, and varied by month. There was good correlation of the prevalence of malaria among pregnant women and infants at the HF level (Spearman rho = 0.6; p < 0.001). This approach is estimated to cost $1.28 for every person tested, with the RDT accounting for 72 % of the cost. CONCLUSIONS: Malaria infection was common and well correlated among pregnant women and infants attending routine health services. Routine screening of these readily accessible populations may offer a practical strategy for continuously tracking malaria trends, particularly seasonal variation. Positivity rates among afebrile individuals presenting for routine care offer an advantage as they are unaffected by the prevalence of other causes of febrile illness, which could influence positivity rates among febrile patients presenting to outpatient clinics. The data presented here suggest that in addition to contributing to clinical management, ongoing screening of pregnant women could be used for routine surveillance and detection of hotspots.

School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania.

Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania.

Taking local ownership: government and household contribution to indoor residual spraying in Zanzibar and mainland Tanzania.

BACKGROUND: While donor funding is instrumental in initiation and implementation of malaria control efforts, national government contributions are key to local ownership and sustainability. This study explored in-kind contributions of local government and households towards the cost of indoor residual spraying (IRS) interventions in Tanzania. METHODS: Data were collected through interviews with local government officials and technical teams in the IRS project. Household contribution was based on provision of water for IRS. Government contributions included government-provided warehouse and office space, vehicles, and staff labour. In-kind contributions were aggregated at the district, regional and national level. Calculations were based on proportion of total costs of IRS from 2010 to 2012. RESULTS: The mainland government provided larger amounts of in-kind contribution in absolute value (mean of US$454 200) compared to Zanzibar (US$89 163). On average, in-kind contribution was 5.5% of total costs in Zanzibar and 2.9% in mainland. The proportion of government in-kind contribution was higher in Zanzibar versus the mainland (86% vs 50%) while household contribution was higher in mainland compared to Zanzibar (50% vs 14%). CONCLUSION: Government involvement, particularly through budgetary allocations and increased in-kind contribution, needs to be encouraged for malaria control efforts to be locally owned, managed and sustained.

Efficacy, persistence and vector susceptibility to pirimiphos-methyl (Actellic 300CS) insecticide for indoor residual spraying in Zanzibar.

BACKGROUND: Indoor residual spraying (IRS) of households with insecticide is a principal malaria vector control intervention in Zanzibar. In 2006, IRS using the pyrethroid lambda-cyhalothrine was introduced in Zanzibar. Following detection of pyrethroid resistance in 2010, an insecticide resistance management plan was proposed, and IRS using bendiocarb was started in 2011. In 2014, bendiocarb was replaced by pirimiphos methyl. This study investigated the residual efficacy of pirimiphos methyl (Actellic 300CS) sprayed on common surfaces of human dwellings in Zanzibar. METHODS: The residual activity of Actellic 300CS was determined over 9 months through bioassay tests that measured the mortality of female Anopheles mosquitoes, exposed to sprayed surfaces under a WHO cone. The wall surfaces included; mud wall, oil or water painted walls, lime washed wall, un-plastered cement block wall and stone blocks. Insecticide susceptibility testing was done to investigate the resistance status of local malaria vectors against Actellic 300CS using WHO protocols; Anopheline species were identified using PCR methods. RESULTS: Baseline tests conducted one-day post-IRS revealed 100% mortality on all sprayed surfaces. The residual efficacy of Actellic 300CS was maintained on all sprayed surfaces up to 8 months post-IRS. However, the bioassay test conducted 9 months post-IRS showed the 24 h mortality rate to be ≤80% for lime wash, mud wall, water paint and stone block surfaces. Only oil paint surface retained the recommended residual efficacy beyond 9 months post-IRS, with mortality maintained at ≥97 %. Results of susceptibility tests showed that malaria vectors in Zanzibar were fully (100%) susceptible to Actellic 300CS. The predominant mosquito vector species was An. arabiensis (76.0%) in Pemba and An. gambiae (83.5%) in Unguja. CONCLUSION: The microencapsulated formulation of pirimiphos methyl (Actellic 300CS) is a highly effective and appropriate insecticide for IRS use in Zanzibar as it showed a relatively prolonged residual activity compared to other products used for the same purpose. The insecticide extends the residual effect of IRS thereby making it possible to effectively protect communities with a single annual spray round reducing overall costs. The insecticide proved to be a useful alternative in insecticide resistance management plans.

Use of insecticide quantification kits to investigate the quality of spraying and decay rate of bendiocarb on different wall surfaces in Kagera region, Tanzania.

BACKGROUND: Bendiocarb was introduced for the first time for Indoor Residual Spraying (IRS) in Tanzania in 2012 as part of the interim national insecticide resistance management plan. This move followed reports of increasingly alarming levels of pyrethroid resistance across the country. This study used the insecticide quantification kit (IQK) to investigate the intra-operational IRS coverage and quality of spraying, and decay rate of bendiocarb on different wall surfaces in Kagera region. METHODS: To assess intra-operational IRS coverage and quality of spraying, 104 houses were randomly selected out of 161,414 sprayed houses. A total of 509 samples (218 in Muleba and 291 in Karagwe) were obtained by scraping the insecticide samples from wall surfaces. To investigate decay rate, 66 houses (36 in Muleba and 30 in Karagwe) were selected and samples were collected monthly for a period of five months. Laboratory testing of insecticide concentration was done using IQK(TM) [Innovative Vector Control Consortium]. RESULTS: Of the 509 samples, 89.5% met the World Health Organization (WHO) recommended concentration (between 100-400 mg/m(2)) for IRS target dosage. The proportion of samples meeting WHO standards varied between Karagwe (84.3%) and Muleba (96.3%) (p < 0.001). Assessment of quality of spraying at house level revealed that Muleba (84.8%) had a significantly higher proportion of households that met the expected target dosage (100-400 mg/m(2)) compared to Karagwe (68.9%) (p < 0.001). The quality of spraying varied across different wall substrates in both districts. Evaluation of bendiocarb decay showed that the proportion of houses with recommended concentration declined from 96.9%, 93.5% and 76.2% at months one, two, and three post IRS, respectively (p-trend = 0.03). The rate of decay increased in the fourth and fifth month post spraying with only 55.9% and 26.3% houses meeting the WHO recommendations, respectively. CONCLUSION: IQK is an important tool for assessing IRS coverage and quality of spraying. The study found adequate coverage of IRS; however, residual life of bendiocarb was observed to be three months. Results suggest that in order to maintain the recommended concentrations with bendiocarb, a second spray cycle should be carried out after three months.

The impact of different sprayable surfaces on the effectiveness of indoor residual spraying using a micro encapsulated formulation of lambda-cyhalothrin against Anopheles gambiae s.s.

BACKGROUND: The type of sprayable surface impacts on residual efficacy of insecticide used in indoor residual spraying (IRS). However, there is limited data on common types of wall surfaces sprayed in Zanzibar and mainland Tanzania where IRS began in 2006 and 2007 respectively. The study investigated residual efficacy of micro-encapsulated lambda-cyhalothrin sprayed on common surfaces of human dwellings and domestic animal shelters in Zanzibar and mainland Tanzania. METHODS: An experimental hut was constructed with different types of materials simulating common sprayable surfaces in Zanzibar and mainland Tanzania. Surfaces included cement plastered wall, mud-daub, white-wash, wood, palm-thatch, galvanized iron-sheets, burnt-bricks, limestone and oil-paint. The World Health Organization (WHO) procedure for IRS was used to spray lambda-cyhalothrin on surfaces at the dose of 20-25 mg/m(2). Residual efficacy of insecticide was monitored through cone bioassay using laboratory-reared mosquitoes; Kisumu strain (R-70) of Anopheles gambiae ss. Cone bioassay was done every fortnight for a period of 152 days. The WHO Pesticide Evaluation Scheme (WHOPES) threshold (80% mortality) was used as cut-off point for acceptable residual efficacy. RESULTS: A total of 5,800 mosquitoes were subjected to contact cone bioassay to test residual efficacy of lambda-cyhalothrin. There was a statistically significant variation in residual efficacy between the different types of wall surfaces (r = 0.24; p < 0.001). Residual efficacy decreased with increasing pH of the substrate (r = -0.5; p < 0.001). Based on WHOPES standards, shorter residual efficacy (42-56 days) was found in wall substrates made of cement, limestone, mud-daub, oil paint and white wash. Burnt bricks retained the residual efficacy up to 134 days while galvanized iron sheets, palm thatch and wood retained the recommended residual efficacy beyond 152 days. CONCLUSION: The study revealed a wide variation in residual efficacy of micro encapsulated formulation of lambda-cyhalothrin across the different types of wall surfaces studied. In areas where malaria transmission is bimodal and wall surfaces with short residual efficacy comprise > 20% of sprayable structures, two rounds of IRS using lambda-cyhalothrin should be considered. Further studies are required to investigate the impact of sprayable surfaces on residual efficacy of other insecticides commonly used for IRS in Zanzibar and mainland Tanzania.

Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar.

BACKGROUND: Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission. METHODS: Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission. RESULTS: Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas. CONCLUSIONS: Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase.

Effect of iron/folic Acid supplementation on the outcome of malaria episodes treated with sulfadoxine-pyrimethamine.

Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.

Contributions of polyclonal malaria, gametocytemia, and pneumonia to infant severe anemia incidence in malaria hyperendemic Pemba, Tanzania.

The causative factors for severe anemia incidence in sub-Saharan Africa are multifactorial. In an observational, longitudinal study of two cohorts of about 300 infants followed-up for six months in a malaria hyperendemic area, the risk factors for severe anemia incidence were clinical malaria and pneumonia, which outweighed nutritional and sociodemographic factors. Severe anemia incidence was 1-2/year at age 2 months, peaked around 6-7/year at age 7-12 months, and decreased back to 1-2/year at age 16-22 months. The age-dependent increase of severe anemia incidence was shown to be parallel to the age-dependent increase of clinical malaria. Previous clinical malaria episodes increased the severe anemia risk by 80%, and gametocyte carriage and pneumonia at prior visit was associated with a six-fold increase and a > 10-fold increase, respectively. The role of pneumonia and malaria as risk factors, and areas for interventions for severe anemia, should not be underestimated.

System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania.

BACKGROUND: Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. METHODS: Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. RESULTS: The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). CONCLUSIONS: Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain high effective coverage, there is need for complimentary distribution strategies between mass distribution campaigns. Considering the community's preferences prior to a mass distribution and addressing the communities concerns through information, education and communication, may improve the LLIN usage.

Malaria incidence and prevalence on Pemba island before the onset of the successful control intervention on the Zanzibar archipelago.

BACKGROUND: Malaria incidence has been reported to decrease substantially in parts of sub-Saharan Africa, including the Zanzibar Archipelago in East Africa. A cohort study with an intensive follow-up on Pemba Island just before the onset of the highly successful malaria control intervention was conducted. The reported estimates of parasite prevalence and incidence can serve as a robust baseline to evaluate the effect size of the successful interventions and the potential contribution of quality controls and other factors associated with research studies in the decreased estimate of transmission. METHODS: In a rural clinic, two successive cohorts of 537 children total aged 2-23 months were followed for six months each with an intensive visitation schedule of bi-weekly follow-up. Robust estimates of incidence and prevalence according to four different malaria definitions were obtained. RESULTS: Malaria incidence and prevalence placed Pemba Island in a hyperendemic rather than holoendemic setting for the years 2003-2005. Overall parasite prevalence was estimated to be 39% - with monthly estimates varying between 30% and 50%. Incidence of malaria varied between 2.3 and 3.8 malaria episodes per year based on a diagnosis of fever and various microscopy-based parasite thresholds and between 4.8 and 5.7 based on a diagnosis of fever and 100 parasites/microliter analogous to detection by rapid diagnostic tests. Both parasite densities and malaria incidence increased with age and rainy season. Malaria incidence also varied substantially between the individual villages within the study area. CONCLUSIONS: Pemba Island was previously considered holo-endemic for Malaria. The data suggest that the transmission situation on Pemba Island was significantly lower in 2003-2005 suggesting a hyper-endemic or meso-endemic transmission environment. The figures were obtained just before the onset of the highly successful malaria control intervention by impregnated bed nets and IRS on the Zanzibar Archipelago and provide robust estimates of the malaria transmission situation prior to the control programme. Together with other published data, the results suggest that malaria transmission had started to decrease before the onset of the control programme. The local heterogeneity in malaria incidence highlights the importance of a micro-epidemiological approach in the context of malaria control and elimination.

Early helminth infections are inversely related to anemia, malnutrition, and malaria and are not associated with inflammation in 6- to 23-month-old Zanzibari children.

Helminths aggravate anemia and malnutrition among school children. We studied this association in a cross-sectional study of 6- to 23-month-old Zanzibari children (N = 2322) and a sub-sample of 690 children matched on age and helminth infection status. Ascaris, hookworm, and Trichuris infections were diagnosed along with recent fever, malaria infection, mid-upper arm circumference (MUAC) and hemoglobin concentration (Hb). Alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP), height, and weight were measured in the sub-sample. Infected children had higher Hb (beta = 5.44 g/L, P < 0.001) and MUAC-for-age Z score (beta = 0.30 Z, P < 0.001) compared with uninfected children after adjusting for covariates. Although helminths were not associated with inflammation, their association with Hb or MUAC-for-age Z score was modified by inflammation. Malaria-infected children were less likely to be infected with helminths (adjusted odds ratios 0.63 [95% confidence interval: 0.49, 0.81]). Non-anemic, better nourished, or non-malaria-infected children may be more exploratory of their environments and therefore increase their exposure to soil-transmitted helminths.

Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections.

The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population.

Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar.

BACKGROUND: The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ("under five") and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar. METHODS AND FINDINGS: Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period. CONCLUSIONS: Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

Risk factors for HIV/AIDS in a low HIV prevalence site of sub-Saharan Africa.

We conducted a hospital-based survey on prevalence and risk factors of HIV-1/2 and other viral infections in Zanzibar archipelago. Blood samples, socio-demographic and behavioural data were collected from 2697 patients. The overall HIV prevalence was 2.9%. About 1.4%, 2.1%, 4.2% of antenatal clinic (ANC) attendees and 2.1%, 3.7%, 5.3% of blood donors were, respectively, HIV-Abs-, HTLV-Abs- and HBs-Ag-positive; 5.5% of blood donors were HCV-affected. Co-infections were rare. Exactly 3.4% of the children aged 6-10 years were HIV-positive. People aged 26-35 years [adjusted odds ratio (AOR) 4.4, 95% CI (confidence interval) 1.72-11.22; P = 0.002], illiterate subjects (AOR 3.6, 95% CI 1.65-7.98; P = 0.001) mobile workers (AOR 7.0, 95% CI 1.41-34.62; P = 0.02) and previously operated patients (AOR 1.9, 95% CI 1.02-3.66; P = 0.04) were at higher risk for HIV/AIDS. Any of the examined factors were associated with hepatitis B virus, hepatitis C virus and human T lymphotropic virus type 1/2 transmission. HIV/AIDS prevention strategies must primarily be addressed to traditional high-risk groups and secondarily to unsafe health care procedures in relatively preserved sub-Saharan areas.

A comparison of methods for detecting the eggs of Ascaris, Trichuris, and hookworm in infant stool, and the epidemiology of infection in Zanzibari infants.

This study compared five methods for detecting the eggs of the human parasitic geohelminths Ascaris, Trichuris, and hookworm in infant stool, and describes the epidemiology of infection in infants from a parasite-endemic area. A total of 424 infants 5-11 months old were enrolled from three villages on Pemba Island, Zanzibar. Methods used included the Kato-Katz technique, formol ethyl acetate sedimentation, modified formol ethyl acetate sedimentation, modified Wisconsin floatation, and simple gravity sedimentation. Of methods used alone, Wisconsin floatation and simple gravity sedimentation each provided the highest sensitivity for detecting eggs of these three geohelminths (89.6%). Of methods used in combination, the Kato-Katz technique/simple gravity sedimentation and Wisconsin floatation/simple gravity sedimentation each provided the highest sensitivity (99.0%). Prevalence of geohelminth infection was 26.5%. Between five and nine months of age the mean prevalence was 9.4%, while at 10 and 11 months of age the mean prevalence was 43.4%. Village prevalence varied from 3.6% to 43.8%. Infant geohelminth infection can occur at a high prevalence, and what method is best depends on research specifics.

Effect of zinc supplementation on mortality in children aged 1-48 months: a community-based randomised placebo-controlled trial.

BACKGROUND: Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba, Zanzibar. METHODS: We enrolled 42,546 children aged 1-36 months, contributing a total of 56,507 child-years in a randomised, double-blind, placebo-controlled trial in Pemba, Zanzibar. Randomisation was by household. 21 274 children received daily supplementation with zinc 10 mg (5 mg in children younger than 12 months) for mean 484.7 days (SD 306.6). 21,272 received placebo. The primary endpoint was overall mortality, and analysis was by intention to treat. This study is registered as an International Standard Randomised Clinical Trial, number ISRCTN59549825. FINDINGS: Overall, there was a non-significant 7% (95% CI -6% to 19%; p=0.29) reduction in the relative risk of all-cause mortality associated with zinc supplementation. INTERPRETATION: We believe that a meta-analysis of all studies of mortality and morbidity, will help to make evidence-based recommendations for the role of zinc supplementation in public health policy to improve mortality, morbidity, growth, and development in young children.