Search

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

Haiti is committed to malaria elimination by 2020. Following a 2010 earthquake and cholera epidemic, Haiti capitalized on investments in its health system to refocus on malaria elimination. Efforts, including expanding diagnostics, ensuring efficacy of standard treatments, building institutional capacity, and strengthening surveillance were undertaken to complement the broad health system strengthening activities. These efforts led to the adoption and scale-up of malaria rapid diagnostic tests as a diagnostic modality. In addition, drug-resistant monitoring has been established in the country, along with the development of molecular testing capacity for the Plasmodium falciparum parasite at the National Public Health Laboratory. The development and piloting of surveillance activities to include an enhanced community-based approach for testing and treatment of patients has increased the ability of the Ministry of Health to map foci of transmission and respond promptly to outbreaks. The reinforcement of evidence-based approaches coupled with strong collaboration among the Ministry of Health and partners has demonstrated that malaria elimination by 2020 is a realistic prospect.

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

Mass drug administration (MDA) was a component of many malaria programs during the eradication era, but later was seldomly deployed due to concerns regarding efficacy and feasibility and fear of accelerating drug resistance. Recently, however, there has been renewed interest in the role of MDA as an elimination tool. Following a 2013 Cochrane Review that focused on the quantitative effects of malaria MDA, we have conducted a systematic, qualitative review of published, unpublished, and gray literature documenting past MDA experiences. We have also consulted with field experts, using their historical experience to provide an informed, contextual perspective on the role of MDA in malaria elimination. Substantial knowledge gaps remain and more research is necessary, particularly on optimal target population size, methods to improve coverage, and primaquine safety. Despite these gaps, MDA has been used successfully to control and eliminate Plasmodium falciparum and P. vivax malaria in the past, and should be considered as part of a comprehensive malaria elimination strategy in specific settings., (© The American Society of Tropical Medicine and Hygiene.)

Artemisinin combination therapies are available in private outlets, but patient adherence might be compromised by poor advice from dispensers. In this cluster randomized trial in drug shops in Tanzania, 42 of 82 selected shops were randomized to receive text message reminders about what advice to provide when dispensing artemether-lumefantrine (AL). Eligible patients purchasing AL at shops in both arms were followed up at home and questioned about each dose taken. Dispensers were interviewed regarding knowledge of AL dispensing practices and receipt of the malaria-related text messages. We interviewed 904 patients and 110 dispensers from 77 shops. Although there was some improvement in dispenser knowledge, there was no difference between arms in adherence measured as completion of all doses (intervention 68.3%, control 69.8%, p [adjusted] = 0.6), or as completion of each dose at the correct time (intervention 33.1%, control 32.6%, p [adjusted] = 0.9). Further studies on the potential of text messages to improve adherence are needed., (© The American Society of Tropical Medicine and Hygiene.)

The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection., (© The American Society of Tropical Medicine and Hygiene.)

Haiti's Ministry of Public Health and Population collaborated with global partners to enhance malaria surveillance in two disaster-affected areas within 3 months of the January 2010 earthquake. Data were collected between March 4 and April 9, 2010 by mobile medical teams. Malaria rapid diagnostic tests (RDTs) were used for case confirmation. A convenience sample of 1,629 consecutive suspected malaria patients was included. Of these patients, 1,564 (96%) patients had malaria RDTs performed, and 317 (20.3%) patients were positive. Of the 317 case-patients with a positive RDT, 278 (87.7%) received chloroquine, 8 (2.5%) received quinine, and 31 (9.8%) had no antimalarial treatment recorded. Our experience shows that mobile medical teams trained in the use of malaria RDTs had a high rate of testing suspected malaria cases and that the majority of patients with positive RDTs received appropriate antimalarial treatment. Malaria RDTs were useful in the post-disaster setting where logistical and technical constraints limited the use of microscopy.

Rapid diagnostic tests (RDTs) were developed as an alternative to microscopy for malaria diagnosis. The RDTs detect malaria parasite antigen(s) in whole blood with high sensitivity and specificity. We assessed health worker malaria treatment practices after the introduction of RDTs in peripheral health facilities without microscopy. From December 2007 to October 2008, we introduced histidine-rich protein II (HRP-2)-based ParaHIT RDTs for routine use in 12 health facilities in Rufiji District, Tanzania. Health workers received training on how to perform RDTs for patients 5 years of age or older with fever or suspected malaria. Children < 5 years of age were to be treated empirically per national guidelines. Among the 30,195 patients seen at these 12 health facilities, 10,737 (35.6%) were tested with an RDT for malaria. 88.3% (9,405/10,648) of tested patients reported fever or history of fever and 2.7% (289/10,677) of all tested individuals were children < 5 years of age. The RDT results were recorded for 10,650 patients (99.2%). Among the 5,488 (51.5%) RDT-positive patients, 5,256 (98.6%) were treated with an appropriate first-line antimalarial per national guidelines (artemether-lumefantrine or quinine). Among the 5,162 RDT-negative patients, only 205 (4.0%) were treated with an antimalarial. Other reported treatments included antibiotics and antipyretics. Implementation of RDTs in rural health facilities resulted in high adherence to national treatment guidelines. Patients testing negative by RDT were rarely treated with antimalarials. Unapproved antimalarials were seldom used. Health workers continued to follow guidelines for the empiric treatment of febrile children.

Histidine-rich protein II (HRP2)-based malaria rapid diagnostic tests (RDTs) have shown high sensitivity and specificity for detecting Plasmodium falciparum malaria in a variety of study settings. However, RDTs are susceptible to heat and humidity and variation in individual performance, which may affect their use in field settings. We evaluated sensitivity and specificity of RDTs during routine use for malaria case management in peripheral health facilities. From December 2007 to October 2008, HRP2-based ParaHIT-f RDTs were introduced in 12 facilities without available microscopy in Rufiji District, Tanzania. Health workers received a single day of instruction on how to perform an RDT and thick blood smear. Job aids, Integrated Management of Childhood Illness guidelines, and national malaria treatment algorithms were reviewed. For quality assurance (QA), thick blood smears for reference microscopy were collected for 2 to 3 days per week from patients receiving RDTs; microscopy was not routinely performed at the health facilities. Slides were stained and read centrally within 72 hours of collection by a reference microscopist. When RDT and blood smear results were discordant, blood smears were read by additional reference microscopists blinded to earlier results. Facilities were supervised monthly by the district laboratory supervisor or a member of the study team. Ten thousand six hundred fifty (10,650) patients were tested with RDTs, and 51.5% (5,488/10,650) had a positive test result. Blood smear results were available for 3,914 patients, of whom 40.1% (1,577/3,914) were positive for P. falciparum malaria. Overall RDT sensitivity was 90.7% (range by facility 85.7-96.5%) and specificity was 73.5% (range 50.0-84.3%). Sensitivity increased with increasing parasite density. Successful implementation of RDTs was achieved in peripheral health facilities with adequate training and supervision. Quality assurance is essential to the adequate performance of any laboratory test. Centralized staining and reading of blood smears provided useful monitoring of RDT performance. However, this level of QA may not be sustainable nationwide.

Rapid diagnostic tests (RDTs) represent an alternative to microscopy for malaria diagnosis and have shown high sensitivity and specificity in a variety of study settings. Current World Health Organization (WHO) guidelines for quality control of RDTs provide detailed instructions on pre-field testing, but offer little guidance for quality assurance once RDTs are deployed in health facilities. From September 2006 to April 2007, we introduced a histidine-rich protein II (HRP2)-based RDT (Paracheck) for suspected malaria cases five years of age and older in nine health facilities in Rufiji District, Tanzania, to assess sensitivity and specificity of RDTs in routine use at rural health facilities. Thick blood smears were collected for all patients tested with RDTs and stained and read by laboratory personnel in each facility. Thick smears were subsequently reviewed by a reference microscopist to determine RDT sensitivity and specificity. In all nine health facilities, there were significant problems with the quality of staining and microscopy. Sensitivity and specificity of RDTs were difficult to assess given the poor quality of routine blood smear staining. Mean operational sensitivity of RDTs based on reference microscopy was 64.8%, but varied greatly by health facility, range 18.8-85.9%. Sensitivity of RDTs increased with increasing parasite density. Specificity remained high at 87.8% despite relatively poor slide quality. Institution of quality control of RDTs based on poor quality blood smear staining may impede reliable measurement of sensitivity and specificity and undermine confidence in the new diagnostic. There is an urgent need for the development of alternative quality control procedures for rapid diagnostic tests that can be performed at the facility level.

Malaria's relationship with socioeconomic status at the macroeconomic level has been established. This is the first study to explore this relationship at the microeconomic (household) level and estimate the direction of association. Malaria prevalence was measured by parasitemia, and household socioeconomic status was measured using an asset based index. Results from an instrumental variable probit model suggest that socioeconomic status is negatively associated with malaria parasitemia. Other variables that are significantly associated with parasitemia include age of the individual, use of a mosquito net on the night before interview, the number of people living in the household, whether the household was residing at their farm home at the time of interview, household wall construction, and the region of residence. Matching estimators indicate that malaria parasitemia is associated with reduced household socioeconomic status.

Use of insecticide-treated bednets (ITNs) to prevent malaria remains low, and effective distribution strategies are needed. An integrated child health campaign with free distribution of 162,254 untreated bednets bundled with insecticide, measles vaccination, vitamin A, and mebendazole for children < 5 years old ("under-5s") was conducted in Lindi Region, Tanzania. We conducted a representative household survey 3 months after the campaign. Altogether, 574 households with 354 under-5s were visited. In households with an under-5, possession of bednets and ITNs increased from 60.9% to 90.7% (P < 0.001) and from 16.5% to 37.3% (P < 0.001), respectively. Increases occurred in all wealth quintiles and equity improved. Reported bednet and ITN use the previous night among under-5s was 46.3% and 21.5%, respectively. Integrated campaigns rapidly and equitably increase bednet possession and use meriting continued large-scale implementation. However, our study found that bednets were rarely treated; thus, future campaigns should provide factory-treated long-lasting ITNs. Low ITN use underscores the need for further efforts to increase use after campaigns.

Artemisinin-containing antimalarial combination therapies are recommended to confront drug-resistant Plasmodium falciparum malaria. Among the questions surrounding whether these complex multidose treatments will be practical is to what extent patients complete the recommended doses. Combination therapy through coadministration of sulfadoxine-pyrimethamine plus artesunate was introduced as a first-line treatment for uncomplicated malaria in one district in Tanzania. Interventions to optimize correct use were also implemented. We observed 453 patient encounters at one health facility and recorded key practices as health workers dispensed the combination. A total of 253 patients were followed-up at 24 or 48 hours. Complete adherence measured at 48 hours reached 75.0%, based on self-report and tablet counts. This is substantially better than reported elsewhere and compares favorably with intervention studies to optimize adherence to chloroquine. Counseling about what to do if a patient vomits appears to have been an independent risk factor for nonadherence.

Prior to implementation of a randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) in western Kenya, ethnographic studies were conducted to understand local perceptions of disease, sleeping patterns, and other factors that might affect use of ITNs. Educational activities took place prior to distribution, but immediately after distribution in Asembo only approximately half of the ITNs were in use. A qualitative study was then conducted to identify the community's perceptions about ITNs and the ITN project. While participants ranked malaria as important and recognized that malaria prevention could be beneficial, they believed ITNs would be only partly effective due to the perception that malaria has multiple causes. Concerns expressed included fear of the insecticide, thought by some to be a toxic family planning aid, the taking of blood during clinical studies, and the mixing up of family ITNs during net re-treatment, which would violate cultural taboos. Attempts were made to allay fears by improved communication on these subjects and modification of the study design.

A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.

Estimates of mortality in children less than five years old using government civil registration statistics (passive surveillance) were compared against statistics generated by active demographic surveillance during a randomized controlled trial of permethrin-treated bed nets (ITNs) in western Kenya. Mortality rates were two-fold lower when estimated through civil registration compared with active prospective surveillance (rate ratio [RR] = 0.51, 95% confidence interval [CI] = 0.44-0.59). While civil registration underestimated deaths, particularly in the neonatal period, the age distribution of deaths in children 1-59 months of age was the same as with active surveillance. Seasonal mortality trends were also similar. There was no agreement between cause of death recorded by active and passive surveillance. Verbal autopsy estimated that half of all deaths were associated with malaria and pneumonia, but civil registration markedly under-reported these illnesses; incidence RR (95% CI) = 0.18 (0.14-0.24), and 0.05 (0.03-0.08), respectively, while over-reporting deaths due to measles (RR = 15.5 [95% CI = 7.3-33.2]). Government statistics under-represent mortality, particularly neonatal mortality, in children less than five years of age in rural areas of Kenya. They can provide accurate information on the age-distribution of deaths among children 1-59 months old, and on seasonal trends, but not on disease-specific mortality.

Randomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it.

A study of mothers' perceptions regarding bed nets and malaria was conducted before and after a randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) in western Kenya. Awareness about the trial and the rationale for bed net use increased by the end of the trial. Knowledge that mosquitoes caused malaria also increased; however, a higher proportion of mothers from control, rather than intervention villages, cited this (44.4% versus 27.9%; P < 0.001). Mothers from intervention villages were more knowledgeable about the use and maintenance of bed nets and re-treatment with insecticide. Both groups specified advantages of ITNs. Mothers from intervention villages noted practical advantages such as protection against bedbugs and falling roof debris. Few (< 1%) mothers indicated that ITNs protected children against malaria. Intervention homes used significantly fewer mosquito coils, insect spray, medicines, and burned cow dung less often compared with those in control villages. Mothers were willing to pay approximately 4.5 U.S. dollars for a regular bed net, but only 10.5 U.S. cents (intervention) and 0.036 (control) for re-treating a bed net. This study suggests that, despite two years of experience of use, bed nets and insecticides would not be purchased as a household priority in this impoverished rural community.

This paper describes the study design and methods used in a large community-based, group-randomized, controlled trial of permethrin-treated bed nets (ITNs) in an area with intense, perennial malaria transmission in western Kenya conducted between 1996 and 1999. A multi-disciplinary framework was used to explore the efficacy of ITNs in the reduction of all-cause mortality in children less than five years old, the clinical, entomologic, immunologic, and economic impact of ITNs, the social and behavioral determinants of ITN use, and the use of a geographic information system to allow for spatial analyses of these outcomes. Methodologic difficulties encountered in such large-scale field trials are discussed.