Meredith McMorrow

Outbreak of Variant Influenza A(H3N2) Virus in the United States

During an outbreak of H3N2v variant influenza, we identified 306 cases in ten states. Most cases reported agricultural fair attendance and/or contact with swine prior to illness. We found no evidence of efficient or sustained person-to-person transmission of H3N2v.

Diagnosis of Malaria

Malaria is a leading cause of morbidity and mortality worldwide. Prompt diagnosis and treatment are critical factors in reducing morbidity and mortality, as delayed treatment of malaria increases the risk of death. Microscopy has long been the standard of malaria diagnosis, but newer diagnostic tests now offer advantages in certain settings. Malaria diagnosis is complicated by the fact that acquired immunity to malaria can result in asymptomatic infections. In a symptomatic (febrile) patient, no existing malaria diagnostic test can distinguish malarial illness from parasitemia with concomitant fever of another cause. In this review we discuss the available malaria diagnostic tests, appropriate applications for each, and the challenges of malaria diagnosis in both endemic and non-endemic settings.

Quality assurance of rapid diagnostic tests for malaria in routine patient care in rural Tanzania.

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.

Health workers' use of malaria rapid diagnostic tests (RDTs) to guide clinical decision making in rural dispensaries, Tanzania.

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.

Measles outbreak in South Africa, 2003-2005.

OBJECTIVES Measles was virtually eliminated in South Africa following control activities in 1996/7. However, from July 2003 to November 2005, 1676 laboratory-confirmed measles cases were reported in South Africa. We investigated the outbreaks cause and the role of HIV. DESIGN We traced laboratory-confirmed case-patients residing in the Johannesburg metropolitan (JBM) and O. R. Tambo districts. We interviewed laboratory--or epidemiologically confirmed case-patients or their caregivers to determine vaccination status and, in JBM, HIV status. We calculated vaccine effectiveness using the screening method. SETTING Household survey in JBM and O. R. Tambo districts. Outcome measures. Vaccine effectiveness, case-fatality rate, and hospitalisations. RESULTS In JBM, 109 case-patients were investigated. Of the 57 case-patients eligible for immunisation, 27 (47.4%) were vaccinated. Fourteen (12.8%) case-patients were HIV infected, 46 (42.2%) were HIV uninfected, and 49 (45.0%) had unknown HIV status. Among children aged 12-59 months, vaccine effectiveness was 85% (95% confidence interval (CI): 63, 94) for all children, 63% for HIV infected, 75% for HIV uninfected, and 96% for children with unknown HIV status. (Confidence intervals were not calculated for sub-groups owing to small sample size.) In O. R. Tambo district, 157 case-patients were investigated. Among the 138 case-patients eligible for immunisation, 41 (29.7%) were vaccinated. Vaccine effectiveness was 89% (95% CI 77, 95). CONCLUSIONS The outbreaks primary cause was failure to vaccinate enough of the population to prevent endemic measles transmission. Although vaccine effectiveness might have been lower in HIV-infected than in uninfected children, population vaccine effectiveness remained high.

Artemisinin-based combinations versus amodiaquine plus sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali

BackgroundBecause of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL) or artesunate-amodiaquine (AS+AQ) are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs.MethodsFrom July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP), and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP), was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish new from recrudescent Plasmodium falciparum infections.Results397 children 6 to 59 months of age with uncomplicated Plasmodium falciparum malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR) were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p < 0.001); after PCR correction ACPR rates were similar among treatment groups: 95.4%, 96.9%, and 99.2% respectively (p = 0.17). Mean haemoglobin concentration increased across all treatment groups from Day 0 (9.82 ± 1.68 g/dL) to Day 28 (10.78 ± 1.49 g/dL) (p < 0.001), with the greatest improvement occurring in children treated with AQ+SP. On Day 2, the prevalence of parasitaemia was significantly greater among children treated with AQ+SP (50.8%) than in children treated with AS+AQ (10.5%) or AS+SP (10.8%) (p < 0.001). No significant difference in gametocyte carriage was found between groups during the follow-up period.ConclusionThe combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated P. falciparum infection in Mali and appears to have the added value of longer protective effect against new infection.

In‐vivo efficacy of amodiaquine‐artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya

Objectives  To assess the efficacy of amodiaquine‐artesunate in an area with high chloroquine resistance in western Kenya.

A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya

BackgroundArtemether-lumefantrine (AL) was adopted as first-line treatment for uncomplicated malaria in Kenya in 2006. Monitoring drug efficacy at regular intervals is essential to prevent unnecessary morbidity and mortality. The efficacy of AL and dihydroartemisinin-piperaquine (DP) were evaluated for the treatment of uncomplicated malaria in children aged six to 59 months in western Kenya.MethodsFrom October 2010 to August 2011, children with fever or history of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in an in vivo efficacy trial in accordance with World Health Organization (WHO) guidelines. The children were randomized to treatment with a three-day course of AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment initiation.ResultsA total of 137 children were enrolled in each treatment arm. There were no early treatment failures and all children except one had cleared parasites by day 3. Polymerase chain reaction (PCR)-uncorrected adequate clinical and parasitological response rate (ACPR) was 61% in the AL arm and 83% in the DP arm at day 28 (p = 0.001). PCR-corrected ACPR at day 28 was 97% in the AL group and 99% in the DP group, and it was 96% in both arms at day 42.ConclusionsAL and DP remain efficacious for the treatment of uncomplicated malaria among children in western Kenya. The longer half-life of piperaquine relative to lumefantrine may provide a prophylactic effect, accounting for the lower rate of re-infection in the first 28 days after treatment in the DP arm.

Malaria Survey in Post-Earthquake Haiti—2010

Haitis 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.

The Increase of Imported Malaria Acquired in Haiti among US Travelers in 2010

From 2004 to 2009, the number of malaria cases reported in Haiti increased nearly fivefold. The effect of the 2010 earthquake and its aftermath on malaria transmission in Haiti is not known. Imported malaria cases in the United States acquired in Haiti tripled from 2009 to 2010, likely reflecting both the increased number of travelers arriving from Haiti and the increased risk of acquiring malaria infection in Haiti. The demographics of travelers and the proportion of severe cases are similar to those statistics reported in previous years. Non-adherence to malaria chemoprophylaxis remains a nearly universal modifiable risk factor among these cases.