The incidence and clinical burden of respiratory syncytial virus disease identified through hospital outpatient presentations in Kenyan children

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting. Methods We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence. Results Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively. Conclusion The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis

Use and limitations of malaria rapid diagnostic testing by community health workers in war-torn Democratic Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Accurate and practical malaria diagnostics, such as immunochromatographic rapid diagnostic tests (RDTs), have the potential to avert unnecessary treatments and save lives. Volunteer community health workers (CHWs) represent a potentially valuable human resource for expanding this technology to where it is most needed, remote rural communities in sub-Saharan Africa with limited health facilities and personnel. This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo, a tropical African setting ravaged by human conflict.</p> <p>Methods</p> <p>Prospective cohort study, satisfaction questionnaire and decision analysis.</p> <p>Results</p> <p>Twelve CHWs were trained to safely and accurately perform and interpret RDTs, then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children. CHWs were uniformly positive in evaluating RDTs for their utility and ease of use. However, high malaria prevalence in this cohort (93% by RDTs, 88% by light microscopy) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children, as evidenced by findings from a simplified decision analysis.</p> <p>Conclusions</p> <p>CHWs can safely and effectively use RDTs in their management of febrile children; however, cost-effectiveness of RDTs is limited in zones of high malaria prevalence.</p

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

<p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum </it>samples in an endemic field setting.</p> <p>Methods</p> <p>From January to April 2010, blood samples with <it>P. falciparum </it>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.</p> <p>Results</p> <p>A total of 873/7,543 (11.6%) samples showed <it>P. falciparum</it>, 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.</p> <p>Conclusion</p> <p>Prozone occurs at different frequency and intensity in HRP-2 RDTs and may decrease diagnostic accuracy in the most affected RDTs.</p

From In Vivo to In Vitro: Dynamic Analysis of Plasmodium falciparum var Gene Expression Patterns of Patient Isolates during Adaptation to Culture

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, plays a crucial role in disease virulence through its involvement in binding to various host cellular receptors during infection. Growing evidence suggests that differential expression of the various var subgroups may be involved in parasite virulence. To further explore this issue, we have collected isolates from symptomatic patients in south China-Myanmar border, and characterized their sequence diversity and transcription profiles over time of var gene family, and cytoadherence properties from the time of their initial collection and extending through a two month period of adaptation to culture. Initially, we established a highly diverse, DBLα (4 cysteines) subtype-enriched, but unique local repertoire of var-DBL1α sequences by cDNA cloning and sequencing. Next we observed a rapid transcriptional decline of upsA- and upsB-subtype var genes at ring stage through qRT-PCR assays, and a switching event from initial ICAM-I binding to the CD36-binding activity during the first week of adaptive cultivation in vitro. Moreover, predominant transcription of upsA var genes was observed to be correlated with those isolates that showed a higher parasitemia at the time of collection and the ICAM-1-binding phenotype in culture. Taken together, these data indicate that the initial stage of adaptive process in vitro significantly influences the transcription of virulence-related var subtypes and expression of PfEMP1 variants. Further, the specific upregulation of the upsA var genes is likely linked to the rapid propagation of the parasite during natural infection due to the A-type PfEMP1 variant-mediated growth advantages

Too poor to pay: charging for insecticide-treated bednets in highland Kenya.

WHO has proposed malaria control as a means to alleviate poverty. One of its targets includes a 30-fold increase in insecticide-treated nets (ITNs) in the next 5 years. How this service will be financed remains unclear. In July 2000, 390 homesteads in rural highland Kenya were interviewed on their willingness to pay for ITNs. The costs to a household of protecting themselves with ITNs were compared with current household expenditure. Homesteads expressed a willingness to pay for ITNs, but the amounts offered were not sufficient to cover the costs of providing this service without donor support to meet the difference. Furthermore, as most household expenditure was allocated to basic needs these interventions were 'unaffordable'. The cost of protecting a household with ITNs would be equivalent to sending three children to primary school for a year. The aspiration by poor rural homesteads to protect themselves with ITNs is not compatible with their ability to pay. One option to have an immediate equitable impact on ITN coverage and break the cycle between malaria and poverty is to provide this service free of charge

Too poor to pay: charging for insecticide-treated bednets in highland Kenya.

WHO has proposed malaria control as a means to alleviate poverty. One of its targets includes a 30-fold increase in insecticide-treated nets (ITNs) in the next 5 years. How this service will be financed remains unclear. In July 2000, 390 homesteads in rural highland Kenya were interviewed on their willingness to pay for ITNs. The costs to a household of protecting themselves with ITNs were compared with current household expenditure. Homesteads expressed a willingness to pay for ITNs, but the amounts offered were not sufficient to cover the costs of providing this service without donor support to meet the difference. Furthermore, as most household expenditure was allocated to basic needs these interventions were 'unaffordable'. The cost of protecting a household with ITNs would be equivalent to sending three children to primary school for a year. The aspiration by poor rural homesteads to protect themselves with ITNs is not compatible with their ability to pay. One option to have an immediate equitable impact on ITN coverage and break the cycle between malaria and poverty is to provide this service free of charge

Free bednets to pregnant women through antenatal clinics in Kenya: a cheap, simple and equitable approach to delivery.

Kenya's National Malaria Strategy states that insecticide-treated nets (ITNs) would be considered as a free service to pregnant women assuming sufficient financial commitment from donors. In 2001, United Nation's Children's Fund (UNICEF) and the Government of Kenya brokered support to procure and distribute nets and K-O TABs (deltamethrin) to 70 000 pregnant women in 35 districts throughout Kenya around Africa Malaria Day. This intervention represented the single largest operational distribution of ITN services in Kenya to date, and this study evaluates its success, limitations and costs. The tracking process from the central level through to antenatal clinic (ANC) facilities suggests that of the 70 000 nets procured, 37 206 nets (53%) had been distributed to pregnant women throughout the country within 12 weeks. One-fifth of the nets procured (14 117) had gone out to individuals other than pregnant women, most of these at the request of the district teams, with only 2870 nets estimated to have gone astray at the ANC facilities. At 12 weeks, the remaining 18 677 nets were still in storage awaiting distribution, with more than two-thirds having reached the district, and nearly half already being held at ANC facilities. The cost of getting a net and K-O TAB to an ANC facility ready for distribution to a pregnant woman was US$3.81. Accounting for the 14 117 nets that had gone to other users, the cost for an ITN received by a pregnant woman was US$ 5.26. Delivering ITNs free to pregnant women through ANCs uses an existing system (with positive spin-offs of low delivery cost and simple logistics), is equitable (as it not only targets those who can afford it) and can have the added benefits of strengthening ANC service, delivery and use