The usefulness of rapid diagnostic tests in the new context of low malaria transmission in zanzibar.

BACKGROUND\ud \ud We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.\ud \ud METHODS AND FINDINGS\ud \ud We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups.\ud \ud CONCLUSIONS\ud \ud The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT01002066

Incidence and Risk Factors for Newborn Umbilical Cord Infections on Pemba Island, Zanzibar, Tanzania

BACKGROUND: Few community-based data exist on the frequency of cord infection signs in low resource settings, especially in Sub-Saharan Africa. We developed simple sign-based definitions of omphalitis and estimated incidence and risk factors for infection over a range of severity among neonates in Pemba, Zanzibar, Tanzania. METHODS: Infants\u27 umbilical stump was assessed on days 1, 3, 5, 7, 10, and 14 after birth for presence of pus, redness, swelling, and foul odor. Infection incidence and proportion of affected infants was estimated for 6 separate combinations of these signs. Two definitions were examined for associations between infection and selected potential risk factors using multivariate analysis. RESULTS: Nine thousand five hundred fifty cord assessments (in 1653 infants) were conducted. The proportion of affected infants ranged from 16 (1.0%, moderate to severe redness with pus discharge) to 199 (12.0%, pus and foul odor), while single signs were observed in \u3e20% of infants. Median time to onset of infection was 3 to 4 days; 90% of infections occurred by age 7 days. Breast-feeding within the first hour after birth was associated with lower risk of infection in multivariate analyses, while other maternal, and infant and care practices were generally not associated. CONCLUSIONS: Signs of omphalitis occur frequently and predominately in the first week of life among newborns in Pemba, Tanzania. Infection definitions relying on single signs without classifying severity level may overestimate burden. Redness with pus or redness at the moderate or severe level if pus is absent is more appropriate for estimating burden or during evaluation of interventions to reduce infection. © 2009 by Lippincott Williams & Wilkins

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar : Aetiologies, Antibiotic Treatment and Outcome

BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low

Study flow chart.

<p>(BS = blood smear, FP = filter paper, PCR = polymerase chain reaction.).</p

Prescription of anti-malarial medicines, antibiotics and antipyretics by rapid diagnostic test (RDT) result and age group.

*<p>Data on specific age categories (5–14 y and >14 y) were missing from14 patients.</p

Baseline characteristics.

<p>Domestic = History of travel within Zanzibar.</p><p>Abroad = History of travel outside Zanzibar.</p><p>ITN = Insecticide-treated nets.</p><p>LLIN = long-lasting insecticidal nets.</p

Rapid diagnostic test (RDT) sensitivity, specificity, positive and negative predictive value against polymerase chain reaction (PCR) and blood smear (BS) microscopy.

*<p>For calculations of sensitivity and specificity the absolute numbers in the RDT negative group were multiplied with a factor of 5.14 to account for that only a sub-sample, i.e. 733 of 3768, in this group were subjected to blood sampling on filter paper for PCR.</p>**<p>For calculations of sensitivity and specificity the absolute numbers in the RDT negative group were multiplied with a factor of 5.01 to account for that only a sub-sample, i.e. 739 of 3768, in this group were subjected to blood sampling for BS microscopy.</p

Distribution of <i>P. falciparum</i> positive rapid diagnostic test (RDT), polymerase chain reaction (PCR) and blood smear (BS) microscopy results as well as microscopy determined parasite density across age groups.

*<p>Data on specific age categories (5–14 y and >14 y) were missing from14 patients.</p

IMCI classifications associated with fever.

<p>IMCI classifications associated with fever.</p

Flow chart from investigations and management to final diagnoses.

<p>Flow chart from investigations and management to final diagnoses.</p