Microscopy Quality Control in Médecins Sans Frontières Programs in Resource-Limited Settings

Derryck Klarkowski and Daniel Orozco describe the Médecins Sans Frontières program for monitoring the quality of microscopy for malaria, pulmonary tuberculosis, and leishmaniasis

An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India

BACKGROUND: Plasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures. METHODS: Children aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard. RESULTS: In all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%. CONCLUSIONS: Determine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas

Forecasting malaria incidence based on monthly case reports and environmental factors in Karuzi, Burundi, 1997–2003

BACKGROUND: The objective of this work was to develop a model to predict malaria incidence in an area of unstable transmission by studying the association between environmental variables and disease dynamics. METHODS: The study was carried out in Karuzi, a province in the Burundi highlands, using time series of monthly notifications of malaria cases from local health facilities, data from rain and temperature records, and the normalized difference vegetation index (NDVI). Using autoregressive integrated moving average (ARIMA) methodology, a model showing the relation between monthly notifications of malaria cases and the environmental variables was developed. RESULTS: The best forecasting model (R2adj = 82%, p < 0.0001 and 93% forecasting accuracy in the range +/- 4 cases per 100 inhabitants) included the NDVI, mean maximum temperature, rainfall and number of malaria cases in the preceding month. CONCLUSION: This model is a simple and useful tool for producing reasonably reliable forecasts of the malaria incidence rate in the study area

Long-term field performance of a polyester-based long-lasting insecticidal mosquito net in rural Uganda

<p>Abstract</p> <p>Background</p> <p>In order to evaluate whether criteria for LLIN field performance (phase III) set by the WHO Pesticide Evaluation Scheme are met, first and second generations of one of these products, PermaNet^®, a polyester net using the coating technology were tested.</p> <p>Methods</p> <p>A randomized, double blinded study design was used comparing LLIN to conventionally treated nets and following LLIN for three years under regular household use in rural conditions. Primary outcome measures were deltamethrin residue and bioassay performance (60 minute knock-down and 24 hour mortality after a three minute exposure) using a strain of <it>Anopheles gambiae s.s</it>. sensitive to pyrethroid insecticides.</p> <p>Results</p> <p>Baseline concentration of deltamethrin was within targets for all net types but was rapidly lost in conventionally treated nets and first generation PermaNet^®with median of 0.7 and 2.5 mg/m²after six months respectively. In contrast, second generation PermaNet^®retained insecticide well and had 41.5% of baseline dose after 36 months (28.7 mg/m²). Similarly, vector mortality and knockdown dropped to 18% and 70% respectively for first generation LLIN after six months but remained high (88.5% and 97.8% respectively) for second generation PermaNet^®after 36 months of follow up at which time 90.0% of nets had either a knockdown rate ≥ 95% or mortality rate ≥ 80%.</p> <p>Conclusion</p> <p>Second generation PermaNet^®showed excellent results after three years of field use and fulfilled the WHOPES criteria for LLIN. Loss of insecticide on LLIN using coating technology under field conditions was far more influenced by factors associated with handling rather than washing.</p

Reader technique as a source of variability in determining malaria parasite density by microscopy

BACKGROUND: Accurate identification and quantification of malaria parasites are critical for measuring clinical trial outcomes. Positive and negative diagnosis is usually sufficient for the assessment of therapeutic outcome, but vaccine or prophylactic drug trials require measuring density of infection as a primary endpoint. Microscopy is the most established and widely-used technique for quantifying parasite densities in the blood. METHODS: Results obtained by 24–27 expert malaria microscopists, who had independently read 895 slides from 35 donors, were analysed to understand how reader technique contributes to discrepancy in measurements of parasite density over a wide range of densities. RESULTS: Among these 35 donations, standard deviations ranged from 30% to 250% of the mean parasite density and the percent discrepancy was inversely correlated with the mean parasite density. The number of white blood cells indexed and whether parasites were counted in the thick film or thin film were shown to significantly contribute to discrepancy amongst microscopists. CONCLUSION: Errors in microscopy measurements are not widely appreciated or addressed but have serious consequences for efficacy trials, including possibly abandoning promising vaccine candidates

Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.

Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool

Community referral in home management of malaria in western Uganda: A case series study

BACKGROUND: Home Based Management of fever (HBM) was introduced as a national policy in Uganda to increase access to prompt presumptive treatment of malaria. Pre-packed Chloroquine/Fansidar combination is distributed free of charge to febrile children <5 years. Persisting fever or danger signs are referred to the health centre. We assessed overall referral rate, causes of referral, referral completion and reasons for non-completion under the HBM strategy. METHODS: A case-series study was performed during 20 weeks in a West-Ugandan sub-county with an under-five population of 3,600. Community drug distributors (DDs) were visited fortnightly and recording forms collected. Referred children were located and primary caretaker interviewed in the household. Referral health facility records were studied for those stating having completed referral. RESULTS: Overall referral rate was 8% (117/1454). Fever was the main reason for mothers to seek DD care and for DDs to refer. Twenty-six of the 28 (93%) "urgent referrals" accessed referral care but 8 (31%) delayed >24 hours. Waiting for antimalarial drugs to finish caused most delays. Of 32 possible pneumonias only 16 (50%) were urgently referred; most delayed ≥ 2 days before accessing referral care. CONCLUSION: The HBM has high referral compliance and extends primary health care to the communities by maintaining linkages with formal health services. Referral non-completion was not a major issue but failure to recognise pneumonia symptoms and delays in referral care access for respiratory illnesses may pose hazards for children with acute respiratory infections. Extending HBM to also include pneumonia may increase prompt and effective care of the sick child in sub-Saharan Africa

Adherence of community caretakers of children to pre-packaged antimalarial medicines (HOMAPAK(®)) among internally displaced people in Gulu district, Uganda

BACKGROUND: In 2002, home-based management of fever (HBMF) was introduced in Uganda, to improve access to prompt, effective antimalarial treatment of all fevers in children under 5 years. Implementation is through community drug distributors (CDDs) who distribute pre-packaged chloroquine plus sulfadoxine-pyrimethamine (HOMAPAK(®)) free of charge to caretakers of febrile children. Adherence of caretakers to this regimen has not been studied. METHODS: A questionnaire-based survey combined with inspection of blister packaging was conducted to investigate caretakers' adherence to HOMAPAK(®). The population surveyed consisted of internally displaced people (IDPs) from eight camps. RESULTS: A total of 241 caretakers were interviewed. 95.0% (CI: 93.3% – 98.4%) of their children had received the correct dose for their age and 52.3% of caretakers had retained the blister pack. Assuming correct self-reporting, the overall adherence was 96.3% (CI: 93.9% – 98.7%). The nine caretakers who had not adhered had done so because the child had improved, had vomited, did not like the taste of the tablets, or because they forgot to administer the treatment. For 85.5% of cases treatment had been sought within 24 hours. Blister packaging was considered useful by virtually all respondents, mainly because it kept the drugs clean and dry. Information provided on, and inside, the package was of limited use, because most respondents were illiterate. However, CDDs had often told caretakers how to administer the treatment. For 39.4% of respondents consultation with the CDD was their reported first action when their child has fever and 52.7% stated that they consult her/him if the child does not get better. CONCLUSION: In IDP camps, the HBMF strategy forms an important component of medical care for young children. In case of febrile illness, most caretakers obtain prompt and adequate antimalarial treatment, and adhere to it. A large proportion of malaria episodes are thus likely to be treated before complications can arise. Implementation in the IDP camps now needs to focus on improving monitoring, supervision and general support to CDDs, as well as on targeting them and caretakers with educational messages. The national treatment policy for uncomplicated malaria has recently been changed to artemether-lumefantrine. Discussions on a suitable replacement combination for HBMF are well advanced, and have raised new questions about adherence

Land use change alters malaria transmission parameters by modifying temperature in a highland area of Uganda

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73403/1/j.1365-3156.2000.00551.x.pd

HIV-1 prevalence and factors associated with infection in the conflict-affected region of North Uganda

BACKGROUND: Since 1986, northern Uganda has been severely affected by civil strife with most of its population currently living internally displaced in protected camps. This study aims at estimating the HIV-1 prevalence among this population and the factors associated with infection. METHODS: In June-December 2005, a total of 3051 antenatal clinics attendees in Gulu, Kitgum and Pader districts were anonymously tested for HIV-1 infection as part of routine sentinel surveillance. Factors associated with the infection were evaluated using logistic regression models. RESULTS: The age-standardised HIV-1 prevalence was 10.3%, 9.1% and 4.3% in the Gulu, Kitgum and Pader district, respectively. The overall prevalence in the area comprised of these districts was 8.2% when data was weighted according to the districts' population size. Data from all sites combined show that, besides older women [20–24 years: adjusted odds ratio (AOR) = 1.96, 95% confidence interval (CI): 1.29–2.97; 25–29 years: AOR = 2.01, 95% CI: 1.30–3.11; ≥ 30 years: AOR = 1.91, 95% CI: 1.23–2.97], unmarried women (AOR = 1.47, 95% CI: 1.06–2.04), and those with a partner with a non-traditional occupation (AOR = 1.62, 95% CI: 1.18–2.21), women living outside of protected camps for internally displaced persons have a higher risk of being HIV-1 infected than internally displaced women (AOR = 1.55, 95% CI: 1.15–2.08). CONCLUSION: Although published data from Gulu district show a declining HIV-1 prevalence trend that is consistent with that observed at the national level since 1993, the prevalence in North Uganda is still high. Internally displaced women have a lower risk of being infected probably because of their reduced mobility and accessibility, and increased access to health prevention services