Impact of ivermectin and vector control on onchocerciasis transmission in Togo: Assessing the empirical evidence on trends in infection and entomological indicators.

BACKGROUND: The World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection. METHODOLOGY/PRINCIPAL FINDINGS: We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas). CONCLUSIONS/SIGNIFICANCE: Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

The effects of a peripartum strategy to prevent and treat primary postpartum haemorrhage at health facilities in Niger: a longitudinal, 72-month study.

BACKGROUND: Primary postpartum haemorrhage is the principal cause of birth-related maternal mortality in most settings and has remained persistently high in severely resource-constrained countries. We evaluate the impact of an intervention that aims to halve maternal mortality caused by primary postpartum haemorrhage within 2 years, nationwide in Niger. METHODS: In this 72-month longitudinal study, we analysed the effects of a primary postpartum haemorrhage intervention in hospitals and health centres in Niger, using data on maternal birth outcomes assessed and recorded by the facilities' health professionals and reported once per month at the national level. Reported data were monitored, compiled, and analysed by a non-governmental organisation collaborating with the Ministry of Health. All births in all health facilities in which births occurred, nationwide, were included, with no exclusion criteria. After a preintervention survey, brief training, and supplies distribution, Niger implemented a nationwide primary postpartum haemorrhage prevention and three-step treatment strategy using misoprostol, followed if needed by an intrauterine condom tamponade, and a non-inflatable anti-shock garment, with a specific set of organisational public health tools, aiming to reduce primary postpartum haemorrhage mortality. FINDINGS: Among 5 382 488 expected births, 2 254 885 (41·9%) occurred in health facilities, of which information was available on 1 380 779 births from Jan 1, 2015, to Dec 31, 2020, with reporting increasing considerably over time. Primary postpartum mortality decreased from 82 (32·16%; 95% CI 25·58-39·92) of 255 health facility maternal deaths in the 2013 preintervention survey to 146 (9·53%; 8·05-11·21) of 1532 deaths among 343 668 births in 2020. Primary postpartum haemorrhage incidence varied between 1900 (2·10%; 2·01-2·20) of 90 453 births and 4758 (1·47%; 1·43-1·52) of 322 859 births during 2015-20, an annual trend of 0·98 (95% CI 0·97-0·99; p<0·0001). INTERPRETATION: Primary postpartum haemorrhage morbidity and mortality declined rapidly nationwide. Because each treatment technology that was used has shown some efficacy when used alone, a strategic combination of these treatments can reasonably attain outcomes of this magnitude. Niger's strategy warrants testing in other low-income and perhaps some middle-income settings. FUNDING: The Government of Norway, the Government of Niger, the Kavli Trust (Kavlifondet), the InFiL Foundation, and individuals in Norway, the UK, and the USA. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study.

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.

Comparison of platforms for testing antibodies to Chlamydia trachomatis antigens in the Democratic Republic of the Congo and Togo.

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis (Ct), is targeted for elimination as a public health problem. Serological testing for antibodies is promising for surveillance; determining useful thresholds will require collection of serological data from settings with different prevalence of the indicator trachomatous inflammation-follicular (TF). Dried blood spots were collected during trachoma mapping in two districts each of Togo and Democratic Republic of the Congo. Anti-Ct antibodies were detected by multiplex bead assay (MBA) and three different lateral flow assays (LFA) and seroprevalence and seroconversion rate (SCR) were determined. By most tests, the district with > 5% TF (the elimination threshold) had five-sixfold higher seroprevalence and tenfold higher SCR than districts with < 5% TF. The agreement between LFA and MBA was improved using a black latex developing reagent. These data show optimization of antibody tests against Ct to better differentiate districts above or below trachoma elimination thresholds.

Monitoring migrant groups as a post-validation surveillance approach to contain the potential reemergence of lymphatic filariasis in Togo.

BACKGROUND: In March 2017, Togo was declared the first country in sub-Saharan Africa to eliminate lymphatic filariasis as a public health problem, but post-validation surveillance has been lacking. In some areas of the country, migrant groups from neighboring countries that are still endemic for LF pose a risk of reintroduction of LF to Togo. The objective of this study was to identify the risk posed by migrant groups by measuring their prevalence of LF infection and investigating any positive case using Togo's case investigation algorithm to prevent resurgence of LF and sustain Togo's elimination success. METHOD: A cross-sectional study was conducted in 2018 in the northernmost region of the country. Three migrant populations were identified: (i) nomadic Peuhls, (ii) Togolese members of local communities who migrate annually to neighboring countries for seasonal labor, and (iii) refugees from Ghana who came to Togo because of a communal conflict in Ghana. A questionnaire was designed to collect data on demographics and history of LF and MDA; all participants were tested for circulating filariasis antigen (CFA) using the filariasis test strip (FTS). Any CFA-positive case was confirmed with nocturnal microfilaremia. RESULTS: Refugees, seasonal economic migrants and nomadic Peuhls represented 42.1%, 31.4% and 26.5% of the study participants, respectively. The overall prevalence of CFA was 4.2% (58/1391) with the highest prevalence in the nomadic Peuhl group (11.9%), but only one of them (0.07%) was confirmed positive with nocturnal microfilaremia. Using the case investigation algorithm, no other positive case was identified in the positive case's surroundings. CONCLUSION: This study demonstrates that nomadic Peuhls, with a CFA prevalence of 11.9%, pose a potential risk for reintroduction of LF into Togo while Ghanaian refugees and seasonal economic migrants do not appear to pose a significant risk. Periodic monitoring of migrants, especially the nomadic Peuhl population, is a potential post-validation surveillance approach that could be used to promptly detect any LF cluster that may arise.

Assessment of the usefulness of anti-Wb123 antibody for post-elimination surveillance of lymphatic filariasis.

BACKGROUND: The World Health Organization has targeted lymphatic filariasis (LF) for elimination as a public health problem and recommends, among other measures, post-elimination surveillance of LF. The identification of sensitive and specific surveillance tools is therefore a research priority. The Wuchereria bancrofti-specific antigen Wb123-based enzyme-linked immunosorbent assay (Wb123 ELISA) detects antibodies to the recombinant Wb123 antigen of W. bancrofti and may be useful as a surveillance tool for LF. Six years after stopping mass drug administration to eliminate LF and recording successful results on two post-treatment transmission assessment surveys, a study was conducted in Togo aimed at helping to identify the role of the Wb123 ELISA in post-validation surveillance of LF. METHODS: This was a cross-sectional study in eight previously LF-endemic districts and one non-endemic district in Togo. In each sub-district of these nine districts, two schools were selected and 15 children aged 6 to 9 years old at each school provided finger-stick blood for testing for antibodies to Wb123 using the Filaria Detect™ IgG4 ELISA kit® (InBios, International, Inc., Seattle, WA, USA). RESULTS: A total of 2654 children aged 6 to 9 years old were tested in 134 schools in the nine districts. Overall, 4.7% (126/2654) children tested positive for antibodies to the Wb123 antigen of W. bancrofti. The prevalence of Wb123 antibodies varied across the eight previously endemic LF districts, from 1.56 to 6.62%. The highest prevalence, 6.99%, was found in the non-endemic district, but this was not significantly different from the average of all the LF districts (4.49%, P = 0.062). CONCLUSIONS: The Wb123 ELISA was positive in 4.7% of Togolese school-age children who were almost certainly unexposed to LF. This apparent lack of specificity in the Togo context makes it difficult to establish a seroprevalence threshold that could serve to signal LF resurgence in the country, precluding the use of this test for post-validation surveillance in Togo. There remains a need to develop a useful and reliable test for post-elimination surveillance for LF in humans.

Impact of community-based integrated mass drug administration on schistosomiasis and soil-transmitted helminth prevalence in Togo.

BACKGROUND: Togo has conducted annual, integrated, community-based mass drug administration (MDA) for soil-transmitted helminths (STH) and schistosomiasis since 2010. Treatment frequency and target populations are determined by disease prevalence, as measured by baseline surveys in 2007 and 2009, and WHO guidelines. Reported programmatic treatment coverage has averaged over 94%. Togo conducted a cross-sectional survey in 2015 to assess the impact of four to five years of MDA on these diseases. METHODOLOGY/PRINCIPAL FINDINGS: In every sub-district in the country outside the capital, the same schools were visited as at baseline and a sample of fifteen children age 6 to 9 years old was drawn. Each child submitted urine and a stool sample. Urine samples were tested by dipstick for the presence of blood as a proxy measure of Schistosoma haematobium infection. Stool samples were analyzed by the Kato-Katz method for STH and Schistosoma mansoni. At baseline, 17,100 children were enrolled at 1,129 schools in 562 sub-districts; in 2015, 16,890 children were enrolled at the same schools. The overall prevalence of both STH and schistosomiasis declined significantly, from 31.5% to 11.6% for STH and from 23.5% to 5.0% for schistosomiasis (p<0.001 in both instances). Egg counts from both years were available only for hookworm and S. mansoni; intensity of infection decreased significantly for both infections from 2009 to 2015 (p<0.001 for both infections). In areas with high baseline prevalence, rebound of hookworm infection was noted in children who had not received albendazole in the past 6 months. CONCLUSIONS/SIGNIFICANCE: After four to five years of MDA in Togo, the prevalence and intensity of STH and schistosomiasis infection were significantly reduced compared to baseline. Data on STH indicate that stopping MDA in areas with high baseline prevalence may result in significant rebound of infection. Togo's findings may help refine treatment recommendations for these diseases.

Surveillance for lymphatic filariasis after stopping mass drug administration in endemic districts of Togo, 2010-2015.

BACKGROUND: Togo is a country previously endemic for lymphatic filariasis (LF). In 2010, following nine years of mass drug administration (MDA) for LF, the country established a post-treatment surveillance (PTS) system. We present here the results of these PTS activities, carried out from 2010 to 2015, as well as the findings of follow-up investigations in 2016 to confirm the absence of infection in previously infected individuals. METHODS: The routine surveillance established in 2010 consisted of a network of 47 laboratories, which searched for Wuchereria bancrofti microfilaria on nocturnal blood smears collected for malaria diagnosis and an additional network of 20 peripheral health facilities, which collected dried blood spots and tested them for Og4C3 antigen. Two transmission assessment surveys (TAS) were also undertaken, as recommended by WHO, in 2012 and 2015. Any positive case identified through any surveillance activity was immediately retested by nocturnal smear and confirmed cases were immediately investigated by screening family members and neighboring household members. In 2016, 32 of the 40 positive cases detected during TAS or laboratory and health facility network activities were traced and whether confirmed positive by nocturnal smear or not were tested again simultaneously by filariasis test strip (FTS), Og4C3 and a nocturnal blood smear to rule out any active infection. RESULTS: From 2010 to 2015, the laboratory network identified one microfilaria-positive individual (0.0% of 26,584 persons tested) and the peripheral health facility network detected 19 Og4C3-positive individuals (0.28% of 6788 persons tested). All 19 Og4C3 cases were negative for microfilaremia by nocturnal blood smear. In the 2012 and 2015 TAS, thirteen and six ICT/FTS positive cases, respectively, were identified, which were significantly below the critical cut-off (18-20 cases) across all evaluation units. Three of the six ICT/FTS-positive cases from the 2015 TAS were positive by nocturnal smear; immediate investigation identified one additional microfilaria-positive individual. Epidemiological investigation revealed that four of the five cases of microfilaremia were imported from another country in the region. In 2016, 32 of the 40 positive cases detected by at least one test during all surveillance activities were traced: four (12.5%) individuals were still positive by FTS but all 32 individuals were negative for microfilaremia and Og4C3 antigen. CONCLUSION: The results of post-treatment surveillance in Togo have demonstrated that W. bancrofti filariasis is no longer of public health concern in Togo, more than six years after stopping MDA. Every possible effort should be made to maintain surveillance in order to promptly detect any resurgence and preserve this achievement.

The associations between water and sanitation and hookworm infection using cross-sectional data from Togo's national deworming program.

BACKGROUND: Sustainable control of soil-transmitted helminths requires a combination of chemotherapy treatment and environmental interventions, including access to safe drinking water, sufficient water for hygiene, use of clean sanitation facilities, and handwashing (WASH). We quantified associations between home-, school-, and community-level WASH characteristics and hookworm infection-both prevalence and eggs per gram of stool (intensity)-among Togolese school children in the context of community-based chemotherapy treatments administered in the country from 2010 through 2014. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from two surveys conducted by the Togo Ministry of Health: a school-based survey of students aged 6-9 years across Togo conducted in 2009 and a follow-up survey in 2015, after four to five years of preventive chemotherapy. Data were available for 16,473 students attending 1,129 schools in 2009 and for 16,890 students from 1,126 schools in 2015. Between surveys, children in study schools received 0 to 8 rounds of deworming chemotherapy treatments. Few WASH conditions (only unimproved drinking water) were found to be significantly associated with the presence or absence of hookworms in an individual; however, quantitative eggs per gram of feces was associated with availability of unimproved drinking water, availability of improved drinking water either on or off school grounds, having a handwashing station with water available, and access to a sex-separate non-private or private latrine. The association between school WASH conditions and hookworm infection or burden often depended on the 2009 prevalence of infection, as more WASH characteristics were found to be significant predictors of infection among schools with high underlying endemicity of hookworm. CONCLUSIONS/SIGNIFICANCE: Our findings emphasize the complex and often inconsistent or unpredictable relationship between WASH and hookworm. Specifically, we found that while preventive chemotherapy appeared to dramatically reduce hookworm infection, WASH was associated with infection intensity.

The cost-effectiveness of 10 antenatal syphilis screening and treatment approaches in Peru, Tanzania, and Zambia.

OBJECTIVE: Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women. METHODS: Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results. RESULTS: Although this analysis found screening using RPR to be relatively cheap, most (>70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women. CONCLUSION: This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings.

Pilot community-mobilization program reduces maternal and perinatal mortality and prevents obstetric fistula in Niger.

OBJECTIVE: To assess the impact of a pilot community-mobilization program on maternal and perinatal mortality and obstetric fistula in Niger. METHODS: In the program, village volunteers identify and evacuate women with protracted labor, provide education, and collect data on pregnancies, births, and deaths. These data were used to calculate the reduction in maternal mortality, perinatal mortality, and obstetric fistula in the program area from July 2008 to June 2011. RESULTS: The birth-related maternal mortality fell by 73.0% between years 1 and 3 (P<0.001), from 630 (95% confidence interval [CI] 448-861) to 170 (95% CI 85-305) deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P<0.001), from 35 (95% CI 31-40) to 13 (95% CI 10-16) deaths per 1000 births. No deaths due to obstructed labor were reported after the lead-in period (February to June 2008). Seven cases of community-acquired fistula were reported between February 2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no cases were recorded. CONCLUSION: Community mobilization helped to prevent obstetric fistula and birth-related deaths of women and infants in a large, remote, resource-poor area.

Comparison of anaemia and parasitaemia as indicators of malaria control in household and EPI-health facility surveys in Malawi.

BACKGROUND: The World Health Organization has recommended that anaemia be used as an additional indicator to monitor malaria burden at the community level as malaria interventions are nationally scaled up. To date, there are no published evaluations of this recommendation. METHODS: To evaluate this recommendation, a comparison of anaemia and parasitaemia among 6-30 month old children was made during two repeated cross-sectional household (HH) and health facility (HF) surveys in six districts across Malawi at baseline (2005) and in a follow-up survey (2008) after a scale up of malaria control interventions. RESULTS: HH net ownership did not increase between the years (50.5% vs. 49.8%), but insecticide treated net (ITN) ownership increased modestly from 41.5% (95% CI: 37.2%-45.8%) in 2005 to 45.3% (95% CI: 42.6%-48.0%) in 2008. ITN use by children 6-30 months old, who were living in HH with at least one net, increased from 73.6% (95% CI:68.2%-79.1%) to 80.0% (95% CI:75.9%-84.1%) over the three-year period. This modest increase in ITN use was associated with a decrease in moderate to severe anaemia (Hb <8 g/dl) from 18.4% (95% CI:14.9%-21.8%) in 2005 to 15.4% (13.2%-17.7%) in 2008, while parasitaemia, measured as positive-slide microscopy, decreased from 18.9% (95% CI:14.7%-23.2%) to 16.9% (95% CI:13.8%-20.0%), a relative reduction of 16% and 11%, respectively. In HF surveys, anaemia prevalence decreased from 18.3% (95% CI: 14.9%-21.7%) to 15.4% (95% CI: 12.7%-18.2%), while parasitaemia decreased from 30.6% (95% CI: 25.7%-35.5%) to 13.2% (95% CI: 10.6%-15.8%), a relative reduction of 15% and 57%, respectively. CONCLUSION: Increasing access to effective malaria prevention was associated with a reduced burden of malaria in young Malawian children. Anaemia measured at the HF level at time of routine vaccination may be a good surrogate indicator for its measurement at the HH level in evaluating national malaria control programmes.

Developing national treatment policy for falciparum malaria in Africa: Malawi experience.

The emergence and spread across sub-Saharan Africa of Plasmodium falciparum resistant to the inexpensive antimalarials chloroquine and sulfadoxine-pyrimethamine has worsened the health and hampered the socio-economic development of affected countries, a situation that calls for urgent review of malaria treatment policies in these countries. The Roll Back Malaria (RBM) initiative promotes strong partnerships for implementing effective malaria control measures. The development of clear policies to guide such implementation at country level offers a way of assessing the achievement of set milestones in this collaborative venture. In this article we describe the policy development process for the treatment of falciparum malaria in Africa, based on experience in Malawi, where the first-line drug treatment was recently changed from sulfadoxine-pyrimethamine to an artemisinin combination therapy.

Diagnosis of malaria: challenges for clinicians in endemic and non-endemic regions.

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.

Using malarial retinopathy to improve the classification of children with cerebral malaria.

The mechanisms leading to death in cerebral malaria (CM) remain unclear. We compared clinical and laboratory data among children with CM, categorized by ocular fundus findings, to elucidate differences that suggest different underlying pathological processes. From 1999-2005, standard examinations, treatment and record keeping were used for children with a clinical diagnosis of CM. Children were divided into ocular subgroups: normal fundus (N), malarial retinopathy (R), or papilloedema alone (P) and appropriate statistical tests were used to compare clinical and laboratory findings among groups. Eight hundred and eighty children who had eye examinations within 6 h of admission were included in the analysis. The groups differed significantly in case-fatality rates: Group P, 44.4% (95% CI 25.3-63.2), Group R, 18.0% (95% CI 15.6-22.3) and Group N, 7.0% (95% CI 4.2-9.8). There were also significant differences among the groups in blood pressure, prevalence of deep breathing, haematocrit, parasite density, platelet concentration and, among survivors, hours taken to recover from coma. Differences among groups suggest that different underlying pathophysiological processes are operating in children with CM defined by existing criteria. Our proposed classification, by improving the specificity of diagnosis, would enhance consistency among different study sites and prove useful in future research studies.

Cost-effectiveness of on-site antenatal screening to prevent congenital syphilis in rural eastern Cape Province, Republic of South Africa.

OBJECTIVES: On-site screening and same-day treatment of maternal syphilis in underresourced settings can avert greater numbers of congenital syphilis cases, but health outcomes and associated costs must be evaluated jointly. METHODS: We used decision analysis to estimate the incremental cost-effectiveness of two on-site antenatal syphilis screening strategies to avert congenital infections-qualitative RPR (on-site RPR) and treponemal immunochromatographic strip assay (on-site ICS)-compared to the current practice (off-site RPR/TPHA). FINDINGS: With antenatal active syphilis prevalence of 6.3%, the incremental cost-effectiveness of on-site ICS in averting congenital infections was estimated to be USD104, averting 82% of cases expected in absence of a program. The incremental cost-effectiveness of off-site RPR/TPHA was USD82 but would avert only 55% of congenital syphilis cases. On-site RPR was dominated by the other screening strategies. CONCLUSIONS: In settings of high maternal syphilis prevalence, on-site antenatal screening with ICS is a cost-effective approach to reduce the incidence of congenital syphilis.

Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome.

BACKGROUND: Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. METHODS: From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. RESULTS: Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. CONCLUSIONS: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.

On-site rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics.

OBJECTIVES: Congenital syphilis is a significant cause of adverse pregnancy outcomes. In South Africa, rural clinics perform antenatal screening offsite, but unreliable transport and poor client follow up impede effective treatment. We compared 3 syphilis screening strategies at rural clinics: on-site rapid plasma reagin (RPR), on-site treponemal immunochromatographic strip (ICS) test, and the standard practice offsite RPR with Treponema pallidum hemagglutination assay (RPR/TPHA). METHODS: Eight rural clinics performed the on-site RPR and ICS tests and provided immediate treatment. Results were compared with RPR/TPHA at a reference laboratory. Chart reviews at 8 standard practice clinics established diagnosis and treatment rates for offsite RPR/TPHA. FINDINGS: Seventy-nine (6.3%) of 1,250 women screened on-site had active syphilis according to the reference laboratory. The on-site ICS resulted in the highest percentage of pregnant women correctly diagnosed and treated for syphilis (89.4% ICS, 63.9% on-site RPR, 60.8% offsite RPR/TPHA). The on-site RPR had low sensitivity (71.4% for high-titer syphilis). The offsite approach suffered from poor client return rates. One percent of women screened with the ICS may have received penicillin unnecessarily. There were no adverse treatment outcomes. CONCLUSIONS: The on-site ICS test can reduce syphilis-related adverse outcomes of pregnancy through accurate diagnosis and immediate treatment of pregnant women with syphilis.