Malaria and respiratory syncytial virus as causes of acute febrile illness in an urban paediatric population in Ghana.

Background: The sub-Saharan region of Africa is endemic for malaria, and fever is often assumed to be malaria. In Ghana, about 3.7 million cases were reported in 2011, with 24.4% of these laboratory-confirmed. Other causes of febrile illness, including respiratory syncytial virus (RSV), are prevalent in developing countries like Ghana. There is very little data on the prevalence of this virus in the country. This study determined the proportion of acute febrile illness in an urban paediatric population that was due to malaria or RSV. Methods: A hospital based surveillance system recruited children below five years of age reporting with fever (axillary temperature ≥ 37.5°C) at the outpatient department of an urban hospital from February 2009 to February 2010. Consenting parents/guardians were interviewed, the medical history of the child was taken and the child clinically examined. Thick blood film from capillary blood taken through a finger prick, was Giemsa-stained and microscopically examined for malaria parasites to confirm malaria diagnosis. Nasopharyngeal aspirate was also examined for RSV by polymerase chain reaction. Results: Out of 481 febrile children, 51(10.8%) were positive for malaria whilst 75 (15.4%) were positive for RSV. Seven of the 75 RSV-positive cases (9.3%) were co-infected with malaria. Based on judgement by clinicians, over 80% of the febrile children were diagnosed and treated as having malaria either alone or in combination with other diseases. Conclusion: Not all febrile episodes in malaria-endemic regions are due to malaria. The diagnosis and subsequent treatment of patients based solely on clinical diagnosis leads to an over diagnosis of malaria. Improvement in the guidelines and facilities for the diagnosis of non-malaria febrile illness leads to improved malaria diagnosis. Clinicians should be looking for other causes of fever rather than treating all fevers as malaria.

Rapid mapping of schistosomiasis and other neglected tropical diseases in the context of integrated control programmes in Africa.

There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (1) mapping schistosomiasis across Africa using available epidemiological data and, more recently, climate-based risk prediction; (2) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (3) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified.

Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.

BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).

What happened to the IUD in Ghana?

The intrauterine contraceptive device (IUD) is a safe and reversible contraceptive method that requires little effort on the part of the user. Once inserted, it offers 10 years of protection against pregnancy. However, its use in Ghana has stagnated in relation to other contraceptive methods. An exploratory study was, therefore, conducted to examine the client, provider and system characteristics that affect the demand for IUD. Data were gathered through secondary analysis, in-depth interviews, focus group discussions and simulated client survey. The stagnating demand for IUD is attributed to clients' perceptions and rumours about IUD. The fear of excessive bleeding and weight loss discourages potential users. The product design was also perceived to be unacceptable. Demand creation for the IUD has been poor and the number of providers with practical experience of insertion is insufficient. Contrary to the belief that providers' bias contributes to the decline in use, findings show that providers have a favourable attitude towards the product.

The use of spatial analysis in mapping the distribution of bancroftian filariasis in four West African countries.

The geographical distribution of human infection with Wuchereria bancrofti was investigated in four West African countries (Benin, Burkina Faso, Ghana and Togo), using a commercial immunochromatographic test for filarial antigen. Efforts were made to cover each health-system implementation unit and to ensure no sampling point was >50 km from another, but otherwise the 401 study communities were selected at random. The aim was to enable spatial analysis of the data, to provide a prediction of the overall spatial relationships of the infection. The results, which were subjected to an independent random validation in Burkina Faso and Ghana, revealed that prevalence in the adult population of some communities exceeded 70% and that, over large areas of Burkina Faso, community prevalences were between 30% and 50%. Most of Togo, southern Benin and much of southern Ghana appeared completely free of the infection. Although there were foci on the Ghanaian coast with prevalences of 10%-30%, such high prevalences did not extend into coastal Togo or costal Benin. The prevalence map produced should be useful in prioritizing areas for filariasis control, identifying potential overlap with ivermectin-distribution activities undertaken by onchocerciasis-control programmes, and enabling inter-country and sub-regional planning to be initiated. The results indicate that bancroftian filariasis is more widely distributed in arid areas of Burkina Faso than hitherto recognized and that the prevalences of infection have remained fairly stable for at least 30 years. The campaign to eliminate lymphatic filariasis as a public-health problem in Africa will require significantly more resources (human, financial, and logistic) than previously anticipated.

Improving adherence to malaria treatment for children: the use of pre-packed chloroquine tablets vs. chloroquine syrup.

Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa. Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality. In many countries, chloroquine syrup is the mainstay of malaria treatment for children under five. Not only is syrup more expensive than tablets, adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions. We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup. Children aged 0--5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by random assignment. The principal caregivers were interviewed at home on day 4 after attending the clinic. Of the 155 caregivers given pre-packed tablets, 91% (n=141) adhered to the recommended dosage, while only 42% (n=61) of 144 who were provided syrup did. Only 20% of caregivers who received syrup used an accurate 5 ml measure. The cost of treatment with tablets was about one-quarter that of syrup and 62% (n=96) of caregivers preferred tablets. Pre-packed chloroquine tablets are a viable alternative to syrup.

Impact of prepackaging antimalarial drugs on cost to patients and compliance with treatment.

OBJECTIVE: To examine the extent to which district health teams could reduce the burden of malaria, a continuing major cause of mortality and morbidity, in a situation where severe resource constraints existed and integrated care was provided. METHODS: Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy. FINDINGS: Compliance improved by approximately 20% in both adults and children. There were 50% reductions in cost to patients, waiting time at dispensaries and drug wastage at facilities. The intervention, which tended to improve both case and drug management at facilities, was well accepted by health staff and did not involve them in additional working time. CONCLUSION: The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance.

Community-directed treatment: the way forward to eliminating lymphatic filariasis as a public-health problem in Ghana.

The elimination of lymphatic filariasis as a public-health problem is currently dependent on the delivery of annual drug treatments to at least 80% of the eligible members of endemic populations for at least 5 years. However, for various reasons, this goal may not be achievable by the health systems of most endemic countries in sub-Saharan Africa, particularly if treatment is not community-directed. In Ghana, community-directed ivermectin treatment involving the regular public-health services at the implementation level (ComDT/HS) has recently been compared with mass-treatment in which only the health services participated (HST). Health staff and the target communities appreciated the ComDT/HS approach more than the HST approach and were more willing to participate in the community-directed scheme. The treatment coverage achieved by ComDT/HS (74.5%) was not only much higher than that of HST (43.5%) but also probably adequate for filariasis elimination. HST coverage was particularly poor in villages located > 5 km from a health facility, but distance from such a facility had no significant effect on treatment coverage in the ComDT/HS arm. As virtually all the subjects who received drugs swallowed them, compliance with treatment was not a problem. The ComDT/HS approach is therefore recommended, especially for areas where access to health facilities is poor and the health workers are over-stretched. The implications of these findings for the global programme for filariasis elimination are discussed.

The use of grid sampling methodology for rapid assessment of the distribution of bancroftian filariasis.

The recent World Health Assembly Resolution to eliminate lymphatic filariasis as a public health problem once more brings to the fore the need for reliable data for the effective planning of disease control programmes. Most countries do not have data on the distribution of lymphatic filariasis and are therefore not in the position to initiate control programmes based on sound baseline data. We tested in Ghana in 1998-99 a method for the Rapid Assessment of the Geographical Distribution of Bancroftian Filariasis (RAGFIL) that uses a spatial sampling grid with 50 km between sampled villages, rapid assessment surveys for filariasis prevalence in the sampled villages and spatial analysis to estimate the geographical distribution of filariasis throughout the study area. The prevalence contours obtained with the 50 x 50-km sampling grid were operationally similar to those obtained with a 25 x 25-km grid. The predicted prevalence was not statistically different from the sample survey prevalence in 57 independent villages and the 50 x 50-km grid appears adequate for rapid mapping of filariasis. For the purpose of filariasis mapping, the antigen test would seem a better diagnostic test than clinical examination for hydrocoele. We recommend that a regional approach to mapping be used because of the importance of cross-border foci as demonstrated by our findings from the north of Ghana. Application of the method will provide the minimal information required for effective planning of treatment programmes, and will facilitate estimation of the number of people to be treated. It will also help improve estimates of the number of people at risk and affected, and of the burden of disease due to lymphatic filariasis in Africa.

Impact of single-dose ivermectin on community microfilaria load in bancroftian filariasis infection: two years post treatment.

The concept of annual single-dose treatment for the control and possible interruption of transmission of lymphatic filariasis has brought much hope to the previously hopeless disease. The logistics for implementing this enormous public health intervention have wide ramifications and will depend on the efficiency of drug delivery and distribution at various levels of the health system. In sub-Saharan Africa, where the public health services are inadequate, this becomes even more important. Six communities in southern Ghana known to be endemic for filariasis were treated with single-dose ivermectin in January/February 1997 as part of pilot programme activities. The 1998 treatment could not take place because of unavailability of the drug. The 1999 community microfilaraemia prevalence and intensity were reduced by only 25.5% and 39.5% of pre-treatment levels, respectively. The implications of any shortfalls on the drug delivery system on the goal of elimination of lymphatic filariasis are discussed.

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

The clinical epidemiology and prospects for control of lymphatic filariasis in Africa.

This paper reviews some of the current opinions in the epidemiology and control of lymphatic filariasis in general and in Africa in particular in view of the current global initiative to eliminate the disease as a public health problem. Despite some gaps in the knowledge of the natural history of the disease, there are sufficient tools available for initiating control activities. The focus of filariasis research should therefore shift towards operational research in the application of these tools.

The relationship between infection and disease in Wuchereria bancrofti infection in Ghana.

The relationship between infection and clinical disease in Wuchereria bancrofti infection was investigated in a community-based study in different endemic areas in Ghana. At the individual level, there was no association between acute adenolymphangitis and infection (microfilaraemia) status. There was a negative association between infection status and lymphoedema/elephantiasis, but a positive association with hydrocele; however, the intensity of infection was negatively associated with both elephantiasis and hydrocele. The community prevalence of infection was strongly associated with the prevalence of clinical filariasis (especially hydrocele). There was a strong positive association between the prevalence of infection in males and the odds of a case of hydrocele being microfilaraemic, suggesting that there is no acquired immunity to reinfection in cases of hydrocele. The pathophysiologies of elephantiasis and hydrocele may therefore differ from one another, and require further investigation.

Evaluation of the filter paper blood collection method for detecting Og4C3 circulating antigen in bancroftian filariasis.

Serological diagnosis of filariasis is generally known to be more reliable than detection of microfilariae. The recently developed Og4C3 enzyme-linked immunosorbent assay (ELISA) for detecting Wuchereria bancrofti circulating antigen has been shown to be very sensitive in diagnosing filiariasis using serum samples. The commercially available form of this ELISA, using whole blood collected on filter paper, has not been validated independently. We evaluated the sensitivity of this new method against standard 20 microL night blood films in 1808 paired samples from 18 communities in different endemic areas of Ghana. The diagnostic performance of the method was consistently low in all but 2 communities (sensitivity = 50.3%). This method of diagnosing filariasis is not suitable for field use in its present form.

Prevalence of hydrocele as a rapid diagnostic index for lymphatic filariasis.

The real burden of lymphatic filariasis in most endemic areas remains unknown even thought it is a major public health problem in many tropical countries, particularly in sub-saharan African. The nocturnal periodicity of the parasite requires parasitological examinations to be done at night. The aim of this study was to develop and validate rapid epidemiological assessment tools for the community diagnosis of lymphatic filariasis, that may be used in the future to determine the distribution of the disease and identify high risk communities in Ghana. Twenty communities with varying endemicity of filariasis were sampled from 3 endemic districts. Community members were selected for the study using a modified Expanded Programme for Immunization (EPI) cluster sampling technique. The prevalence of hydrocele was high (range 4.5-40.75%, mean = 17.78%) and the community prevalence of microfilaraemia correlated well with that of hydrocele (r = 0.84). The findings suggest that it is possible to obtain reliable and valid estimates of the community burden of lymphatic filariasis using the prevalence of hydrocele as a diagnostic index.