Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses.

BACKGROUND: The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. METHODS: In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. FINDINGS: Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages. INTERPRETATION: Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention. FUNDING: US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship.

Maternal determinants of diarrhea in children under five in Lubumbashi, Democratic Republic of the Congo.

Diarrheal diseases are one of the leading causes of death among children younger than 5 years of age in the world in general and in sub-Saharan Africa in particular. Mothers are predominantly responsible for child care and housekeeping in this region. The objective of this study was to determine the prevalence of diarrhea and identify its maternal determinants in children under five in the city of Lubumbashi. A cross-sectional study conducted throughout March 2018 collected data from 299 mothers through a household survey. A pretested structured questionnaire was used to collect data in face-to-face interviews. The prevalence of diarrhea in children under 5 in Lubumbashi was 35.8%. In the univariate analysis, the variables associated with diarrhea were single motherhood, soap-free handwashing after latrine use, and the presence of feces around the latrines. Multivariate analysis revealed that the presence of feces around latrines (OR adjusted = 2.12 [1.18-3.80]) was associated with diarrhea. Defective cleaning by mothers, specifically their failure to keep latrine areas clean and free of feces, is associated with the risk of diarrhea in children under five in the study area. A hygiene intervention program must be designed to promote healthy behavior to alleviate the burden of diarrhea in children.

Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda.

BACKGROUND: Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. METHODS: We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. RESULTS: We recruited 612 mothers, median age 23years (IQR 20-28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6-7.0) IU/mL with 9 (17.6%) having levels≥105IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. CONCLUSION: Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission.

A preliminary study for the treatment of cervical colposcopic lesions with the biological compound AV2.

OBJECTIVE: To evaluate the efficacy of Anti Viral 2 (AV2) in the regression of moderate and severe colposcopic lesions, when com- pared to placebo. MATERIALS AND METHODS: Women, aged over 18 years with a colposcopic diagnosis of moderate to severe dysplasia were randomized to receive either two applications of AV2 or placebo within four days. Both examining physician and patients were blinded to the treatment option. Follow-up colposcopy was performed on days 11, 2 1, and 60. RESULTS: A total of 50 patients were enrolled in this study. There was no statistically significant difference in screening entry criteria between the two groups. The results showed that the application of AV2 yielded a reduction of more than 50% for 21 out of 28 (75%) patients who received the active treatment versus a 0% for the comparable placebo group (p < 0.00 1). CONCLUSIONS: The authors conclude that AV2 can have a place in the treatment of colposcopically-detected cervical lesions. Due to the proven broad spectrum antiviral activity of AV2, a plausible explanation is that the lesions regress due to deactivation of the virus. Further trials with larger numbers and detailed cytology and histology are needed to confirm these results.

Small angle light scattering assay for the detection of malaria infection.

The diagnosis of malaria, caused by Plasmodium spp., still remains a challenging process. Especially in low-income countries, a rapid user-friendly method is needed for the efficient care of the patient. A small-angle light scattering device consisting of hardware and software was developed. Using the DNA-binding dye SYBR Green, malaria infections could be distinguished in healthy red blood cells infected with Plasmodium. Subsequently, samples from parasite positive and negative patients living in a hyper-endemic area of Kinshasa, DRC were assessed. The scatter profiles were distinct and malaria infection could be detected using the Giemsa stain. Although these results are preliminary, they indicate that the device has the potential to be used as a new diagnostic tool for the detection of Malaria infection.

Validation of an apicoplast genome target for the detection of Plasmodium species using polymerase chain reaction and loop mediated isothermal amplification.

The genome of the Plasmodium apicoplast, which has a higher copy number compared with current targets for molecular diagnosis of malaria, appears to be a suitable target for detection of submicroscopic infections that are capable of sustaining transmission. Novel primers targeting a conserved segment of the apicoplast (PFC10_AP|0010:rRNA) were designed and used in a number of different high throughput platforms such as single-step PCR (ssPCR), nested PCR (nPCR) and loop-mediated isothermal amplification (LAMP) for parasite detection. Replicates of ten-fold serial dilutions of Plasmodium falciparum 3D7 DNA, with equivalent parasite density ranges of 200,000 to 0.2 parasites/µL, were used to determine the limit of detection and repeatability of each assay. A panel of 184 archived DNA samples extracted from either EDTA whole blood or dried blood spots, from across West Africa and South East Asia was used to determine the diagnostic performance of the assays. All assays amplified the 2 parasites/µL dilution except the ssPCR, which amplified two of the three replicates. Using an 18S rRNA PCR as reference, the sensitivity was 98% (95% CI 93-100%) for the LAMP assay, 87% (95% CI 79-93%) for ssPCR and 100% (95% CI 97-100%) for nPCR. Specificity was 91% (95% CI 83-96%) for LAMP, 82% (95% CI 72-90%) for ssPCR and 66% (95% CI 54-76%) for nPCR. The apicoplast genome-based nPCR detected more positive samples overall than the reference method. Discrepant samples were confirmed as true positives using a probe-based real-time quantitative PCR assay. The results show that the apicoplast genome is a suitable target for molecular diagnosis of malaria.

Integration of diagnosis and treatment of sleeping sickness in primary healthcare facilities in the Democratic Republic of the Congo.

BACKGROUND: Control of human African trypanosomiasis (HAT) in the Democratic Republic of Congo (DRC) has always been a vertical programme, although attempts at integration in general health services were made in recent years. Now that HAT prevalence is declining, the integration question becomes even more crucial. We studied the level of attainment of integration of HAT case detection and management in primary care centres in two high-prevalence districts in the province of Bandundu, DRC. METHODS: We visited all 43 first-line health centres of Mushie and Kwamouth districts, conducted structured interviews and inspected facilities using a standardised checklist. We focused on: availability of well trained staff - besides HAT, we also tested for knowledge on tuberculosis; availability of equipment, consumables and supplies; and utilisation of the services. RESULTS: All health centres were operating but most were poorly equipped, and attendance rates were very low. We observed a median of 14 outpatient consultations per facility (IQR 8-21) in the week prior to our visit, that is two patients per day. The staff had good knowledge on presenting symptoms, diagnosis and treatment of both HAT and tuberculosis. Nine centres were accredited by the national programme as HAT diagnosis and treatment centres, but the most sensitive diagnostic confirmation test, the mini-anion exchange centrifugation technique (mAECT), was not present in any. Although all nine were performing the CATT screening test, only two had the required cold chain in working order. CONCLUSION: In these high-prevalence districts in DRC, staff is well-acquainted with HAT but lack the tools required for an adequate diagnostic procedure. Attendance rates of these primary care centres are extremely low, making timely recognition of a resurgence of HAT unlikely in the current state of affairs.

Interactions between malaria and human immunodeficiency virus anno 2014.

Possible pathophysiological, clinical and epidemiological interactions between human immunodeficiency virus (HIV) and tropical pathogens, especially malaria parasites, constitute a concern in tropical areas. Two decades of research have shown that HIV-related immunosuppression is correlated with increased malaria infection, burden, and treatment failure, and with complicated malaria, irrespective of immune status. The recent role out of antiretroviral therapies and new antimalarials, such as artemisinin combination therapies, raise additional concerns regarding possible synergistic and antagonistic effects on efficacy and toxicity. Co-trimoxazole, which is used to prevent opportunistic infections, has been shown to have strong antimalarial prophylactic properties, despite its long-term use and increasing antifolate resistance. The administration of efavirenz, a non-nucleoside reverse transcriptase inhibitor, with amodiaquine-artesunate has been associated with increased toxicity. Recent in vivo observations have confirmed that protease inhibitors have strong antimalarial properties. Ritonavir-boosted lopinavir and artemether-lumefantrine have a synergistic effect in terms of improved malaria treatment outcomes, with no apparent increase in the risk of toxicity. Overall, for the prevention and treatment of malaria in HIV-infected populations, the current standard of care is similar to that in non-HIV-infected populations. The available data show that the wider use of insecticide-treated bed-nets, co-trimoxazole prophylaxis and antiretroviral therapy might substantially reduce the morbidity of malaria in HIV-infected patients. These observations show that those accessing care for HIV infection are now, paradoxically, well protected from malaria. These findings therefore highlight the need for confirmatory diagnosis of malaria in HIV-infected individuals receiving these interventions, and the provision of different artemisinin-based combination therapies to treat malaria only when the diagnosis is confirmed.

Village health workers in Bihar, India: an untapped resource in the struggle against kala-azar.

INTRODUCTION: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent; important components of early case finding and treatment are entrusted to the primary health care system (PHC). In an earlier study in Bihar, India, we discovered some major shortcomings in implementation, in particular related to monitoring of treatment and treatment outcomes. These shortcomings could be addressed through involvement of village health workers. In the current study we assessed knowledge, attitude and practice of these village health workers in relation to VL. Main objective was to assess the feasibility of their involvement in VL control. METHODS: We obtained a list of auxiliary nurses/midwives and accredited social health activists for the highly endemic district of Muzaffarpur. We randomly sampled 100 auxiliary nurses and 100 activists, who were visited in their homes for an interview. Questions were asked on knowledge, attitude and practice related to visceral leishmaniasis and to tuberculosis. RESULTS: Auxiliary nurses and activists know the presenting symptoms of visceral leishmaniasis, they know how it is diagnosed but they are not aware of the recommended first-line treatment. Many are already involved in tuberculosis control and are very well aware of the treatment modalities of tuberculosis, but few are involved in control of visceral leishmaniasis control. They are well organised, have strong links to the primary healthcare system and are ready to get more involved in visceral leishmaniasis control. CONCLUSION: To ensure adequate monitoring of visceral leishmaniasis treatment and treatment outcomes, the control programme urgently needs to consider involving auxiliary nurses and activists.

Predictors of antiretroviral treatment-associated tuberculosis in Ethiopia: a nested case-control study.

Little is known about the predictors of antiretroviral treatment (ART)-associated tuberculosis (TB) in developing nations. The objective of this study was to determine predictors of ART-associated TB in adults with HIV infection at Jimma University Hospital, Ethiopia. A nested case-control study was conducted in October 2009. The study population consisted of adults with HIV infection (aged >14 years) who developed active TB in the first six months since ART initiation and controls that did not develop active TB. Data were collected using a structured and pretested questionnaire. Cox proportions hazards analysis was done to determine predictors of ART-associated TB. A total of 357 patients (119 cases and 238 controls) participated in the study. After six months of follow-up, cumulative incidence of ART-associated TB was 5.2% (123/2355). Forty (33.6%) cases were lost to follow-up after they developed ART-associated TB and 11 (9.2%) died. Fifty-one (21.4%) controls interrupted ART and 11 (4.6%) died. A CD4 lymphocyte count increase >0.5/µL/day (adjusted hazard ratio [AHR] = 19.80, 95% confidence interval [CI]: 9.52, 41.12, P < 0.001), a base-line CD4 lymphocyte count <200 cells/µL (AHR = 9.59, 95% CI: 2.36, 39.04, P = 0.002), World Health Organization (WHO) clinical stage 3 or 4 (AHR = 3.04, 95% CI: 1.62, 5.69, P < 0.001), night sweats during ART initiation (AHR = 1.53, 95% CI: 1.06, 2.21, P < 0.001) and high ART adherence (AHR = 1.30, 95% CI: 1.13, 1.50, P < 0.001) were independent predictors of ART-associated TB. HIV-infected adults with these risk factors should be followed cautiously for the development of ART-associated TB. Good ART adherence and a good immunological response during ART were associated with ART-associated TB, most likely because of an immune reconstitution inflammatory syndrome unmasking the TB.

Earlobe reconstruction with a reverse-flow chondrocutaneous flap.

Many techniques have been described for earlobe reconstruction, but a stable and satisfactory shape has not always been obtained, mainly because of secondary retraction. A method of creating an earlobe using a reverse-flow postauricular chondrocutaneous flap combined with a cutaneous flap is presented. No skin graft is needed. The result was stable at 2 years follow-up.

Circumferential torsoplasty.

Abdominoplasty procedures are often unsatisfactory in correcting body deformities remaining after massive weight loss. Lateral flanks, hip rolls and buttock ptosis need also to be addressed surgically. To achieve a more noticeable improvement in body contour, a circumferential torsoplasty procedure was performed in 30 patients during the years 1993-1997. Twenty of them had had a gastroplasty procedure before with a mean weight loss of 49.5 kg. Mean operative time was 210 min (range 150-420 min). The total resection weight ranged from 2 to 8.96 kg (mean 4.3 kg). Mean operative blood loss was 635 ml (range 300-1900 min). The mean hospital stay was 12 days. Minor complications occurred in four patients and major complications in one. Both patients and surgeons considered the outcome very satisfactory.

Verrucous carcinoma of the nail bed.

Verrucous carcinoma is a rare, highly keratinizing variant of squamous cell carcinoma of the skin or mucosae characterized by a local aggressiveness but a low potential for metastasis. The plantar form is also known as epithelioma cuniculatum. Fingers and toes are rarely affected, and tumors of the nail bed are exceptional. Clinically, the lesion presents like a wart and is then often misdiagnosed. Treatment of choice is wide surgical excision. A case of verrucous carcinoma of the nail apparatus is presented, and diagnosis is discussed.

Iatrogenic posterior interosseous nerve palsy following an elbow fracture.

Posterior interosseous nerve palsy following elbow surgery is not uncommon. Nevertheless, precise etiology of the palsy is rarely described in the literature. In this paper the possible causes of the posterior interosseous nerve palsy are reviewed and an uncommon iatrogenic lesion after surgical treatment of an elbow fracture is reported.

Heterotopic brain tissue in the scalp.

A posterior midline cutaneous lesion in the scalp of a 15-month-old child was excised. Clinical examination, extensive investigations and finally surgery revealed no intracranial connection. Histologically, the lesion was composed of well differentiated meningeal, glial and cerebral tissues, establishing it to be heterotopic brain tissue. Even when all preoperative procedures exclude the diagnosis of cephaloceles, surgeons should keep in mind the possibility of an intracranial connection of any midline scalp lesion in a child and the subsequent risk of meningitis.

Simultaneous bilateral facial reconstruction of a Barraquer-Simons lipodystrophy with free TRAM flaps.

Barraquer-Simons lipodystrophy is a rare disorder of unknown origin characterized by a progressive atrophy of the subcutaneous fat of the upper part of the body. Renal disease with abnormalities of complement factors is the most frequent accompanying feature. A case is presented in which bilateral facial contour has been restored simultaneously with two deepithelialized TRAM flaps.

Free TRAM flap for lower-extremity reconstruction.

The usefulness of TRAM flaps is well-established. Their use in soft-tissue reconstruction of the lower limbs is illustrated. The flaps allow coverage of soft-tissue defects with good quality skin, and add bulk to enhance leg contour. Three cases are presented, and the advantages of this flap are discussed.